Inhibitors of the proteasome suppress homologous DNA recombination in mammalian cells.

Science.gov (United States)

Murakawa, Yasuhiro; Sonoda, Eiichiro; Barber, Louise J; Zeng, Weihua; Yokomori, Kyoko; Kimura, Hiroshi; Niimi, Atsuko; Lehmann, Alan; Zhao, Guang Yu; Hochegger, Helfrid; Boulton, Simon J; Takeda, Shunichi

2007-09-15

Proteasome inhibitors are novel antitumor agents against multiple myeloma and other malignancies. Despite the increasing clinical application, the molecular basis of their antitumor effect has been poorly understood due to the involvement of the ubiquitin-proteasome pathway in multiple cellular metabolisms. Here, we show that treatment of cells with proteasome inhibitors has no significant effect on nonhomologous end joining but suppresses homologous recombination (HR), which plays a key role in DNA double-strand break (DSB) repair. In this study, we treat human cells with proteasome inhibitors and show that the inhibition of the proteasome reduces the efficiency of HR-dependent repair of an artificial HR substrate. We further show that inhibition of the proteasome interferes with the activation of Rad51, a key factor for HR, although it does not affect the activation of ATM, gammaH2AX, or Mre11. These data show that the proteasome-mediated destruction is required for the promotion of HR at an early step. We suggest that the defect in HR-mediated DNA repair caused by proteasome inhibitors contributes to antitumor effect, as HR plays an essential role in cellular proliferation. Moreover, because HR plays key roles in the repair of DSBs caused by chemotherapeutic agents such as cisplatin and by radiotherapy, proteasome inhibitors may enhance the efficacy of these treatments through the suppression of HR-mediated DNA repair pathways.

Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

DEFF Research Database (Denmark)

Klein, Ditte Kjærsgaard; Hoffmann, Saskia; Ahlskog, Johanna K

2015-01-01

an important role in checkpoint control following ionizing radiation. Cyclin F-depleted cells initiate checkpoint signalling after ionizing radiation, but fail to maintain G2 phase arrest and progress into mitosis prematurely. Importantly, cyclin F suppresses the B-Myb-driven transcriptional programme...... that promotes accumulation of crucial mitosis-promoting proteins. Cyclin F interacts with B-Myb via the cyclin box domain. This interaction is important to suppress cyclin A-mediated phosphorylation of B-Myb, a key step in B-Myb activation. In summary, we uncover a regulatory mechanism linking the F-box protein...

Assessing Suppression in Amblyopic Children With a Dichoptic Eye Chart.

Science.gov (United States)

Birch, Eileen E; Morale, Sarah E; Jost, Reed M; De La Cruz, Angie; Kelly, Krista R; Wang, Yi-Zhong; Bex, Peter J

2016-10-01

Suppression has a key role in the etiology of amblyopia, and contrast-balanced binocular treatment can overcome suppression and improve visual acuity. Quantitative assessment of suppression could have a role in managing amblyopia. We describe a novel eye chart to assess suppression in children. We enrolled 100 children (7-12 years; 63 amblyopic, 25 nonamblyopic with strabismus or anisometropia, 12 controls) in the primary cohort and 22 children (3-6 years; 13 amblyopic, 9 nonamblyopic) in a secondary cohort. Letters were presented on a dichoptic display (5 letters per line). Children wore polarized glasses so that each eye saw a different letter chart. At each position, the identity of the letter and its contrast on each eye's chart differed. Children read 8 lines of letters for each of 3 letter sizes. The contrast balance ratio was the ratio at which 50% of letters seen by the amblyopic eye were reported. Amblyopic children had significantly higher contrast balance ratios for all letter sizes compared to nonamblyopic children and controls, requiring 4.6 to 5.6 times more contrast in the amblyopic eye compared to the fellow eye (P amblyopia treatment was correlated with change in contrast balance ratio (r ranged from 0.43-0.62 for the 3 letter sizes). Severity of suppression can be monitored as part of a routine clinical exam in the management of amblyopia in children.

The key role of extracellular vesicles in the metastatic process.

Science.gov (United States)

Zhao, Hongyun; Achreja, Abhinav; Iessi, Elisabetta; Logozzi, Mariantonia; Mizzoni, Davide; Di Raimo, Rossella; Nagrath, Deepak; Fais, Stefano

2018-01-01

Extracellular vesicles (EVs), including exosomes, have a key role in the paracrine communication between organs and compartments. EVs shuttle virtually all types of biomolecules such as proteins, lipids, nucleic acids, metabolites and even pharmacological compounds. Their ability to transfer their biomolecular cargo into target cells enables EVs to play a key role in intercellular communication that can regulate cellular functions such as proliferation, apoptosis and migration. This has led to the emergence of EVs as a key player in tumor growth and metastasis through the formation of "tumor niches" in target organs. Recent data have also been shown that EVs may transform the microenvironment of primary tumors thus favoring the selection of cancer cells with a metastatic behavior. The release of EVs from resident non-malignant cells may contribute to the metastatic processes as well. However, cancer EVs may induce malignant transformation in resident mesenchymal stem cells, suggesting that the metastatic process is not exclusively due to circulating tumor cells. In this review, we outline and discuss evidence-based roles of EVs in actively regulating multiple steps of the metastatic process and how we can leverage EVs to impair metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantitative proteomics reveals that peroxidases play key roles in post-flooding recovery in soybean roots.

Science.gov (United States)

Khan, Mudassar Nawaz; Sakata, Katsumi; Hiraga, Susumu; Komatsu, Setsuko

2014-12-05

Soybean is an important legume crop that exhibits markedly reduced growth and yields under flooding conditions. To unravel the mechanisms involved in recovery after flooding in soybean root, gel-free proteomic analysis was performed. Morphological analysis revealed that growth suppression was more severe with increased flooding duration. Out of a total of 1645 and 1707 identified proteins, 73 and 21 proteins were changed significantly during the recovery stage following 2 and 4 days flooding, respectively. Based on the proteomic, clustering, and in silico protein-protein interaction analyses, six key enzymes were analyzed at the mRNA level. Lipoxygenase 1, which was increased at the protein level during the recovery period, was steadily down-regulated at the mRNA level. The peroxidase superfamily protein continuously increased in abundance during the course of recovery and was up-regulated at the mRNA level. HAD acid phosphatase was decreased at the protein level and down-regulated at the transcript level, while isoflavone reductase and an unknown protein were increased at both the protein and mRNA levels. Consistent with these findings, the enzymatic activity of peroxidase was decreased under flooding stress but increased significantly during the recovery sage. These results suggest that peroxidases might play key roles in post-flooding recovery in soybean roots through the scavenging of toxic radicals.

Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression

International Nuclear Information System (INIS)

Ramos, Gerardo; Kazimi, Nasser; Nghiem, Dat X.; Walterscheid, Jeffrey P.; Ullrich, Stephen E.

2004-01-01

Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependant manner. The release of biological response modifiers, particularly prostaglandin E 2 (PGE 2 ), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE 2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE 2 secretion. Jet fuel-induced PGE 2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin

Social hierarchy and depression: the role of emotion suppression.

Science.gov (United States)

Langner, Carrie A; Epel, Elissa S; Matthews, Karen A; Moskowitz, Judith T; Adler, Nancy E

2012-01-01

Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depressive symptoms in a community sample of women. Low social power was related to greater depressive symptoms, and this relationship was partially mediated by emotion suppression. Study 2 examined education as a proxy for social hierarchy position, anger suppression, and depressive symptoms in a national, longitudinal cohort study (The coronary artery risk development in young adults [CARDIA] study; Cutter et al., 1991). Much as in study 1, low education levels were correlated with greater depressive symptoms, and this relationship was partially mediated by anger suppression. Further, suppression mediated the relationship between low education and subsequent depression up to 15 years later. These findings support the theory that social hierarchy affects mental health in part through a process of emotion suppression.

The role of inducer cells in mediating in vitro suppression of feline immunodeficiency virus replication

International Nuclear Information System (INIS)

Phadke, Anagha P.; Choi, In-Soo; Li Zhongxia; Weaver, Eric; Collisson, Ellen W.

2004-01-01

CD8 + T-cell-mediated suppression of feline immunodeficiency virus (FIV) replication has been described by several groups, although the mechanisms of activation and conditions for viral suppression vary with the methodologies. We have previously reported that CD8 + T-cell-mediated suppression of FIV replication required inducer cell stimulation of the effector cells. The focus of the present study was to examine the essential role of inducer cells required for the induction of this soluble anti-FIV activity. Both FIV-PPR-infected T cells and feline skin fibroblasts (FSF) infected with an alphavirus vector expressing FIV capsid or the irrelevant antigen lacZ, stimulated autologous or heterologous effector cells to produce supernatants that suppressed FIV replication. Thus, induction of this suppression of FIV replication did not strictly require autologous inducer cells and did not require the presence of FIV antigen. Anti-viral activity correlated with the presence of CD8 + T cells. Suppression was maximal when the inducer cells and the effector cells were in contact with each other, because separation of the inducer and effector cells by a 0.45-μm membrane reduced FIV suppression by approximately 50%. These findings emphasize the importance for membrane antigen interactions and cytokines in the optimal induction of effector cell synthesis of the soluble anti-FIV activity

The interpretation of mu suppression as an index of mirror neuron activity: past, present and future.

Science.gov (United States)

Hobson, Hannah M; Bishop, Dorothy V M

2017-03-01

Mu suppression studies have been widely used to infer the activity of the human mirror neuron system (MNS) in a number of processes, ranging from action understanding, language, empathy and the development of autism spectrum disorders (ASDs). Although mu suppression is enjoying a resurgence of interest, it has a long history. This review aimed to revisit mu's past, and examine its recent use to investigate MNS involvement in language, social processes and ASDs. Mu suppression studies have largely failed to produce robust evidence for the role of the MNS in these domains. Several key potential shortcomings with the use and interpretation of mu suppression, documented in the older literature and highlighted by more recent reports, are explored here.

Improving ART programme retention and viral suppression are key to maximising impact of treatment as prevention - a modelling study.

Science.gov (United States)

McCreesh, Nicky; Andrianakis, Ioannis; Nsubuga, Rebecca N; Strong, Mark; Vernon, Ian; McKinley, Trevelyan J; Oakley, Jeremy E; Goldstein, Michael; Hayes, Richard; White, Richard G

2017-08-09

UNAIDS calls for fewer than 500,000 new HIV infections/year by 2020, with treatment-as-prevention being a key part of their strategy for achieving the target. A better understanding of the contribution to transmission of people at different stages of the care pathway can help focus intervention services at populations where they may have the greatest effect. We investigate this using Uganda as a case study. An individual-based HIV/ART model was fitted using history matching. 100 model fits were generated to account for uncertainties in sexual behaviour, HIV epidemiology, and ART coverage up to 2015 in Uganda. A number of different ART scale-up intervention scenarios were simulated between 2016 and 2030. The incidence and proportion of transmission over time from people with primary infection, post-primary ART-naïve infection, and people currently or previously on ART was calculated. In all scenarios, the proportion of transmission by ART-naïve people decreases, from 70% (61%-79%) in 2015 to between 23% (15%-40%) and 47% (35%-61%) in 2030. The proportion of transmission by people on ART increases from 7.8% (3.5%-13%) to between 14% (7.0%-24%) and 38% (21%-55%). The proportion of transmission by ART dropouts increases from 22% (15%-33%) to between 31% (23%-43%) and 56% (43%-70%). People who are currently or previously on ART are likely to play an increasingly large role in transmission as ART coverage increases in Uganda. Improving retention on ART, and ensuring that people on ART remain virally suppressed, will be key in reducing HIV incidence in Uganda.

Feeding by whiteflies suppresses downstream jasmonic acid signaling by eliciting salicylic acid signaling.

Science.gov (United States)

Zhang, Peng-Jun; Li, Wei-Di; Huang, Fang; Zhang, Jin-Ming; Xu, Fang-Cheng; Lu, Yao-Bin

2013-05-01

Phloem-feeding whiteflies in the species complex Bemisia tabaci cause extensive crop damage worldwide. One of the reasons for their "success" is their ability to suppress the effectual jasmonic acid (JA) defenses of the host plant. However, little is understood about the mechanisms underlying whitefly suppression of JA-regulated defenses. Here, we showed that the expression of salicylic acid (SA)-responsive genes (EDS1 and PR1) in Arabidopsis thaliana was significantly enhanced during feeding by whitefly nymphs. Whereas upstream JA-responsive genes (LOX2 and OPR3) also were induced, the downstream JA-responsive gene (VSP1) was repressed, i.e., whiteflies only suppressed downstream JA signaling. Gene-expression analyses with various Arabidopsis mutants, including NahG, npr-1, ein2-1, and dde2-2, revealed that SA signaling plays a key role in the suppression of downstream JA defenses by whitefly feeding. Assays confirmed that SA activation enhanced whitefly performance by suppressing downstream JA defenses.

Context shapes social judgments of positive emotion suppression and expression.

Science.gov (United States)

Kalokerinos, Elise K; Greenaway, Katharine H; Casey, James P

2017-02-01

It is generally considered socially undesirable to suppress the expression of positive emotion. However, previous research has not considered the role that social context plays in governing appropriate emotion regulation. We investigated a context in which it may be more appropriate to suppress than express positive emotion, hypothesizing that positive emotion expressions would be considered inappropriate when the valence of the expressed emotion (i.e., positive) did not match the valence of the context (i.e., negative). Six experiments (N = 1,621) supported this hypothesis: when there was a positive emotion-context mismatch, participants rated targets who suppressed positive emotion as more appropriate, and evaluated them more positively than targets who expressed positive emotion. This effect occurred even when participants were explicitly made aware that suppressing targets were experiencing mismatched emotion for the context (e.g., feeling positive in a negative context), suggesting that appropriate emotional expression is key to these effects. These studies are among the first to provide empirical evidence that social costs to suppression are not inevitable, but instead are dependent on context. Expressive suppression can be a socially useful emotion regulation strategy in situations that call for it. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Vital Signs-HIV Care Saves Lives: Viral Suppression is Key

Centers for Disease Control (CDC) Podcasts

This podcast is based on the December 2014 CDC Vital Signs report. For people living with HIV, Viral suppression is critical. By getting tested and taking HIV medicines, individuals living with HIV can achieve very low levels of HIV in the body.

The nonstructural proteins of Nipah virus play a key role in pathogenicity in experimentally infected animals.

Directory of Open Access Journals (Sweden)

Misako Yoneda

Full Text Available Nipah virus (NiV P gene encodes P protein and three accessory proteins (V, C and W. It has been reported that all four P gene products have IFN antagonist activity when the proteins were transiently expressed. However, the role of those accessory proteins in natural infection with NiV remains unknown. We generated recombinant NiVs lacking V, C or W protein, rNiV(V-, rNiV(C-, and rNiV(W-, respectively, to analyze the functions of these proteins in infected cells and the implications in in vivo pathogenicity. All the recombinants grew well in cell culture, although the maximum titers of rNiV(V- and rNiV(C- were lower than the other recombinants. The rNiV(V-, rNiV(C- and rNiV(W- suppressed the IFN response as well as the parental rNiV, thereby indicating that the lack of each accessory protein does not significantly affect the inhibition of IFN signaling in infected cells. In experimentally infected golden hamsters, rNiV(V- and rNiV(C- but not the rNiV(W- virus showed a significant reduction in virulence. These results suggest that V and C proteins play key roles in NiV pathogenicity, and the roles are independent of their IFN-antagonist activity. This is the first report that identifies the molecular determinants of NiV in pathogenicity in vivo.

HIV Care Saves Lives: Viral Suppression is Key PSA (:60)

Centers for Disease Control (CDC) Podcasts

This 60 second Public Service Announcement is based on the December 2014 Vital Signs. For people living with HIV, Viral suppression is critical. By getting tested and taking HIV medicines, individuals living with HIV can achieve very low levels of HIV in the body.

Nuclear EMP: key suppression device parameters for EMP hardening

International Nuclear Information System (INIS)

Durgin, D.L.; Brown, R.M.

1975-03-01

The electrical transients induced by EMP exhibit unique characteristics which differ considerably from transients associated with other phenomena such as lightning, switching, and circuit malfunctions. The suppression techniques developed to handle more common transients, though not necessarily the same devices, can be used for EMP damage protection. The suppression devices used for circuit level EMP protection are referred to as Terminal Protection Devices (TPD). Little detailed data describing the response of TPD's to EMP-related transients have been published. While most vendors publish specifications for TPD performance, there is little standardization of parameters and TPD response models are not available. This lack of parameter standardization has resulted in a proliferation of test data that is sometimes conflicting and often not directly comparable. This paper derives and/or defines a consistent set of parameters based on EMP circuit hardening requirements and on measurable component parameters and is concerned only with use of TPD's to prevent permanent damage. Three sets of parameters pertaining to pertinent TPD functional characteristics were defined as follows: standby parameters, protection parameters, and failure parameters. These parameters are used to evaluate a representative sample of TPD's and the results are presented in matrix form to facilitate the selection of devices for specific hardening problems

Novel "Elements" of Immune Suppression within the Tumor Microenvironment.

Science.gov (United States)

Gurusamy, Devikala; Clever, David; Eil, Robert; Restifo, Nicholas P

2017-06-01

Adaptive evolution has prompted immune cells to use a wide variety of inhibitory signals, many of which are usurped by tumor cells to evade immune surveillance. Although tumor immunologists often focus on genes and proteins as mediators of immune function, here we highlight two elements from the periodic table-oxygen and potassium-that suppress the immune system in previously unappreciated ways. While both are key to the maintenance of T-cell function and tissue homeostasis, they are exploited by tumors to suppress immuno-surveillance and promote metastatic spread. We discuss the temporal and spatial roles of these elements within the tumor microenvironment and explore possible therapeutic interventions for effective and promising anticancer therapies. Cancer Immunol Res; 5(6); 426-33. ©2017 AACR . ©2017 American Association for Cancer Research.

Conformational flexibility of BECN1: Essential to its key role in autophagy and beyond: BECN1 Structure and Mechanism

Energy Technology Data Exchange (ETDEWEB)

Mei, Yang [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050; Glover, Karen [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050; Su, Minfei [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050; Sinha, Sangita C. [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050

2016-08-13

BECN1 (Beclin 1), a highly conserved eukaryotic protein, is a key regulator of autophagy, a cellular homeostasis pathway, and also participates in vacuolar protein sorting, endocytic trafficking, and apoptosis. BECN1 is important for embryonic development, the innate immune response, tumor suppression, and protection against neurodegenerative disorders, diabetes, and heart disease. BECN1 mediates autophagy as a core component of the class III phosphatidylinositol 3-kinase complexes. However, the exact mechanism by which it regulates the activity of these complexes, or mediates its other diverse functions is unclear. BECN1 interacts with several diverse protein partners, perhaps serving as a scaffold or interaction hub for autophagy. Based on extensive structural, biophysical and bioinformatics analyses, BECN1 consists of an intrinsically disordered region (IDR), which includes a BH3 homology domain (BH3D); a flexible helical domain (FHD); a coiled-coil domain (CCD); and a β-α-repeated autophagy-specific domain (BARAD). Each of these BECN1 domains mediates multiple diverse interactions that involve concomitant conformational changes. Thus, BECN1 conformational flexibility likely plays a key role in facilitating diverse protein interactions. Further, BECN1 conformation and interactions are also modulated by numerous post-translational modifications. A better structure-based understanding of the interplay between different BECN1 conformational and binding states, and the impact of post-translational modifications will be essential to elucidating the mechanism of its multiple biological roles.

Social Hierarchy and Depression: The Role of Emotion Suppression

OpenAIRE

Langner, Carrie A.; Epel, Elissa; Matthews, Karen; Moskowitz, Judith T.; Adler, Nancy

2012-01-01

Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depre...

Why expressive suppression does not pay? Cognitive costs of negative emotion suppression: The mediating role of subjective tense-arousal

Directory of Open Access Journals (Sweden)

Szczygieł Dorota

2015-09-01

Full Text Available The aim of this paper was to contribute to a broader understanding of the cognitive consequences of expressive suppression. Specifically, we examined whether the deteriorating effect of expressive suppression on cognitive functioning is caused by tense arousal enhanced by suppression. Two experiments were performed in order to test this prediction. In both studies we tested the effect of expressive suppression on working memory, as measured with a backwards digit-span task (Study 1, N = 43 and anagram problem-solving task (Study 2, N = 60. In addition, in Study 2 we tested whether expressive suppression degrades memory of the events that emerged during the period of expressive suppression. Both studies were conducted in a similar design: Participants watched a film clip which evoked negative emotions (i.e. disgust in Study 1 and a combination of sadness and anxiety in Study 2 under the instruction to suppress those negative emotions or (in the control condition to simply watch the film. The results of these experiments lead to three conclusions. First, the results reveal that expressive suppression degrades memory of the events that emerged during the period of expressive suppression and leads to poorer performance on working memory tasks, as measured with a backwards digit-span task and anagram problem-solving task. Second, the results indicate that expressive suppression leads to a significant increase in subjective tense arousal. Third, the results support our prediction that expressive suppression decreases cognitive performance through its effects on subjective tense arousal. The results of the Study 1 show that tense arousal activated during expressive suppression of disgust fully mediates the negative effect of suppression on working memory as measured with a backwards digit-span task. The results of Study 2 reveal that subjective tense arousal elicited while suppressing sadness and anxiety mediates both the effect of suppression on

Vitamin K3 suppressed inflammatory and immune responses in a redox-dependent manner.

Science.gov (United States)

Checker, Rahul; Sharma, Deepak; Sandur, Santosh K; Khan, Nazir M; Patwardhan, Raghavendra S; Kohli, Vineet; Sainis, Krishna B

2011-08-01

Recent investigations suggest that cellular redox status may play a key role in the regulation of several immune functions. Treatment of lymphocytes with vitamin K3 (menadione) resulted in a significant decrease in cellular GSH/GSSG ratio and concomitant increase in the ROS levels. It also suppressed Concanavalin A (Con A)-induced proliferation and cytokine production in lymphocytes and CD4 + T cells in vitro. Immunosuppressive effects of menadione were abrogated only by thiol containing antioxidants. Mass spectrometric analysis showed that menadione directly interacted with thiol antioxidant GSH. Menadione completely suppressed Con A-induced activation of ERK, JNK and NF-κB in lymphocytes. It also significantly decreased the homeostasis driven proliferation of syngeneic CD4 + T cells. Further, menadione significantly delayed graft-vs-host disease morbidity and mortality in mice. Menadione suppressed phytohemagglutinin-induced cytokine production in human peripheral blood mononuclear cells. These results reveal that cellular redox perturbation by menadione is responsible for significant suppression of lymphocyte responses.

A role for PML in innate immunity

NARCIS (Netherlands)

A. Lunardi (Andrea); M. Gaboli (Mirella); M. Giorgio (Marco); R. Rivi (Roberta); A. Bygrave (Anne); D.D. Drabek (Dubravka); E.A. Dzierzak (Elaine); M. Fagioli (Marta); L. Salmena (Leonardo); M. Antoniou (Michael); M. Botto (Marina); C. Cordon-Cardo (Carlos); L. Luzzatto (Lucio); P.G. Pelicci; F.G. Grosveld (Frank); P.P. Pandolfi

2011-01-01

textabstractThe promyelocytic leukemia gene (PML) of acute promyelocytic leukemia is an established tumor suppressor gene with critical functions in growth suppression, induction of apoptosis, and cellular senescence. Interestingly, although less studied, PML seems to play a key role also in immune

Bromodomain and Extra Terminal (BET Inhibitor Suppresses Macrophage-Driven Steroid-Resistant Exacerbations of Airway Hyper-Responsiveness and Inflammation.

Directory of Open Access Journals (Sweden)

Thi Hiep Nguyen

Full Text Available Exacerbations of asthma are linked to significant decline in lung function and are often poorly controlled by corticosteroid treatment. Clinical investigations indicate that viral and bacterial infections play crucial roles in the onset of steroid-resistant inflammation and airways hyperresponsiveness (AHR that are hallmark features of exacerbations. We have previously shown that interferon γ (IFNγ and lipopolysaccharide (LPS cooperatively activate pulmonary macrophages and induce steroid-resistant airway inflammation and AHR in mouse models. Furthermore, we have established a mouse model of respiratory syncytial virus (RSV-induced exacerbation of asthma, which exhibits macrophage-dependent, steroid-resistant lung disease. Emerging evidence has demonstrated a key role for bromo- and extra-terminal (BET proteins in the regulation of inflammatory gene expression in macrophages. We hypothesised that BET proteins may be involved in the regulation of AHR and airway inflammation in our steroid-resistant exacerbation models.We investigated the effects of a BET inhibitor (I-BET-762 on the development of steroid-resistant AHR and airway inflammation in two mouse models. I-BET-762 administration decreased macrophage and neutrophil infiltration into the airways, and suppressed key inflammatory cytokines in both models. I-BET treatment also suppressed key inflammatory cytokines linked to the development of steroid-resistant inflammation such as monocyte chemoattractant protein 1 (MCP-1, keratinocyte-derived protein chemokine (KC, IFNγ, and interleukin 27 (IL-27. Attenuation of inflammation was associated with suppression of AHR.Our results suggest that BET proteins play an important role in the regulation of steroid-resistant exacerbations of airway inflammation and AHR. BET proteins may be potential targets for the development of future therapies to treat steroid-resistant inflammatory components of asthma.

A role for suppressed skeletal muscle thermogenesis in pathways from weight fluctuations to the insulin resistance syndrome.

Science.gov (United States)

Dulloo, A G

2005-08-01

An impressive body of epidemiological evidence suggests that a history of large perturbations in body weight earlier in life, independently of excess weight, is a risk factor for later development of insulin-related complications, namely central obesity, type 2 diabetes and cardiovascular disease. Such an increased risk has been reported in men and women who in young adulthood experienced weight fluctuations that involved weight recovery after weight loss caused by disease, famine or voluntary 'yoyo' dieting, and is particularly strong when the weight fluctuations occurred much earlier in life and are characterized by catch-up growth after foetal and/or neonatal growth retardation. As the phase of weight recovery/catch-up growth is associated with both hyperinsulinaemia and an accelerated rate for recovering fat mass (i.e. catch-up fat), the questions arise as to whether, why and how processes that regulate catch-up fat might predispose to hyperinsulinaemia and to insulin-related diseases. In addressing these issues, this paper first reviews evidence for the existence of an adipose-specific control of thermogenesis, whose suppression contributes to the phenomenon of catch-up fat during weight recovery/catch-up growth. It subsequently concentrates upon recent findings suggesting that: (i) such suppression of thermogenesis directed at catch-up fat is accompanied by a redistribution of glucose from skeletal muscle to white adipose tissue, and (ii) substrate cycling between de novo lipogenesis and lipid oxidation can operate as a thermogenic effector in skeletal muscle in response to signalling interactions between leptin and insulin - two key 'adiposity' hormones implicated in the peripheral control of substrate metabolism. These new findings are integrated into the proposal that, in its 'evolutionary adaptive' role to spare glucose for rapid rebuilding of the fat stores, suppressed thermogenesis in skeletal muscle - via inhibition of substrate cycling between de novo

Vital Signs-HIV Care Saves Lives: Viral Suppression is Key

Centers for Disease Control (CDC) Podcasts

2014-11-25

This podcast is based on the December 2014 CDC Vital Signs report. For people living with HIV, Viral suppression is critical. By getting tested and taking HIV medicines, individuals living with HIV can achieve very low levels of HIV in the body.  Created: 11/25/2014 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 11/25/2014.

HIV Care Saves Lives: Viral Suppression is Key PSA (:60)

Centers for Disease Control (CDC) Podcasts

2014-11-25

This 60 second Public Service Announcement is based on the December 2014 Vital Signs. For people living with HIV, Viral suppression is critical. By getting tested and taking HIV medicines, individuals living with HIV can achieve very low levels of HIV in the body.  Created: 11/25/2014 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 11/25/2014.

Functional inhibition of UQCRB suppresses angiogenesis in zebrafish

Energy Technology Data Exchange (ETDEWEB)

Cho, Yoon Sun; Jung, Hye Jin [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Seok, Seung Hyeok [Department of Microbiology and Immunology, Institute for Experimental Animals, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Payumo, Alexander Y.; Chen, James K. [Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305 (United States); Kwon, Ho Jeong, E-mail: kwonhj@yonsei.ac.kr [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

2013-04-19

Highlights: ► This is the first functional characterization of UQCRB in vivo model. ► Angiogenesis is inhibited with UQCRB loss of function in zebrafish. ► UQCRB is introduced as a prognostic marker for mitochondria- and angiogenesis-related diseases. -- Abstract: As a subunit of mitochondrial complex III, UQCRB plays an important role in complex III stability, electron transport, and cellular oxygen sensing. Herein, we report UQCRB function regarding angiogenesis in vivo with the zebrafish (Danio rerio). UQCRB knockdown inhibited angiogenesis in zebrafish leading to the suppression of VEGF expression. Moreover, the UQCRB-targeting small molecule terpestacin also inhibited angiogenesis and VEGF levels in zebrafish, supporting the role of UQCRB in angiogenesis. Collectively, UQCRB loss of function by either genetic and pharmacological means inhibited angiogenesis, indicating that UQCRB plays a key role in this process and can be a prognostic marker of angiogenesis- and mitochondria-related diseases.

Functional inhibition of UQCRB suppresses angiogenesis in zebrafish

International Nuclear Information System (INIS)

Cho, Yoon Sun; Jung, Hye Jin; Seok, Seung Hyeok; Payumo, Alexander Y.; Chen, James K.; Kwon, Ho Jeong

2013-01-01

Highlights: ► This is the first functional characterization of UQCRB in vivo model. ► Angiogenesis is inhibited with UQCRB loss of function in zebrafish. ► UQCRB is introduced as a prognostic marker for mitochondria- and angiogenesis-related diseases. -- Abstract: As a subunit of mitochondrial complex III, UQCRB plays an important role in complex III stability, electron transport, and cellular oxygen sensing. Herein, we report UQCRB function regarding angiogenesis in vivo with the zebrafish (Danio rerio). UQCRB knockdown inhibited angiogenesis in zebrafish leading to the suppression of VEGF expression. Moreover, the UQCRB-targeting small molecule terpestacin also inhibited angiogenesis and VEGF levels in zebrafish, supporting the role of UQCRB in angiogenesis. Collectively, UQCRB loss of function by either genetic and pharmacological means inhibited angiogenesis, indicating that UQCRB plays a key role in this process and can be a prognostic marker of angiogenesis- and mitochondria-related diseases

Targeting acceptance in the management of food craving: The mediating roles of eating styles and thought suppression.

Science.gov (United States)

Coffino, Jaime A; Heiss, Sydney; Hormes, Julia M

2018-04-01

Food craving is now widely considered to be a cognitively motivated state. Acceptance-based treatments are effective in reducing the adverse impact of food cravings on consumption, via a hypothesized decrease in experiential avoidance. The mechanisms that drive the success of acceptance-based management of craving remain to be empirically tested. This study examined the role of eating styles and thought suppression as mediators in the relationship between experiential avoidance and craving. Participants (n = 298, 51.5% female) completed the Food Craving Acceptance and Awareness Questionnaire (FAAQ), the Dutch Eating Behavior Questionnaire (DEBQ), the White Bear Suppression Inventory (WBSI; a measure of thought suppression), and the reduced version of the Food Craving Questionnaire- Trait (FCQ-T-r). Scores on the FAAQ were inversely associated with scores on the FCQ-T-r, DEBQ, and WBSI; FCQ-T-r scores were positively correlated with scores on the DEBQ and WBSI (all p styles and thought suppression, acceptance remained a significant predictor of craving. Results thus provide initial evidence that eating styles and thought suppression mediate the relationship between food-specific experiential avoidance and food craving. Findings lay the foundation for future study of the proximal antecedents of food cravings and lend preliminary support for targeting thought suppression and eating styles in acceptance-based approaches to the management of craving. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Role of Thought Suppression, Meta-Cognitive Factors and Negative Emotions in Prediction of Substance Dependency Disorder

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Omid Saed

2011-08-01

Full Text Available Introduction: This study investigated the role of thought suppression, meta- cognitive factors, and negative emotions in predicting of substance dependency disorder. Method: Subjects were 70 patients with substance dependence disorder and 70 normal individuals (total 140. Substance dependants were selected of outpatient treatment centers and the normal sample was selected of the general population too. Sampling methods in both samples were convenience sampling. All people were assessed by MCQ-30, White Bear Suppression Inventory, and Beck’s Anxiety and Depression Questionnaires. For data analysis, discriminant analysis were used. Results: Negative meta-cognitive beliefs about worry, depression, and thought suppression were the most significant predictors of substance dependence disorder. Conclusion: Through meta-cognitive beliefs, thought suppression and negative emotion (especially depression, substance dependency disorder can be predicted. Based on this model can be used to take a substance dependency disorder prevention approach and psychotherapy approach (based on cognitive and meta-cognitive therapies. In addition, the findings of this research can be applied in clinical and counseling environments to help substance dependant clients.

An efficient approach to suppress the negative role of contrarian oscillators in synchronization

Science.gov (United States)

Zhang, Xiyun; Ruan, Zhongyuan; Liu, Zonghua

2013-09-01

It has been found that contrarian oscillators usually take a negative role in the collective behaviors formed by conformist oscillators. However, experiments revealed that it is also possible to achieve a strong coherence even when there are contrarians in the system such as neuron networks with both excitable and inhibitory neurons. To understand the underlying mechanism of this abnormal phenomenon, we here consider a complex network of coupled Kuramoto oscillators with mixed positive and negative couplings and present an efficient approach, i.e., tit-for-tat strategy, to suppress the negative role of contrarian oscillators in synchronization and thus increase the order parameter of synchronization. Two classes of contrarian oscillators are numerically studied and a brief theoretical analysis is provided to explain the numerical results.

Co-operative suppression of inflammatory responses in human dendritic cells by plant proanthocyanidins and products from the parasitic nematode Trichuris suis

DEFF Research Database (Denmark)

Williams, Andrew R; Klaver, Elsenoor J; Laan, Lisa C

2017-01-01

Interactions between dendritic cells (DCs) and environmental, dietary and pathogen antigens play a key role in immune homeostasis and regulation of inflammation. Dietary polyphenols such as proanthocyanidins (PAC) may reduce inflammation, and we therefore hypothesized that PAC may suppress lipopo...

Resilience in homeless youth: the key role of self-esteem.

Science.gov (United States)

Kidd, Sean; Shahar, Golan

2008-04-01

This study examined the protective role of self-esteem, social involvement, and secure attachment among homeless youths. These protective factors were examined as they ameliorate risks among 208 homeless youths surveyed in New York City and Toronto. Both mental and physical health indicators were employed in this study, including loneliness, feeling trapped, suicidal ideation, subjective health status, and substance use. Self-esteem emerged as a key protective factor, predicting levels of loneliness, feeling trapped, and suicide ideation, and buffering against the deleterious effect of fearful attachment on loneliness. Findings highlight the role of the self-concept in risk and resilience among homeless youth. Copyright 2008 APA, all rights reserved.

Human MLH1 suppresses the insertion of telomeric sequences at intra-chromosomal sites in telomerase-expressing cells

Science.gov (United States)

Jia, Pingping; Chastain, Megan; Zou, Ying; Her, Chengtao

2017-01-01

Abstract Aberrant formation of interstitial telomeric sequences (ITSs) promotes genome instabilities. However, it is unclear how aberrant ITS formation is suppressed in human cells. Here, we report that MLH1, a key protein involved in mismatch repair (MMR), suppresses telomeric sequence insertion (TSI) at intra-chromosomal regions. The frequency of TSI can be elevated by double-strand break (DSB) inducer and abolished by ATM/ATR inhibition. Suppression of TSI requires MLH1 recruitment to DSBs, indicating that MLH1's role in DSB response/repair is important for suppressing TSI. Moreover, TSI requires telomerase activity but is independent of the functional status of p53 and Rb. Lastly, we show that TSI is associated with chromosome instabilities including chromosome loss, micronuclei formation and chromosome breakage that are further elevated by replication stress. Our studies uncover a novel link between MLH1, telomerase, telomere and genome stability. PMID:28180301

MiR-124 suppresses cell proliferation in hepatocellular carcinoma by targeting PIK3CA

International Nuclear Information System (INIS)

Lang, Qingbo; Ling, Changquan

2012-01-01

Highlights: ► PIK3CA is a novel target of miR-124 in HepG2 cells. ► MiR-124 suppresses cell proliferation by downregulating PIK3CA expression. ► MiR-124 regulates the PI3K/Akt pathway in HepG2 cells. ► MiR-124 overexpression inhibits the tumorigenesis in nude mice. -- Abstract: MicroRNAs (miRNAs) have crucial roles in the development and progression of human cancers, including hepatocellular carcinoma (HCC). Recent studies have shown that microRNA-124 (miR-124) was downregulated in HCC; however, the underlying mechanisms by which miR-124 suppresses tumorigenesis in HCC are largely unknown. In this study, we report that phosphoinositide 3-kinase catalytic subunit alpha (PIK3CA) is a novel target of miR-124 in HepG2 cells. Overexpression of miR-124 resulted in decreased expression of PIK3CA at both mRNA and protein levels. We found that miR-124 overexpression markedly suppressed cell proliferation by inducing G1-phase cell-cycle arrest in vitro. Consistent with the restoring miR-124 expression, PIK3CA knockdown suppressed cell proliferation, whereas overexpression of PIK3CA abolished the suppressive effect of miR-124. Mechanistic studies showed that miR-124-mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. The expressions of Akt and mTOR, key components of the PI3K/Akt pathway, were all downregulated. Moreover, we found overexpressed miR-124 effectively repressed tumor growth in xenograft animal experiments. Taken together, our results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA.

MiR-124 suppresses cell proliferation in hepatocellular carcinoma by targeting PIK3CA

Energy Technology Data Exchange (ETDEWEB)

Lang, Qingbo [Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Ling, Changquan, E-mail: lingchangquan@hotmail.com [Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

2012-09-21

Highlights: Black-Right-Pointing-Pointer PIK3CA is a novel target of miR-124 in HepG2 cells. Black-Right-Pointing-Pointer MiR-124 suppresses cell proliferation by downregulating PIK3CA expression. Black-Right-Pointing-Pointer MiR-124 regulates the PI3K/Akt pathway in HepG2 cells. Black-Right-Pointing-Pointer MiR-124 overexpression inhibits the tumorigenesis in nude mice. -- Abstract: MicroRNAs (miRNAs) have crucial roles in the development and progression of human cancers, including hepatocellular carcinoma (HCC). Recent studies have shown that microRNA-124 (miR-124) was downregulated in HCC; however, the underlying mechanisms by which miR-124 suppresses tumorigenesis in HCC are largely unknown. In this study, we report that phosphoinositide 3-kinase catalytic subunit alpha (PIK3CA) is a novel target of miR-124 in HepG2 cells. Overexpression of miR-124 resulted in decreased expression of PIK3CA at both mRNA and protein levels. We found that miR-124 overexpression markedly suppressed cell proliferation by inducing G1-phase cell-cycle arrest in vitro. Consistent with the restoring miR-124 expression, PIK3CA knockdown suppressed cell proliferation, whereas overexpression of PIK3CA abolished the suppressive effect of miR-124. Mechanistic studies showed that miR-124-mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. The expressions of Akt and mTOR, key components of the PI3K/Akt pathway, were all downregulated. Moreover, we found overexpressed miR-124 effectively repressed tumor growth in xenograft animal experiments. Taken together, our results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA.

Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression.

Directory of Open Access Journals (Sweden)

Alejo Efeyan

Full Text Available Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability.

Key role of microRNA-15a in the KLF4 suppressions of proliferation and angiogenesis in endothelial and vascular smooth muscle cells

International Nuclear Information System (INIS)

Zheng, Xuemei; Li, Aiqin; Zhao, Liang; Zhou, Tengfei; Shen, Qiang; Cui, Qinghua; Qin, Xiaomei

2013-01-01

Highlights: •This is the first demonstration that miR-15a is a novel target gene of KLF4. •A novel finding that KLF4 increases the expression of miR-15a in ECs and VSMCs. •The novel mechanism is that KLF4 inhibits the proliferation of ECs via miR-15a. •The novel mechanism is that KLF4 inhibits the proliferation of VSMCs via miR-15. •miR-15a mediates the anti-angiogenic activity of KLF4. -- Abstract: While recent insights indicate that the transcription factor Krüppel-like factor 4 (KLF4) is indispensable for vascular homeostasis, its exact role in proliferation and angiogenesis and how it functions remain unresolved. Thus, the aim of the present study was to evaluate the role of KLF4 in the proliferations of endothelial and vascular smooth muscle cells, as well as the angiogenesis. The overexpression of KLF4 in endothelial cells significantly impaired tube formation. KLF4 inhibited the formation of a vascular network in implanted Matrigel plugs in nude mice. Importantly, we found that KLF4 significantly upregulated the miR-15a expression in endothelial cells and vascular smooth muscle cells, and conversely, KLF4 depletion reduced the amount of miR-15a. Furthermore, KLF4 blocked cell cycle progression and decreased cyclin D1 expression in endothelial cells and vascular smooth muscle cells through the induction of miR-15a. Intriguingly, the delivery of a miR-15a antagomir to nude mice resulted in marked attenuation of the anti-angiogenic effect of KLF4. Collectively, our present study provide the first evidence that miR-15a as a direct transcriptional target of KLF4 that mediates the anti-proliferative and anti-angiogenic actions of KLF4, which indicates that KLF4 upregulation of miR-15a may represent a therapeutic option to suppress proliferative vascular disorders

Key role of microRNA-15a in the KLF4 suppressions of proliferation and angiogenesis in endothelial and vascular smooth muscle cells

Energy Technology Data Exchange (ETDEWEB)

Zheng, Xuemei; Li, Aiqin; Zhao, Liang; Zhou, Tengfei; Shen, Qiang [Institute of Cardiovascular Science, Peking University Health Science Center, Beijing 100191 (China); Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, Peking University Health Science Center, Beijing 100191 (China); Cui, Qinghua [Department of Biomedical Informatics, Peking University Health Science Center, Beijing 100191 (China); Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, Peking University Health Science Center, Beijing 100191 (China); Qin, Xiaomei, E-mail: xmqin@bjmu.edu.cn [Institute of Cardiovascular Science, Peking University Health Science Center, Beijing 100191 (China); Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, Peking University Health Science Center, Beijing 100191 (China)

2013-08-09

Highlights: •This is the first demonstration that miR-15a is a novel target gene of KLF4. •A novel finding that KLF4 increases the expression of miR-15a in ECs and VSMCs. •The novel mechanism is that KLF4 inhibits the proliferation of ECs via miR-15a. •The novel mechanism is that KLF4 inhibits the proliferation of VSMCs via miR-15. •miR-15a mediates the anti-angiogenic activity of KLF4. -- Abstract: While recent insights indicate that the transcription factor Krüppel-like factor 4 (KLF4) is indispensable for vascular homeostasis, its exact role in proliferation and angiogenesis and how it functions remain unresolved. Thus, the aim of the present study was to evaluate the role of KLF4 in the proliferations of endothelial and vascular smooth muscle cells, as well as the angiogenesis. The overexpression of KLF4 in endothelial cells significantly impaired tube formation. KLF4 inhibited the formation of a vascular network in implanted Matrigel plugs in nude mice. Importantly, we found that KLF4 significantly upregulated the miR-15a expression in endothelial cells and vascular smooth muscle cells, and conversely, KLF4 depletion reduced the amount of miR-15a. Furthermore, KLF4 blocked cell cycle progression and decreased cyclin D1 expression in endothelial cells and vascular smooth muscle cells through the induction of miR-15a. Intriguingly, the delivery of a miR-15a antagomir to nude mice resulted in marked attenuation of the anti-angiogenic effect of KLF4. Collectively, our present study provide the first evidence that miR-15a as a direct transcriptional target of KLF4 that mediates the anti-proliferative and anti-angiogenic actions of KLF4, which indicates that KLF4 upregulation of miR-15a may represent a therapeutic option to suppress proliferative vascular disorders.

Quantitative measurement of interocular suppression in anisometropic amblyopia: a case-control study.

Science.gov (United States)

Li, Jinrong; Hess, Robert F; Chan, Lily Y L; Deng, Daming; Yang, Xiao; Chen, Xiang; Yu, Minbin; Thompson, Benjamin

2013-08-01

The aims of this study were to assess (1) the relationship between interocular suppression and visual function in patients with anisometropic amblyopia, (2) whether suppression can be simulated in matched controls using monocular defocus or neutral density filters, (3) the effects of spectacle or rigid gas-permeable contact lens correction on suppression in patients with anisometropic amblyopia, and (4) the relationship between interocular suppression and outcomes of occlusion therapy. Case-control study (aims 1-3) and cohort study (aim 4). Forty-five participants with anisometropic amblyopia and 45 matched controls (mean age, 8.8 years for both groups). Interocular suppression was assessed using Bagolini striated lenses, neutral density filters, and an objective psychophysical technique that measures the amount of contrast imbalance between the 2 eyes that is required to overcome suppression (dichoptic motion coherence thresholds). Visual acuity was assessed using a logarithm minimum angle of resolution tumbling E chart and stereopsis using the Randot preschool test. Interocular suppression assessed using dichoptic motion coherence thresholds. Patients exhibited significantly stronger suppression than controls, and stronger suppression was correlated significantly with poorer visual acuity in amblyopic eyes. Reducing monocular acuity in controls to match that of cases using neutral density filters (luminance reduction) resulted in levels of interocular suppression comparable with that in patients. This was not the case for monocular defocus (optical blur). Rigid gas-permeable contact lens correction resulted in less suppression than spectacle correction, and stronger suppression was associated with poorer outcomes after occlusion therapy. Interocular suppression plays a key role in the visual deficits associated with anisometropic amblyopia and can be simulated in controls by inducing a luminance difference between the eyes. Accurate quantification of suppression

Benzyl isothiocyanate suppresses pancreatic tumor angiogenesis and invasion by inhibiting HIF-α/VEGF/Rho-GTPases: pivotal role of STAT-3.

Directory of Open Access Journals (Sweden)

Srinivas Reddy Boreddy

Full Text Available Our previous studies have shown that benzyl isothiocyanate (BITC suppresses pancreatic tumor growth by inhibiting STAT-3; however, the exact mechanism of tumor growth suppression was not clear. Here we evaluated the effects and mechanism of BITC on pancreatic tumor angiogenesis. Our results reveal that BITC significantly inhibits neovasularization on rat aorta and Chicken-Chorioallantoic membrane. Furthermore, BITC blocks the migration and invasion of BxPC-3 and PanC-1 pancreatic cancer cells in a dose dependant manner. Moreover, secretion of VEGF and MMP-2 in normoxic and hypoxic BxPC-3 and PanC-1 cells was significantly suppressed by BITC. Both VEGF and MMP-2 play a critical role in angiogenesis and metastasis. Our results reveal that BITC significantly suppresses the phosphorylation of VEGFR-2 (Tyr-1175, and expression of HIF-α. Rho-GTPases, which are regulated by VEGF play a crucial role in pancreatic cancer progression. BITC treatment reduced the expression of RhoC whereas up-regulated the expression of tumor suppressor RhoB. STAT-3 over-expression or IL-6 treatment significantly induced HIF-1α and VEGF expression; however, BITC substantially suppressed STAT-3 as well as STAT-3-induced HIF-1α and VEGF expression. Finally, in vivo tumor growth and matrigel-plug assay show reduced tumor growth and substantial reduction of hemoglobin content in the matrigel plugs and tumors of mice treated orally with 12 µmol BITC, indicating reduced tumor angiogenesis. Immunoblotting of BITC treated tumors show reduced expression of STAT-3 phosphorylation (Tyr-705, HIF-α, VEGFR-2, VEGF, MMP-2, CD31 and RhoC. Taken together, our results suggest that BITC suppresses pancreatic tumor growth by inhibiting tumor angiogenesis through STAT-3-dependant pathway.

A Limited Role of p53 on the Ability of a Hexane Fraction of American Ginseng to Suppress Mouse Colitis

Directory of Open Access Journals (Sweden)

Deepak Poudyal

2012-01-01

Full Text Available Ulcerative colitis (UC is debilitating and carries a high colon cancer risk. Apoptosis of inflammatory cells is a key mechanism regulating UC. We have recently shown that American ginseng (AG, and to a greater extent, a Hexane fraction of AG (HAG can cause apoptosis and suppress mouse colitis through a p53-mediated mechanism. Here, we tested the hypothesis that HAG suppresses colitis through a p53 mechanism. We found only a limited impact of p53 in the ability of HAG to induce inflammatory cell apoptosis and suppress mouse colitis in vitro and in vivo. Finally, we asked whether HAG could cause cell cycle arrest of HCT116 colon cancer cells in vitro. Interestingly, HAG caused a G1 arrest of such cells independent of p53 status. Findings are significant because HAG suppresses colitis and associated colon cancer, and mutation in p53 is observed in most colitis-driven colon cancers. Therefore, HAG might be very effective in targeting the inflammatory cells and cancer cells since it induces apoptosis of inflammatory cells and cell cycle arrest in both p53−/− and WT p53 colon cancer cells.

Induction of regulatory T cells: A role for probiotics and prebiotics to suppress autoimmunity.

Science.gov (United States)

Dwivedi, Mitesh; Kumar, Prasant; Laddha, Naresh C; Kemp, E Helen

2016-04-01

Regulatory T cells (Tregs) are comprised of a heterogeneous population of cells that play a vital role in suppressing inflammation and maintaining immune tolerance. Given the crucial role of Tregs in maintaining immune homeostasis, it is probably not surprising that many microbial species and their metabolites have the potential to induce Tregs. There is now great interest in the therapeutic potential of probiotics and prebiotics based strategies for a range of autoimmune disorders. This review will summarise recent findings concerning the role of probiotics and prebiotics in induction of Tregs to ameliorate the autoimmune conditions. In addition, the article is focused to explain the different mechanisms of Treg induction and function by these probiotics and prebiotics, based on the available studies till date. The article further proposes that induction of Tregs by probiotics and prebiotics could lead to the development of new therapeutic approach towards curbing the autoimmune response and as an alternative to detrimental immunosuppressive drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Propylthiouracil Attenuates Experimental Pulmonary Hypertension via Suppression of Pen-2, a Key Component of Gamma-Secretase.

Directory of Open Access Journals (Sweden)

Ying-Ju Lai

Full Text Available Gamma-secretase-mediated Notch3 signaling is involved in smooth muscle cell (SMC hyper-activity and proliferation leading to pulmonary arterial hypertension (PAH. In addition, Propylthiouracil (PTU, beyond its anti-thyroid action, has suppressive effects on atherosclerosis and PAH. Here, we investigated the possible involvement of gamma-secretase-mediated Notch3 signaling in PTU-inhibited PAH. In rats with monocrotaline-induced PAH, PTU therapy improved pulmonary arterial hypertrophy and hemodynamics. In vitro, treatment of PASMCs from monocrotaline-treated rats with PTU inhibited their proliferation and migration. Immunocyto, histochemistry, and western blot showed that PTU treatment attenuated the activation of Notch3 signaling in PASMCs from monocrotaline-treated rats, which was mediated via inhibition of gamma-secretase expression especially its presenilin enhancer 2 (Pen-2 subunit. Furthermore, over-expression of Pen-2 in PASMCs from control rats increased the capacity of migration, whereas knockdown of Pen-2 with its respective siRNA in PASMCs from monocrotaline-treated rats had an opposite effect. Transfection of PASMCs from monocrotaline-treated rats with Pen-2 siRNA blocked the inhibitory effect of PTU on PASMC proliferation and migration, reflecting the crucial role of Pen-2 in PTU effect. We present a novel cell-signaling paradigm in which overexpression of Pen-2 is essential for experimental pulmonary arterial hypertension to promote motility and growth of smooth muscle cells. Propylthiouracil attenuates experimental PAH via suppression of the gamma-secretase-mediated Notch3 signaling especially its presenilin enhancer 2 (Pen-2 subunit. These findings provide a deep insight into the pathogenesis of PAH and a novel therapeutic strategy.

Differential roles of resistance to proactive interference and suppression of prepotent responses in overgeneral memory.

Science.gov (United States)

Comas, Michelle; Valentino, Kristin; Johnson, Anne F; Gibson, Bradley S; Taylor, Courtney

2018-06-12

Overgeneral memory (OGM), difficulty in retrieving specific autobiographical memories, is a robust phenomenon related to the onset and course of depressive and posttraumatic stress disorders. Inhibitory mechanisms are theorized to underlie OGM; however, empirical support for this link is equivocal. The current study examines the differential roles of two aspects of inhibitory control in association with OGM: suppression of prepotent responses and resistance to proactive interference (PI). Only resistance to PI was expected to be negatively related to OGM, whereby individuals with greater ability to resist PI would have reduced OGM. Participants (n = 49) completed a self-report measure of depressive symptoms and engaged in two tasks aimed at assessing resistance to PI and suppression of prepotent responses. Participants also completed a task assessing overgeneral autobiographical memory. As hypothesized, resistance to PI, but not suppression of prepotent responses negatively predicted OGM above and beyond the influence of depressive symptoms. Because a double dissociation was not examined, we cannot address the potential independence of the submechanisms of inhibitory control that we assessed. Results exemplify the differential associations of two components of inhibition and OGM, suggesting that resistance to PI, in particular, may contribute to the development and/or maintenance of OGM and associated depressive disorders. Directions for future research are discussed. Copyright © 2018. Published by Elsevier Ltd.

Oncogenic roles of TOPK and MELK, and effective growth suppression by small molecular inhibitors in kidney cancer cells.

Science.gov (United States)

Kato, Taigo; Inoue, Hiroyuki; Imoto, Seiya; Tamada, Yoshinori; Miyamoto, Takashi; Matsuo, Yo; Nakamura, Yusuke; Park, Jae-Hyun

2016-04-05

T-lymphokine-activated killer cell-originated protein kinase (TOPK) and maternal embryonic leucine zipper kinase (MELK) have been reported to play critical roles in cancer cell proliferation and maintenance of stemness. In this study, we investigated possible roles of TOPK and MELK in kidney cancer cells and found their growth promotive effect as well as some feedback mechanism between these two molecules. Interestingly, the blockade of either of these two kinases effectively caused downregulation of forkhead box protein M1 (FOXM1) activity which is known as an oncogenic transcriptional factor in various types of cancer cells. Small molecular compound inhibitors against TOPK (OTS514) and MELK (OTS167) effectively suppressed the kidney cancer cell growth, and the combination of these two compounds additively worked and showed the very strong growth suppressive effect on kidney cancer cells. Collectively, our results suggest that both TOPK and MELK are promising molecular targets for kidney cancer treatment and that dual blockade of OTS514 and OTS167 may bring additive anti-tumor effects with low risk of side effects.

Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression

International Nuclear Information System (INIS)

Ikuta, Togo; Kurosumi, Masafumi; Yatsuoka, Toshimasa; Nishimura, Yoji

2016-01-01

Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc"M"i"n"/"+mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression. - Highlights: • In the normal intestine, AhR was mainly localized in stroma containing immune cells. • In the tumor tissue, AhR expression was found in both stromal and tumor cells. • AhR knockdown promoted cell growth in colon cancer cell lines.

Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression

Energy Technology Data Exchange (ETDEWEB)

Ikuta, Togo, E-mail: togo@cancer-c.pref.saitama.jp [Department of Cancer Prevention, Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Kurosumi, Masafumi, E-mail: mkurosumi@cancer-c.pref.saitama.jp [Division of Pathology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Yatsuoka, Toshimasa, E-mail: yatsuoka-gi@umin.ac.jp [Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Nishimura, Yoji, E-mail: yojinish@cancr-c.pref.saitama.jp [Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan)

2016-05-01

Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc{sup Min/+}mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression. - Highlights: • In the normal intestine, AhR was mainly localized in stroma containing immune cells. • In the tumor tissue, AhR expression was found in both stromal and tumor cells. • AhR knockdown promoted cell growth in colon cancer cell lines.

Strategies for Supporting Physician-Scientists in Faculty Roles: A Narrative Review With Key Informant Consultations.

Science.gov (United States)

Lingard, Lorelei; Zhang, Peter; Strong, Michael; Steele, Margaret; Yoo, John; Lewis, James

2017-10-01

Physician-scientists are a population in decline globally. Solutions to reverse this decline often have focused on the training pipeline. Less attention has been paid to reducing attrition post training, when physician-scientists take up faculty roles. However, this period is a known time of vulnerability because of the pressures of clinical duties and the long timeline to securing independent research funding. This narrative review explored existing knowledge regarding how best to support physician-scientists for success in their faculty roles. The authors searched the Medline, Embase, ERIC, and Cochrane Library databases for articles published from 2000 to 2016 on this topic and interviewed key informants in 2015 to solicit their input on the review results. The authors reviewed 78 articles and interviewed 16 key informants. From the literature, they developed a framework of organizational (facilitate mentorship, foster community, value the physician-scientist role, minimize financial barriers) and individual (develop professional and research skills) strategies for supporting physician-scientists. They also outlined key knowledge gaps representing topics either rarely or never addressed in the reviewed articles (percent research time, structural hypocrisy, objective assessment, group metrics, professional identity). The key informants confirmed the identified strategies and discussed how the gaps were particularly important and impactful. This framework offers a basis for assessing an organization's existing support strategies, identifying outstanding needs, and developing targeted programming. The identified gaps require attention, as they threaten to undermine the benefits of existing support strategies.

The role of thyrotropin suppression in patients with differentiated thyroid carcinoma.

LENUS (Irish Health Repository)

Deasy, J

2010-07-01

Thyroid carcinoma is the commonest endocrine malignancy. The majority of these are differentiated thyroid carcinomas, which have a good overall prognosis. Treatment includes surgical excision, radio-iodine ablation and long-term thyrotropin suppression. The degree and length of suppression required, as well as the potential side-effect remain controversial. Therefore, the aim of this study was to establish the degree of thyrotropin suppression achieved in a cohort of patients with differentiated thyroid carcinoma. A retrospective review was performed of a prospectively maintained database. All patients with a diagnosis of differentiated thyroid carcinoma between January 1998 and January 2008 were identified. Demographic data, pathological stage and the treatment that the patient received was documented. TSH and free T4 levels were identified at specific time points post-operatively. Eighty-eight patients with differentiated thyroid carcinoma were identified. Seventy patients (79.5%) were female. The mean age was 55, with a range of 18 to 79 years. The majority of patients underwent a total thyroidectomy (n=79; 89.7%) and of those 29 (32.9%) had an associated modified neck dissection. Accurate follow-up was available on forty-nine patients. TSH and free T4 were measured at 3 and 6 months, as well as at 1 and 2 years post-operatively. Adequate TSH suppression was taken at a level < 0.1 mU\\/L. The majority of patients (69.5%) had achieved adequate TSH suppression at 2 years. However, 65% of these same patients had a high free T4 at 2 years indicating a degree of hyperthyroidism. This study has demonstrated that TSH suppression is being adequately achieved in the majority of patients with differentiated thyroid carcinoma. However, this must be carefully weighed against the potential detrimental side-effects of long-term sub-clinical hyperthyroidism.

Suppression Pools: paradigm of the thermalhydraulic effect on severe accidents

International Nuclear Information System (INIS)

Herranz, L. E.; Lopez del Pra, C.

