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Sample records for key suppressive role

  1. Double positive CD4+CD8+ T cells: key suppressive role in the production of autoantibodies in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Yongkang Wu

    2014-01-01

    Full Text Available Background & objectives: The presence of CD4+CD8+ (double positive T cells (DPT in the target organs of several autoimmune diseases has been reported. The aim of this study was to investigate the pathogenic role of DPT in systemic lupus erythematosus (SLE. Methods: A total of 175 SLE cases and 125 matched healthy controls were investigated for CD3+, CD4+, CD8+ lymphocytes and DPT by flow cytometry. Serum samples from SLE patients and controls were tested for antinuclear antibody (ANA, anti-double strain deoxyribonucleic acid (anti-dsDNA, anti-U1 ribonucleoprotein (anti-U1 RNP, anti-sjogren syndrome A (anti-SSA, anti-ribosomal P protein (anti-rib-P, anti-Smith (anti-Sm, anti-Sjogren syndrome B (anti-SSB, complement 3 (C3 and complement 4 (C4. Results: The DPT median and 5-95 per cent range of SLE cases and healthy controls were 0.50 [0.10-2.60] and 0.80 [0.20-2.74] respectively (P<0.001. SLE patients were divided into a ≥1:1000 subgroup and a <1:1000 subgroup according to the ANA titre. The DPT of the former subgroup was significantly lower than that of the latter (P=0.032. The DPT medians of positive subgroups with anti-dsDNA (P<0.001, anti-U1RNP (P=0.018, anti-SSA (P=0.021 or anti-rib-P (P=0.039 were also significantly lower than the negative subgroups. Likewise, DPT was significantly lower in SLE subgroups with low concentration of C3 or C4 than those with high concentration (P<0.006. Interpretation & conclusions: Our findings show that the DPT cells may play a key suppressive role in the production of autoantibodies in SLE. Direct evidence that DPT regulates the pathogenesis of SLE needs to be investigated in future work.

  2. A key role of microRNA-29b for the suppression of colon cancer cell migration by American ginseng.

    Directory of Open Access Journals (Sweden)

    Deepak Poudyal

    Full Text Available Metastasis of colon cancer cells increases the risk of colon cancer mortality. We have recently shown that American ginseng prevents colon cancer, and a Hexane extract of American Ginseng (HAG has particularly potent anti-inflammatory and anti-cancer properties. Dysregulated microRNA (miR expression has been observed in several disease conditions including colon cancer. Using global miR expression profiling, we observed increased miR-29b in colon cancer cells following exposure to HAG. Since miR-29b plays a role in regulating the migration of cancer cells, we hypothesized that HAG induces miR-29b expression to target matrix metalloproteinase-2 (MMP-2 thereby suppressing the migration of colon cancer cells. Results are consistent with this hypothesis. Our study supports the understanding that targeting MMP-2 by miR-29b is a mechanism by which HAG suppresses the migration of colon cancer cells.

  3. 8C.03: A KEY ROLE FOR ENDOTHELIN-1 IN THE PATHOGENESIS OF PREECLAMPSIA AND THE ASSOCIATED SUPPRESSION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM.

    Science.gov (United States)

    Verdonk, K; Saleh, L; Smilde, J E; van Ingen, M M; Garrelds, I M; Friesema, E C; Russcher, H; Steegers, E A P; van den Meiracker, A H; Visser, W; Danser, A H J

    2015-06-01

    aldosterone argues against studies reporting that a high anti-angiogenic state, via a reduction of adrenal capillary density, selectively suppresses aldosterone. Since ET-1 also was a major determinant of PCR, our data reveal a key role for ET-1 in the pathogenesis of PE.

  4. Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression.

    Science.gov (United States)

    Verdonk, Koen; Saleh, Langeza; Lankhorst, Stephanie; Smilde, J E Ilse; van Ingen, Manon M; Garrelds, Ingrid M; Friesema, Edith C H; Russcher, Henk; van den Meiracker, Anton H; Visser, Willy; Danser, A H Jan

    2015-06-01

    Women with preeclampsia display low renin-angiotensin-aldosterone system activity and a high antiangiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor levels. To investigate whether renin-angiotensin-aldosterone system suppression in preeclampsia is because of this disturbed angiogenic balance, we measured mean arterial pressure, creatinine, endothelin-1 (ET-1), and renin-angiotensin-aldosterone system components in pregnant women with a high (≥85; n=38) or low (<85; n=65) soluble Fms-like tyrosine kinase-1/placental growth factor ratio. Plasma ET-1 levels were increased in women with a high ratio, whereas their plasma renin activity and plasma concentrations of renin, angiotensinogen, and aldosterone were decreased. Plasma renin activity-aldosterone relationships were identical in both the groups. Multiple regression analysis revealed that plasma renin concentration correlated independently with mean arterial pressure and plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine kinase-1 and negatively with plasma renin concentration, and urinary protein correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma levels of renin and angiotensinogen in the high-ratio group, their urinary levels of these components were elevated. Correction for albumin revealed that this was because of increased glomerular filtration. Subcutaneous arteries obtained from patients with preeclampsia displayed an enhanced, AT2 receptor-mediated response to angiotensin II. In conclusion, a high antiangiogenic state associates with ET-1 activation, which together with the increased mean arterial pressure may underlie the parallel reductions in renin and aldosterone in preeclampsia. Because ET-1 also was a major determinant of urinary protein, our data reveal a key role for ET-1 in the pathogenesis of preeclampsia. Finally, the enhanced angiotensin responsiveness

  5. The suppression of tomato defence response genes upon potato cyst nematode infection indicates a key regulatory role of miRNAs.

    Science.gov (United States)

    Święcicka, Magdalena; Skowron, Waldemar; Cieszyński, Piotr; Dąbrowska-Bronk, Joanna; Matuszkiewicz, Mateusz; Filipecki, Marcin; Koter, Marek Daniel

    2017-04-01

    Potato cyst nematode Globodera rostochiensis is an obligate parasite of solanaceous plants, triggering metabolic and morphological changes in roots which may result in substantial crop yield losses. Previously, we used the cDNA-AFLP to study the transcriptional dynamics in nematode infected tomato roots. Now, we present the rescreening of already published, upregulated transcript-derived fragment dataset using the most current tomato transcriptome sequences. Our reanalysis allowed to add 54 novel genes to 135, already found as upregulated in tomato roots upon G. rostochiensis infection (in total - 189). We also created completely new catalogue of downregulated sequences leading to the discovery of 76 novel genes. Functional classification of candidates showed that the 'wound, stress and defence response' category was enriched in the downregulated genes. We confirmed the transcriptional dynamics of six genes by qRT-PCR. To place our results in a broader context, we compared the tomato data with Arabidopsis thaliana, revealing similar proportions of upregulated and downregulated genes as well as similar enrichment of defence related transcripts in the downregulated group. Since transcript suppression is quite common in plant-nematode interactions, we assessed the possibility of miRNA-mediated inverse correlation on several tomato sequences belonging to NB-LRR and receptor-like kinase families. The qRT-PCR of miRNAs and putative target transcripts showed an opposite expression pattern in 9 cases. These results together with in silico analyses of potential miRNA targeting to the full repertoire of tomato R-genes show that miRNA mediated gene suppression may be a key regulatory mechanism during nematode parasitism. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. 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

  7. 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.

  8. The role of suppression in amblyopia.

    Science.gov (United States)

    Li, Jingrong; Thompson, Benjamin; Lam, Carly S Y; Deng, Daming; Chan, Lily Y L; Maehara, Goro; Woo, George C; Yu, Minbin; Hess, Robert F

    2011-06-13

    This study had three main goals: to assess the degree of suppression in patients with strabismic, anisometropic, and mixed amblyopia; to establish the relationship between suppression and the degree of amblyopia; and to compare the degree of suppression across the clinical subgroups within the sample. Using both standard measures of suppression (Bagolini lenses and neutral density [ND] filters, Worth 4-Dot test) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, the degree of suppression in 43 amblyopic patients with strabismus, anisometropia, or a combination of both was quantified. There was good agreement between the quantitative measures of suppression made with the new dichoptic motion threshold technique and measurements made with standard clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot test). The degree of suppression was found to correlate directly with the degree of amblyopia within our clinical sample, whereby stronger suppression was associated with a greater difference in interocular acuity and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history. These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

  9. 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.

  10. 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.

  11. 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

  12. Interleukin 35: A Key Mediator of Suppression and the Propagation of Infectious Tolerance

    Directory of Open Access Journals (Sweden)

    Brian M Olson

    2013-10-01

    Full Text Available The importance of regulatory T cells in balancing the effector arm of the immune system is well documented, playing a central role in preventing autoimmunity, facilitating graft tolerance following organ transplantation, and having a detrimental impact on the development of anti-tumor immunity. These regulatory responses use a variety of mechanisms to mediate suppression, including soluble factors. While IL-10 and TGF-β are the most commonly studied immunosuppressive cytokines, the recently identified IL-35 has been shown to have potent suppressive function in vitro and in vivo. Furthermore, not only does IL-35 have the ability to directly suppress effector T cell responses, it is also able to expand regulatory responses by propagating infectious tolerance and generating a potent population of IL-35-expressing inducible regulatory T cells. In this review, we summarize research characterizing the structure and function of IL-35, examine its role in disease, and discuss how it can contribute to the induction of a distinct population of inducible regulatory T cells.

  13. 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

  14. Roles for miR-375 in Neuroendocrine Differentiation and Tumor Suppression via Notch Pathway Suppression in Merkel Cell Carcinoma.

    Science.gov (United States)

    Abraham, Karan J; Zhang, Xiao; Vidal, Ricardo; Paré, Geneviève C; Feilotter, Harriet E; Tron, Victor A

    2016-04-01

    Dysfunction of key miRNA pathways regulating basic cellular processes is a common driver of many cancers. However, the biological roles and/or clinical applications of such pathways in Merkel cell carcinoma (MCC), a rare but lethal cutaneous neuroendocrine (NE) malignancy, have yet to be determined. Previous work has established that miR-375 is highly expressed in MCC tumors, but its biological role in MCC remains unknown. Herein, we show that elevated miR-375 expression is a specific feature of well-differentiated MCC cell lines that express NE markers. In contrast, miR-375 is strikingly down-regulated in highly aggressive, undifferentiated MCC cell lines. Enforced miR-375 expression in these cells induced NE differentiation, and opposed cancer cell viability, migration, invasion, and survival, pointing to tumor-suppressive roles for miR-375. Mechanistically, miR-375-driven phenotypes were caused by the direct post-transcriptional repression of multiple Notch pathway proteins (Notch2 and RBPJ) linked to cancer and regulation of cell fate. Thus, we detail a novel molecular axis linking tumor-suppressive miR-375 and Notch with NE differentiation and cancer cell behavior in MCC. Our findings identify miR-375 as a putative regulator of NE differentiation, provide insight into the cell of origin of MCC, and suggest that miR-375 silencing may promote aggressive cancer cell behavior through Notch disinhibition. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. Worry, problem elaboration and suppression of imagery: the role of concreteness.

    Science.gov (United States)

    Stöber, J

    1998-01-01

    Both lay concept and scientific theory claim that worry may be helpful for defining and analyzing problems. Recent studies, however, indicate that worrisome problem elaborations are less concrete than worry-free problem elaborations. This challenges the problem solving view of worry because abstract problem analyses are unlikely to lead to concrete problem solutions. Instead the findings support the avoidance theory of worry which claims that worry suppresses aversive imagery. Following research findings in the dual-coding framework [Paivio, A. (1971). Imagery and verbal processes. New York: Holt, Rhinehart and Winston; Paivio, A. (1986). Mental representations: a dual coding approach. New York: Oxford University Press.], the present article proposes that reduced concreteness may play a central role in the understanding of worry. First, reduced concreteness can explain how worry reduces imagery. Second, it offers an explanation why worrisome problem analyses are unlikely to arrive at solutions. Third, it provides a key for the understanding of worry maintenance.

  2. 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.

  3. A limited role for suppression in the central field of individuals with strabismic amblyopia.

    Science.gov (United States)

    Barrett, Brendan T; Panesar, Gurvinder K; Scally, Andrew J; Pacey, Ian E

    2012-01-01

    Although their eyes are pointing in different directions, people with long-standing strabismic amblyopia typically do not experience double-vision or indeed any visual symptoms arising from their condition. It is generally believed that the phenomenon of suppression plays a major role in dealing with the consequences of amblyopia and strabismus, by preventing images from the weaker/deviating eye from reaching conscious awareness. Suppression is thus a highly sophisticated coping mechanism. Although suppression has been studied for over 100 years the literature is equivocal in relation to the extent of the retina that is suppressed, though the method used to investigate suppression is crucial to the outcome. There is growing evidence that some measurement methods lead to artefactual claims that suppression exists when it does not. Here we present the results of an experiment conducted with a new method to examine the prevalence, depth and extent of suppression in ten individuals with strabismic amblyopia. Seven subjects (70%) showed no evidence whatsoever for suppression and in the three individuals who did (30%), the depth and extent of suppression was small. Suppression may play a much smaller role in dealing with the negative consequences of strabismic amblyopia than previously thought. Whereas recent claims of this nature have been made only in those with micro-strabismus our results show extremely limited evidence for suppression across the central visual field in strabismic amblyopes more generally. Instead of suppressing the image from the weaker/deviating eye, we suggest the visual system of individuals with strabismic amblyopia may act to maximise the possibilities for binocular co-operation. This is consistent with recent evidence from strabismic and amblyopic individuals that their binocular mechanisms are intact, and that, just as in visual normals, performance with two eyes is better than with the better eye alone in these individuals.