2016-01-01

Influence of thermal-hydrualic phenomena on severe accident unforlding is beyond question. The present paper supports this statement on two key aspects of a severe accident: preservation of containment integrity and transport of fission products once released from fuel. To illustrate them, the attention is focused on suppression pools performance and, particularly, on some recent findings stemming from authors research of Fukushima scenarios. Gas behvaior at the injection point and its later evolution, potential axial and/or azimuthal stratification of the aqueous body or water saturation state, are some of the processes tha more strongly affect the role of pools as a mass and energy sink. They are described and discussed in detail. (Author)

Confirming the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials by PECVD

Science.gov (United States)

Liu, Yulin; Lin, Jinghuang; Jia, Henan; Chen, Shulin; Qi, Junlei; Qu, Chaoqun; Cao, Jian; Feng, Jicai; Fei, Weidong

2017-11-01

In order to confirm the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials (NCMs), here we report a novel strategy to create different Ar+ ion states in situ in plasma enhanced chemical vapor deposition (PECVD) by separating catalyst film from the substrate. Different bombardment environments on either side of the catalyst film were created simultaneously to achieve multi-layered structural NCMs. Results showed that Ar+ ion bombardment is crucial and complex for the growth of NCMs. Firstly, Ar+ ion bombardment has both positive and negative effects on carbon nanotubes (CNTs). On one hand, Ar+ ions can break up the graphic structure of CNTs and suppress thin CNT nucleation and growth. On the other hand, Ar+ ion bombardment can remove redundant carbon layers on the surface of large catalyst particles which is essential for thick CNTs. As a result, the diameter of the CNTs depends on the Ar+ ion state. As for vertically oriented few-layer graphene (VFG), Ar+ ions are essential and can even convert the CNTs into VFG. Therefore, by combining with the catalyst separation method, specific or multi-layered structural NCMs can be obtained by PECVD only by changing the intensity of Ar+ ion bombardment, and these special NCMs are promising in many fields.

Confirming the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials by PECVD.

Science.gov (United States)

Liu, Yulin; Lin, Jinghuang; Jia, Henan; Chen, Shulin; Qi, Junlei; Qu, Chaoqun; Cao, Jian; Feng, Jicai; Fei, Weidong

2017-11-24

In order to confirm the key role of Ar + ion bombardment in the growth feature of nanostructured carbon materials (NCMs), here we report a novel strategy to create different Ar + ion states in situ in plasma enhanced chemical vapor deposition (PECVD) by separating catalyst film from the substrate. Different bombardment environments on either side of the catalyst film were created simultaneously to achieve multi-layered structural NCMs. Results showed that Ar + ion bombardment is crucial and complex for the growth of NCMs. Firstly, Ar + ion bombardment has both positive and negative effects on carbon nanotubes (CNTs). On one hand, Ar + ions can break up the graphic structure of CNTs and suppress thin CNT nucleation and growth. On the other hand, Ar + ion bombardment can remove redundant carbon layers on the surface of large catalyst particles which is essential for thick CNTs. As a result, the diameter of the CNTs depends on the Ar + ion state. As for vertically oriented few-layer graphene (VFG), Ar + ions are essential and can even convert the CNTs into VFG. Therefore, by combining with the catalyst separation method, specific or multi-layered structural NCMs can be obtained by PECVD only by changing the intensity of Ar + ion bombardment, and these special NCMs are promising in many fields.

Role of cyclic nucleotide-dependent actin cytoskeletal dynamics:Ca(2+](i and force suppression in forskolin-pretreated porcine coronary arteries.

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Kyle M Hocking

Full Text Available Initiation of force generation during vascular smooth muscle contraction involves a rise in intracellular calcium ([Ca(2+]i and phosphorylation of myosin light chains (MLC. However, reversal of these two processes alone does not account for the force inhibition that occurs during relaxation or inhibition of contraction, implicating that other mechanisms, such as actin cytoskeletal rearrangement, play a role in the suppression of force. In this study, we hypothesize that forskolin-induced force suppression is dependent upon changes in actin cytoskeletal dynamics. To focus on the actin cytoskeletal changes, a physiological model was developed in which forskolin treatment of intact porcine coronary arteries (PCA prior to treatment with a contractile agonist resulted in complete suppression of force. Pretreatment of PCA with forskolin suppressed histamine-induced force generation but did not abolish [Ca(2+]i rise or MLC phosphorylation. Additionally, forskolin pretreatment reduced filamentous actin in histamine-treated tissues, and prevented histamine-induced changes in the phosphorylation of the actin-regulatory proteins HSP20, VASP, cofilin, and paxillin. Taken together, these results suggest that forskolin-induced complete force suppression is dependent upon the actin cytoskeletal regulation initiated by the phosphorylation changes of the actin regulatory proteins and not on the MLC dephosphorylation. This model of complete force suppression can be employed to further elucidate the mechanisms responsible for smooth muscle tone, and may offer cues to pathological situations, such as hypertension and vasospasm.

Molecular Targets of Nutraceuticals Derived from Dietary Spices: Potential Role in Suppression of Inflammation and Tumorigenesis

Science.gov (United States)

Aggarwal, Bharat B.; Van Kuiken, Michelle E.; Iyer, Laxmi H.; Harikumar, Kuzhuvelil B.; Sung, Bokyung

2011-01-01

Despite the fact cancer is primarily a preventable disease, recent statistics indicate cancer will become the number one killer worldwide in 2010. Since certain cancers are more prevalent in the people of some countries than others, suggests the role of lifestyle. For instance cancer incidence among people from the Indian subcontinent, where most spices are consumed, is much lower than that in the Western World. Spices have been consumed for centuries for a variety of purposes—as flavoring agents, colorants, and preservatives. However, there is increasing evidence for the importance of plant-based foods in regular diet to lowering the risk of most chronic diseases, so spices are now emerging as more than just flavor aids, but as agents that can not only prevent but may even treat disease. In this article, we discuss the role of 41 common dietary spices with over 182 spice-derived nutraceuticals for their effects against different stages of tumorigenesis. Besides suppressing inflammatory pathways, spice-derived nutraceuticals can suppress survival, proliferation, invasion, and angiogenesis of tumor cells. We discuss how spice-derived nutraceuticals mediate such diverse effects and what their molecular targets are. Overall our review suggests “adding spice to your life” may serve as a healthy and delicious way to ward off cancer and other chronic diseases. PMID:19491364

Corporate strategy in turbulent environments: Key roles of the corporate level

OpenAIRE

Caldart, Adrian A.; Ricart, Joan E.

2006-01-01

This paper analyzes the evolution during the period 1986-2002 of the corporate strategy of Lujan, a highly successful car components manufacturer headquartered in Spain, as a way to explore how the corporate level influences the successful evolution of a company exposed to a "turbulent" environment over a long period. We find that the corporate level plays three key roles. First, it drives a firm's evolution by developing a cognitive representation of the firm's competitive landscape. Second,...

The E2F transcription factors: key regulators of cell proliferation

DEFF Research Database (Denmark)

Müller, H; Helin, K

2000-01-01

Ever since its discovery, the RB-1 gene and the corresponding protein, pRB, have been a focal point of cancer research. The isolation of E2F transcription factors provided the key to our current understanding of RB-1 function in the regulation of the cell cycle and in tumor suppression....... It is becoming more and more evident that the regulatory circuits governing the cell cycle are very complex and highly interlinked. Certain aspects of RB-1 function, for instance its role in differentiation, cannot be easily explained by the current models of pRB-E2F interaction. One reason is that pRB has...

PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma

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Asoka Banno

2018-01-01

Full Text Available Asthma affects approximately 300 million people worldwide, significantly impacting quality of life and healthcare costs. While current therapies are effective in controlling many patients' symptoms, a large number continue to experience exacerbations or treatment-related adverse effects. Alternative therapies are thus urgently needed. Accumulating evidence has shown that the peroxisome proliferator-activated receptor (PPAR family of nuclear hormone receptors, comprising PPARα, PPARβ/δ, and PPARγ, is involved in asthma pathogenesis and that ligand-induced activation of these receptors suppresses asthma pathology. PPAR agonists exert their anti-inflammatory effects primarily by suppressing pro-inflammatory mediators and antagonizing the pro-inflammatory functions of various cell types relevant to asthma pathophysiology. Experimental findings strongly support the potential clinical benefits of PPAR agonists in the treatment of asthma. We review current literature, highlighting PPARs' key role in asthma pathogenesis and their agonists' therapeutic potential. With additional research and rigorous clinical studies, PPARs may become attractive therapeutic targets in this disease.

The role of type III effectors from Xanthomonas axonopodis pv. manihotis in virulence and suppression of plant immunity.

Science.gov (United States)

Medina, Cesar Augusto; Reyes, Paola Andrea; Trujillo, Cesar Augusto; Gonzalez, Juan Luis; Bejarano, David Alejandro; Montenegro, Nathaly Andrea; Jacobs, Jonathan M; Joe, Anna; Restrepo, Silvia; Alfano, James R; Bernal, Adriana

2018-03-01

Xanthomonas axonopodis pv. manihotis (Xam) causes cassava bacterial blight, the most important bacterial disease of cassava. Xam, like other Xanthomonas species, requires type III effectors (T3Es) for maximal virulence. Xam strain CIO151 possesses 17 predicted T3Es belonging to the Xanthomonas outer protein (Xop) class. This work aimed to characterize nine Xop effectors present in Xam CIO151 for their role in virulence and modulation of plant immunity. Our findings demonstrate the importance of XopZ, XopX, XopAO1 and AvrBs2 for full virulence, as well as a redundant function in virulence between XopN and XopQ in susceptible cassava plants. We tested their role in pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI) using heterologous systems. AvrBs2, XopR and XopAO1 are capable of suppressing PTI. ETI suppression activity was only detected for XopE4 and XopAO1. These results demonstrate the overall importance and diversity in functions of major virulence effectors AvrBs2 and XopAO1 in Xam during cassava infection. © 2017 BSPP AND JOHN WILEY & SONS LTD.

Dipeptidyl Peptidase-4 Inhibitor Anagliptin Prevents Intracranial Aneurysm Growth by Suppressing Macrophage Infiltration and Activation.

Science.gov (United States)

Ikedo, Taichi; Minami, Manabu; Kataoka, Hiroharu; Hayashi, Kosuke; Nagata, Manabu; Fujikawa, Risako; Higuchi, Sei; Yasui, Mika; Aoki, Tomohiro; Fukuda, Miyuki; Yokode, Masayuki; Miyamoto, Susumu

2017-06-19

Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP-4 (dipeptidyl peptidase-4) inhibitors have anti-inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP-4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model. IAs were surgically induced in 7-week-old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin. We measured the morphologic parameters of aneurysms over time and their local inflammatory responses. To investigate the molecular mechanisms, we used lipopolysaccharide-treated RAW264.7 macrophages. In the anagliptin-treated group, aneurysms were significantly smaller 2 to 4 weeks after IA induction. Anagliptin inhibited the accumulation of macrophages in IAs, reduced the expression of MCP-1 (monocyte chemotactic protein 1), and suppressed the phosphorylation of p65. In lipopolysaccharide-stimulated RAW264.7 cells, anagliptin treatment significantly reduced the production of tumor necrosis factor α, MCP-1, and IL-6 (interleukin 6) independent of GLP-1 (glucagon-like peptide 1), the key mediator in the antidiabetic effects of DPP-4 inhibitors. Notably, anagliptin activated ERK5 (extracellular signal-regulated kinase 5), which mediates the anti-inflammatory effects of statins, in RAW264.7 macrophages. Preadministration with an ERK5 inhibitor blocked the inhibitory effect of anagliptin on MCP-1 and IL-6 expression. Accordingly, the ERK5 inhibitor also counteracted the suppression of p65 phosphorylation in vitro. A DPP-4 inhibitor, anagliptin, prevents the growth of IAs via its anti-inflammatory effects on macrophages. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Thyroxin hormone suppression treatment

International Nuclear Information System (INIS)

Samuel, A.M.

1999-01-01

One of the important modalities of treatment of thyroid cancer (TC) after surgery is the administration of thyroxin as an adjuvant treatment. The analysis supports the theory that thyroid suppression plays an important role in patient management. 300 μg of thyroxin, as this is an adequate dose for suppression is given. Ideally the dose should be tailored by testing s-TSH levels. However, since a large number of the patients come from out station cities and villages this is impractical. We therefore depend on clinical criteria of hyperthyroid symptoms and adjust the dose. Very few patients need such adjustment

The role of primary care in adult weight management: qualitative interviews with key stakeholders in weight management services

OpenAIRE

Blane, David N.; Macdonald, Sara; Morrison, David; O’Donnell, Catherine A.

2017-01-01

Background Primary care has a key role to play in the prevention and management of obesity, but there remain barriers to engagement in weight management by primary care practitioners. The aim of this study was to explore the views of key stakeholders in adult weight management services on the role of primary care in adult weight management. Methods Qualitative study involving semi-structured interviews with nine senior dietitians involved in NHS weight management from seven Scottish health bo...

Compton suppression gamma ray spectrometry

International Nuclear Information System (INIS)

Landsberger, S.; Iskander, F.Y.; Niset, M.; Heydorn, K.

2002-01-01

In the past decade there have been many studies to use Compton suppression methods in routine neutron activation analysis as well as in the traditional role of low level gamma ray counting of environmental samples. On a separate path there have been many new PC based software packages that have been developed to enhance photopeak fitting. Although the newer PC based algorithms have had significant improvements, they still suffer from being effectively used in weak gamma ray lines in natural samples or in neutron activated samples that have very high Compton backgrounds. We have completed a series of experiments to show the usefulness of Compton suppression. As well we have shown the pitfalls when using Compton suppression methods for high counting deadtimes as in the case of neutron activated samples. We have also investigated if counting statistics are the same both suppressed and normal modes. Results are presented in four separate experiments. (author)

The role of TGFBI in mesothelioma and breast cancer: association with tumor suppression

International Nuclear Information System (INIS)

Li, Bingyan; Wen, Gengyun; Zhao, Yongliang; Tong, Jian; Hei, Tom K

2012-01-01

Transforming growth factor β induced (TGFBI) product, an extracellular matrix (ECM) protein, has been implicated as a putative tumor suppressor in recent studies. Our previous findings revealed that expression of TGFBI gene is down-regulated in a variety of cancer cell lines and clinical tissue samples. In this study, ectopic expression of TGFBI was used to ascertain its role as a tumor suppressor and to determine the underlying mechanism of mesothelioma and breast cancer. Cells were stably transfected with pRc/CMV2-TGFBI and pRc/CMV2-empty vector with Lipofectamine Plus. Ectopic expression of TGFBI was quantified by using quantitative PCR and Western-blotting. Characterization of cell viability was assessed using growth curve, clonogenic survival and soft agar growth. The potential of tumor formation was evaluated by an in vivo mouse model. Cell cycle was analyzed via flow cytometry. Expressions of p21, p53, p16 and p14 were examined using Western-blotting. Senescent cells were sorted by using a Senescence β-Galactosidase Staining Kit. Telomerase activity was measured using quantitative telomerase detection kit. In this study, an ectopic expression of TGFBI in two types of cancer cell lines, a mesothelioma cell line NCI-H28 and a breast cancer cell line MDA-MB-231 was found to have reduced the cellular growth, plating efficiency, and anchorage-independent growth. The tumorigenicity of these cancer cell lines as determined by subcutaneous inoculation in nude mice was similarly suppressed by TGFBI expression. Likewise, TGFBI expression reduced the proportion of S-phase while increased the proportion of G1 phase in these cells. The redistribution of cell cycle phase after re-expression of TGFBI was correspondent with transiently elevated expression of p21 and p53. The activities of senescence-associated β-galactosidase and telomerase were enhanced in TGFBI-transfected cells. Collectively, these results imply that TGFBI plays a suppressive role in the development

Novel Pectate Lyase Genes of Heterodera glycines Play Key Roles in the Early Stage of Parasitism.

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Huan Peng

Full Text Available Pectate lyases are known to play a key role in pectin degradation by catalyzing the random cleavage of internal polymer linkages (endo-pectinases. In this paper, four novel cDNAs, designated Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7, that encode pectate lyases were cloned and characterized from the soybean cyst nematode, Heterodera glycines. The predicted protein sequences of HG-PEL-3, HG-PEL-4 and HG-PEL-6 differed significantly in both their amino acid sequences and their genomic structures from other pectate lyases of H. glycines (HG-PEL-1, HG-PEL-2 and HG-PEL-7. A phylogenetic study revealed that the pectate lyase proteins of H. glycines are clustered into distinct clades and have distinct numbers and positioning of introns, which suggests that the pectate lyase genes of H. glycines may have evolved from at least two ancestral genes. A Southern blot analysis revealed that multiple Hg-pel-6-like genes were present in the H. glycines genome. In situ hybridization showed that four novel pectate lyases (Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7 were actively transcribed in the subventral esophageal gland cells. A semi-quantitative RT-PCR assay supported the finding that the expression of these genes was strong in the egg, pre-parasitic second-stage juvenile (J2 and early parasitic J2 stages and that it declined in further developmental stages of the nematode. This expression pattern suggests that these proteins play a role in the migratory phase of the nematode life cycle. Knocking down Hg-pel-6 using in vitro RNA interference resulted in a 46.9% reduction of the number of nematodes that invaded the plants and a 61.5% suppression of the development of H. glycines females within roots compared to the GFP-dsRNA control. Plant host-derived RNAi induced the silencing of the Hg-pel-6gene, which significantly reduced the nematode infection levels at 7 Days post inoculation (dpi. Similarly, this procedure reduced the number of female adults at 40 dpi

Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival

International Nuclear Information System (INIS)

Rubert, Joëlle; Qian, Zhiyan; Andraos, Rita; Guthy, Daniel A; Radimerski, Thomas

2011-01-01

The JAK2 V617F mutation plays a major role in the pathogenesis of myeloproliferative neoplasms and is found in the vast majority of patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia or from primary myelofibrosis. The V617F mutation is thought to provide hematopoietic stem cells and myeloid progenitors with a survival and proliferation advantage. It has previously been shown that activated JAK2 promotes cell survival by upregulating the anti-apoptotic STAT5 target gene Bcl-xL. In this study, we have investigated the role of additional apoptotic players, the pro-apoptotic protein Bim as well as the anti-apoptotic protein Mcl-1. Pharmacological inhibition of JAK2/STAT5 signaling in JAK2 V617F mutant SET-2 and MB-02 cells was used to study effects on signaling, cell proliferation and apoptosis by Western blot analysis, WST-1 proliferation assays and flow cytometry. Cells were transfected with siRNA oligos to deplete candidate pro- and anti-apoptotic proteins. Co-immunoprecipitation assays were performed to assess the impact of JAK2 inhibition on complexes of pro- and anti-apoptotic proteins. Treatment of JAK2 V617F mutant cell lines with a JAK2 inhibitor was found to trigger Bim activation. Furthermore, Bim depletion by RNAi suppressed JAK2 inhibitor-induced cell death. Bim activation following JAK2 inhibition led to enhanced sequestration of Mcl-1, besides Bcl-xL. Importantly, Mcl-1 depletion by RNAi was sufficient to compromise JAK2 V617F mutant cell viability and sensitized the cells to JAK2 inhibition. We conclude that Bim and Mcl-1 have key opposing roles in regulating JAK2 V617F cell survival and propose that inactivation of aberrant JAK2 signaling leads to changes in Bim complexes that trigger cell death. Thus, further preclinical evaluation of combinations of JAK2 inhibitors with Bcl-2 family antagonists that also tackle Mcl-1, besides Bcl-xL, is warranted to assess the therapeutic potential

TRAF6 is essential for maintenance of regulatory T cells that suppress Th2 type autoimmunity.

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Go Muto

Full Text Available Regulatory T cells (Tregs maintain immune homeostasis by limiting inflammatory responses. TRAF6 plays a key role in the regulation of innate and adaptive immunity by mediating signals from various receptors including the T-cell receptor (TCR. T cell-specific deletion of TRAF6 has been shown to induce multiorgan inflammatory disease, but the role of TRAF6 in Tregs remains to be investigated. Here, we generated Treg-specific TRAF6-deficient mice using Foxp3-Cre and TRAF6-flox mice. Treg-specific TRAF6-deficient (cKO mice developed allergic skin diseases, arthritis, lymphadenopathy and hyper IgE phenotypes. Although TRAF6-deficient Tregs possess similar in vitro suppression activity compared to wild-type Tregs, TRAF6-deficient Tregs did not suppress colitis in lymphopenic mice very efficiently due to reduced number of Foxp3-positive cells. In addition, the fraction of TRAF6-deficient Tregs was reduced compared with wild-type Tregs in female cKO mice without inflammation. Moreover, adoptive transfer of Foxp3 (+ Tregs into Rag2(-/- mice revealed that TRAF6-deficient Tregs converted into Foxp3(- cells more rapidly than WT Tregs under lymphopenic conditions. Fate-mapping analysis also revealed that conversion of Tregs from Foxp3(+ to Foxp3(- (exFoxp3 cells was accelerated in TRAF6-deficient Tregs. These data indicate that TRAF6 in Tregs plays important roles in the maintenance of Foxp3 in Tregs and in the suppression of pathogenic Th2 type conversion of Tregs.

ITE Suppresses Angiogenic Responses in Human Artery and Vein Endothelial Cells: Differential Roles of AhR.

Science.gov (United States)

Li, Yan; Wang, Kai; Zou, Qing-Yun; Jiang, Yi-Zhou; Zhou, Chi; Zheng, Jing

2017-12-01

Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor is involved in regulation of many essential biological processes including vascular development and angiogenesis. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an AhR ligand, which regulates immune responses and cancer cell growth. However, the roles of the ITE/AhR pathway in mediating placental angiogenesis remains elusive. Here, we determined if ITE affected placental angiogenic responses via AhR in human umbilical vein (HUVECs) and artery endothelial (HUAECs) cells in vitro. We observed that ITE dose- and time-dependently inhibited proliferation and viability of HUAECs and HUVECs, whereas it inhibited migration of HUAECs, but not HUVECs. While AhR siRNA significantly suppressed AhR protein expression in HUVECs and HUAECs, it attenuated the ITE-inhibited angiogenic responses of HUAECs, but not HUVECs. Collectively, ITE suppressed angiogenic responses of HUAECs and HUVECs, dependent and independent of AhR, respectively. These data suggest that ITE may regulate placental angiogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

4-1BB Signaling in Conventional T Cells Drives IL-2 Production That Overcomes CD4+CD25+FoxP3+ T Regulatory Cell Suppression.

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Hampartsoum B Barsoumian

Full Text Available Costimulation with the recombinant SA-4-1BBL agonist of 4-1BB receptor on conventional CD4+ T cells (Tconvs overcomes the suppression mediated by naturally occurring CD4+CD25+FoxP3+ T regulatory cells (Tregs. The mechanistic basis of this observation has remained largely unknown. Herein we show that Tconvs, but not Tregs, are the direct target of SA-4-1BBL-mediated evasion of Treg suppression. IL-2 produced by Tconvs in response to 4-1BB signaling is both necessary and sufficient for overcoming Treg suppression. Supernatant from Tconvs stimulated with SA-4-1BBL contains high levels of IL-2 and overcomes Treg suppression in ex vivo Tconv:Treg cocultures. Removal of IL-2 from such supernatant restores Treg suppression and repletion of Tconv:Treg cocultures with exogenous recombinant IL-2 overcomes suppression. This study establishes 4-1BB signaling as a key circuit that regulates physical and functional equilibrium between Tregs and Tconvs with important implications for immunotherapy for indications where a fine balance between Tregs and Teffs plays a decisive role.

Buddleja officinalis suppresses high glucose-induced vascular smooth muscle cell proliferation: role of mitogen-activated protein kinases, nuclear factor-kappaB and matrix metalloproteinases.

Science.gov (United States)

Lee, Yun Jung; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

2010-02-01

Diabetes mellitus is a well-established risk factor for vascular diseases caused by atherosclerosis. In the development of diabetic atherogenesis, vascular smooth muscle cell proliferation is recognized as a key event. Thus, we aimed to investigate whether an ethanol extract of Buddleja officinalis (EBO) suppresses high glucose-induced proliferation in primary cultured human aortic smooth muscle cells (HASMC). [(3)H]-thymidine incorporation revealed that incubation of HASMC with a high concentration of glucose (25 mmol/L) increased cell proliferation. The expression levels of cell cycle protein were also increased by treatment with high glucose concentration. Pretreatment of HASMC with EBO significantly attenuated the increase of high glucose-induced cell proliferation as well as p38 mitogen-activated protein kinases (MAPK) and JNK phosphorylation. EBO suppressed high glucose-induced matrix metalloproteinase (MMP)-9 activity in a dose-dependent manner. In addition, EBO suppressed nuclear factor-kappaB (NF-kappaB) nuclear translocation and transcriptional activity in high glucose conditions. Taken together, the present data suggest that EBO could suppress high glucose-induced atherosclerotic processes through inhibition of p38, JNK, NF-kappaB and MMP signal pathways in HASMC.

The neural basis of suppression and amblyopia in strabismus.

Science.gov (United States)

Sengpiel, F; Blakemore, C

1996-01-01

The neurophysiological consequences of artificial strabismus in cats and monkeys have been studied for 30 years. However, until very recently no clear picture has emerged of neural deficits that might account for the powerful interocular suppression that strabismic humans experience, nor for the severe amblyopia that is often associated with convergent strabismus. Here we review the effects of squint on the integrative capacities of the primary visual cortex and propose a hypothesis about the relationship between suppression and amblyopia. Most neurons in the visual cortex of normal cats and monkeys can be excited through either eye and show strong facilitation during binocular stimulation with contours of similar orientation in the two eyes. But in strabismic animals, cortical neurons tend to fall into two populations of monocularly excitable cells and exhibit suppressive binocular interactions that share key properties with perceptual suppression in strabismic humans. Such interocular suppression, if prolonged and asymmetric (with input from the squinting eye habitually suppressed by that from the fixating eye), might lead to neural defects in the representation of the deviating eye and hence to amblyopia.

Celecoxib inhibits osteoblast maturation by suppressing the expression of Wnt target genes

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Akihiro Nagano

2017-01-01

Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs have been shown to impair bone healing. We previously reported that in colon cancer cells, celecoxib, a COX-2-selective NSAID, inhibited the canonical Wnt/β-catenin signaling pathway. Since this pathway also plays an important role in osteoblast growth and differentiation, we examined the effect of celecoxib on maturation of osteoblast-like cell line MC3T3-E1. Celecoxib induced degradation of transcription factor 7-like 2, a key transcription factor of the canonical Wnt pathway. Subsequently, we analyzed the effect of celecoxib on two osteoblast differentiation markers; runt-related transcription factor 2 (RUNX2 and alkaline phosphatase (ALP, both of which are the products of the canonical Wnt pathway target genes. Celecoxib inhibited the expression of both RUNX2 and ALP by suppressing their promoter activity. Consistent with these observations, celecoxib also strongly inhibited osteoblast-mediated mineralization. These results suggest that celecoxib inhibits osteoblast maturation by suppressing Wnt target genes, and this could be the mechanism that NSAIDs inhibit bone formation and fracture healing.

Same pattern, different mechanism: Locking onto the role of key species in seafloor ecosystem process.

Science.gov (United States)

Woodin, Sarah Ann; Volkenborn, Nils; Pilditch, Conrad A; Lohrer, Andrew M; Wethey, David S; Hewitt, Judi E; Thrush, Simon F

2016-05-27

Seafloor biodiversity is a key mediator of ecosystem functioning, but its role is often excluded from global budgets or simplified to black boxes in models. New techniques allow quantification of the behavior of animals living below the sediment surface and assessment of the ecosystem consequences of complex interactions, yielding a better understanding of the role of seafloor animals in affecting key processes like primary productivity. Combining predictions based on natural history, behavior of key benthic species and environmental context allow assessment of differences in functioning and process, even when the measured ecosystem property in different systems is similar. Data from three sedimentary systems in New Zealand illustrate this. Analysis of the behaviors of the infaunal ecosystem engineers in each system revealed three very different mechanisms driving ecosystem function: density and excretion, sediment turnover and surface rugosity, and hydraulic activities and porewater bioadvection. Integrative metrics of ecosystem function in some cases differentiate among the systems (gross primary production) and in others do not (photosynthetic efficiency). Analyses based on behaviors and activities revealed important ecosystem functional differences and can dramatically improve our ability to model the impact of stressors on ecosystem and global processes.

Chk1 suppressed cell death

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Meuth Mark

2010-09-01

Full Text Available Abstract The role of Chk1 in the cellular response to DNA replication stress is well established. However recent work indicates a novel role for Chk1 in the suppression of apoptosis following the disruption of DNA replication or DNA damage. This review will consider these findings in the context of known pathways of Chk1 signalling and potential applications of therapies that target Chk1.

Respective roles and interactions of T-lymphocyte and PGE2-mediated monocyte suppressive activities in human newborns and mothers at the time of delivery

International Nuclear Information System (INIS)

Durandy, A.; Fischer, A.; Mamas, S.; Dray, F.; Griscelli, C.

1982-01-01

Recently the concept of a poorly functional humoral immune response in the newborn was proposed. Data have been presented indicating that the impaired newborn B cell maturation, as shown in vitro in a pokeweed mitogen-induced B cell maturation system, is due both to an immaturity of lymphocyte subsets and to an increased suppressive T activity. In the present work, we present evidence that there exists a predominance of a naturally occurring T lymphocyte suppressive activity in the cord blood in that the removal of the suppressive activity by irradiation allows a normal maturation of newborn B cells. Such normal maturation of newborn B cells can also be obtained using mixed cultures of adult T cells and newborn B cells. Newborn suppressor T cells belong to both EA gamma (+) and EA gamma (-) fractions, and it is not known whether these two groups do or do not belong to different subsets. The PGE2-dependent monocyte suppressive activity does not play any role in the suppression observed in newborns since newborn monocytes are poorly suppressive and since they produce a smaller amount of PGE2 than adult monocytes. Some observations suggest, on the contrary, that the suppressive T lymphocytes can regulate the level of the PGE2-dependent monocyte suppressive activity. It should be noticed that similar observations about T lymphocyte and PGE2-dependent monocyte suppressive activities have been made at the same time using mothers' cells. These observations suggest the possibility that such changes in B cell immune regulation may result from an interaction between maternal and fetal lymphoid cells

Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections.

Science.gov (United States)

Sordillo, Peter P; Helson, Lawrence

2015-01-01

The terminal stage of Ebola and other viral diseases is often the onset of a cytokine storm, the massive overproduction of cytokines by the body's immune system. The actions of curcumin in suppressing cytokine release and cytokine storm are discussed. Curcumin blocks cytokine release, most importantly the key pro-inflammatory cytokines, interleukin-1, interleukin-6 and tumor necrosis factor-α. The suppression of cytokine release by curcumin correlates with clinical improvement in experimental models of disease conditions where a cytokine storm plays a significant role in mortality. The use of curcumin should be investigated in patients with Ebola and cytokine storm. Intravenous formulations may allow achievement of therapeutic blood levels of curcumin. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Comparison is key.

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Stone, Mark H; Stenner, A Jackson

2014-01-01

Several concepts from Georg Rasch's last papers are discussed. The key one is comparison because Rasch considered the method of comparison fundamental to science. From the role of comparison stems scientific inference made operational by a properly developed frame of reference producing specific objectivity. The exact specifications Rasch outlined for making comparisons are explicated from quotes, and the role of causality derived from making comparisons is also examined. Understanding causality has implications for what can and cannot be produced via Rasch measurement. His simple examples were instructive, but the implications are far reaching upon first establishing the key role of comparison.

Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress.

Science.gov (United States)

Cai, Yanxue; Zhang, Xianwen; Zhou, Xiaoshuang; Wu, Xiaoli; Li, Yanhui; Yao, Jianhua; Bai, Jie

2017-03-01

Parkinson's disease (PD) is a neurodegenerative disease. Nicotine has been reported to have the role in preventing Parkinson's disease. However, its mechanism is still unclear. In present study we found that nicotine suppressed 1-methyl-4-phenylpyridinium ion(MPP + ) toxicity in PC12 cells by MTT assay. The expression of thioredoxin-1(Trx-1) was decreased by MPP + , which was restored by nicotine. The nicotine suppressed expressions of Glucose-regulated protein 78(GRP78/Bip) and C/EBP homologous protein (CHOP) induced by MPP + . The methyllycaconitine (MLA), the inhibitor of α7nAChR and LY294002, the inhibitor of phosphatidylinositol 3-kinase (PI3K) blocked the suppressions of above molecules, respectively. Consistently, pretreatment with nicotine ameliorated the motor ability, restored the declines of Trx-1 and tyrosine hydroxylase (TH), and suppressed the expressions of Bip and CHOP induced by 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Our results suggest that nicotine plays role in resisting MPP + /MPTP neurotoxicity through activating the α7nAChR/PI3K/Trx-1 pathway and suppressing ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.

Suppressing Structural Colors of Photocatalytic Optical Coatings on Glass: The Critical Role of SiO2.

Science.gov (United States)

Li, Ronghua; Boudot, Mickael; Boissière, Cédric; Grosso, David; Faustini, Marco

2017-04-26

The appearance of structural colors on coated-glass is a critical esthetical drawback toward industrialization of photocatalytic coatings on windows for architecture or automobile. Herein we describe a rational approach to suppress the structural color of mesoporous TiO 2 -based coatings preserving photoactivity and mechanical stiffness. Addition of SiO 2 as third component is discussed. Ti x Si (1-x) O 2 mesoporous coatings were fabricated by one-step liquid deposition process through the evaporation induced self-assembling and characterized by GI-SAXS, GI-WAXS, electron microscopies, and in situ Environmental Ellipsometry Porosimetry. Guided by optical simulation, we investigated the critical role of SiO 2 on the optical responses of the films but also on the structural, mechanical, and photocatalytic properties, important requirements to go toward real applications. We demonstrate that adding SiO 2 to porous TiO 2 allows tuning and suppression of structural colors through refractive index matching and up to 160% increase in mechanical stiffening of the films. This study leads us to demonstrate an example of "invisible" coating, in which the light reflection is angle- and thickness-independent, and exhibiting high porosity, mechanical stiffness, and photoactivity.

Basic roles of key molecules connected with NMDAR signaling pathway on regulating learning and memory and synaptic plasticity

Institute of Scientific and Technical Information of China (English)

Hui Wang; Rui-Yun Peng

2016-01-01

With key roles in essential brain functions ranging from the long-term potentiation (LTP) to synaptic plasticity,the N-methyl-D-aspartic acid receptor (NMDAR) can be considered as one of the fundamental glutamate receptors in the central nervous system.The role of NMDA R was first identified in synaptic plasticity and has been extensively studied.Some molecules,such as Ca2+,postsynaptic density 95 (PSD-95),calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ),protein kinase A (PKA),mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate (cAMP) responsive element binding protein (CREB),are of special importance in learning and memory.This review mainly focused on the new research of key molecules connected with learning and memory,which played important roles in the NMDAR signaling pathway.

Redundant mechanisms are involved in suppression of default cell fates during embryonic mesenchyme and notochord induction in ascidians.

Science.gov (United States)

Kodama, Hitoshi; Miyata, Yoshimasa; Kuwajima, Mami; Izuchi, Ryoichi; Kobayashi, Ayumi; Gyoja, Fuki; Onuma, Takeshi A; Kumano, Gaku; Nishida, Hiroki

2016-08-01

During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure. Copyright © 2016 Elsevier Inc. All rights reserved.

Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via Suppression of TBK1

Directory of Open Access Journals (Sweden)

Nur Aziz

2018-05-01

Full Text Available Interferon regulatory factor (IRF-3 is known to have a critical role in viral and bacterial innate immune responses by regulating the production of type I interferon (IFN. Thymoquinone (TQ is a compound derived from black cumin (Nigella sativa L. and is known to regulate immune responses by affecting transcription factors associated with inflammation, including nuclear factor-κB (NF-κB and activator protein-1 (AP-1. However, the role of TQ in the IRF-3 signaling pathway has not been elucidated. In this study, we explored the molecular mechanism of TQ-dependent regulation of enzymes in IRF-3 signaling pathways using the lipopolysaccharide (LPS-stimulated murine macrophage-like RAW264.7 cell line. TQ decreased mRNA expression of the interferon genes IFN-α and IFN-β in these cells. This inhibition was due to its suppression of the transcriptional activation of IRF-3, as shown by inhibition of IRF-3 PRD (III-I luciferase activity as well as the phosphorylation pattern of IRF-3 in the immunoblotting experiment. Moreover, TQ targeted the autophosphorylation of TANK-binding kinase 1 (TBK1, an upstream key enzyme responsible for IRF-3 activation. Taken together, these findings suggest that TQ can downregulate IRF-3 activation via inhibition of TBK1, which would subsequently decrease the production of type I IFN. TQ also regulated IRF-3, one of the inflammatory transcription factors, providing a novel insight into its anti-inflammatory activities.

Suppressive mechanisms in visual motion processing: From perception to intelligence.

Science.gov (United States)

Tadin, Duje

2015-10-01

Perception operates on an immense amount of incoming information that greatly exceeds the brain's processing capacity. Because of this fundamental limitation, the ability to suppress irrelevant information is a key determinant of perceptual efficiency. Here, I will review a series of studies investigating suppressive mechanisms in visual motion processing, namely perceptual suppression of large, background-like motions. These spatial suppression mechanisms are adaptive, operating only when sensory inputs are sufficiently robust to guarantee visibility. Converging correlational and causal evidence links these behavioral results with inhibitory center-surround mechanisms, namely those in cortical area MT. Spatial suppression is abnormally weak in several special populations, including the elderly and individuals with schizophrenia-a deficit that is evidenced by better-than-normal direction discriminations of large moving stimuli. Theoretical work shows that this abnormal weakening of spatial suppression should result in motion segregation deficits, but direct behavioral support of this hypothesis is lacking. Finally, I will argue that the ability to suppress information is a fundamental neural process that applies not only to perception but also to cognition in general. Supporting this argument, I will discuss recent research that shows individual differences in spatial suppression of motion signals strongly predict individual variations in IQ scores. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

CRP and SAA1 Haplotypes Are Associated with Both C-Reactive Protein and Serum Amyloid A Levels: Role of Suppression Effects

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Yu-Lin Ko

2016-01-01

Full Text Available To test the statistical association of the CRP and SAA1 locus variants with their corresponding circulating levels and metabolic and inflammatory biomarker levels by using mediation analysis, a sample population of 599 Taiwanese subjects was enrolled and five CRP and four SAA1 variants were genotyped. Correlation analysis revealed that C-reactive protein (CRP and serum amyloid A (SAA levels were significantly associated with multiple metabolic phenotypes and inflammatory marker levels. Our data further revealed a significant association of CRP and SAA1 variants with both CRP and SAA levels. Mediation analysis revealed that SAA levels suppressed the association between SAA1 genotypes/haplotypes and CRP levels and that CRP levels suppressed the association between CRP haplotypes and SAA levels. In conclusion, genetic variants at the CRP and SAA1 loci independently affect both CRP and SAA levels, and their respective circulating levels act as suppressors. These results provided further evidence of the role of the suppression effect in biological science and may partially explain the missing heritability in genetic association studies.

Activation of lysosomal function in the course of autophagy via mTORC1 suppression and autophagosome-lysosome fusion.

Science.gov (United States)

Zhou, Jing; Tan, Shi-Hao; Nicolas, Valérie; Bauvy, Chantal; Yang, Nai-Di; Zhang, Jianbin; Xue, Yuan; Codogno, Patrice; Shen, Han-Ming

2013-04-01

Lysosome is a key subcellular organelle in the execution of the autophagic process and at present little is known whether lysosomal function is controlled in the process of autophagy. In this study, we first found that suppression of mammalian target of rapamycin (mTOR) activity by starvation or two mTOR catalytic inhibitors (PP242 and Torin1), but not by an allosteric inhibitor (rapamycin), leads to activation of lysosomal function. Second, we provided evidence that activation of lysosomal function is associated with the suppression of mTOR complex 1 (mTORC1), but not mTORC2, and the mTORC1 localization to lysosomes is not directly correlated to its regulatory role in lysosomal function. Third, we examined the involvement of transcription factor EB (TFEB) and demonstrated that TFEB activation following mTORC1 suppression is necessary but not sufficient for lysosomal activation. Finally, Atg5 or Atg7 deletion or blockage of the autophagosome-lysosome fusion process effectively diminished lysosomal activation, suggesting that lysosomal activation occurring in the course of autophagy is dependent on autophagosome-lysosome fusion. Taken together, this study demonstrates that in the course of autophagy, lysosomal function is upregulated via a dual mechanism involving mTORC1 suppression and autophagosome-lysosome fusion.

The Key Success and Strategic Role of Accrual Based Accounting Implementation

Directory of Open Access Journals (Sweden)

Surepno Surepno

2015-09-01

Full Text Available Central Government policy to adopt accrual-based accounting system providing consequences for local governments to apply accrual accounting in the financial statements. Empirical evidence shows that the readiness of the local government in Indonesia in the process of implementation of accrual accounting is still relatively low. This study aimed to analyze the success of Semarang Government in implementing accrual accounting. This study also analyzes the offender's response to the implementation of the strategic role of accrual accounting in transparency and accountability. Furthermore, the method used in this study is a qualitative approach to perform a case study at the Department of Finance and Asset Management Area (DPKAD Semarang by means of interviewing the key actors of implementation. The results showed that the successful implementation of accrual accounting Semarang government is supported by four main strategies, namely management commitment, regulatory development, information systems development and human resource development. Furthermore, based on the conclusions of the implementers shows that accrual accounting has a strategic role in increasing transparency and accountability through financial reporting.

Assessing the Role of Energy in Development and Climate Policies - Conceptual Approach and Key Indicators

DEFF Research Database (Denmark)

Halsnæs, Kirsten; Garg, Amit

2011-01-01

The paper discusses a number of key conceptual issues related to the role of energy in development and its potential synergies and tradeoffs with climate change. The relationship between economic development and energy over time is discussed and illustrated by data from China, India and South...... Africa, and some other countries. It concludes that energy plays an important role as a productivity enhancing factor in economic development and in human well being. Several policy goals related to sustainable development, energy, and climate can be integrated. However, meeting all these policy goals...

Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.

Science.gov (United States)

Papaspyridonos, Marianna; Matei, Irina; Huang, Yujie; do Rosario Andre, Maria; Brazier-Mitouart, Helene; Waite, Janelle C; Chan, April S; Kalter, Julie; Ramos, Ilyssa; Wu, Qi; Williams, Caitlin; Wolchok, Jedd D; Chapman, Paul B; Peinado, Hector; Anandasabapathy, Niroshana; Ocean, Allyson J; Kaplan, Rosandra N; Greenfield, Jeffrey P; Bromberg, Jacqueline; Skokos, Dimitris; Lyden, David

2015-04-29

A central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.

Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1

NARCIS (Netherlands)

Singhmar, Pooja; Huo, XiaoJiao; Eijkelkamp, Niels; Berciano, Susana Rojo; Baameur, Faiza; Mei, Fang C; Zhu, Yingmin; Cheng, Xiaodong; Hawke, David; Mayor, Federico; Murga, Cristina; Heijnen, Cobi J.; Kavelaars, Annemieke

2016-01-01

cAMP signaling plays a key role in regulating pain sensitivity. Here, we uncover a previously unidentified molecular mechanism in which direct phosphorylation of the exchange protein directly activated by cAMP 1 (EPAC1) by G protein kinase 2 (GRK2) suppresses Epac1-to-Rap1 signaling, thereby

Suppression of allene oxide synthase 3 in potato increases degree of arbuscular mycorrhizal fungal colonization.

Science.gov (United States)

Morcillo, Rafael Jorge León; Navarrete, María Isabel Tamayo; Bote, Juan Antonio Ocampo; Monguio, Salomé Prat; García-Garrido, José Manuel

2016-01-15

Arbuscular mycorrhizal (AM) is a mutually beneficial interaction among higher plants and soil fungi of the phylum Glomeromycota. Numerous studies have pointed that jasmonic acid plays an important role in the development of the intraradical fungus. This compound belongs to a group of biologically active compounds known as oxylipins which are derived from the oxidative metabolism of polyunsaturated fatty acids. Studies of the regulatory role played by oxylipins in AM colonization have generally focused on jasmonates, while few studies exist on the 9-LOX pathway of oxylipins during AM formation. Here, the cDNA of Allene oxide synthase 3 (AOS3), a key enzyme in the 9-LOX pathway, was used in the RNA interference (RNAi) system to transform potato plants in order to suppress its expression. Results show increases in AOS3 gene expression and 9-LOX products in roots of wild type potato mycorrhizal plants. The suppression of AOS3 gene expression increases the percentage of root with mycorrhizal colonization at early stages of AM formation. AOS3 RNA interference lead to an induction of LOXA and 13-LOX genes, a reduction in AOS3 derived 9-LOX oxylipin compounds and an increase in jasmonic acid content, suggesting compensation between 9 and 13-LOX pathways. The results in a whole support the hypothesis of a regulatory role for the 9-LOX oxylipin pathway during mycorrhization. Copyright © 2015 Elsevier GmbH. All rights reserved.

Interleukin-4 Supports the Suppressive Immune Responses Elicited by Regulatory T Cells

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Wei-Cheng Yang

2017-11-01

Full Text Available Interleukin-4 (IL-4 has been considered as one of the tolerogenic cytokines in many autoimmune animal models and clinical settings. Despite its role in antagonizing pathogenic Th1 responses, little is known about whether IL-4 possesses functions that affect regulatory T cells (Tregs. Tregs are specialized cells responsible for the maintenance of peripheral tolerance through their immune modulatory capabilities. Interestingly, it has been suggested that IL-4 supplement at a high concentration protects responder T cells (Tresps from Treg-mediated immune suppression. In addition, such supplement also impedes TGF-β-induced Treg differentiation in vitro. However, these phenomena may contradict the tolerogenic role of IL-4, and the effects of IL-4 on Tregs are therefore needed to be further elucidated. In this study, we utilized IL-4 knockout (KO mice to validate the role of IL-4 on Treg-mediated immune suppression. Although IL-4 KO and control animals harbor similar frequencies of Tregs, Tregs from IL-4 KO mice weakly suppressed autologous Tresp activation. In addition, IL-4 deprivation impaired the ability of Tregs to modulate immune response, whereas IL-4 supplementation reinforced IL-4 KO Tregs in their function in suppressing Tresps. Finally, the presence of IL-4 was associated with increased cell survival and granzyme expression of Tregs. These results suggest the essential role of IL-4 in supporting Treg-mediated immune suppression, which may benefit the development of therapeutic strategies for autoimmune diseases.

Suppression of synaptic plasticity by fullerenol in rat hippocampus in vitro

Directory of Open Access Journals (Sweden)

Wang XX

2016-09-01

Full Text Available Xin-Xing Wang,1,2,* Ying-Ying Zha,3,* Bo Yang,1 Lin Chen,1,2 Ming Wang1,2 1CAS Key Laboratory of Brain Function and Diseases, 2Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 3Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu, Anhui, People’s Republic of China *These authors contributed equally to this work Abstract: Fullerenol, a water-soluble fullerene derivative, has attracted much attention due to its bioactive properties, including the antioxidative properties and free radical scavenging ability. Due to its superior nature, fullerenol represents a promising diagnostic, therapeutic, and protective agent. Therefore, elucidation of the possible side effects of fullerenol is important in determining its potential role. In the present study, we investigated the acute effects of 5 µM fullerenol on synaptic plasticity in hippocampal brain slices of rats. Incubation with fullerenol for 20 minutes significantly decreased the peak of paired-pulse facilitation and long-term potentiation, indicating that fullerenol suppresses the short- and long-term synaptic plasticity of region I of hippocampus. We found that fullerenol depressed the activity and the expression of nitric oxide (NO synthase in hippocampus. In view of the important role of NO in synaptic plasticity, the inhibition of fullerenol on NO synthase may contribute to the suppression of synaptic plasticity. These findings may facilitate the evaluation of the side effects of fullerenol. Keywords: fullerenol, hippocampal slice, nitric oxide synthase, synaptic plasticity, oxidative stress

The clinical role of lecturers in nursing in Ireland: perceptions from key stakeholder groups in nurse education on the role.

Science.gov (United States)

Meskell, Pauline; Murphy, Kathleen; Shaw, David

2009-10-01

The clinical role of lecturers in nursing has been a focus of debate since the integration of nurse education into higher education institutions. The purpose of this paper is to report the findings from the preliminary phase of a study, undertaken to investigate the perceptions of key stakeholder groups in nurse education, regarding the current clinical role of nurse lecturers in Ireland. A descriptive exploratory design was used involving focus group and individual interviews, soliciting views of purposefully selected educationalists, clinicians, policy formulators and students. The issue was examined from a policy perspective, aiming to collectively represent views of all participant groups. This approach facilitated a more complete picture of perceptions of the role to emerge, to better inform future decision making. Twenty two focus group interviews and twenty one individual interviews were conducted. Content analysis was used to identify themes. All groups were in agreement that role definition was urgently required to dispel ambiguities surrounding what the clinical role should involve. Conflicting views were evident among groups regarding lecturers' clinical credibility, visibility and teaching effectiveness. Findings highlight the essential nature of nurse lecturers engaging with clinical areas to maintain their skills, demonstrate a value for the practice component of the role and provide a link between education and practice.

Efflux inhibitor suppresses Streptococcus mutans virulence properties.

Science.gov (United States)

Zeng, Huihui; Liu, Jia; Ling, Junqi

2017-04-01

It is well established that efflux pumps play important roles in bacterial pathogenicity and efflux inhibitors (EIs) have been proved to be effective in suppressing bacterial virulence properties. However, little is known regarding the EI of Streptococcus mutans, a well-known caries-inducing bacterium. In this study, we identified the EI of S. mutans through ethidium bromide efflux assay and investigated how EI affected S. mutans virulence regarding the cariogenicity and stress response. Results indicated that reserpine, the identified EI, suppressed acid tolerance, mutacin production and transformation efficiency of S. mutans, and modified biofilm architecture and extracellular polysaccharide distribution. Suppressed glycosyltransferase activity was also noted after reserpine exposure. The data from quantitative real-time-PCR demonstrated that reserpine significantly altered the expression profile of quorum-sensing and virulence-associated genes. These findings suggest that reserpine represents a promising adjunct anticariogenic agent in that it suppresses virulence properties of S. mutans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

LENUS (Irish Health Repository)

Abdel Aziz, Mohamed T

2011-05-05

Abstract Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl 4 , rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation

Critical role of heme oxygenase-1 in Foxp3-mediated immune suppression

International Nuclear Information System (INIS)

Choi, Byung-Min; Pae, Hyun-Ock; Jeong, Young-Ran; Kim, Young-Myeong; Chung, Hun-Taeg

2005-01-01

Foxp3, which encodes the transcription factor scurfin, is indispensable for the development and function of CD4 + CD25 + regulatory T cells (Treg). Recent data suggest conversion of peripheral CD4 + CD25 - naive T cells to CD4 + CD25 + Treg by acquisition of Foxp3 through costimulation with TCR and TGF-β or forced expression of the gene. One critical question is how Foxp3 causes T cells to become regulatory. In the present work, we demonstrate that Foxp3 can induce heme oxygenase-1 (HO-1) expression and subsequently such regulatory phenotypes as the suppression of nontransfected cells in a cell-cell contact-dependent manner as well as impaired proliferation and production of cytokines upon stimulation in Jurkat T cells. Moreover, we confirm the expression of both Foxp3 and HO-1 in peripheral CD4 + CD25 + Treg and suppressive function of the cells are relieved by the inhibition of HO-1 activity. In summary, we demonstrate that Foxp3 induces HO-1 expression and HO-1 engages in Foxp3-mediated immune suppression

The pressure suppression system

International Nuclear Information System (INIS)

Aust, E.

1985-01-01

Nuclear plants with boiling water reactors have a safety containment with a pressure suppression system (PSS). Proceeding on significant self-developments, today the three PSS-lines of General Electric Co. (GE), Kraftwerk Union AG (KWU) and ASEA-ATOM are predominant, which are currently represented by the MARK III type, the KWU type 72 and the BWR 75 containment. In addition, there are special developments for the nuclear ship propulsion and for the pressurized water reactors in the Soviet Union. Key design values of the PSS allow a first valuation of its loads during a hypothetical loss-of-coolant accident. (orig.) [de

Mindfulness-based cognitive therapy for depressed individuals improves suppression of irrelevant mental-sets.

Science.gov (United States)

Greenberg, Jonathan; Shapero, Benjamin G; Mischoulon, David; Lazar, Sara W

2017-04-01

An impaired ability to suppress currently irrelevant mental-sets is a key cognitive deficit in depression. Mindfulness-based cognitive therapy (MBCT) was specifically designed to help depressed individuals avoid getting caught in such irrelevant mental-sets. In the current study, a group assigned to MBCT plus treatment-as-usual (n = 22) exhibited significantly lower depression scores and greater improvements in irrelevant mental-set suppression compared to a wait-list plus treatment-as-usual (n = 18) group. Improvements in mental-set-suppression were associated with improvements in depression scores. Results provide the first evidence that MBCT can improve suppression of irrelevant mental-sets and that such improvements are associated with depressive alleviation.

Reassessing the Concept of Emotional Labour in Student Nurse Education: Role of Link Lecturers and Mentors in a Time of Change.

Science.gov (United States)

Smith, Pam; Gray, Benjamin

2001-01-01

Interviews with nursing students and nurses revealed how nurses undertake emotional labor--the induction or suppression of feeling in order to sustain a caring environment. Instructors and mentors in clinical settings play a key role in fostering reflective learning and providing emotional support. (Contains 33 references.) (SK)

Connecting metabolism and reproduction: roles of central energy sensors and key molecular mediators.

Science.gov (United States)

Roa, Juan; Tena-Sempere, Manuel

2014-11-01

It is well established that pubertal activation of the reproductive axis and maintenance of fertility are critically dependent on the magnitude of body energy reserves and the metabolic state of the organism. Hence, conditions of impaired energy homeostasis often result in deregulation of puberty and reproduction, whereas gonadal dysfunction can be associated with the worsening of the metabolic profile and, eventually, changes in body weight. While much progress has taken place in our knowledge about the neuroendocrine mechanisms linking metabolism and reproduction, our understanding of how such dynamic interplay happens is still incomplete. As paradigmatic example, much has been learned in the last two decades on the reproductive roles of key metabolic hormones (such as leptin, insulin and ghrelin), their brain targets and the major transmitters and neuropeptides involved. Yet, the molecular mechanisms whereby metabolic information is translated and engages into the reproductive circuits remain largely unsolved. In this work, we will summarize recent developments in the characterization of the putative central roles of key cellular energy sensors, such as mTOR, in this phenomenon, and will relate these with other molecular mechanisms likely contributing to the brain coupling of energy balance and fertility. In doing so, we aim to provide an updated view of an area that, despite still underdeveloped, may be critically important to fully understand how reproduction and metabolism are tightly connected in health and disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses.

Science.gov (United States)

Liu, Yingqi; Zhu, Zixiang; Zhang, Miaotao; Zheng, Haixue

2015-10-28

Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.

Perillyl alcohol suppresses antigen-induced immune responses in the lung

International Nuclear Information System (INIS)

Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko; Dohi, Makoto

2014-01-01

Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4 + T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4 + T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects

High Concentration of Melatonin Regulates Leaf Development by Suppressing Cell Proliferation and Endoreduplication in Arabidopsis.

Science.gov (United States)

Wang, Qiannan; An, Bang; Shi, Haitao; Luo, Hongli; He, Chaozu

2017-05-05

N -acetyl-5-methoxytryptamine (Melatonin), as a crucial messenger in plants, functions in adjusting biological rhythms, stress tolerance, plant growth and development. Several studies have shown the retardation effect of exogenous melatonin treatment on plant growth and development. However, the in vivo role of melatonin in regulating plant leaf growth and the underlying mechanism are still unclear. In this study, we found that high concentration of melatonin suppressed leaf growth in Arabidopsis by reducing both cell size and cell number. Further kinetic analysis of the fifth leaves showed that melatonin remarkably inhibited cell division rate. Additionally, flow cytometic analysis indicated that melatonin negatively regulated endoreduplication during leaf development. Consistently, the expression analysis revealed that melatonin regulated the transcriptional levels of key genes of cell cycle and ribosome. Taken together, this study suggests that high concentration of melatonin negatively regulated the leaf growth and development in Arabidopsis , through modulation of endoreduplication and the transcripts of cell cycle and ribosomal key genes.

MicroRNA regulation of cancer metabolism: role in tumour suppression

Czech Academy of Sciences Publication Activity Database

Tomasetti, M.; Santarelli, L.; Neužil, Jiří; Dong, L.

2014-01-01

Roč. 19, part a SI (2014), s. 29-38 ISSN 1567-7249 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : MicroRNA * Mitochondria * Tumour suppression Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.249, year: 2014

MR staging of pelvic endometriosis. Role of fat-suppression T1-weighted images

International Nuclear Information System (INIS)

Oishi-Tanaka, Yumiko; Itai, Yuji; Anno, Izumi; Matsumoto, Kunihiko; Ebihara, Reiko; Nishida, Masato

1996-01-01

We examined whether MR can determine the stage of endometriosis according to the scoring system established and revised by the American Fertility Society (r-AFS), a system which is widely used by gynecologists. We also studied the utility of fat suppression T 1 -weighted images in improving accuracy. Seventeen patients with endometriosis examined by conventional MR were included in this study. All the patients had surgically proved stage III or IV disease. We determined the stage by MR using the following criteria according to the r-AFS system: adnexal masses without normal ovarian tissue were considered deep ovarian lesions, while those with normal tissue were considered superficial. A lack of fat between the lesion and surrounding structures was considered a dense adhesion, and hyperintense spots were considered peritoneal implants. The MR scores of patients with and without fat suppression were correlated with the surgical scores. MR staging corresponded to surgical staging in 15 of the 17 patients. In eight patients, peritoneal implants of less than 1.5 cm were depicted only by fat-suppression images. However, these lesions did not change the score significantly. MR imaging could determine the stage in advanced endometriosis. Fat-suppression could highlight smaller implants. These tiny lesions had little clinical meaning in these advanced cases; however, the clinical value of this technique should be evaluated in milder disease. (author)

Determining the key drivers and mitigating factors that influence the role of the Nurse and/or Midwife Consultant: a cross-sectional survey.

Science.gov (United States)

Fernandez, Ritin S; Sheppard-Law, Suzanne; Manning, Vicki

2017-06-01

Globally, many nurses and midwives are working at an advanced practice level. The role of a Nurse and/or Midwife Consultant encompasses a diverse and complex interaction between five specified domains namely Clinical Service and Consultancy, Clinical Leadership, Research, Education, and Clinical Services Planning and Management. The objective of this replication study was to identify the key drivers and mitigating factors that impact the role of Australian Nurse and/or Midwife Consultants. Cross-sectional survey. The study was conducted in a large metropolitan health district in Sydney, Australia. Participants for this study consisted of all Nurse and/or Midwife Consultants working within a health district in New South Wales (NSW). Data were collected by an anonymous online survey. Key drivers and mitigating factors perceived to influence their role were identified using previously implemented instruments. Data were analysed using SPSS version 21. Responses were obtained from 122 Nurse and/or Midwife Consultants. The number of years of experience as a Nurse and/or Midwife Consultant ranged from 6 months to 25.5 years. Personal attributes which included personal motivation and own communication skills were identified as key drivers to role performance with a mean score of 7.7±0.6. Other key drivers included peer support, organisational culture, personal attributes, professional learning, Nurse and/or Midwife Consultant experience, and collaborative relationships. Of the 14 mitigating factors to the role, the most common factors were lack of resources to set up and develop the role (2.6 ± 0.9), lack of secretarial support (2.6 ± 1.1), lack of managerial support (2.45 ± 1.1), and lack of understanding of the role by other health professionals (2.40 ± 0.8). Understanding the key drivers and mitigating factors that influence the role of the Nurse and/or Midwife Consultant is important for healthcare managers. Given the changing landscape of nursing

Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression.

Science.gov (United States)

Woodham, Andrew W; Raff, Adam B; Raff, Laura M; Da Silva, Diane M; Yan, Lisa; Skeate, Joseph G; Wong, Michael K; Lin, Yvonne G; Kast, W Martin

2014-05-15

High-risk human papillomaviruses (HPVs) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cells in a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the APC of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. In this study, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by small interfering RNA downregulation of A2t significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC class II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein.

Mothers' responses to children's negative emotions and child emotion regulation: the moderating role of vagal suppression.

Science.gov (United States)

Perry, Nicole B; Calkins, Susan D; Nelson, Jackie A; Leerkes, Esther M; Marcovitch, Stuart

2012-07-01

The current study examined the moderating effect of children's cardiac vagal suppression on the association between maternal socialization of negative emotions (supportive and nonsupportive responses) and children's emotion regulation behaviors. One hundred and ninety-seven 4-year-olds and their mothers participated. Mothers reported on their reactions to children's negative emotions and children's regulatory behaviors. Observed distraction, an adaptive self-regulatory strategy, and vagal suppression were assessed during a laboratory task designed to elicit frustration. Results indicated that children's vagal suppression moderated the association between mothers' nonsupportive emotion socialization and children's emotion regulation behaviors such that nonsupportive reactions to negative emotions predicted lower observed distraction and lower reported emotion regulation behaviors when children displayed lower levels of vagal suppression. No interaction was found between supportive maternal emotion socialization and vagal suppression for children's emotion regulation behaviors. Results suggest physiological regulation may serve as a buffer against nonsupportive emotion socialization. Copyright © 2011 Wiley Periodicals, Inc.

Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology

International Nuclear Information System (INIS)

De Fabo, E.C.; Noonan, F.P.

1983-01-01

UV irradiation of mice causes a systemic immune alteration that can be detected either by suppression of the immunologic rejection of UV-induced tumors, or by suppression of contact hypersensitivity (CHS). Suppression of these two immunologic responses has similar photobiologic characteristics and in both cases is associated with the generation of antigen-specific suppressor T cells. To identify whether a specific photoreceptor for this effect exists, the relative wavelength effectiveness (action spectrum) was determined for the UV-induced suppression of CHS. Narrow bands of UV (half bandwidth 3 nm) were used at 10 wavelengths from 250 to 320 nm to obtain dose-response curves. The action spectrum derived from the dose-response curves has a maximum between 260 and 270 nm, a shoulder at 280-290 nm, and declines steadily to approximately 3% of maximum at 320 nm. The finding of such a clearly defined wavelength dependence implies the presence of a specific photoreceptor for this effect. Removing the stratum corneum by tape stripping before UV irradiation prevented the suppression of CHS using 254-nm radiation, suggesting the photoreceptor is superficially located in the skin. The hypothesis is advanced that the photoreceptor for systemic UV-induced immunosuppression of contact hypersensitivity may be urocanic acid. As such, it may also play a role in UV-induced carcinogenesis via the production of tumor-specific suppressor cells

Perillyl alcohol suppresses antigen-induced immune responses in the lung

Energy Technology Data Exchange (ETDEWEB)

Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Dohi, Makoto, E-mail: mdohi-tky@umin.ac.jp [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Institute of Respiratory Immunology, Shibuya Clinic for Respiratory Diseases and Allergology, Tokyo (Japan)

2014-01-03

Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4{sup +} T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4{sup +} T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects.

AMP-Activated Protein Kinase: An Ubiquitous Signaling Pathway With Key Roles in the Cardiovascular System.

Science.gov (United States)

Salt, Ian P; Hardie, D Grahame

2017-05-26

The AMP-activated protein kinase (AMPK) is a key regulator of cellular and whole-body energy homeostasis, which acts to restore energy homoeostasis whenever cellular energy charge is depleted. Over the last 2 decades, it has become apparent that AMPK regulates several other cellular functions and has specific roles in cardiovascular tissues, acting to regulate cardiac metabolism and contractile function, as well as promoting anticontractile, anti-inflammatory, and antiatherogenic actions in blood vessels. In this review, we discuss the role of AMPK in the cardiovascular system, including the molecular basis of mutations in AMPK that alter cardiac physiology and the proposed mechanisms by which AMPK regulates vascular function under physiological and pathophysiological conditions. © 2017 American Heart Association, Inc.

A weed suppressive index for spring barley (Hordeum vulgare) varieties

DEFF Research Database (Denmark)

Hansen, P K; Kristensen, K; Willas, J

2008-01-01

A screening programme for crop variety competitiveness would ideally be based on only a few, non-destructive measurements of key growth traits. In this study we measured the weed suppressive ability of 79 varieties of spring barley in two ways: (i) directly, by weed coverage assessments under wee...

Burn injury suppresses human dermal dendritic cell and Langerhans cell function

NARCIS (Netherlands)

van den Berg, Linda M.; de Jong, Marein A. W. P.; Witte, Lot de; Ulrich, Magda M. W.; Geijtenbeek, Teunis B. H.

2011-01-01

Human skin contains epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) that are key players in induction of adaptive immunity upon infection. After major burn injury, suppressed adaptive immunity has been observed in patients. Here we demonstrate that burn injury affects adaptive

The Arabidopsis Transcription Factor AtTCP15 Regulates Endoreduplication by Modulating Expression of Key Cell-cycle Genes

Institute of Scientific and Technical Information of China (English)

Zi-Yu Li; Bin Li; Ai-Wu Dong

2012-01-01

Plant cells frequently undergo endoreduplication,a modified cell cycle in which genome is repeatedly replicated without cytokinesis.As the key step to achieve final size and function for cells,endoreduplication is prevalent during plant development.However,mechanisms to control the balance between endoreduplication and mitotic cell division are still poorly understood.Here,we show that the Arabidopsis TCP (CINCINNATA-like TEOSINTE BRANCHED1-CYCLOIDEA-PCF)-family transcription factor gene AtTCP15 is expressed in trichomes,as well as in rapidly dividing and vascular tissues.Expression of AtTCP15SRDX,AtTCP15 fused with a SRDX repressor domain,induces extra endoreduplication in trichomes and cotyledon cells in transgenic Arabidopsis.On the contrary,overexpression of AtTCP15 suppresses endoreduplication in trichomes and other examined cells.Misregulation of AtTCP15 affects the expression of several important genes involved in cell-cycle regulation.AtTCP15 protein binds directly to the promoter regions of CYCA2;3 and RETINOBLASTOMA-RELATED (RBR) genes,which play key roles in endoreduplication.Taken together,AtTCP15 plays an important role in regulating endoreduplication during Arabidopsis development.

Perceptual learning of motion direction discrimination with suppressed and unsuppressed MT in humans: an fMRI study.

Directory of Open Access Journals (Sweden)

Benjamin Thompson

Full Text Available The middle temporal area of the extrastriate visual cortex (area MT is integral to motion perception and is thought to play a key role in the perceptual learning of motion tasks. We have previously found, however, that perceptual learning of a motion discrimination task is possible even when the training stimulus contains locally balanced, motion opponent signals that putatively suppress the response of MT. Assuming at least partial suppression of MT, possible explanations for this learning are that 1 training made MT more responsive by reducing motion opponency, 2 MT remained suppressed and alternative visual areas such as V1 enabled learning and/or 3 suppression of MT increased with training, possibly to reduce noise. Here we used fMRI to test these possibilities. We first confirmed that the motion opponent stimulus did indeed suppress the BOLD response within hMT+ compared to an almost identical stimulus without locally balanced motion signals. We then trained participants on motion opponent or non-opponent stimuli. Training with the motion opponent stimulus reduced the BOLD response within hMT+ and greater reductions in BOLD response were correlated with greater amounts of learning. The opposite relationship between BOLD and behaviour was found at V1 for the group trained on the motion-opponent stimulus and at both V1 and hMT+ for the group trained on the non-opponent motion stimulus. As the average response of many cells within MT to motion opponent stimuli is the same as their response to non-directional flickering noise, the reduced activation of hMT+ after training may reflect noise reduction.

Antibody-mediated allotype suppression in adult mice: the role of antigen, effector isotype and regulatory T cells.

Science.gov (United States)

Curling, E M; Dresser, D W

1984-10-01

It has been reported (Contemp. Top. Immunobiol. 1974. 3:41) that allotype-specific T suppressor cells can be induced after monoclonal anti-allotype treatment of neonatal (BALB/c X SJL)F1 (Igha/b) mice. Here we show that (BALB/c X CB20)F1 adult-derived spleen cells (SC) are, by contrast, potently suppressed by monoclonal allotype-specific reagents, (when transferred into irradiated BALB/c recipients) in the absence of primary T suppressor cell induction. Such suppression is only induced in activated B cells [exposed to lipopolysaccharide or sheep red blood cells (SRBC)], and is probably dependent on the isotype of the anti-allotype sera administered. For example, two independently produced IgG1 monoclonal reagents raised against the Igh-1b allotype were poorly suppressive or nonsuppressive, whereas an IgG3 and an IgG2a monoclonal antibody induced a 90% suppression of the target allotype in transferred adult SC. It was found that suppression was not due to a depletion of antigen-specific T cell help since: (a) the addition of SRBC-educated T cells did not break suppression and (b) suppressed SC were as good a source of T cell help as normal SC, in the response of virgin or memory B cell (Thy-1-depleted) responses to SRBC in vivo. Suppression was maintained in suppressed cells which had been rechallenged with SRBC after transfer into a second irradiated recipient, but was not induced in normal SC when these were admixed with an equal number from this suppressed SC population. These findings point to a possible mechanism for the regulation of B cell expression, through the formation of an antibody-Ig receptor complex at the surface of the B lymphocyte. After complexing the target cell is either deleted or inactivated. The response to SRBC was reduced or ablated for at least 70 days after treatment with a single dose of anti-allotype serum.

Boosting up quantum key distribution by learning statistics of practical single-photon sources

International Nuclear Information System (INIS)

Adachi, Yoritoshi; Yamamoto, Takashi; Koashi, Masato; Imoto, Nobuyuki

2009-01-01

We propose a simple quantum-key-distribution (QKD) scheme for practical single-photon sources (SPSs), which works even with a moderate suppression of the second-order correlation g (2) of the source. The scheme utilizes a passive preparation of a decoy state by monitoring a fraction of the signal via an additional beam splitter and a detector at the sender's side to monitor photon-number splitting attacks. We show that the achievable distance increases with the precision with which the sub-Poissonian tendency is confirmed in higher photon-number distribution of the source, rather than with actual suppression of the multiphoton emission events. We present an example of the secure key generation rate in the case of a poor SPS with g (2) =0.19, in which no secure key is produced with the conventional QKD scheme, and show that learning the photon-number distribution up to several numbers is sufficient for achieving almost the same distance as that of an ideal SPS.

MOF Suppresses Replication Stress and Contributes to Resolution of Stalled Replication Forks.

Science.gov (United States)

Singh, Dharmendra Kumar; Pandita, Raj K; Singh, Mayank; Chakraborty, Sharmistha; Hambarde, Shashank; Ramnarain, Deepti; Charaka, Vijaya; Ahmed, Kazi Mokim; Hunt, Clayton R; Pandita, Tej K

2018-03-15

The human MOF (hMOF) protein belongs to the MYST family of histone acetyltransferases and plays a critical role in transcription and the DNA damage response. MOF is essential for cell proliferation; however, its role during replication and replicative stress is unknown. Here we demonstrate that cells depleted of MOF and under replicative stress induced by cisplatin, hydroxyurea, or camptothecin have reduced survival, a higher frequency of S-phase-specific chromosome damage, and increased R-loop formation. MOF depletion decreased replication fork speed and, when combined with replicative stress, also increased stalled replication forks as well as new origin firing. MOF interacted with PCNA, a key coordinator of replication and repair machinery at replication forks, and affected its ubiquitination and recruitment to the DNA damage site. Depletion of MOF, therefore, compromised the DNA damage repair response as evidenced by decreased Mre11, RPA70, Rad51, and PCNA focus formation, reduced DNA end resection, and decreased CHK1 phosphorylation in cells after exposure to hydroxyurea or cisplatin. These results support the argument that MOF plays an important role in suppressing replication stress induced by genotoxic agents at several stages during the DNA damage response. Copyright © 2018 American Society for Microbiology.

Histone Deacetylase Inhibitors Antagonize Distinct Pathways to Suppress Tumorigenesis of Embryonal Rhabdomyosarcoma.

Directory of Open Access Journals (Sweden)

Terra Vleeshouwer-Neumann

Full Text Available Embryonal rhabdomyosarcoma (ERMS is the most common soft tissue cancer in children. The prognosis of patients with relapsed or metastatic disease remains poor. ERMS genomes show few recurrent mutations, suggesting that other molecular mechanisms such as epigenetic regulation might play a major role in driving ERMS tumor biology. In this study, we have demonstrated the diverse roles of histone deacetylases (HDACs in the pathogenesis of ERMS by characterizing effects of HDAC inhibitors, trichostatin A (TSA and suberoylanilide hydroxamic acid (SAHA; also known as vorinostat in vitro and in vivo. TSA and SAHA suppress ERMS tumor growth and progression by inducing myogenic differentiation as well as reducing the self-renewal and migratory capacity of ERMS cells. Differential expression profiling and pathway analysis revealed downregulation of key oncogenic pathways upon HDAC inhibitor treatment. By gain-of-function, loss-of-function, and chromatin immunoprecipitation (ChIP studies, we show that Notch1- and EphrinB1-mediated pathways are regulated by HDACs to inhibit differentiation and enhance migratory capacity of ERMS cells, respectively. Our study demonstrates that aberrant HDAC activity plays a major role in ERMS pathogenesis. Druggable targets in the molecular pathways affected by HDAC inhibitors represent novel therapeutic options for ERMS patients.

Out of mind, out of sight: perceptual consequences of memory suppression.

Science.gov (United States)

Kim, Kyungmi; Yi, Do-Joon

2013-04-01

In the present study, the effect of memory suppression on subsequent perceptual processing of visual objects was examined within a modified think/no-think paradigm. Suppressing memories of visual objects significantly impaired subsequent perceptual identification of those objects when they were briefly encountered (Experiment 1) and when they were presented in noise (Experiment 2), relative to performance on baseline items for which participants did not undergo suppression training. However, in Experiment 3, when perceptual identification was performed on mirror-reversed images of to-be-suppressed objects, no impairment was observed. These findings, analogous to those showing forgetting of suppressed words in long-term memory, suggest that suppressing memories of visual objects might be mediated by direct inhibition of perceptual representations, which, in turn, impairs later perception of them. This study provides strong support for the role of inhibitory mechanisms in memory control and suggests a tight link between higher-order cognitive operations and perceptual processing.

Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression1

Science.gov (United States)

Woodham, Andrew W.; Raff, Adam B.; Raff, Laura M.; Da Silva, Diane M.; Yan, Lisa; Skeate, Joseph G.; Wong, Michael K.; Lin, Yvonne G.; Kast, W. Martin

2014-01-01

High-risk human papillomaviruses (HPV) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cellsin a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the antigen presenting cells of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. Here, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by siRNA downregulation of A2t, significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein. PMID:24719459

Insights into the key roles of epigenetics in matrix macromolecules-associated wound healing.

Science.gov (United States)

Piperigkou, Zoi; Götte, Martin; Theocharis, Achilleas D; Karamanos, Nikos K

2017-10-24

Extracellular matrix (ECM) is a dynamic network of macromolecules, playing a regulatory role in cell functions, tissue regeneration and remodeling. Wound healing is a tissue repair process necessary for the maintenance of the functionality of tissues and organs. This highly orchestrated process is divided into four temporally overlapping phases, including hemostasis, inflammation, proliferation and tissue remodeling. The dynamic interplay between ECM and resident cells exerts its critical role in many aspects of wound healing, including cell proliferation, migration, differentiation, survival, matrix degradation and biosynthesis. Several epigenetic regulatory factors, such as the endogenous non-coding microRNAs (miRNAs), are the drivers of the wound healing response. microRNAs have pivotal roles in regulating ECM composition during wound healing and dermal regeneration. Their expression is associated with the distinct phases of wound healing and they serve as target biomarkers and targets for systematic regulation of wound repair. In this article we critically present the importance of epigenetics with particular emphasis on miRNAs regulating ECM components (i.e. glycoproteins, proteoglycans and matrix proteases) that are key players in wound healing. The clinical relevance of miRNA targeting as well as the delivery strategies designed for clinical applications are also presented and discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Beliefs about emotions mediate the relationship between emotional suppression and quality of life in irritable bowel syndrome.

Science.gov (United States)

Bowers, Hannah; Wroe, Abigail

2016-01-01

Cross-sectional and experimental research has demonstrated an association between emotional suppression and IBS. However, the relationship is not well understood. To examine the relationships between emotional suppression, we compare the measures of beliefs about emotions and quality of life in irritable bowel syndrome (IBS) with healthy controls. Online questionnaires measured beliefs about emotions, emotional suppression and IBS-related quality of life in participants with (n = 87) and without (n = 37) IBS. Mediation analyses and group comparisons were used to explore the role of emotional suppression and beliefs about emotions in this sample. IBS participants held significantly more beliefs about the unacceptability of emotions compared to healthy controls despite no differences in emotional suppression. The relationship between beliefs about emotions and quality of life was not mediated by emotional suppression. However, the relationship between emotional suppression and quality of life was mediated by beliefs about emotions. The findings suggest a role of beliefs about emotions and emotional suppression in IBS, where emotional suppression may relate to changes in beliefs about emotions and consequently quality of life. This is discussed in relation to the cognitive-behavioural model of medically unexplained symptoms.

Monitoring the HIV continuum of care in key populations across Europe and Central Asia.

Science.gov (United States)

Brown, A E; Attawell, K; Hales, D; Rice, B D; Pharris, A; Supervie, V; Van Beckhoven, D; Delpech, V C; An der Heiden, M; Marcus, U; Maly, M; Noori, T

2018-05-08

The aim of the study was to measure and compare national continuum of HIV care estimates in Europe and Central Asia in three key subpopulations: men who have sex with men (MSM), people who inject drugs (PWID) and migrants. Responses to a 2016 European Centre for Disease Prevention and Control (ECDC) survey of 55 European and Central Asian countries were used to describe continuums of HIV care for the subpopulations. Data were analysed using three frameworks: Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets; breakpoint analysis identifying reductions between adjacent continuum stages; quadrant analysis categorizing countries using 90% cut-offs for continuum stages. Overall, 29 of 48 countries reported national data for all HIV continuum stages (numbers living with HIV, diagnosed, receiving treatment and virally suppressed). Six countries reported all stages for MSM, seven for PWID and two for migrants. Thirty-one countries did not report data for MSM (34 for PWID and 41 for migrants). In countries that provided key-population data, overall, 63%, 40% and 41% of MSM, PWID and migrants living with HIV were virally suppressed, respectively (compared with 68%, 65% and 68% nationally, for countries reporting key-population data). Variation was observed between countries, with higher outcomes in subpopulations in Western Europe compared with Eastern Europe and Central Asia. Few reporting countries can produce the continuum of HIV care for the three key populations. Where data are available, differences exist in outcomes between the general and key populations. While MSM broadly mirror national outcomes (in the West), PWID and migrants experience poorer treatment and viral suppression. Countries must develop continuum measures for key populations to identify and address inequalities. © 2018 British HIV Association.

Assessing the Role of ETHYLENE RESPONSE FACTOR Transcriptional Repressors in Salicylic Acid-Mediated Suppression of Jasmonic Acid-Responsive Genes.

Science.gov (United States)

Caarls, Lotte; Van der Does, Dieuwertje; Hickman, Richard; Jansen, Wouter; Verk, Marcel C Van; Proietti, Silvia; Lorenzo, Oscar; Solano, Roberto; Pieterse, Corné M J; Van Wees, Saskia C M

2017-02-01

Salicylic acid (SA) and jasmonic acid (JA) cross-communicate in the plant immune signaling network to finely regulate induced defenses. In Arabidopsis, SA antagonizes many JA-responsive genes, partly by targeting the ETHYLENE RESPONSE FACTOR (ERF)-type transcriptional activator ORA59. Members of the ERF transcription factor family typically bind to GCC-box motifs in the promoters of JA- and ethylene-responsive genes, thereby positively or negatively regulating their expression. The GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Here, we investigated whether SA-induced ERF-type transcriptional repressors, which may compete with JA-induced ERF-type activators for binding at the GCC-box, play a role in SA/JA antagonism. We selected ERFs that are transcriptionally induced by SA and/or possess an EAR transcriptional repressor motif. Several of the 16 ERFs tested suppressed JA-dependent gene expression, as revealed by enhanced JA-induced PDF1.2 or VSP2 expression levels in the corresponding erf mutants, while others were involved in activation of these genes. However, SA could antagonize JA-induced PDF1.2 or VSP2 in all erf mutants, suggesting that the tested ERF transcriptional repressors are not required for SA/JA cross-talk. Moreover, a mutant in the co-repressor TOPLESS, that showed reduction in repression of JA signaling, still displayed SA-mediated antagonism of PDF1.2 and VSP2. Collectively, these results suggest that SA-regulated ERF transcriptional repressors are not essential for antagonism of JA-responsive gene expression by SA. We further show that de novo SA-induced protein synthesis is required for suppression of JA-induced PDF1.2, pointing to SA-stimulated production of an as yet unknown protein that suppresses JA-induced transcription. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Research on Strong Clutter Suppression for Gaofen-3 Dual-Channel SAR/GMTI

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Mingjie Zheng

2018-03-01

Full Text Available In spaceborne synthetic aperture radar (SAR, moving targets are almost buried in ground clutter due to the wide clutter Doppler spectrum and the restricted pulse repetition frequency (PRF, which increases the difficulty of moving target detection. Clutter suppression is one of the key issues in the spaceborne SAR moving target indicator operation. In this paper, we describe the clutter suppression principle and analyze the influence of amplitude and phase error on clutter suppression. In the following, a novel dual-channel SAR clutter suppression algorithm is proposed, which is suitable for the Gaofen-3(GF-3 SAR sensor. The proposed algorithm consists of three technique steps, namely adaptive two-dimensional (2D channel calibration, refined amplitude error correction and refined phase error correction. After channel error is corrected by these procedures, the clutter component, especially a strong clutter component, can be well suppressed. The validity of the proposed algorithm is verified by GF-3 SAR real data which demonstrates the ground moving-target indication (GMTI capability of GF-3 SAR sensor.

A Novel Meloidogyne incognita Effector Misp12 Suppresses Plant Defense Response at Latter Stages of Nematode Parasitism

Science.gov (United States)

Xie, Jialian; Li, Shaojun; Mo, Chenmi; Wang, Gaofeng; Xiao, Xueqiong; Xiao, Yannong

2016-01-01

Secreted effectors in plant root-knot nematodes (RKNs, or Meloidogyne spp.) play key roles in their parasite processes. Currently identified effectors mainly focus on the early stage of the nematode parasitism. There are only a few reports describing effectors that function in the latter stage. In this study, we identified a potential RKN effector gene, Misp12, that functioned during the latter stage of parasitism. Misp12 was unique in the Meloidogyne spp., and highly conserved in Meloidogyne incognita. It encoded a secretory protein that specifically expressed in the dorsal esophageal gland, and highly up-regulated during the female stages. Transient expression of Misp12-GUS-GFP in onion epidermal cell showed that Misp12 was localized in cytoplast. In addition, in planta RNA interference targeting Misp12 suppressed the expression of Misp12 in nematodes and attenuated parasitic ability of M. incognita. Furthermore, up-regulation of jasmonic acid (JA) and salicylic acid (SA) pathway defense-related genes in the virus-induced silencing of Misp12 plants, and down-regulation of SA pathway defense-related genes in Misp12-expressing plants indicated the gene might be associated with the suppression of the plant defense response. These results demonstrated that the novel nematode effector Misp12 played a critical role at latter parasitism of M. incognita. PMID:27446188

Weight Suppression Predicts Bulimic Symptoms at 20-year Follow-up: The Mediating Role of Drive for Thinness

Science.gov (United States)

Bodell, Lindsay P.; Brown, Tiffany A.; Keel, Pamela K.

2016-01-01

Weight suppression predicts the onset and maintenance of bulimic syndromes. Despite this finding, no study has examined psychological mechanisms contributing to these associations using a longitudinal design. Given societal pressures to be thin and an actual history of higher weight, it is possible that greater weight suppression contributes to increased fear of gaining weight and preoccupation with being thin, which increase vulnerability to eating disorders. The present study investigated whether greater drive for thinness mediates associations between weight suppression and bulimic symptoms over long-term follow-up. Participants were women (n = 1190) and men (n = 509) who completed self-report surveys in college and 10- and 20- years later. Higher weight suppression at baseline predicted higher bulimic symptoms at 20-year follow-up (p symptoms, body mass index, and drive for thinness. Increased drive for thinness at 10-year follow-up mediated this effect. Findings highlight the long-lasting effect of weight suppression on bulimic symptoms and suggest that preoccupation with thinness may help maintain this association. Future studies would benefit from incorporating other hypothesized consequences of weight suppression, including biological factors, into risk models. PMID:27808544

Desensitization of delayed-type hypersensitivity in mice: suppressive environment

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Takashi Katsura

1993-01-01

Full Text Available The systemic injection of high doses of antigen into a preimmunized animal results in transient unresponsiveness of cell-mediated immune responses. This phenomenon is known as desensitization. Serum interleukin 2 (IL-2 activity was found transiently in desensitized mice at 3 h after the antigen challenge. These mice could not reveal antigen nonspecific delayed-type hypersensitivity (DTH 1 d after the challenge. Specific suppression of DTH was observed at later stages. Sera from 3 h desensitized mice showed suppressive effects on DTH in preo immunized mice. Administration of recombinant IL-2 into preimmunized mice led to the failure of development of DTH to antigens. These observations suggest that IL-2 plays an important role in the suppressive environment.

MR staging of pelvic endometriosis. Role of fat-suppression T{sub 1}-weighted images

Energy Technology Data Exchange (ETDEWEB)

Oishi-Tanaka, Yumiko; Itai, Yuji; Anno, Izumi; Matsumoto, Kunihiko; Ebihara, Reiko; Nishida, Masato [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

1996-05-01

We examined whether MR can determine the stage of endometriosis according to the scoring system established and revised by the American Fertility Society (r-AFS), a system which is widely used by gynecologists. We also studied the utility of fat suppression T{sub 1}-weighted images in improving accuracy. Seventeen patients with endometriosis examined by conventional MR were included in this study. All the patients had surgically proved stage III or IV disease. We determined the stage by MR using the following criteria according to the r-AFS system: adnexal masses without normal ovarian tissue were considered deep ovarian lesions, while those with normal tissue were considered superficial. A lack of fat between the lesion and surrounding structures was considered a dense adhesion, and hyperintense spots were considered peritoneal implants. The MR scores of patients with and without fat suppression were correlated with the surgical scores. MR staging corresponded to surgical staging in 15 of the 17 patients. In eight patients, peritoneal implants of less than 1.5 cm were depicted only by fat-suppression images. However, these lesions did not change the score significantly. MR imaging could determine the stage in advanced endometriosis. Fat-suppression could highlight smaller implants. These tiny lesions had little clinical meaning in these advanced cases; however, the clinical value of this technique should be evaluated in milder disease. (author)

Myeloid-derived suppressor cells mediate immune suppression in spinal cord injury.

Science.gov (United States)

Wang, Lei; Yu, Wei-bo; Tao, Lian-yuan; Xu, Qing

2016-01-15

Spinal cord injury (SCI) is characterized by the loss of motor and sensory functions in areas below the level of the lesion and numerous accompanying deficits. Previous studies have suggested that myeloid-derived suppressor cell (MDSC)-induced immune depression may play a pivotal role in the course of SCI. However, the concrete mechanism of these changes regarding immune suppression remains unknown. Here, we created an SCI mouse model to gain further evidence regarding the relationship between MDSCs following SCI and T lymphocyte suppression. We showed that in the SCI mouse model, the expanding MDSCs have the capacity to suppress T cell proliferation, and this suppression could be reversed by blocking the arginase. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract

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Ohnuma, Tomokazu; Matsumoto, Takashi; Itoi, Ayano; Kawana, Ayako; Nishiyama, Takahito; Ogura, Kenichiro [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan); Hiratsuka, Akira, E-mail: hiratuka@toyaku.ac.jp [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan)

2011-10-07

Highlights: {yields} We found a novel inhibitor of Nrf2 known as a chemoresistance factor. {yields} Overexpressed Nrf2 in lung cancer cells was suppressed by Cinnamomi Cortex extract. {yields} Cytotoxic action of anticancer drugs in cells treated with the extract was enhanced. {yields} Procyanidin tetramers and pentamers were active components in suppressing Nrf2. -- Abstract: Nuclear factor-E2-related factor 2 (Nrf2) is an important cytoprotective transcription factor because Nrf2-regulated enzymes play a key role in antioxidant and detoxification processes. Recent studies have reported that lung cancer cells overexpressing Nrf2 exhibit increased resistance to chemotherapy. Suppression of overexpressed Nrf2 is needed for a new therapeutic approach against lung cancers. In the present study, we found that Cinnamomi Cortex extract (CCE) has an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells with high Nrf2 activity. Moreover, we demonstrated that CCE significantly enhances sensitivity of A549 cells to the cytotoxic action of doxorubicin and etoposide as well as increasing the intracellular accumulation of both drugs. These results suggest that CCE might be an effective concomitant agent to reduce anticancer drug resistance derived from Nrf2 overexpression. Bioactivity-guided fractionation revealed that procyanidin tetramers and pentamers contained in CCE were active components in suppressing Nrf2.

Suppression of subthreshold characteristics variation for junctionless multigate transistors using high-k spacers

International Nuclear Information System (INIS)

Lou, Haijun; Zhang, Baili; Li, Dan; Lin, Xinnan; He, Jin; Chan, Mansun

2015-01-01

In this work, the high-k spacer is proposed to suppress the subthreshold characteristics variation of junctionless multigate transistor (JMT) with non-ideal sidewall angle for the first time. It is demonstrated that the variation of subthreshold characteristics induced by the changing sidewall angle is efficiently suppressed by high-k spacers due to the enhanced corner effect through the fringe capacitance, and the electrostatic integrity of JMTs is also improved at sub-22 nm gate length. Two key parameters of high-k spacer, the thickness and length, have been optimized in terms of the suppression of subthreshold characteristics variation. Then their optimal values are proposed. The benefit of high-k spacer makes JMTs more scalable. (paper)

Emotional suppression explains the link between early life stress and plasma oxytocin.

Science.gov (United States)

Mohiyeddini, Changiz; Opacka-Juffry, Jolanta; Gross, James J

2014-01-01

Early life stress (ELS) has been found to be associated with lower concentrations of plasma oxytocin (OT) in adulthood. It is not yet clear, however, what mechanisms underlie this association. The goal of the present study was to test the role of emotional suppression as an intervening variable between ELS in childhood and plasma OT. In a nonclinical sample of 90 men, ELS, emotional suppression, and plasma OT were assessed. Emotional suppression was positively associated with ELS (r = 0.37, p emotion regulation strategy - was not correlated with ELS or plasma OT concentrations. Cross-sectional regression analyses revealed that the ELS explained variance in plasma OT via emotional suppression. Moderation analyses revealed that the combination of high ELS and high emotional suppression was associated with the lowest concentrations of plasma oxytocin. These findings are consistent with the view that emotional suppression may be one pathway linking ELS and OT.

Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout

International Nuclear Information System (INIS)

Sandhu, Navdeep; Vijayan, Mathilakath M.

2011-01-01

Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000 nM) for 4 h either in the presence or absence of ACTH (0.5 IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of

Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout

Energy Technology Data Exchange (ETDEWEB)

Sandhu, Navdeep [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada); Vijayan, Mathilakath M., E-mail: mvijayan@uwaterloo.ca [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada)

2011-05-15

Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000 nM) for 4 h either in the presence or absence of ACTH (0.5 IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of

Suppressive effect of AMP-activated protein kinase on the epithelial-mesenchymal transition in retinal pigment epithelial cells.

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Ryo Matoba

Full Text Available The epithelial-mesenchymal transition (EMT in retinal pigment epithelial (RPE cells plays a central role in the development of proliferative vitreoretinopathy (PVR. The purpose of this study was to investigate the effect of AMP-activated protein kinase (AMPK, a key regulator of energy homeostasis, on the EMT in RPE cells. In this study, EMT-associated formation of cellular aggregates was induced by co-stimulation of cultured ARPE-19 cells with tumor necrosis factor (TNF-α (10 ng/ml and transforming growth factor (TGF-β2 (5 ng/ml. 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR, a potent activator of AMPK, significantly suppressed TNF-α and TGF-β2-induced cellular aggregate formation (p < 0.01. Dipyridamole almost completely reversed the suppressive effect of AICAR, whereas 5'-amino-5'-deoxyadenosine restored aggregate formation by approximately 50%. AICAR suppressed the downregulation of E-cadherin and the upregulation of fibronectin and α-smooth muscle actin by TNF-α and TGF-β2. The levels of matrix metalloproteinase (MMP-2, MMP-9, interleukin-6, and vascular endothelial growth factor were significantly decreased by AICAR. Activation of the mitogen-activated protein kinase and mammalian target of rapamycin pathways, but not the Smad pathway, was inhibited by AICAR. These findings indicate that AICAR suppresses the EMT in RPE cells at least partially via activation of AMPK. AMPK is a potential target molecule for the prevention and treatment of PVR, so AICAR may be a promising candidate for PVR therapy.

Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

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Logan Richard M

2010-03-01

Full Text Available Abstract Background Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

Energy Technology Data Exchange (ETDEWEB)

Peng, Ting; Wang, Wei-Na, E-mail: weina63@aliyun.com; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

2015-06-15

Highlights: • Cd{sup 2+} induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd{sup 2+}. • DsRNA-suppression of LvCdc42 and MAPKs during Cd{sup 2+} stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd{sup 2+} stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd{sup 2+}. They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses.

Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

International Nuclear Information System (INIS)

Peng, Ting; Wang, Wei-Na; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

2015-01-01

Highlights: • Cd 2+ induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd 2+ . • DsRNA-suppression of LvCdc42 and MAPKs during Cd 2+ stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd 2+ stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd 2+ . They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses

Testosterone Suppression of CRH-stimulated Cortisol in Men

OpenAIRE

Rubinow, David R.; Roca, Catherine A.; Schmidt, Peter J.; Danaceau, Merry A.; Putnam, Karen; Cizza, Giovanni; Chrousos, George; Nieman, Lynnette

2005-01-01

Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in ten men (ages 18–45) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower ...

Roles and responsibilities of pharmacists with respect to natural health products: key informant interviews.

Science.gov (United States)

Olatunde, Shade; Boon, Heather; Hirschkorn, Kristine; Welsh, Sandy; Bajcar, Jana

2010-03-01

Although many pharmacies sell natural health products (NHPs), there is no clear definition as to the roles and responsibilities (if any) of pharmacists with respect to these products. The purpose of this study was to explore pharmacy and stakeholder leaders' perceptions of pharmacists' professional NHP roles and responsibilities. Semi-structured key informant interviews were conducted with pharmacy leaders (n=17) and stakeholder (n=18) leaders representing consumers, complementary and alternative medicine practitioners, conventional health care practitioners, and industry across Canada. All participants believed a main NHP responsibility for pharmacists was in safety monitoring, although a one challenge identified in the interviews was pharmacists' general lack of NHP knowledge; however, stakeholder leaders did not expect pharmacists to be experts, but should have a basic level of knowledge about NHPs. Participants described pharmacists' professional roles and responsibilities for NHPs as similar to those for over-the-counter drugs; more awareness of existing NHP-related pharmacy policies is needed, and pharmacy owners/managers should provide additional training to ensure front-line pharmacists have appropriate knowledge of NHPs sold in the pharmacy. Copyright 2010 Elsevier Inc. All rights reserved.

MEK5 suppresses osteoblastic differentiation

Energy Technology Data Exchange (ETDEWEB)

Kaneshiro, Shoichi [Department of Orthopaedic Surgery, Japan Community Health Care Organization Osaka Hospital, 4-2-78 Fukushima, Fukushima Ward, Osaka City, Osaka 553-0003 (Japan); Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Otsuki, Dai; Yoshida, Kiyoshi; Yoshikawa, Hideki [Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Higuchi, Chikahisa, E-mail: c-higuchi@umin.ac.jp [Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

2015-07-31

Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. - Highlights: • MEK5 inhibitor BIX02189 suppresses proliferation of osteoblasts. • MEK5 knockdown and MEK5 inhibitor promote differentiation of osteoblasts. • MEK5 overexpression inhibits differentiation of osteoblasts.

Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling.

Science.gov (United States)

Moon, Seungtae; Lee, Yong-Kyu; Lee, Sang-Wang; Um, Soo-Jong

2017-10-07

BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. However, its regulation via glycosylation and its role in embryonic stem (ES) cells are poorly defined. BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). Here, we confirmed the physical interaction and investigated its functional significance. The O-GlcNAcylation of BAP1, which requires OGT, was examined in vivo and in vitro, and was proven using alloxan, an OGT inhibitor. OGT promoted the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation. The repressive activity of BAP1 was relieved by alloxan but exacerbated by PUGNAc, an O-GlcNAcase (OGA) inhibitor. Finally, we addressed the role of O-GlcNAcylation in the RA-induced differentiation of murine ES cells. Alkaline phosphatase staining revealed the cooperation of RA and alloxan for impairing the pluripotency of ES cells. This cooperation was also observed by measuring the size of embryonic bodies and the expression of Sox2, a pluripotency marker. Overall, our data suggest that OGT-mediated O-GlcNAcylation of BAP1 prefers the maintenance of pluripotency, whereas its inhibition facilitates RA-induced differentiation in ES cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Mode of ATM-dependent suppression of chromosome translocation

Energy Technology Data Exchange (ETDEWEB)

Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

2011-12-09

Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways

Directory of Open Access Journals (Sweden)

Radhakrishnan Sridhar

2010-05-01

Full Text Available Abstract Background Obesity is a global phenomenon and is associated with various types of cancer, including colon cancer. There is a growing interest for safe and effective bioactive compounds that suppress the risk for obesity-promoted colon cancer. Resveratrol (trans-3, 4', 5,-trihydroxystilbene, a stilbenoid found in the skin of red grapes and peanuts suppresses many types of cancers by regulating cell proliferation and apoptosis through a variety of mechanisms, however, resveratrol effects on obesity-promoted colon cancer are not clearly established. Methods We investigated the anti-proliferative effects of resveratrol on HT-29 and SW480 human colon cancer cells in the presence and absence of insulin like growth factor-1 (IGF-1; elevated during obesity and elucidated the mechanisms of action using IGF-1R siRNA in HT-29 cells which represents advanced colon carcinogenesis. Results Resveratrol (100-150 μM exhibited anti-proliferative properties in HT-29 cells even after IGF-1 exposure by arresting G0/G1-S phase cell cycle progression through p27 stimulation and cyclin D1 suppression. Treatment with resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation. Targeted suppression of IGF-1R using IGF-1R siRNA also affected these signaling pathways in a similar manner. Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein, whereas IGF-1R siRNA treatment did not affect apoptosis. Our data suggests that resveratrol not only suppresses cell proliferation by inhibiting IGF-1R and its downstream signaling pathways similar to that of IGF-1R siRNA but also enhances apoptosis via activation of the p53 pathway. Conclusions For the first time, we report that resveratrol suppresses colon cancer cell proliferation and elevates apoptosis even in the presence of IGF-1 via suppression of IGF-1R/Akt/Wnt signaling pathways and

Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways

International Nuclear Information System (INIS)

Vanamala, Jairam; Reddivari, Lavanya; Radhakrishnan, Sridhar; Tarver, Chris

2010-01-01

Obesity is a global phenomenon and is associated with various types of cancer, including colon cancer. There is a growing interest for safe and effective bioactive compounds that suppress the risk for obesity-promoted colon cancer. Resveratrol (trans-3, 4', 5,-trihydroxystilbene), a stilbenoid found in the skin of red grapes and peanuts suppresses many types of cancers by regulating cell proliferation and apoptosis through a variety of mechanisms, however, resveratrol effects on obesity-promoted colon cancer are not clearly established. We investigated the anti-proliferative effects of resveratrol on HT-29 and SW480 human colon cancer cells in the presence and absence of insulin like growth factor-1 (IGF-1; elevated during obesity) and elucidated the mechanisms of action using IGF-1R siRNA in HT-29 cells which represents advanced colon carcinogenesis. Resveratrol (100-150 μM) exhibited anti-proliferative properties in HT-29 cells even after IGF-1 exposure by arresting G 0 /G 1 -S phase cell cycle progression through p27 stimulation and cyclin D1 suppression. Treatment with resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation. Targeted suppression of IGF-1R using IGF-1R siRNA also affected these signaling pathways in a similar manner. Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein, whereas IGF-1R siRNA treatment did not affect apoptosis. Our data suggests that resveratrol not only suppresses cell proliferation by inhibiting IGF-1R and its downstream signaling pathways similar to that of IGF-1R siRNA but also enhances apoptosis via activation of the p53 pathway. For the first time, we report that resveratrol suppresses colon cancer cell proliferation and elevates apoptosis even in the presence of IGF-1 via suppression of IGF-1R/Akt/Wnt signaling pathways and activation of p53, suggesting its potential role as a

Testosterone suppression of CRH-stimulated cortisol in men.

Science.gov (United States)

Rubinow, David R; Roca, Catherine A; Schmidt, Peter J; Danaceau, Merry A; Putnam, Karen; Cizza, Giovanni; Chrousos, George; Nieman, Lynnette

2005-10-01

Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in 10 men (ages 18-45 years) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower (pcortisol area under the curve was lower at a trend level (pcortisol : ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (pcortisol. These data demonstrate that testosterone regulates CRH-stimulated HPA axis activity in men, with the divergent effects on ACTH and cortisol suggesting a peripheral (adrenal) locus for the suppressive effects on cortisol. Our results further demonstrate that the enhanced stimulated HPA axis activity previously described in young men compared with young women cannot be ascribed to an activational upregulation of the axis by testosterone.

Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation

DEFF Research Database (Denmark)

Connolly, Brian M; Choi, Eun Young; Gårdsvoll, Henrik

2010-01-01

the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure...... a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor....

Myeloma cells suppress osteoblasts through sclerostin secretion

Energy Technology Data Exchange (ETDEWEB)

Colucci, S; Brunetti, G; Oranger, A [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Mori, G [Department of Biomedical Science, University of Foggia, Foggia (Italy); Sardone, F [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Specchia, G; Rinaldi, E; Curci, P; Liso, V [Department of Emergency and Organ Transplantation, Hematology Section, Bari University Medical School, Bari (Italy); Passeri, G [Department of Internal Medicine and Biomedical Sciences, Center for Metabolic Bone Diseases, University of Parma, Parma (Italy); Zallone, A [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Rizzi, R [Department of Emergency and Organ Transplantation, Hematology Section, Bari University Medical School, Bari (Italy); Grano, M [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy)

2011-06-01

Wingless-type (Wnt) signaling through the secretion of Wnt inhibitors Dickkopf1, soluble frizzled-related protein-2 and -3 has a key role in the decreased osteoblast (OB) activity associated with multiple myeloma (MM) bone disease. We provide evidence that another Wnt antagonist, sclerostin, an osteocyte-expressed negative regulator of bone formation, is expressed by myeloma cells, that is, human myeloma cell lines (HMCLs) and plasma cells (CD138+ cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. We demonstrated that BM stromal cells (BMSCs), differentiated into OBs and co-cultured with HMCLs showed, compared with BMSCs alone, reduced expression of major osteoblastic-specific proteins, decreased mineralized nodule formation and attenuated the expression of members of the activator protein 1 transcription factor family (Fra-1, Fra-2 and Jun-D). Moreover, in the same co-culture system, the addition of neutralizing anti-sclerostin antibodies restored OB functions by inducing nuclear accumulation of β-catenin. We further demonstrated that the upregulation of receptor activator of nuclear factor κ-B ligand and the downregulation of osteoprotegerin in OBs were also sclerostin mediated. Our data indicated that sclerostin secretion by myeloma cells contribute to the suppression of bone formation in the osteolytic bone disease associated to MM.

The Role of Biotechnology in Sustainable Agriculture: Views and Perceptions among Key Actors in the Swedish Food Supply Chain

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Karin Edvardsson Björnberg

2015-06-01

Full Text Available Researchers have put forward agricultural biotechnology as one possible tool for increasing food production and making agriculture more sustainable. In this paper, it is investigated how key actors in the Swedish food supply chain perceive the concept of agricultural sustainability and the role of biotechnology in creating more sustainable agricultural production systems. Based on policy documents and semi-structured interviews with representatives of five organizations active in producing, processing and retailing food in Sweden, an attempt is made to answer the following three questions: How do key actors in the Swedish food supply chain define and operationalize the concept of agricultural sustainability? Who/what influences these organizations’ sustainability policies and their respective positions on agricultural biotechnology? What are the organizations’ views and perceptions of biotechnology and its possible role in creating agricultural sustainability? Based on collected data, it is concluded that, although there is a shared view of the core constituents of agricultural sustainability among the organizations, there is less explicit consensus on how the concept should be put into practice or what role biotechnology can play in furthering agricultural sustainability.

Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity.

Science.gov (United States)

Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

2016-05-23

The uroguanylin-GUCY2C gut-brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ER(T2)-Rosa-STOP(loxP/loxP)-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms

Quests for justice and mechanisms of suppression in Flint, Michigan

DEFF Research Database (Denmark)

Rutt, Rebecca Leigh; Bluwstein, Jevgeniy

2017-01-01

There is widespread acknowledgment of the crisis nature and injustices around water quality and access in Flint since mid-2014. This crisis led to different forms of grassroots activism demanding political accountability, transparency, and redress. However, residents' experiences and their needs...... and demands in response to the crisis have been largely ignored. This article explores the mechanisms of suppression at work in obscuring these needs and demands. Specifically, it sheds light on the role of the public sector, the media, and the academic institutions in reproducing these mechanisms...... of suppression. The article situates the struggles over political accountability within the neoliberalization of public administration and government through emergency management. Capital accumulation can continue and intensifies, whereas emergency management further contributes to suppressing public dissent...

A protein interaction mechanism for suppressing the mechanosensitive Piezo channels.

Science.gov (United States)

Zhang, Tingxin; Chi, Shaopeng; Jiang, Fan; Zhao, Qiancheng; Xiao, Bailong

2017-11-27

Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca 2+ ATPase (SERCA), including the widely expressed SERCA2, as Piezo interacting proteins. SERCA2 strategically suppresses Piezo1 via acting on a 14-residue-constituted intracellular linker connecting the pore-module and mechanotransduction-module. Mutating the linker impairs mechanogating and SERCA2-mediated modulation of Piezo1. Furthermore, the synthetic linker-peptide disrupts the modulatory effects of SERCA2, demonstrating the key role of the linker in mechanogating and regulation. Importantly, the SERCA2-mediated regulation affects Piezo1-dependent migration of endothelial cells. Collectively, we identify SERCA-mediated regulation of Piezos and the functional significance of the linker, providing important insights into the mechanogating and regulation mechanisms of Piezo channels.

Sensitivity to Sunburn Is Associated with Susceptibility to Ultraviolet Radiation–Induced Suppression of Cutaneous Cell–Mediated Immunity

Science.gov (United States)

Kelly, Deirdre A.; Young, Antony R.; McGregor, Jane M.; Seed, Paul T.; Potten, Christopher S.; Walker, Susan L.

2000-01-01

Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer. PMID:10662801

Andrographolide suppresses preadipocytes proliferation through glutathione antioxidant systems abrogation.

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Chen, Wei; Su, Hongming; Feng, Lina; Zheng, Xiaodong

2016-07-01

Oxidative stress is considered to play a profound role in lipid storage and whole-body energy homeostasis. Inhibition of preadipocytes proliferation by natural products is one of the strategies to prevent obesity. Andrographolide, a small molecule, has been reported to possess versatile bioactivities. However, molecular mechanism underlying the potential effect of andrographolide on preadipocytes proliferation remains obscure. In the present study, 3T3-L1 preadipocytes were employed to determine whether andrographolide could affect the proliferation of preadipocytes. Our results demonstrated andrographolide suppressed 3T3-L1 preadipocytes proliferation. The casual relationship analysis indicated that andrographolide (10 and 20μg/ml) appeared to exert the proliferation inhibitory effect through suppression of glutathione peroxidase 1 (GPX1) activity and depleting GSH by promoting its efflux in 3T3-L1 preadipocytes, which subsequently resulted in 2.06-2.41 fold increase in ROS accumulation. Excessive ROS eruption could account for oxidative damage to mitochondrial membranes as well as ultimately inhibition of cell proliferation. Taken together, our study reveals that suppression of GPX1 and GSH depletion by andrographolide seems to play a critical role in the inhibition of 3T3-L1 preadipocytes proliferation, which might have implication for obesity prevention and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

Science.gov (United States)

Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

2013-10-01

Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

Increased suppression of oncolytic adenovirus carrying mutant k5 on colorectal tumor

International Nuclear Information System (INIS)

Fan Junkai; Xiao Tian; Gu Jinfa; Wei Na; He Lingfeng; Ding Miao; Liu Xinyuan

2008-01-01

Angiogenesis plays a key role in the development of a wide variety of malignant tumors. The approach of targeting antiangiogenesis has become an important field of cancer gene therapy. In this study, the antiangiogenesis protein K5 (the kringle 5 of human plasminogen) has been mutated by changing leucine71 to arginine to form mK5. Then the ZD55-mK5, which is an oncolytic adenovirus expressing mK5, was constructed. It showed stronger inhibition on proliferation of human umbilical vein endothelial cell. Moreover, in tube formation and embryonic chorioallantoic membrane assay, ZD55-mK5 exhibited more effective antiangiogenesis than ZD55-K5. In addition, ZD55-mK5 generated obvious suppression on the growth of colorectal tumor xenografts and prolonged the life span of nude mice. These results indicate that ZD55-mK5 is a potent agent for inhibiting the tumor angiogenesis and tumor growth

Distinct roles for soil fungal and bacterial communities associated with the suppression of vanilla Fusarium wilt disease

NARCIS (Netherlands)

Xiong, Wu; Li, Rong; Ren, Yi; Liu, Chen; Zhao, Qingyun; Wu, Huasong; Jousset, Alexandre; Shen, Qirong

2017-01-01

Characterizing microbial communities associated with disease-suppressive soil is an important first step toward understanding the potential of microbiota to protect crops against plant pathogens. In the present study, we compared microbial communities in suppressive- and conducive-soils associated

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Gordijn, Maartje S.; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2012-01-01

Background Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Gordijn, Maartje S.; Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2015-01-01

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2017-01-01

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

Semantic Keys and Reading

Directory of Open Access Journals (Sweden)

Zev bar-Lev

2016-12-01

Full Text Available Semantic Keys are elements (word-parts of written language that give an iconic, general representation of the whole word’s meaning. In written Sino-Japanese the “radical” or semantic components play this role. For example, the character meaning ‘woman, female’ is the Semantic Key of the character for Ma ‘Mama’ (alongside the phonetic component Ma, which means ‘horse’ as a separate character. The theory of semantic Keys in both graphic and phonemic aspects is called qTheory or nanosemantics. The most innovative aspect of the present article is the hypothesis that, in languages using alphabetic writing systems, the role of Semantic Key is played by consonants, more specifically the first consonant. Thus, L meaning ‘LIFT’ is the Semantic Key of English Lift, Ladle, Lofty, aLps, eLevator, oLympus; Spanish Leva, Lecantarse, aLto, Lengua; Arabic aLLah, and Hebrew① ªeL-ºaL ‘upto-above’ (the Israeli airline, Polish Lot ‘flight’ (the Polish airline; Hebrew ªeL, ªeLohim ‘God’, and haLLeluyah ‘praise-ye God’ (using Parallels, ‘Lift up God’. Evidence for the universality of the theory is shown by many examples drawn from various languages, including Indo-European Semitic, Chinese and Japanese. The theory reveals hundreds of relationships within and between languages, related and unrelated, that have been “Hiding in Plain Sight”, to mention just one example: the Parallel between Spanish Pan ‘bread’ and Mandarin Fan ‘rice’.

Role of Oxidative Stress in the Suppression of Immune Responses in Peripheral Blood Mononuclear Cells Exposed to Combustible Tobacco Product Preparation.

Science.gov (United States)

Arimilli, Subhashini; Schmidt, Eckhardt; Damratoski, Brad E; Prasad, G L

2017-10-01

Cigarette smoking is a major risk factor for several human diseases. Chronic inflammation, resulting from increased oxidative stress, has been suggested as a mechanism that contributes to the increased susceptibility of smokers to cancer and microbial infections. We have previously shown that whole-smoke conditioned medium (WS-CM) and total particulate matter (TPM) prepared from Kentucky 3R4F reference cigarettes [collectively called as combustible tobacco product preparations (TPPs)] potently suppressed agonist-stimulated cytokine secretion and target cell killing in peripheral blood mononuclear cells (PBMCs). Here we have investigated the role of oxidative stress from TPPs, which alters inflammatory responses in vitro. Particularly, we investigated the mechanisms of WS-CM-induced suppression of select cytokine secretions in Toll-like receptor (TLR) agonist-stimulated cells and target cell killing by effector cells in PBMCs. Pretreatment with N-acetyl cysteine (NAC), a precursor of reduced glutathione and an established anti-oxidant, protected against DNA damage and cytotoxicity caused by exposure to WS-CM. Similarly, secretion of tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 in response to TLR-4 stimulation was restored by pretreatment with NAC. Target cell killing, a functional measure of cytolytic cells in PBMCs, is suppressed by WS-CM. Pretreatment with NAC restored the target cell killing in WS-CM treated PBMCs. This was accompanied by higher perforin levels in the effector cell populations. Collectively, these data suggest that reducing oxidative stress caused by cigarette smoke components restores select immune responses in this ex vivo model.

Agroecology: the key role of arbuscular mycorrhizas in ecosystem services.

Science.gov (United States)

Gianinazzi, Silvio; Gollotte, Armelle; Binet, Marie-Noëlle; van Tuinen, Diederik; Redecker, Dirk; Wipf, Daniel

2010-11-01

The beneficial effects of arbuscular mycorrhizal (AM) fungi on plant performance and soil health are essential for the sustainable management of agricultural ecosystems. Nevertheless, since the 'first green revolution', less attention has been given to beneficial soil microorganisms in general and to AM fungi in particular. Human society benefits from a multitude of resources and processes from natural and managed ecosystems, to which AM make a crucial contribution. These resources and processes, which are called ecosystem services, include products like food and processes like nutrient transfer. Many people have been under the illusion that these ecosystem services are free, invulnerable and infinitely available; taken for granted as public benefits, they lack a formal market and are traditionally absent from society's balance sheet. In 1997, a team of researchers from the USA, Argentina and the Netherlands put an average price tag of US $33 trillion a year on these fundamental ecosystem services. The present review highlights the key role that the AM symbiosis can play as an ecosystem service provider to guarantee plant productivity and quality in emerging systems of sustainable agriculture. The appropriate management of ecosystem services rendered by AM will impact on natural resource conservation and utilisation with an obvious net gain for human society.

Fatal attraction? Intraguild facilitation and suppression among predators

Science.gov (United States)

Sivy, Kelly J.; Pozzanghera, Casey B.; Grace, James B.; Prugh, Laura R.

2017-01-01

Competition and suppression are recognized as dominant forces that structure predator communities. Facilitation via carrion provisioning, however, is a ubiquitous interaction among predators that could offset the strength of suppression. Understanding the relative importance of these positive and negative interactions is necessary to anticipate community-wide responses to apex predator declines and recoveries worldwide. Using state-sponsored wolf (Canis lupus) control in Alaska as a quasi experiment, we conducted snow track surveys of apex, meso-, and small predators to test for evidence of carnivore cascades (e.g., mesopredator release). We analyzed survey data using an integrative occupancy and structural equation modeling framework to quantify the strengths of hypothesized interaction pathways, and we evaluated fine-scale spatiotemporal responses of nonapex predators to wolf activity clusters identified from radio-collar data. Contrary to the carnivore cascade hypothesis, both meso- and small predator occupancy patterns indicated guild-wide, negative responses of nonapex predators to wolf abundance variations at the landscape scale. At the local scale, however, we observed a near guild-wide, positive response of nonapex predators to localized wolf activity. Local-scale association with apex predators due to scavenging could lead to landscape patterns of mesopredator suppression, suggesting a key link between occupancy patterns and the structure of predator communities at different spatial scales.

Fatal Attraction? Intraguild Facilitation and Suppression among Predators.

Science.gov (United States)

Sivy, Kelly J; Pozzanghera, Casey B; Grace, James B; Prugh, Laura R

2017-11-01

Competition and suppression are recognized as dominant forces that structure predator communities. Facilitation via carrion provisioning, however, is a ubiquitous interaction among predators that could offset the strength of suppression. Understanding the relative importance of these positive and negative interactions is necessary to anticipate community-wide responses to apex predator declines and recoveries worldwide. Using state-sponsored wolf (Canis lupus) control in Alaska as a quasi experiment, we conducted snow track surveys of apex, meso-, and small predators to test for evidence of carnivore cascades (e.g., mesopredator release). We analyzed survey data using an integrative occupancy and structural equation modeling framework to quantify the strengths of hypothesized interaction pathways, and we evaluated fine-scale spatiotemporal responses of nonapex predators to wolf activity clusters identified from radio-collar data. Contrary to the carnivore cascade hypothesis, both meso- and small predator occupancy patterns indicated guild-wide, negative responses of nonapex predators to wolf abundance variations at the landscape scale. At the local scale, however, we observed a near guild-wide, positive response of nonapex predators to localized wolf activity. Local-scale association with apex predators due to scavenging could lead to landscape patterns of mesopredator suppression, suggesting a key link between occupancy patterns and the structure of predator communities at different spatial scales.

Water relations, gas exchange and growth of dominant and suppressed shoots of Arbutus unedo L.

Science.gov (United States)

Castell, C; Terradas, J

1995-06-01

Basal shoots produced by Arbutus unedo L. after cutting at ground level vary in size and growth rate, and are classified accordingly as dominant or suppressed. The suppressed shoots eventually cease growth and die. In this study, we investigated the role of light and water in the competition among shoots of A. unedo. Dominant and suppressed shoots of A. unedo showed similar leaf water potentials and tissue water relations over the year, suggesting that water status is not responsible for the lack of flushing in suppressed shoots. Although suppressed shoots did not flush under low light, they showed many characteristics of shade-tolerant plants. Leaves of suppressed shoots had lower leaf conductance and light-saturated photosynthetic rate, and higher specific leaf area than leaves of dominant shoots. We conclude that light was the main resource determining competition among shoots and the death of suppressed shoots.

Security-enhanced chaos communication with time-delay signature suppression and phase encryption.

Science.gov (United States)

Xue, Chenpeng; Jiang, Ning; Lv, Yunxin; Wang, Chao; Li, Guilan; Lin, Shuqing; Qiu, Kun

2016-08-15

A security-enhanced chaos communication scheme with time delay signature (TDS) suppression and phase-encrypted feedback light is proposed, in virtue of dual-loop feedback with independent high-speed phase modulation. We numerically investigate the property of TDS suppression in the intensity and phase space and quantitatively discuss security of the proposed system by calculating the bit error rate of eavesdroppers who try to crack the system by directly filtering the detected signal or by using a similar semiconductor laser to synchronize the link signal and extract the data. The results show that TDS embedded in the chaotic carrier can be well suppressed by properly setting the modulation frequency, which can keep the time delay a secret from the eavesdropper. Moreover, because the feedback light is encrypted, without the accurate time delay and key, the eavesdropper cannot reconstruct the symmetric operation conditions and decode the correct data.

Error suppression and error correction in adiabatic quantum computation: non-equilibrium dynamics

International Nuclear Information System (INIS)

Sarovar, Mohan; Young, Kevin C

2013-01-01

While adiabatic quantum computing (AQC) has some robustness to noise and decoherence, it is widely believed that encoding, error suppression and error correction will be required to scale AQC to large problem sizes. Previous works have established at least two different techniques for error suppression in AQC. In this paper we derive a model for describing the dynamics of encoded AQC and show that previous constructions for error suppression can be unified with this dynamical model. In addition, the model clarifies the mechanisms of error suppression and allows the identification of its weaknesses. In the second half of the paper, we utilize our description of non-equilibrium dynamics in encoded AQC to construct methods for error correction in AQC by cooling local degrees of freedom (qubits). While this is shown to be possible in principle, we also identify the key challenge to this approach: the requirement of high-weight Hamiltonians. Finally, we use our dynamical model to perform a simplified thermal stability analysis of concatenated-stabilizer-code encoded many-body systems for AQC or quantum memories. This work is a companion paper to ‘Error suppression and error correction in adiabatic quantum computation: techniques and challenges (2013 Phys. Rev. X 3 041013)’, which provides a quantum information perspective on the techniques and limitations of error suppression and correction in AQC. In this paper we couch the same results within a dynamical framework, which allows for a detailed analysis of the non-equilibrium dynamics of error suppression and correction in encoded AQC. (paper)

Cost-effectiveness analysis and efficient use of the pharmaceutical budget: the key role of clinical pharmacologists.