  4. A limited role for suppression in the central field of individuals with strabismic amblyopia.

    Directory of Open Access Journals (Sweden)

    Brendan T Barrett

    Full Text Available BACKGROUND: Although their eyes are pointing in different directions, people with long-standing strabismic amblyopia typically do not experience double-vision or indeed any visual symptoms arising from their condition. It is generally believed that the phenomenon of suppression plays a major role in dealing with the consequences of amblyopia and strabismus, by preventing images from the weaker/deviating eye from reaching conscious awareness. Suppression is thus a highly sophisticated coping mechanism. Although suppression has been studied for over 100 years the literature is equivocal in relation to the extent of the retina that is suppressed, though the method used to investigate suppression is crucial to the outcome. There is growing evidence that some measurement methods lead to artefactual claims that suppression exists when it does not. METHODOLOGY/RESULTS: Here we present the results of an experiment conducted with a new method to examine the prevalence, depth and extent of suppression in ten individuals with strabismic amblyopia. Seven subjects (70% showed no evidence whatsoever for suppression and in the three individuals who did (30%, the depth and extent of suppression was small. CONCLUSIONS: Suppression may play a much smaller role in dealing with the negative consequences of strabismic amblyopia than previously thought. Whereas recent claims of this nature have been made only in those with micro-strabismus our results show extremely limited evidence for suppression across the central visual field in strabismic amblyopes more generally. Instead of suppressing the image from the weaker/deviating eye, we suggest the visual system of individuals with strabismic amblyopia may act to maximise the possibilities for binocular co-operation. This is consistent with recent evidence from strabismic and amblyopic individuals that their binocular mechanisms are intact, and that, just as in visual normals, performance with two eyes is better than

  5. 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.

  6. Phytochelatins play a key role in arsenic accumulation and tolerance in the aquatic macrophyte Wolffia globosa

    International Nuclear Information System (INIS)

    Zhang Xin; Uroic, M. Kalle; Xie Wanying; Zhu Yongguan; Chen Baodong; McGrath, Steve P.; Feldmann, Jörg; Zhao Fangjie

    2012-01-01

    The rootless duckweed Wolffia globosa can accumulate and tolerate relatively large amounts of arsenic (As); however, the underlying mechanisms were unknown. W. globosa was exposed to different concentrations of arsenate with or without L-buthionine sulphoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase. Free thiol compounds and As(III)–thiol complexes were identified and quantified using HPLC – high resolution ICP-MS – accurate mass ESI-MS. Without BSO, 74% of the As accumulated in the duckweed was complexed with phytochelatins (PCs), with As(III)–PC 4 and As(III)–PC 3 being the main species. BSO was taken up by the duckweed and partly deaminated. The BSO treatment completely suppressed the synthesis of PCs and the formation of As(III)–PC complexes, and also inhibited the reduction of arsenate to arsenite. BSO markedly decreased both As accumulation and As tolerance in W. globosa. The results demonstrate an important role of PCs in detoxifying As and enabling As accumulation in W. globosa. - Highlights: ► W. globosa can accumulate and tolerate relatively large amounts of arsenic. ► Majority of the As accumulated in W. globosa was complexed with phytochelatins (PCs). ► As(III)–PC 4 and As(III)–PC 3 are the main complex species. ► Complexation of arsenite with phytochelatins plays a key role in As tolerance and accumulation. - Complexation of arsenite with phytochelatins plays a key role in both arsenic tolerance and accumulation in the aquatic macrophyte Wolffia globosa.

  7. A Limited Role for Suppression in the Central Field of Individuals with Strabismic Amblyopia

    OpenAIRE

    Barrett, Brendan T.; Panesar, Gurvinder K.; Scally, Andrew J.; Pacey, Ian E.

    2012-01-01

    BACKGROUND: Although their eyes are pointing in different directions, people with long-standing strabismic amblyopia typically do not experience double-vision or indeed any visual symptoms arising from their condition. It is generally believed that the phenomenon of suppression plays a major role in dealing with the consequences of amblyopia and strabismus, by preventing images from the weaker/deviating eye from reaching conscious awareness. Suppression is thus a highly sophisticated coping m...

  8. Suppression of 9-cis-epoxycarotenoid dioxygenase, which encodes a key enzyme in abscisic acid biosynthesis, alters fruit texture in transgenic tomato.

    Science.gov (United States)

    Sun, Liang; Sun, Yufei; Zhang, Mei; Wang, Ling; Ren, Jie; Cui, Mengmeng; Wang, Yanping; Ji, Kai; Li, Ping; Li, Qian; Chen, Pei; Dai, Shengjie; Duan, Chaorui; Wu, Yan; Leng, Ping

    2012-01-01

    Cell wall catabolism during fruit ripening is under complex control and is key for fruit quality and shelf life. To examine the role of abscisic acid (ABA) in tomato (Solanum lycopersicum) fruit ripening, we suppressed SlNCED1, which encodes 9-cis-epoxycarotenoid dioxygenase (NCED), a key enzyme in the biosynthesis of ABA. To suppress SlNCED1 specifically in tomato fruits, and thus avoid the pleiotropic phenotypes associated with ABA deficiency, we used an RNA interference construct driven by the fruit-specific E8 promoter. ABA accumulation and SlNCED1 transcript levels in the transgenic fruit were down-regulated to between 20% and 50% of the levels measured in the control fruit. This significant reduction in NCED activity led to a down-regulation in the transcription of genes encoding major cell wall catabolic enzymes, specifically polygalacturonase (SlPG), pectin methyl esterase (SlPME), β-galactosidase precursor mRNA (SlTBG), xyloglucan endotransglycosylase (SlXET), endo-1,4-β-cellulose (SlCels), and expansin (SlExp). This resulted in an increased accumulation of pectin during ripening. In turn, this led to a significant extension of the shelf life to 15 to 29 d compared with a shelf life of only 7 d for the control fruit and an enhancement of fruit firmness at the mature stage by 30% to 45%. In conclusion, ABA affects cell wall catabolism during tomato fruit ripening via down-regulation of the expression of major catabolic genes (SlPG, SlPME, SlTBG, SlXET, SlCels, and SlExp).

  9. Suppression of 9-cis-Epoxycarotenoid Dioxygenase, Which Encodes a Key Enzyme in Abscisic Acid Biosynthesis, Alters Fruit Texture in Transgenic Tomato1[W][OA

    Science.gov (United States)

    Sun, Liang; Sun, Yufei; Zhang, Mei; Wang, Ling; Ren, Jie; Cui, Mengmeng; Wang, Yanping; Ji, Kai; Li, Ping; Li, Qian; Chen, Pei; Dai, Shengjie; Duan, Chaorui; Wu, Yan; Leng, Ping

    2012-01-01

    Cell wall catabolism during fruit ripening is under complex control and is key for fruit quality and shelf life. To examine the role of abscisic acid (ABA) in tomato (Solanum lycopersicum) fruit ripening, we suppressed SlNCED1, which encodes 9-cis-epoxycarotenoid dioxygenase (NCED), a key enzyme in the biosynthesis of ABA. To suppress SlNCED1 specifically in tomato fruits, and thus avoid the pleiotropic phenotypes associated with ABA deficiency, we used an RNA interference construct driven by the fruit-specific E8 promoter. ABA accumulation and SlNCED1 transcript levels in the transgenic fruit were down-regulated to between 20% and 50% of the levels measured in the control fruit. This significant reduction in NCED activity led to a down-regulation in the transcription of genes encoding major cell wall catabolic enzymes, specifically polygalacturonase (SlPG), pectin methyl esterase (SlPME), β-galactosidase precursor mRNA (SlTBG), xyloglucan endotransglycosylase (SlXET), endo-1,4-β-cellulose (SlCels), and expansin (SlExp). This resulted in an increased accumulation of pectin during ripening. In turn, this led to a significant extension of the shelf life to 15 to 29 d compared with a shelf life of only 7 d for the control fruit and an enhancement of fruit firmness at the mature stage by 30% to 45%. In conclusion, ABA affects cell wall catabolism during tomato fruit ripening via down-regulation of the expression of major catabolic genes (SlPG, SlPME, SlTBG, SlXET, SlCels, and SlExp). PMID:22108525

  10. 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

  11. 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.

  12. 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

  13. ROLE AND IMPORTANCE OF KEY PERFORMANCE INDICATORS MEASUREMENT

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. 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

  16. 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.

  17. Gatekeepers’ Roles as a Fundamental Key in Money Laundering

    Directory of Open Access Journals (Sweden)

    Paku Utama

    2016-08-01

    Full Text Available This study examines problem of money laundering and identifies role of gatekeepers in utilising their expertise to conceal the proceeds of crime. In order to successfully prevent and investigate money laundering, we need to understand the development of anti-money laundering regime and how country like Indonesia adopts this development into its domestic regulations. Nevertheless, it is crucial to comprehend gatekeepers utilising various money laundering mechanisms and offshore financial centres. Scrutinised cases from Indonesia and corporate practices from Singapore on this study highlight how gatekeepers operate in the private sector, wittingly or unwittingly, use their expert knowledge of the international financial system to facilitate criminals and to secure the movement of the proceeds of crime globally. 

  18. Understanding earthquakes: The key role of radar images

    International Nuclear Information System (INIS)

    Atzori, Simone

    2013-01-01

    The investigation of the fault rupture underlying earthquakes greatly improved thanks to the spread of radar images. Following pioneer applications in the eighties, Interferometry from Synthetic Aperture Radar (InSAR) gained a prominent role in geodesy. Its capability to measure millimetric deformations for wide areas and the increased data availability from the early nineties, made InSAR a diffused and accepted analysis tool in tectonics, though several factors contribute to reduce the data quality. With the introduction of analytical or numerical modeling, InSAR maps are used to infer the source of an earthquake by means of data inversion. Newly developed algorithms, known as InSAR time-series, allowed to further improve the data accuracy and completeness, strengthening the InSAR contribution even in the study of the inter- and post-seismic phases. In this work we describe the rationale at the base of the whole processing, showing its application to the New Zealand 2010–2011 seismic sequence

  19. Understanding earthquakes: The key role of radar images

    Energy Technology Data Exchange (ETDEWEB)

    Atzori, Simone, E-mail: simone.atzori@ingv.it [Istituto Nazionale di Geofisica e Vulcanologia, Rome (Italy)

    2013-08-21

    The investigation of the fault rupture underlying earthquakes greatly improved thanks to the spread of radar images. Following pioneer applications in the eighties, Interferometry from Synthetic Aperture Radar (InSAR) gained a prominent role in geodesy. Its capability to measure millimetric deformations for wide areas and the increased data availability from the early nineties, made InSAR a diffused and accepted analysis tool in tectonics, though several factors contribute to reduce the data quality. With the introduction of analytical or numerical modeling, InSAR maps are used to infer the source of an earthquake by means of data inversion. Newly developed algorithms, known as InSAR time-series, allowed to further improve the data accuracy and completeness, strengthening the InSAR contribution even in the study of the inter- and post-seismic phases. In this work we describe the rationale at the base of the whole processing, showing its application to the New Zealand 2010–2011 seismic sequence.

  20. Poison gas and thefirst World War: key role ofpharmacists.

    Science.gov (United States)

    Bonnemain, Bruno

    2016-06-01

    Poison gas has been the subject of attention from the French army (Grand Quartier General). The 22sd of April 1915, General Joffre decided that the General Direction for Health Service was in charge of the protection of troops against what he called "this new mode of terror, disease, and death". Actions are been launched to found ways for the protection means and to obtain for the army at least equivalent weapons. Pharmacists will have a leading role thanks to their knowledge in chemistry. Research laboratories were working in two areas: individual protection and production of aggressive agents. Paul Lebeau, Gabriel Bertrand, Alexandre Degrez, Charles Moureu were among many others very committed to fight and remains at the top and to react quickly to ennemy's attacks. At the end of the war, Paul Lebeau received the Legion d'Honneur medal for his contribution to war. The school of pharmacy was recognized as faculty of pharmacy, by a decree of May 14th, 1920. The knowledge that were obtained during this period will be used for the second World War, but the chemical weapon was not much used, as opposed to more recent usage in Vietnam, Irak and Syria.

  1. Metabolism plays the key roles in Th cells differentiation

    Directory of Open Access Journals (Sweden)

    A. Hosseinzadeh

    2016-12-01

    Full Text Available The increasing rate of autoimmunity in recent decades cannot be related to only genetic instabilities and disorders. Diet can directly influence our health. Studies have shown that there is a relationship between nutritional elements and alteration in the immune system. Among immune cells, the function of T lymphocyte is important in directing immune response. T CD4+ cells lead other immune cells to respond to pathogens by secreting cytokines. HIV+ patients, who have largely lost their T CD4+ cells, are susceptible to opportunistic infections, which do not normally affect healthy people. It seems that the metabolism of T cells is critical for their differentiation and their consequent functions. After activation, T cells need to undergo clonal expansion, which is a high energy- consuming process. Studies have shown that specific metabolites deprivation or their excess supply affects T CD4+cells subsets differentiation. Abnormal induction of subsets of T CD4+ cells causes some autoimmunity reactions and hyper-sensitivity as well, which may result from imbalance of diet uptake. In this mini-review, we describe the findings about fatty acids, glucose, amino acids, and vitamins, which are effective in determining the fates of T CD4+ cells. These findings may help us uncover the role of diet in autoimmune diseases.

  2. Parliamentarians play key role in linking population and social development.

    Science.gov (United States)

    1995-01-01

    Mr. Hirofunti Ando, Deputy Executive Director of the UNFPA, delivered the statement of Dr. Nafis Sadik, Executive Director of the UNFPA at the International Meeting of Parliamentarians on Population and Social Development. The International Conference of Parliamentarians on Population and Development (ICPPD) in Cairo in September 1994 made a significant impact on the attitudes and support of parliamentarians regarding population issues. The Asian Forum of Parliamentarians on Population and Development (AFPPD) brought together a group of parliamentarians from all over the world to discuss population issues and social development. The World Summit included in its deliberations the accumulated experiences of earlier international conferences dealing with social economic issues. The ICPD Program of Action addressed concerns relevant to the agenda of the Social Summit: the crucial contribution that early population stabilization will make towards the attainment of sustainable development; the significant role of integrated policies on population and development in creating employment; the importance of population policies and programs in alleviating poverty; the contributions of reproductive health policies, including high-quality family planning services, to the enhancement of the status of women and to the achievement of gender equality; the synergy between education, family planning, and the general improvement of the human condition; and the relationship between population pressures, poverty, and environmental degradation. The ICPD Program of Action also identified critically important population and development objectives, such as ensuring access to education, especially of girls; reducing infant, child, and maternal mortality; and providing universal access to reproductive health and family planning services. Now the challenge is to mobilize the necessary resources for the Social Summit.

  3. The role of epidermal cytokines in the generation of cutaneous immune reactions and ultraviolet radiation-induced immune suppression

    International Nuclear Information System (INIS)

    Ullrich, S.E.

    1995-01-01

    The immune suppression generated by UV exposure is a major risk factor for skin cancer patients. This finding has fuelled efforts to understand the mechanisms involved in the immune suppression induced by exposure to UV radiation. This article reviews the recent findings on the role of epidermal cytokines in the generation of an immune response and their role in the induction of immune suppression induced by UV exposure. (UK)

  4. The key role of eyewitnesses in rapid earthquake impact assessment

    Science.gov (United States)

    Bossu, Rémy; Steed, Robert; Mazet-Roux, Gilles; Roussel, Frédéric; Etivant, Caroline

    2014-05-01

    published after validation. Quake Catcher Networks (QCN) where a cheap USB MEMS motion sensors transform a PC in a seismic station are being deployed in Thessaloniki and Patras (Greece) in collaboration with Stanford University and the USGS. Flashsourcing is also used which is the analysis in real time of traffic surges observed on EMSC's earthquake information website; these surges are caused by the natural convergence of eyewitnesses who rush to the Internet to investigate the cause of the shaking that they have just felt. Within 5 minutes and independently of any seismic data, this detects felt earthquakes, maps the felt area and can detect the presence of damage. We will also explain the roles of social networks in optimising data collection and how citizen involvement has changed our earthquake information services.

  5. Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

    Science.gov (United States)

    van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

    2012-10-01

    The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

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

    Directory of Open Access Journals (Sweden)

    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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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...

  20. 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.

  1. 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,...

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. [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.

  16. 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.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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.

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

    Science.gov (United States)

    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.

  4. 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)

  5. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

  7. p38 mitogen-activated protein kinase plays a key role in regulating MAPKAPK2 expression

    International Nuclear Information System (INIS)

    Sudo, Tatsuhiko; Kawai, Kayoko; Matsuzaki, Hiroshi; Osada, Hiroyuki

    2005-01-01

    One of three major families of the mitogen-activated kinases (MAPK), p38 as well as JNK, has been shown to transduce extracellular stress stimuli into cellular responses by phospho-relay cascades. Among p38 families, p38α is a widely characterized isoform and the biological phenomena are explained by its kinase activity regulating functions of its downstream substrates. However, its specific contributions to each phenomenon are yet not fully elucidated. For better understanding of the role of MAPKs, especially p38α, we utilized newly established mouse fibroblast cell lines originated from a p38α null mouse, namely, a parental cell line without p38α gene locus, knockout of p38α (KOP), Zeosin-resistant (ZKOP), revertant of p38α (RKOP), and Exip revertant (EKOP). EKOP is smaller in size but grows faster than the others. Although comparable amounts of ERK and JNK are expressed in each cell line, ERK is highly phosphorylated in EKOP even in normal culture conditions. Serum stimulation after serum starvation led to ERK phosphorylation in RKOP and ZKOP, but not in EKOP as much. On the contrary, relative phosphorylation level of JNK to total JNK in response to UV was low in RKOP. And its phosphorylation as well as total JNK is slightly lower in EKOP. RKOP is less sensitive to UV irradiation as judged by the survival rate. Stress response upon UV or sorbitol stimuli, leading to mitogen activate protein kinase activated kinase 2 (MAPKAPK2) phosphorylation, was only observed in RKOP. Further experiments reveal that MAPKAPK2 expression is largely suppressed in ZKOP and EKOP. Its expression was recovered by re-introduction of p38α. The loss of MAPKAPK2 expression accompanied by the defect of p38α is confirmed in an embryonic extract prepared from p38α null mice. These data demonstrate that p38 signal pathway is regulated not only by phosphorylation but also by modulation of the expression of its component. Together, we have established cell lines that can be used in

  8. Resolving Key Uncertainties in Subsurface Energy Recovery: One Role of In Situ Experimentation and URLs (Invited)

    Science.gov (United States)

    Elsworth, D.

    2013-12-01

    Significant uncertainties remain and influence the recovery of energy from the subsurface. These uncertainties include the fate and transport of long-lived radioactive wastes that result from the generation of nuclear power and have been the focus of an active network of international underground research laboratories dating back at least 35 years. However, other nascent carbon-free energy technologies including conventional and EGS geothermal methods, carbon-neutral methods such as carbon capture and sequestration and the utilization of reduced-carbon resources such as unconventional gas reservoirs offer significant challenges in their effective deployment. We illustrate the important role that in situ experiments may play in resolving behaviors at extended length- and time-scales for issues related to chemical-mechanical interactions. Significantly, these include the evolution of transport and mechanical characteristics of stress-sensitive fractured media and their influence of the long-term behavior of the system. Importantly, these interests typically relate to either creating reservoirs (hydroshearing in EGS reservoirs, artificial fractures in shales and coals) or maintaining seals at depth where the permeating fluids may include mixed brines, CO2, methane and other hydrocarbons. Critical questions relate to the interaction of these various fluid mixtures and compositions with the fractured substrate. Important needs are in understanding the roles of key processes (transmission, dissolution, precipitation, sorption and dynamic stressing) on the modification of effective stresses and their influence on the evolution of permeability, strength and induced seismicity on the resulting development of either wanted or unwanted fluid pathways. In situ experimentation has already contributed to addressing some crucial issues of these complex interactions at field scale. Important contributions are noted in understanding the fate and transport of long-lived wastes

  9. 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.

    2013-10-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. Hidden keys to survival: the type, density, pattern and functional role of emperor penguin body feathers.

    Science.gov (United States)

    Williams, Cassondra L; Hagelin, Julie C; Kooyman, Gerald L

    2015-10-22

    Antarctic penguins survive some of the harshest conditions on the planet. Emperor penguins breed on the sea ice where temperatures drop below -40°C and forage in -1.8°C waters. Their ability to maintain 38°C body temperature in these conditions is due in large part to their feathered coat. Penguins have been reported to have the highest contour feather density of any bird, and both filoplumes and plumules (downy feathers) are reported absent in penguins. In studies modelling the heat transfer properties and the potential biomimetic applications of penguin plumage design, the insulative properties of penguin plumage have been attributed to the single afterfeather attached to contour feathers. This attribution of the afterfeather as the sole insulation component has been repeated in subsequent studies. Our results demonstrate the presence of both plumules and filoplumes in the penguin body plumage. The downy plumules are four times denser than afterfeathers and play a key, previously overlooked role in penguin survival. Our study also does not support the report that emperor penguins have the highest contour feather density. © 2015 The Author(s).

  13. 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.

  14. 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.

  15. On the key role of droughts in the dynamics of summer fires in Mediterranean Europe.

    Science.gov (United States)

    Turco, Marco; von Hardenberg, Jost; AghaKouchak, Amir; Llasat, Maria Carmen; Provenzale, Antonello; Trigo, Ricardo M

    2017-03-06

    Summer fires frequently rage across Mediterranean Europe, often intensified by high temperatures and droughts. According to the state-of-the-art regional fire risk projections, in forthcoming decades climate effects are expected to become stronger and possibly overcome fire prevention efforts. However, significant uncertainties exist and the direct effect of climate change in regulating fuel moisture (e.g. warmer conditions increasing fuel dryness) could be counterbalanced by the indirect effects on fuel structure (e.g. warmer conditions limiting fuel amount), affecting the transition between climate-driven and fuel-limited fire regimes as temperatures increase. Here we analyse and model the impact of coincident drought and antecedent wet conditions (proxy for the climatic factor influencing total fuel and fine fuel structure) on the summer Burned Area (BA) across all eco-regions in Mediterranean Europe. This approach allows BA to be linked to the key drivers of fire in the region. We show a statistically significant relationship between fire and same-summer droughts in most regions, while antecedent climate conditions play a relatively minor role, except in few specific eco-regions. The presented models for individual eco-regions provide insights on the impacts of climate variability on BA, and appear to be promising for developing a seasonal forecast system supporting fire management strategies.

  16. Induction of AGAMOUS gene expression plays a key role in ripening of tomato sepals in vitro.

    Science.gov (United States)

    Ishida, B K; Jenkins, S M; Say, B

    1998-03-01

    In vitro culture of VFNT Cherry tomato sepals (calyx) at 16-21 degrees C results in developmental changes that are similar to those that occur in fruit tissue [10]. Sepals become swollen, red, and succulent, produce ethylene, and have increased levels of polygalacturonase RNA. They also produce many flavor volatiles characteristic of ripe tomato fruit and undergo similar changes in sugar content [11]. We examined the expression of the tomato AGAMOUS gene, TAG1, in ripening, in vitro sepal cultures and other tissues from the plant and found that TAG1 RNA accumulates to higher levels than expected from data from other plants. Contrary to reports on the absence of AGAMOUS in sepals, TAG1 RNA levels in green sepals from greenhouse-grown plants is detectable, its concentration increasing with in vitro ripening to levels that were even higher than in red, ripe fruit. Sepals of fruit on transgenic tomato plants that expressed TAG1 ectopically were induced by low temperature to ripen in vivo, producing lycopene and undergoing cell wall softening as is characteristic of pericarpic tissue. We therefore propose that the induction of elevated TAG1 gene expression plays a key role in developmental changes that result in sepal ripening.

  17. 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...

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

    Science.gov (United States)

    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.

  19. 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

  20. 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

  1. Psychophysical research progress of interocular suppression in amblyopic visual system

    Directory of Open Access Journals (Sweden)

    Jing-Jing Li

    2016-03-01

    Full Text Available Some recent animal experiments and psychophysical studies indicate that patients with amblyopia have a structurally intact binocular visual system that is rendered functionally monocular due to suppression, and interocular suppression is a key mechanism in visual deficits experienced by patients with amblyopia. The aim of this review is to provide an overview of recent psychophysical findings that have investigated the important role of interocular suppression in amblyopia, the measurement and modulation of suppression, and new dichoptic treatment intervention that directly target suppression.

  2. 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

  3. 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.

  4. Key role of lipid management in nitrogen and aroma metabolism in an evolved wine yeast strain.

    Science.gov (United States)

    Rollero, Stéphanie; Mouret, Jean-Roch; Sanchez, Isabelle; Camarasa, Carole; Ortiz-Julien, Anne; Sablayrolles, Jean-Marie; Dequin, Sylvie

    2016-02-09

    Fermentative aromas play a key role in the organoleptic profile of young wines. Their production depends both on yeast strain and fermentation conditions. A present-day trend in the wine industry consists in developing new strains with aromatic properties using adaptive evolution approaches. An evolved strain, Affinity™ ECA5, overproducing esters, was recently obtained. In this study, dynamics of nitrogen consumption and of the fermentative aroma synthesis of the evolved and its ancestral strains were compared and coupled with a transcriptomic analysis approach to better understand the metabolic reshaping of Affinity™ ECA5. Nitrogen assimilation was different between the two strains, particularly amino acids transported by carriers regulated by nitrogen catabolite repression. We also observed differences in the kinetics of fermentative aroma production, especially in the bioconversion of higher alcohols into acetate esters. Finally, transcriptomic data showed that the enhanced bioconversion into acetate esters by the evolved strain was associated with the repression of genes involved in sterol biosynthesis rather than an enhanced expression of ATF1 and ATF2 (genes coding for the enzymes responsible for the synthesis of acetate esters from higher alcohols). An integrated approach to yeast metabolism-combining transcriptomic analyses and online monitoring data-showed differences between the two strains at different levels. Differences in nitrogen source consumption were observed suggesting modifications of NCR in the evolved strain. Moreover, the evolved strain showed a different way of managing the lipid source, which notably affected the production of acetate esters, likely because of a greater availability of acetyl-CoA for the evolved strain.

  5. Psychophysical research progress of interocular suppression in amblyopic visual system

    OpenAIRE

    Jing-Jing Li; Yi Huang

    2016-01-01

    Some recent animal experiments and psychophysical studies indicate that patients with amblyopia have a structurally intact binocular visual system that is rendered functionally monocular due to suppression, and interocular suppression is a key mechanism in visual deficits experienced by patients with amblyopia. The aim of this review is to provide an overview of recent psychophysical findings that have investigated the important role of interocular suppression in amblyopia, the measurement an...

  6. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Role of suppressed hepatocellular regeneration and Ca2+ in chlordecone-potentiated CCl4 hepatotoxicity

    International Nuclear Information System (INIS)

    Bell, A.N.