Science.gov (United States)

Edlin, Richard; Round, Jeff; Hulme, Claire; McCabe, Christopher

2010-09-01

The purpose of this paper is to provide information about cost-effectiveness analysis and the roles of clinical pharmacologists generally in providing efficient health care. The paper highlights the potential consequences of 'off-label prescribing' and 'indication creep' behaviour given slower growth (or potential cuts) in the NHS budget. This paper highlights the key roles of clinical pharmacologists in delivering an efficient health care system when resources are allocated using cost-effectiveness analyses. It describes what cost-effectiveness analysis (CEA) is and how incremental cost-effectiveness ratios (ICERs) are used to identify efficient options. After outlining the theoretical framework within which using CEA can promote the efficient allocation of the health care budget, it considers the place of disinvestment within achieving efficient resource allocation. Clinical pharmacologists are argued to be critical to providing improved population health under CEA-based resource allocation processes because of their roles in implementation and disinvestment. Given that the challenges facing the United Kingdom National Health Service (NHS) are likely to increase, this paper sets out the stark choices facing clinical pharmacologists.

Suppressive and immunoprotective functions of Tregs

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Pushpa ePandiyan

2011-11-01

Full Text Available CD4+CD25+Foxp3+ T lymphocytes, known as regulatory T cells or Tregs, have been proposed to be a lineage of professional immune suppressive cells that exclusively counteract the effects of the immunoprotective "helper" and "cytotoxic" lineages of T lymphocytes. Here we discuss new concepts on the mechanisms and functions of Tregs. There are several key points we emphasize: 1. Tregs exert suppressive effects both directly on effector T cells and indirectly through antigen-presenting cells (APCs; 2. Regulation can occur through a novel mechanism of cytokine consumption to regulate as opposed to the usual mechanism of cytokine/chemokine production; 3. In cases where CD4+ effector T cells are directly inhibited by Tregs, it is chiefly through a mechanism of lymphokine withdrawal apoptosis leading to polyclonal deletion (PCD; and 4. Contrary to the current view, we discuss new evidence that Tregs, similar to other T cells lineages, can promote protective immune responses in certain infectious contexts (Pandiyan et al. 2011; Chen et al 2011. Although these points are at variance to varying degrees with the standard model of Treg behavior, we will recount developing findings that support these new concepts.

Exogenous regucalcin suppresses the growth of human liver cancer HepG2 cells in vitro.

Science.gov (United States)

Yamaguchi, Masayoshi; Murata, Tomiyasu

2018-04-05

Regucalcin, which its gene is localized on the X chromosome, plays a pivotal role as a suppressor protein in signal transduction in various types of cells and tissues. Regucalcin gene expression has been demonstrated to be suppressed in various tumor tissues of animal and human subjects, suggesting a potential role of regucalcin in carcinogenesis. Regucalcin, which is produced from the tissues including liver, is found to be present in the serum of human subjects and animals. This study was undertaken to determine the effects of exogenous regucalcin on the proliferation in cloned human hepatoma HepG2 cells in vitro. Proliferation of HepG2 cells was suppressed after culture with addition of regucalcin (0.01 – 10 nM) into culture medium. Exogenous regucalcin did not reveal apoptotic cell death in HepG2 cells in vitro. Suppressive effects of regucalcin on cell proliferation were not enhanced in the presence of various signaling inhibitors including tumor necrosis factor-α (TNF-α), Bay K 8644, PD98059, staurosporine, worthomannin, 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) or gemcitabine, which were found to suppress the proliferation. In addition, exogenous regucalcin suppressed the formation of colonies of cultured hepatoma cells in vitro. These findings demonstrated that exogenous regucalcin exhibits a suppressive effect on the growth of human hepatoma HepG2 cells, proposing a strategy with the gene therapy for cancer treatment.

The measurement and treatment of suppression in amblyopia.

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Black, Joanna M; Hess, Robert F; Cooperstock, Jeremy R; To, Long; Thompson, Benjamin

2012-12-14

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current estimates put the prevalence of amblyopia at approximately 1-3%(1-3), the majority of cases being monocular(2). Amblyopia is most frequently caused by ocular misalignment (strabismus), blur induced by unequal refractive error (anisometropia), and in some cases by form deprivation. Although amblyopia is initially caused by abnormal visual input in infancy, once established, the visual deficit often remains when normal visual input has been restored using surgery and/or refractive correction. This is because amblyopia is the result of abnormal visual cortex development rather than a problem with the amblyopic eye itself(4,5) . Amblyopia is characterized by both monocular and binocular deficits(6,7) which include impaired visual acuity and poor or absent stereopsis respectively. The visual dysfunction in amblyopia is often associated with a strong suppression of the inputs from the amblyopic eye under binocular viewing conditions(8). Recent work has indicated that suppression may play a central role in both the monocular and binocular deficits associated with amblyopia(9,10) . Current clinical tests for suppression tend to verify the presence or absence of suppression rather than giving a quantitative measurement of the degree of suppression. Here we describe a technique for measuring amblyopic suppression with a compact, portable device(11,12) . The device consists of a laptop computer connected to a pair of virtual reality goggles. The novelty of the technique lies in the way we present visual stimuli to measure suppression. Stimuli are shown to the amblyopic eye at high contrast while the contrast of the stimuli shown to the non-amblyopic eye are varied. Patients perform a simple signal/noise task that allows for a precise measurement of the strength of excitatory binocular interactions. The contrast offset at which

Hepatic NPC1L1 overexpression ameliorates glucose metabolism in diabetic mice via suppression of gluconeogenesis.

Science.gov (United States)

Kurano, Makoto; Hara, Masumi; Satoh, Hiroaki; Tsukamoto, Kazuhisa

2015-05-01

Inhibition of intestinal NPC1L1 by ezetimibe has been demonstrated to improve glucose metabolism in rodent models; however, the role of hepatic NPC1L1 in glucose metabolism has not been elucidated. In this study, we analyzed the effects of hepatic NPC1L1 on glucose metabolism. We overexpressed NPC1L1 in the livers of lean wild type mice, diet-induced obesity mice and db/db mice with adenoviral gene transfer. We found that in all three mouse models, hepatic NPC1L1 overexpression lowered fasting blood glucose levels as well as blood glucose levels on ad libitum; in db/db mice, hepatic NPC1L1 overexpression improved blood glucose levels to almost the same as those found in lean wild type mice. A pyruvate tolerance test revealed that gluconeogenesis was suppressed by hepatic NPC1L1 overexpression. Further analyses revealed that hepatic NPC1L1 overexpression decreased the expression of FoxO1, resulting in the reduced expression of G6Pase and PEPCK, key enzymes in gluconeogenesis. These results indicate that hepatic NPC1L1 might have distinct properties of suppressing gluconeogenesis via inhibition of FoxO1 pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Suppressed Belief

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Komarine Romdenh-Romluc

2009-12-01

Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

Consequences of stereotype suppression and internal suppression motivation : A self-regulation approach

NARCIS (Netherlands)

Gordijn, Ernestine H; Hindriks, Inge; Koomen, W; Dijksterhuis, Ap; van Knipppenberg, A.

The present research studied the effects of suppression of stereotypes on subsequent stereotyping. Moreover, the moderating influence of motivation to suppress stereotypes was examined. The first three experiments showed that suppression of stereotypes leads to the experience of engaging in

Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma.

Science.gov (United States)

Morisawa, Ayaka; Okui, Tatsuo; Shimo, Tsuyoshi; Ibaragi, Soichiro; Okusha, Yuka; Ono, Mitsuaki; Nguyen, Thi Thu Ha; Hassan, Nur Mohammad Monsur; Sasaki, Akira

2018-03-01

Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically where one of the mechanisms responsible for the invasion into facial bones occurs via the activation of osteoclasts. Copper has been demonstrated to play a key role in skeletal remodeling. However, the role of copper in cancer-associated bone destruction is thus far unknown. Lysyl oxidase (LOX) is a copper-dependent enzyme that promotes osteoclastogenesis. In the present study, we investigated the effects of copper on HNSCC with bone invasion by the copper chelator, ammonium tetrathiomolybdate (TM) in vitro and in vivo. We demonstrate that TM blocks the proliferation of HNSCC cells, inhibits LOX activation and decreases the expression of the receptor activator of nuclear factor-κB ligand (RANKL) in osteoblasts and osteocytes, subsequently suppressing bone destruction. These findings suggest that copper is a potential target for the treatment of HNSCCs associated with bone destruction.

A Role for PML in Innate Immunity

Science.gov (United States)

Lunardi, Andrea; Gaboli, Mirella; Giorgio, Marco; Rivi, Roberta; Bygrave, Anne; Antoniou, Michael; Drabek, Dubravka; Dzierzak, Elaine; Fagioli, Marta; Salmena, Leonardo; Botto, Marina; Cordon-Cardo, Carlos; Luzzatto, Lucio; Pelicci, Pier Giuseppe; Grosveld, Frank; Pandolfi, Pier Paolo

2011-01-01

The promyelocytic leukemia gene (PML) of acute promyelocytic leukemia is an established tumor suppressor gene with critical functions in growth suppression, induction of apoptosis, and cellular senescence. Interestingly, although less studied, PML seems to play a key role also in immune response to viral infection. Herein, we report that Pml −/− mice spontaneously develop an atypical invasive and lethal granulomatous lesion known as botryomycosis (BTM). In Pml −/− mice, BTM is the result of impaired function of macrophages, whereby they fail to become activated and are thus unable to clear pathogenic microorganisms. Accordingly, Pml −/− mice are resistant to lipopolysaccharide (LPS)–induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-κB prosurvival pathway. These results not only shed light on a new fundamental function of PML in innate immunity, but they also point to a proto-oncogenic role for PML in certain cellular and pathological contexts. PMID:21779477

When passion makes the heart grow colder: the role of passion in alternative goal suppression.

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Bélanger, Jocelyn J; Lafrenière, Marc-André K; Vallerand, Robert J; Kruglanski, Arie W

2013-01-01

Quality of goal engagement and alternative goal suppression were investigated in this research. Integrating the dualistic model of passion (Vallerand et al., 2003) with goal-systems theory (Kruglanski et al., 2002), we hypothesized that obsessive passion--associated with recurrent goal-conflicts--would predict greater alternative goal suppression (i.e., goal-shielding) than would harmonious passion--characterized by effective synthesis of the passionate activity with other life domains. Results from 5 laboratory studies supported these hypotheses. In Study 1, participants' dispositional measures of harmonious and obsessive passion were correlated with an implicit measure of goal-shielding. Obsessive (but not harmonious) passion predicted the suppression of alternative goals and the progressive inhibition of unfamiliar goals. In Study 2, we extended these findings by demonstrating the interrelation between quality of goal engagement and goal-commitment such that goal-shielding effects were enhanced, but only for goals in conflict with other life domains (vs. well-integrated goals). In Study 3, the causal influence of passion on goal-shielding was supported via an experimental manipulation of passion. In Study 4, we replicated and extended Studies 1 and 3 by experimentally demonstrating that obsessive (but not harmonious) passion is a mindset conducive to the development of inhibitory links with alternative goals. Study 5 explored the psychological costs associated with repeated unconscious goal suppression by examining its effects on the depletion of self-regulatory resources. Collectively, the present results suggest that the qualitative distinction between obsessive and harmonious passion has implications for the goal-shielding effect and for subsequent self-regulatory behavior.

Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.

Science.gov (United States)

Benton, Tami; Lynch, Kevin; Dubé, Benoit; Gettes, David R; Tustin, Nancy B; Ping Lai, Jian; Metzger, David S; Blume, Joshua; Douglas, Steven D; Evans, Dwight L

2010-11-01

To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down-regulate human immunodeficiency virus (HIV) infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/acquired immune deficiency syndrome. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system. The 5-HT transporter and 5-HT receptors are widely distributed throughout the central nervous and immune systems. Depression has been associated with suppression of natural killer cells and CD8(+) lymphocytes, key regulators of HIV infection. Ex vivo models for acute and chronic HIV infection were used to study the effects of citalopram on HIV viral infection and replication in 48 depressed and nondepressed women. For both the acute and chronic infection models, HIV reverse transcriptase activity was measured in the citalopram treatment condition and the control condition. The SSRI significantly down-regulated the reverse transcriptase response in both the acute and chronic infection models. Specifically, citalopram significantly decreased the acute HIV infectivity of macrophages. Citalopram also significantly decreased HIV viral replication in the latently infected T-cell line and in the latently infected macrophage cell line. There was no difference in down-regulation by depression status. These studies suggest that an SSRI enhances natural killer/CD8 noncytolytic HIV suppression in HIV/acquired immune deficiency syndrome and decreases HIV viral infectivity of macrophages, ex vivo, suggesting the need for in vivo studies to determine a potential role for agents targeting serotonin in the host defense against HIV.

TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia

Science.gov (United States)

Naeser, Margaret A.; Martin, Paula I.; Theoret, Hugo; Kobayashi, Masahito; Fregni, Felipe; Nicholas, Marjorie; Tormos, Jose M.; Steven, Megan S.; Baker, Errol H.; Pascual-Leone, Alvaro

2011-01-01

This study sought to discover if an optimum 1 cm2 area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1 Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions. PMID:21864891

Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion

Science.gov (United States)

Luisier, Raphaëlle; Unterberger, Elif B.; Goodman, Jay I.; Schwarz, Michael; Moggs, Jonathan; Terranova, Rémi; van Nimwegen, Erik

2014-01-01

Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis. PMID:24464994

The role of veterinarian in the monitoring programs of mastitis control

Science.gov (United States)

Maletić, M.; Magaš, V.; Maletić, J.

2017-09-01

Mastitis is the most common and the most expensive disease of dairy cows. It is followed by a large number of direct and indirect costs that burden the farm’s budget and lead to major economic and health losses. The veterinarian at the farm plays a key role in implementing a protocol of biosecurity measures, a protocol of control, therapy, and the suppression of clinical and subclinical mastitis. In order to successfully implement these measures, a good communication between a veterinarian and a farm staff who performs milking procedures is necessary in order to detect and treat all cases of mastitis in time.

Pathogenesis of herpes simplex virus in B cell-suppressed mice: the relative roles of cell-mediated and humoral immunity.

Science.gov (United States)

Kapoor, A K; Nash, A A; Wildy, P

1982-07-01

B cell responses of Balb/c mice were suppressed using sheep anti-mouse IgM serum. At 4 weeks, both B cell-suppressed and normal littermates were infected in the ear pinna with herpes simplex virus type 1 (HSV-1). The B cell-suppressed mice failed to produce neutralizing herpes antibodies in their sera but had a normal cell-mediated immunity (CMI) response as measured by a delayed hypersensitivity skin test. Although the infection was eliminated from the ear in both B cell-suppressed and normal mice by day 10 after infection, there was an indication that B cell-suppressed mice had a more florid primary infection of the peripheral and central nervous system and also a higher incidence of a latent infection. These results support the hypothesis that antibody is important in restricting the spread of virus to the central nervous system, whereas CMI is important in clearing the primary infection in the ear pinna.

Simulation of Axial Combustion Instability Development and Suppression in Solid Rocket Motors

Directory of Open Access Journals (Sweden)

David R. Greatrix

2009-03-01

Full Text Available In the design of solid-propellant rocket motors, the ability to understand and predict the expected behaviour of a given motor under unsteady conditions is important. Research towards predicting, quantifying, and ultimately suppressing undesirable strong transient axial combustion instability symptoms necessitates a comprehensive numerical model for internal ballistic simulation under dynamic flow and combustion conditions. An updated numerical model incorporating recent developments in predicting negative and positive erosive burning, and transient, frequency-dependent combustion response, in conjunction with pressure-dependent and acceleration-dependent burning, is applied to the investigation of instability-related behaviour in a small cylindrical-grain motor. Pertinent key factors, like the initial pressure disturbance magnitude and the propellant's net surface heat release, are evaluated with respect to their influence on the production of instability symptoms. Two traditional suppression techniques, axial transitions in grain geometry and inert particle loading, are in turn evaluated with respect to suppressing these axial instability symptoms.

Secure key distribution by swapping quantum entanglement

International Nuclear Information System (INIS)

Song, Daegene

2004-01-01

We report two key distribution schemes achieved by swapping quantum entanglement. Using two Bell states, two bits of secret key can be shared between two distant parties that play symmetric and equal roles. We also address eavesdropping attacks against the schemes

Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

Science.gov (United States)

Kamoshida, Go; Kikuchi-Ueda, Takane; Nishida, Satoshi; Tansho-Nagakawa, Shigeru; Ubagai, Tsuneyuki; Ono, Yasuo

2018-01-01

Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs), has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA), and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections. PMID:29467765

Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

Directory of Open Access Journals (Sweden)

Go Kamoshida

2018-02-01

Full Text Available Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs, has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA, and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections.

How does thought-action fusion relate to responsibility attitudes and thought suppression to aggravate the obsessive-compulsive symptoms?

Science.gov (United States)

Altın, Müjgan; Gençöz, Tülin

2011-01-01

Comprehensive cognitive theories of obsessive compulsive disorder (OCD) propose that clinical obsessions and compulsions arise from specific sorts of dysfunctional beliefs and appraisals, such as inflated sense of responsibility, thought-action fusion (TAF), and thought suppression. The present study aimed to examine the mediator roles of responsibility and thought suppression between TAF and obsessive-compulsive symptoms. Specifically, it aimed to explore the relative effects of TAF factors (i.e. morality and likelihood) on inflated sense of responsibility and on thought suppression to increase the obsessive qualities of intrusions. Two hundred and eighty-three Turkish undergraduate students completed a battery of measures on responsibility, thought suppression, TAF, OC symptoms, and depression. A series of hierarchical regression analyses, where depressive symptoms were controlled for, indicated that TAF-morality and TAF-likelihood follow different paths toward OC symptoms. Although TAF-morality associated with inflated sense of responsibility, TAF-likelihood associated with thought suppression efforts, and in turn these factors increased OC symptoms. These findings provide support for the critical role of sense of responsibility and thought suppression between the relationship of TAF and OC symptoms. Findings were discussed in line with the literature.

NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis.

Science.gov (United States)

Hirota, Simon A; Ng, Jeffrey; Lueng, Alan; Khajah, Maitham; Parhar, Ken; Li, Yan; Lam, Victor; Potentier, Mireille S; Ng, Kelvin; Bawa, Misha; McCafferty, Donna-Marie; Rioux, Kevin P; Ghosh, Subrata; Xavier, Ramnik J; Colgan, Sean P; Tschopp, Jurg; Muruve, Daniel; MacDonald, Justin A; Beck, Paul L

2011-06-01

Attenuated innate immune responses to the intestinal microbiota have been linked to the pathogenesis of Crohn's disease (CD). Recent genetic studies have revealed that hypofunctional mutations of NLRP3, a member of the NOD-like receptor (NLR) superfamily, are associated with an increased risk of developing CD. NLRP3 is a key component of the inflammasome, an intracellular danger sensor of the innate immune system. When activated, the inflammasome triggers caspase-1-dependent processing of inflammatory mediators, such as IL-1β and IL-18. In the current study we sought to assess the role of the NLRP3 inflammasome in the maintenance of intestinal homeostasis through its regulation of innate protective processes. To investigate this role, Nlrp3(-/-) and wildtype mice were assessed in the dextran sulfate sodium and 2,4,6-trinitrobenzenesulfonic acid models of experimental colitis. Nlrp3(-/-) mice were found to be more susceptible to experimental colitis, an observation that was associated with reduced IL-1β, reduced antiinflammatory cytokine IL-10, and reduced protective growth factor TGF-β. Macrophages isolated from Nlrp3(-/-) mice failed to respond to bacterial muramyl dipeptide. Furthermore, Nlrp3-deficient neutrophils exhibited reduced chemotaxis and enhanced spontaneous apoptosis, but no change in oxidative burst. Lastly, Nlrp3(-/-) mice displayed altered colonic β-defensin expression, reduced colonic antimicrobial secretions, and a unique intestinal microbiota. Our data confirm an essential role for the NLRP3 inflammasome in the regulation of intestinal homeostasis and provide biological insight into disease mechanisms associated with increased risk of CD in individuals with NLRP3 mutations. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

Deconstructing continuous flash suppression.

Science.gov (United States)

Yang, Eunice; Blake, Randolph

2012-03-08

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

Dexamethasone suppression test

Science.gov (United States)

DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

Role of syrphid larvae and other predators in suppressing aphid infestations in organic lettuce on California's Central Coast.

Science.gov (United States)

Smith, Hugh A; Chaney, William E; Bensen, Tiffany A

2008-10-01

Organic lettuce, Lactuca sativa L., growers on the Central Coast of California rely on conservation biological control to manage Nasonovia ribisnigri Mosley (Hemiptera: Aphididae) and other aphid pests of lettuce. In 2006, we carried out five replicated field trials to determine the importance of syrphid larvae in the suppression of N. ribisnigri and other aphids infesting organic romaine lettuce. We used Entrust, a spinosad-based insecticide approved for use on organic farms, to suppress syrphid larvae in aphid-infested romaine. Romaine treated with Entrust was unmarketable at harvest because of aphid infestation, whereas insecticide-free romaine was marketable. Syrphid larvae composed 85% or more of total predators in most trials, and they were the only predators consistently recovered from romaine that was infested with aphids early and largely aphid-free by harvest. The species mix of nonsyrphid predators varied from site to site. Applications of Entrust suppressed nonsyrphid predators in two trials, and so was an imperfect tool for selectively suppressing syrphid larvae. The relative importance of syrphid larvae and other predators in the conservation biological control of aphids in organic romaine is discussed. We conclude that syrphid larvae are primarily responsible for the suppression of aphids in organic romaine on California's Central Coast.

Deconstructing continuous flash suppression

OpenAIRE

Yang, Eunice; Blake, Randolph

2012-01-01

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in co...

Suppression of External NADPH Dehydrogenase—NDB1 in Arabidopsis thaliana Confers Improved Tolerance to Ammonium Toxicity via Efficient Glutathione/Redox Metabolism

Science.gov (United States)

Podgórska, Anna; Borysiuk, Klaudia; Tarnowska, Agata; Jakubiak, Monika; Burian, Maria; Rasmusson, Allan G.

2018-01-01

Environmental stresses, including ammonium (NH4+) nourishment, can damage key mitochondrial components through the production of surplus reactive oxygen species (ROS) in the mitochondrial electron transport chain. However, alternative electron pathways are significant for efficient reductant dissipation in mitochondria during ammonium nutrition. The aim of this study was to define the role of external NADPH-dehydrogenase (NDB1) during oxidative metabolism of NH4+-fed plants. Most plant species grown with NH4+ as the sole nitrogen source experience a condition known as “ammonium toxicity syndrome”. Surprisingly, transgenic Arabidopsis thaliana plants suppressing NDB1 were more resistant to NH4+ treatment. The NDB1 knock-down line was characterized by milder oxidative stress symptoms in plant tissues when supplied with NH4+. Mitochondrial ROS accumulation, in particular, was attenuated in the NDB1 knock-down plants during NH4+ treatment. Enhanced antioxidant defense, primarily concerning the glutathione pool, may prevent ROS accumulation in NH4+-grown NDB1-suppressing plants. We found that induction of glutathione peroxidase-like enzymes and peroxiredoxins in the NDB1-surpressing line contributed to lower ammonium-toxicity stress. The major conclusion of this study was that NDB1 suppression in plants confers tolerance to changes in redox homeostasis that occur in response to prolonged ammonium nutrition, causing cross tolerance among plants. PMID:29747392

Legacy effects of anaerobic soil disinfestation on soil bacterial community composition and production of pathogen-suppressing volatiles

NARCIS (Netherlands)

Os, van G.J.; Agtmaal, van M.; Hol, G.; Hundscheid, M.P.J.; Runia, W.T.; Hordijk, C.; Boer, de W.

2015-01-01

There is increasing evidence that microbial volatiles (VOCs) play an important role in natural suppression of soil-borne diseases, but little is known on the factors that influence production of suppressing VOCs. In the current study we examined whether a stress-induced change in soil microbial

Legacy effects of anaerobic soil disinfestation on soil bacterial community composition and production of pathogen-suppressing volatiles

NARCIS (Netherlands)

van Agtmaal, Maaike; van Os, Gera; Hol, Gera; Hundscheid, M.P.J.; Runia, Willemien; Hordijk, Cees; De Boer, Wietse

2015-01-01

BACKGROUND: There is increasing evidence that microbial volatiles (VOCs) play an important role in natural suppression of soil-borne diseases, but little is known on the factors that influence production of suppressing VOCs. In the current study we examined whether a stress-induced change in soil

Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion

International Nuclear Information System (INIS)

Ellis, Lixia Z.; Liu, Weimin; Luo, Yuchun; Okamoto, Miyako; Qu, Dovina; Dunn, Jeffrey H.; Fujita, Mayumi

2011-01-01

Highlights: ► EGCG inhibits melanoma cell growth at physiological doses (0.1–1 μM). ► EGCG inhibits melanoma cell growth via inflammasomes and IL-1β suppression. ► Inflammasomes and IL-1β could be potential targets for future melanoma therapeutics. -- Abstract: Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has been demonstrated to possess anti-inflammatory, antioxidant, anti-mutagenic and anti-carcinogenic properties. The anti-melanoma effect of EGCG has been previously suggested, but no clear mechanism of action has been established. In this study, we demonstrated that EGCG inhibits melanoma cell growth at physiological doses (0.1–1 μM). In the search for mechanisms of EGCG-mediated melanoma cell suppression, we found that NF-κB was inhibited, and that reduced NF-κB activity was associated with decreased IL-1β secretion from melanoma cells. Since inflammasomes are involved in IL-1β secretion, we investigated whether IL-1β suppression was mediated by inflammasomes, and found that EGCG treatment led to downregulation of the inflammasome component, NLRP1, and reduced caspase-1 activation. Furthermore, silencing the expression of NLRP1 abolished EGCG-induced inhibition of tumor cell proliferation both in vitro and in vivo, suggesting a key role of inflammasomes in EGCG efficacy. This paper provides a novel mechanism for EGCG-induced melanoma inhibition: inflammasome downregulation → decreased IL-1β secretion → decreased NF-κB activities → decreased cell growth. In addition, it suggests inflammasomes and IL-1β could be potential targets for future melanoma therapeutics.

Virus-mediated suppression of host non-self recognition facilitates horizontal transmission of heterologous viruses.

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Songsong Wu

2017-03-01

Full Text Available Non-self recognition is a common phenomenon among organisms; it often leads to innate immunity to prevent the invasion of parasites and maintain the genetic polymorphism of organisms. Fungal vegetative incompatibility is a type of non-self recognition which often induces programmed cell death (PCD and restricts the spread of molecular parasites. It is not clearly known whether virus infection could attenuate non-self recognition among host individuals to facilitate its spread. Here, we report that a hypovirulence-associated mycoreovirus, named Sclerotinia sclerotiorum mycoreovirus 4 (SsMYRV4, could suppress host non-self recognition and facilitate horizontal transmission of heterologous viruses. We found that cell death in intermingled colony regions between SsMYRV4-infected Sclerotinia sclerotiorum strain and other tested vegetatively incompatible strains was markedly reduced and inhibition barrage lines were not clearly observed. Vegetative incompatibility, which involves Heterotrimeric guanine nucleotide-binding proteins (G proteins signaling pathway, is controlled by specific loci termed het (heterokaryon incompatibility loci. Reactive oxygen species (ROS plays a key role in vegetative incompatibility-mediated PCD. The expression of G protein subunit genes, het genes, and ROS-related genes were significantly down-regulated, and cellular production of ROS was suppressed in the presence of SsMYRV4. Furthermore, SsMYRV4-infected strain could easily accept other viruses through hyphal contact and these viruses could be efficiently transmitted from SsMYRV4-infected strain to other vegetatively incompatible individuals. Thus, we concluded that SsMYRV4 is capable of suppressing host non-self recognition and facilitating heterologous viruses transmission among host individuals. These findings may enhance our understanding of virus ecology, and provide a potential strategy to utilize hypovirulence-associated mycoviruses to control fungal diseases.

Screening for suppression in young children: the Polaroid Suppression test

NARCIS (Netherlands)

Pott, J.W.R.; Oosterveen, DK; Van Hof-van Duin, J

1998-01-01

Background: Assessment of monocular visual impairment during screening of young children is often hampered by lack of cooperation. Because strabismus, amblyopia, or anisometropia may lead to monocular suppression during binocular viewing conditions, a test was developed to screen far suppression in

Suppression Pools: paradigm of the thermalhydraulic effect on severe accidents; Piscinas de Supresion: Paradigma del efecto de la thermohidraulica durante accidentes severos

Energy Technology Data Exchange (ETDEWEB)

Herranz, L. E.; Lopez del Pra, C.

2016-08-01

Influence of thermal-hydrualic phenomena on severe accident unforlding is beyond question. The present paper supports this statement on two key aspects of a severe accident: preservation of containment integrity and transport of fission products once released from fuel. To illustrate them, the attention is focused on suppression pools performance and, particularly, on some recent findings stemming from authors research of Fukushima scenarios. Gas behvaior at the injection point and its later evolution, potential axial and/or azimuthal stratification of the aqueous body or water saturation state, are some of the processes tha more strongly affect the role of pools as a mass and energy sink. They are described and discussed in detail. (Author)

MRI correlates of interaction between gender and expressive suppression among the Chinese population.

Science.gov (United States)

Wang, Kangcheng; Huang, Hui; Chen, Li; Hou, Xin; Zhang, Yong; Yang, Junyi; Hao, Xin; Qiu, Jiang

2017-04-07

Expressive suppression is a kind of emotion regulation strategies by suppressing behaviors related to emotional responding. Despite the amount of behavioral research on expressive suppression, the structural and functional mechanisms underlying the interaction between gender and expressive suppression in Chinese healthy subjects have remained unknown. In the current study, we assessed the levels of expressive suppression and acquired the structural and functional imaging data from 273 Chinese individuals. A nearly automatic cortical processing technique was used to calculate cortical thickness for each subject. The results from cortical thickness analyses revealed a significant interaction between gender and expressive suppression in the superior frontal gyrus. Then, we conducted the whole-brain functional connectivity analysis with the seed of the superior frontal gyrus to explore the functionally related regions of brain. Subsequent analysis of the interaction between gender and expressive suppression indicated a significant functional connectivity between the superior frontal gyrus and default mode network (DMN) core regions, including the medial prefrontal cortex, precuneus and parahippocampal gyrus. Our results provided the robust empirical evidence illustrating the role of the superior frontal gyrus and DMN in gender difference of expressive suppression among the Chinese population. These findings might have implications for understanding gender difference in emotion processing and regulation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Suppression of nemo-like kinase by miR-71 in Echinococcus multilocularis.

Science.gov (United States)

Guo, Xiaola; Zhang, Xueyong; Yang, Jing; Jin, Xiaoliang; Ding, Juntao; Xiang, Haitao; Ayaz, Mazhar; Luo, Xuenong; Zheng, Yadong

2017-12-01

Echinococcus multilocularis metacestodes are a causative pathogen for alveolar echinococcosis in human beings, and have been found to express miRNAs including emu-miR-71. miR-71 is evolutionarily conserved and highly expressed across platyhelminths, but little is known about its role. Here it was shown that emu-miR-71 was differentially expressed in protoscoleces and was unlikely to be expressed in neoblasts. The results of the luciferase assay indicated that emu-miR-71 was able to bind in vitro to the 3'-UTR of emu-nlk, encoding a key regulator of cell division, causing significant downregulation of luciferase activity (p < 0.01) compared to the negative control and the construct with mutations in the binding site. Consistent with the decreased luciferase activity, transfection of emu-miR-71 mimics into protoscoleces notably repressed emu-NLK (p < 0.05). These results demonstrate the suppression of emu-nlk by emu-miR-71, potentially involved in the protoscolex development. Copyright © 2017 Elsevier Inc. All rights reserved.

Presentation of MSc in Higher Education Dissertation School Meeting : What are the key dimensions of the personal tutor role for nurse education today?,

OpenAIRE

Leddington, Susan

2012-01-01

Presentation of MSc in Higher Education Dissertation School Meeting : What are the key dimensions of the personal tutor role for nurse education today?, A literature review, Missenden Abbey, June 2009, presentation

Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

Science.gov (United States)

Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

2012-06-01

What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

Characterisation of the nociceptive phenotype of suppressible galanin overexpressing transgenic mice

Directory of Open Access Journals (Sweden)

Wynick David

2010-10-01

Full Text Available Abstract The neuropeptide galanin is widely expressed in both the central and peripheral nervous systems and is involved in many diverse biological functions. There is a substantial data set that demonstrates galanin is upregulated after injury in the DRG, spinal cord and in many brain regions where it plays a predominantly antinociceptive role in addition to being neuroprotective and pro-regenerative. To further characterise the role of galanin following nerve injury, a novel transgenic line was created using the binary transgenic tet-off system, to overexpress galanin in galaninergic tissue in a suppressible manner. The double transgenic mice express significantly more galanin in the DRG one week after sciatic nerve section (axotomy compared to WT mice and this overexpression is suppressible upon administration of doxycycline. Phenotypic analysis revealed markedly attenuated allodynia when galanin is overexpressed and an increase in allodynia following galanin suppression. This novel transgenic line demonstrates that whether galanin expression is increased at the time of nerve injury or only after allodynia is established, the neuropeptide is able to reduce neuropathic pain behaviour. These new findings imply that administration of a galanin agonist to patients with established allodynia would be an effective treatment for neuropathic pain.

Mechanisms underlying UV-induced immune suppression

International Nuclear Information System (INIS)

Ullrich, Stephen E.

2005-01-01

Skin cancer is the most prevalent form of human neoplasia. Estimates suggest that in excess of one million new cases of skin cancer will be diagnosed this year alone in the United States (www.cancer.org/statistics). Fortunately, because of their highly visible location, skin cancers are more rapidly diagnosed and more easily treated than other types of cancer. Be that as it may, approximately 10,000 Americans a year die from skin cancer. The cost of treating non-melanoma skin cancer is estimated to be in excess of US$ 650 million a year [J.G. Chen, A.B. Fleischer, E.D. Smith, C. Kancler, N.D. Goldman, P.M. Williford, S.R. Feldman, Cost of non-melanoma skin cancer treatment in the United States, Dermatol. Surg. 27 (2001) 1035-1038], and when melanoma is included, the estimated cost of treating skin cancer in the United States is estimated to rise to US$ 2.9 billion annually (www.cancer.org/statistics). Because the morbidity and mortality associated with skin cancer is a major public health problem, it is important to understand the mechanisms underlying skin cancer development. The primary cause of skin cancer is the ultraviolet (UV) radiation found in sunlight. In addition to its carcinogenic potential, UV radiation is also immune suppressive. In fact, data from studies with both experimental animals and biopsy proven skin cancer patients suggest that there is an association between the immune suppressive effects of UV radiation and its carcinogenic potential. The focus of this manuscript will be to review the mechanisms underlying the induction of immune suppression following UV exposure. Particular attention will be directed to the role of soluble mediators in activating immune suppression

Acoustic transmission resonance and suppression through double-layer subwavelength hole arrays

International Nuclear Information System (INIS)

Liu Zhifeng; Jin Guojun

2010-01-01

We present a theoretical study of acoustic waves passing through double-layer subwavelength hole arrays. The acoustic transmission resonance and suppression are observed. There are three mechanisms responsible for the transmission resonance: the excitation of geometrically induced acoustic surface waves, the Fabry-Perot resonance in a hole cavity (I-FP resonance) and the Fabry-Perot resonance between two plates (II-FP resonance). We can differentiate these mechanisms via the dispersion relation of acoustic modes supported by the double-layer structure. It is confirmed that the coupling between two single-layer perforated plates, associated with longitudinal interval and lateral displacement, plays a crucial role in modulating the transmission properties. The strong coupling between two plates can induce the splitting of the transmission peak, while the decoupling between plates leads to the appearance of transmission suppression. By analyzing the criterion derived for transmission suppression, we conclude that it is the destructive interference between the diffracted waves and the direct transmission waves assisted by the I-FP resonance of the first plate that leads to the decoupling between plates and then the transmission suppression.

Parenting Stressors and Young Adolescents’ Depressive Symptoms: Does High Vagal Suppression Offer Protection?

Science.gov (United States)

Fletcher, Anne C.; Buehler, Cheryl; Buchanan, Christy M.; Weymouth, Bridget B.

2017-01-01

Grounded in a dual-risk, biosocial perspective of developmental psychopathology, this study examined the role of higher vagal suppression in providing young adolescents protection from four parenting stressors. It was expected that lower vagal suppression would increase youth vulnerability to the deleterious effects of these parenting stressors. Depressive symptoms were examined as a central marker of socioemotional difficulties during early adolescence. The four parenting stressors examined were interparental hostility, maternal use of harsh discipline, maternal inconsistent discipline, and maternal psychological control. Participants were 68 young adolescents (Grade 6) and their mothers. Greater vagal suppression provided protection (i.e., lower depressive symptoms) from interparental hostility, harsh discipline, and maternal psychological control for boys but not for girls. PMID:27979628

The Influence of Thought Suppression and Cognitive Load on Intrusions and Memory Processes following an Analogue Stressor

Science.gov (United States)

Nixon, Reginald D. V.; Cain, Neralie; Nehmy, Thomas; Seymour, Melanie

2009-01-01

Ironic Process Theory and the role of thought suppression have been used in part to explain the phenomenon of intrusive memories in various disorders, including posttraumatic stress disorder. How thought suppression interacts with other cognitive processes believed to be instrumental in the development of traumatic intrusive memory is unclear. In…

GdCl3 reduces hyperglycaemia through Akt/FoxO1-induced suppression of hepatic gluconeogenesis in Type 2 diabetic mice.

Science.gov (United States)

Wang, Qian; Wang, Ning; Dong, Mei; Chen, Fang; Li, Zhong; Chen, Yuanyuan

2014-07-01

GdCl3 (gadolinium chloride) has been shown to reduce blood glucose; however, the underlying mechanism remains unclear. Liver gluconeogenesis is an important pathway involved in the maintenance of glucose homoeostasis. The aim of the present study was to investigate the role of GdCl3 in hepatic gluconeogenesis and explore the precise molecular mechanism. Animals from a classical Type 2 diabetic mouse model, created by exposing C57BL/6J mice to a high-fat diet for 4 months, were treated with GdCl3 or saline. Body weight, blood glucose and insulin sensitivity were monitored. It was observed that GdCl3 significantly reduced blood glucose levels and improved insulin sensitivity. A pyruvate tolerance test showed further that GdCl3 suppressed gluconeogenesis in diabetic mice. In the livers of GdCl3-treated mice, the expression of Pepck (phosphoenolpyruvate carboxykinase) and G6pase (glucose-6-phosphatase), the key enzymes in gluconeogenesis, were dramatically reduced. Furthermore, experiments in hepatocarcinoma cells revealed that GdCl3 activated the Akt pathway to promote the phosphorylation of FoxO1 (forkhead box O1), leading to the suppression of gluconeogenesis by reducing the expression of PEPCK and G6Pase and resulting in decreased cellular production of glucose. Comparable results were observed in the livers of GdCl3-treated mice. In addition, we have shown that GdCl3 augmented the role of insulin to control hepatic glucose production. We conclude that GdCl3 reduces hyperglycaemia via the Akt/FoxO1-induced suppression of hepatic gluconeogenesis, both in Type 2 diabetic mice (in vivo) and in hepatocarcinoma cells (in vitro), suggesting that GdCl3 may be a potential therapeutic agent for diabetes.

Waves of visibility: probing the depth of inter-ocular suppression with transient and sustained targets

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Lisandro eKaunitz

2014-07-01

Full Text Available In order to study non-conscious visual processing, researchers render otherwise consciously perceived images into invisible stimuli. Through the years, several psychophysical techniques have been developed for this purpose. Yet the comparison of experimental results across techniques remains a difficult task as the depth of suppression depends on the interactions between the type of stimuli and the suppression methods employed. This poses a limit to the inferences that researchers make about the extent of non-conscious processes. We investigated the mechanisms underlying inter-ocular suppression during continuous flash suppression (CFS and dichoptic visual masking using a transient onset target stimulus and a variety of stimulus / mask temporal manipulations. We show that target duration, timing of target onset, and mask frequency are key aspects of inter-ocular suppression during CFS with transient targets. The differences between our results and sustained target CFS studies suggest that two distinct mechanisms are involved in the detection of transient and prolonged target stimuli during CFS. Our results provide insight into the dynamics of CFS together with evidence for similarities between transient target CFS and dichoptic visual masking.

Antimicrobial Nanoplexes meet Model Bacterial Membranes: the key role of Cardiolipin

Science.gov (United States)

Marín-Menéndez, Alejandro; Montis, Costanza; Díaz-Calvo, Teresa; Carta, Davide; Hatzixanthis, Kostas; Morris, Christopher J.; McArthur, Michael; Berti, Debora

2017-01-01

Antimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-assembled complexes (nanoplexes). Confocal microscopy revealed that nanoplexes efficiently transfect bacterial cells, consistently with biological efficacy on animal models. To understand the factors affecting the delivery process, liposomes with varying compositions, taken as model synthetic bilayers, were challenged with nanoplexes and investigated with Scattering and Fluorescence techniques. Thanks to the combination of results on bacteria and synthetic membrane models we demonstrate for the first time that the prokaryotic-enriched anionic lipid Cardiolipin (CL) plays a key-role in the TFDs delivery to bacteria. Moreover, we can hypothesize an overall TFD delivery mechanism, where bacterial membrane reorganization with permeability increase and release of the TFD from the nanoplexes are the main factors. These results will be of great benefit to boost the development of oligonucleotides-based antimicrobials of superior efficacy.

Optogenetic and pharmacological suppression of spatial clusters of face neurons reveal their causal role in face gender discrimination.

Science.gov (United States)

Afraz, Arash; Boyden, Edward S; DiCarlo, James J

2015-05-26

Neurons that respond more to images of faces over nonface objects were identified in the inferior temporal (IT) cortex of primates three decades ago. Although it is hypothesized that perceptual discrimination between faces depends on the neural activity of IT subregions enriched with "face neurons," such a causal link has not been directly established. Here, using optogenetic and pharmacological methods, we reversibly suppressed the neural activity in small subregions of IT cortex of macaque monkeys performing a facial gender-discrimination task. Each type of intervention independently demonstrated that suppression of IT subregions enriched in face neurons induced a contralateral deficit in face gender-discrimination behavior. The same neural suppression of other IT subregions produced no detectable change in behavior. These results establish a causal link between the neural activity in IT face neuron subregions and face gender-discrimination behavior. Also, the demonstration that brief neural suppression of specific spatial subregions of IT induces behavioral effects opens the door for applying the technical advantages of optogenetics to a systematic attack on the causal relationship between IT cortex and high-level visual perception.

IL-1Ra: its role in rheumatoid arthritis

Directory of Open Access Journals (Sweden)

M. Cutolo

2011-09-01

Full Text Available Interleukin-1 (IL-1 is one of the pivotal cytokines in initiating and driving the processes of rheumatoid arthritis (RA, and the body’s natural response, IL-1 receptor antagonist (IL-1Ra, has been shown conclusively to block its effects. IL-1 mediate several clinical symptoms of the inflammatory reaction (i.e. fever, pain, sleep disturbances. IL-1 is considered a key mediator in RA joint damage because of its greater capacity (greater than TNF of increasing matrix degradation by inducing the production of MMPs and PGE2 in synovial cells, as well by its role as mediator of bone and cartilage destruction. In addition, IL-1 decreases the repair process by suppressing matrix synthesis and shows a strong synergism with TNF in inducing many inflammatory genes at both local and systemic level. The induced endogenous production of IL-1Ra, in presence of the RA synovitis, is too low to contrast the high affinity of IL-1 for the cell receptors. Therefore, IL-1Ra presence should result in very effective prevention of IL-1 signal transduction particularly in the inflammatory site. In laboratory and animal studies inhibition of IL-1 by either antibodies to IL-1 or IL-1Ra proved beneficial to the outcome. IL-1Ra is a member of the IL-1 superfamily. The effects of different DMARDs on IL-1Ra levels in RA patients support the important role that selected anticytokine treatments might exert in the pathophysiology of the disease. However, since anti TNFα therapy it is not effective in all RA patients, nor does it fully control the arthritic process in affected joints of good responders and complete TNF suppression should be avoided, the combined treatment with intermediate doses of TNF and IL-1 blockers, reaching synergistic suppression of arthritis, seems warranted in RA.

Neighbour tolerance, not suppression, provides competitive advantage to non-native plants.

Science.gov (United States)

Golivets, Marina; Wallin, Kimberly F

2018-05-01

High competitive ability has often been invoked as a key determinant of invasion success and ecological impacts of non-native plants. Yet our understanding of the strategies that non-natives use to gain competitive dominance remains limited. Particularly, it remains unknown whether the two non-mutually exclusive competitive strategies, neighbour suppression and neighbour tolerance, are equally important for the competitive advantage of non-native plants. Here, we analyse data from 192 peer-reviewed studies on pairwise plant competition within a Bayesian multilevel meta-analytic framework and show that non-native plants outperform their native counterparts due to high tolerance of competition, as opposed to strong suppressive ability. Competitive tolerance ability of non-native plants was driven by neighbour's origin and was expressed in response to a heterospecific native but not heterospecific non-native neighbour. In contrast to natives, non-native species were not more suppressed by hetero- vs. conspecific neighbours, which was partially due to higher intensity of intraspecific competition among non-natives. Heterogeneity in the data was primarily associated with methodological differences among studies and not with phylogenetic relatedness among species. Altogether, our synthesis demonstrates that non-native plants are competitively distinct from native plants and challenges the common notion that neighbour suppression is the primary strategy for plant invasion success. © 2018 John Wiley & Sons Ltd/CNRS.

Singular and combined effects of thought suppression and anxiety induction on frequency of threatening thoughts: An experimental investigation

NARCIS (Netherlands)

Cougle, J.R.; Smits, J.A.J.; Lee, H.J.; Powers, M.B.; Telch, M.J.

2005-01-01

The suppression of unwanted thoughts has been hypothesized to play an important role in the maintenance of clinical disorders such as OCD and PTSD. The present study sought to examine the singular and combined effects of thought suppression instructions and anxiety induction (as induced by an

MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4*

Science.gov (United States)

Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai; Wang, Chunxia; Guo, Feifan

2015-01-01

Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1 (FOXO1) transcriptional activity. Finally, liver-specific miR-214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. PMID:25657009

Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

International Nuclear Information System (INIS)

Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

2015-01-01

Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice. �

Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

Energy Technology Data Exchange (ETDEWEB)

Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng, E-mail: zhouqs@suda.edu.cn

2015-10-15

Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice. �

Screening and Characterization of Potentially Suppressive Soils against Gaeumannomyces graminis under Extensive Wheat Cropping by Chilean Indigenous Communities.

Science.gov (United States)

Durán, Paola; Jorquera, Milko; Viscardi, Sharon; Carrion, Victor J; Mora, María de la Luz; Pozo, María J

2017-01-01

Wheat production around the world is severely compromised by the occurrence of "take-all" disease, which is caused by the soil-borne pathogen Gaeumannomyces graminis var. tritici (Ggt). In this context, suppressive soils are those environments in which plants comparatively suffer less soil-borne pathogen diseases than expected, owing to native soil microorganism activities. In southern Chile, where 85% of the national cereal production takes place, several studies have suggested the existence of suppressive soils under extensive wheat cropping. Thus, this study aimed to screen Ggt-suppressive soil occurrence in 16 locations managed by indigenous "Mapuche" communities, using extensive wheat cropping for more than 10 years. Ggt growth inhibition in vitro screenings allowed the identification of nine putative suppressive soils. Six of these soils, including Andisols and Ultisols, were confirmed to be suppressive, since they reduced take-all disease in wheat plants growing under greenhouse conditions. Suppressiveness was lost upon soil sterilization, and recovered by adding 1% of the natural soil, hence confirming that suppressiveness was closely associated to the soil microbiome community composition. Our results demonstrate that long-term extensive wheat cropping, established by small Mapuche communities, can generate suppressive soils that can be used as effective microorganism sources for take-all disease biocontrol. Accordingly, suppressive soil identification and characterization are key steps for the development of environmentally-friendly and efficient biotechnological applications for soil-borne disease control.

Key-Phenomenon and Religious Meaning

Directory of Open Access Journals (Sweden)

Lomuscio Vincenzo

2017-09-01

Full Text Available In this paper I develop a phenomenology of religious experience through the notion of keyphenomenon. My analysis moves from a general phenomenology of situation, in which we have to relate different phenomena according to a sense. What does “according to a sense” mean? My suggestion is that we should look for a relationship among these data when we find a key-phenomenon (among a series of phenomena that would enlighten all the others. This key-phenomenon would show a non-phenomenal meaning which would make all the others understandable. Each other datum, therefore, becomes the witness of invisible meaning through a key-witness. The key-phenomenon we choose determines the role (i.e., the truth of each datum within its situation. This phenomenological relationship belongs to both the sense of day-life situations, and that one of possible religious situations. If the religious interpretation of a situation depends on our choice of key-phenomenon, or key-witness, we have to define what kind of keyphenomenon constitutes a religious intuition.

Functional role for suppression of the insular-striatal circuit in modulating interoceptive effects of alcohol.

Science.gov (United States)

Jaramillo, Anel A; Agan, Verda E; Makhijani, Viren H; Pedroza, Stephen; McElligott, Zoe A; Besheer, Joyce

2017-09-27

The insular cortex (IC) is a region proposed to modulate, in part, interoceptive states and motivated behavior. Interestingly, IC dysfunction and deficits in interoceptive processing are often found among individuals with substance-use disorders. Furthermore, the IC projects to the nucleus accumbens core (AcbC), a region known to modulate the discriminative stimulus/interoceptive effects of alcohol and other drug-related behaviors. Therefore, the goal of the present work was to investigate the possible role of the IC ➔ AcbC circuit in modulating the interoceptive effects of alcohol. Thus, we utilized a chemogenetic technique (hM4D i designer receptor activation by designer drugs) to silence neuronal activity in the IC of rats trained to discriminate alcohol (1 g/kg, IG) versus water using an operant or Pavlovian alcohol discrimination procedure. Chemogenetic silencing of the IC or IC ➔ AcbC neuronal projections resulted in potentiated sensitivity to the interoceptive effects of alcohol in both the operant and Pavlovian tasks. Together, these data provide critical evidence for the nature of the complex IC circuitry and, specifically, suppression of the insular-striatal circuit in modulating behavior under a drug stimulus control. © 2017 Society for the Study of Addiction.

Aging and repeated thought suppression success.

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Ann E Lambert

Full Text Available Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility.

The views of key leaders in South Africa on implementation of family medicine: critical role in the district health system.

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Moosa, Shabir; Mash, Bob; Derese, Anselme; Peersman, Wim

2014-06-25

Integrated team-based primary care is an international imperative. This is required more so in Africa, where fragmented verticalised care dominates. South Africa is trying to address this with health reforms, including Primary Health Care Re-engineering. Family physicians are already contributing to primary care despite family medicine being only fully registered as a full specialty in South Africa in 2008. However the views of leaders on family medicine and the role of family physicians is not clear, especially with recent health reforms. The aim of this study was to understand the views of key government and academic leaders in South Africa on family medicine, roles of family physicians and human resource issues. This was a qualitative study with academic and government leaders across South Africa. In-depth interviews were conducted with sixteen purposively selected leaders using an interview guide. Thematic content analysis was based on the framework method. Whilst family physicians were seen as critical to the district health system there was ambivalence on their leadership role and 'specialist' status. National health reforms were creating both threats and opportunities for family medicine. Three key roles for family physicians emerged: supporting referrals; clinical governance/quality improvement; and providing support to community-oriented care. Respondents' urged family physicians to consolidate the development and training of family physicians, and shape human resource policy to include family physicians. Family physicians were seen as critical to the district health system in South Africa despite difficulties around their precise role. Whilst their role was dominated by filling gaps at district hospitals to reduce referrals it extended to clinical governance and developing community-oriented primary care - a tall order, requiring strong teamwork. Innovative team-based service delivery is possible despite human resource challenges, but requires family

Comparative Microbiome Analysis of a Fusarium Wilt Suppressive Soil and a Fusarium Wilt Conducive Soil From the Châteaurenard Region

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Katarzyna Siegel-Hertz

2018-04-01

Full Text Available Disease-suppressive soils are soils in which specific soil-borne plant pathogens cause only limited disease although the pathogen and susceptible host plants are both present. Suppressiveness is in most cases of microbial origin. We conducted a comparative metabarcoding analysis of the taxonomic diversity of fungal and bacterial communities from suppressive and non-suppressive (conducive soils as regards Fusarium wilts sampled from the Châteaurenard region (France. Bioassays based on Fusarium wilt of flax confirmed that disease incidence was significantly lower in the suppressive soil than in the conducive soil. Furthermore, we succeeded in partly transferring Fusarium wilt-suppressiveness to the conducive soil by mixing 10% (w/w of the suppressive soil into the conducive soil. Fungal diversity differed significantly between the suppressive and conducive soils. Among dominant fungal operational taxonomic units (OTUs affiliated to known genera, 17 OTUs were detected exclusively in the suppressive soil. These OTUs were assigned to the Acremonium, Chaetomium, Cladosporium, Clonostachys, Fusarium, Ceratobasidium, Mortierella, Penicillium, Scytalidium, and Verticillium genera. Additionally, the relative abundance of specific members of the bacterial community was significantly higher in the suppressive and mixed soils than in the conducive soil. OTUs found more abundant in Fusarium wilt-suppressive soils were affiliated to the bacterial genera Adhaeribacter, Massilia, Microvirga, Rhizobium, Rhizobacter, Arthrobacter, Amycolatopsis, Rubrobacter, Paenibacillus, Stenotrophomonas, and Geobacter. Several of the fungal and bacterial genera detected exclusively or more abundantly in the Fusarium wilt-suppressive soil included genera known for their activity against F. oxysporum. Overall, this study supports the potential role of known fungal and bacterial genera in Fusarium wilt suppressive soils from Châteaurenard and pinpoints new bacterial and fungal

Parenting stressors and young adolescents' depressive symptoms: Does high vagal suppression offer protection?

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Fletcher, Anne C; Buehler, Cheryl; Buchanan, Christy M; Weymouth, Bridget B

2017-03-01

Grounded in a dual-risk, biosocial perspective of developmental psychopathology, this study examined the role of higher vagal suppression in providing young adolescents protection from four parenting stressors. It was expected that lower vagal suppression would increase youth vulnerability to the deleterious effects of these parenting stressors. Depressive symptoms were examined as a central marker of socioemotional difficulties during early adolescence. The four parenting stressors examined were interparental hostility, maternal use of harsh discipline, maternal inconsistent discipline, and maternal psychological control. Participants were 68 young adolescents (Grade 6) and their mothers. Greater vagal suppression provided protection (i.e., lower depressive symptoms) from interparental hostility, harsh discipline, and maternal psychological control for boys but not for girls. Copyright © 2016 Elsevier Inc. All rights reserved.

Differences Between Expressive Suppression and Cognitive Reappraisal Between Heart Disease and Generalal Population

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Seyyed Mohammad Reza Mirlohi

2017-09-01

Full Text Available Aim: Heart disease and emotional disorders often co-occur, but effective role in dysregulation of heart disease that is often overlooked. Evidence suggests that people with heart disease are more problems in regulating their emotions. The study compared the re-evaluation of cognitive emotion regulation commonly used two strategies- and suppression- between heart disease and the general population. Methods: Sixty men (30 with heart complaints and 30 without the condition were selected by convenience sampling method and they responded to the Emotion Regulation Questionnaire (Gross and John and a demographic questionnaire responded. To analyze the results and descriptive statistics such as frequency tables and inferential statistics, independent T-test was used SPSS software was used. Results: The result shows that heart disease and general population re-evaluation strategies groups (P<0.01. This is not only different from the strategy reassessment, but in different repression, too. (P <0.001. Conclusion: The results showed that heart disease and general population used different strategies to regulate their emotions. The key to finding the heart disease group prefer repression to regulate their emotions.

Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

International Nuclear Information System (INIS)

Pols, Thijs W.H.; Ottenhoff, Roelof; Vos, Mariska; Levels, Johannes H.M.; Quax, Paul H.A.; Meijers, Joost C.M.; Pannekoek, Hans; Groen, Albert K.; Vries, Carlie J.M. de

2008-01-01

NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits SREBP1c expression. This results in decreased SREBP1c activity as is illustrated by reduced expression of its target genes stearoyl-coA desaturase-1, mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the LDL receptor, and provides a mechanism for the physiological changes observed in response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

Puerarin Suppresses the Self-Renewal of Murine Embryonic Stem Cells by Inhibition of REST-MiR-21 Regulatory Pathway.

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Yin, Mengmeng; Yuan, Yin; Cui, Yurong; Hong, Xian; Luo, Hongyan; Hu, Xinwu; Tang, Ming; Hescheler, Jurgen; Xi, Jiaoya

2015-01-01

Puerarin shows a wide range of biological activities, including affecting the cardiac differentiation from murine embryonic stem (mES) cells. However, little is known about its effect and mechanism of action on the self-renewal of mES cells. This study aimed to determine the effect of puerarin on the self-renewal and pluripotency of mES cells and its underlying mechanisms. RT-PCR and real-time PCR were used to detect the transcripts of core transcription factors, specific markers for multiple lineages, REST and microRNA-21 (miR-21). Colony-forming assay was performed to estimate the self-renewal capacity of mES cells. Western blotting and wortmannin were employed to explore the role of PI3K/Akt signaling pathway in the inhibitory action of puerarin on REST transcript. Transfected mES cells with antagomir21 were used to confirm the role of miR-21 in the action of puerarin on cell self-renewal. Puerarin significantly decreased the percentage of the self-renewal colonies, and suppressed the transcripts of Oct4, Nanog, Sox2, c-Myc and REST. Besides, PECAM, NCAM and miR-21 were up-regulated both under the self-renewal conditions and at day 4 of differentiation. The PI3K inhibitor wortmannin successfully reversed the mRNA expression changes of REST, Nanog and Sox2. Transfection of antagomir21 efficiently reversed the effects of puerarin on mES cells self-renewal. Inhibition of REST-miR-21 regulatory pathway may be the key mechanism of puerarin-induced suppression of mES cells self-renewal.

Negative Correlation between Circulating CD4+FOXP3+CD127− Regulatory T Cells and Subsequent Antibody Responses to Infant Measles Vaccine but Not Diphtheria–Tetanus–Pertussis Vaccine Implies a Regulatory Role

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Jorjoh Ndure

2017-08-01

Full Text Available Regulatory T cells (Tregs play a key homeostatic role by suppressing immune responses. They have been targeted in mouse and human cancer studies to improve vaccine immunogenicity and tumor clearance. A number of commercially available drugs and experimental vaccine adjuvants have been shown to target Tregs. Infants have high numbers of Tregs and often have poor responses to vaccination, yet the role Tregs play in controlling vaccine immunogenicity has not been explored in this age group. Herein, we explore the role of CD4+FOXP3+CD127− Tregs in controlling immunity in infant males and females to vaccination with diphtheria–tetanus–whole cell pertussis (DTP and/or measles vaccine (MV. We find correlative evidence that circulating Tregs at the time of vaccination suppress antibody responses to MV but not DTP; and Tregs 4 weeks after DTP vaccination may suppress vaccine-specific cellular immunity. This opens the exciting possibility that Tregs may provide a future target for improved vaccine responses in early life, including reducing the number of doses of vaccine required. Such an approach would need to be safe and the benefits outweigh the risks, thus further research in this area is required.

Suppression of superconductivity in Nb by IrMn in IrMn/Nb bilayers

KAUST Repository

Wu, B. L.