    1987-01-01

    The mechanism by which the chlorinated pesticide chlordecone (CD; Kepone) potentiates CCl 4 -induced hepatotoxicity and lethality was investigated. It was hypothesized that perturbations in Ca 2+ homeostasis, greater than those observed with a low dose of CCl 4 alone, in concert with a suppression of hepatocellular regeneration induced by CD alone or by CD + CCl 4 are responsible, at least in part, for CD-potentiated CCl 4 hepatotoxicity. Ca 2+ homeostasis was evaluated by measuring total cell Ca 2+ and 45 Ca 2+ uptake in viable isolated hepatocyte suspension obtained from normal and CD-pretreated rats receiving CCl 4 in vivo. In the normal rats in vivo CCL challenge did not affect 45 Ca 2+ uptake by viable isolated hepatocytes. In contrast, 45 Ca 2+ uptake was inhibited in viable isolated hepatocytes obtained from rats exposed to CD + CCl 4

  10. Follistatin during pregnancy and its potential role as an ovarian suppressing agent.

    Science.gov (United States)

    Köninger, Angela; Schmidt, Börge; Damaske, Daniela; Birdir, Cahit; Enekwe, Antje; Kimmig, Rainer; Strowitzki, Thomas; Gellhaus, Alexandra

    2017-05-01

    Ovarian quiescence is a common condition during pregnancy. In vitro, follistatin, an antagonist of follicle-stimulating hormone, blocks follicular development at early stages, and its serum levels increase during pregnancy. A possible surrogate biomarker of ovarian arrest during pregnancy is a decrease in anti-mullerian hormone (AMH) levels followed by an increase in these levels on the second day after labor. The purpose of this study was to determine whether follistatin could act as an ovarian-suppressing agent during pregnancy. Follistatin levels and AMH levels were determined at various stages of pregnancy and postpartum. The follistatin and AMH levels of 69 patients were retrospectively determined with the AMH Gen II ELISA and with the Human Follistatin Quantikine ELISA Kit. For 49 patients, samples were available from various trimesters for cross-sectional analysis; for the other 20, samples were available longitudinally from day one before labor and then daily on days 1 through 4 after labor. Statistical significance was determined with linear regression, the Friedman rank sum test and the Wilcoxon-Nemenyi-McDonald-Thompson post hoc test. The behavior of follistatin levels was exactly opposite that of AMH levels: Follistatin levels increased significantly during pregnancy and on the first day after parturition but declined afterwards, whereas AMH levels decreased significantly during pregnancy and increased after labor. Follistatin can induce ovarian arrest during pregnancy. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Role of Gd-DTPA enhanced fat-suppression MR imaging on ovarian tumors

    International Nuclear Information System (INIS)

    Kang, Heoung Keun; Moon, Woong Jae; Seo, Jeong Jin; Kim, Jae Kyu; Park, Jin Gyoon; Choi, Ho Sun

    1995-01-01

    To determine the value of Gd-DTPA enhanced fat-suppression (GEFS) MR imaging in the characterization and differentiation of benign from malignant ovarian tumors. MRI findings of thirty-seven patients with surgically proved 44 ovarian tumors (30 benign, 14 malignant) were studied retrospectively. MR imaging with conventional spin echo (CSE; T1-weighted image TR/TE 450/20, T2-weighted image TR/TE 3500/30, 90) and GEFS were performed with a 1.5T GE signa. MRI findings of tumors including cystic or solid, wall and septal thickness, necrosis, invasion to adjacent organ, ascites and lymphadenopathy were assessed separately by using CSE and GEFS images, and then tumors were characterized as benign or malignant. Compared with CSE image, GEFS MR image showed better visualization of solid component in 5 malignant lesions, wall thickness in 5 malignant and 1 benign lesions, septal thickness in 3 malignant and 1 benign lesions, necrosis in 1 malignant lesion, and adjacent soft tissue invasion in 5 malignant lesions. Correct characterization of malignant tumors was increased from 71% on CSE image to 93% on GEFS image. However, correct characterization of benign tumors was 93% on both images. GEFS MR imaging could be useful for characterization of ovarian tumors, especially in malignant cases, and employed for differentiation of benign from malignant tumors

  12. The role of radial particle pinches in ELM suppression by resonant magnetic perturbations

    International Nuclear Information System (INIS)

    Stacey, W.M.; Evans, T.E.

    2011-01-01

    The force balance in the plasma edge in a matched pair of DIII-D (Luxon 2002 Nucl. Fusion 42 6149) tokamak discharges with and without resonant magnetic perturbations (RMPs) is evaluated in order to investigate the effects on particle transport of RMP applied for the purpose of suppressing edge-localized modes (ELMs). Experimental data are used to evaluate the radial and toroidal force balances, which may be written as a pinch-diffusion relation for the radial ion flux to facilitate investigation of transport effects. The radial electric field in the H-mode plasma had a sharp negative dip in the steep gradient region of the edge pedestal, associated with which was a large inward pinch velocity. The main effect of RMP was to make the edge electric field less negative or more positive, reducing this strong negative dip in the radial electric field (even reversing it from negative to positive over some regions), thereby reducing the strong inward particle pinch in the edge of an H-mode discharge, thus causing a reduction in edge density below the ELM threshold.

  13. The role of rare earth oxide nanoparticles in suppressing the photobleaching of fluorescent organic dyes

    Science.gov (United States)

    Guha, Anubhav; Basu, Anindita

    2013-03-01

    Organic dyes are widely used for both industrial as well as in scientific applications such as the fluorescent tagging of materials. However the process of photobleaching can rapidly degrade dye fluorescence rendering the material non-functional. Thus exploring novel methods for preventing photobleaching can have widespread benefits. In this work we show that the addition of minute quantities of rare earth (RE) oxide nanoparticles can significantly suppress the photobleaching of dyes. The fluorescence of Rhodamine and AlexaFluor dyes was measured as a function of time with and without the addition of CeO2 and La2O3 nanoparticle additives (two RE oxides that contain an oxygen vacancy based defect structure), as well as with FeO nanoparticles (which has an oxygen excess stoichiometry). We find that the rare earth oxides significantly prolonged the lifetimes of the dyes. The results allow us to develop a model based upon the presence of oxygen vacancies defects that allow the RE oxides to act as oxygen scavengers. This enables the RE oxide particles to effectively remove reactive oxygen free radicals generated in the dye solutions during the photoabsorption process. Current affiliation: Harvard University

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. A Novel Ras Effector Pathway Found to Play Significant Role in Tumor Suppression | Poster

    Science.gov (United States)

    By Nancy Parrish, Staff Writer; photo by Richard Frederickson, Staff Photographer Normal cells have mechanisms to prevent the development of cancer. Among these is a type of tumor suppressor mechanism known as oncogene-induced senescence, or OIS, which halts the uncontrolled growth of cells caused by mutations in oncogenes. The oncogene Ras plays a crucial role in inducing OIS

  19. 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.

  20. Increasing Physical Activity among Adults with Disabilities: Doctors Can Play a Key Role

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Dianna Carroll, a senior health scientist with CDC’s Division of Human Development and Disability, talks about the role of doctors and other health professionals in increasing physical activity among adults with disabilities.

  1. KEYING AND ROLE PLAY IN BUSINESS COMMUNICATION: GENDER, AGE AND RACE CUES

    Directory of Open Access Journals (Sweden)

    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.

  2. Thioredoxin plays a key role in retinal neuropathy prior to endothelial damage in diabetic mice

    OpenAIRE

    Ren, Xiang; Li, Chen; Liu, Junli; Zhang, Chenghong; Fu, Yuzhen; Wang, Nina; Ma, Haiying; Lu, Heyuan; Kong, Hui; Kong, Li

    2017-01-01

    Diabetes is a chronic metabolic syndrome that results in changes in carbohydrate, lipid and protein metabolism. With diabetes for a long time, it increases the risk of diabetic retinopathy (DR) and long-term morbidity and mortality. Moreover, emerging evidence suggests that neuron damage occurs earlier than microvascular complications in DR patients, but the underlying mechanism is unclear. We investigated diabetes-induced retinal neuropathy and elucidated key molecular events to identify new...

  3. The key role of causal explanation in the climate change issue

    Directory of Open Access Journals (Sweden)

    Francesca Pongiglione

    2012-06-01

    Full Text Available The basis for adoption of pro-environment behaviour is the understanding of causal passages within climate dynamics. The understanding of the causes of climate change is necessary in order to be able to take mitigation actions  (the subject needs to be aware of his role as a causal agent. Conversely, the understanding of the consequences of climate change is essential in motivating action (the subject must be aware of the risks caused by it in order to prevent them. The case of ozone depletion confirms this view: the understanding of its causal dynamics played a determining role in people’s behavioural response.

  4. Insights into the key roles of proteoglycans in breast cancer biology and translational medicine

    DEFF Research Database (Denmark)

    Theocharis, Achilleas D.; Skandalis, Spyros S.; Neill, Thomas

    2015-01-01

    of proteoglycans on tumor and stromal cell membranes affects cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Despite the high complexity and heterogeneity of breast cancer, the rapid evolution in our knowledge that proteoglycans are among the key players in the breast tumor...... in the proteoglycans that will be presented herein provides the potential for multiple layers of regulation of breast tumor behavior. This review summarizes recent developments concerning the biology of selected proteoglycans in breast cancer, and presents potential targeted therapeutic approaches based on their novel...

  5. Host association of Borrelia burgdorferi sensu lato--the key role of host complement.

    Science.gov (United States)

    Kurtenbach, Klaus; De Michelis, Simona; Etti, Susanne; Schäfer, Stefanie M; Sewell, Henna-Sisko; Brade, Volker; Kraiczy, Peter

    2002-02-01

    Borrelia burgdorferi sensu lato (s.l.), the tick-borne agent of Lyme borreliosis, is a bacterial species complex comprising 11 genospecies. Here, we discuss whether the delineation of genospecies is ecologically relevant. We provide evidence that B. burgdorferi s.l. is structured ecologically into distinct clusters that are host specific. An immunological model for niche adaptation is proposed that suggests the operation of complement-mediated selection in the midgut of the feeding tick. We conclude that vertebrate hosts rather than tick species are the key to Lyme borreliosis spirochaete diversity.

  6. Change Management and the SENCo Role: Developing Key Performance Indicators of Inclusivity

    Science.gov (United States)

    Done, Elizabeth; Murphy, Mike; Bedford, Clare

    2016-01-01

    This article highlights the changing role of special educational needs co-ordinators (SENCos) in England. SENCos are now required to manage change strategically and deliver inclusive school cultures. A school-based evaluative study undertaken by a teacher who is studying for the postgraduate National Award for SEN Co-ordination (NASENCO) for…

  7. Change Management and the SENCo Role: Developing Key Performance Indicators in the Strategic Development of Inclusivity

    Science.gov (United States)

    Done, Liz; Murphy, Mike; Watt, Mia

    2016-01-01

    This article follows an earlier publication highlighting the changing role of special educational needs co-ordinators (SENCos) in England. SENCos are now required to manage change strategically and deliver inclusive school cultures. School-based action research undertaken by a teacher studying for the postgraduate National Award for SEN…

  8. Make Time to Recharge: Growth and Renewal Play Key Roles in Sustaining School Leaders

    Science.gov (United States)

    Drago-Severson, Ellie; Blum-DeStefano, Jessica

    2015-01-01

    Being a school leader in any role is hard, gratifying, and a gift of love. While it can be enormously satisfying to serve students, teachers, families, and school communities, leaders need to refill themselves in order to continue giving to others. This article highlights a learning-oriented model of leadership development and capacity building…

  9. Replicative Stress and the FHIT Gene: Roles in Tumor Suppression, Genome Stability and Prevention of Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Karras, Jenna R.; Paisie, Carolyn A.; Huebner, Kay, E-mail: kay.huebner@osumc.edu [Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210 (United States)

    2014-06-04

    The fragile FHIT gene, encompassing the chromosomal fragile site FRA3B, is an early target of DNA damage in precancerous cells. While vulnerable to DNA damage itself, FHIT protein expression is essential to protect from DNA damage-induced cancer initiation and progression by modulating genome stability, oxidative stress and levels of accumulating DNA damage. Thus, FHIT, whose expression is lost or reduced in many human cancers, is a tumor suppressor and genome caretaker whose loss initiates genome instability in preneoplastic lesions. Ongoing studies are seeking more detailed understanding of the role of FHIT in the cellular response to oxidative damage. This review discusses the relationship between FHIT, reactive oxygen species production, and DNA damage in the context of cancer initiation and progression.

  10. 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

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Increasing Physical Activity among Adults with Disabilities: Doctors Can Play a Key Role

    Centers for Disease Control (CDC) Podcasts

    2014-04-22

    In this podcast, Dr. Dianna Carroll, a senior health scientist with CDC’s Division of Human Development and Disability, talks about the role of doctors and other health professionals in increasing physical activity among adults with disabilities.  Created: 4/22/2014 by National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 5/7/2014.

  15. Histidine Metabolism and IGPD Play a Key Role in Cefquinome Inhibiting Biofilm Formation of Staphylococcus xylosus

    Directory of Open Access Journals (Sweden)

    Yong-hui Zhou

    2018-04-01

    Full Text Available Staphylococcus xylosus (S. xylosus is an AT-rich and coagulase-negative Staphylococcus (CNS. It is normally regarded as non-pathogenic, however, recent studies have demonstrated that it is related to human opportunistic infections and bovine mastitis. In addition, S. xylosus strains have the ability to form biofilm. Biofilms are also involved in chronic infections and antibiotic resistance, there are only a few reports about cefquinome inhibiting S. xylosus biofilm formation and the protein targets of cefquinome. In our study, we found that sub-MICs of cefquinome were sufficient to inhibit biofilm formation. To investigate the potential protein targets of cefquinome, we used iTRAQ for the analyses of cells at two different conditions: 1/2-MIC (0.125 μg/mL cefquinome treatment and no treatment. Using iTRAQ technique and KEGG database analysis, we found that proteins differently expression in histidine metabolism pathway may play a role in the process by which 1/2-MIC (0.125 μg/mL cefquinome inhibits S. xylosus biofilm formation. Interestingly, we found a sharply down-regulated enzyme [A0A068E9J3 imidazoleglycerol-phosphate dehydratase (IGPD] involved in histidine metabolism pathway in cefquinome-treated cells. We demonstrated the important role of IGPD in sub-MICs cefquinome inhibiting biofilm formation of S. xylosus by gene (hisB knockout, IGPD enzyme activity and histidine content assays. Thus, our data sheds light on important role of histidine metabolism in S. xylosus biofilm formation; especially, IGPD involved in histidine metabolism might play a crucial role in sub-MICs cefquinome inhibition of biofilm formation of S. xylosus, and we propose IGPD as an attractive protein target of cefquinome.

  16. The key role of supply chain actors in groundwater irrigation development in North Africa

    Science.gov (United States)

    Lejars, Caroline; Daoudi, Ali; Amichi, Hichem

    2017-09-01

    The role played by supply chain actors in the rapid development of groundwater-based irrigated agriculture is analyzed. Agricultural groundwater use has increased tremendously in the past 50 years, leading to the decline of water tables. Groundwater use has enabled intensification of existing farming systems and ensured economic growth. This "groundwater economy" has been growing rapidly due to the initiative of farmers and the involvement of a wide range of supply chain actors, including suppliers of equipment, inputs retailers, and distributors of irrigated agricultural products. In North Africa, the actors in irrigated production chains often operate at the margin of public policies and are usually described as "informal", "unstructured", and as participating in "groundwater anarchy". This paper underlines the crucial role of supply chain actors in the development of groundwater irrigation, a role largely ignored by public policies and rarely studied. The analysis is based on three case studies in Morocco, Tunisia and Algeria, and focuses on the horticultural sub-sector, in particular on onions and tomatoes, which are irrigated high value crops. The study demonstrates that although supply chain actors are catalyzers of the expansion of groundwater irrigation, they could also become actors in adaptation to the declining water tables. Through their informal activities, they help reduce market risks, facilitate credit and access to subsidies, and disseminate innovation. The interest associated with making these actors visible to agricultural institutions is discussed, along with methods of getting them involved in the management of the resource on which they depend.

  17. The PICALM protein plays a key role in iron homeostasis and cell proliferation.

    Directory of Open Access Journals (Sweden)

    Paula B Scotland

    Full Text Available The ubiquitously expressed phosphatidylinositol binding clathrin assembly (PICALM protein associates with the plasma membrane, binds clathrin, and plays a role in clathrin-mediated endocytosis. Alterations of the human PICALM gene are present in aggressive hematopoietic malignancies, and genome-wide association studies have recently linked the PICALM locus to late-onset Alzheimer's disease. Inactivating and hypomorphic Picalm mutations in mice cause different degrees of severity of anemia, abnormal iron metabolism, growth retardation and shortened lifespan. To understand PICALM's function, we studied the consequences of PICALM overexpression and characterized PICALM-deficient cells derived from mutant fit1 mice. Our results identify a role for PICALM in transferrin receptor (TfR internalization and demonstrate that the C-terminal PICALM residues are critical for its association with clathrin and for the inhibitory effect of PICALM overexpression on TfR internalization. Murine embryonic fibroblasts (MEFs that are deficient in PICALM display several characteristics of iron deficiency (increased surface TfR expression, decreased intracellular iron levels, and reduced cellular proliferation, all of which are rescued by retroviral PICALM expression. The proliferation defect of cells that lack PICALM results, at least in part, from insufficient iron uptake, since it can be corrected by iron supplementation. Moreover, PICALM-deficient cells are particularly sensitive to iron chelation. Taken together, these data reveal that PICALM plays a critical role in iron homeostasis, and offer new perspectives into the pathogenesis of PICALM-associated diseases.

  18. RE: Forests and forest management plays a key role in mitigating climate change

    DEFF Research Database (Denmark)

    Bentsen, Niclas Scott; Nord-Larsen, Thomas; Larsen, Søren

    2016-01-01

    as also reported by Naudts et al. By ignoring the link between forestry and fossil carbon pools and not considering development in the absence of forest management, there is no accounting for the effect on GHG emissions, and no basis for estimating the contribution of forest management to cl......The report by Naudts et al. concludes that forest management in Europe during the last 260 years has failed to result in net CO2 removal from the atmosphere. The authors have reached this conclusion through their failure to consider a key factor in their otherwise comprehensive analysis....... The authors present an analysis of net carbon emissions from forest, but omit substitution effects related to the link between forest management and the fossil carbon pool. The link between fossil and terrestrial carbon pools is however critical for modelling climate impacts. To conclude as they do...

  19. Hypoxia-inducible factor-1 alpha has a key role in hypoxic preconditioning.

    Science.gov (United States)

    Taie, Satoshi; Ono, Junichiro; Iwanaga, Yasuyuki; Tomita, Shuhei; Asaga, Takehiko; Chujo, Kosuke; Ueki, Masaaki

    2009-08-01

    Sublethal hypoxia induces tolerance to subsequent hypoxic insults in a process known as hypoxic preconditioning (HP). Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key transcription protein involved in the mechanism of HP. In this study, we investigated the effects of HP on tissue oxygenation and expression of HIF-1 alpha gene targets in the brain using neural cell-specific HIF-1 alpha-deficient mice. The animals were exposed to 8% oxygen for 3 hours. Twenty-four hours later, the oxygen partial pressure (pO(2)) of brain tissue and gene expression were measured during hypoxia. HP improved the pO(2) of brain tissue during subsequent hypoxia with upregulated inducible nitric oxide synthase in wild-type mice, whereas HP had no detectable effect in the mutant mice. Our results indicate that the protective effects of HP may be partially mediated by improving tissue oxygenation via HIF-1 alpha and inducible nitric oxide synthase.

  20. Mitochondrial concept of leukemogenesis: key role of oxygen-peroxide effects.

    Science.gov (United States)

    Lyu, Boris N; Ismailov, Sanzhar B; Ismailov, Bolat; Lyu, Marina B

    2008-11-11

    The high sensitivity of hematopoietic cells, especially stem cells, to radiation and to pro-oxidative and other leukemogenic agents is related to certain of their morphological and metabolic features. It is attributable to the low (minimal) number of active mitochondria and the consequently slow utilization of O2 entering the cell. This results in an increased intracellular partial pressure of O2 (pO2) and increased levels of reactive oxygen (ROS) and nitrogen (RNS) species, and a Delta(PO - AO) imbalance between the pro-oxidative (PO) and antioxidative (AO) constituents. Because excessive O2 is toxic, we suggest that hematopoietic cells exist in a kind of unstable dynamic balance. This suggestion is based on the idea that mitochondria not only consume O2 in the process of ATP production but also constitute the main anti-oxygenic stage in the cell's protective antioxidative system. Variations in the mitochondrial base capacity (quantity and quality of mitochondria) constitute an important and highly efficient channel for regulating the oxidative stress level within a cell.The primary target for leukemogenic agents is the few mitochondria within the hematopoietic stem cell. Disturbance and weakening of their respiratory function further enhances the initial pro-oxidative state of the cell. This readily results in peroxygenation stress, creating the necessary condition for inducing leukemogenesis. We propose that this is the main cause of all related genetic and other disorders in the cell. ROS, RNS and peroxides act as signal molecules affecting redox-sensitive transcription factors, enzymes, oncogenes and other effectors. Thereby, they influence the expression and suppression of many genes, as well as the course and direction of proliferation, differentiation, leukemogenesis and apoptosis.Differentiation of leukemic cells is blocked at the precursor stage. While the transformation of non-hematopoietic cells into tumor cells starts during proliferation

  1. The key incident monitoring and management system - history and role in quality improvement.

    Science.gov (United States)

    Badrick, Tony; Gay, Stephanie; Mackay, Mark; Sikaris, Ken

    2018-01-26

    The determination of reliable, practical Quality Indicators (QIs) from presentation of the patient with a pathology request form through to the clinician receiving the report (the Total Testing Process or TTP) is a key step in identifying areas where improvement is necessary in laboratories. The Australasian QIs programme Key Incident Monitoring and Management System (KIMMS) began in 2008. It records incidents (process defects) and episodes (occasions at which incidents may occur) to calculate incident rates. KIMMS also uses the Failure Mode Effects Analysis (FMEA) to assign quantified risk to each incident type. The system defines risk as incident frequency multiplied by both a harm rating (on a 1-10 scale) and detection difficulty score (also a 1-10 scale). Between 2008 and 2016, laboratories participating rose from 22 to 69. Episodes rose from 13.2 to 43.4 million; incidents rose from 114,082 to 756,432. We attribute the rise in incident rate from 0.86% to 1.75% to increased monitoring. Haemolysis shows the highest incidence (22.6% of total incidents) and the highest risk (26.68% of total risk). "Sample is suspected to be from the wrong patient" has the second lowest frequency, but receives the highest harm rating (10/10) and detection difficulty score (10/10), so it is calculated to be the 8th highest risk (2.92%). Similarly, retracted (incorrect) reports QI has the 10th highest frequency (3.9%) but the harm/difficulty calculation confers the second highest risk (11.17%). TTP incident rates are generally low (less than 2% of observed episodes), however, incident risks, their frequencies multiplied by both ratings of harm and discovery difficulty scores, concentrate improvement attention and resources on the monitored incident types most important to manage.

  2. THE KEY ROLE OF SOLAR DYNAMICS IN THE CHROMOSPHERIC HANLE POLARIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Carlin, E. S.; Bianda, M., E-mail: escarlin@irsol.ch [Istituto Ricerche Solari Locarno, 6600 Locarno (Switzerland)

    2016-11-01

    The quantum theory of polarized light allows one to model scattering in the solar atmosphere for inferring its properties. This powerful approach has revealed two key long-standing problems in solar physics: the puzzling dilemmas between theory and observations in several anomalously polarized spectral lines and the need for inferring the ubiquitous weak chromospheric magnetic fields, which requires discriminating the Hanle effect in dynamic optically thick plasmas. However, the ever-present dynamics, i.e., the temporal evolution of heatings and macroscopic motions, has been widely disregarded when modeling and interpreting the scattering polarization. This has hindered a consistent theoretical solution to the puzzle while falsifying the Hanle diagnosis. Here, we show that the dynamical evolution is a keystone for solving both problems because its systematic impact allows an explanation of the observations from “anomalous” instantaneous polarization signals. Evolution accounted for, we reproduce amplitudes and (spectral and spatial) shapes of the Ca i 4227 Å polarization at solar disk center, identifying a restrictive arrangement of magnetic fields, kinematics, heatings, and spatio-temporal resolution. We find that the joint action of dynamics, Hanle effect, and low temporal resolutions mimics Zeeman linear polarization profiles, the true weak-field Zeeman signals being negligible. Our results allow reinterpretation of many polarization signals of the solar spectra and support time-dependent scattering polarization as a powerful tool for deciphering the spatio-temporal distribution of chromospheric heatings and fields. This approach may be a key aid in developing the Hanle diagnosis for the solar atmosphere.

  3. Cytosolic NADP+-dependent isocitrate dehydrogenase plays a key role in lipid metabolism.

    Science.gov (United States)

    Koh, Ho-Jin; Lee, Su-Min; Son, Byung-Gap; Lee, Soh-Hyun; Ryoo, Zae Young; Chang, Kyu-Tae; Park, Jeen-Woo; Park, Dong-Chan; Song, Byoung J; Veech, Richard L; Song, Hebok; Huh, Tae-Lin

    2004-09-17

    NADPH is an essential cofactor for many enzymatic reactions including glutathione metabolism and fat and cholesterol biosynthesis. We have reported recently an important role for mitochondrial NADP(+)-dependent isocitrate dehydrogenase in cellular defense against oxidative damage by providing NADPH needed for the regeneration of reduced glutathione. However, the role of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is still unclear. We report here for the first time that IDPc plays a critical role in fat and cholesterol biosynthesis. During differentiation of 3T3-L1 adipocytes, both IDPc enzyme activity and its protein content were increased in parallel in a time-dependent manner. Increased expression of IDPc by stable transfection of IDPc cDNA positively correlated with adipogenesis of 3T3-L1 cells, whereas decreased IDPc expression by an antisense IDPc vector retarded adipogenesis. Furthermore, transgenic mice with overexpressed IDPc exhibited fatty liver, hyperlipidemia, and obesity. In the epididymal fat pads of the transgenic mice, the expressions of adipocyte-specific genes including peroxisome proliferator-activated receptor gamma were markedly elevated. The hepatic and epididymal fat pad contents of acetyl-CoA and malonyl-CoA in the transgenic mice were significantly lower, whereas the total triglyceride and cholesterol contents were markedly higher in the liver and serum of transgenic mice compared with those measured in wild type mice, suggesting that the consumption rate of those lipogenic precursors needed for fat biosynthesis must be increased by elevated IDPc activity. Taken together, our findings strongly indicate that IDPc would be a major NADPH producer required for fat and cholesterol synthesis.