2013-10-10

Effect of antiferromagnet on superconductivity has been investigated in IrMn/Nb bilayers. Significant suppression of both transition temperature (Tc) and lower critical field (Hc1) of Nb is found in IrMn/Nb bilayers as compared to a single layer Nb of same thickness; the suppression effect is even stronger than that of a ferromagnet in NiFe/Nb bilayers. The addition of an insulating MgO layer at the IrMn-Nb interface nearly restores Tc to that of the single layer Nb, but Hc1 still remains suppressed. These results suggest that, in addition to proximity effect and magnetic impurity scattering, magnetostatic interaction also plays a role in suppressing superconductivity of Nb in IrMn/Nb bilayers. In addition to reduced Tc and Hc1, the IrMn layer also induces broadening in the transition temperature of Nb, which can be accounted for by a finite distribution of stray field from IrMn.

Suppressed Alpha Oscillations Predict Intelligibility of Speech and its Acoustic Details

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Weisz, Nathan

2012-01-01

Modulations of human alpha oscillations (8–13 Hz) accompany many cognitive processes, but their functional role in auditory perception has proven elusive: Do oscillatory dynamics of alpha reflect acoustic details of the speech signal and are they indicative of comprehension success? Acoustically presented words were degraded in acoustic envelope and spectrum in an orthogonal design, and electroencephalogram responses in the frequency domain were analyzed in 24 participants, who rated word comprehensibility after each trial. First, the alpha power suppression during and after a degraded word depended monotonically on spectral and, to a lesser extent, envelope detail. The magnitude of this alpha suppression exhibited an additional and independent influence on later comprehension ratings. Second, source localization of alpha suppression yielded superior parietal, prefrontal, as well as anterior temporal brain areas. Third, multivariate classification of the time–frequency pattern across participants showed that patterns of late posterior alpha power allowed best for above-chance classification of word intelligibility. Results suggest that both magnitude and topography of late alpha suppression in response to single words can indicate a listener's sensitivity to acoustic features and the ability to comprehend speech under adverse listening conditions. PMID:22100354

Review of key concepts in magnetic resonance physics

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Moore, Michael M. [Penn State Hershey Children' s Hospital, Department of Radiology, The Pennsylvania State College of Medicine, Hershey, PA (United States); Chung, Taylor [UCSF Benioff Children' s Hospital Oakland, Department of Diagnostic Imaging, Oakland, CA (United States)

2017-05-15

MR physics can be a challenging subject for practicing pediatric radiologists. Although many excellent texts provide very comprehensive reviews of the field of MR physics at various levels of understanding, the authors of this paper explain several key concepts in MR physics that are germane to clinical practice in a non-rigorous but practical fashion. With the basic understanding of these key concepts, practicing pediatric radiologists can build on their knowledge of current clinical MR techniques and future advances in MR applications. Given the challenges of both the increased need for rapid imaging in non-sedated children and the rapid physiological cardiovascular and respiratory motion in pediatric patients, many advances in complex MR techniques are being applied to imaging these children. The key concepts are as follows: (1) structure of a pulse sequence, (2) k-space, (3) ''trade-off triangle'' and (4) fat suppression. This review is the first of five manuscripts in a minisymposium on pediatric MR. The authors' goal for this review is to aid in understanding the MR techniques described in the subsequent manuscripts on brain imaging and body imaging in this minisymposium. (orig.)

Review of key concepts in magnetic resonance physics.

Science.gov (United States)

Moore, Michael M; Chung, Taylor

2017-05-01

MR physics can be a challenging subject for practicing pediatric radiologists. Although many excellent texts provide very comprehensive reviews of the field of MR physics at various levels of understanding, the authors of this paper explain several key concepts in MR physics that are germane to clinical practice in a non-rigorous but practical fashion. With the basic understanding of these key concepts, practicing pediatric radiologists can build on their knowledge of current clinical MR techniques and future advances in MR applications. Given the challenges of both the increased need for rapid imaging in non-sedated children and the rapid physiological cardiovascular and respiratory motion in pediatric patients, many advances in complex MR techniques are being applied to imaging these children. The key concepts are as follows: (1) structure of a pulse sequence, (2) k-space, (3) "trade-off triangle" and (4) fat suppression. This review is the first of five manuscripts in a minisymposium on pediatric MR. The authors' goal for this review is to aid in understanding the MR techniques described in the subsequent manuscripts on brain imaging and body imaging in this minisymposium.

Bile Routing Modification Reproduces Key Features of Gastric Bypass in Rat.

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Goncalves, Daisy; Barataud, Aude; De Vadder, Filipe; Vinera, Jennifer; Zitoun, Carine; Duchampt, Adeline; Mithieux, Gilles

2015-12-01

To evaluate the role of bile routing modification on the beneficial effects of gastric bypass surgery on glucose and energy metabolism. Gastric bypass surgery (GBP) promotes early improvements in glucose and energy homeostasis in obese diabetic patients. A suggested mechanism associates a decrease in hepatic glucose production to an enhanced intestinal gluconeogenesis. Moreover, plasma bile acids are elevated after GBP and bile acids are inhibitors of gluconeogenesis. In male Sprague-Dawley rats, we performed bile diversions from the bile duct to the midjejunum or the mid-ileum to match the modified bile delivery in the gut occurring in GBP. Body weight, food intake, glucose tolerance, insulin sensitivity, and food preference were analyzed. The expression of gluconeogenesis genes was evaluated in both the liver and the intestine. Bile diversions mimicking GBP promote an increase in plasma bile acids and a marked improvement in glucose control. Bile bioavailability modification is causal because a bile acid sequestrant suppresses the beneficial effects of bile diversions on glucose control. In agreement with the inhibitory role of bile acids on gluconeogenesis, bile diversions promote a blunting in hepatic glucose production, whereas intestinal gluconeogenesis is increased in the gut segments devoid of bile. In rats fed a high-fat-high-sucrose diet, bile diversions improve glucose control and dramatically decrease food intake because of an acquired disinterest in fatty food. This study shows that bile routing modification is a key mechanistic feature in the beneficial outcomes of GBP.

The Role of Competition in Support of Socio-Political Stability and Suppression of Corruption

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Юлий Анатольевич Нисневич

2009-09-01

Full Text Available Fair, transparent and professional competition is the basis of functioning and dynamic stabilization of political system. Further broadening of economical, political and informational freedom and competition is a requirement for lowering of corruption and securing of effectiveness of application of special legal and administrative measures for its suppression.

The transcription factor NFATp plays a key role in susceptibility to TB in mice.

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Laura E Via

Full Text Available In T cells, the transcription factor nuclear factor of activated T cells p (NFATp is a key regulator of the cytokine genes tumor necrosis factor (TNF and interferon-γ (IFN-γ. Here, we show that NFATp-deficient (NFATp(-/- mice have a dramatic and highly significant increase in mortality after Mycobacterium tuberculosis (MTb infection as compared to mortality of control animals after MTb infection. Animals deficient in NFATp have significantly impaired levels of TNF and IFN-γ transcription and protein expression in naïve or total CD4(+ T cells, but display wild-type levels of TNF mRNA or protein from MTb-stimulated dendritic cells (DC. The rapid mortality and disease severity observed in MTb-infected NFATp(-/- mice is associated with dysregulated production of TNF and IFN-γ in the lungs, as well as with increased levels of TNF, in their serum. Furthermore, global blocking of TNF production by injection of a TNF neutralizaing agent at 6 weeks, but not 12 weeks, post-MTb-infection further decreased the survival rate of both wild-type and NFATp(-/- mice, indicating an early role for TNF derived from cells from the monocyte lineage in containment of infection. These results thus demonstrate that NFATp plays a critical role in immune containment of TB disease in vivo, through the NFATp-dependent expression of TNF and IFN-γ in T cells.

A pilot study examining diagnostic differences among exercise and weight suppression in bulimia nervosa and binge eating disorder.

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Cook, Brian J; Steffen, Kristine J; Mitchell, James E; Otto, Maxwell; Crosby, Ross D; Cao, Li; Wonderlich, Stephen A; Crow, Scott; Hill, Laura; Le Grange, Daniel; Powers, Pauline

2015-05-01

The objective of this study was to investigate diagnostic differences in weight suppression (e.g., the difference between one's current body weight and highest non-pregnancy adult body weight) and exercise among Bulimia Nervosa (BN) and Binge Eating Disorder (BED). Because exercise may be a key contributor to weight suppression in BN, we were interested in examining the potential moderating effect of exercise on weight suppression in BN or BED. Participants with BN (n = 774) and BED (n = 285) completed self-report surveys of weight history, exercise and eating disorder symptoms. Generalised linear model analyses were used to examine the associations among diagnosis, exercise frequency and their interaction on weight suppression. Exercise frequency and BN/BED diagnosis were both associated with weight suppression. Additionally, exercise frequency moderated the relationship between diagnosis and weight suppression. Specifically, weight suppression was higher in BN than in BED among those with low exercise frequency but comparable in BN and BED among those with high exercise frequency. Our results suggest that exercise frequency may contribute to different weight suppression outcomes among BN and BED. This may inform clinical implications of exercise in these disorders. Specifically, much understanding of the differences among exercise frequency and the compensatory use of exercise in BN and BED is needed. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

MicroRNA-214 suppresses gluconeogenesis by targeting activating transcriptional factor 4.

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Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai; Wang, Chunxia; Guo, Feifan

2015-03-27

Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1 (FOXO1) transcriptional activity. Finally, liver-specific miR-214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Suppression of neurotoxic lesion-induced seizure activity: evidence for a permanent role for the hippocampus in contextual memory.

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Fraser T Sparks

Full Text Available Damage to the hippocampus (HPC using the excitotoxin N-methyl-D-aspartate (NMDA can cause retrograde amnesia for contextual fear memory. This amnesia is typically attributed to loss of cells in the HPC. However, NMDA is also known to cause intense neuronal discharge (seizure activity during the hours that follow its injection. These seizures may have detrimental effects on retrieval of memories. Here we evaluate the possibility that retrograde amnesia is due to NMDA-induced seizure activity or cell damage per se. To assess the effects of NMDA induced activity on contextual memory, we developed a lesion technique that utilizes the neurotoxic effects of NMDA while at the same time suppressing possible associated seizure activity. NMDA and tetrodotoxin (TTX, a sodium channel blocker, are simultaneously infused into the rat HPC, resulting in extensive bilateral damage to the HPC. TTX, co-infused with NMDA, suppresses propagation of seizure activity. Rats received pairings of a novel context with foot shock, after which they received NMDA-induced, TTX+NMDA-induced, or no damage to the HPC at a recent (24 hours or remote (5 weeks time point. After recovery, the rats were placed into the shock context and freezing was scored as an index of fear memory. Rats with an intact HPC exhibited robust memory for the aversive context at both time points, whereas rats that received NMDA or NMDA+TTX lesions showed a significant reduction in learned fear of equal magnitude at both the recent and remote time points. Therefore, it is unlikely that observed retrograde amnesia in contextual fear conditioning are due to disruption of non-HPC networks by propagated seizure activity. Moreover, the memory deficit observed at both time points offers additional evidence supporting the proposition that the HPC has a continuing role in maintaining contextual memories.

Activated T cells sustain myeloid-derived suppressor cell-mediated immune suppression

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Damuzzo, Vera; Francescato, Samuela; Pozzuoli, Assunta; Berizzi, Antonio; Mocellin, Simone; Rossi, Carlo Riccardo; Bronte, Vincenzo; Mandruzzato, Susanna

2016-01-01

The expansion of myeloid derived suppressor cells (MDSCs), a suppressive population able to hamper the immune response against cancer, correlates with tumor progression and overall survival in several cancer types. We have previously shown that MDSCs can be induced in vitro from precursors present in the bone marrow and observed that these cells are able to actively proliferate in the presence of activated T cells, whose activation level is critical to drive the suppressive activity of MDSCs. Here we investigated at molecular level the mechanisms involved in the interplay between MDSCs and activated T cells. We found that activated T cells secrete IL-10 following interaction with MDSCs which, in turn, activates STAT3 phosphorylation on MDSCs then leading to B7-H1 expression. We also demonstrated that B7-H1+ MDSCs are responsible for immune suppression through a mechanism involving ARG-1 and IDO expression. Finally, we show that the expression of ligands B7-H1 and MHC class II both on in vitro-induced MDSCs and on MDSCs in the tumor microenvironment of cancer patients is paralleled by an increased expression of their respective receptors PD-1 and LAG-3 on T cells, two inhibitory molecules associated with T cell dysfunction. These findings highlight key molecules and interactions responsible for the extensive cross-talk between MDSCs and activated T cells that are at the basis of immune suppression. PMID:26700461

Factors affecting fire suppression costs as identified by incident management teams

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Janie Canton-Thompson; Brooke Thompson; Krista Gebert; David Calkin; Geoff Donovan; Greg Jones

2006-01-01

This study uses qualitative sociological methodology to discover information and insights about the role of Incident Management Teams in wildland fire suppression costs. We interviewed 48 command and general staff members of Incident Management Teams throughout the United States. Interviewees were asked about team structure, functioning, and decision making as a...

[Key role played by the gut associated lymphoid tissue during human immunodeficiency virus infection].

Science.gov (United States)

Vergnon-Miszczycha, Delphine; Lucht, Frédéric; Roblin, Xavier; Pozzetto, Bruno; Paul, Stéphane; Bourlet, Thomas

2015-12-01

The gut associated lymphoid tissue (GALT) is the site of numerous immunological disturbances during HIV-1 infection. It constitutes the largest reservoir for HIV, not or very poorly susceptible to antiretroviral therapy (ART), making it a major obstacle to HIV cure. Moreover, the GALT is involved in systemic immune activation in HIV-infected individuals: intestinal damage due to viral replication and severe CD4(+) T cell depletion in the GALT leads to microbial translocation, a key driver of immune activation, and in turn, disease progression. In this review, we describe the role of the GALT in HIV infection and we discuss therapeutic options to decrease the intestinal viral reservoir and to preserve immune function in the gut of HIV-infected people. Achieving these goals is necessary for a long-term infection control after the interruption of ART. © 2015 médecine/sciences – Inserm.

Screening and Characterization of Potentially Suppressive Soils against Gaeumannomyces graminis under Extensive Wheat Cropping by Chilean Indigenous Communities

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Paola Durán

2017-08-01

Full Text Available Wheat production around the world is severely compromised by the occurrence of “take-all” disease, which is caused by the soil-borne pathogen Gaeumannomyces graminis var. tritici (Ggt. In this context, suppressive soils are those environments in which plants comparatively suffer less soil-borne pathogen diseases than expected, owing to native soil microorganism activities. In southern Chile, where 85% of the national cereal production takes place, several studies have suggested the existence of suppressive soils under extensive wheat cropping. Thus, this study aimed to screen Ggt-suppressive soil occurrence in 16 locations managed by indigenous “Mapuche” communities, using extensive wheat cropping for more than 10 years. Ggt growth inhibition in vitro screenings allowed the identification of nine putative suppressive soils. Six of these soils, including Andisols and Ultisols, were confirmed to be suppressive, since they reduced take-all disease in wheat plants growing under greenhouse conditions. Suppressiveness was lost upon soil sterilization, and recovered by adding 1% of the natural soil, hence confirming that suppressiveness was closely associated to the soil microbiome community composition. Our results demonstrate that long-term extensive wheat cropping, established by small Mapuche communities, can generate suppressive soils that can be used as effective microorganism sources for take-all disease biocontrol. Accordingly, suppressive soil identification and characterization are key steps for the development of environmentally-friendly and efficient biotechnological applications for soil-borne disease control.

miR-181c-BRK1 axis plays a key role in actin cytoskeleton-dependent T cell function.

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Lim, Shok Ping; Ioannou, Nikolaos; Ramsay, Alan G; Darling, David; Gäken, Joop; Mufti, Ghulam J

2018-05-01

MicroRNAs are short endogenous noncoding RNAs that play pivotal roles in a diverse range of cellular processes. The miR-181 family is important in T cell development, proliferation, and activation. In this study, we have identified BRK1 as a potential target of miR-181c using a dual selection functional assay and have showed that miR-181c regulates BRK1 by translational inhibition. Given the importance of miR-181 in T cell function and the potential role of BRK1 in the involvement of WAVE2 complex and actin polymerization in T cells, we therefore investigated the influence of miR-181c-BRK1 axis in T cell function. Stimulation of PBMC derived CD3 + T cells resulted in reduced miR-181c expression and up-regulation of BRK1 protein expression, suggesting that miR-181c-BRK1 axis is important in T cell activation. We further showed that overexpression of miR-181c or suppression of BRK1 resulted in inhibition of T cell activation and actin polymerization coupled with defective lamellipodia generation and immunological synapse formation. Additionally, we found that BRK1 silencing led to reduced expressions of other proteins in the WAVE2 complex, suggesting that the impairment of T cell actin dynamics was a result of the instability of the WAVE2 complex following BRK1 depletion. Collectively, we demonstrated that miR-181c reduces BRK1 protein expression level and highlighted the important role of miR-181c-BRK1 axis in T cell activation and actin polymerization-mediated T cell functions. ©2018 Society for Leukocyte Biology.

Suppression of IL-6 Gene by shRNA Augments Gemcitabine Chemosensitization in Pancreatic Adenocarcinoma Cells

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Hai-Bo Xing

2018-01-01

Full Text Available Pancreatic adenocarcinoma has an exceedingly poor prognosis, accounting for five-year survival of less than 5%. Presently, improving the efficacy of pancreatic adenocarcinoma treatment has been the focus of medical researchers worldwide. Recently, it has been suggested that deregulation of interleukin- (IL- 6 is caused by a key gene involved in the beginning and development of pancreatic adenocarcinoma. Herein, we investigated whether suppression of IL-6 could augment gemcitabine sensitivity in the PANC-1 cells. We found considerably higher expression of IL-6 in pancreatic adenocarcinoma tissues than that in the adjacent nontumorous tissues. Suppression of IL-6 by shRNA resulted in apoptosis as well as inhibition of cell proliferation and tumorigenicity. In addition, suppression of IL-6 remarkably promoted antitumor effect of gemcitabine, indicating that the combination of shRNA targeting IL-6 with gemcitabine may provide a potential clinical approach for pancreatic cancer therapy.

Dynamics of Interocular Suppression in Amblyopic Children during Electronically Monitored Occlusion Therapy: First Insight.

Science.gov (United States)

Kehrein, Stephan; Kohnen, Thomas; Fronius, Maria

2016-06-01

Interocular suppression is assumed to be the mechanism leading to impaired visual acuity, especially in strabismic amblyopia. Little is known about the dynamics of suppression during treatment. The aim of our study was to assess the development of the depth of suppression and its relation to changes in visual acuity during electronically monitored occlusion treatment. In a prospective pilot study, 15 amblyopes (8 with and 7 without strabismus) aged 5 to 16 years (mean 10.24 years) were examined before initiation of patching and then every 3 to 6 weeks for 4 months. To quantify suppression, a red filter ladder (Sbisa bar) was used, attenuating the image of the dominant eye until the patients reported a binocular perception (diplopia, rivalry, color mixture) or a change in eye dominance. Acuity was assessed with crowded Landolt rings. Daily occlusion was recorded using occlusion dose monitors. The depth of interocular suppression showed a biphasic change: it increased significantly during the first month (P=0.02), while visual acuity improved (mean 0.14 log units ±0.13; Pocclusion and suppression changes was not statistically significant. This first insight into the functional changes during electronically monitored patching suggests a complex relationship between visual acuity and interocular suppression that seems to be influenced by the presence of strabismus. Knowledge of the dynamics of interocular suppression is crucial for enhancing the outcome of occlusion treatment and also for the evaluation of its future role compared to emerging dichoptic treatments.

Key Principles of Superfund Remedy Selection

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Guidance on the primary considerations of remedy selection which are universally applicable at Superfund sites. Key guidance here include: Rules of Thumb for Superfund Remedy Selection and Role of the Baseline Risk Assessment.

Global suppression of electrocortical activity in unilateral perinatal thalamic stroke.

LENUS (Irish Health Repository)

Kharoshankaya, Liudmila

2014-07-01

We present an unusual case of persistent generalized electroencephalography (EEG) suppression and right-sided clonic seizures in a male infant born at 40(+2) weeks\\' gestation, birthweight 3240g, with an isolated unilateral thalamic stroke. The EEG at 13 hours after birth showed a generalized very low amplitude background pattern, which progressed to frequent electrographic seizures over the left hemisphere. The interictal background EEG pattern remained grossly abnormal over the next 48 hours, showing very low background amplitudes (<10μV). Magnetic resonance imaging revealed an isolated acute left-sided thalamic infarction. This is the first description of severe global EEG suppression caused by an isolated unilateral thalamic stroke and supports the role of the thalamus as the control centre for cortical electrical activity.

Compressibility and rotation effects on transport suppression in magnetohydrodynamic turbulence

International Nuclear Information System (INIS)

Yoshizawa, A.

1996-01-01

Compressibility and rotation effects on turbulent transports in magnetohydrodynamic (MHD) flows under arbitrary mean field are investigated using a Markovianized two-scale statistical approach. Some new aspects of MHD turbulence are pointed out in close relation to plasma compressibility. Special attention is paid to the turbulent electromotive force, which plays a central role in the generation of magnetic and velocity fluctuations. In addition to plasma rotation, the interaction between compressibility and magnetic fields is shown to bring a few factors suppressing MHD fluctuations and, eventually, density and temperature transports, even in the presence of steep mean density and temperature gradients. This finding is discussed in the context of the turbulence-suppression mechanism in the tokamak close-quote s high-confinement modes. copyright 1996 American Institute of Physics

Pressure suppressing device

International Nuclear Information System (INIS)

Naito, Makoto.

1980-01-01

Purpose: To prevent the pressure in the reactor container from excessively increasing even when vapor leaks from the dry well to a space of the suppression chamber, without passing though the suppression pool at the time of loss of coolant accident. Constitution: When vapor of a high temperature and a high pressure at the time of loss of coolant accident flows from the dry well to the suppression chamber without passing through suppression pool water, vapor dose not condense with pool water, and therefore the pressure within the chamber abnormally increases. For this reason, this abnormal pressure is detected by a pressure detector thereby to start the operations of a blower and a pump. By starting the blower, the pressure in the dry well becomes lower than the pressure in the chamber, and vapor entirely passes through the pool water and entirely condenses with the pool water. By starting the pump, the pool water is sprayed over the space of the chamber, and vapor in the space is condensed. (Yoshino, Y.)

Distinguishing among potential mechanisms of singleton suppression.

Science.gov (United States)

Gaspelin, Nicholas; Luck, Steven J

2018-04-01

Previous research has revealed that people can suppress salient stimuli that might otherwise capture visual attention. The present study tests between 3 possible mechanisms of visual suppression. According to first-order feature suppression models , items are suppressed on the basis of simple feature values. According to second-order feature suppression models , items are suppressed on the basis of local discontinuities within a given feature dimension. According to global-salience suppression models , items are suppressed on the basis of their dimension-independent salience levels. The current study distinguished among these models by varying the predictability of the singleton color value. If items are suppressed by virtue of salience alone, then it should not matter whether the singleton color is predictable. However, evidence from probe processing and eye movements indicated that suppression is possible only when the color values are predictable. Moreover, the ability to suppress salient items developed gradually as participants gained experience with the feature that defined the salient distractor. These results are consistent with first-order feature suppression models, and are inconsistent with the other models of suppression. In other words, people primarily suppress salient distractors on the basis of their simple features and not on the basis of salience per se. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A study on suppressing transmittance fluctuations for air-gapped Glan-type polarizing prisms

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Zhang, Chuanfa; Li, Dailin; Zhu, Huafeng; Li, Chuanzhi; Jiao, Zhiyong; Wang, Ning; Xu, Zhaopeng; Wang, Xiumin; Song, Lianke

2018-05-01

Light intensity transmittance is a key parameter for the design of polarizing prisms, while sometimes its experimental curves based on spatial incident angle presents periodical fluctuations. Here, we propose a novel method for completely suppressing these fluctuations via setting a glued error angle in the air gap of Glan-Taylor prisms. The proposal consists of: an accurate formula of the intensity transmittance for Glan-Taylor prisms, a numerical simulation and a contrast experiment of Glan-Taylor prisms for analyzing the causes of the fluctuations, and a simple method for accurately measuring the glued error angle. The result indicates that when the setting glued error angle is larger than the critical angle for a certain polarizing prism, the fluctuations can be completely suppressed, and a smooth intensity transmittance curve can be obtained. Besides, the critical angle in the air gap for suppressing the fluctuations is decreased with the increase of beam spot size. This method has the advantage of having less demand for the prism position in optical systems.

The rhizosphere microbial community in a multiple parallel mineralization system suppresses the pathogenic fungus Fusarium oxysporum

Science.gov (United States)

Fujiwara, Kazuki; Iida, Yuichiro; Iwai, Takashi; Aoyama, Chihiro; Inukai, Ryuya; Ando, Akinori; Ogawa, Jun; Ohnishi, Jun; Terami, Fumihiro; Takano, Masao; Shinohara, Makoto

2013-01-01

The rhizosphere microbial community in a hydroponics system with multiple parallel mineralization (MPM) can potentially suppress root-borne diseases. This study focused on revealing the biological nature of the suppression against Fusarium wilt disease, which is caused by the fungus Fusarium oxysporum, and describing the factors that may influence the fungal pathogen in the MPM system. We demonstrated that the rhizosphere microbiota that developed in the MPM system could suppress Fusarium wilt disease under in vitro and greenhouse conditions. The microbiological characteristics of the MPM system were able to control the population dynamics of F. oxysporum, but did not eradicate the fungal pathogen. The roles of the microbiological agents underlying the disease suppression and the magnitude of the disease suppression in the MPM system appear to depend on the microbial density. F. oxysporum that survived in the MPM system formed chlamydospores when exposed to the rhizosphere microbiota. These results suggest that the microbiota suppresses proliferation of F. oxysporum by controlling the pathogen's morphogenesis and by developing an ecosystem that permits coexistence with F. oxysporum. PMID:24311557

Suppression criteria of parasitic mode oscillations in a gyrotron beam tunnel

Science.gov (United States)

Kumar, Nitin; Singh, Udaybir; Singh, T. P.; Sinha, A. K.

2011-02-01

This paper presents the design criteria of the parasitic mode oscillations suppression for a periodic, ceramic, and copper loaded gyrotron beam tunnel. In such a type of beam tunnel, the suppression of parasitic mode oscillations is an important design problem. A method of beam-wave coupling coefficient and its mathematical formulation are presented. The developed design criteria are used in the beam tunnel design of a 42 GHz gyrotron to be developed for the Indian TOKAMAK system. The role of the thickness and the radius of the beam tunnel copper rings to obtain the developed design criteria are also discussed. The commercially available electromagnetic code CST and the electron trajectory code EGUN are used for the simulations.

Suppression criteria of parasitic mode oscillations in a gyrotron beam tunnel

International Nuclear Information System (INIS)

Kumar, Nitin; Singh, Udaybir; Sinha, A. K.; Singh, T. P.

2011-01-01

This paper presents the design criteria of the parasitic mode oscillations suppression for a periodic, ceramic, and copper loaded gyrotron beam tunnel. In such a type of beam tunnel, the suppression of parasitic mode oscillations is an important design problem. A method of beam-wave coupling coefficient and its mathematical formulation are presented. The developed design criteria are used in the beam tunnel design of a 42 GHz gyrotron to be developed for the Indian TOKAMAK system. The role of the thickness and the radius of the beam tunnel copper rings to obtain the developed design criteria are also discussed. The commercially available electromagnetic code CST and the electron trajectory code EGUN are used for the simulations.

Performance Improvement of Raman Distributed Temperature System by Using Noise Suppression

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Li, Jian; Li, Yunting; Zhang, Mingjiang; Liu, Yi; Zhang, Jianzhong; Yan, Baoqiang; Wang, Dong; Jin, Baoquan

2018-06-01

In Raman distributed temperature system, the key factor for performance improvement is noise suppression, which seriously affects the sensing distance and temperature accuracy. Therefore, we propose and experimentally demonstrate dynamic noise difference algorithm and wavelet transform modulus maximum (WTMM) to de-noising Raman anti-Stokes signal. Experimental results show that the sensing distance can increase from 3 km to 11.5 km and the temperature accuracy increases to 1.58 °C at the sensing distance of 10.4 km.

Pyrroloquinoline-quinone suppresses liver fibrogenesis in mice.

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Dongwei Jia

Full Text Available Liver fibrosis represents the consequences of a sustained wound healing response to chronic liver injuries, and its progression toward cirrhosis is the major cause of liver-related morbidity and mortality worldwide. However, anti-fibrotic treatment remains an unconquered area for drug development. Accumulating evidence indicate that oxidative stress plays a critical role in liver fibrogenesis. In this study, we found that PQQ, a natural anti-oxidant present in a wide variety of human foods, exerted potent anti-fibrotic and ROS-scavenging activity in Balb/C mouse models of liver fibrosis. The antioxidant activity of PQQ was involved in the modulation of multiple steps during liver fibrogenesis, including chronic liver injury, hepatic inflammation, as well as activation of hepatic stellate cells and production of extracellular matrix. PQQ also suppressed the up-regulation of RACK1 in activated HSCs in vivo and in vitro. Our data suggest that PQQ suppresses oxidative stress and liver fibrogenesis in mice, and provide rationale for the clinical application of PQQ in the prevention and treatment of liver fibrosis.

Effective suppression of thermoelectric voltage in nonlocal spin-valve measurement

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Ariki, Taisei; Nomura, Tatsuya; Ohnishi, Kohei; Kimura, Takashi

2017-06-01

We demonstrate that the background signal in the nonlocal spin-valve measurement can be sufficiently suppressed by optimizing the electrode design of the lateral spin valve. A relatively long length scale of heat propagation produces spin-independent thermoelectric signals under the combination of the Peltier and Seebeck effects. These unfavorable signals can be reduced by mixing the Peltier effects in two transparent ferromagnetic/nonmagnetic junctions. Proper understanding of the contribution from the heat current in no spin-current area is a key for effective reduction of the spin-independent background signal.

Thyroid suppression test with dextrothyroxine

International Nuclear Information System (INIS)

Rosenthal, D.; Fridman, J.; Ribeiro, H.B.

1978-01-01

The classic thyroid suppression test with triiodothyronine (l-T 3 ) has been shown to be efficient as an auxiliary method in the diagnosis of thyroid diseases, but should not be performed on elderly patients or on those with heart disease or a tendency to tachycardia. Since these subjects seem able to support a short period of dextro-thyronine (d-T 4 ) feeding, we compared the effect of d-T 4 and l-T 3 on the 24 hours thyroid uptake in euthyroid and hyperthyroid subjects. After basal radio-iodine uptake determination, 99 patients without hyperthyroidism and 27 with Graves' disease were randomly divided in 2 groups; one received 100μg of l-T 3 per day and the other 4 mg of d-T 4 per day, both groups being treated for a period of 10 days. At the end of this suppression period the 24 hours radio-iodine uptake was measured again and the percentual suppression index (S.I.) calculated. Since the comparison of the two groups showed no difference between the suppressive effect of l-T 3 and d-T 4 in euthyroid subjects, while dextro-thyronine, as levo-triiodothyronine, did not suppress the 24 hours uptake of hyperthyroid patients, l-T 3 or d-T 4 can be used interchangeably to test thyroid suppressibility. In the euthyroid subjects the normal range for the post-suppression uptake was 0-17.1% and for the suppression index 54,7.100% [pt

Prostaglandin E2 and Transforming Growth Factor-β Play a Critical Role in Suppression of Allergic Airway Inflammation by Adipose-Derived Stem Cells.

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Kyu-Sup Cho

Full Text Available The role of soluble factors in the suppression of allergic airway inflammation by adipose-derived stem cells (ASCs remains to be elucidated. Moreover, the major soluble factors responsible for the immunomodulatory effects of ASCs in allergic airway diseases have not been well documented. We evaluated the effects of ASCs on allergic inflammation in asthmatic mice treated with a prostaglandin E2 (PGE2 inhibitor or transforming growth factor-β (TGF-β neutralizing antibodies.Asthmatic mice were injected intraperitoneally with a PGE2 inhibitor or TGF-β neutralizing antibodies at approximately the same time as ASCs injection and were compared with non-treated controls. In asthmatic mice, ASCs significantly reduced airway hyperresponsiveness, the number of total inflammatory cells and eosinophils in the bronchoalveolar lavage fluid (BALF, eosinophilic inflammation, goblet cell hyperplasia, and serum total and allergen-specific IgE and IgG1. ASCs significantly inhibited Th2 cytokines, such as interleukin (IL-4, IL-5, and IL-13, and enhanced the Th1 cytokine (Interferon-γ and regulatory cytokines (IL-10 and TGF-β in the BALF and lung draining lymph nodes (LLNs. ASCs engraftment caused significant increases in the regulatory T cell (Treg and IL-10+ T cell populations in LLNs. However, blocking PGE2 or TGF-β eliminated the immunosuppressive effect of ASCs in allergic airway inflammation.ASCs are capable of secreting PGE2 and TGF-β, which may play a role in inducing Treg expansion. Furthermore, treatment with a PGE2 inhibitor or TGF-β neutralizing antibodies eliminated the beneficial effect of ASCs treatment in asthmatic mice, suggesting that PGE2 and TGF-β are the major soluble factors responsible for suppressing allergic airway inflammation.

Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity

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Masako Isokawa

2016-01-01

Full Text Available GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca2+]i and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing [Ca2+]i. A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition, mediated by endogenous cannabinoids that require a [Ca2+]i rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI persisted in the absence of a [Ca2+]i rise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robust Ca2+-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.

Contrasting Roles of Dopamine and Noradrenaline in the Motivational Properties of Social Play Behavior in Rats.

Science.gov (United States)

Achterberg, E J Marijke; van Kerkhof, Linda W M; Servadio, Michela; van Swieten, Maaike M H; Houwing, Danielle J; Aalderink, Mandy; Driel, Nina V; Trezza, Viviana; Vanderschuren, Louk J M J

2016-02-01

Social play behavior, abundant in the young of most mammalian species, is thought to be important for social and cognitive development. Social play is highly rewarding, and as such, the expression of social play depends on its pleasurable and motivational properties. Since the motivational properties of social play have only sporadically been investigated, we developed a setup in which rats responded for social play under a progressive ratio schedule of reinforcement. Dopaminergic neurotransmission plays a key role in incentive motivational processes, and both dopamine and noradrenaline have been implicated in the modulation of social play behavior. Therefore, we investigated the role of dopamine and noradrenaline in the motivation for social play. Treatment with the psychostimulant drugs methylphenidate and cocaine increased responding for social play, but suppressed its expression during reinforced play periods. The dopamine reuptake inhibitor GBR-12909 increased responding for social play, but did not affect its expression, whereas the noradrenaline reuptake inhibitor atomoxetine decreased responding for social play as well as its expression. The effects of methylphenidate and cocaine on responding for social play, but not their play-suppressant effects, were blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. In contrast, pretreatment with the α2-adrenoceptor antagonist RX821002 prevented the play-suppressant effect of methylphenidate, but left its effect on responding for social play unaltered. In sum, the present study introduces a novel method to study the incentive motivational properties of social play behavior in rats. Using this paradigm, we demonstrate dissociable roles for dopamine and noradrenaline in social play behavior: dopamine stimulates the motivation for social play, whereas noradrenaline negatively modulates the motivation for social play behavior and its expression.

Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

Energy Technology Data Exchange (ETDEWEB)

Lee, So-Yeon; Kim, Sun Ki [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Jee, Won-Hee [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Catholic University of Korea, Diagnostic Radiology, Seoul St. Mary' s Hospital, School of Medicine, Seoul (Korea, Republic of); Kim, Jung-Man [Catholic University of Korea, Department of Orthopedic Surgery, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of)

2011-02-15

To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using {kappa} coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with ({kappa} = 0.87) or without ({kappa} = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

International Nuclear Information System (INIS)

Lee, So-Yeon; Kim, Sun Ki; Jee, Won-Hee; Kim, Jung-Man

2011-01-01

To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using κ coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with (κ = 0.87) or without (κ = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

ROLE AND IMPORTANCE OF KEY PERFORMANCE INDICATORS MEASUREMENT

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Rade Stanković

2011-03-01

Full Text Available Key performance indicators are financial and non financial indicators that organizations use inorder to estimate and fortify how successful they are, aiming previously established long lastinggoals. Appropriate selection of indicators that will be used for measuring is of a greatest importance.Process organization of business is necessary to be constitute in order to realize such effective andefficient system or performance measuring via KPI. Process organization also implies customerorientation and necessary flexibility in nowadays condition of global competition.Explanation of process organization, the way of KPI selection, and practical example of KPImeasuring in Toyota dealerships are presented in this paper.

Key role of symbiotic dinitrogen fixation in tropical forest secondary succession

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Batterman, Sarah A.; Hedin, Lars O.; van Breugel, Michiel; Ransijn, Johannes; Craven, Dylan J.; Hall, Jefferson S.

2013-10-01

Forests contribute a significant portion of the land carbon sink, but their ability to sequester CO2 may be constrained by nitrogen, a major plant-limiting nutrient. Many tropical forests possess tree species capable of fixing atmospheric dinitrogen (N2), but it is unclear whether this functional group can supply the nitrogen needed as forests recover from disturbance or previous land use, or expand in response to rising CO2 (refs 6, 8). Here we identify a powerful feedback mechanism in which N2 fixation can overcome ecosystem-scale deficiencies in nitrogen that emerge during periods of rapid biomass accumulation in tropical forests. Over a 300-year chronosequence in Panama, N2-fixing tree species accumulated carbon up to nine times faster per individual than their non-fixing neighbours (greatest difference in youngest forests), and showed species-specific differences in the amount and timing of fixation. As a result of fast growth and high fixation, fixers provided a large fraction of the nitrogen needed to support net forest growth (50,000kg carbon per hectare) in the first 12years. A key element of ecosystem functional diversity was ensured by the presence of different N2-fixing tree species across the entire forest age sequence. These findings show that symbiotic N2 fixation can have a central role in nitrogen cycling during tropical forest stand development, with potentially important implications for the ability of tropical forests to sequester CO2.

Key role of symbiotic dinitrogen fixation in tropical forest secondary succession.

Science.gov (United States)

Batterman, Sarah A; Hedin, Lars O; van Breugel, Michiel; Ransijn, Johannes; Craven, Dylan J; Hall, Jefferson S

2013-10-10

Forests contribute a significant portion of the land carbon sink, but their ability to sequester CO2 may be constrained by nitrogen, a major plant-limiting nutrient. Many tropical forests possess tree species capable of fixing atmospheric dinitrogen (N2), but it is unclear whether this functional group can supply the nitrogen needed as forests recover from disturbance or previous land use, or expand in response to rising CO2 (refs 6, 8). Here we identify a powerful feedback mechanism in which N2 fixation can overcome ecosystem-scale deficiencies in nitrogen that emerge during periods of rapid biomass accumulation in tropical forests. Over a 300-year chronosequence in Panama, N2-fixing tree species accumulated carbon up to nine times faster per individual than their non-fixing neighbours (greatest difference in youngest forests), and showed species-specific differences in the amount and timing of fixation. As a result of fast growth and high fixation, fixers provided a large fraction of the nitrogen needed to support net forest growth (50,000 kg carbon per hectare) in the first 12 years. A key element of ecosystem functional diversity was ensured by the presence of different N2-fixing tree species across the entire forest age sequence. These findings show that symbiotic N2 fixation can have a central role in nitrogen cycling during tropical forest stand development, with potentially important implications for the ability of tropical forests to sequester CO2.

Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk.

Science.gov (United States)

Cornford, Andrea S; Barkan, Ariel L; Hinko, Alexander; Horowitz, Jeffrey F

2012-11-15

Previously, we reported that overeating for only a few days markedly suppressed the secretion of growth hormone (GH). The purpose of the present study was to determine the role of this reduction in GH concentration on key metabolic adaptations that occur during 2 wk of overeating. Nine nonobese, healthy adults were admitted to the hospital for 2 wk, during which time they ate ∼4,000 kcal/day (70 kcal·kg fat-free mass(-1)·day(-1); 50% carbohydrate, 35% fat, and 15% protein), and their plasma GH concentration was allowed to decline naturally (control). An additional eight subjects underwent the same overeating intervention and received exogenous GH treatment (GHT) administered in four daily injections to mimic physiological GH secretion throughout the 2-wk overeating period. We measured plasma insulin and glucose concentrations in the fasting and postprandial state as well as fasting lipolytic rate, proteolytic rate, and fractional synthetic rate (FSR) using stable-isotope tracer methods. GHT prevented the fall in plasma GH concentration, maintaining plasma GH concentration at baseline levels (1.2 ± 0.2 ng/ml), which increased fasting and postprandial assessments of insulin resistance (P overeating also blunted the increase in systemic proteolysis (P overeating. In conclusion, our main findings suggest that the suppression in GH secretion that naturally occurs during the early stages of overeating may help attenuate the insulin resistance and hyperlipidemia that typically accompany overeating.

GHSR deficiency suppresses neointimal formation in injured mouse arteries

International Nuclear Information System (INIS)

Li, Jing; Zhang, Man; Wang, Mo; Wang, Zhipeng; Liu, Yahan; Zhang, Weizhen; Wang, Nanping

2016-01-01

Growth hormone secretagogue receptor (GHSR) is involved in appetite regulation and energy homeostasis. In the present study, we examined the role of GHSR in neointimal formation following vascular injury. In the mouse model of femoral artery wire injury, we found that vessel intima-to-media ratio was significantly reduced in GHSR deficiency (GHSR −/− ) mice compared with that in wild-type mice. Immunohistochemical staining showed that the smooth muscle cell (SMCs) in the neointima were significantly decreased in the injured arteries of GHSR −/− mice which was associated with decreased SMC proliferation and migration. Furthermore, immunoblotting demonstrated that, in cultured rat aortic SMCs, small interfering RNA-mediated GHSR knockdown suppressed the activation of Akt and ERK1/2 signaling pathway. These findings suggested a novel role of GHSR in neointimal formation likely via promoting the proliferation and migration of SMCs involving Akt and ERK1/2 signaling. Therefore, GHSR may be a potential therapeutic target in restenosis and vascular remodeling. - Highlights: • GHSR deficiency inhibits neointimal formation after vascular injury. • GHSR deficiency suppresses SMCs numbers in vivo. • Knockdown GHSR represses SMCs proliferation and migration in vitro. • Knockdown GHSR inhibited Akt and ERK1/2 phosphorylation in SMCs.

Myostatin Suppression of Akirin1 Mediates Glucocorticoid-Induced Satellite Cell Dysfunction

Science.gov (United States)

Dong, Yanjun; Pan, Jenny S.; Zhang, Liping

2013-01-01

Glucocorticoids production is increased in many pathological conditions that are associated with muscle loss, but their role in causing muscle wasting is not fully understood. We have demonstrated a new mechanism of glucocorticoid-induced muscle atrophy: Dexamethasone (Dex) suppresses satellite cell function contributing to the development of muscle atrophy. Specifically, we found that Dex decreases satellite cell proliferation and differentiation in vitro and in vivo. The mechanism involved Dex-induced upregulation of myostatin and suppression of Akirin1, a promyogenic gene. When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth. In addition, silencing myostatin in myoblasts or satellite cells prevented Dex from suppressing Akirin1 expression and cellular proliferation and differentiation. Finally, overexpression of Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation, theses improvements were no longer suppressed by Dex. We conclude that glucocorticoids stimulate myostatin which inhibits Akirin1 expression and the reparative functions of satellite cells. These responses attribute to muscle atrophy. Thus, inhibition of myostatin or increasing Akirin1 expression could lead to therapeutic strategies for improving satellite cell activation and enhancing muscle growth in diseases associated with increased glucocorticoid production. PMID:23516508

Myostatin suppression of Akirin1 mediates glucocorticoid-induced satellite cell dysfunction.

Directory of Open Access Journals (Sweden)

Yanjun Dong

Full Text Available Glucocorticoids production is increased in many pathological conditions that are associated with muscle loss, but their role in causing muscle wasting is not fully understood. We have demonstrated a new mechanism of glucocorticoid-induced muscle atrophy: Dexamethasone (Dex suppresses satellite cell function contributing to the development of muscle atrophy. Specifically, we found that Dex decreases satellite cell proliferation and differentiation in vitro and in vivo. The mechanism involved Dex-induced upregulation of myostatin and suppression of Akirin1, a promyogenic gene. When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth. In addition, silencing myostatin in myoblasts or satellite cells prevented Dex from suppressing Akirin1 expression and cellular proliferation and differentiation. Finally, overexpression of Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation, theses improvements were no longer suppressed by Dex. We conclude that glucocorticoids stimulate myostatin which inhibits Akirin1 expression and the reparative functions of satellite cells. These responses attribute to muscle atrophy. Thus, inhibition of myostatin or increasing Akirin1 expression could lead to therapeutic strategies for improving satellite cell activation and enhancing muscle growth in diseases associated with increased glucocorticoid production.

An active role for endogenous beta-1,3-glucanase genes in transgene-mediated co-suppression in tobacco.

Science.gov (United States)

Sanders, Matthew; Maddelein, Wendy; Depicker, Anna; Van Montagu, Marc; Cornelissen, Marc; Jacobs, John

2002-11-01

Post-transcriptional gene silencing (PTGS) is characterized by the accumulation of short interfering RNAs that are proposed to mediate sequence-specific degradation of cognate and secondary target mRNAs. In plants, it is unclear to what extent endogenous genes contribute to this process. Here, we address the role of the endogenous target genes in transgene-mediated PTGS of beta-1,3-glucanases in tobacco. We found that mRNA sequences of the endogenous glucanase glb gene with varying degrees of homology to the Nicotiana plumbaginifolia gn1 transgene are targeted by the silencing machinery, although less efficiently than corresponding transgene regions. Importantly, we show that endogene-specific nucleotides in the glb sequence provide specificity to the silencing process. Consistent with this finding, small sense and antisense 21- to 23-nucleotide RNAs homologous to the endogenous glb gene were detected. Combined, these data demonstrate that a co-suppressed endogenous glucan ase gene is involved in signal amplification and selection of homologous targets, and show that endogenous genes can actively participate in PTGS in plants. The findings are introduced as a further sophistication of the post-transciptional silencing model.

CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment.

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Han, Yan; Wu, Chunlei; Wang, Jing; Liu, Na

2017-05-01

The major cause of death in osteosarcoma is the invasion and metastasis. Better understanding of the molecular mechanism of osteosarcoma invasion is essential in developing effective tumor-suppressive therapies. Interaction between chemokine receptors plays a crucial role in regulating osteosarcoma invasion. Here, we investigated the relationship between CXCR7 and CXCR4 in osteosarcoma invasion induced by bone marrow microenvironment. Human bone marrow mesenchymal stem cells were co-cultured with osteosarcoma cells to mimic actual bone marrow microenvironment. Osteosarcoma cell invasion and CXCL12/CXCR4 activation were observed within this co-culture model. Interestingly, in this co-culture model, osteosarcoma cell invasion was not inhibited by suppressing CXCR4 expression with neutralizing antibody or specific inhibitor AMD3100. Downstream signaling extracellular signal-regulated kinase and signal transducer and activator of transcription 3 were not significantly affected by CXCR4 inhibition. However, suppressing CXCR4 led to CXCR7 upregulation. Constitutive expression of CXCR7 could maintain osteosarcoma cell invasion when CXCR4 was suppressed. Simultaneously, inhibiting CXCR4 and CXCR7 compromised osteosarcoma invasion in co-culture system and suppressed extracellular signal-regulated kinase and signal transducer and activator of transcription 3 signals. Moreover, bone marrow microenvironment, not CXCL12 alone, is required for CXCR7 activation after CXCR4 suppression. Taken together, suppressing CXCR4 is not enough to impede osteosarcoma invasion in bone marrow microenvironment since CXCR7 is activated to sustain invasion. Therefore, inhibiting both CXCR4 and CXCR7 could be a promising strategy in controlling osteosarcoma invasion.

Identification of differential gene expression in in vitro FSH treated pig granulosa cells using suppression subtractive hybridization

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Tosser-Klopp G

2006-07-01

Full Text Available Abstract FSH, which binds to specific receptors on granulosa cells in mammals, plays a key role in folliculogenesis. Its biological activity involves stimulation of intercellular communication and upregulation of steroidogenesis, but the entire spectrum of the genes regulated by FSH has yet to be fully characterized. In order to find new regulated transcripts, however rare, we have used a Suppression Subtractive Hybridization approach (SSH on pig granulosa cells in primary culture treated or not with FSH. Two SSH libraries were generated and 76 clones were sequenced after selection by differential screening. Sixty four different sequences were identified, including 3 novel sequences. Experiments demonstrated the presence of 25 regulated transcripts. A gene ontology analysis of these 25 genes revealed (1 catalytic; (2 transport; (3 signal transducer; (4 binding; (5 anti-oxidant and (6 structural activities. These findings may deepen our understanding of FSH's effects. Particularly, they suggest that FSH is involved in the modulation of peroxidase activity and remodelling of chromatin.

Understanding the social effects of emotion regulation: the mediating role of authenticity for individual differences in suppression.

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English, Tammy; John, Oliver P

2013-04-01

Individuals differ in the strategies they use to regulate their emotions (e.g., suppression, reappraisal), and these regulatory strategies can differentially influence social outcomes. However, the mechanisms underlying these social effects remain to be specified. We examined one potential mediator that arises directly from emotion-regulatory effort (expression of positive emotion), and another mediator that does not involve emotion processes per se, but instead results from the link between regulation and self-processes (subjective inauthenticity). Across three studies, only inauthenticity mediated the link between habitual use of suppression and poor social functioning (lower relationship satisfaction, lower social support). These findings replicated across individuals socialized in Western and East Asian cultural contexts, younger and older adults, when predicting social functioning concurrently and a decade later, and even when broader adjustment was controlled. Thus, the social costs of suppression do not seem to be due to reduced positive emotion expression but rather the incongruence between inner-self and outer-behavior. Reappraisal was not consistently related to social functioning. Implications of these findings for emotion processes, self processes, and interpersonal relationships are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Interocular suppression

Science.gov (United States)

Tuna, Ana Rita; Almeida Neves Carrega, Filipa; Nunes, Amélia Fernandes

2017-08-01

The objective of this work is to quantify the suppressive imbalance, based on the manipulation of ocular luminance, between a group of subjects with normal binocular vision and a group of subjects with amblyopia. The result reveals that there are statistically significant differences in interocular dominance between two groups, evidencing a greater suppressive imbalance in amblyopic subjects. The technique used, proved to be a simple, easy to apply and economic method, for quantified ocular dominance. It is presented as a technique with the potential to accompany subjects with a marked dominance in one of the eyes that makes fusion difficult.

Suppression of dissipation in a laser-driven qubit by white noise

Energy Technology Data Exchange (ETDEWEB)

Yan, Lei-Lei [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); University of the Chinese Academy of Sciences, Beijing 100049 (China); Zhang, Jian-Qi [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Jing, Jun, E-mail: junjing@jlu.edu.cn [Institute of Atomic and Molecular Physics and Provincial Key Laboratory of Applied Atomic and Molecular Spectroscopy, Jilin University, Changchun 130012 (China); Feng, Mang, E-mail: mangfeng@wipm.ac.cn [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China)

2015-10-16

Decoherence of an open quantum system could be universally slowed down via ultra-fast modulation including regular, concatenated, random and even noisy control pulse sequences. We propose two noisy control schemes for a laser-driven qubit in order to suppress the dissipation induced by the environment, where employment of a weak driving laser is to alleviate the requirement for the control pulse strength down to the microwave regime. Calculations and analyses are based on a dynamical decoupling approach governed by the quantum-state-diffusion equation and the standard perturbation theory. The schemes can be applied to various systems, such as the cold atoms and quantum dots, manipulated by lasers for quantum information processing. - Highlights: • Two noisy control schemes for a laser-driven qubit are proposed. • Inspiring dissipation-suppression process is demonstrated both analytically and numerically. • The fidelity improvement is specified for the trapped ion by controlling the key parameters.

Volatile suppressing method for radioactive iodine

International Nuclear Information System (INIS)

Ohara, Atsushi; Haruguchi, Keiko.

1997-01-01

In the present invention, a metal plate is disposed above the pool water surface of a suppression chamber disposed to a reactor container in order to reduce evaporation of radioactive iodine released from a suppression pool. A metal plate is disposed above the pool water surface of the suppression chamber disposed to the reactor container. In addition, a metal plate is disposed around the space connecting a bent tube extending from a dry well to underwater of suppression pool water and a gas bent tube extending from the suppression chamber to an emergency gas processing system. Spray water is supplied for cooling the suppression chamber d as a means for cooling the metal plate. Then, among iodine released to the suppression chamber, elemental iodine liberated from the pool water is deposited on the surface of the metal plate, and the amount of iodine to be flown into and processed by an emergency gas processing system or a filter bent system can be reduced. (T.M.)

Expression levels of novel cytokine IL-32 in periodontitis and its role in the suppression of IL-8 production by human gingival fibroblasts stimulated with Porphyromonas gingivalis

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Kazuhisa Ouhara

2012-03-01

Full Text Available Background:IL-32 was recently found to be elevated in the tissue of rheumatoid arthritis and inflammatory bowel disease. Periodontitis is a chronic inflammatory disease caused by polymicrobial infections that result in soft tissue destruction and alveolar bone loss. Although IL-32 is also thought to be associated with periodontal disease, its expression and possible role in periodontal tissue remain unclear. Therefore, this study investigated the expression patterns of IL-32 in healthy and periodontally diseased gingival tissue. The expression of IL-32 in cultured human gingival fibroblasts (HGF as well as effects of autocrine IL-32 on IL-8 production from HGF were also examined.Methods:Periodontal tissue was collected from both healthy volunteers and periodontitis patients, and immunofluorescent staining was performed in order to determine the production of IL-32. Using real-time PCR and ELISA, mRNA expression and protein production of IL-32 in HGF, stimulated by Porphyromonas gingivalis (Pg, were also investigated.Results:Contrary to our expectation, the production of IL-32 in the periodontitis patients was significantly lower than in the healthy volunteers. According to immunofluorescent microscopy, positive staining for IL-32 was detected in prickle and basal cell layers in the epithelium as well as fibroblastic cells in connective tissue. Addition of fixed Pg in vitro was found to suppress the otherwise constitutive expression of IL-32 mRNA and protein in HGF. However, recombinant IL-32 in vitro inhibited the expression of IL-8 mRNA by HGF stimulated with Pg. Interestingly, anti-IL-32 neutralizing antibody upregulated the IL-8 mRNA expression in non-stimulated HGF, indicating that constitutive expression of IL-32 in HGF suppressed IL-8 mRNA expression in the absence of bacterial stimulation.Conclusion:These results indicate that IL-32 is constitutively produced by HGF which can be suppressed by Pg and may play a role in the downregulation

Androgen-androgen receptor system improves chronic inflammatory conditions by suppressing monocyte chemoattractant protein-1 gene expression in adipocytes via transcriptional regulation

Energy Technology Data Exchange (ETDEWEB)

Morooka, Nobukatsu, E-mail: amorooka@gunma-u.ac.jp [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Ueguri, Kei [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Yee, Karen Kar Lye [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Human Resources Cultivation Center, Gunma University, 1-5-1 Tenjin-cho, Kiryushi, Gunma, 376-8515 (Japan); Yanase, Toshihiko [Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, 814-0180 (Japan); Sato, Takashi [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan)

2016-09-02

Age-related decreases in sex hormones are closely related to chronic inflammation in obesity and metabolic diseases. Particularly, the molecular basis of androgen activity in regulating inflammation and controlling metabolism remains largely unknown. Obese adipocytes secrete monocyte chemoattractant protein-1 (MCP-1), a key chemokine that promotes the infiltration of monocytes/macrophages into adipose tissue, thereby leading to metabolic disorders. Here, we studied the role of androgen-androgen receptor (AR) action in regulating MCP-1 expression in adipose tissue. We observed the induction of Mcp-1 expression in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. Additionally, Mcp-1 expression was upregulated by culturing in conditioned medium derived from inflammatory macrophages (M1-Mφ) containing tumor necrosis factor-alpha (TNF-α). We found that sex hormones downregulated TNF-α-induced Mcp-1 and interleukin (Il)-6 expression in 3T3-L1 adipocytes. Furthermore, luciferase-reporter analysis indicated that MCP-1 promoter activity was predominantly suppressed by dihydrotestosterone (DHT)-AR interactions through functional canonical nuclear factor-kappa B (NF-κB) sites, whereas non-canonical NF-κB site containing important flanking sequences exhibited minor contributions to DHT-AR transcriptional repression. These findings suggested that androgen-AR suppressed obesity-induced chronic inflammation in adipose tissue. - Highlights: • DHT, non-aromatizable androgen suppresses Mcp-1 expression in adipocytes. • Mcp-1 transcription was negatively regulated by DHT-AR action. • DHT-AR selectively regulates Mcp-1 transcription through distinct NF-κB sites.

Androgen-androgen receptor system improves chronic inflammatory conditions by suppressing monocyte chemoattractant protein-1 gene expression in adipocytes via transcriptional regulation

International Nuclear Information System (INIS)

Morooka, Nobukatsu; Ueguri, Kei; Yee, Karen Kar Lye; Yanase, Toshihiko; Sato, Takashi

2016-01-01

Age-related decreases in sex hormones are closely related to chronic inflammation in obesity and metabolic diseases. Particularly, the molecular basis of androgen activity in regulating inflammation and controlling metabolism remains largely unknown. Obese adipocytes secrete monocyte chemoattractant protein-1 (MCP-1), a key chemokine that promotes the infiltration of monocytes/macrophages into adipose tissue, thereby leading to metabolic disorders. Here, we studied the role of androgen-androgen receptor (AR) action in regulating MCP-1 expression in adipose tissue. We observed the induction of Mcp-1 expression in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. Additionally, Mcp-1 expression was upregulated by culturing in conditioned medium derived from inflammatory macrophages (M1-Mφ) containing tumor necrosis factor-alpha (TNF-α). We found that sex hormones downregulated TNF-α-induced Mcp-1 and interleukin (Il)-6 expression in 3T3-L1 adipocytes. Furthermore, luciferase-reporter analysis indicated that MCP-1 promoter activity was predominantly suppressed by dihydrotestosterone (DHT)-AR interactions through functional canonical nuclear factor-kappa B (NF-κB) sites, whereas non-canonical NF-κB site containing important flanking sequences exhibited minor contributions to DHT-AR transcriptional repression. These findings suggested that androgen-AR suppressed obesity-induced chronic inflammation in adipose tissue. - Highlights: • DHT, non-aromatizable androgen suppresses Mcp-1 expression in adipocytes. • Mcp-1 transcription was negatively regulated by DHT-AR action. • DHT-AR selectively regulates Mcp-1 transcription through distinct NF-κB sites.

miR-497 suppresses epithelial–mesenchymal transition and metastasis in colorectal cancer cells by targeting fos-related antigen-1

Directory of Open Access Journals (Sweden)

Zhang N

2016-10-01

Full Text Available Nan Zhang,1 Quan Shen,2 Pingping Zhang3 1Department of General Surgery, First Affiliated Hospital of Henan University of Chinese Medicine, 2Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, Zhengzhou, 3Department of Integrated Chinese and Western Medicine, Tianjin First Central Hospital, Tianjin, People’s Republic of China Objective: MicroRNAs have key roles in tumor metastasis. The acquisition of metastatic capability by cancer cells is associated with epithelial–mesenchymal transition (EMT. Here, we describe the role and molecular mechanism of miR-497 in colorectal cancer (CRC cell EMT, migration, and invasion.Methods: Quantitative real-time polymerase chain reaction and Western blot assays were performed to detect the expression levels of miR-497 and Fos-related antigen-1 (Fra-1 in the CRC cells. HCT116 and SW480 cells with miR-497 overexpression or Fra-1 low expression were constructed by lipofection. Target prediction and luciferase reporter assays were performed to investigate whether Fra-1 is one of the targets of miR-497. Western blot and Transwell assays were performed to detect the effects of miR-497 and Fra-1 on CRC cell EMT, migration and invasion.Results: We searched the miRanda, TargetScan, and PicTar databases and found that Fra-1, a key driver of CRC metastasis, is a potential target of miR-497. Quantitative real-time polymerase chain reaction and Western blot analysis verified downregulation of miR-497 and upregulation of Fra-1 in CRC cells. Western blot and Transwell assays showed that overexpression of miR-497 suppresses CRC cell EMT, migration, and invasion. Luciferase gene reporter assay revealed that Fra-1 is a downstream target of miR-497 as miR-497 bound directly to the 3' untranslated region of Fra-1 messenger RNA. An inverse correlation was also found between miR-497 and Fra-1 in HCT116 and SW480 cells. Furthermore, knockdown of Fra-1 recuperated the effects of miR-497 overexpression

Suppression of in vitro cell-mediated lympholysis generation by alloactivated lymphocytes. Examination of radioresistant suppressive activity

International Nuclear Information System (INIS)

Orosz, C.G.; Ferguson, R.M.

1986-01-01

We investigated the radioresistant (1000 rads) suppression of CML generation mediated by alloactivated murine splenocytes. Suppressive cells were generated in MLCs by stimulation of (A X 6R)F1 splenocytes with irradiated C57BL/10 splenocytes. Suppressive cells could lyse targets bearing H-2b alloantigens, but would not lyse parental B10.T(6R) or B10.A targets. Suppressive activity was detected by including the alloactivated (A X 6R)F1 cells in B10.T(6R) anti-B10.A(1R) MLCs. Relative to the suppressive (A X 6R)F1 cells, the B10.A(1R) lymphocytes display both parental and suppressor-inducing alloantigens. In the absence of a suppressive population, B10.A(1R) stimulators cause B10.T(6R) splenocytes to generate cytolytic activity specific for both H-2Db (suppressor-inducing) and H-2Kk (suppressor-borne) target determinants. The irradiated, alloactivated (A X 6R)F1 cells decrease the H-2Db-specific CML generated in this system, thus mediating apparent antigen-specific suppression. However, cytolytic activity concomitantly generated in the same culture against the unrelated H-2Kk target determinants is similarly reduced by the (A X 6R)F1 cells. Thus, radioresistant suppression by alloactivated splenocytes is not necessarily antigen-specific. The irradiated (A X 6R)F1 cells would not suppress the generation of H-2Kk-specific CTL in B10.T(6R) anti-B10.A MLCs. Hence, the irradiated (A X 6R)F1 cells can impede CML generation against third-party alloantigens if, and only if, those alloantigens are coexpressed with suppressor-inducing alloantigens on the stimulator cells in suppressed MLCs. Similar results were also obtained using a different histoincompatible lymphocyte combination

Role of Active Listening and Listening Effort on Contralateral Suppression of Transient Evoked Otoacousic Emissions.

Science.gov (United States)

Kalaiah, Mohan Kumar; Theruvan, Nikhitha B; Kumar, Kaushlendra; Bhat, Jayashree S

2017-04-01

The present study aimed to investigate the effect of active listening and listening effort on the contralateral suppression of transient evoked otoacoustic emissions (CSTEOAEs). Twenty eight young adults participated in the study. Transient evoked otoacoustic emissions (TEOAEs) were recorded using 'linear' clicks at 60 dB peSPL, in three contralateral noise conditions. In condition 1, TEOAEs were obtained in the presence of white noise in the contralateral ear. While, in condition 2, speech was embedded into white noise at +3, -3, and -9 dB signal-to-noise ratio (SNR) and delivered to the contralateral ear. The SNR was varied to investigate the effect of listening effort on the CSTEOAE. In condition 3, speech was played backwards and embedded into white noise at -3 dB SNR. The conditions 1 and 3 served as passive listening condition and the condition 2 served as active listening condition. In active listening condition, the participants categorized the words in to two groups (e.g., animal and vehicle). CSTEOAE was found to be largest in the presence of white noise, and the amount of CSTEOAE was not significantly different between active and passive listening conditions (condition 2 and 3). Listening effort had an effect on the CSTEOAE, the amount of suppression increased with listening effort, when SNR was decreased from +3 dB to -3 dB. However, when the SNR was further reduced to -9 dB, there was no further increase in the amount of CSTEOAE, instead there was a reduction in the amount of suppression. The findings of the present study show that listening effort might affect CSTEOAE.

How to inhibit a distractor location? Statistical learning versus active, top-down suppression.

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Wang, Benchi; Theeuwes, Jan

2018-05-01

Recently, Wang and Theeuwes (Journal of Experimental Psychology: Human Perception and Performance, 44(1), 13-17, 2018a) demonstrated the role of lingering selection biases in an additional singleton search task in which the distractor singleton appeared much more often in one location than in all other locations. For this location, there was less capture and selection efficiency was reduced. It was argued that statistical learning induces plasticity within the spatial priority map such that particular locations that are high likely to contain a distractor are suppressed relative to all other locations. The current study replicated these findings regarding statistical learning (Experiment 1) and investigated whether similar effects can be obtained by cueing the distractor location in a top-down way on a trial-by-trial basis. The results show that top-down cueing of the distractor location with long (1,500 ms; Experiment 2) and short stimulus-onset symmetries (SOAs) (600 ms; Experiment 3) does not result in suppression: The amount of capture nor the efficiency of selection was affected by the cue. If anything, we found an attentional benefit (instead of the suppression) for the short SOA. We argue that through statistical learning, weights within the attentional priority map are changed such that one location containing a salient distractor is suppressed relative to all other locations. Our cueing experiments show that this effect cannot be accomplished by active, top-down suppression. Consequences for recent theories of distractor suppression are discussed.

Distracted by the Unthought - Suppression and Reappraisal of Mind Wandering under Stereotype Threat.

Science.gov (United States)

Schuster, Carolin; Martiny, Sarah E; Schmader, Toni

2015-01-01

Previous research has found that subtle reminders of negative stereotypes about one's group can lead individuals to underperform on stereotype-relevant tests (e.g., women in math, ethnic minorities on intelligence tests). This so called stereotype threat effect can contribute to systematic group differences in performance that can obscure the true abilities of certain social groups and thereby sustain social inequalities. In the present study, we examined processes underlying stereotype threat effects on women's math performance, specifically focusing on the role of suppression of mind wandering (i.e., task-irrelevant thinking) in stereotype threat (ST) and no threat (NT) situations. Based on a process model of stereotype threat effects on performance, we hypothesized that women under stereotype threat spontaneously suppress mind wandering, and that this suppression impairs performance. An alternative regulation strategy that prevents suppression (i.e., reappraising task-irrelevant thoughts as normal) was predicted to prevent stereotype threat effects on performance. We manipulated stereotype threat (ST vs. NT) and cognitive regulation strategy (suppression, reappraisal, or no strategy) and measured women's performance on a math and a concentration task (N = 113). We expected three groups to perform relatively more poorly: Those in ST with either no strategy or suppression and those in NT with a suppression strategy. We tested the performance of these groups against the remaining three groups hypothesized to perform relatively better: those in NT with no strategy or reappraisal and those in ST with reappraisal. The results showed the expected pattern for participants' math performance, but not for concentration achievement. This pattern suggests that ineffective self-regulation by suppressing mind wandering can at least partly explain stereotype threat effects on performance, whereas a reappraisal strategy can prevent this impairment. We discuss implications for

Human Gut-Derived Commensal Bacteria Suppress CNS Inflammatory and Demyelinating Disease.

Science.gov (United States)

Mangalam, Ashutosh; Shahi, Shailesh K; Luckey, David; Karau, Melissa; Marietta, Eric; Luo, Ningling; Choung, Rok Seon; Ju, Josephine; Sompallae, Ramakrishna; Gibson-Corley, Katherine; Patel, Robin; Rodriguez, Moses; David, Chella; Taneja, Veena; Murray, Joseph

2017-08-08

The human gut is colonized by a large number of microorganisms (∼10 13 bacteria) that support various physiologic functions. A perturbation in the healthy gut microbiome might lead to the development of inflammatory diseases, such as multiple sclerosis (MS). Therefore, gut commensals might provide promising therapeutic options for treating MS and other diseases. We report the identification of human gut-derived commensal bacteria, Prevotella histicola, which can suppress experimental autoimmune encephalomyelitis (EAE) in a human leukocyte antigen (HLA) class II transgenic mouse model. P. histicola suppresses disease through the modulation of systemic immune responses. P. histicola challenge led to a decrease in pro-inflammatory Th1 and Th17 cells and an increase in the frequencies of CD4 + FoxP3 + regulatory T cells, tolerogenic dendritic cells, and suppressive macrophages. Our study provides evidence that the administration of gut commensals may regulate a systemic immune response and may, therefore, have a possible role in treatment strategies for MS. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The rhizosphere microbial community in a multiple parallel mineralization system suppresses the pathogenic fungus Fusarium oxysporum.

Science.gov (United States)

Fujiwara, Kazuki; Iida, Yuichiro; Iwai, Takashi; Aoyama, Chihiro; Inukai, Ryuya; Ando, Akinori; Ogawa, Jun; Ohnishi, Jun; Terami, Fumihiro; Takano, Masao; Shinohara, Makoto

2013-12-01

The rhizosphere microbial community in a hydroponics system with multiple parallel mineralization (MPM) can potentially suppress root-borne diseases. This study focused on revealing the biological nature of the suppression against Fusarium wilt disease, which is caused by the fungus Fusarium oxysporum, and describing the factors that may influence the fungal pathogen in the MPM system. We demonstrated that the rhizosphere microbiota that developed in the MPM system could suppress Fusarium wilt disease under in vitro and greenhouse conditions. The microbiological characteristics of the MPM system were able to control the population dynamics of F. oxysporum, but did not eradicate the fungal pathogen. The roles of the microbiological agents underlying the disease suppression and the magnitude of the disease suppression in the MPM system appear to depend on the microbial density. F. oxysporum that survived in the MPM system formed chlamydospores when exposed to the rhizosphere microbiota. These results suggest that the microbiota suppresses proliferation of F. oxysporum by controlling the pathogen's morphogenesis and by developing an ecosystem that permits coexistence with F. oxysporum. © 2013 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Background intercomparison with escape-suppressed germanium detectors in underground mines

Energy Technology Data Exchange (ETDEWEB)

Szuecs, Tamas; Bemmerer, Daniel [Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden (Germany)

2014-07-01

A key requirement for underground nuclear astrophysics experiments is the very low background level in germanium detectors underground. The reference for these purposes is the world's so far only underground accelerator laboratory for nuclear astrophysics, LUNA. LUNA is located deep underground in the Gran Sasso laboratory in Italy, shielded from cosmic rays by 1400 m of rock. The background at LUNA was studied in detail using an escape-suppressed Clover-type HPGe detector. Exactly the same detector was subsequently transported to the Felsenkeller underground laboratory in Dresden, shielded by 45 m of rock, and the background was shown to be only a factor of three higher than at LUNA when comparing the escape-suppressed spectra, with interesting consequences for underground nuclear astrophysics. As the next step of a systematic study of the effects of a combination of active and passive shielding on the cosmic ray induced background, this detector is now being brought to the ''Reiche Zeche'' mine in Freiberg/Sachsen, shielded by 150 m of rock. The data from the Freiberg measurement are shown and discussed.

Bearings with a key role in nuclear reactor safety

International Nuclear Information System (INIS)

Jackson, J.

1981-01-01

The most critical period during the operation of heavy-duty pumps occurs at run-up, when sudden high loads coincide with below normal oil pressure. When those pumps are a key component of a nuclear reactor safety-system, reliability takes on a special meaning. Electricite de France recently invited a British company, Michell Bearings, to find a solution to these 'black-start' problems, the details of which are described in the following article

Role of suppression of the inward rectifier current in terminal action potential repolarization in the failing heart.

Science.gov (United States)

Klein, Michael G; Shou, Matie; Stohlman, Jayna; Solhjoo, Soroosh; Haigney, Myles; Tidwell, Richard R; Goldstein, Robert E; Flagg, Thomas P; Haigney, Mark C

2017-08-01

The failing heart exhibits an increased arrhythmia susceptibility that is often attributed to action potential (AP) prolongation due to significant ion channel remodeling. The inwardly rectifying K + current (I K1 ) has been reported to be reduced, but its contribution to shaping the AP waveform and cell excitability in the failing heart remains unclear. The purpose of this study was to define the effect of I K1 suppression on the cardiac AP and excitability in the normal and failing hearts. We used electrophysiological and pharmacological approaches to investigate I K1 function in a swine tachy-pacing model of heart failure (HF). Terminal repolarization of the AP (TRAP; the time constant of the exponential fit to terminal repolarization) was markedly prolonged in both myocytes and arterially perfused wedges from animals with HF. TRAP was increased by 54.1% in HF myocytes (P < .001) and 26.2% in HF wedges (P = .014). The increase in TRAP was recapitulated by the potent and specific I K1 inhibitor, PA-6 (pentamidine analog 6), indicating that I K1 is the primary determinant of the final phase of repolarization. Moreover, we find that I K1 suppression reduced the ratio of effective refractory period to AP duration at 90% of repolarization, permitting re-excitation before full repolarization, reduction of AP upstroke velocity, and likely promotion of slow conduction. Using an objective measure of terminal repolarization, we conclude that I K1 is the major determinant of the terminal repolarization time course. Moreover, suppression of I K1 prolongs repolarization and reduces postrepolarization refractoriness without marked effects on the overall AP duration. Collectively, these findings demonstrate how I K1 suppression may contribute to arrhythmogenesis in the failing heart. Published by Elsevier Inc.

RNAi suppression of Arogenate Dehydratase1 reveals that phenylalanine is synthesized predominantly via the arogenate pathway in petunia petals.

Science.gov (United States)

Maeda, Hiroshi; Shasany, Ajit K; Schnepp, Jennifer; Orlova, Irina; Taguchi, Goro; Cooper, Bruce R; Rhodes, David; Pichersky, Eran; Dudareva, Natalia

2010-03-01

l-Phe, a protein building block and precursor of numerous phenolic compounds, is synthesized from prephenate via an arogenate and/or phenylpyruvate route in which arogenate dehydratase (ADT) or prephenate dehydratase, respectively, plays a key role. Here, we used Petunia hybrida flowers, which are rich in Phe-derived volatiles, to determine the biosynthetic routes involved in Phe formation in planta. Of the three identified petunia ADTs, expression of ADT1 was the highest in petunia petals and positively correlated with endogenous Phe levels throughout flower development. ADT1 showed strict substrate specificity toward arogenate, although with the lowest catalytic efficiency among the three ADTs. ADT1 suppression via RNA interference in petunia petals significantly reduced ADT activity, levels of Phe, and downstream phenylpropanoid/benzenoid volatiles. Unexpectedly, arogenate levels were unaltered, while shikimate and Trp levels were decreased in transgenic petals. Stable isotope labeling experiments showed that ADT1 suppression led to downregulation of carbon flux toward shikimic acid. However, an exogenous supply of shikimate bypassed this negative regulation and resulted in elevated arogenate accumulation. Feeding with shikimate also led to prephenate and phenylpyruvate accumulation and a partial recovery of the reduced Phe level in transgenic petals, suggesting that the phenylpyruvate route can also operate in planta. These results provide genetic evidence that Phe is synthesized predominantly via arogenate in petunia petals and uncover a novel posttranscriptional regulation of the shikimate pathway.

Obesity-induced endoplasmic reticulum stress suppresses nuclear factor-Y expression.

Science.gov (United States)

Liu, Yulan; Zhang, Yuwei; Zhang, Yanjie; Zhang, Jinlong; Liu, Yin; Feng, Peiqun; Su, Zhiguang

2017-02-01

Nuclear transcription factor Y (NF-Y) is an evolutionarily conserved transcription factor composed of three subunits, NF-YA, NF-YB, and NF-YC. NF-Y plays crucial roles in pre-adipocyte maintenance and/or commitment to adipogenesis. NF-YA dysfunction in adipocyte resulted in an age-dependent progressive loss of adipose tissue associated with metabolic complications. Endoplasmic reticulum (ER) stress has emerged as an important mediator in the pathogenesis of obesity. However, it is not known if NF-YA is involved in the ER stress-mediated pathogenesis of obesity. We first examined the effects of ER stress on the NF-YA expression in cultured 3T3-L1 adipocytes; then in ob/ob genetic obesity mice, we tested the effect of chemical chaperones alleviating ER stress on the expression levels of NF-YA. Subsequently, we inhibited the new mRNA synthesis using actinomycin D in 3T3-L1 cells to explore the mechanism modulating NF-YA expression. Finally, we evaluated the involvement of PPARg in the regulation of NF-YA expression by ER stress. We demonstrated that both obesity- and chemical chaperone -induced ER stress suppressed NF-YA expression and alleviation of ER stress by chemical chaperone could recover NF-YA expression in ob/ob mice. Moreover, we showed that ER stress suppressed NF-YA mRNA transcription through the involvement of peroxisome proliferator-activated receptor gamma (PPARg). Activation of PPARg ameliorates the ER stress-induced NF-YA suppression. Our findings may point to a possible role of NF-YA in stress conditions that occur in chronic obesity, ER stress might be involved in the pathogenesis of obesity through NF-YA depletion.

Usefulness of fat suppression MR imagings for head and neck cancers

International Nuclear Information System (INIS)

Kitagawa, Yoshimasa; Ishii, Yasuo; Morihiro, Hironori; Ogasawara, Toshiyuki

1996-01-01

Large amounts of fat and complex anatomy make the head and neck region one of the more challenging areas for MR imagings. The high signal intensity of fat on T1 weighted images (T1W1) has limited the utility of Gd-DTPA in imaging of head and neck lesions. The contrast enhanced lesions may have T1W1 signal intensity similar to fat, which results in diagnostic difficulty. A fat suppression technique used in conjunction with Gd-DTPA ensures that enhancing lesions will not be obscured by high signal from the surrounding fat or by chemical shift artifact. We evaluated the role or chemical shift imagings for fat suppression in the depiction of 15 patients with head and neck cancers. Gd-DTPA-enhanced fat suppression T1W1 were compared with conventional pre and postcontrast T1- and T2W1 using a four-point grading system (Grade 0-3) in detecting and defining the extent of primary lesions and lymphnodes. Gd-DTPA-enhanced fat suppression T1W1 (average score 2.93) which had a score of 3 in 14 patients, were superior to conventional T1W1 (0.73), postcontrast T1W1 (1.80) and T2W1 (1.67). Gd-DTPA enhanced fat suppression T1W1 were particularly beneficial in the detection of central necrosis or extracapsular invasion of neck lymphnodes as well as in defining the extent of tumor invasion to fat-containing areas such as bone marrow or cheek. Our data suggested that fat suppression technique was extremely useful to delineate the primary tumors and regional lymphnodes without increasing scan time or image postprocessing. (author)

Inflammasome Inhibition Suppresses Alveolar Cell Permeability Through Retention of Neuregulin-1 (NRG-1

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Rajanbabu Venugopal

2015-07-01

Full Text Available Background: Neuregulin (NRG-1-human epidermal receptor (HER-2 signaling pathway is a key regulator of IL-1β-mediated pulmonary inflammation and epithelial permeability. The inflammasome is a newly discovered molecular platform required for caspase-1 activation and maturation of IL-1β. However, the role of the inflammasome in NRG-1-HER2 signaling-mediated alveolar cell permeability is unknown. Methods: The inflammasome was activated or inhibited in THP-1 cells; supernatants from these cells were added to A549 cells and human small airway epithelial cells (HSAEC. The protein expression of NRG-1 and phospho-HER2 (pHER2 were measured by Western blot analysis and epithelial permeability was measured using Lucifer yellow dye. Results: Results reveal that alveolar permeability in A549 cells and HSAEC is increased when treated with supernatants of inflammasome-activated THP-1 cells. Alveolar permeability is significantly suppressed when treated with supernatant of inflammasome-inhibited THP-1 cells. Inflammasome-mediated permeability is decreased when A549 cells and HSAEC are pretreated with IL-1β receptor antagonist (IL-1βRA. In addition, HER2 kinase inhibitor AG825 or NRG-1 inhibitor TAPI inhibits inflammasome-mediated permeability in A549 cells and HSAEC demonstrating critical roles of IL-1β, NRG-1, and HER2 in inflammasome-mediated alveolar permeability. Conclusion: These findings suggest that inflammasome-induced alveolar cell permeability is mediated by NRG-1/HER2 signaling through IL-1β regulation.

Binocular Therapy for Childhood Amblyopia Improves Vision Without Breaking Interocular Suppression.

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Bossi, Manuela; Tailor, Vijay K; Anderson, Elaine J; Bex, Peter J; Greenwood, John A; Dahlmann-Noor, Annegret; Dakin, Steven C

2017-06-01

Amblyopia is a common developmental visual impairment characterized by a substantial difference in acuity between the two eyes. Current monocular treatments, which promote use of the affected eye by occluding or blurring the fellow eye, improve acuity, but are hindered by poor compliance. Recently developed binocular treatments can produce rapid gains in visual function, thought to be as a result of reduced interocular suppression. We set out to develop an effective home-based binocular treatment system for amblyopia that would engage high levels of compliance but that would also allow us to assess the role of suppression in children's response to binocular treatment. Balanced binocular viewing therapy (BBV) involves daily viewing of dichoptic movies (with "visibility" matched across the two eyes) and gameplay (to monitor compliance and suppression). Twenty-two children (3-11 years) with anisometropic (n = 7; group 1) and strabismic or combined mechanism amblyopia (group 2; n = 6 and 9, respectively) completed the study. Groups 1 and 2 were treated for a maximum of 8 or 24 weeks, respectively. The treatment elicited high levels of compliance (on average, 89.4% ± 24.2% of daily dose in 68.23% ± 12.2% of days on treatment) and led to a mean improvement in acuity of 0.27 logMAR (SD 0.22) for the amblyopic eye. Importantly, acuity gains were not correlated with a reduction in suppression. BBV is a binocular treatment for amblyopia that can be self-administered at home (with remote monitoring), producing rapid and substantial benefits that cannot be solely mediated by a reduction in interocular suppression.

Pressure suppression pool mixing in passive advanced BWR plants

International Nuclear Information System (INIS)

Gamble, Robert E.; Nguyen, Thuy T.; Shiralkar, Bharat S.; Peterson, Per F.; Greif, Ralph; Tabata, H.

2001-01-01

In the SBWR passive boiling water reactor, the long-term post-accident containment pressure is determined by the combination of noncondensible gas pressure and steam pressure in the wetwell gas space. The suppression pool (SP) surface temperature, which determines the vapor partial pressure, is very important to overall containment performance. Therefore, the thermal stratification of the SP due to blowdown is of primary importance. This work looks at the various phases and phenomena present during the blowdown event and identifies those that are important to thermal stratification, and the scaling necessary to model them in reduced size tests. This is important in determining which of the large body of blowdown to SP data is adequate for application to the stratification problem. The mixing by jets from the main vents is identified as the key phenomena influencing the thermal response of the suppression pool and analytical models are developed to predict the jet influence on thermal stratification. The analytical models are implemented into a system simulation code, TRACG, and used to model thermal stratification behavior in a scaled test facility. The results show good general agreement with the test data

Attentional selection and suppression in children and adults.

Science.gov (United States)

Sun, Meirong; Wang, Encong; Huang, Jing; Zhao, Chenguang; Guo, Jialiang; Li, Dongwei; Sun, Li; Du, Boqi; Ding, Yulong; Song, Yan

2018-05-15

The fundamental role of covert spatial attention is to enhance the processing of attended items while simultaneously ignoring irrelevant items. However, relatively little is known about how brain electrophysiological activities associated with target selection and distractor suppression are involved as they develop and become fully functional. The current study aimed to identify the neurophysiological bases of the development of covert spatial attention, focusing on electroencephalographic (EEG) markers of attentional selection (N2pc) and suppression (P D ). EEG data were collected from healthy young adults and typically developing children (9-15 years old) as they searched for a shape singleton target in either the absence or the presence of a salient-but-irrelevant color singleton distractor. The ERP results showed that a lateral shape target elicited a smaller N2pc in children compared with adults regardless of whether a distractor was present or not. Moreover, the target-elicited N2pc was always followed by a similar positivity in both age groups. Counterintuitively, a lateral salient-but-irrelevant distractor elicited a large P D in children with low behavioral accuracy, whereas high-accuracy children exhibited a small and "adult-like" P D . More importantly, we found no evidence for a correlation between the target-elicited N2pc and the distractor-elicited P D in either age group. Our results provide neurophysiological evidence for the developmental differences between target selection and distractor suppression. Compared with adults, 9-15-year-old children deploy insufficient attentional selection resources to targets but use "adult-like" or even more attentional suppression resources to resist irrelevant distractors. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=NhWapx0d75I. © 2018 John Wiley & Sons Ltd.

Quantifying the influence of previously burned areas on suppression effectiveness and avoided exposure: A case study of the Las Conchas Fire

Science.gov (United States)

Matthew P. Thompson; Patrick Freeborn; Jon D. Rieck; Dave Calkin; Julie W. Gilbertson-Day; Mark A. Cochrane; Michael S. Hand

2016-01-01

We present a case study of the Las Conchas Fire (2011) to explore the role of previously burned areas (wildfires and prescribed fires) on suppression effectiveness and avoided exposure. Methodological innovations include characterisation of the joint dynamics of fire growth and suppression activities, development of a fire line effectiveness framework, and...

MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma.

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Lu-Kai Wang

Full Text Available Non-small cell lung cancers (NSCLCs cause high mortality worldwide, and the cancer progression can be activated by several genetic events causing receptor dysregulation, including mutation or amplification. MicroRNAs are a group of small non-coding RNA molecules that function in gene silencing and have emerged as the fine-tuning regulators during cancer progression. MiR-133a is known as a key regulator in skeletal and cardiac myogenesis, and it acts as a tumor suppressor in various cancers. This study demonstrates that miR-133a expression negatively correlates with cell invasiveness in both transformed normal bronchial epithelial cells and lung cancer cell lines. The oncogenic receptors in lung cancer cells, including insulin-like growth factor 1 receptor (IGF-1R, TGF-beta receptor type-1 (TGFBR1, and epidermal growth factor receptor (EGFR, are direct targets of miR-133a. MiR-133a can inhibit cell invasiveness and cell growth through suppressing the expressions of IGF-1R, TGFBR1 and EGFR, which then influences the downstream signaling in lung cancer cell lines. The cell invasive ability is suppressed in IGF-1R- and TGFBR1-repressed cells and this phenomenon is mediated through AKT signaling in highly invasive cell lines. In addition, by using the in vivo animal model, we find that ectopically-expressing miR-133a dramatically suppresses the metastatic ability of lung cancer cells. Accordingly, patients with NSCLCs who have higher expression levels of miR-133a have longer survival rates compared with those who have lower miR-133a expression levels. In summary, we identified the tumor suppressor role of miR-133a in lung cancer outcome prognosis, and we demonstrated that it targets several membrane receptors, which generally produce an activating signaling network during the progression of lung cancer.

Multirate flutter suppression system design for the Benchmark Active Controls Technology Wing

Science.gov (United States)

Berg, Martin C.; Mason, Gregory S.

1994-01-01

To study the effectiveness of various control system design methodologies, the NASA Langley Research Center initiated the Benchmark Active Controls Project. In this project, the various methodologies will be applied to design a flutter suppression system for the Benchmark Active Controls Technology (BACT) Wing (also called the PAPA wing). Eventually, the designs will be implemented in hardware and tested on the BACT wing in a wind tunnel. This report describes a project at the University of Washington to design a multirate flutter suppression system for the BACT wing. The objective of the project was two fold. First, to develop a methodology for designing robust multirate compensators, and second, to demonstrate the methodology by applying it to the design of a multirate flutter suppression system for the BACT wing. The contributions of this project are (1) development of an algorithm for synthesizing robust low order multirate control laws (the algorithm is capable of synthesizing a single compensator which stabilizes both the nominal plant and multiple plant perturbations; (2) development of a multirate design methodology, and supporting software, for modeling, analyzing and synthesizing multirate compensators; and (3) design of a multirate flutter suppression system for NASA's BACT wing which satisfies the specified design criteria. This report describes each of these contributions in detail. Section 2.0 discusses our design methodology. Section 3.0 details the results of our multirate flutter suppression system design for the BACT wing. Finally, Section 4.0 presents our conclusions and suggestions for future research. The body of the report focuses primarily on the results. The associated theoretical background appears in the three technical papers that are included as Attachments 1-3. Attachment 4 is a user's manual for the software that is key to our design methodology.

[Elucidation of key genes in sex determination in genetics teaching].

Science.gov (United States)

Li, Meng; He, Zhumei

2014-06-01

Sex is an important and complex feature of organisms, which is controlled by the genetic and environmental factors. The genetic factors, i.e., genes, are vital in sex determination. However, not all the related genes play the same roles, and some key genes play a vital role in the sex determination and differentiation. With the development of the modern genetics, a great progress on the key genes has been made in sex determination. In this review, we summarize the mechanism of sex determination and the strategy of how to study the key genes in sex determination. It will help us to understand the mechanism of sex determination better in the teaching of genetics.

Water dynamics clue to key residues in protein folding

International Nuclear Information System (INIS)

Gao, Meng; Zhu, Huaiqiu; Yao, Xin-Qiu; She, Zhen-Su

2010-01-01

A computational method independent of experimental protein structure information is proposed to recognize key residues in protein folding, from the study of hydration water dynamics. Based on all-atom molecular dynamics simulation, two key residues are recognized with distinct water dynamical behavior in a folding process of the Trp-cage protein. The identified key residues are shown to play an essential role in both 3D structure and hydrophobic-induced collapse. With observations on hydration water dynamics around key residues, a dynamical pathway of folding can be interpreted.

Memory suppression trades prolonged fear and sleep-dependent fear plasticity for the avoidance of current fear

Science.gov (United States)

Kuriyama, Kenichi; Honma, Motoyasu; Yoshiike, Takuya; Kim, Yoshiharu

2013-07-01

Sleep deprivation immediately following an aversive event reduces fear by preventing memory consolidation during homeostatic sleep. This suggests that acute insomnia might act prophylactically against the development of posttraumatic stress disorder (PTSD) even though it is also a possible risk factor for PTSD. We examined total sleep deprivation and memory suppression to evaluate the effects of these interventions on subsequent aversive memory formation and fear conditioning. Active suppression of aversive memory impaired retention of event memory. However, although the remembered fear was more reduced in sleep-deprived than sleep-control subjects, suppressed fear increased, and seemed to abandon the sleep-dependent plasticity of fear. Active memory suppression, which provides a psychological model for Freud's ego defense mechanism, enhances fear and casts doubt on the potential of acute insomnia as a prophylactic measure against PTSD. Our findings bring into question the role of sleep in aversive-memory consolidation in clinical PTSD pathophysiology.

TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation

International Nuclear Information System (INIS)

Shibata, Mio; Sato, Tomonobu; Nukiwa, Ryota; Ariga, Tadashi; Hatakeyama, Shigetsugu

2012-01-01

Highlights: ► NF-κB plays an important role in cell survival and carcinogenesis. ► TRIM45 negatively regulates TNFα-induced NF-κB-mediated transcription. ► TRIM45 overexpression suppresses cell growth. ► TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth. -- Abstract: The NF-κB signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-κB is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-κB signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin–proteasome system. It has been reported that overexpression of TRIM45, one of the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNFα-induced NF-κB-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-κB signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth.

Live Candida albicans Suppresses Production of Reactive Oxygen Species in Phagocytes▿ †

Science.gov (United States)

Wellington, Melanie; Dolan, Kristy; Krysan, Damian J.

2009-01-01

Production of reactive oxygen species (ROS) is an important aspect of phagocyte-mediated host responses. Since phagocytes play a crucial role in the host response to Candida albicans, we examined the ability of Candida to modulate phagocyte ROS production. ROS production was measured in the murine macrophage cell line J774 and in primary phagocytes using luminol-enhanced chemiluminescence. J774 cells, murine polymorphonuclear leukocytes (PMN), human monocytes, and human PMN treated with live C. albicans produced significantly less ROS than phagocytes treated with heat-killed C. albicans. Live C. albicans also suppressed ROS production in murine bone marrow-derived macrophages from C57BL/6 mice, but not from BALB/c mice. Live C. albicans also suppressed ROS in response to external stimuli. C. albicans and Candida glabrata suppressed ROS production by phagocytes, whereas Saccharomyces cerevisiae stimulated ROS production. The cell wall is the initial point of contact between Candida and phagocytes, but isolated cell walls from both heat-killed and live C. albicans stimulated ROS production. Heat-killed C. albicans has increased surface exposure of 1,3-β-glucan, a cell wall component that can stimulate phagocytes. To determine whether surface 1,3-β-glucan exposure accounted for the difference in ROS production, live C. albicans cells were treated with a sublethal dose of caspofungin to increase surface 1,3-β-glucan exposure. Caspofungin-treated C. albicans was fully able to suppress ROS production, indicating that suppression of ROS overrides stimulatory signals from 1,3-β-glucan. These studies indicate that live C. albicans actively suppresses ROS production in phagocytes in vitro, which may represent an important immune evasion mechanism. PMID:18981256

Pressure suppression device

International Nuclear Information System (INIS)

Mizumachi, Wataru; Fukuda, Akira; Kitaguchi, Hidemi; Shimizu, Toshiaki.

1976-01-01

Object: To relieve and absorb impact wave vibrations caused by steam and non-condensed gases releasing into the pressure suppression chamber at the time of an accident. Structure: The reactor container is filled with inert gases. A safety valve attached main steam pipe is provided to permit the excessive steam to escape, the valve being communicated with the pressure suppression chamber through an exhaust pipe. In the pressure suppression chamber, a doughnut-like cylindrical outer wall is filled at its bottom with pool water to condense the high temperature vapor released through the exhaust pipe. A head portion of a vent tube which leads the exhaust pipe is positioned at the top, and a down comer and an exhaust vent tube are locked by means of steady rests. At the bottom is mounted a pressure adsorber device which adsorbs a pressure from the pool water. (Kamimura, M.)

Anodal transcranial direct current stimulation reduces psychophysically measured surround suppression in the human visual cortex.

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Daniel P Spiegel

Full Text Available Transcranial direct current stimulation (tDCS is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN, was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex.

Anger suppression, interdependent self-construal, and depression among Asian American and European American college students.

Science.gov (United States)

Cheung, Rebecca Y M; Park, Irene J K

2010-10-01

The present study tested a theoretical model of emotion regulation (Yap, Sheeber, & Allen, 2007) in a sample of Asian American and European American college students (N = 365). Specifically, the mediating role of anger suppression in the effect of temperament and family processes on depressive symptoms was tested across race and levels of interdependent self-construal (a culturally based self orientation emphasizing connectedness with others). Next, the moderation of the suppression-depression relation was tested by race and interdependent self-construal. Results indicated that the hypothesized model fit well across Asian American and European American students, as well as those with high versus low levels of interdependent self-construal. Anger suppression was a significant mediator of the hypothesized indirect effects on depressive symptoms. Moreover, race and interdependent self-construal moderated the suppression-depression link, such that Asian American status and a stronger interdependent self-construal attenuated the relation between anger suppression and depressive symptoms. Understanding both universal and culture-specific aspects of emotion regulation in the development of depressive symptoms will be essential for sound theory, future research, and effective prevention and intervention efforts across diverse populations. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Association Between Energy Balance and Metabolic Hormone Suppression During Ultraendurance Exercise.

Science.gov (United States)

Geesmann, Bjoern; Gibbs, Jenna C; Mester, Joachim; Koehler, Karsten

2017-08-01

Ultraendurance athletes often accumulate an energy deficit when engaging in ultraendurance exercise, and on completion of the exercise, they exhibit endocrine changes that are reminiscent of starvation. However, it remains unclear whether these endocrine changes are a result of the exercise per se or secondary to the energy deficit and, more important, whether these changes can be attenuated by increased dietary intake. The goal of the study was to assess the relationship between changes in key metabolic hormones after ultraendurance exercise and measures of energy balance. Metabolic hormones, as well as energy intake and expenditure, were assessed in 14 well-trained male cyclists who completed a 1230-km ultraendurance cycling event. After completion of the event, serum testosterone (-67% ± 18%), insulin-like growth factor-1 (IGF-1) (-45% ± 8%), and leptin (-79% ± 9%) were significantly suppressed (P deficit to a 3593-kcal surplus. The marked suppression of testosterone, IGF-1, and leptin after ultraendurance exercise is comparable to changes occurring during acute starvation. The suppression of IGF-1, but not that of other metabolic hormones, was strongly associated with the magnitude of the energy deficit, indicating that athletes who attained a greater energy deficit exhibited a more pronounced drop in IGF-1. Future studies are needed to determine whether increased dietary intake can attenuate the endocrine response to ultraendurance exercise.

Effect of land use and soil organic matter quality on the structure and function of microbial communities in pastoral soils: Implications for disease suppression.

Science.gov (United States)

Dignam, Bryony E A; O'Callaghan, Maureen; Condron, Leo M; Kowalchuk, George A; Van Nostrand, Joy D; Zhou, Jizhong; Wakelin, Steven A

2018-01-01

Cropping soils vary in extent of natural suppression of soil-borne plant diseases. However, it is unknown whether similar variation occurs across pastoral agricultural systems. We examined soil microbial community properties known to be associated with disease suppression across 50 pastoral fields varying in management intensity. The composition and abundance of the disease-suppressive community were assessed from both taxonomic and functional perspectives. Pseudomonas bacteria were selected as a general taxonomic indicator of disease suppressive potential, while genes associated with the biosynthesis of a suite of secondary metabolites provided functional markers (GeoChip 5.0 microarray analysis). The composition of both the Pseudomonas communities and disease suppressive functional genes were responsive to land use. Underlying soil properties explained 37% of the variation in Pseudomonas community structure and up to 61% of the variation in the abundance of disease suppressive functional genes. Notably, measures of soil organic matter quality, C:P ratio, and aromaticity of the dissolved organic matter content (carbon recalcitrance), influenced both the taxonomic and functional disease suppressive potential of the pasture soils. Our results suggest that key components of the soil microbial community may be managed on-farm to enhance disease suppression and plant productivity.

Suppression and revival of oscillation in indirectly coupled limit cycle oscillators

International Nuclear Information System (INIS)

Sharma, P.R.; Kamal, N.K.; Verma, U.K.; Suresh, K.; Thamilmaran, K.; Shrimali, M.D.

2016-01-01

Highlights: • The phenomena of suppression and revival of oscillations are studied in indirectly coupled nonlinear oscillators. • The decay parameter and a feedback factor play a crucial role in emergent dynamical behavior of oscillators. • The critical curves for different dynamical regions are obtained analytically using linear stability analysis. • Electronic circuit experiments demonstrate these emergent dynamical states. - Abstract: We study the phenomena of suppression and revival of oscillations in a system of limit cycle oscillators coupled indirectly via a dynamic local environment. The dynamics of the environment is assumed to decay exponentially with time. We show that for appropriate coupling strength, the decay parameter of the environment plays a crucial role in the emergent dynamics such as amplitude death (AD) and oscillation death (OD). We also show that introducing a feedback factor in the diffusion term revives the oscillations in this system. The critical curves for the regions of different emergent states as a function of coupling strength, decay parameter of the environment and feedback factor in the coupling are obtained analytically using linear stability analysis. These results are found to be consistent with the numerics and are also observed experimentally.

Sodium fire suppression

International Nuclear Information System (INIS)

Malet, J.C.

1979-01-01

Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

Sodium fire suppression

Energy Technology Data Exchange (ETDEWEB)

Malet, J C [DSN/SESTR, Centre de Cadarache, Saint-Paul-lez-Durance (France)

1979-03-01

Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

Emotional suppression and depressive symptoms in women newly diagnosed with early breast cancer.

Science.gov (United States)

Li, Lingyan; Yang, Yanjie; He, Jincai; Yi, Jinyao; Wang, Yuping; Zhang, Jinqiang; Zhu, Xiongzhao

2015-10-24

early breast cancer reported clinical or severe depressive symptoms. As well, these patients presented a controlled emotion coping style. Emotional suppression was associated with the level of depressive symptoms in women newly diagnosed with breast cancer. Anger suppression might play a unique role in the depressive symptoms among women newly diagnosed with breast cancer.

The novel GrCEP12 peptide from the plant-parasitic nematode Globodera rostochiensis suppresses flg22-mediated PTI.

Science.gov (United States)

Chen, Shiyan; Chronis, Demosthenis; Wang, Xiaohong

2013-09-01

The potato cyst nematode Globodera rostochiensis is a biotrophic pathogen that secretes effector proteins into host root cells to promote successful plant parasitism. In addition to the role in generating within root tissue the feeding cells essential for nematode development, (1) nematode secreted effectors are becoming recognized as suppressors of plant immunity. (2)(-) (4) Recently we reported that the effector ubiquitin carboxyl extension protein (GrUBCEP12) from G. rostochiensis is processed into free ubiquitin and a 12-amino acid GrCEP12 peptide in planta. Transgenic potato lines overexpressing the derived GrCEP12 peptide showed increased susceptibility to G. rostochiensis and to an unrelated bacterial pathogen Streptomyces scabies, suggesting that GrCEP12 has a role in suppressing host basal defense or possibly pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) during the parasitic interaction. (3) To determine if GrCEP12 functions as a PTI suppressor we evaluated whether GrCEP12 suppresses flg22-induced PTI responses in Nicotiana benthamiana. Interestingly, we found that transient expression of GrCEP12 in N. benthamiana leaves suppressed reactive oxygen species (ROS) production and the induction of two PTI marker genes triggered by the bacterial PAMP flg22, providing direct evidence that GrCEP12 indeed has an activity in PTI suppression.

Comparative Metatranscriptomics of Wheat Rhizosphere Microbiomes in Disease Suppressive and Non-suppressive Soils for Rhizoctonia solani AG8

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Helen L. Hayden

2018-05-01

Full Text Available The soilborne fungus Rhizoctonia solani anastomosis group (AG 8 is a major pathogen of grain crops resulting in substantial production losses. In the absence of resistant cultivars of wheat or barley, a sustainable and enduring method for disease control may lie in the enhancement of biological disease suppression. Evidence of effective biological control of R. solani AG8 through disease suppression has been well documented at our study site in Avon, South Australia. A comparative metatranscriptomic approach was applied to assess the taxonomic and functional characteristics of the rhizosphere microbiome of wheat plants grown in adjacent fields which are suppressive and non-suppressive to the plant pathogen R. solani AG8. Analysis of 12 rhizosphere metatranscriptomes (six per field was undertaken using two bioinformatic approaches involving unassembled and assembled reads. Differential expression analysis showed the dominant taxa in the rhizosphere based on mRNA annotation were Arthrobacter spp. and Pseudomonas spp. for non-suppressive samples and Stenotrophomonas spp. and Buttiauxella spp. for the suppressive samples. The assembled metatranscriptome analysis identified more differentially expressed genes than the unassembled analysis in the comparison of suppressive and non-suppressive samples. Suppressive samples showed greater expression of a polyketide cyclase, a terpenoid biosynthesis backbone gene (dxs and many cold shock proteins (csp. Non-suppressive samples were characterised by greater expression of antibiotic genes such as non-heme chloroperoxidase (cpo which is involved in pyrrolnitrin synthesis, and phenazine biosynthesis family protein F (phzF and its transcriptional activator protein (phzR. A large number of genes involved in detoxifying reactive oxygen species (ROS and superoxide radicals (sod, cat, ahp, bcp, gpx1, trx were also expressed in the non-suppressive rhizosphere samples most likely in response to the infection of wheat

Drowning stars: reassessing the role of astrocytes in brain edema.

Science.gov (United States)

Thrane, Alexander S; Rangroo Thrane, Vinita; Nedergaard, Maiken

2014-11-01

Edema formation frequently complicates brain infarction, tumors, and trauma. Despite the significant mortality of this condition, current treatment options are often ineffective or incompletely understood. Recent studies have revealed the existence of a brain-wide paravascular pathway for cerebrospinal (CSF) and interstitial fluid (ISF) exchange. The current review critically examines the contribution of this 'glymphatic' system to the main types of brain edema. We propose that in cytotoxic edema, energy depletion enhances glymphatic CSF influx, whilst suppressing ISF efflux. We also argue that paravascular inflammation or 'paravasculitis' plays a critical role in vasogenic edema. Finally, recent advances in diagnostic imaging of glymphatic function may hold the key to defining the edema profile of individual patients, and thus enable more targeted therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

In-Flight Suppressant Deployment Temperatures

National Research Council Canada - National Science Library

Bein, Donald

2006-01-01

.... An assessment is made of the model output versus some aircraft measurement data, fire suppressant boiling point criterion, as well as the history of altitude/temperature at which fire suppressants have been deployed...

Distracted by the Unthought – Suppression and Reappraisal of Mind Wandering under Stereotype Threat

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Schuster, Carolin; Martiny, Sarah E.; Schmader, Toni

2015-01-01

Previous research has found that subtle reminders of negative stereotypes about one’s group can lead individuals to underperform on stereotype-relevant tests (e.g., women in math, ethnic minorities on intelligence tests). This so called stereotype threat effect can contribute to systematic group differences in performance that can obscure the true abilities of certain social groups and thereby sustain social inequalities. In the present study, we examined processes underlying stereotype threat effects on women’s math performance, specifically focusing on the role of suppression of mind wandering (i.e., task-irrelevant thinking) in stereotype threat (ST) and no threat (NT) situations. Based on a process model of stereotype threat effects on performance, we hypothesized that women under stereotype threat spontaneously suppress mind wandering, and that this suppression impairs performance. An alternative regulation strategy that prevents suppression (i.e., reappraising task-irrelevant thoughts as normal) was predicted to prevent stereotype threat effects on performance. We manipulated stereotype threat (ST vs. NT) and cognitive regulation strategy (suppression, reappraisal, or no strategy) and measured women’s performance on a math and a concentration task (N = 113). We expected three groups to perform relatively more poorly: Those in ST with either no strategy or suppression and those in NT with a suppression strategy. We tested the performance of these groups against the remaining three groups hypothesized to perform relatively better: those in NT with no strategy or reappraisal and those in ST with reappraisal. The results showed the expected pattern for participants’ math performance, but not for concentration achievement. This pattern suggests that ineffective self-regulation by suppressing mind wandering can at least partly explain stereotype threat effects on performance, whereas a reappraisal strategy can prevent this impairment. We discuss

Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: A novel mechanism in muscle-bone communication.

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Qin, Yiwen; Peng, Yuanzhen; Zhao, Wei; Pan, Jianping; Ksiezak-Reding, Hanna; Cardozo, Christopher; Wu, Yingjie; Divieti Pajevic, Paola; Bonewald, Lynda F; Bauman, William A; Qin, Weiping

2017-06-30

Muscle and bone are closely associated in both anatomy and function, but the mechanisms that coordinate their synergistic action remain poorly defined. Myostatin, a myokine secreted by muscles, has been shown to inhibit muscle growth, and the disruption of the myostatin gene has been reported to cause muscle hypertrophy and increase bone mass. Extracellular vesicle-exosomes that carry microRNA (miRNA), mRNA, and proteins are known to perform an important role in cell-cell communication. We hypothesized that myostatin may play a crucial role in muscle-bone interactions and may promote direct effects on osteocytes and on osteocyte-derived exosomal miRNAs, thereby indirectly influencing the function of other bone cells. We report herein that myostatin promotes expression of several bone regulators such as sclerostin (SOST), DKK1, and RANKL in cultured osteocytic (Ocy454) cells, concomitant with the suppression of miR-218 in both parent Ocy454 cells and derived exosomes. Exosomes produced by Ocy454 cells that had been pretreated with myostatin could be taken up by osteoblastic MC3T3 cells, resulting in a marked reduction of Runx2, a key regulator of osteoblastic differentiation, and in decreased osteoblastic differentiation via the down-regulation of the Wnt signaling pathway. Importantly, the inhibitory effect of myostatin-modified osteocytic exosomes on osteoblast differentiation is completely reversed by expression of exogenous miR-218, through a mechanism involving miR-218-mediated inhibition of SOST. Together, our findings indicate that myostatin directly influences osteocyte function and thereby inhibits osteoblastic differentiation, at least in part, through the suppression of osteocyte-derived exosomal miR-218, suggesting a novel mechanism in muscle-bone communication. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Mechanisms of RhoGDI2 Mediated Lung Cancer Epithelial-Mesenchymal Transition Suppression

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Huiyan Niu

2014-11-01

Full Text Available Background: The aim of this study was to evaluate the function of RhoGDI2 in lung cancer epithelial-mesenchymal transition (EMT process and to illustrate the underlying mechanisms that will lead to improvement of lung cancer treatment. Methods: The RhoGDI2 knock-down and overexpressing A549 cell lines were first constructed. The influence of RhoGDI2 on cytoskeleton in A549 cells was studied using two approaches: G-LISA-based Rac1 activity measurement and immunostaining-based F-actin distribution. The expression levels of key EMT genes were analyzed using real time quantitative polymerase chain reaction (RT-qPCR, western blot and immunostaining in untreated and RhoGDI2 knock-down or overexpressing A549 cells in both in vivo and in vitro experimental settings. Results: Our study showed that the activity of Rac1, a key gene that is crucial for the initiation and metastasis of human lung adenocarcinoma, causing the redistribution of F-actin with partial loss of cell-cell adhesions and stress fibers, was significantly suppressed by RhoGDI2. RhoGDI2 promoted the expression of EMT marker gene E-cadherin and repressed EMT promoting genes Slug, Snail, α-SMA in both A549 cells and lung and liver organs derived from the mouse models. Knocking-down RhoGDI2 induced abnormal morphology for lung organs. Conclusion: These findings indicate that RhoGDI2 repressed the activity of Rac1 and may be involved in the rearrangement of cytoskeleton in lung cancer cells. RhoGDI2 suppresses the metastasis of lung cancer mediated through EMT by regulating the expression of key genes such as E-cadherin, Slug, Snail and α-SMA in both in vivo and in vitro models.

An Identification Key for Selecting Methods for Sustainability Assessments

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Michiel C. Zijp

2015-03-01

Full Text Available Sustainability assessments can play an important role in decision making. This role starts with selecting appropriate methods for a given situation. We observed that scientists, consultants, and decision-makers often do not systematically perform a problem analyses that guides the choice of the method, partly related to a lack of systematic, though sufficiently versatile approaches to do so. Therefore, we developed and propose a new step towards method selection on the basis of question articulation: the Sustainability Assessment Identification Key. The identification key was designed to lead its user through all important choices needed for comprehensive question articulation. Subsequently, methods that fit the resulting specific questions are suggested by the key. The key consists of five domains, of which three determine method selection and two the design or use of the method. Each domain consists of four or more criteria that need specification. For example in the domain “system boundaries”, amongst others, the spatial and temporal scales are specified. The key was tested (retrospectively on a set of thirty case studies. Using the key appeared to contribute to improved: (i transparency in the link between the question and method selection; (ii consistency between questions asked and answers provided; and (iii internal consistency in methodological design. There is latitude to develop the current initial key further, not only for selecting methods pertinent to a problem definition, but also as a principle for associated opportunities such as stakeholder identification.

Key to Language Learning Success

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Oktavian Mantiri

2015-01-01

Full Text Available This paper looks at the important elements of language learning and teaching i.e. the role of teachers as well as the attitude and motivation of learners. Teachers undoubtedly play crucial roles in students’ language learning outcome which could ignite or diminish students’ motivation. Positive attitudes and motivation – instrumental or integrative and intrinsic or extrinsic – are key to successful learning. Therefore it is paramount for language teachers as well as learners to know these roles and nurture the best possible ways where language teaching and learning will thrive. This paper also suggested that both stake-holders should be open to holistic approach of language learning and that other factors such as the environment could play an important part in language teaching and learning success.

Effects of lesions of the dorsal noradrenergic bundle on conditioned suppression to a CS and to a contextual background stimulus.

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Tsaltas, E; Schugens, M M; Gray, J A

1989-01-01

The aim of the experiment was to determine whether the dorsal noradrenergic bundle (DB) plays a role in conditioning to context. Rats received either bilateral lesions of the DB by local injection of 6-hydroxydopamine, vehicle injections only, or sham operations. All animals were then trained to barpress for food on a variable interval (VI) schedule. Two 5-min intrusion periods were superimposed on the VI baseline during each session. An 'envelope' stimulus (flashing light) was on throughout each intrusion period. In addition, embedded in the two intrusion periods of each session, there occurred 8 presentations of a 'punctate' conditioned stimulus (CS) (a 15-s clicker), and 8 presentations of a 0.5-s footshock. Within each surgical condition rats were randomly allocated to one of three conditioning groups, receiving 100%, 50% or 0% temporal association between CS and shock. Conditioning to the punctate CS and to the context provided by the envelope stimulus was assessed by the degree of suppression of the barpress response relative to the VI baseline. Responding was most suppressed in the punctate CS in the 100 and 50% conditions, and most suppressed in the envelope stimulus in the 0% condition. DB lesions released response suppression to the punctate CS, had no effect on suppression to the envelope stimulus, and reduced sensitivity to CS-shock probability as measured by response suppression during the punctate CS. These results confirm previous reports that DB lesions alleviate response suppression to shock-associated cues, identify some of the parameters that affect this phenomenon, but fail to support a role for the DB in contextual conditioning.

AF10 plays a key role in the survival of uncommitted hematopoietic cells.

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Raquel Chamorro-Garcia

Full Text Available Hematopoiesis is a complex process regulated by both cell intrinsic and cell extrinsic factors. Alterations in the expression of critical genes during hematopoiesis can modify the balance between stem cell differentiation and proliferation, and may ultimately give rise to leukemia and other diseases. AF10 is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. The link between AF10 and leukemia, together with the known interactions between AF10 and hematopoietic regulators, suggests that AF10 may be important in hematopoiesis and in leukemic transformation. Here we show that AF10 is important for proper hematopoietic differentiation. The induction of hematopoietic differentiation in both human hematopoietic cell lines and murine total bone marrow cells triggers a decrease of AF10 mRNA and protein levels, particularly in stem cells and multipotent progenitors. Gain- and loss-of-function studies demonstrate that over- or under-expression of AF10 leads to apoptotic cell death in stem cells and multipotent progenitors. We conclude that AF10 plays a key role in the maintenance of multipotent hematopoietic cells.

Suppression effects on musical and verbal memory.

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Schendel, Zachary A; Palmer, Caroline

2007-06-01

Three experiments contrasted the effects of articulatory suppression on recognition memory for musical and verbal sequences. In Experiment 1, a standard/comparison task was employed, with digit or note sequences presented visually or auditorily while participants remained silent or produced intermittent verbal suppression (saying "the") or musical suppression (singing "la"). Both suppression types decreased performance by equivalent amounts, as compared with no suppression. Recognition accuracy was lower during suppression for visually presented digits than during that for auditorily presented digits (consistent with phonological loop predictions), whereas accuracy was equivalent for visually presented notes and auditory tones. When visual interference filled the retention interval in Experiment 2, performance with visually presented notes but not digits was impaired. Experiment 3 forced participants to translate visually presented music sequences by presenting comparison sequences auditorily. Suppression effects for visually presented music resembled those for digits only when the recognition task required sensory translation of cues.

Suppress to feel and remember less: Neural correlates of explicit and implicit emotional suppression on perception and memory.

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Katsumi, Yuta; Dolcos, Sanda

2018-02-09

Available evidence suggests that emotion regulation can modulate both immediate (emotional experience) and long-term (episodic memory) effects of emotion, and that both explicit and implicit forms may be effective. However, neural mechanisms by which explicit and implicit emotional suppression affect these phenomena remain unclear, particularly regarding their effects on memory. In this study, participants rated the emotional content of negative and neutral images, following explicit (verbal instructions) or implicit (priming) induction of emotional suppression goals, during functional magnetic resonance imaging. Participants' memory for the images was tested one week later. Behaviorally, explicit suppression reduced emotional ratings of negative images, whereas both explicit and implicit suppression reduced subsequent memory. At the neural level, the engagement of explicit suppression was uniquely associated with decreased activity in the amygdala (AMY), during emotional ratings, and in the AMY and inferior frontal gyrus (IFG), during successful encoding. Although both explicit and implicit suppression diminished functional connectivity between these regions and the hippocampus (HC) linked to successful encoding, explicit suppression was uniquely associated with interference with AMY-HC interactions, which no longer predicted subsequent memory for the explicitly-suppressed items. Overall, these findings advance our understanding of the common and dissociable mechanisms of explicit and implicit emotional suppression on perception and memory, and suggest their impact on both bottom-up and top-down mechanisms involved in emotion-cognition interactions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pur-Alpha Induces JCV Gene Expression and Viral Replication by Suppressing SRSF1 in Glial Cells.

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Ilker Kudret Sariyer

Full Text Available PML is a rare and fatal demyelinating disease of the CNS caused by the human polyomavirus, JC virus (JCV, which occurs in AIDS patients and those on immunosuppressive monoclonal antibody therapies (mAbs. We sought to identify mechanisms that could stimulate reactivation of JCV in a cell culture model system and targeted pathways which could affect early gene transcription and JCV T-antigen production, which are key steps of the viral life cycle for blocking reactivation of JCV. Two important regulatory partners we have previously identified for T-antigen include Pur-alpha and SRSF1 (SF2/ASF. SRSF1, an alternative splicing factor, is a potential regulator of JCV whose overexpression in glial cells strongly suppresses viral gene expression and replication. Pur-alpha has been most extensively characterized as a sequence-specific DNA- and RNA-binding protein which directs both viral gene transcription and mRNA translation, and is a potent inducer of the JCV early promoter through binding to T-antigen.Pur-alpha and SRSF1 both act directly as transcriptional regulators of the JCV promoter and here we have observed that Pur-alpha is capable of ameliorating SRSF1-mediated suppression of JCV gene expression and viral replication. Interestingly, Pur-alpha exerted its effect by suppressing SRSF1 at both the protein and mRNA levels in glial cells suggesting this effect can occur independent of T-antigen. Pur-alpha and SRSF1 were both localized to oligodendrocyte inclusion bodies by immunohistochemistry in brain sections from patients with HIV-1 associated PML. Interestingly, inclusion bodies were typically positive for either Pur-alpha or SRSF1, though some cells appeared to be positive for both proteins.Taken together, these results indicate the presence of an antagonistic interaction between these two proteins in regulating of JCV gene expression and viral replication and suggests that they play an important role during viral reactivation leading to

Acetylation Is Crucial for p53-Mediated Ferroptosis and Tumor Suppression

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Shang-Jui Wang

2016-10-01

Full Text Available Although previous studies indicate that loss of p53-mediated cell cycle arrest, apoptosis, and senescence does not completely abrogate its tumor suppression function, it is unclear how the remaining activities of p53 are regulated. Here, we have identified an acetylation site at lysine K98 in mouse p53 (or K101 for human p53. Whereas the loss of K98 acetylation (p53K98R alone has very modest effects on p53-mediated transactivation, simultaneous mutations at all four acetylation sites (p534KR: K98R+ 3KR[K117R+K161R+K162R] completely abolish its ability to regulate metabolic targets, such as TIGAR and SLC7A11. Notably, in contrast to p533KR, p534KR is severely defective in suppressing tumor growth in mouse xenograft models. Moreover, p534KR is still capable of inducing the p53-Mdm2 feedback loop, but p53-dependent ferroptotic responses are markedly abrogated. Together, these data indicate the critical role of p53 acetylation in ferroptotic responses and its remaining tumor suppression activity.

Suppressing supersymmetric flavor violations through quenched gaugino-flavor interactions

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Wells, James D.; Zhao, Yue

2017-06-01

Realizing that couplings related by supersymmetry (SUSY) can be disentangled when SUSY is broken, it is suggested that unwanted flavor and C P -violating SUSY couplings may be suppressed via quenched gaugino-flavor interactions, which may be accomplished by power-law running of sfermion anomalous dimensions. A simple theoretical framework to accomplish this is exemplified, where a strongly coupled conformal field theory is achieved after SUSY is softly broken. The defeated constraints are tallied. One key implication of the scenario is the expectation of enhanced top, bottom and tau production at the LHC, accompanied by large missing energy. Also, direct detection signals of dark matter may be more challenging to find than in conventional SUSY scenarios.

Suppressing turbulence of self-propelling rods by strongly coupled passive particles.