  4. Amygdalar glutamatergic neuronal systems play a key role on the hibernating state of hamsters

    Directory of Open Access Journals (Sweden)

    Facciolo Rosa

    2011-01-01

    Full Text Available Abstract Background Excitatory transmitting mechanisms are proving to play a critical role on neuronal homeostasis conditions of facultative hibernators such as the Syrian golden hamster. Indeed works have shown that the glutamatergic system of the main olfactory brain station (amygdala is capable of controlling thermoregulatory responses, which are considered vital for the different hibernating states. In the present study the role of amygdalar glutamatergic circuits on non-hibernating (NHIB and hibernating (HIB hamsters were assessed on drinking stimuli and subsequently compared to expression variations of some glutamatergic subtype mRNA levels in limbic areas. For this study the two major glutamatergic antagonists and namely that of N-methyl-D-aspartate receptor (NMDAR, 3-(+-2-carboxypiperazin-4-yl-propyl-1-phosphonate (CPP plus that of the acid α-amine-3-hydroxy-5-metil-4-isoxazol-propionic receptor (AMPAR site, cyano-7-nitro-quinoxaline-2,3-dione (CNQX were infused into the basolateral amygdala nucleus. Attempts were made to establish the type of effects evoked by amygdalar glutamatergic cross-talking processes during drinking stimuli, a response that may corroborate their major role at least during some stages of this physiological activity in hibernators. Results From the behavioral results it appears that the two glutamatergic compounds exerted distinct effects. In the first case local infusion of basolateral complexes (BLA with NMDAR antagonist caused very great (p Conclusion We conclude that predominant drinking events evoked by glutamatergic mechanisms, in the presence of prevalently down regulated levels of NR1/2A of some telencephalic and hypothalamic areas appear to constitute an important neuronal switch at least during arousal stage of hibernation. The establishment of the type of glutamatergic subtypes that are linked to successful hibernating states, via drinking stimuli, may have useful bearings toward sleeping disorders.

  5. How coaching can play a key role in the development of nurse managers.

    Science.gov (United States)

    Westcott, Liz

    2016-09-01

    The aim of this study was to explore empirically the role that coaching plays in the development of nurse managers in order to inform further research and policy makers about the potential utility and value of this means of development. There is evidence of the importance of the role of nurse managers who are first line managers of a team of nurses within any health sector. However, there appears to be little understanding of the United Kingdom wide scope of nurse manager development across the United Kingdom and the means to increase its effectiveness. At the same time, it appears that some nurse managers receive coaching to help in their development. This is a mixed methods study, using a pragmatist paradigm. Data was gathered from a quantitative survey and qualitative interviews. This paper is reporting the results of the qualitative interviews only. Twenty-one qualitative interviews were undertaken with nurse managers, coaches and directors of nursing to draw out their own experiences of coaching for nurse managers. Thematic analysis framework was used for data interrogation, identifying new patterns and emerging themes. Themes that emerged from interviews include how nurse managers were introduced to coaching, how they balanced transitions, the role of reflection, the value of relationships and overlaps between clinical supervision, mentoring and coaching. Findings show that following coaching, nurse managers gained increased resilience, confidence and better coping mechanisms. This resulted in perceived improved team management and cohesion and appeared to lead to better quality of care for patients. This study suggests the importance of nurse managers accessing coaching, to enable transformational leadership of their teams of nurses. It suggests also the importance of organisations supporting a coaching culture, to ensure staff satisfaction, motivation and improved quality of patient care. © 2016 John Wiley & Sons Ltd.

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

    DEFF Research Database (Denmark)

    Batterman, Sarah A.; Hedin, Lars O.; Van Breugel, Michiel

    2013-01-01

    Forests contribute a significant portion of the land carbon sink, but their ability to sequester CO 2 may be constrained by nitrogen, a major plant-limiting nutrient. Many tropical forests possess tree species capable of fixing atmospheric dinitrogen (N 2), but it is unclear whether this function...... tree species across the entire forest age sequence. These findings show that symbiotic N 2 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 CO 2....

  7. A novel microglial subset plays a key role in myelinogenesis in developing brain

    DEFF Research Database (Denmark)

    Wlodarczyk, Agnieszka; Holtman, Inge; Krueger, Martin

    2017-01-01

    Microglia are resident macrophages of the central nervous system that contribute to homeostasis and neuroinflammation. Although known to play an important role in brain development, their exact function has not been fully described. Here we show that in contrast to healthy adult and inflammation......-activated cells, neonatal microglia show a unique myelinogenic and neurogenic phenotype. A CD11c+ microglial subset that predominates in primary myelinating areas of the developing brain expresses genes for neuronal and glial survival, migration and differentiation. These cells are the major source of insulin...

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

    Science.gov (United States)

    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

  9. Key role of European rabbits in the conservation of the Western Mediterranean basin hotspot.

    Science.gov (United States)

    Delibes-Mateos, Miguel; Delibes, Miguel; Ferreras, Pablo; Villafuerte, Rafael

    2008-10-01

    The Mediterranean Basin is a global hotspot of biodiversity. Hotspots are said to be experiencing a major loss of habitat, but an added risk could be the decline of some species having a special role in ecological relationships of the system. We reviewed the role of European rabbits (Oryctolagus cuniculus) as a keystone species in the Iberian Peninsula portion of the Mediterranean hotspot. Rabbits conspicuously alter plant species composition and vegetation structure through grazing and seed dispersal, which creates open areas and preserves plant species diversity. Moreover, rabbit latrines have a demonstrable effect on soil fertility and plant growth and provide new feeding resources for many invertebrate species. Rabbit burrows provide nest sites and shelter for vertebrates and invertebrates. In addition, rabbits serve as prey for a number of predators, including the critically endangered Iberian lynx (Lynx pardinus) and Spanish Imperial Eagle (Aquila adalberti). Thus, the Mediterranean ecosystem of the Iberian Peninsula should be termed "the rabbit's ecosystem." To our knowledge, this is the first empirical support for existence of a multifunctional keystone species in a global hotspot of biodiversity. Rabbit populations have declined drastically on the Iberian Peninsula, with potential cascading effects and serious ecological and economic consequences. From this perspective, rabbit recovery is one of the biggest challenges for conservation of the Mediterranean Basin hotspot.

  10. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    2008-09-01

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  11. CD155/PVR plays a key role in cell motility during tumor cell invasion and migration

    International Nuclear Information System (INIS)

    Sloan, Kevin E; Ilag, Leodevico L; Jay, Daniel G; Eustace, Brenda K; Stewart, Jean K; Zehetmeier, Carol; Torella, Claudia; Simeone, Marina; Roy, Jennifer E; Unger, Christine; Louis, David N

    2004-01-01

    Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration. We developed a functional proteomic screen to identify mediators of tumor cell invasion. This screen couples Fluorophore Assisted Light Inactivation (FALI) to a scFv antibody library to systematically inactivate surface proteins expressed by human fibrosarcoma cells followed by a high-throughput assessment of transwell invasion. Using this screen, we have identified CD155 (the poliovirus receptor) as a mediator of tumor cell invasion through its role in migration. Knockdown of CD155 by FALI or by RNAi resulted in a significant decrease in transwell migration of HT1080 fibrosarcoma cells towards a serum chemoattractant. CD155 was found to be highly expressed in multiple cancer cell lines and primary tumors including glioblastoma (GBM). Knockdown of CD155 also decreased migration of U87MG GBM cells. CD155 is recruited to the leading edge of migrating cells where it colocalizes with actin and αv-integrin, known mediators of motility and adhesion. Knockdown of CD155 also altered cellular morphology, resulting in cells that were larger and more elongated than controls when plated on a Matrigel substrate. These results implicate a role for CD155 in mediating tumor cell invasion and migration and suggest that CD155 may contribute to tumorigenesis

  12. The key role of CYC2 during meiosis in Tetrahymena thermophila.

    Science.gov (United States)

    Xu, Qianlan; Wang, Ruoyu; Ghanam, A R; Yan, Guanxiong; Miao, Wei; Song, Xiaoyuan

    2016-04-01

    Meiotic recombination is carried out through a specialized pathway for the formation and repair of DNA double-strand breaks (DSBs) made by the Spo11 protein. The present study shed light on the functional role of cyclin, CYC2, in Tetrahymena thermophila which has transcriptionally high expression level during meiosis process. Knocking out the CYC2 gene results in arrest of meiotic conjugation process at 2.5-3.5 h after conjugation initiation, before the meiosis division starts, and in company with the absence of DSBs. To investigate the underlying mechanism of this phenomenon, a complete transcriptome profile was performed between wild-type strain and CYC2 knock-out strain. Functional analysis of RNA-Seq results identifies related differentially expressed genes (DEGs) including SPO11 and these DEGs are enriched in DNA repair/mismatch repair (MMR) terms in homologous recombination (HR), which indicates that CYC2 could play a crucial role in meiosis by regulating SPO11 and participating in HR.

  13. Genetic Disruption of 2-Arachidonoylglycerol Synthesis Reveals a Key Role for Endocannabinoid Signaling in Anxiety Modulation

    Directory of Open Access Journals (Sweden)

    Brian C. Shonesy

    2014-12-01

    Full Text Available Summary: Endocannabinoid (eCB signaling has been heavily implicated in the modulation of anxiety and depressive behaviors and emotional learning. However, the role of the most-abundant endocannabinoid 2-arachidonoylglycerol (2-AG in the physiological regulation of affective behaviors is not well understood. Here, we show that genetic deletion of the 2-AG synthetic enzyme diacylglycerol lipase α (DAGLα in mice reduces brain, but not circulating, 2-AG levels. DAGLα deletion also results in anxiety-like and sex-specific anhedonic phenotypes associated with impaired activity-dependent eCB retrograde signaling at amygdala glutamatergic synapses. Importantly, acute pharmacological normalization of 2-AG levels reverses both phenotypes of DAGLα-deficient mice. These data suggest 2-AG deficiency could contribute to the pathogenesis of affective disorders and that pharmacological normalization of 2-AG signaling could represent an approach for the treatment of mood and anxiety disorders. : The role of the primary endogenous cannabinoid 2-AG in mood and anxiety regulation is not well understood. Shonesy et al. show that deletion of a primary 2-AG synthetic enzyme, DAGLα, results in anxiety and sex-specific depressive phenotypes, which can be rapidly reversed by pharmacological normalization of endocannabinoid levels.

  14. Closing the Loop: Key Role of Iron in Metal-Bearing Waste Recycling

    Directory of Open Access Journals (Sweden)

    Sedlakova-Kadukova J.

    2017-09-01

    Full Text Available The role of iron in metal-bearing waste bioleaching was studied. Four various types of waste (printed circuit boards (PCBs, Ni-Cd batteries, alkaline batteries and Li-ion batteries were treated by bioleaching using the acidophilic bacteria A. ferrooxidans and A. thiooxidans (separately or in mixture. Role of main leaching agents (Fe3+ ions or sulphuric acid was simulated in abiotic experiments. Results showed that oxidation abilities of Fe3+ ions were crucial for recovery of Cu and Zn from PCBs, with the efficiencies of 88% and 100%, respectively. To recover 68% of Ni from PCBs, and 55% and 100% of Ni and Cd, respectively, from Ni-Cd batteries both oxidation action and hydrolysis of Fe3+ were required. The importance of Fe2+ ions as a reducing agent was showed in bioleaching of Co from Li-ion batteries and Mn from alkaline batteries. The efficiency of the processes has increased by 70% and 40% in Co and Mn bioleaching, respectively, in the presence of Fe2+ ions. Based on the results we suggest the integrated biometallurgical model of metal-bearing waste recycling in the effort to develop zero-waste and less energy-dependent technologies.

  15. Strengthening a consolidated memory: the key role of the reconsolidation process.

    Science.gov (United States)

    Forcato, Cecilia; Fernandez, Rodrigo S; Pedreira, María E

    2014-01-01

    The reconsolidation hypothesis posits that the presentation of a specific cue, previously associated with a life event, makes the stored memory pass from a stable to a reactivated state. In this state, memory is again labile and susceptible to different agents, which may either damage or improve the original memory. Such susceptibility decreases over time and leads to a re-stabilization phase known as reconsolidation process. This process has been assigned two biological roles: memory updating, which suggests that destabilization of the original memory allows the integration of new information into the background of the original memory; and memory strengthening, which postulates that the labilization-reconsolidation process strengthens the original memory. The aim of this review is to analyze the strengthening as an improvement obtained only by triggering such process without any other treatment. In our lab, we have demonstrated that when triggering the labilization-reconsolidation process at least once the original memory becomes strengthened and increases its persistence. We have also shown that repeated labilization-reconsolidation processes strengthened the original memory by enlarging its precision, and said reinforced memories were more resistant to interference. Finally, we have shown that the strengthening function is not operative in older memories. We present and discuss both our findings and those of others, trying to reveal the central role of reconsolidation in the modification of stored information. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Mitochondrial concept of leukemogenesis: key role of oxygen-peroxide effects

    Directory of Open Access Journals (Sweden)

    Ismailov Bolat

    2008-11-01

    Full Text Available Abstract Background and hypothesis The high sensitivity of hematopoietic cells, especially stem cells, to radiation and to pro-oxidative and other leukemogenic agents is related to certain of their morphological and metabolic features. It is attributable to the low (minimal number of active mitochondria and the consequently slow utilization of O2 entering the cell. This results in an increased intracellular partial pressure of O2 (pO2 and increased levels of reactive oxygen (ROS and nitrogen (RNS species, and a Δ(PO – AO imbalance between the pro-oxidative (PO and antioxidative (AO constituents. Proposed mechanism Because excessive O2 is toxic, we suggest that hematopoietic cells exist in a kind of unstable dynamic balance. This suggestion is based on the idea that mitochondria not only consume O2 in the process of ATP production but also constitute the main anti-oxygenic stage in the cell's protective antioxidative system. Variations in the mitochondrial base capacity (quantity and quality of mitochondria constitute an important and highly efficient channel for regulating the oxidative stress level within a cell. The primary target for leukemogenic agents is the few mitochondria within the hematopoietic stem cell. Disturbance and weakening of their respiratory function further enhances the initial pro-oxidative state of the cell. This readily results in peroxygenation stress, creating the necessary condition for inducing leukemogenesis. We propose that this is the main cause of all related genetic and other disorders in the cell. ROS, RNS and peroxides act as signal molecules affecting redox-sensitive transcription factors, enzymes, oncogenes and other effectors. Thereby, they influence the expression and suppression of many genes, as well as the course and direction of proliferation, differentiation, leukemogenesis and apoptosis. Differentiation of leukemic cells is blocked at the precursor stage. While the transformation of non

  17. Spread of Zika virus:The key role of mosquito vector control

    Institute of Scientific and Technical Information of China (English)

    Giovanni Benelli

    2016-01-01

    Mosquitoes (Diptera: Culicidae) represent a key threat for millions of humans and ani-mals worldwide, since they act as vectors for important parasites and pathogens, including malaria, filariasis and a wide number of arboviruses. The recent outbreaks of Zika virus infections occurring in South America, Central America, and the Caribbean, represent the most recent four arrivals of important arboviruses in the western hemi-sphere, over the last 20 years, namely dengue, West Nile virus, and chikungunya. Since there are no specific treatments for Zika virus and the other arboviruses mentioned above, it should be highlighted that the eco-friendly and effective control of mosquito vectors is of pivotal importance. Besides radiation, transgenic and symbiont-based mosquito control approaches, an effective option may be the employ of biological control agents of mosquito young instars, in presence of ultra-low quantities of green-synthesized nano-particles, which magnify their predation efficiency. Furthermore, behaviour-based control tools relying on the employ of swarming behaviour manipulation (i.e. the“lure and kill”approach), pheromone traps, sound traps need further research attention. In particular, detailed basic information on the physical and chemical cues routing mosquito swarming and mating dynamics is urgently required.

  18. Spread of Zika virus:The key role of mosquito vector control

    Institute of Scientific and Technical Information of China (English)

    Giovanni Benelli

    2016-01-01

    Mosquitoes(Diptera: Culicidae) represent a key threat for millions of humans and animals worldwide, since they act as vectors for important parasites and pathogens,including malaria, filariasis and a wide number of arboviruses. The recent outbreaks of Zika virus infections occurring in South America, Central America, and the Caribbean,represent the most recent four arrivals of important arboviruses in the western hemisphere, over the last 20 years, namely dengue, West Nile virus, and chikungunya. Since there are no specific treatments for Zika virus and the other arboviruses mentioned above,it should be highlighted that the eco-friendly and effective control of mosquito vectors is of pivotal importance. Besides radiation, transgenic and symbiont-based mosquito control approaches, an effective option may be the employ of biological control agents of mosquito young instars, in presence of ultra-low quantities of green-synthesized nanoparticles, which magnify their predation efficiency. Furthermore, behaviour-based control tools relying on the employ of swarming behaviour manipulation(i.e. the "lure and kill"approach), pheromone traps, sound traps need further research attention. In particular,detailed basic information on the physical and chemical cues routing mosquito swarming and mating dynamics is urgently required.

  19. From rapid place learning to behavioral performance: a key role for the intermediate hippocampus.

    Directory of Open Access Journals (Sweden)

    Tobias Bast

    2009-04-01

    Full Text Available Rapid place encoding by hippocampal neurons, as reflected by place-related firing, has been intensely studied, whereas the substrates that translate hippocampal place codes into behavior have received little attention. A key point relevant to this translation is that hippocampal organization is characterized by functional-anatomical gradients along the septotemporal axis: Whereas the ability of hippocampal neurons to encode accurate place information declines from the septal to temporal end, hippocampal connectivity to prefrontal and subcortical sites that might relate such place information to behavioral-control processes shows an opposite gradient. We examined in rats the impact of selective lesions to relevant parts of the hippocampus on behavioral tests requiring place learning (watermaze procedures and on in vivo electrophysiological models of hippocampal encoding (long-term potentiation [LTP], place cells. We found that the intermediate hippocampus is necessary and largely sufficient for behavioral performance based on rapid place learning. In contrast, a residual septal pole of the hippocampus, although displaying intact electrophysiological indices of rapid information encoding (LTP, precise place-related firing, and rapid remapping, failed to sustain watermaze performance based on rapid place learning. These data highlight the important distinction between hippocampal encoding and the behavioral performance based on such encoding, and suggest that the intermediate hippocampus, where substrates of rapid accurate place encoding converge with links to behavioral control, is critical to translate rapid (one-trial place learning into navigational performance.

  20. Aroma extraction dilution analysis of Sauternes wines. Key role of polyfunctional thiols.

    Science.gov (United States)

    Bailly, Sabine; Jerkovic, Vesna; Marchand-Brynaert, Jacqueline; Collin, Sonia

    2006-09-20

    The aim of the present work was to investigate Sauternes wine aromas. In all wine extracts, polyfunctional thiols were revealed to have a huge impact. A very strong bacon-petroleum odor emerged at RI = 845 from a CP-Sil5-CB column. Two thiols proved to participate in this perception: 3-methyl-3-sulfanylbutanal and 2-methylfuran-3-thiol. A strong synergetic effect was evidenced between the two compounds. The former, never mentioned before in wines, and not found in the musts of this study, is most probably synthesized during fermentation. 3-Methylbut-2-ene-1-thiol, 3-sulfanylpropyl acetate, 3-sulfanylhexan-1-ol, and 3-sulfanylheptanal also contribute to the global aromas of Sauternes wines. Among other key odorants, the presence of a varietal aroma (alpha-terpineol), sotolon, fermentation alcohols (3-methylbutan-1-ol and 2-phenylethanol) and esters (ethyl butyrate, ethyl hexanoate, and ethyl isovalerate), carbonyls (trans-non-2-enal and beta-damascenone), and wood flavors (guaiacol, vanillin, eugenol, beta-methyl-gamma-octalactone, and Furaneol) is worth stressing.

  1. The key role of patrilineal inheritance in shaping the genetic variation of Dagestan highlanders.

    Science.gov (United States)

    Caciagli, Laura; Bulayeva, Kazima; Bulayev, Oleg; Bertoncini, Stefania; Taglioli, Luca; Pagani, Luca; Paoli, Giorgio; Tofanelli, Sergio

    2009-12-01

    The Caucasus region is a complex cultural and ethnic mosaic, comprising populations that speak Caucasian, Indo-European and Altaic languages. Isolated mountain villages (auls) in Dagestan still preserve high level of genetic and cultural diversity and have patriarchal societies with a long history of isolation. The aim of this study was to understand the genetic history of five Dagestan highland auls with distinct ethnic affiliation (Avars, Chechens-Akkins, Kubachians, Laks, Tabasarans) using markers on the male-specific region of the Y chromosome. The groups analyzed here are all Muslims but speak different languages all belonging to the Nakh-Dagestanian linguistic family. The results show that the Dagestan ethnic groups share a common Y-genetic background, with deep-rooted genealogies and rare alleles, dating back to an early phase in the post-glacial recolonization of Europe. Geography and stochastic factors, such as founder effect and long-term genetic drift, driven by the rigid structuring of societies in groups of patrilineal descent, most likely acted as mutually reinforcing key factors in determining the high degree of Y-genetic divergence among these ethnic groups.

  2. When cooperation begets cooperation: the role of key individuals in galvanizing support.

    Science.gov (United States)

    McAuliffe, Katherine; Wrangham, Richard; Glowacki, Luke; Russell, Andrew F

    2015-12-05

    Life abounds with examples of conspecifics actively cooperating to a common end, despite conflicts of interest being expected concerning how much each individual should contribute. Mathematical models typically find that such conflict can be resolved by partial-response strategies, leading investors to contribute relatively equitably. Using a case study approach, we show that such model expectations can be contradicted in at least four disparate contexts: (i) bi-parental care; (ii) cooperative breeding; (iii) cooperative hunting; and (iv) human cooperation. We highlight that: (a) marked variation in contributions is commonplace; and (b) individuals can often respond positively rather than negatively to the contributions of others. Existing models have surprisingly limited power in explaining these phenomena. Here, we propose that, although among-individual variation in cooperative contributions will be influenced by differential costs and benefits, there is likely to be a strong genetic or epigenetic component. We then suggest that selection can maintain high investors (key individuals) when their contributions promote support by increasing the benefits and/or reducing the costs for others. Our intentions are to raise awareness in--and provide testable hypotheses of--two of the most poorly understood, yet integral, questions regarding cooperative ventures: why do individuals vary in their contributions and when does cooperation beget cooperation? © 2015 The Author(s).

  3. Key processes shaping the current role and operation of higher education institutions in society

    Directory of Open Access Journals (Sweden)

    Piróg Danuta

    2016-03-01

    Full Text Available The concurrent processes of globalisation, computerisation, and integration shape and constantly modify developmental factors and generate multidirectional social changes. Among social life fields, one of them has been particularly sensitive to the impact of those processes and has remained in clear feedback relationship with them is education, including university-level education. This article aims to present some reflections on the key processes which influence the environment of higher education institutions’ activity and on what their impact specifically is. The factors taken into account include: the transformation of the political and economic system, integration with the European higher education area, the market shift of education, evolving social demands towards higher education institutions and society’s attitude towards work. As knowledge has become an asset largely affecting the quality of life of people and society, universities have changed their focus from searching for and exploring truth, good and beauty in the world towards becoming innovation centres, transferring knowledge as offering their educational services. In this article, those trends have been exemplified in relation to geography degree programmes, and shown through an evolution of the model of the university. Based on a review of the literature, it seems that the processes discussed also concern geography degree programmes, and the future operation of these programmes closely depends on whether they can maintain their care for high quality education coupled with genuine efforts to ensure the smooth transition of graduates into the labour market.

  4. Developmental programming: the concept, large animal models, and the key role of uteroplacental vascular development.

    Science.gov (United States)

    Reynolds, L P; Borowicz, P P; Caton, J S; Vonnahme, K A; Luther, J S; Hammer, C J; Maddock Carlin, K R; Grazul-Bilska, A T; Redmer, D A

    2010-04-01

    Developmental programming refers to the programming of various bodily systems and processes by a stressor of the maternal system during pregnancy or during the neonatal period. Such stressors include nutritional stress, multiple pregnancy (i.e., increased numbers of fetuses in the gravid uterus), environmental stress (e.g., high environmental temperature, high altitude, prenatal steroid exposure), gynecological immaturity, and maternal or fetal genotype. Programming refers to impaired function of numerous bodily systems or processes, leading to poor growth, altered body composition, metabolic dysfunction, and poor productivity (e.g., poor growth, reproductive dysfunction) of the offspring throughout their lifespan and even across generations. A key component of developmental programming seems to be placental dysfunction, leading to altered fetal growth and development. We discuss various large animal models of developmental programming and how they have and will continue to contribute to our understanding of the mechanisms underlying altered placental function and developmental programming, and, further, how large animal models also will be critical to the identification and application of therapeutic strategies that will alleviate the negative consequences of developmental programming to improve offspring performance in livestock production and human medicine.

  5. Spread of Zika virus: The key role of mosquito vector control

    Directory of Open Access Journals (Sweden)

    Giovanni Benelli

    2016-06-01

    Full Text Available Mosquitoes (Diptera: Culicidae represent a key threat for millions of humans and animals worldwide, since they act as vectors for important parasites and pathogens, including malaria, filariasis and a wide number of arboviruses. The recent outbreaks of Zika virus infections occurring in South America, Central America, and the Caribbean, represent the most recent four arrivals of important arboviruses in the western hemisphere, over the last 20 years, namely dengue, West Nile virus, and chikungunya. Since there are no specific treatments for Zika virus and the other arboviruses mentioned above, it should be highlighted that the eco-friendly and effective control of mosquito vectors is of pivotal importance. Besides radiation, transgenic and symbiont-based mosquito control approaches, an effective option may be the employ of biological control agents of mosquito young instars, in presence of ultra-low quantities of green-synthesized nanoparticles, which magnify their predation efficiency. Furthermore, behaviour-based control tools relying on the employ of swarming behaviour manipulation (i.e. the “lure and kill” approach, pheromone traps, sound traps need further research attention. In particular, detailed basic information on the physical and chemical cues routing mosquito swarming and mating dynamics is urgently required.

  6. The Expanding Role of Traceability in Seafood: Tools and Key Initiatives.

    Science.gov (United States)

    Lewis, Sara G; Boyle, Mariah

    2017-08-01

    In the last decade, a range of drivers within the seafood sector have incentivized the application of traceability to issues beyond food safety and inventory management. Some of the issues motivating the expanded use of traceability within the global seafood sector include: increased media attention on the legal and social risks within some seafood supply chains, governmental traceability requirements, private-sector sustainability commitments, and others. This article begins with an overview of these topics in the seafood industry, and why many nongovernment organizations (NGOs), companies, and government actors have turned to traceability as a tool to address them. We discuss how traceability connects to key requirements of environmental sustainability and social responsibility. Later, we review the range of traceability services, tools, software solutions, and the due diligence measures that are currently being leveraged within the seafood sector. The paper concludes with a discussion of several NGO- and industry-led traceability initiatives that are examples of seafood traceability improvements. © 2017 Institute of Food Technologists®.