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Su, Yen-Shuo; Wang, Hao-Chen; I, Lin

2015-03-01

The strong turbulence suppression, mainly for large-scale modes, of two-dimensional self-propelling rods, by increasing the long-range coupling strength Γ of low-concentration passive particles, is numerically demonstrated. It is found that large-scale collective rod motion in forms of swirls or jets is mainly contributed from well-aligned dense patches, which can push small poorly aligned rod patches and uncoupled passive particles. The more efficient momentum transfer and dissipation through increasing passive particle coupling leads to the formation of a more ordered and slowed down network of passive particles, which competes with coherent dense active rod clusters. The frustration of active rod alignment ordering and coherent motion by the passive particle network, which interrupt the inverse cascading of forming large-scale swirls, is the key for suppressing collective rod motion with scales beyond the interpassive distance, even in the liquid phase of passive particles. The loosely packed active rods are weakly affected by increasing passive particle coupling due to the weak rod-particle interaction. They mainly contribute to the small-scale modes and high-speed motion.

FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin

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Kode, Aruna; Mosialou, Ioanna; Silva, Barbara C.; Rached, Marie-Therese; Zhou, Bin; Wang, Ji; Townes, Tim M.; Hen, Rene; DePinho, Ronald A.; Guo, X. Edward; Kousteni, Stavroula

2012-01-01

Serotonin is a critical regulator of bone mass, fulfilling different functions depending on its site of synthesis. Brain-derived serotonin promotes osteoblast proliferation, whereas duodenal-derived serotonin suppresses it. To understand the molecular mechanisms of duodenal-derived serotonin action on osteoblasts, we explored its transcriptional mediation in mice. We found that the transcription factor FOXO1 is a crucial determinant of the effects of duodenum-derived serotonin on bone formation We identified two key FOXO1 complexes in osteoblasts, one with the transcription factor cAMP-responsive element–binding protein 1 (CREB) and another with activating transcription factor 4 (ATF4). Under normal levels of circulating serotonin, the proliferative activity of FOXO1 was promoted by a balance between its interaction with CREB and ATF4. However, high circulating serotonin levels prevented the association of FOXO1 with CREB, resulting in suppressed osteoblast proliferation. These observations identify FOXO1 as the molecular node of an intricate transcriptional machinery that confers the signal of duodenal-derived serotonin to inhibit bone formation. PMID:22945629

Key role for efflux in the preservative susceptibility and adaptive resistance of Burkholderia cepacia complex bacteria.

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Rushton, Laura; Sass, Andrea; Baldwin, Adam; Dowson, Christopher G; Donoghue, Denise; Mahenthiralingam, Eshwar

2013-07-01

Bacteria from the Burkholderia cepacia complex (Bcc) are encountered as industrial contaminants, and little is known about the species involved or their mechanisms of preservative resistance. Multilocus sequence typing (MLST) revealed that multiple Bcc species may cause contamination, with B. lata (n = 17) and B. cenocepacia (n = 11) dominant within the collection examined. At the strain level, 11 of the 31 industrial sequence types identified had also been recovered from either natural environments or clinical infections. Minimal inhibitory (MIC) and minimum bactericidal (MBC) preservative concentrations varied across 83 selected Bcc strains, with industrial strains demonstrating increased tolerance for dimethylol dimethyl hydantoin (DMDMH). Benzisothiazolinone (BIT), DMDMH, methylisothiazolinone (MIT), a blend of 3:1 methylisothiazolinone-chloromethylisothiazolinone (M-CMIT), methyl paraben (MP), and phenoxyethanol (PH), were all effective anti-Bcc preservatives; benzethonium chloride (BC) and sodium benzoate (SB) were least effective. Since B. lata was the dominant industrial Bcc species, the type strain, 383(T) (LMG 22485(T)), was used to study preservative tolerance. Strain 383 developed stable preservative tolerance for M-CMIT, MIT, BIT, and BC, which resulted in preservative cross-resistance and altered antibiotic susceptibility, motility, and biofilm formation. Transcriptomic analysis of the B. lata 383 M-CMIT-adapted strain demonstrated that efflux played a key role in its M-CMIT tolerance and elevated fluoroquinolone resistance. The role of efflux was corroborated using the inhibitor l-Phe-Arg-β-napthylamide, which reduced the MICs of M-CMIT and ciprofloxacin. In summary, intrinsic preservative tolerance and stable adaptive changes, such as enhanced efflux, play a role in the ability of Bcc bacteria to cause industrial contamination.

Rapamycin delays growth of Wnt-1 tumors in spite of suppression of host immunity

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Svirshchevskaya, Elena V; Mariotti, Jacopo; Wright, Mollie H; Viskova, Natalia Y; Telford, William; Fowler, Daniel H; Varticovski, Lyuba

2008-01-01

Rapamycin, an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. However, the role of Rapamycin-induced immune suppression on tumor progression has not been examined. We developed a transplantation model for generation of mammary tumors in syngeneic recipients that can be used to address the role of the immune system on tumor progression. We examined the effect of Rapamycin on the immune system and growth of MMTV-driven Wnt-1 mammary tumors which were transplanted into irradiated and bone marrow-reconstituted, or naïve mice. Rapamycin induced severe immunosuppression and significantly delayed the growth of Wnt-1 tumors. T cell depletion in spleen and thymus and reduction in T cell cytokine secretion were evident within 7 days of therapy. By day 20, splenic but not thymic T cell counts, and cytokine secretion recovered. We determined whether adoptive T cell therapy enhances the anti-cancer effect using ex vivo generated Rapamycin-resistant T cells. However, T cell transfer during Rapamycin therapy did not improve the outcome relative to drug therapy alone. Thus, we could not confirm that suppression of T cell immunity contributes to tumor growth in this model. Consistent with suppression of the mTOR pathway, decreased 4E-BP1, p70 S6-kinase, and S6 protein phosphorylation correlated with a decrease in Wnt-1 tumor cell proliferation. Rapamycin has a direct anti-tumor effect on Wnt-1 breast cancer in vivo that involves inhibition of the mTOR pathway at doses that also suppress host immune responses

High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation[S

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McGrath, Kristine C.; Li, Xiao Hong; Whitworth, Phillippa T.; Kasz, Robert; Tan, Joanne T.; McLennan, Susan V.; Celermajer, David S.; Barter, Philip J.; Rye, Kerry-Anne; Heather, Alison K.

2014-01-01

Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation. PMID:24347528

Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune Suppression

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Theresa L. Whiteside

2016-10-01

Full Text Available Tumor-derived exosomes (TEX are emerging as critical components of an intercellular information network between the tumor and the host. The tumor escapes from the host immune system by using a variety of mechanisms designed to impair or eliminate anti-tumor immunity. TEX carrying a cargo of immunoinhibitory molecules and factors represent one such mechanism. TEX, which are present in all body fluids of cancer patients, deliver negative molecular or genetic signals to immune cells re-programming their functions. Although TEX can also stimulate immune activity, in the microenvironments dominated by the tumor, TEX tend to mediate immune suppression thus promoting tumor progression. The TEX content, in part resembling that of the parent cell, may serve as a source of cancer biomarkers. TEX also interfere with immune therapies. A better understanding of TEX and their contribution to cancer progression and cancer patients’ response to immune therapies represents a challenging new field of investigation.

Suppression of Langerhans cell activation is conserved amongst human papillomavirus α and β genotypes, but not a µ genotype.

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Da Silva, Diane M; Movius, Carly A; Raff, Adam B; Brand, Heike E; Skeate, Joseph G; Wong, Michael K; Kast, W Martin

2014-03-01

Human papillomavirus (HPV) has evolved mechanisms that allow it to evade the human immune system. Studies have shown HPV-mediated suppression of activation of Langerhans cells (LC) is a key mechanism through which HPV16 evades initial immune surveillance. However, it has not been established whether high- and low-risk mucosal and cutaneous HPV genotypes share a common mechanism of immune suppression. Here, we demonstrate that LC exposed to capsids of HPV types 18, 31, 45, 11, (alpha-papillomaviruses) and HPV5 (beta-papillomavirus) similarly suppress LC activation, including lack of costimulatory molecule expression, lack of cytokine and chemokine secretion, lack of migration, and deregulated cellular signaling. In contrast, HPV1 (mu-papillomavirus) induced costimulatory molecule and cytokine upregulation, but LC migration and cellular signaling was suppressed. These results suggest that alpha and beta HPV genotypes, and partially a mu genotype, share a conserved mechanism of immune escape that enables these viruses to remain undetected in the absence of other inflammatory events. Copyright © 2014 Elsevier Inc. All rights reserved.

Phosphoinositides: Key modulators of energy metabolism☆

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Bridges, Dave; Saltiel, Alan R.

2014-01-01

Phosphoinositides are key players in many trafficking and signaling pathways. Recent advances regarding the synthesis, location and functions of these lipids have dramatically improved our understanding of how and when these lipids are generated and what their roles are in animal physiology. In particular, phosphoinositides play a central role in insulin signaling, and manipulation of PtdIns(3,4,5)P3 levels in particular, may be an important potential therapeutic target for the alleviation of insulin resistance associated with obesity and the metabolic syndrome. In this article we review the metabolism, regulation and functional roles of phosphoinositides in insulin signaling and the regulation of energy metabolism. This article is part of a Special Issue entitled Phosphoinositides. PMID:25463477

miR-644a Inhibits Cellular Proliferation and Invasion via Suppression of CtBP1 in Gastric Cancer Cells.

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Li, Yingchao; Yan, Xiaoni; Ren, Li; Li, Yang

2018-01-19

Epithelial-mesenchymal transition (EMT) is one of the most important mechanisms in the metastasis of various cancers, including gastric cancer (GC). In this study, we explored the putative significance of miR-644a and its role in EMT-mediated metastasis of GC. We first detected the expression of miR-644a in a cohort of 107 GC tissues using quantitative RT-PCR. The expression of miR-644a was suppressed in GC tissues and was associated with a later clinical stage and tumor metastasis. Restoring the expression of miR-644a could significantly suppress the migration and invasion of HGC-27 and SGC-7901 cells, which might be correlated to its suppressive effect on the EMT process. We also found that carboxyl-terminal-binding protein 1 (CtBP1) was a putative target gene of miR-644a in GC and might be involved in the suppressive effect. Collectively, through targeting CtBP1-mediated suppression of the EMT process, miR-644a might suppress the tumor metastasis of GC cells.

Pulse sequences for suppressing leakage in single-qubit gate operations

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Ghosh, Joydip; Coppersmith, S. N.; Friesen, Mark

2017-06-01

Many realizations of solid-state qubits involve couplings to leakage states lying outside the computational subspace, posing a threat to high-fidelity quantum gate operations. Mitigating leakage errors is especially challenging when the coupling strength is unknown, e.g., when it is caused by noise. Here we show that simple pulse sequences can be used to strongly suppress leakage errors for a qubit embedded in a three-level system. As an example, we apply our scheme to the recently proposed charge quadrupole (CQ) qubit for quantum dots. These results provide a solution to a key challenge for fault-tolerant quantum computing with solid-state elements.

Fear Expression Suppresses Medial Prefrontal Cortical Firing in Rats.

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Thomas F Giustino

Full Text Available The medial prefrontal cortex (mPFC plays a crucial role in emotional learning and memory in rodents and humans. While many studies suggest a differential role for the prelimbic (PL and infralimbic (IL subdivisions of mPFC, few have considered the relationship between neural activity in these two brain regions recorded simultaneously in behaving animals. Importantly, how concurrent PL and IL activity relate to conditioned freezing behavior is largely unknown. Here we used single-unit recordings targeting PL and IL in awake, behaving rats during the acquisition and expression of conditioned fear. On Day 1, rats received either signaled or unsignaled footshocks in the recording chamber; an auditory conditioned stimulus (CS preceded signaled footshocks. Twenty-four hours later, animals were returned to the recording chamber (modified to create a novel context where they received 5 CS-alone trials. After fear conditioning, both signaled and unsignaled rats exhibited high levels of post-shock freezing that was associated with an enduring suppression of mPFC spontaneous firing, particularly in the IL of signaled rats. Twenty-four hours later, CS presentation produced differential conditioned freezing in signaled and unsignaled rats: freezing increased in rats that had received signaled shocks, but decreased in animals in the unsignaled condition (i.e., external inhibition. This group difference in CS-evoked freezing was mirrored in the spontaneous firing rate of neurons in both PL and IL. Interestingly, differences in PL and IL firing rate highly correlated with freezing levels. In other words, in the signaled group IL spontaneous rates were suppressed relative to PL, perhaps limiting IL-mediated suppression of fear and allowing PL activity to dominate performance, resulting in high levels of freezing. This was not observed in the unsignaled group, which exhibited low freezing. These data reveal that the activity of mPFC neurons is modulated by both

Tolerogenic CX3CR1+ B cells suppress food allergy-induced intestinal inflammation in mice.

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Liu, Z Q; Wu, Y; Song, J P; Liu, X; Liu, Z; Zheng, P Y; Yang, P C

2013-10-01

B lymphocytes are an important cell population of the immune regulation; their role in the regulation of food allergy has not been fully understood yet. This study aims to investigate the role of a subpopulation of tolerogenic B cells (TolBC) in the generation of regulatory T cells (Treg) and in the suppression of food allergy-induced intestinal inflammation in mice. The intestinal mucosa-derived CD5+ CD19+ CX3CR1+ TolBCs were characterized by flow cytometry; a mouse model of intestinal T helper (Th)2 inflammation was established to assess the immune regulatory role of this subpopulation of TolBCs. A subpopulation of CD5+ CD19+ CX3CR1+ B cells was detected in the mouse intestinal mucosa. The cells also expressed transforming growth factor (TGF)-β and carried integrin alpha v beta 6 (αvβ6). Exposure to recombinant αvβ6 and anti-IgM antibody induced naive B cells to differentiate into the TGF-β-producing TolBCs. Coculturing this subpopulation of TolBCs with Th0 cells generated CD4+ CD25+ Foxp3+ Tregs. Adoptive transfer with the TolBCs markedly suppressed the food allergy-induced intestinal Th2 pattern inflammation in mice. CD5+ CD19+ CX3CR1+ TolBCs are capable of inducing Tregs in the intestine and suppress food allergy-related Th2 pattern inflammation in mice. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Repetition Suppression in the Left Inferior Frontal Gyrus Predicts Tone Learning Performance.

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Asaridou, Salomi S; Takashima, Atsuko; Dediu, Dan; Hagoort, Peter; McQueen, James M

2016-06-01

Do individuals differ in how efficiently they process non-native sounds? To what extent do these differences relate to individual variability in sound-learning aptitude? We addressed these questions by assessing the sound-learning abilities of Dutch native speakers as they were trained on non-native tone contrasts. We used fMRI repetition suppression to the non-native tones to measure participants' neuronal processing efficiency before and after training. Although all participants improved in tone identification with training, there was large individual variability in learning performance. A repetition suppression effect to tone was found in the bilateral inferior frontal gyri (IFGs) before training. No whole-brain effect was found after training; a region-of-interest analysis, however, showed that, after training, repetition suppression to tone in the left IFG correlated positively with learning. That is, individuals who were better in learning the non-native tones showed larger repetition suppression in this area. Crucially, this was true even before training. These findings add to existing evidence that the left IFG plays an important role in sound learning and indicate that individual differences in learning aptitude stem from differences in the neuronal efficiency with which non-native sounds are processed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The effect of quercetin nanoparticle on cervical cancer progression by inducing apoptosis, autophagy and anti-proliferation via JAK2 suppression.

Science.gov (United States)

Luo, Cheng-Lin; Liu, Yu-Qiong; Wang, Peng; Song, Chun-Hua; Wang, Kai-Juan; Dai, Li-Ping; Zhang, Jian-Ying; Ye, Hua

2016-08-01

Cervical cancer is a cause of cancer death, making it as the one of the most common cause for death among women globally. Though many studies before have explored a lot for cervical cancer prevention and treatment, there are still a lot far from to know based on the molecular mechanisms. Janus kinase 2 (JAK2) has been reported to play an essential role in the progression of apoptosis, autophagy and proliferation for cells. We loaded gold-quercetin into poly (dl-lactide-co-glycolide) nanoparticles to cervical cancer cells due to the propertities of quercetin in ameliorating cellular processes and the easier absorbance of nanoparticles. Here, in our study, quercetin nanoparticles (NQ) were administrated to cells to investigate the underlying mechanism by which the cervical cancer was regulated. First, JAK2-inhibited carvical cancer cell lines were involved for our experiments in vitro and in vivo. Western blotting, quantitative RT-PCR (qRT-PCR), ELISA, Immunohistochemistry, and flow-cytometric analysis were used to determine the key signaling pathway regulated by JAK2 for cervical cancer progression. And the role of quercetin nanoparticles was determined during the process. Data here indicated that JAK2, indeed, expressed highly in cancer cell lines compared to the normal cervical cells. And apoptosis and autophagy were found in JAK2-inhibited cancer cells through activating Caspase-3, and suppressing Cyclin-D1 and mTOR regulated by Signal Transducer and Activator of Transcription (STAT) 3/5 and phosphatidylinositide 3-kinase/protein kinases (PI3K/AKT) signaling pathway. The cervical cancer cells proliferation was inhibited. Further, tumor size and weight were reduced by inhibition of JAK2 in vivo experiments. Notably, administration with quercetin nanoparticles displayed similar role with JAK2 suppression, which could inhibit cervical cancer cells proliferation, invasion and migration. In addition, autophogy and apoptosis were induced, promoting cervical cancer cell

Nuclear energy: a key role despite problems

International Nuclear Information System (INIS)

Anderson, E.V.

1977-01-01

Nuclear energy is projected to be the fastest growing power source and a key to meeting power demands in spite of the many problems facing the nuclear industry in the form of delays, protests, and cancellations. Pressures for a nuclear moratorium will slow the industry, Mr. Anderson feels, but in the long run nuclear reactors will make up an increasing share of the power generating capacity. The Arthur D. Little Co. projects a fourfold increase between 1975 and 1985 on the basis of 10-year lead times for construction of nuclear power plants. Half the new generating capacity after 1985 will be nuclear. Problems besetting every stage of the nuclear fuel cycle result from debates over proliferation, waste disposal, reactor safety, and environmental damage and lead to controversy over regulations and licensing. U.S. utilities are not ordering reactors, but manufacturers are finding markets in other countries. Financial difficulties have kept domestic utilities from undertaking large investment programs until they can resolve problems of fuel costs and rate structures. New construction is inevitable, however, to meet future electrical requirements. Nuclear companies, which number nearly 1300 manufacturers and service providers, need to develop a better public image by working together to demonstrate their ability to manage the risks and uncertainties

The regulation of the chloroplast proton motive force plays a key role for photosynthesis in fluctuating light.

Science.gov (United States)

Armbruster, Ute; Correa Galvis, Viviana; Kunz, Hans-Henning; Strand, Deserah D

2017-06-01

Plants use sunlight as their primary energy source. During photosynthesis, absorbed light energy generates reducing power by driving electron transfer reactions. These are coupled to the transfer of protons into the thylakoid lumen, generating a proton motive force (pmf) required for ATP synthesis. Sudden alterations in light availability have to be met by regulatory mechanisms to avoid the over-accumulation of reactive intermediates and maximize energy efficiency. Here, the acidification of the lumen, as an intermediate product of photosynthesis, plays an important role by regulating photosynthesis in response to excitation energy levels. Recent findings reveal pmf regulation and the modulation of its composition as key determinants for efficient photosynthesis, plant growth, and survival in fluctuating light environments. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Deconstructing Interocular Suppression: Attention and Divisive Normalization.

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Hsin-Hung Li

2015-10-01

Full Text Available In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression, the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature and divisive normalization contribute to interocular suppression.

Deconstructing Interocular Suppression: Attention and Divisive Normalization.

Science.gov (United States)

Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J

2015-10-01

In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression.

Psychopathology and Thought Suppression: A Quantitative Review

Science.gov (United States)

Magee, Joshua C.; Harden, K. Paige; Teachman, Bethany A.

2012-01-01

Recent theories of psychopathology have suggested that thought suppression intensifies the persistence of intrusive thoughts, and proposed that difficulty with thought suppression may differ between groups with and without psychopathology. The current meta-analytic review evaluates empirical evidence for difficulty with thought suppression as a function of the presence and specific type of psychopathology. Based on theoretical proposals from the psychopathology literature, diagnosed and analogue samples were expected to show greater recurrence of intrusive thoughts during thought suppression attempts than non-clinical samples. However, results showed no overall differences in the recurrence of thoughts due to thought suppression between groups with and without psychopathology. There was, nevertheless, variation in the recurrence of thoughts across different forms of psychopathology, including relatively less recurrence during thought suppression for samples with symptoms of Obsessive-Compulsive Disorder, compared to non-clinical samples. However, these differences were typically small and provided only mixed support for existing theories. Implications for cognitive theories of intrusive thoughts are discussed, including proposed mechanisms underlying thought suppression. PMID:22388007

The Yin and Yang of Invariant Natural Killer T Cells in Tumor Immunity—Suppression of Tumor Immunity in the Intestine

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Ying Wang

2018-01-01

Full Text Available CD1d-restricted invariant natural killer T (iNKT cells are known as early responding, potent regulatory cells of immune responses. Besides their established role in the regulation of inflammation and autoimmune disease, numerous studies have shown that iNKT cells have important functions in tumor immunosurveillance and control of tumor metastasis. Tumor-infiltrating T helper 1 (TH1/cytotoxic T lymphocytes have been associated with a positive prognosis. However, inflammation has a dual role in cancer and chronic inflammation is believed to be a driving force in many cancers as exemplified in patients with inflammatory bowel disease that have an increased risk of colorectal cancer. Indeed, NKT cells promote intestinal inflammation in human ulcerative colitis, and the associated animal model, indicating that NKT cells may favor tumor development in intestinal tissue. In contrast to other cancers, recent data from animal models suggest that iNKT cells promote tumor formation in the intestine by supporting an immunoregulatory tumor microenvironment and suppressing TH1 antitumor immunity. Here, we review the role of iNKT cells in suppression of tumor immunity in light of iNKT-cell regulation of intestinal inflammation. We also discuss suppression of immunity in other situations as well as factors that may influence whether iNKT cells have a protective or an immunosuppressive and tumor-promoting role in tumor immunity.

How fire history, fire suppression practices and climate change affect wildfire regimes in Mediterranean landscapes.

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Lluís Brotons

Full Text Available Available data show that future changes in global change drivers may lead to an increasing impact of fires on terrestrial ecosystems worldwide. Yet, fire regime changes in highly humanised fire-prone regions are difficult to predict because fire effects may be heavily mediated by human activities We investigated the role of fire suppression strategies in synergy with climate change on the resulting fire regimes in Catalonia (north-eastern Spain. We used a spatially-explicit fire-succession model at the landscape level to test whether the use of different firefighting opportunities related to observed reductions in fire spread rates and effective fire sizes, and hence changes in the fire regime. We calibrated this model with data from a period with weak firefighting and later assess the potential for suppression strategies to modify fire regimes expected under different levels of climate change. When comparing simulations with observed fire statistics from an eleven-year period with firefighting strategies in place, our results showed that, at least in two of the three sub-regions analysed, the observed fire regime could not be reproduced unless taking into account the effects of fire suppression. Fire regime descriptors were highly dependent on climate change scenarios, with a general trend, under baseline scenarios without fire suppression, to large-scale increases in area burnt. Fire suppression strategies had a strong capacity to compensate for climate change effects. However, strong active fire suppression was necessary to accomplish such compensation, while more opportunistic fire suppression strategies derived from recent fire history only had a variable, but generally weak, potential for compensation of enhanced fire impacts under climate change. The concept of fire regime in the Mediterranean is probably better interpreted as a highly dynamic process in which the main determinants of fire are rapidly modified by changes in landscape

How fire history, fire suppression practices and climate change affect wildfire regimes in Mediterranean landscapes.

Science.gov (United States)

Brotons, Lluís; Aquilué, Núria; de Cáceres, Miquel; Fortin, Marie-Josée; Fall, Andrew

2013-01-01

Available data show that future changes in global change drivers may lead to an increasing impact of fires on terrestrial ecosystems worldwide. Yet, fire regime changes in highly humanised fire-prone regions are difficult to predict because fire effects may be heavily mediated by human activities We investigated the role of fire suppression strategies in synergy with climate change on the resulting fire regimes in Catalonia (north-eastern Spain). We used a spatially-explicit fire-succession model at the landscape level to test whether the use of different firefighting opportunities related to observed reductions in fire spread rates and effective fire sizes, and hence changes in the fire regime. We calibrated this model with data from a period with weak firefighting and later assess the potential for suppression strategies to modify fire regimes expected under different levels of climate change. When comparing simulations with observed fire statistics from an eleven-year period with firefighting strategies in place, our results showed that, at least in two of the three sub-regions analysed, the observed fire regime could not be reproduced unless taking into account the effects of fire suppression. Fire regime descriptors were highly dependent on climate change scenarios, with a general trend, under baseline scenarios without fire suppression, to large-scale increases in area burnt. Fire suppression strategies had a strong capacity to compensate for climate change effects. However, strong active fire suppression was necessary to accomplish such compensation, while more opportunistic fire suppression strategies derived from recent fire history only had a variable, but generally weak, potential for compensation of enhanced fire impacts under climate change. The concept of fire regime in the Mediterranean is probably better interpreted as a highly dynamic process in which the main determinants of fire are rapidly modified by changes in landscape, climate and

How Fire History, Fire Suppression Practices and Climate Change Affect Wildfire Regimes in Mediterranean Landscapes

Science.gov (United States)

Brotons, Lluís; Aquilué, Núria; de Cáceres, Miquel; Fortin, Marie-Josée; Fall, Andrew

2013-01-01

Available data show that future changes in global change drivers may lead to an increasing impact of fires on terrestrial ecosystems worldwide. Yet, fire regime changes in highly humanised fire-prone regions are difficult to predict because fire effects may be heavily mediated by human activities We investigated the role of fire suppression strategies in synergy with climate change on the resulting fire regimes in Catalonia (north-eastern Spain). We used a spatially-explicit fire-succession model at the landscape level to test whether the use of different firefighting opportunities related to observed reductions in fire spread rates and effective fire sizes, and hence changes in the fire regime. We calibrated this model with data from a period with weak firefighting and later assess the potential for suppression strategies to modify fire regimes expected under different levels of climate change. When comparing simulations with observed fire statistics from an eleven-year period with firefighting strategies in place, our results showed that, at least in two of the three sub-regions analysed, the observed fire regime could not be reproduced unless taking into account the effects of fire suppression. Fire regime descriptors were highly dependent on climate change scenarios, with a general trend, under baseline scenarios without fire suppression, to large-scale increases in area burnt. Fire suppression strategies had a strong capacity to compensate for climate change effects. However, strong active fire suppression was necessary to accomplish such compensation, while more opportunistic fire suppression strategies derived from recent fire history only had a variable, but generally weak, potential for compensation of enhanced fire impacts under climate change. The concept of fire regime in the Mediterranean is probably better interpreted as a highly dynamic process in which the main determinants of fire are rapidly modified by changes in landscape, climate and

In the suppression of regge cut contributions

International Nuclear Information System (INIS)

Chia, S.P.

1975-07-01

It is shown that contributions of reggeon-pomeron cuts are suppressed in amplitudes with opposite natural to the reggeon. This suppression grows logarithmically with energy. The suppression in the πP cut is, however, found to be weak. Consequence on conspiracy is discussed

Closing the water cycle - the key role of water and wastewater management in a circular economy

Science.gov (United States)

Uhlenbrook, Stefan; Connor, Rick; Koncagul, Engin; Ortigara, Angela

2017-04-01

Planetary water boundaries are exceeded locally and regionally as water demand and use are escalating and per capita water availability is decreasing. However, wastewater represents an alternative yet reliable source containing for instance, nutrients (for use as fertilizer) and metals that can be extracted, and can be a source of energy. These characteristics mean that water and wastewater are set to play a key role in the circular economy. Furthermore, wastewater use can generate business opportunities and enhance water, food and energy security, therefore helping to alleviate poverty. However, to increase the collection, treatment and use of wastewater, investments in infrastructure and appropriate (low cost) technologies are needed. Ensuring the development of human and institutional capacity is also essential for proper wastewater management. The UN World Water Assessment Programme (WWAP) produces together with several UN-Water Members and Partners the annual World Water Development Report (WWDR). Its 2017 edition "Wastewater: The Untapped Resource" focuses on the critical role of wastewater management for vibrant economies, resilient societies and the maintenance of a healthy environment. Wastewater issues play also a central role in the 2030 Agenda for Sustainable Development, most notably through Sustainable Development Goal (SDG) target 6.3 that aims to improve water quality by reducing the proportion of untreated wastewater released to the environment and increasing its recycling and safe reuse globally. This target is interlinked with several other targets of SDG 6 ('the water goal') as well as to several other SDGs that relate to, poverty reduction, health, energy and food security, among others. The main policy-relevant messages of the WWDR 2017 will be introduced and linked to socio-hydrological approaches. These messages are an important input to the implementation of the water research agenda of the Panta Rhei initiative of IAHS.

Lipid profiling demonstrates that suppressing Arabidopsis phospholipase Dδ retards ABA-promoted leaf senescence by attenuating lipid degradation.

Directory of Open Access Journals (Sweden)

Yanxia Jia

Full Text Available Senescence is the last phase of the plant life cycle and has an important role in plant development. Degradation of membrane lipids is an essential process during leaf senescence. Several studies have reported fundamental changes in membrane lipids and phospholipase D (PLD activity as leaves senesce. Suppression of phospholipase Dα1 (PLDα1 retards abscisic acid (ABA-promoted senescence. However, given the absence of studies that have profiled changes in the compositions of membrane lipid molecules during leaf senescence, there is no direct evidence that PLD affects lipid composition during the process. Here, we show that application of n-butanol, an inhibitor of PLD, and N-Acylethanolamine (NAE 12∶0, a specific inhibitor of PLDα1, retarded ABA-promoted senescence to different extents. Furthermore, phospholipase Dδ (PLDδ was induced in leaves treated with ABA, and suppression of PLDδ retarded ABA-promoted senescence in Arabidopsis. Lipid profiling revealed that detachment-induced senescence had different effects on plastidic and extraplastidic lipids. The accelerated degradation of plastidic lipids during ABA-induced senescence in wild-type plants was attenuated in PLDδ-knockout (PLDδ-KO plants. Dramatic increases in phosphatidic acid (PA and decreases in phosphatidylcholine (PC during ABA-induced senescence were also suppressed in PLDδ-KO plants. Our results suggest that PLDδ-mediated hydrolysis of PC to PA plays a positive role in ABA-promoted senescence. The attenuation of PA formation resulting from suppression of PLDδ blocks the degradation of membrane lipids, which retards ABA-promoted senescence.

A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

Science.gov (United States)

Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

2016-07-29

Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens.

[The advances of suppression in research of amblyopia].

Science.gov (United States)

Liu, S; Liu, H

2016-04-11

Suppression that is the result of interocular competition is an important machanism of amblyopia. The imbalance of suppression may lead the consequence to amblyopia. In the early study, researchers had raised the theory of II. Quadratic Summation which had revealed the relationship of interocular interaction and suppression. In some basic researches, other studies had showed the most possible anatomic location of suppression. Recently, researchers found a new method to quantify the interocular suppression named the noise model. Further studies found a novel disinhibition therapy to treat amblyopia. We summarized the research advances in suppression and disinhibition treatment in amblyopia. (Chin J Ophthalmol, 2016, 52: 305-308).

Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages

International Nuclear Information System (INIS)

Kinoshita, Hiroyuki; Matsumura, Takeshi; Ishii, Norio; Fukuda, Kazuki; Senokuchi, Takafumi; Motoshima, Hiroyuki; Kondo, Tatsuya; Taketa, Kayo; Kawasaki, Shuji; Hanatani, Satoko; Takeya, Motohiro; Nishikawa, Takeshi; Araki, Eiichi

2013-01-01

Highlights: ► We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ► Apocynin prevented atherosclerotic lesion formation. ► Apocynin suppressed ROS production in aorta and in macrophages. ► Apocynin suppressed cytokine expression and cell proliferation in macrophages. ► Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progression of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE –/– ) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE –/– mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE –/– mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis

Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages

Energy Technology Data Exchange (ETDEWEB)

Kinoshita, Hiroyuki [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Ishii, Norio; Fukuda, Kazuki; Senokuchi, Takafumi; Motoshima, Hiroyuki; Kondo, Tatsuya; Taketa, Kayo; Kawasaki, Shuji; Hanatani, Satoko [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Takeya, Motohiro [Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Nishikawa, Takeshi; Araki, Eiichi [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)

2013-02-08

Highlights: ► We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ► Apocynin prevented atherosclerotic lesion formation. ► Apocynin suppressed ROS production in aorta and in macrophages. ► Apocynin suppressed cytokine expression and cell proliferation in macrophages. ► Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progression of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE{sup –/–}) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE{sup –/–} mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE{sup –/–} mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis.

Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae-Sung, E-mail: Jae.Kim@surgery.ufl.edu; Wang, Jin-Hee, E-mail: jin-hee.wang@surgery.ufl.edu; Biel, Thomas G., E-mail: Thomas.Biel@surgery.ufl.edu; Kim, Do-Sung, E-mail: do-sung.kim@surgery.med.ufl.edu; Flores-Toro, Joseph A., E-mail: Joseph.Flores-Toro@surgery.ufl.edu; Vijayvargiya, Richa, E-mail: rvijayvargiya@ufl.edu; Zendejas, Ivan, E-mail: ivan.zendejas@surgery.ufl.edu; Behrns, Kevin E., E-mail: Kevin.Behrns@surgery.ufl.edu

2013-12-15

Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 μM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R. - Highlights: • A mechanism of carbamazepine (CBZ)-induced cytoprotection in livers is proposed. • Impaired autophagy is a key event contributing to lethal reperfusion injury. • The importance of autophagy is extended and confirmed in an in vivo model. • CBZ is a potential

Evidence for the Role of BAG3 in Mitochondrial Quality Control in Cardiomyocytes.

Science.gov (United States)

Tahrir, Farzaneh G; Knezevic, Tijana; Gupta, Manish K; Gordon, Jennifer; Cheung, Joseph Y; Feldman, Arthur M; Khalili, Kamel

2017-04-01

Mitochondrial abnormalities impact the development of myofibrillar myopathies. Therefore, understanding the mechanisms underlying the removal of dysfunctional mitochondria from cells is of great importance toward understanding the molecular events involved in the genesis of cardiomyopathy. Earlier studies have ascribed a role for BAG3 in the development of cardiomyopathy in experimental animals leading to the identification of BAG3 mutations in patients with heart failure which may play a part in the onset of disease development and progression. BAG3 is co-chaperone of heat shock protein 70 (HSP70), which has been shown to modulate apoptosis and autophagy, in several cell models. In this study, we explore the potential role of BAG3 in mitochondrial quality control. We demonstrate that siRNA mediated suppression of BAG3 production in neonatal rat ventricular cardiomyocytes (NRVCs) significantly elevates the level of Parkin, a key component of mitophagy. We found that both BAG3 and Parkin are recruited to depolarized mitochondria and promote mitophagy. Suppression of BAG3 in NRVCs significantly reduces autophagy flux and eliminates clearance of Tom20, an essential import receptor for mitochondria proteins, after induction of mitophagy. These observations suggest that BAG3 is critical for the maintenance of mitochondrial homeostasis under stress conditions, and disruptions in BAG3 expression impact cardiomyocyte function. J. Cell. Physiol. 232: 797-805, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Role of Active Listening and Listening Effort on Contralateral Suppression of Transient Evoked Otoacousic Emissions

OpenAIRE

Kalaiah, Mohan Kumar; Theruvan, Nikhitha B; Kumar, Kaushlendra; Bhat, Jayashree S

2017-01-01

Background and Objectives The present study aimed to investigate the effect of active listening and listening effort on the contralateral suppression of transient evoked otoacoustic emissions (CSTEOAEs). Subjects and Methods Twenty eight young adults participated in the study. Transient evoked otoacoustic emissions (TEOAEs) were recorded using ?linear? clicks at 60 dB peSPL, in three contralateral noise conditions. In condition 1, TEOAEs were obtained in the presence of white noise in the con...

Poppers: more evidence of suppressed immunity.

Science.gov (United States)

James, J S

1999-08-20

Evidence from studies in mice shows that exposure to isobutyl nitrite suppresses the immune system. This immune suppression allows for bacterial growth in the lungs and livers of infected mice and can inhibit the ability of mediastinal lymph nodes to respond to antigen-specific stimulation. The mechanism for immune suppression may be a reduction in CD4+ and CD8+ T cell populations in the mediastinal lymph nodes following pulmonary infection with Listeria monocytogenes.

Objective assessment of subjective tinnitus through contralateral suppression of otoacoustic emissions by white noise; suggested cut-off points.

Science.gov (United States)

Riga, M; Komis, A; Maragkoudakis, P; Korres, G; Danielides, V

2016-12-01

Normative otoacoustic emission (OAE) suppression values are currently lacking and the role of cochlear efferent innervation in tinnitus is controversial. The aim of this study was to investigate the association between tinnitus and medial olivocochlear bundle (MOCB) malfunction. Potential suppression amplitude cut-off criteria that could differentiate participants with tinnitus from those without were sought. Mean suppression amplitudes of transient evoked OAEs and distortion product OAEs by contralateral white noise (50 dBSL) were recorded. Six mean suppression amplitudes criteria were validated as possible cut-off points. The population consisted of normal hearing (n = 78) or presbycusic adults (n = 19) with tinnitus or without (n = 28 and 13, respectively) chronic tinnitus (in total, n = 138 78 females/60males, aged 49 ± 14 years). Participants with mean suppression values lower than 0.5-1 dBSPL seem to present a high probability to report tinnitus (specificity 88-97%). On the other hand, participants with mean suppression values larger than 2-2.5dBSPL seem to present a high probability of the absence of tinnitus (sensitivity 87-99%). Correlations were stronger among participants with bilateral presence or absence of tinnitus. This study seem to confirm an association between tinnitus and low suppression amplitudes (<1 dBSPL), which might evolve into an objective examination tool, supplementary to conventional audiological testing.

Knockdown of p53 suppresses Nanog expression in embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Abdelalim, Essam Mohamed, E-mail: emohamed@qf.org.qa [Qatar Biomedical Research Institute, Qatar Foundation, Doha 5825 (Qatar); Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan); Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia (Egypt); Tooyama, Ikuo [Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan)

2014-01-10

Highlights: •We investigate the role of p53 in ESCs in the absence of DNA damage. •p53 knockdown suppresses ESC proliferation. •p53 knockdown downregulates Nanog expression. •p53 is essential for mouse ESC self-renewal. -- Abstract: Mouse embryonic stem cells (ESCs) express high levels of cytoplasmic p53. Exposure of mouse ESCs to DNA damage leads to activation of p53, inducing Nanog suppression. In contrast to earlier studies, we recently reported that chemical inhibition of p53 suppresses ESC proliferation. Here, we confirm that p53 signaling is involved in the maintenance of mouse ESC self-renewal. RNA interference-mediated knockdown of p53 induced downregulation of p21 and defects in ESC proliferation. Furthermore, p53 knockdown resulted in a significant downregulation in Nanog expression at 24 and 48 h post-transfection. p53 knockdown also caused a reduction in Oct4 expression at 48 h post-transfection. Conversely, exposure of ESCs to DNA damage caused a higher reduction of Nanog expression in control siRNA-treated cells than in p53 siRNA-treated cells. These data show that in the absence of DNA damage, p53 is required for the maintenance of mouse ESC self-renewal by regulating Nanog expression.

Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

International Nuclear Information System (INIS)

Park, Sung-Dong; Cheon, So Yeong; Park, Tae-Yoon; Shin, Bo-Young; Oh, Hyunju; Ghosh, Sankar; Koo, Bon-Nyeo; Lee, Sang-Kyou

2015-01-01

Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. - Highlights: • The nt-p65-TMD is intra-nuclear interactomic inhibitor of endogenous p65. • The nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines. • The excellent therapeutic potential of nt-p65-TMD was confirmed in sepsis model

Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

Energy Technology Data Exchange (ETDEWEB)

Park, Sung-Dong [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Cheon, So Yeong [Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Park, Tae-Yoon; Shin, Bo-Young [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Oh, Hyunju; Ghosh, Sankar [Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Koo, Bon-Nyeo, E-mail: koobn@yuhs.ac [Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Sang-Kyou, E-mail: sjrlee@yonsei.ac.kr [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

2015-08-28

Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. - Highlights: • The nt-p65-TMD is intra-nuclear interactomic inhibitor of endogenous p65. • The nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines. • The excellent therapeutic potential of nt-p65-TMD was confirmed in sepsis model.

Regional Extent of Peripheral Suppression in Amblyopia.

Science.gov (United States)

Babu, Raiju J; Clavagnier, Simon; Bobier, William R; Thompson, Benjamin; Hess, Robert F

2017-04-01

Previously, we have mapped amblyopic eye suppression within the central 20° of the visual field and observed a gradient of suppression that is strongest in central vision and weakens with increasing eccentricity. In this study, using a large dichoptic display, we extend our novel suppression mapping approach further into the periphery (from 20°-60°) to assess whether suppression continues to decline with eccentricity or plateaus. Sixteen participants with amblyopia (10 with strabismus, 6 with anisometropia without strabismus; mean age: 37.9 ± 11 years) and six normal observers (mean age: 28.3 ± 5 years) took part. The visual stimulus (60° diameter), viewed from 57 cm, was composed of four concentric annuli (5° radius) with alternate contrast polarities starting from an eccentricity of 10°. Each annulus was divided into eight sectors subtending 45° of visual angle. Participants adjusted the contrast of a single sector presented to the fellow eye to match the perceived contrast of the remaining stimulus elements that were presented to the amblyopic eye. A matching contrast that was lower in the fellow eye than the amblyopic eye indicated suppression. Patients with strabismus exhibited significantly stronger interocular suppression than controls across all eccentricities (P = 0.01). Patients with anisometropia did not differ from controls (P = 0.58). Suppression varied significantly with eccentricity (P = 0.005) but this effect did not differ between patient groups (P = 0.217). In amblyopia, suppression is present beyond the central 10° in patients with strabismus. Suppression becomes weaker at greater eccentricities and this may enable peripheral fusion that could be used by binocular treatment methods.

Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model

Energy Technology Data Exchange (ETDEWEB)

Xiao, Fei; Zhai, Zanjing; Jiang, Chuan; Liu, Xuqiang; Li, Haowei; Qu, Xinhua [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Ouyang, Zhengxiao [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 (China); Fan, Qiming; Tang, Tingting [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Qin, An, E-mail: dr.qinan@gmail.com [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Gu, Dongyun, E-mail: dongyungu@gmail.com [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Engineering Research Center of Digital Medicine and Clinical Translation, Ministry of Education of PR China (China); School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030 (China)

2015-01-01

Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure. - Highlights: • Geraniin suppresses osteoclasts formation and function in vitro. • Geraniin impairs RANKL-induced nuclear factor-κB and ERK signaling pathway. • Geraniin suppresses osteolysis in vivo. • Geraniin may be used for treating osteoclast related diseases.

The hydroxyflavone, fisetin, suppresses mast cell activation induced by interaction with activated T cell membranes

Science.gov (United States)

Nagai, K; Takahashi, Y; Mikami, I; Fukusima, T; Oike, H; Kobori, M

2009-01-01

Background and purpose: Cell-to-cell interactions between mast cells and activated T cells are increasingly recognized as a possible mechanism in the aetiology of allergic or non-allergic inflammatory disorders. To determine the anti-allergic effect of fisetin, we examined the ability of fisetin to suppress activation of the human mast cell line, HMC-1, induced by activated Jurkat T cell membranes. Experimental approach: HMC-1 cells were incubated with or without fisetin for 15 min and then co-cultured with Jurkat T cell membranes activated by phorbol-12-myristate 13-acetate for 16 h. We determined gene expression in activated HMC-1 cells by DNA microarray and quantitative reverse transcription (RT)-PCR analysis. We also examined activation of the transcription factor NF-κB and MAP kinases (MAPKs) in activated HMC-1 cells. Key results: Fisetin suppresses cell spreading and gene expression in HMC-1 cells stimulated by activated T cell membranes. Additionally, we show that these stimulated HMC-1 cells expressed granzyme B. The stimulatory interaction also induced activation of NF-κB and MAPKs; these activations were suppressed by fisetin. Fisetin also reduced the amount of cell surface antigen CD40 and intercellular adhesion molecule-1 (ICAM-1) on activated HMC-1 cells. Conclusions and implications: Fisetin suppressed activation of HMC-1 cells by activated T cell membranes by interfering with cell-to-cell interaction and inhibiting the activity of NF-κB and MAPKs and thereby suppressing gene expression. Fisetin may protect against the progression of inflammatory diseases by limiting interactions between mast cells and activated T cells. PMID:19702784

Helminth-induced regulatory T cells and suppression of allergic responses.

Science.gov (United States)

Logan, Jayden; Navarro, Severine; Loukas, Alex; Giacomin, Paul

2018-05-28

Infection with helminths has been associated with lower rates of asthma and other allergic diseases. This has been attributed, in part, to the ability of helminths to induce regulatory T cells that suppress inappropriate immune responses to allergens. Recent compelling evidence suggests that helminths may promote regulatory T cell expansion or effector functions through either direct (secretion of excretory/secretory molecules) or indirect mechanisms (regulation of the microbiome). This review will discuss key findings from human immunoepidemiological observations, studies using animal models of disease, and clinical trials with live worm infections, discussing the therapeutic potential for worms and their secreted products for treating allergic inflammation. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

The emerging role of Big Data in key development issues: Opportunities, challenges, and concerns

Directory of Open Access Journals (Sweden)

Nir Kshetri

2014-12-01

Full Text Available This paper presents a review of academic literature, policy documents from government organizations and international agencies, and reports from industries and popular media on the trends in Big Data utilization in key development issues and its worthwhileness, usefulness, and relevance. By looking at Big Data deployment in a number of key economic sectors, it seeks to provide a better understanding of the opportunities and challenges of using it for addressing key issues facing the developing world. It reviews the uses of Big Data in agriculture and farming activities in developing countries to assess the capabilities required at various levels to benefit from Big Data. It also provides insights into how the current digital divide is associated with and facilitated by the pattern of Big Data diffusion and its effective use in key development areas. It also discusses the lessons that developing countries can learn from the utilization of Big Data in big corporations as well as in other activities in industrialized countries.

Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Takahashi, Nobuhiko; Yoshizaki, Takayuki; Hiranaka, Natsumi; Suzuki, Takeshi; Yui, Tomoo; Akanuma, Masayoshi; Kanazawa, Kaoru; Yoshida, Mika; Naito, Sumiyoshi; Fujiya, Mikihiro; Kohgo, Yutaka; Ieko, Masahiro

2013-01-01

Highlights: ► Lipin-1 involves lipid metabolism, adipocyte differentiation, and inflammation. ► Adipose lipin-1 expression is reduced in obesity. ► ER stress suppresses lipin-1 expression in 3T3-L1 adipocytes. ► Activation of PPAR-γ recovers ER stress-induced lipin-1 reduction. -- Abstract: Lipin-1 plays crucial roles in the regulation of lipid metabolism and cell differentiation in adipocytes. In obesity, adipose lipin-1 mRNA expression is decreased and positively correlated with systemic insulin sensitivity. Amelioration of the lipin-1 depletion might be improved dysmetabolism. Although some cytokines such as TNF-α and interleukin-1β reduces adipose lipin-1 expression, the mechanism of decreased adipose lipin-1 expression in obesity remains unclear. Recently, endoplasmic reticulum (ER) stress is implicated in the pathogenesis of obesity. Here we investigated the role of ER stress on the lipin-1 expression in 3T3-L1 adipocytes. We demonstrated that lipin-1 expression was suppressed by the treatment with ER stress inducers (tunicamycin and thapsigargin) at transcriptional level. We also showed that constitutive lipin-1 expression could be maintained by peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes. Activation of peroxisome proliferator-activated receptor-γ recovered the ER stress-induced lipin-1 suppression. These results suggested that ER stress might be involved in the pathogenesis of obesity through lipin-1 depletion

Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes

Energy Technology Data Exchange (ETDEWEB)

Takahashi, Nobuhiko, E-mail: ntkhs@hoku-iryo-u.ac.jp [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Yoshizaki, Takayuki [Innovation Center, Kagoshima University, 1-21-40, Korimoto, Kagoshima 890-0065 (Japan); Hiranaka, Natsumi; Suzuki, Takeshi [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yui, Tomoo; Akanuma, Masayoshi [Department of Fixed Prosthodontics and Oral Implantology, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Kanazawa, Kaoru [Department of Dental Anesthesiology, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yoshida, Mika; Naito, Sumiyoshi [Department of Clinical Laboratory, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Fujiya, Mikihiro; Kohgo, Yutaka [Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Ieko, Masahiro [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan)

2013-02-01

Highlights: ► Lipin-1 involves lipid metabolism, adipocyte differentiation, and inflammation. ► Adipose lipin-1 expression is reduced in obesity. ► ER stress suppresses lipin-1 expression in 3T3-L1 adipocytes. ► Activation of PPAR-γ recovers ER stress-induced lipin-1 reduction. -- Abstract: Lipin-1 plays crucial roles in the regulation of lipid metabolism and cell differentiation in adipocytes. In obesity, adipose lipin-1 mRNA expression is decreased and positively correlated with systemic insulin sensitivity. Amelioration of the lipin-1 depletion might be improved dysmetabolism. Although some cytokines such as TNF-α and interleukin-1β reduces adipose lipin-1 expression, the mechanism of decreased adipose lipin-1 expression in obesity remains unclear. Recently, endoplasmic reticulum (ER) stress is implicated in the pathogenesis of obesity. Here we investigated the role of ER stress on the lipin-1 expression in 3T3-L1 adipocytes. We demonstrated that lipin-1 expression was suppressed by the treatment with ER stress inducers (tunicamycin and thapsigargin) at transcriptional level. We also showed that constitutive lipin-1 expression could be maintained by peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes. Activation of peroxisome proliferator-activated receptor-γ recovered the ER stress-induced lipin-1 suppression. These results suggested that ER stress might be involved in the pathogenesis of obesity through lipin-1 depletion.

CONDITIONS FOR CSR MICROBUNCHING GAIN SUPPRESSION

Energy Technology Data Exchange (ETDEWEB)

Tsai, Cheng Ying [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Douglas, David R. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Li, Rui [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Tennant, Christopher D. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); di Mitri, Simone [Elettra–Sincrotrone Trieste, 34149 Basovizza, Trieste, Italy

2016-05-01

The coherent synchrotron radiation (CSR) of a high brightness electron beam traversing a series of dipoles, such as transport arcs, may result in phase space degradation. On one hand, the CSR can perturb electron transverse motion in dispersive regions along the beamline, causing emittance growth. On the other hand, the CSR effect on the longitudinal beam dynamics could result in microbunching gain enhancement. For transport arcs, several schemes have been proposed* to suppress the CSR-induced emittance growth. Similarly, several scenarios have been introduced** to suppress CSR-induced microbunching gain, which however mostly aim for linac-based machines. In this paper we try to provide sufficient conditions for suppression of CSR-induced microbunching gain along a transport arc, analogous to*. Several example lattices are presented, with the relevant microbunching analyses carried out by our semi-analytical Vlasov solver***. The simulation results show that lattices satisfying the proposed conditions indeed have microbunching gain suppressed. We expect this analysis can shed light on lattice design approach that could suppress the CSR-induced microbunching gain.

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study.

Science.gov (United States)

Kilduff, Claire E; Counter, Melanie J; Thomas, Gareth A; Harrison, Nicholas K; Hope-Gill, Benjamin D

2014-01-01

Chronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. Eighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks. Total reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70). This study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use

Two Alkaloids from Bulbs of Lycoris sanguinea MAXIM. Suppress PEPCK Expression by Inhibiting the Phosphorylation of CREB.

Science.gov (United States)

Yun, Young Sook; Tajima, Miki; Takahashi, Shigeru; Takahashi, Yuji; Umemura, Mariko; Nakano, Haruo; Park, Hyun Sun; Inoue, Hideshi

2016-10-01

In the fasting state, gluconeogenesis is upregulated by glucagon. Glucagon stimulates cyclic adenosine monophosphate production, which induces the expression of key enzymes for gluconeogenesis, such as cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), which are involved in gluconeogenesis through the protein kinase A/cAMP response element-binding protein (CREB) pathway. Using a luciferase reporter gene assay, a methanol extract of the bulbs of Lycoris sanguinea M AXIM. var. kiushiana Makino was found to suppress cAMP-enhanced PEPCK-C promoter activity. In addition, two alkaloids, lycoricidine and lycoricidinol, in the extract were identified as active constituents. In forskolin-stimulated human hepatoma cells, these alkaloids suppressed the expression of a reporter gene under the control of cAMP response element and also prevented increases in the endogenous levels of phosphorylated CREB and PEPCK mRNA expression. These results suggest that lycoricidine and lycoricidinol suppress PEPCK-C expression by inhibiting the phosphorylation of CREB and may thus have the potential to prevent excessive gluconeogenesis in type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Behavioral and EEG evidence for auditory memory suppression

Directory of Open Access Journals (Sweden)

Maya Elizabeth Cano

2016-03-01

Full Text Available The neural basis of motivated forgetting using the Think/No-Think (TNT paradigm is receiving increased attention with a particular focus on the mechanisms that enable memory suppression. However, most TNT studies have been limited to the visual domain. To assess whether and to what extent direct memory suppression extends across sensory modalities, we examined behavioral and electroencephalographic (EEG effects of auditory Think/No-Think in healthy young adults by adapting the TNT paradigm to the auditory modality. Behaviorally, suppression of memory strength was indexed by prolonged response times during the retrieval of subsequently remembered No-Think words. We examined task-related EEG activity of both attempted memory retrieval and inhibition of a previously learned target word during the presentation of its paired associate. Event-related EEG responses revealed two main findings: 1 a centralized Think > No-Think positivity during auditory word presentation (from approximately 0-500ms, and 2 a sustained Think positivity over parietal electrodes beginning at approximately 600ms reflecting the memory retrieval effect which was significantly reduced for No-Think words. In addition, word-locked theta (4-8 Hz power was initially greater for No-Think compared to Think during auditory word presentation over fronto-central electrodes. This was followed by a posterior theta increase indexing successful memory retrieval in the Think condition.The observed event-related potential pattern and theta power analysis are similar to that reported in visual Think/No-Think studies and support a modality non-specific mechanism for memory inhibition. The EEG data also provide evidence supporting differing roles and time courses of frontal and parietal regions in the flexible control of auditory memory.

Suppression of iron-regulatory hepcidin by vitamin D.

Science.gov (United States)

Bacchetta, Justine; Zaritsky, Joshua J; Sea, Jessica L; Chun, Rene F; Lisse, Thomas S; Zavala, Kathryn; Nayak, Anjali; Wesseling-Perry, Katherine; Westerman, Mark; Hollis, Bruce W; Salusky, Isidro B; Hewison, Martin

2014-03-01

The antibacterial protein hepcidin regulates the absorption, tissue distribution, and extracellular concentration of iron by suppressing ferroportin-mediated export of cellular iron. In CKD, elevated hepcidin and vitamin D deficiency are associated with anemia. Therefore, we explored a possible role for vitamin D in iron homeostasis. Treatment of cultured hepatocytes or monocytes with prohormone 25-hydroxyvitamin D or active 1,25-dihydroxyvitamin D decreased expression of hepcidin mRNA by 0.5-fold, contrasting the stimulatory effect of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D on related antibacterial proteins such as cathelicidin. Promoter-reporter and chromatin immunoprecipitation analyses indicated that direct transcriptional suppression of hepcidin gene (HAMP) expression mediated by 1,25-dihydroxyvitamin D binding to the vitamin D receptor caused the decrease in hepcidin mRNA levels. Suppression of HAMP expression was associated with a concomitant increase in expression of the cellular target for hepcidin, ferroportin protein, and decreased expression of the intracellular iron marker ferritin. In a pilot study with healthy volunteers, supplementation with a single oral dose of vitamin D (100,000 IU vitamin D2) increased serum levels of 25D-hydroxyvitamin D from 27±2 ng/ml before supplementation to 44±3 ng/ml after supplementation (P<0.001). This response was associated with a 34% decrease in circulating levels of hepcidin within 24 hours of vitamin D supplementation (P<0.05). These data show that vitamin D is a potent regulator of the hepcidin-ferroportin axis in humans and highlight a potential new strategy for the management of anemia in patients with low vitamin D and/or CKD.

Behavioral and EEG Evidence for Auditory Memory Suppression.

Science.gov (United States)

Cano, Maya E; Knight, Robert T

2016-01-01

The neural basis of motivated forgetting using the Think/No-Think (TNT) paradigm is receiving increased attention with a particular focus on the mechanisms that enable memory suppression. However, most TNT studies have been limited to the visual domain. To assess whether and to what extent direct memory suppression extends across sensory modalities, we examined behavioral and electroencephalographic (EEG) effects of auditory TNT in healthy young adults by adapting the TNT paradigm to the auditory modality. Behaviorally, suppression of memory strength was indexed by prolonged response time (RTs) during the retrieval of subsequently remembered No-Think words. We examined task-related EEG activity of both attempted memory retrieval and inhibition of a previously learned target word during the presentation of its paired associate. Event-related EEG responses revealed two main findings: (1) a centralized Think > No-Think positivity during auditory word presentation (from approximately 0-500 ms); and (2) a sustained Think positivity over parietal electrodes beginning at approximately 600 ms reflecting the memory retrieval effect which was significantly reduced for No-Think words. In addition, word-locked theta (4-8 Hz) power was initially greater for No-Think compared to Think during auditory word presentation over fronto-central electrodes. This was followed by a posterior theta increase indexing successful memory retrieval in the Think condition. The observed event-related potential pattern and theta power analysis are similar to that reported in visual TNT studies and support a modality non-specific mechanism for memory inhibition. The EEG data also provide evidence supporting differing roles and time courses of frontal and parietal regions in the flexible control of auditory memory.

Measuring Public Leadership: Developing Scales for Four Key Public Leadership Roles

NARCIS (Netherlands)

Tummers, Lars; Knies, Eva|info:eu-repo/dai/nl/313875421

2016-01-01

This article on public leadership contributes to the literature by (1) focusing on the ‘public’ aspect of leadership and (2) developing quantitative scales for measuring four public leadership roles. These roles all refer to the extent to which public leaders actively support their employees in

Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice.

Science.gov (United States)

Xu, Bing; Jiang, Mingzuo; Chu, Yi; Wang, Weijie; Chen, Di; Li, Xiaowei; Zhang, Zhao; Zhang, Di; Fan, Daiming; Nie, Yongzhan; Shao, Feng; Wu, Kaichun; Liang, Jie

2017-12-20

Gasdermin D (GSDMD)-executed programmed necrosis is involved in inflammation and controls interleukin (IL)-1β release. However, the role of GSDMD in non-alcoholic steatohepatitis (NASH) remains unclear. We investigated the role of GSDMD in the pathogenesis of steatohepatitis. Human liver tissues from patients with non-alcoholic fatty liver disease (NAFLD) and control individuals were obtained to evaluate GSDMD expression. Gsdmd knockout (Gsdmd -/- ) mice, obese db/db mice and their wild-type (WT) littermates were fed with methionine-choline deficient (MCD) or control diet to induce steatohepatitis. The Gsdmd -/- and WT mice were also used in a high-fat diet (HFD)-induced NAFLD model. In addition, Alb-Cre mice were administered an adeno-associated virus (AAV) vector that expressed the gasdermin-N domain (AAV9-FLEX-GSDMD-N) and were fed with either MCD or control diet for 10 days. GSDMD and its pyroptosis-inducing fragment GSDMD-N were upregulated in liver tissues of human NAFLD/NASH. Importantly, hepatic GSDMD-N protein levels were significantly higher in human NASH and correlated with the NAFLD activity score and fibrosis. GSDMD-N remained a potential biomarker for the diagnosis of NASH. MCD-fed Gsdmd -/- mice exhibit decreased severity of steatosis and inflammation compared with WT littermates. GSDMD was associated with the secretion of pro-inflammatory cytokines (IL-1β, TNF-α, and MCP-1 [CCL2]) and persistent activation of the NF-ĸB signaling pathway. Gsdmd -/- mice showed lower steatosis, mainly because of reduced expression of the lipogenic gene Srebp1c (Srebf1) and upregulated expression of lipolytic genes, including Pparα, Aco [Klk15], Lcad [Acadl], Cyp4a10 and Cyp4a14. Alb-Cre mice administered with AAV9-FLEX-GSDMD-N showed significantly aggravated steatohepatitis when fed with MCD diet. As an executor of pyroptosis, GSDMD plays a key role in the pathogenesis of steatohepatitis, by controlling cytokine secretion, NF-ĸB activation, and lipogenesis

The Stiffness and Damping Characteristics of a Dual-Chamber Air Spring Device Applied to Motion Suppression of Marine Structures

Directory of Open Access Journals (Sweden)

Xiaohui Zeng

2016-03-01

Full Text Available Dual-chamber air springs are used as a key component for vibration isolation in some industrial applications. The working principle of the dual-chamber air spring device as applied to motion suppression of marine structures is similar to that of the traditional air spring, but they differ in their specific characteristics. The stiffness and damping of the dual-chamber air spring device determine the extent of motion suppression. In this article, we investigate the stiffness and damping characteristics of a dual-chamber air spring device applied to marine structure motion suppression using orthogonal analysis and an experimental method. We measure the effects of volume ratio, orifice ratio, excitation amplitude, and frequency on the stiffness and damping of the dual-chamber vibration absorber. Based on the experimental results, a higher-order non-linear regression method is obtained. We achieve a rapid calculation model for dual-chamber air spring stiffness and damping, which can provide guidance to project design.

Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera.

Science.gov (United States)

Gallardo, Miguel; Barrio, Santiago; Fernandez, Marisol; Paradela, Alberto; Arenas, Alicia; Toldos, Oscar; Ayala, Rosa; Albizua, Enriqueta; Jimenez, Ana; Redondo, Santiago; Garcia-Martin, Rosa Maria; Gilsanz, Florinda; Albar, Juan Pablo; Martinez-Lopez, Joaquin

2013-11-19

JAK-STAT signaling through the JAK2V617F mutation is central to the pathogenesis of myeloproliferative neoplasms (MPN). However, other events could precede the JAK2 mutation. The aim of this study is to analyze the phenotypic divergence between polycytemia vera (PV) and essential thrombocytemia (ET) to find novel therapeutics targets by a proteomic and functional approach to identify alternative routes to JAK2 activation. Through 2D-DIGE and mass spectrometry of granulocyte protein from 20 MPN samples, showed differential expression of HSP70 in PV and ET besides other 60 proteins. Immunohistochemistry of 46 MPN bone marrow samples confirmed HSP70 expression. The median of positive granulocytes was 80% in PV (SD 35%) vs. 23% in ET (SD 34.25%). In an ex vivo model KNK437 was used as an inhibition model assay of HSP70, showed dose-dependent inhibition of cell growth and burst formation unit erythroid (BFU-E) in PV and ET, increased apoptosis in the erythroid lineage, and decreased pJAK2 signaling, as well as a specific siRNA for HSP70. These data suggest a key role for HSP70 in proliferation and survival of the erythroid lineage in PV, and may represent a potential therapeutic target in MPN, especially in PV.

Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy.

Science.gov (United States)

Jemail, Leila; Miyao, Masashi; Kotani, Hirokazu; Kawai, Chihiro; Minami, Hirozo; Abiru, Hitoshi; Tamaki, Keiji

2018-04-23

Kupffer cells (KCs) are key players in maintaining tissue homeostasis and are involved in various liver diseases. However, the roles of KCs in the pathogenesis of cholangiopathy are largely unknown. We aimed to investigate the precise roles of KCs in both the progression and regression phases of the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy model. In the early phase of DDC-induced cholangiopathy, the number of KCs significantly increased over time. Moreover, KCs were associated with abnormal phenotypic changes in other liver cells, such as hepatocytes, biliary epithelial cells, liver sinusoidal endothelial cells, and hepatic stellate cells. In contrast, KC depletion by clodronate administration suppressed the progression of the disease, and maintained the phenotypes of other cells. In the regression phase, the numbers of KCs significantly decreased, and the cells redifferentiated to their quiescent state. In contrast, KC depletion delayed the recovery of cells by maintaining other liver cells in an active state. These findings suggest that KCs play detrimental roles in the progression phase; however, they are beneficial in the regression phase by mediating interactions between other liver cells. Our data provide new insights into the roles of KCs in the pathogenesis of cholangiopathy.

Purinergic Receptors: Key Mediators of HIV-1 infection and inflammation

Directory of Open Access Journals (Sweden)

Talia H Swartz

2015-11-01

Full Text Available Human immunodeficiency virus (HIV-1 causes a chronic infection that afflicts more than 38 million individuals worldwide. While the infection can be suppressed with potent anti-retroviral therapies, individuals infected with HIV have elevated levels of inflammation as indicated by increased T cell activation, soluble biomarkers, and associated morbidity and mortality. A single mechanism linking HIV pathogenesis to this inflammation has yet to be identified. Purinergic receptors are known to mediate inflammation and have been shown to be required for HIV-1 infection at the level of HIV-1 membrane fusion. Here we review the literature on the role of purinergic receptors in HIV-1 infection and associated inflammation and describe a role for these receptors as potential therapeutic targets.

Legacy effects of anaerobic soil disinfestation on soil bacterial community composition and production of pathogen-suppressing volatiles

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Maaike evan Agtmaal

2015-07-01

Full Text Available There is increasing evidence that microbial volatiles (VOCs play an important role in natural suppression of soil-borne diseases, but little is known on the factors that influence production of suppressing VOCs. In the current study we examined whether a stress-induced change in soil microbial community composition would affect the production by soils of VOCs suppressing the plant-pathogenic oomycete Pythium. Using pyrosequencing of 16S ribosomal gene fragments we compared the composition of bacterial communities in sandy soils that had been exposed to anaerobic disinfestation (AD, a treatment used to kill harmful soil organisms, with the composition in untreated soils. Three months after the AD treatment had been finished, there was still a clear legacy effect of the former anaerobic stress on bacterial community composition with a strong increase in relative abundance of the phylum Bacteroidetes and a significant decrease of the phyla Acidobacteria, Planctomycetes, Nitrospirae, Chloroflexi and Chlorobi. This change in bacterial community composition coincided with loss of production of Pythium suppressing soil volatiles (VOCs and of suppression of Pythium impacts on Hyacinth root development. One year later, the composition of the bacterial community in the AD soils was reflecting that of the untreated soils. In addition, both production of Pythium-suppressing VOCs and suppression of Pythium in Hyacinth bioassays had returned to the levels of the untreated soil. GC/MS analysis identified several VOCs, among which compounds known to be antifungal, that were produced in the untreated soils but not in the AD soils. These compounds were again produced 15 months after the AD treatment. Our data indicate that soils exposed to a drastic stress can temporarily lose pathogen suppressive characteristics and that both loss and return of these suppressive characteristics coincides with shifts in the soil bacterial community composition. Our data are

In vivo evidence for CD4+ and CD8+ suppressor T cells in vaccination-induced suppression of murine experimental autoimmune thyroiditis

International Nuclear Information System (INIS)

Flynn, J.C.; Kong, Y.C.

1991-01-01

In several experimental autoimmune diseases, including experimental autoimmune thyroiditis (EAT), vaccination with attenuated autoantigen-specific T cells has provided protection against subsequent induction of disease. However, the mechanism(s) of vaccination-induced suppression remains to be clarified. Since the authors have previously shown that suppression generated by pretreatment with mouse thyroglobulin (MTg) or thyroid-stimulating hormone in EAT is mediated by CD4+, not CD8+, suppressor T cells, they examined the role of T cell subsets in vaccination-induced suppression of EAT. Mice were vaccinated with irradiated, MTg-primed, and MTg-activated spleen cells and then challenged. Pretreatment with these cells suppressed EAT induced by immunization with MTg and adjuvant, but not by adoptive transfer of thyroiditogenic cells, suggesting a mechanism of afferent suppression. The activation of suppressor mechanisms did not require CD8+ cells, since mice depleted of CD8+ cells before vaccination showed reduced EAT comparable to control vaccinated mice. Furthermore, depletion of either the CD4+ or the CD8+ subset after vaccination did not significantly abrogate suppression. However, suppression was eliminated by the depletion of both CD4+ and CD8+ cells in vaccinated mice. These results provide evidence for the cooperative effects of CD4+ and CD8+ T cells in vaccination-induced suppression of EAT

Cumulative impact of a clover cover crop on the persistance and efficancy of Beauveria bassiana in suppressing the pecan weevil (Coleoptera: Curculionidae)

Science.gov (United States)

Curculio caryae (Horn), is a key pest of pecans. Endemic levels of the entomopathogenic fungus Beauveria bassiana can occur in pecan orchards and contribute to natural control of C. caryae. Commercial formulations of the fungus can also be applied for suppression of C. caryae. We hypothesized tha...

Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy

DEFF Research Database (Denmark)

Rodger, Alison J; Cambiano, Valentina; Bruun, Tina

2016-01-01

IMPORTANCE: A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. OBJECTIVE: To evaluate the ra...

Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE

DEFF Research Database (Denmark)

Liu, Yawei; Teige, Ingrid; Birnir, Bryndis

2006-01-01

Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflamma......Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS......) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1-TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between...... neurons and T cells results in the conversion of encephalitogenic T cells to CD25+ TGF-beta1+ CTLA-4+ FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4...

The Neurobiological Impact of Ghrelin Suppression after Oesophagectomy

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Conor F. Murphy

2016-12-01

Full Text Available Ghrelin, discovered in 1999, is a 28-amino-acid hormone, best recognized as a stimulator of growth hormone secretion, but with pleiotropic functions in the area of energy homeostasis, such as appetite stimulation and energy expenditure regulation. As the intrinsic ligand of the growth hormone secretagogue receptor (GHS-R, ghrelin appears to have a broad array of effects, but its primary role is still an area of debate. Produced mainly from oxyntic glands in the stomach, but with a multitude of extra-metabolic roles, ghrelin is implicated in complex neurobiological processes. Comprehensive studies within the areas of obesity and metabolic surgery have clarified the mechanism of these operations. As a stimulator of growth hormone (GH, and an apparent inducer of positive energy balance, other areas of interest include its impact on carcinogenesis and tumour proliferation and its role in the cancer cachexia syndrome. This has led several authors to study the hormone in the cancer setting. Ghrelin levels are acutely reduced following an oesophagectomy, a primary treatment modality for oesophageal cancer. We sought to investigate the nature of this postoperative ghrelin suppression, and its neurobiological implications.

The regional extent of suppression: strabismics versus nonstrabismics.

Science.gov (United States)

Babu, Raiju Jacob; Clavagnier, Simon R; Bobier, William; Thompson, Benjamin; Hess, Robert F

2013-10-09

Evidence is accumulating that suppression may be the cause of amblyopia rather than a secondary consequence of mismatched retinal images. For example, treatment interventions that target suppression may lead to better binocular and monocular outcomes. Furthermore, it has recently been demonstrated that the measurement of suppression may have prognostic value for patching therapy. For these reasons, the measurement of suppression in the clinic needs to be improved beyond the methods that are currently available, which provide a binary outcome. We describe a novel quantitative method for measuring the regional extent of suppression that is suitable for clinical use. The method involves a dichoptic perceptual matching procedure at multiple visual field locations. We compare a group of normal controls (mean age: 28 ± 5 years); a group with strabismic amblyopia (four with microesotropia, five with esotropia, and one with exotropia; mean age: 35 ± 10 years); and a group with nonstrabismic anisometropic amblyopia (mean age: 33 ± 12 years). The extent and magnitude of suppression was similar for observers with strabismic and nonstrabismic amblyopia. Suppression was strongest within the central field and extended throughout the 20° field that we measured. Suppression extends throughout the central visual field in both strabismic and anisometropic forms of amblyopia. The strongest suppression occurs within the region of the visual field corresponding to the fovea of the fixing eye.

Benchmark enclosure fire suppression experiments - phase 1 test report.

Energy Technology Data Exchange (ETDEWEB)

Figueroa, Victor G.; Nichols, Robert Thomas; Blanchat, Thomas K.

2007-06-01

A series of fire benchmark water suppression tests were performed that may provide guidance for dispersal systems for the protection of high value assets. The test results provide boundary and temporal data necessary for water spray suppression model development and validation. A review of fire suppression in presented for both gaseous suppression and water mist fire suppression. The experimental setup and procedure for gathering water suppression performance data are shown. Characteristics of the nozzles used in the testing are presented. Results of the experiments are discussed.

Key Competences in vocational education and training

DEFF Research Database (Denmark)

Andersen, Ole Dibbern; Kruse, Katrine

This article presents and discusses how key competences in the school based learning are embedded in the VET curricula during the last five years. It gives an overview of how their role has developed in light of the comprehensive Danish VET reform agreed in 2014 and implemented since August 2015....

Multifaceted effects of synthetic TLR2 ligand and Legionella pneumophilia on Treg-mediated suppression of T cell activation

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Sutmuller Roger PM

2011-03-01

Full Text Available Abstract Background Regulatory T cells (Treg play a crucial role in maintaining immune homeostasis and self-tolerance. The immune suppressive effects of Tregs should however be limited in case effective immunity is required against pathogens or cancer cells. We previously found that the Toll-like receptor 2 (TLR2 agonist, Pam3CysSK4, directly stimulated Tregs to expand and temporarily abrogate their suppressive capabilities. In this study, we evaluate the effect of Pam3CysSK4 and Legionella pneumophila, a natural TLR2 containing infectious agent, on effector T (Teff cells and dendritic cells (DCs individually and in co-cultures with Tregs. Results TLR2 agonists can directly provide a co-stimulatory signal inducing enhanced proliferation and cytokine production of naive CD4+ Teff cells. With respect to cytokine production, DCs appear to be most sensitive to low amounts of TLR agonists. Using wild type and TLR2-deficient cells in Treg suppression assays, we accordingly show that all cells (e.g. Treg, Teff cells and DCs contributed to overcome Treg-mediated suppression of Teff cell proliferation. Furthermore, while TLR2-stimulated Tregs readily lost their ability to suppress Teff cell proliferation, cytokine production by Teff cells was still suppressed. Similar results were obtained upon stimulation with TLR2 ligand containing bacteria, Legionella pneumophila. Conclusions These findings indicate that both synthetic and natural TLR2 agonists affect DCs, Teff cells and Treg directly, resulting in multi-modal modulation of Treg-mediated suppression of Teff cells. Moreover, Treg-mediated suppression of Teff cell proliferation is functionally distinct from suppression of cytokine secretion.

Indirubin-3′-monoxime suppresses amyloid-beta-induced apoptosis by inhibiting tau hyperphosphorylation

Institute of Scientific and Technical Information of China (English)

Shu-gang Zhang; Xiao-shan Wang; Ying-dong Zhang; Qing Di; Jing-ping Shi; Min Qian; Li-gang Xu; Xing-jian Lin; Jie Lu

2016-01-01

Indirubin-3′-monoxime is an effective inhibitor of cyclin-dependent protein kinases, and may play an obligate role in neuronal apopto-sis in Alzheimer’s disease. Here, we found that indirubin-3′-monoxime improved the morphology and increased the survival rate of SH-SY5Y cells exposed to amyloid-beta 25–35 (Aβ25–35), and also suppressed apoptosis by reducing tau phosphorylation at Ser199 and Thr205. Furthermore, indirubin-3′-monoxime inhibited phosphorylation of glycogen synthase kinase-3β (GSK-3β). Our results suggest that in-dirubin-3′-monoxime reduced Aβ25–35-induced apoptosis by suppressing tau hyperphosphorylationvia a GSK-3β-mediated mechanism. Indirubin-3′-monoxime is a promising drug candidate for Alzheimer’s disease.

The link between CD8⁺ T-cell antigen-sensitivity and HIV-suppressive capacity depends on HLA restriction, target epitope and viral isolate.

Science.gov (United States)

Lissina, Anna; Fastenackels, Solène; Inglesias, Maria C; Ladell, Kristin; McLaren, James E; Briceño, Olivia; Gostick, Emma; Papagno, Laura; Autran, Brigitte; Sauce, Delphine; Price, David A; Saez-Cirion, Asier; Appay, Victor

2014-02-20

Although it is established that CD8 T-cell immunity is critical for the control of HIV replication in vivo, the key factors that determine antiviral efficacy are yet to be fully elucidated. Antigen-sensitivity and T-cell receptor (TCR) avidity have been identified as potential determinants of CD8⁺ T-cell efficacy. However, there is no general consensus in this regard because the relationship between these parameters and the control of HIV infection has been established primarily in the context of immunodominant CD8⁺ T-cell responses against the Gag₂₆₃₋₂₇₂ KK10 epitope restricted by human leukocyte antigen (HLA)-B27. To investigate the relationship between antigen-sensitivity, TCR avidity and HIV-suppressive capacity in vitro across epitope specificities and HLA class I restriction elements, we used a variety of techniques to study CD8⁺ T-cell clones specific for Nef₇₃₋₈₂ QK10 and Gag₂₀₋₂₉ RY10, both restricted by HLA-A3, alongside CD8⁺ T-cell clones specific for Gag₂₆₃₋₂₇₂ KK10. For each targeted epitope, the linked parameters of antigen-sensitivity and TCR avidity correlated directly with antiviral efficacy. However, marked differences in HIV-suppressive capacity were observed between epitope specificities, HLA class I restriction elements and viral isolates. Collectively, these data emphasize the central role of the TCR as a determinant of CD8⁺ T-cell efficacy and demonstrate that the complexities of antigen recognition across epitope and HLA class I boundaries can confound simple relationships between TCR engagement and HIV suppression.

Area-wide population suppression of codling moth

International Nuclear Information System (INIS)

Calkins, C.O.; Knight, A.L.; Richardson, G.; Bloem, K.A.

2000-01-01

The area-wide pest population control concept began with E.F. Knipling (1979) in the 1970s. Control of a pest population on individual fields does little to control the overall pest population because only a portion of the population is being affected. Expanding control tactics beyond individual farms tends to suppress the population on a wider scale and frequently results in suppression of the population for more than one year. The Agriculture Research Service (ARS) believes that this concept has not been addressed with the focus and support that it deserves. The ARS Administration made a conscious decision in 1994 to create a series of area-wide programmes funded out of ARS-based funds that had previously been used for pilot tests. These programmes involve a coordinated effort among ARS and university scientists, growers, and fieldmen for agriculture supply centres and fruit packing houses. The first area-wide programme supported by ARS was the codling moth (CM), Cydia pomonella L. (Lepidoptera: Tortricidae) suppression programme. The codling moth is the key pest of pome fruit throughout the western United States (Beers et al. 1993). About half of the insecticides applied on these crops are directed toward this pest. A non-insecticidal control technique, mating disruption (MD), is available to replace the organophosphates. Removal of the hard pesticides directed against this pest would do the most to allow natural enemies to survive and reproduce in the orchards, which in turn would have the effect of reducing secondary pests. Elimination of the pesticides would also remove much of the health risks to workers and would minimise buildup of pesticide resistance. The objectives of the Codling Moth Area-wide Program are to enhance the efficacy of the non-pesticide approach, to demonstrate that mating disruption will work if conducted properly, to develop biological technology to lower costs of control that complement mating disruption, to implement effective

Suppression of immune surveillance in melanoma [Immunotherapy of metastatic melanoma by reversal of immune suppression

Energy Technology Data Exchange (ETDEWEB)

Biggs, M. W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Eiselein, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2001-06-01

In this paper we develop the hypothesis that a significant fraction of patients with advanced melanoma can be successfully treated with immunotherapy. Reversal of antigen-specific immune suppression to melanoma polypeptide antigens is an essential, first step. We postulate the key regulation of CTL responses resides within the CD4+ T-lymphocytes and macrophage/dendritic cells. There is a pluri-potential cell within this regulatory arm that functions either as a Th1 cell or as a suppressor T-cell, Ths, depending on how antigen is presented. We have shown that poliovirus 1 Sabin will lyse human melanoma cells in tissue culture, and a special "vaccine" prepared from this lysis actively stimulates Ths cell function. The Ths arm of the regulatory system can be down-regulated with cyclophosphamide given 24 hours after the vaccine. The capacity to generate a CTL response is retained. The summary conclusion is that a phase 1 clinical trial in advanced melanoma using the special viral-tumor-lysate followed by cyclophosphamide, plus expanded autologous dendritic cells sensitized with the polypeptide epitopes captained in the viral-lysate will produce beneficial results.

Usefulness of combined fat- and fluid-suppressed SPIR-FLAIR images in optic neurits : Comparison with fat-suppressed SPIR or STIR images

International Nuclear Information System (INIS)

Kim, Hye Yeon; Son, Seok Hyun; Eun, Choong Ki; Han, Sang Suk

2001-01-01

To compare the usefulness of combined fat- and fluid-suppressed selective partial inversion recovery-fluid attenuated inversion recovery(SPIR-FLAIR) images in the detection of high signal intensity of the optic nerve in optic neuritis with that of fat-suppressed selective partial inversion recovery(SPIR) or short inversion time inversion recovery(STIR) images. Two radiologists independently analyzed randomly mixed MR images of 16 lesions in 14 patients (M:F=7:7; mean age, 40 years) in whom optic neuritis had been clinically diagnosed. All subjects underwent both SPIR-FLAIR and fat-suppressed SPIR or STIR imaging, in a blind fashion. In order to evaluate the optic nerve, coronal images perpendicular to its long axis were obtained. The detection rate of high signal intensity of the optic nerve, the radiologists preferred imaging sequences, and intersubject consistency of detection were evaluated. 'High signal intensity' was defined as the subjective visual evaluation of increased signal intensity compared with that of the contralateral optic nerve or that of white matter. The mean detection rate of high signal intensity of the optic nerve was 90% for combined fat- and fluid-suppressed SPIR-FLAIR images, and 59% for fat-suppressed SPIR or STIR images. In all cases in which the signal intensity observed on SPIR-FLAIR images was normal, that on fat-suppressed SPIR or STIR images was also normal. The radiologists preferred the contrast properties of SPIR-FLAIR to those of fat-suppressed SPIR or STIR images. In the diagnosis of optic neuritis using MRI, combined fat- and fluid-suppressed SPIR-FLAIR images were more useful for the detection of high signal intensity of the optic nerve than fat-suppressed SPIR or STIR images. For the evaluation of optic neuritis, combined fat- and fluid-suppressed SPIR-FLAIR imaging is superior to fat-suppressed SPIR or STIR imaging

Exploring Genetic Suppression Interactions on a Global Scale

OpenAIRE

van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C.; Yamaguchi, Takafumi N.; Friesen, Helena; Koschwanez, John; Ušaj, Mojca Mattiazzi; Pechlaner, Maria; Takar, Mehmet; Ušaj, Matej; VanderSluis, Benjamin; Andrusiak, Kerry; Bansal, Pritpal; Baryshnikova, Anastasia; Boone, Claire

2016-01-01

Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insig...

M2 FILTER FOR SPECKLE NOISE SUPPRESSION IN BREAST ULTRASOUND IMAGES

Directory of Open Access Journals (Sweden)

E.S. Samundeeswari

2016-11-01

Full Text Available Breast cancer, commonly found in women is a serious life threatening disease due to its invasive nature. Ultrasound (US imaging method plays an effective role in screening early detection and diagnosis of Breast cancer. Speckle noise generally affects medical ultrasound images and also causes a number of difficulties in identifying the Region of Interest. Suppressing speckle noise is a challenging task as it destroys fine edge details. No specific filter is designed yet to get a noise free BUS image that is contaminated by speckle noise. In this paper M2 filter, a novel hybrid of linear and nonlinear filter is proposed and compared to other spatial filters with 3×3 kernel size. The performance of the proposed M2 filter is measured by statistical quantity parameters like MSE, PSNR and SSI. The experimental analysis clearly shows that the proposed M2 filter outperforms better than other spatial filters by 2% high PSNR values with regards to speckle suppression.

Chondromalacia patellae: fat-suppressed MR imaging.

Science.gov (United States)

Rose, P M; Demlow, T A; Szumowski, J; Quinn, S F

1994-11-01

To evaluate the accuracy of fat-suppressed magnetic resonance (MR) imaging in diagnosing chondromalacia patellae. Seventy-one patients underwent fat-suppressed MR imaging and arthroscopy of the patellofemoral compartment. Findings were classified as early or advanced chondromalacia or as normal and were correlated with arthroscopic findings. Early and advanced stages of chondromalacia patellae were reliably detected, with positive predictive values of 85% and 92%, respectively. Specificity in early stages was 94% and in late stages was 98%. However, the overall accuracies did not differ substantially from those reported in studies that did not use fat-suppressed imaging. Axial, fat-suppressed MR imaging accurately depicts changes caused by chondromalacia patellae. Early stages can be seen as intrasubstance changes of increased signal intensity. Results of this study suggest a high degree of specificity in excluding both early and advanced changes.

Suppressed visual looming stimuli are not integrated with auditory looming signals: Evidence from continuous flash suppression.

Science.gov (United States)

Moors, Pieter; Huygelier, Hanne; Wagemans, Johan; de-Wit, Lee; van Ee, Raymond

2015-01-01

Previous studies using binocular rivalry have shown that signals in a modality other than the visual can bias dominance durations depending on their congruency with the rivaling stimuli. More recently, studies using continuous flash suppression (CFS) have reported that multisensory integration influences how long visual stimuli remain suppressed. In this study, using CFS, we examined whether the contrast thresholds for detecting visual looming stimuli are influenced by a congruent auditory stimulus. In Experiment 1, we show that a looming visual stimulus can result in lower detection thresholds compared to a static concentric grating, but that auditory tone pips congruent with the looming stimulus did not lower suppression thresholds any further. In Experiments 2, 3, and 4, we again observed no advantage for congruent multisensory stimuli. These results add to our understanding of the conditions under which multisensory integration is possible, and suggest that certain forms of multisensory integration are not evident when the visual stimulus is suppressed from awareness using CFS.

FOXO1-suppressed miR-424 regulates the proliferation and osteogenic differentiation of MSCs by targeting FGF2 under oxidative stress

Science.gov (United States)

Li, Liangping; Qi, Qihua; Luo, Jiaquan; Huang, Sheng; Ling, Zemin; Gao, Manman; Zhou, Zhiyu; Stiehler, Maik; Zou, Xuenong

2017-02-01

Recently, microRNAs (miRNAs) have been identified as key regulators of the proliferation and differentiation of mesenchymal stem cells (MSCs). Our previous in vivo study and other in vitro studies using miRNA microarrays suggest that miR-424 is involved in the regulation of bone formation. However, the role and mechanism of miR-424 in bone formation still remain unknown. Here, we identified that the downregulation of miR-424 mediates bone formation under oxidative stress, and we explored its underlying mechanism. Our results showed that miR-424 was significantly downregulated in an anterior lumbar interbody fusion model of pigs and in a cell model of oxidative stress induced by H2O2. The overexpression of miR-424 inhibited proliferation and osteogenic differentiation shown by a decrease in alkaline phosphatase (ALP) activity, mineralization and osteogenic markers, including RUNX2 and ALP, whereas the knockdown of miR-424 led to the opposite results. Moreover, miR-424 exerts its effects by targeting FGF2. Furthermore, we found that FOXO1 suppressed miR-424 expression and bound to its promoter region. FOXO1 enhanced proliferation and osteogenic differentiation in part through the miR-424/FGF2 pathway. These results indicated that FOXO1-suppressed miR-424 regulates both the proliferation and osteogenic differentiation of MSCs via targeting FGF2, suggesting that miR-424 might be a potential novel therapeutic strategy for promoting bone formation.

Gyrotactic suppression and emergence of chaotic trajectories of swimming particles in three-dimensional flows

Science.gov (United States)

Richardson, S. I. Heath; Baggaley, A. W.; Hill, N. A.

2018-02-01

We study the effects of imposed three-dimensional flows on the trajectories and mixing of gyrotactic swimming microorganisms and identify phenomena not seen in flows restricted to two dimensions. Through numerical simulation of Taylor-Green and Arnold-Beltrami-Childress (ABC) flows, we explore the role that the flow and the cell shape play in determining the long-term configuration of the cells' trajectories, which often take the form of multiple sinuous and helical "plumelike" structures, even in the chaotic ABC flow. This gyrotactic suppression of Lagrangian chaos persists even in the presence of random noise. Analytical solutions for a number of cases reveal the how plumes form and the nature of the competition between torques acting on individual cells. Furthermore, studies of Lyapunov exponents reveal that, as the ratio of cell swimming speed relative to the flow speed increases from zero, the initial chaotic trajectories are first suppressed and then give way to a second unexpected window of chaotic trajectories at speeds greater than unity, before suppression of chaos at high relative swimming speeds.

Abscisic acid (ABA) and key proteins in its perception and signaling pathways are ancient, but their roles have changed through time.

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Sussmilch, Frances C; Atallah, Nadia M; Brodribb, Timothy J; Banks, Jo Ann; McAdam, Scott A M

2017-09-02

Homologs of the Arabidopsis core abscisic acid (ABA) signaling component OPEN STOMATA1 (OST1) are best known for their role in closing stomata in angiosperm species. We recently characterized a fern OST1 homolog, GAMETOPHYTES ABA INSENSITIVE ON ANTHERDIOGEN 1 (GAIA1), which is not required for stomatal closure in ferns, consistent with physiologic evidence that shows the stomata of these plants respond passively to changes in leaf water status. Instead, gaia1 mutants reveal a critical role in ABA signaling for spore dormancy and sex determination, in a system regulated by antagonism between ABA and the gibberellin (GA)-derived fern hormone antheridiogen (A CE ). ABA and key proteins, including ABA receptors from the PYR/PYL/RCAR family and negative regulators of ABA-signaling from Group A of the type-2C protein phosphatases (PP2Cs), in addition to OST1 homologs, can be found in all terrestrial land plant lineages, ranging from liverworts that lack stomata, to angiosperms. As land plants have evolved and diversified over the past 450 million years, so too have the roles of this important plant hormone and the genes involved in its signaling and perception.

Error-dependent modulation of speech-induced auditory suppression for pitch-shifted voice feedback

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Larson Charles R

2011-06-01

Full Text Available Abstract Background The motor-driven predictions about expected sensory feedback (efference copies have been proposed to play an important role in recognition of sensory consequences of self-produced motor actions. In the auditory system, this effect was suggested to result in suppression of sensory neural responses to self-produced voices that are predicted by the efference copies during vocal production in comparison with passive listening to the playback of the identical self-vocalizations. In the present study, event-related potentials (ERPs were recorded in response to upward pitch shift stimuli (PSS with five different magnitudes (0, +50, +100, +200 and +400 cents at voice onset during active vocal production and passive listening to the playback. Results Results indicated that the suppression of the N1 component during vocal production was largest for unaltered voice feedback (PSS: 0 cents, became smaller as the magnitude of PSS increased to 200 cents, and was almost completely eliminated in response to 400 cents stimuli. Conclusions Findings of the present study suggest that the brain utilizes the motor predictions (efference copies to determine the source of incoming stimuli and maximally suppresses the auditory responses to unaltered feedback of self-vocalizations. The reduction of suppression for 50, 100 and 200 cents and its elimination for 400 cents pitch-shifted voice auditory feedback support the idea that motor-driven suppression of voice feedback leads to distinctly different sensory neural processing of self vs. non-self vocalizations. This characteristic may enable the audio-vocal system to more effectively detect and correct for unexpected errors in the feedback of self-produced voice pitch compared with externally-generated sounds.

Error-dependent modulation of speech-induced auditory suppression for pitch-shifted voice feedback.

Science.gov (United States)

Behroozmand, Roozbeh; Larson, Charles R

2011-06-06

The motor-driven predictions about expected sensory feedback (efference copies) have been proposed to play an important role in recognition of sensory consequences of self-produced motor actions. In the auditory system, this effect was suggested to result in suppression of sensory neural responses to self-produced voices that are predicted by the efference copies during vocal production in comparison with passive listening to the playback of the identical self-vocalizations. In the present study, event-related potentials (ERPs) were recorded in response to upward pitch shift stimuli (PSS) with five different magnitudes (0, +50, +100, +200 and +400 cents) at voice onset during active vocal production and passive listening to the playback. Results indicated that the suppression of the N1 component during vocal production was largest for unaltered voice feedback (PSS: 0 cents), became smaller as the magnitude of PSS increased to 200 cents, and was almost completely eliminated in response to 400 cents stimuli. Findings of the present study suggest that the brain utilizes the motor predictions (efference copies) to determine the source of incoming stimuli and maximally suppresses the auditory responses to unaltered feedback of self-vocalizations. The reduction of suppression for 50, 100 and 200 cents and its elimination for 400 cents pitch-shifted voice auditory feedback support the idea that motor-driven suppression of voice feedback leads to distinctly different sensory neural processing of self vs. non-self vocalizations. This characteristic may enable the audio-vocal system to more effectively detect and correct for unexpected errors in the feedback of self-produced voice pitch compared with externally-generated sounds.

Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR

International Nuclear Information System (INIS)

Tippin, Brigette L; Kwong, Alan M; Inadomi, Michael J; Lee, Oliver J; Park, Jae Man; Materi, Alicia M; Buslon, Virgilio S; Lin, Amy M; Kudo, Lili C; Karsten, Stanislav L; French, Samuel W; Narumiya, Shuh; Urade, Yoshihiro; Salido, Eduardo; Lin, Henry J

2014-01-01

Our earlier work showed that knockout of hematopoietic prostaglandin D synthase (HPGDS, an enzyme that produces prostaglandin D 2 ) caused more adenomas in Apc Min/+ mice. Conversely, highly expressed transgenic HPGDS allowed fewer tumors. Prostaglandin D 2 (PGD 2 ) binds to the prostaglandin D 2 receptor known as PTGDR (or DP1). PGD 2 metabolites bind to peroxisome proliferator-activated receptor γ (PPARG). We hypothesized that Ptgdr or Pparg knockouts may raise numbers of tumors, if these receptors take part in tumor suppression by PGD 2 . To assess, we produced Apc Min/+ mice with and without Ptgdr knockouts (147 mice). In separate experiments, we produced Apc Min/+ mice expressing transgenic lipocalin-type prostaglandin D synthase (PTGDS), with and without heterozygous Pparg knockouts (104 mice). Homozygous Ptgdr knockouts raised total numbers of tumors by 30–40% at 6 and 14 weeks. Colon tumors were not affected. Heterozygous Pparg knockouts alone did not affect tumor numbers in Apc Min/+ mice. As mentioned above, our Pparg knockout assessment also included mice with highly expressed PTGDS transgenes. Apc Min/+ mice with transgenic PTGDS had fewer large adenomas (63% of control) and lower levels of v-myc avian myelocytomatosis viral oncogene homolog (MYC) mRNA in the colon. Heterozygous Pparg knockouts appeared to blunt the tumor-suppressing effect of transgenic PTGDS. However, tumor suppression by PGD 2 was more clearly mediated by receptor PTGDR in our experiments. The suppression mechanism did not appear to involve changes in microvessel density or slower proliferation of tumor cells. The data support a role for PGD 2 signals acting through PTGDR in suppression of intestinal tumors

Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy

NARCIS (Netherlands)

Rodger, Alison J.; Cambiano, Valentina; Bruun, Tina; Vernazza, Pietro; Collins, Simon; van Lunzen, Jan; Corbelli, Giulio Maria; Estrada, Vicente; Geretti, Anna Maria; Beloukas, Apostolos; Asboe, David; Viciana, Pompeyo; Gutiérrez, Félix; Clotet, Bonaventura; Pradier, Christian; Gerstoft, Jan; Weber, Rainer; Westling, Katarina; Wandeler, Gilles; Prins, Jan M.; Rieger, Armin; Stoeckle, Marcel; Kümmerle, Tim; Bini, Teresa; Ammassari, Adriana; Gilson, Richard; Krznaric, Ivanka; Ristola, Matti; Zangerle, Robert; Handberg, Pia; Antela, Antonio; Allan, Sris; Phillips, Andrew N.; Lundgren, Jens; Pompeyo, V.; Trastoy, M.; Palacio, R.; Gutiérrez, F.; Masiá, M.; Padilla, S.; Robledano, C.; Clotet, B.; Coll, P.; Peña, J.; Estrada, V.; Rodrigo, M.; Santiago, E.; Rivero, A.; Antela, A.; Losada, E.

2016-01-01

IMPORTANCE A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. OBJECTIVE To evaluate the rate of

KEYING AND ROLE PLAY IN BUSINESS COMMUNICATION: GENDER, AGE AND RACE CUES

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GABRIELA DUMBRAVĂ

2013-10-01

Full Text Available This study comes as a sequel to other two papers published in this journal in 2010 and 2012 being part of a larger research that approaches business communication from the perspective of Goffman’s theory of the relational dimension of meaning. The paper starts from the premise that meaning is generated within the context of each specific interaction, as a result of a culturally determined process of framing, during which inherited patterns of thought and behavior establish well defined positions from which the interlocutors perceive and respond to one another. It also aims at further analyzing the process of keying by identifying the paradigm shifts that individualize business encounters according to gender, age, and race cues, as well as the communication malfunctions induced by keying errors (misunderstandings, conflict and discrimination.

Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in Protection of Hypoxic Neurons.

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Thauerer, Bettina; Zur Nedden, Stephanie; Baier-Bitterlich, Gabriele

2014-05-01

Serine/threonine protein kinase C-related kinase (PKN/PRK) is a family of three isoenzymes (PKN1, PKN2, PKN3), which are widely distributed in eukaryotic organisms and share the same overall domain structure. The Nterminal region encompasses a conserved repeated domain, termed HR1a-c as well as a HR2/C2 domain. The serine/threonine kinase domain is found in the C-terminal region of the protein and shows high sequence homology to other members of the PKC superfamily. In neurons, PKN1 is the most abundant isoform and has been implicated in a variety of functions including cytoskeletal organization and neuronal differentiation and its deregulation may contribute to neuropathological processes such as amyotrophic lateral sclerosis and Alzheimer's disease. We have recently identified a candidate role of PKN1 in the regulation of neuroprotective processes during hypoxic stress. Our key findings were that: 1) the activity of PKN1 was significantly increased by hypoxia (1% O2) and neurotrophins (nerve growth factor and purine nucleosides); 2) Neuronal cells, deficient of PKN1 showed a decrease of cell viability and neurite formation along with a disturbance of the F-actinassociated cytoskeleton; 3) Purine nucleoside-mediated neuroprotection during hypoxia was severely hampered in PKN1 deficient neuronal cells, altogether suggesting a potentially critical role of PKN1 in neuroprotective processes. This review gives an up-to-date overview of the PKN family with a special focus on the neuroprotective role of PKN1 in hypoxia.

Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.

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Woo, Hae-Mi; Kang, Ji-Hye; Kawada, Teruo; Yoo, Hoon; Sung, Mi-Kyung; Yu, Rina

2007-02-13

Inflammation plays a key role in obesity-related pathologies such as cardiovascular disease, type II diabetes, and several types of cancer. Obesity-induced inflammation entails the enhancement of the recruitment of macrophages into adipose tissue and the release of various proinflammatory proteins from fat tissue. Therefore, the modulation of inflammatory responses in obesity may be useful for preventing or ameliorating obesity-related pathologies. Some spice-derived components, which are naturally occurring phytochemicals, elicit antiobesity and antiinflammatory properties. In this study, we investigated whether active spice-derived components can be applied to the suppression of obesity-induced inflammatory responses. Mesenteric adipose tissue was isolated from obese mice fed a high-fat diet and cultured to prepare an adipose tissue-conditioned medium. Raw 264.7 macrophages were treated with the adipose tissue-conditioned medium with or without active spice-derived components (i.e., diallyl disulfide, allyl isothiocyanate, piperine, zingerone and curcumin). Chemotaxis assay was performed to measure the degree of macrophage migration. Macrophage activation was estimated by measuring tumor necrosis factor-alpha (TNF-alpha), nitric oxide, and monocyte chemoattractant protein-1 (MCP-1) concentrations. The active spice-derived components markedly suppressed the migration of macrophages induced by the mesenteric adipose tissue-conditioned medium in a dose-dependent manner. Among the active spice-derived components studied, allyl isothiocyanate, zingerone, and curcumin significantly inhibited the cellular production of proinflammatory mediators such as TNF-alpha and nitric oxide, and significantly inhibited the release of MCP-1 from 3T3-L1 adipocytes. Our findings suggest that the spice-derived components can suppress obesity-induced inflammatory responses by suppressing adipose tissue macrophage accumulation or activation and inhibiting MCP-1 release from adipocytes

Thought Suppression Research Methods: Paradigms, Theories, Methodological Concerns

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Niczyporuk Aneta

2016-12-01

Full Text Available It is hard to provide an unequivocal answer to the question of whether or not thought suppression is effective. Two thought suppression paradigms - the “white bear” paradigm and the think/no-think paradigm - give mixed results. Generally, “white bear” experiments indicate that thought suppression is counterproductive, while experiments in the think/no-think paradigm suggest that it is possible to effectively suppress a thought. There are also alternative methods used to study thought suppression, for instance the directed forgetting paradigm or the Stroop task. In the article, I describe the research methods used to explore thought suppression efficacy. I focus on the “white bear” and the think/no-think paradigms and discuss theories proposed to explain the results obtained. I also consider the internal and external validity of the methods used.

Accentuation-suppression and scaling

DEFF Research Database (Denmark)

Sørensen, Thomas Alrik; Bundesen, Claus

2012-01-01

The limitations of the visual short-term memory (VSTM) system have become an increasingly popular field of study. One line of inquiry has focused on the way attention selects objects for encoding into VSTM. Using the framework of the Theory of Visual Attention (TVA; Bundesen, 1990 Psychological...... a scaling mechanism modulating the decision bias of the observer and also through an accentuation-suppression mechanism that modulates the degree of subjective relevance of objects, contracting attention around fewer, highly relevant objects while suppressing less relevant objects. These mechanisms may...

Stimulus-specific suppression preserves information in auditory short-term memory.

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Linke, Annika C; Vicente-Grabovetsky, Alejandro; Cusack, Rhodri

2011-08-02

Philosophers and scientists have puzzled for millennia over how perceptual information is stored in short-term memory. Some have suggested that early sensory representations are involved, but their precise role has remained unclear. The current study asks whether auditory cortex shows sustained frequency-specific activation while sounds are maintained in short-term memory using high-resolution functional MRI (fMRI). Investigating short-term memory representations within regions of human auditory cortex with fMRI has been difficult because of their small size and high anatomical variability between subjects. However, we overcame these constraints by using multivoxel pattern analysis. It clearly revealed frequency-specific activity during the encoding phase of a change detection task, and the degree of this frequency-specific activation was positively related to performance in the task. Although the sounds had to be maintained in memory, activity in auditory cortex was significantly suppressed. Strikingly, patterns of activity in this maintenance period correlated negatively with the patterns evoked by the same frequencies during encoding. Furthermore, individuals who used a rehearsal strategy to remember the sounds showed reduced frequency-specific suppression during the maintenance period. Although negative activations are often disregarded in fMRI research, our findings imply that decreases in blood oxygenation level-dependent response carry important stimulus-specific information and can be related to cognitive processes. We hypothesize that, during auditory change detection, frequency-specific suppression protects short-term memory representations from being overwritten by inhibiting the encoding of interfering sounds.

Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis

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Zhang, Cen; Liu, Juan; Zhao, Yuhan; Yue, Xuetian; Zhu, Yu; Wang, Xiaolong; Wu, Hao; Blanco, Felix; Li, Shaohua; Bhanot, Gyan; Haffty, Bruce G; Hu, Wenwei; Feng, Zhaohui

2016-01-01

Glutaminase (GLS) isoenzymes GLS1 and GLS2 are key enzymes for glutamine metabolism. Interestingly, GLS1 and GLS2 display contrasting functions in tumorigenesis with elusive mechanism; GLS1 promotes tumorigenesis, whereas GLS2 exhibits a tumor-suppressive function. In this study, we found that GLS2 but not GLS1 binds to small GTPase Rac1 and inhibits its interaction with Rac1 activators guanine-nucleotide exchange factors, which in turn inhibits Rac1 to suppress cancer metastasis. This function of GLS2 is independent of GLS2 glutaminase activity. Furthermore, decreased GLS2 expression is associated with enhanced metastasis in human cancer. As a p53 target, GLS2 mediates p53’s function in metastasis suppression through inhibiting Rac1. In summary, our results reveal that GLS2 is a novel negative regulator of Rac1, and uncover a novel function and mechanism whereby GLS2 suppresses metastasis. Our results also elucidate a novel mechanism that contributes to the contrasting functions of GLS1 and GLS2 in tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.10727.001 PMID:26751560

Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13-Suppressed Elastin in Airway Fibroblasts in Asthma.

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Ingram, Jennifer L; Slade, David; Church, Tony D; Francisco, Dave; Heck, Karissa; Sigmon, R Wesley; Ghio, Michael; Murillo, Anays; Firszt, Rafael; Lugogo, Njira L; Que, Loretta; Sunday, Mary E; Kraft, Monica

2016-01-01

Elastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV1, 89 ± 3% predicted) and 30 normal control subjects (FEV1, 102 ± 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert's resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV1/FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13-induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13-induced suppression of ELN expression in airway fibroblasts.

The Effect of Learning Disability on Contralateral Suppression of Otoacoustic Emissions in Primary Students

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Saeid Sarough Farahani

2006-06-01

Full Text Available Background and Aim: One of the most significant complaints of children with learning disability (LD is difficulty in understanding speech in the presence of background noise. Different studies have shown that the medial olivocochlear bundle(MOCB may play a role in hearing in noise. The MOCB function can be evaluated by the contralateral suppression of tone burst evoked otoacoustic emissions (TBEOAEs.The aim of the present study was to evaluate frequency specifications of MOCB by the contralateral suppression of TBEOAEs at 1,2,3 and 4 KHz in response to contralateral white noise in LD students. Materials and Methods: This case-control study was conducted on 34 LD students aged 7-11 years and 31 normal students matched for age.The contralateral suppression of TBEOAEs was evaluated by comparing TBEOAEs amplitudes with and without contralateral white noise. Results: In the absence of noise there was no significant difference between TBEOAEs amplitudes of two groups. In the presence of noise significant decrease was seen in TBEOAEs amplitudes at 1,2,3 and 4 KHz in both groups. In LD students the amount of this decrement at 1,2 and 4 KHz was lower than in the normal students. Conclusion: A significant diminished suppression effect at 1,2 and 4 KHz in LD students indicates that at these frequency regions MOCB function was reduced. Therefore it suggests that the assessment of MOCB by evaluating the suppression effect of TBEOAEs included in the test battery approach used in the diagnostic of LD students.

Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin

International Nuclear Information System (INIS)

Fernández-Araujo, A.; Alfonso, A.; Vieytes, M.R.; Botana, L.M.

2015-01-01

Highlights: • YTX activates autophagic cell death after 48 h of treatment. • After 24 h of YTX incubation, the autophagic LC3B expression is increased. • High LC3B levels after 24 h can be related with extrinsic apoptosis activated by YTX. • PDEA4 plays a key role in the autophagy activation. - Abstract: Understanding the mechanism of action of the yessotoxin (YTX) is crucial since this drug has potential pharmacological effects in allergic processes, tumor proliferation and neurodegenerative diseases. It has been described that YTX activates apoptosis after 24 h of treatment, while after 48 h of incubation with the toxin a decrease in cell viability corresponding to cellular differentiation or non-apoptotic cell death was observed. In this paper, these processes were extensively studied by using the erythroleukemia K-562 cell line. On one hand, events of K-562 cell differentiation into erythrocytes after YTX treatment were studied using hemin as positive control of cell differentiation. Cell differentiation was studied through the cyclic nucleotide response element binding (phospho-CREB) and the transferrin receptor (TfR) expression. On the other hand, using rapamycin as positive control, autophagic hallmarks, as non-apoptotic cell death, were studied after toxin exposure. In this case, the mechanistic target of rapamycin (mTOR) and light chain 3B (LC3B) levels were measured to check autophagy activation. The results showed that cell differentiation was not occurring after 48 h of toxin incubation while at this time the autophagy was triggered. Furthermore after 24 h of toxin treatment none of these processes were activated. In addition, the role of the type 4A phosphodiesterase (PDE4A), the intracellular target of YTX, was checked. PDE4A-silencing experiments showed different regulation steps of PDE4A in the autophagic processes triggered either by traditional compounds or YTX. In summary, after 48 h YTX treatment PDE4A-dependent autophagy, as non

Suppression of epithelial ovarian cancer invasion into the omentum by 1α,25-dihydroxyvitamin D3 and its receptor.

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Lungchukiet, Panida; Sun, Yuefeng; Kasiappan, Ravi; Quarni, Waise; Nicosia, Santo V; Zhang, Xiaohong; Bai, Wenlong

2015-04-01

Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer death in women, mainly because it has spread to intraperitoneal tissues such as the omentum in the peritoneal cavity by the time of diagnosis. In the present study, we established in vitro assays, ex vivo omental organ culture system and syngeneic animal tumor models using wild type (WT) and vitamin D receptor (VDR) null mice to investigate the effects of 1α,25-dihydroxyvitamin D3 (1,25D3) and VDR on EOC invasion. Treatment of human EOC cells with 1,25D3 suppressed their migration and invasion in monolayer scratch and transwell assays and ability to colonize the omentum in the ex vivo system, supporting a role for epithelial VDR in interfering with EOC invasion. Furthermore, VDR knockdown in OVCAR3 cells increased their ability to colonize the omentum in the ex vivo system in the absence of 1,25D3, showing a potential ligand-independent suppression of EOC invasion by epithelial VDR. In syngeneic models, ID8 tumors exhibited an increased ability to colonize omenta of VDR null over that of WT mice; pre-treatment of WT, not VDR null, mice with EB1089 reduced ID8 colonization, revealing a role for stromal VDR in suppressing EOC invasion. These studies are the first to demonstrate a role for epithelial and stromal VDR in mediating the activity of 1,25D3 as well as a 1,25D3-independent action of the VDR in suppressing EOC invasion. The data suggest that VDR-based drug discovery may lead to the development of new intervention strategies to improve the survival of patients with EOC at advanced stages. This article is part of a Special Issue entitled "Vitamin D Workshop". Copyright © 2014 Elsevier Ltd. All rights reserved.

Key-value store with internal key-value storage interface

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Bent, John M.; Faibish, Sorin; Ting, Dennis P. J.; Tzelnic, Percy; Gupta, Uday; Grider, Gary; Bonnie, David J.

2018-01-16

A key-value store is provided having one or more key-value storage interfaces. A key-value store on at least one compute node comprises a memory for storing a plurality of key-value pairs; and an abstract storage interface comprising a software interface module that communicates with at least one persistent storage device providing a key-value interface for persistent storage of one or more of the plurality of key-value pairs, wherein the software interface module provides the one or more key-value pairs to the at least one persistent storage device in a key-value format. The abstract storage interface optionally processes one or more batch operations on the plurality of key-value pairs. A distributed embodiment for a partitioned key-value store is also provided.

Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis.

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Phuoc T Tran

Full Text Available KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with Kras(G12D to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy.

Melatonin suppresses acrolein-induced IL-8 production in human pulmonary fibroblasts.

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Kim, Gun-Dong; Lee, Seung Eun; Kim, Tae-Ho; Jin, Young-Ho; Park, Yong Seek; Park, Cheung-Seog

2012-04-01

Cigarette smoke (CS) causes harmful alterations in the lungs and airway structures and functions that characterize chronic obstructive pulmonary disease (COPD). In addition to COPD, active cigarette smoking causes other respiratory diseases and diminishes health status. Furthermore, recent studies show that, α, β-unsaturated aldehyde acrolein in CS induces the production of interleukin (IL)-8, which is known to be related to bronchitis, rhinitis, pulmonary fibrosis, and asthma. In addition, lung and pulmonary fibroblasts secrete IL-8, which has a chemotactic effect on leukocytes, and which in turn, play a critical role in lung inflammation. On the other hand, melatonin regulates circadian rhythm homeostasis in humans and has many other effects, which include antioxidant and anti-inflammatory effects, as demonstrated by the reduced expressions of iNOS, IL-1β, and IL-6 and increased glutathione (GSH) and superoxide dismutase activities. In this study, we investigated whether melatonin suppresses acrolein-induced IL-8 secretion in human pulmonary fibroblasts (HPFs). It was found that acrolein-induced IL-8 production was accompanied by increased levels of phosphorylation of Akt and extracellular signal-regulated kinases (ERK1/2) in HPFs, and that melatonin suppressed IL-8 production in HPFs. These results suggest that melatonin suppresses acrolein-induced IL-8 production via ERK1/2 and phosphatidylinositol 3-kinase (PI3K)/Akt signal inhibition in HPFs. © 2011 John Wiley & Sons A/S.

Human alpha-fetoprotein and prostaglandins suppress human lymphocyte transformation by different mechanisms

International Nuclear Information System (INIS)

Yachnin, S.; Lester, E.P.

1979-01-01

The capacity of human alpha-fetoprotein (HAFP) to suppress human lymphocyte transformation is well established, although some investigators have reported negative results in their efforts to demonstrate this phenomenon. This discrepancy may reside in the fact that not all isolates of HAFP are potent inhibitors of lymphocyte transformation and that the immunosuppressive potency of various HAFP isolates may be correlated with the proportion of certain negatively charged HAFP isomers which they contain. The possibility was considered that noncovalent binding of low-molecular-weight, negatively charged molecules might be partially responsible. Since fatty acids, including certain prostaglandins (PG), are capable of binding to a partly related serum protein, namely, human serum albumin, and since certain prostaglandins are known to be potent suppressors of human lymphocyte transformation, a study was undertaken of the role which prostaglandins might play in HAFP-induced suppression of human lymphocyte transformation

Antiviral RNA silencing suppression activity of Tomato spotted wilt virus NSs protein.

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Ocampo Ocampo, T; Gabriel Peralta, S M; Bacheller, N; Uiterwaal, S; Knapp, A; Hennen, A; Ochoa-Martinez, D L; Garcia-Ruiz, H

2016-06-17

In addition to regulating gene expression, RNA silencing is an essential antiviral defense system in plants. Triggered by double-stranded RNA, silencing results in degradation or translational repression of target transcripts. Viruses are inducers and targets of RNA silencing. To condition susceptibility, most plant viruses encode silencing suppressors that interfere with this process, such as the Tomato spotted wilt virus (TSWV) NSs protein. The mechanism by which NSs suppresses RNA silencing and its role in viral infection and movement remain to be determined. We cloned NSs from the Hawaii isolate of TSWV and using two independent assays show for the first time that this protein restored pathogenicity and supported the formation of local infection foci by suppressor-deficient Turnip mosaic virus and Turnip crinkle virus. Demonstrating the suppression of RNA silencing directed against heterologous viruses establishes the foundation to determine the means used by NSs to block this antiviral process.

Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells

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Cristian Doñas

2013-01-01

Full Text Available Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+ T cells. The forkhead box P3 transcription factor (Foxp3 is a crucial molecule regulating the generation and function of Tregs. Here we show that the foxp3 gene promoter becomes hyperacetylated in in vitro differentiated Tregs compared to naïve CD4+ T cells. We also show that the histone deacetylase inhibitor TSA stimulated the in vitro differentiation of naïve CD4+ T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence of TSA have phenotypical and functional differences from the Tregs generated in the absence of TSA. Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+ Treg cells.

Identifying key research objectives to make European forests greener for bats

Directory of Open Access Journals (Sweden)

Danilo Russo

2016-07-01

Full Text Available Bats are a biodiverse mammal order providing key ecosystem services such as pest suppression, pollination and seed dispersal. Bats are also very sensitive to human actions, and significant declines in many bat populations have been recorded consequently. Many bat species find crucial roosting and foraging opportunities in European forests. Such forests have historically been exploited by humans and are still influenced by harvesting. One of the consequences of this pressure is the loss of key habitat resources, often making forests inhospitable to bats. Despite the legal protection granted to bats across Europe, the impacts of forestry on bats are still often neglected. Because forest exploitation influences forest structure at several spatial scales, economically viable forestry could become more sustainable and even favour bats. We highlight that a positive future for bat conservation that simultaneously benefits forestry is foreseeable, although more applied research is needed to develop sound management. Key future research topics include the detection of factors influencing the carrying capacity of forests, and determining the impacts of forest management and the economic importance of bats in forests. Predictive tools to inform forest managers are much needed, together with greater synergies between forest managers and bat conservationists.

Circulating gluten-specific FOXP3+CD39+ regulatory T cells have impaired suppressive function in patients with celiac disease.

Science.gov (United States)

Cook, Laura; Munier, C Mee Ling; Seddiki, Nabila; van Bockel, David; Ontiveros, Noé; Hardy, Melinda Y; Gillies, Jana K; Levings, Megan K; Reid, Hugh H; Petersen, Jan; Rossjohn, Jamie; Anderson, Robert P; Zaunders, John J; Tye-Din, Jason A; Kelleher, Anthony D

2017-12-01

Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3) + Treg cells. Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4 + T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4 + T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4 + T cells were FOXP3 + CD39 + Treg cells, which reside within the pool of memory CD4 + CD25 + CD127 low CD45RO + Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3 + CD39 + Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. This study provides the first estimation of FOXP3 + CD39 + Treg cell frequency within circulating gluten-specific CD4 + T cells after oral gluten challenge of patients with celiac disease. FOXP3 + CD39 + Treg cells comprised a major proportion of all circulating gluten-specific CD4 + T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key

Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy.

Science.gov (United States)

Arriagada, R; Lê, M G; Spielmann, M; Mauriac, L; Bonneterre, J; Namer, M; Delozier, T; Hill, C; Tursz, T

2005-03-01

The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients suppression significantly decreased the risk of recurrence (P = 0.01). The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.

Experimental Evaluation of Interference Suppression Receivers and Rank Adaptation in 5G Small Cells

DEFF Research Database (Denmark)

Assefa, Dereje; Berardinelli, Gilberto; Catania, Davide

2015-01-01

Advanced receivers are a key component of the 5th Generation (5G) ultra-dense small cells concept given their capability of efficiently dealing with the ever-increasing problem of inter-cell interference. In this paper, we evaluate the potential of interference suppression receivers in real network...... the Interference Rejection Combining (IRC) and Successive Interference Cancellation (SIC) receivers and different rank adaptation approaches. Each node in our software defined radio (SDR) testbed features a 22 MIMO transceiver built with the USRP N200 hardware by Ettus Research. Our experimental results confirm...

Charmonium formation and suppression in nuclear matter

International Nuclear Information System (INIS)

Xu Jiajun; Wang Jia; Zhuang Chao; Zhuang Pengfei

2005-01-01

The coupling Schroedinger equations describing the evolution of cc-bar states in nuclear matter are analytically and systematically solved via perturbation method, and the correlation between charmonium formation and nuclear absorption is investigated. After calculating J/Ψ and Ψ' suppression in nucleon-nucleus collisions and comparing with experiment data, it is found that the formation time effect plays an important rule in charmonium suppression, especially in Ψ' suppression. (authors)

Elucidating the Key Role of a Lewis Base Solvent in the Formation of Perovskite Films Fabricated from the Lewis Adduct Approach.

Science.gov (United States)

Cao, Xiaobing; Zhi, Lili; Li, Yahui; Fang, Fei; Cui, Xian; Yao, Youwei; Ci, Lijie; Ding, Kongxian; Wei, Jinquan

2017-09-27

High-quality perovskite films can be fabricated from Lewis acid-base adducts through molecule exchange. Substantial work is needed to fully understand the formation mechanism of the perovskite films, which helps to further improve their quality. Here, we study the formation of CH 3 NH 3 PbI 3 perovskite films by introducing some dimethylacetamide into the PbI 2 /N,N-dimethylformamide solution. We reveal that there are three key processes during the formation of perovskite films through the Lewis acid-base adduct approach: molecule intercalation of solvent into the PbI 2 lattice, molecule exchange between the solvent and CH 3 NH 3 I, and dissolution-recrystallization of the perovskite grains during annealing. The Lewis base solvents play multiple functions in the above processes. The properties of the solvent, including Lewis basicity and boiling point, play key roles in forming smooth perovskite films with large grains. We also provide some rules for choosing Lewis base additives to prepare high-quality perovskite films through the Lewis adduct approach.