  7. Short-term selective alleviation of glucotoxicity and lipotoxicity ameliorates the suppressed expression of key β-cell factors under diabetic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Shimo, Naoki [Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871 (Japan); Matsuoka, Taka-aki, E-mail: matsuoka@endmet.med.osaka-u.ac.jp [Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871 (Japan); Miyatsuka, Takeshi [Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871 (Japan); Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunky-ku, Tokyo, 113-8421 (Japan); Takebe, Satomi; Tochino, Yoshihiro; Takahara, Mitsuyoshi [Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871 (Japan); Kaneto, Hideaki [Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki-city, Okayama, 701-0192 (Japan); Shimomura, Iichiro [Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871 (Japan)

    2015-11-27

    Alleviation of hyperglycaemia and hyperlipidemia improves pancreatic β-cell function in type 2 diabetes. However, the underlying molecular mechanisms are still not well clarified. In this study, we aimed to elucidate how the expression alterations of key β-cell factors are altered by the short-term selective alleviation of glucotoxicity or lipotoxicity. We treated db/db mice for one week with empagliflozin and/or bezafibrate to alleviate glucotoxicity and/or liptotoxicity, respectively. The gene expression levels of Pdx1 and Mafa, and their potential targets, insulin 1, Slc2a2, and Glp1r, were higher in the islets of empagliflozin-treated mice, and levels of insulin 2 were higher in mice treated with both reagents, than in untreated mice. Moreover, compared to the pretreatment levels, Mafa and insulin 1 expression increased in empagliflozin-treated mice, and Slc2a2 increased in combination-treated mice. In addition, empagliflozin treatment enhanced β-cell proliferation assessed by Ki-67 immunostaining. Our date clearly demonstrated that the one-week selective alleviation of glucotoxicity led to the better expression levels of the key β-cell factors critical for β-cell function over pretreatment levels, and that the alleviation of lipotoxicity along with glucotoxicity augmented the favorable effects under diabetic conditions. - Highlights: • One-week selective reduction of gluco- and lipo-toxicity in db/db mice was performed. • Selective glucotoxicity reduction increases key pancreatic β-cell factors expression. • Selective glucotoxicity reduction improves β-cell factors over pretreatment levels. • Selective glucotoxicity reduction turns β-cell mass toward increase. • Lipotoxicity reduction has additive effects on glucotoxicity reduction.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Mitochondria as key targets of cardioprotection in cardiac ischemic disease: role of thyroid hormone triiodothyronine.

    Science.gov (United States)

    Forini, Francesca; Nicolini, Giuseppina; Iervasi, Giorgio

    2015-03-19

    Ischemic heart disease is the major cause of mortality and morbidity worldwide. Early reperfusion after acute myocardial ischemia has reduced short-term mortality, but it is also responsible for additional myocardial damage, which in the long run favors adverse cardiac remodeling and heart failure evolution. A growing body of experimental and clinical evidence show that the mitochondrion is an essential end effector of ischemia/ reperfusion injury and a major trigger of cell death in the acute ischemic phase (up to 48-72 h after the insult), the subacute phase (from 72 h to 7-10 days) and chronic stage (from 10-14 days to one month after the insult). As such, in recent years scientific efforts have focused on mitochondria as a target for cardioprotective strategies in ischemic heart disease and cardiomyopathy. The present review discusses recent advances in this field, with special emphasis on the emerging role of the biologically active thyroid hormone triiodothyronine (T3).

  10. The Key Role of Epigenetics in the Persistence of Asexual Lineages

    Directory of Open Access Journals (Sweden)

    Emilie Castonguay

    2012-01-01

    Full Text Available Asexual organisms, often perceived as evolutionary dead ends, can be long-lived and geographically widespread. We propose that epigenetic mechanisms could play a crucial role in the evolutionary persistence of these lineages. Genetically identical organisms could rely on phenotypic plasticity to face environmental variation. Epigenetic modifications could be the molecular mechanism enabling such phenotypic plasticity; they can be influenced by the environment and act at shorter timescales than mutation. Recent work on the asexual vertebrate Chrosomus eos-neogaeus (Pisces: Cyprinidae provides broad insights into the contribution of epigenetics in genetically identical individuals. We discuss the extension of these results to other asexual organisms, in particular those resulting from interspecific hybridizations. We finally develop on the evolutionary relevance of epigenetic variation in the context of heritability.

  11. The key role of the scaffold on the efficiency of dendrimer nanodrugs

    Science.gov (United States)

    Caminade, Anne-Marie; Fruchon, Séverine; Turrin, Cédric-Olivier; Poupot, Mary; Ouali, Armelle; Maraval, Alexandrine; Garzoni, Matteo; Maly, Marek; Furer, Victor; Kovalenko, Valeri; Majoral, Jean-Pierre; Pavan, Giovanni M.; Poupot, Rémy

    2015-01-01

    Dendrimers are well-defined macromolecules whose highly branched structure is reminiscent of many natural structures, such as trees, dendritic cells, neurons or the networks of kidneys and lungs. Nature has privileged such branched structures for increasing the efficiency of exchanges with the external medium; thus, the whole structure is of pivotal importance for these natural networks. On the contrary, it is generally believed that the properties of dendrimers are essentially related to their terminal groups, and that the internal structure plays the minor role of an ‘innocent' scaffold. Here we show that such an assertion is misleading, using convergent information from biological data (human monocytes activation) and all-atom molecular dynamics simulations on seven families of dendrimers (13 compounds) that we have synthesized, possessing identical terminal groups, but different internal structures. This work demonstrates that the scaffold of nanodrugs strongly influences their properties, somewhat reminiscent of the backbone of proteins. PMID:26169490

  12. MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Menachery, Vineet D.; Mitchell, Hugh D.; Cockrell, Adam S.; Gralinski, Lisa E.; Yount, Boyd L.; Graham, Rachel L.; McAnarney, Eileen T.; Douglas, Madeline G.; Scobey, Trevor; Beall, Anne; Dinnon, Kenneth; Kocher, Jacob F.; Hale, Andrew E.; Stratton, Kelly G.; Waters, Katrina M.; Baric, Ralph S.; Racaniello, Vincent R.

    2017-08-22

    ABSTRACT

    While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation.In vitroreplication attenuation also extends toin vivomodels, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward.

    IMPORTANCEThe initial emergence and periodic outbreaks of MERS-CoV highlight a continuing threat posed by zoonotic pathogens to global public health. In these studies, mutant virus generation demonstrates the necessity of accessory ORFs in regard to MERS-CoV infection and pathogenesis. With this in mind, accessory ORF functions can be targeted for both therapeutic and vaccine treatments in response to MERS-CoV and related group 2C coronaviruses. In addition, disruption of accessory ORFs in parallel may offer a rapid response platform to attenuation of future emergent strains based on both SARS- and MERS-CoV accessory ORF mutants.

  13. Kalrn plays key roles within and outside of the nervous system

    Directory of Open Access Journals (Sweden)

    Mandela Prashant

    2012-11-01

    Full Text Available Abstract Background The human KALRN gene, which encodes a complex, multifunctional Rho GDP/GTP exchange factor, has been linked to cardiovascular disease, psychiatric disorders and neurodegeneration. Examination of existing Kalrn knockout mouse models has focused only on neuronal phenotypes. However, Kalirin was first identified through its interaction with an enzyme involved in the synthesis and secretion of multiple bioactive peptides, and studies in C.elegans revealed roles for its orthologue in neurosecretion. Results We used a broad array of tests to evaluate the effects of ablating a single exon in the spectrin repeat region of Kalrn (KalSRKO/KO; transcripts encoding Kalrn isoforms containing only the second GEF domain can still be produced from the single remaining functional Kalrn promoter. As expected, KalSRKO/KO mice showed a decrease in anxiety-like behavior and a passive avoidance deficit. No changes were observed in prepulse inhibition of acoustic startle or tests of depression-like behavior. Growth rate, parturition and pituitary secretion of growth hormone and prolactin were deficient in the KalSRKO/KO mice. Based on the fact that a subset of Kalrn isoforms is expressed in mouse skeletal muscle and the observation that muscle function in C.elegans requires its Kalrn orthologue, KalSRKO/KO mice were evaluated in the rotarod and wire hang tests. KalSRKO/KO mice showed a profound decrease in neuromuscular function, with deficits apparent in KalSR+/KO mice; these deficits were not as marked when loss of Kalrn expression was restricted to the nervous system. Pre- and postsynaptic deficits in the neuromuscular junction were observed, along with alterations in sarcomere length. Conclusions Many of the widespread and diverse deficits observed both within and outside of the nervous system when expression of Kalrn is eliminated may reflect its role in secretory granule function and its expression outside of the nervous system.

  14. Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy

    International Nuclear Information System (INIS)

    Casula, Milena; Sini, MariaCristina; Palomba, Grazia; The Italian Melanoma Intergroup; Palmieri, Giuseppe; Muggiano, Antonio; Cossu, Antonio; Budroni, Mario; Caracò, Corrado; Ascierto, Paolo A; Pagani, Elena; Stanganelli, Ignazio; Canzanella, Sergio

    2009-01-01

    Several genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease. A large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16 CDKN2A , BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16 CDKN2A genes. For melanoma susceptibility, investigations at germline level indicated that p16 CDKN2A was exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16 CDKN2A gene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16 CDKN2A silencing). Our findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis

  15. Health and well-being at work: The key role of supervisor support

    Directory of Open Access Journals (Sweden)

    Oliver Hämmig

    2017-12-01

    Full Text Available This study aims to explore whether and in what way social support from different sources and domains makes an additional or different and independent contribution to various health and work-related outcomes. Cross-sectional data were used from an employee survey among the workforces of four service companies from different industries in Switzerland. The study sample covered 5,877 employees of working age. The lack of social support from a spouse, relatives, friends, direct supervisors, closest colleagues at work and other co-workers in case of problems at work and at home were assessed and studied individually and jointly as risk factors with respect to a total number of eight outcomes. Health-related outcomes covered poor self-rated health, musculoskeletal disorders, stress feelings and burnout symptoms. Work-related outcomes included feeling overwhelmed at work, difficulty with switching off after work, job dissatisfaction and intention to turnover. Social support from multiple sources in contrast to only individual sources in both life domains was found to be more frequent in women than in men and proved to be most protective and beneficial with regard to health and well-being at work. However, after mutual adjustment of all single sources of social support from both domains, a lack of supervisor support turned out to be the only or the strongest of the few remaining support measures and statistically significant risk factors for the studied outcomes throughout and by far. Being unable to count on the support of a direct supervisor in case of problems at work and even at home was shown to involve a substantially increased risk of poor health and work-related outcomes (aOR = up to 3.8. Multiple sources of social support, and particularly supervisor support, seem to be important resources of health and well-being at work and need to be considered as key factors in workplace health promotion.

  16. The role of key image notes in CT imaging study interpretation.

    Science.gov (United States)

    Fan, Shu-Feng; Xu, Zhe; He, Hai-Qing; Ding, Jian-Rong; Teng, Gao-Jun

    2011-04-01

    The objective of the study was to investigate the clinical effects of CT key image notes (KIN) in the interpretation of a CT image study. All experiments were approved by the ethics committee of the local district. Six experienced radiologists were equally divided into routine reporting (RR) group and KIN reporting (KIN) group. CT scans of each 100 consecutive cases before and after using KIN technique were randomly selected, and the reports were made by group RR and KIN, respectively. All the reports were again reviewed 3 months later by both groups. All the results with using or not using KIN were interpreted and reinterpreted after 3 months by six clinicians, who were experienced in picture archiving and communication system (PACS) applications and were equally divided into the clinical routine report group and the clinical KIN report group, respectively. The results were statistically analyzed; the time used in making a report, the re-reading time 3 months later, and the consistency of imaging interpretation were determined and compared between groups. After using KIN technique, the time used in making a report was significantly increased (8.77 ± 5.27 vs. 10.53 ± 5.71 min, P < 0.05), the re-reading time was decreased (5.23 ± 2.54 vs. 4.99 ± 1.70 min, P < 0.05), the clinical interpretation and reinterpretation time after 3 months were decreased, and the consistency of the interpretation, reinterpretation between different doctors in different time was markedly improved (P < 0.01). CT report with KIN technique in PACS can significantly improve the consistency of the interpretation and efficiency in routine clinical work.

  17. Health and well-being at work: The key role of supervisor support.

    Science.gov (United States)

    Hämmig, Oliver

    2017-12-01

    This study aims to explore whether and in what way social support from different sources and domains makes an additional or different and independent contribution to various health and work-related outcomes. Cross-sectional data were used from an employee survey among the workforces of four service companies from different industries in Switzerland. The study sample covered 5,877 employees of working age. The lack of social support from a spouse, relatives, friends, direct supervisors, closest colleagues at work and other co-workers in case of problems at work and at home were assessed and studied individually and jointly as risk factors with respect to a total number of eight outcomes. Health-related outcomes covered poor self-rated health, musculoskeletal disorders, stress feelings and burnout symptoms. Work-related outcomes included feeling overwhelmed at work, difficulty with switching off after work, job dissatisfaction and intention to turnover. Social support from multiple sources in contrast to only individual sources in both life domains was found to be more frequent in women than in men and proved to be most protective and beneficial with regard to health and well-being at work. However, after mutual adjustment of all single sources of social support from both domains, a lack of supervisor support turned out to be the only or the strongest of the few remaining support measures and statistically significant risk factors for the studied outcomes throughout and by far. Being unable to count on the support of a direct supervisor in case of problems at work and even at home was shown to involve a substantially increased risk of poor health and work-related outcomes (aOR = up to 3.8). Multiple sources of social support, and particularly supervisor support, seem to be important resources of health and well-being at work and need to be considered as key factors in workplace health promotion.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Key Role of Drug Shops and Pharmacies for Family Planning in Urban Nigeria and Kenya.

    Science.gov (United States)

    Corroon, Meghan; Kebede, Essete; Spektor, Gean; Speizer, Ilene

    2016-12-23

    The Family Planning 2020 initiative aims to reach 120 million new family planning users by 2020. Drug shops and pharmacies are important private-sector sources of contraception in many contexts but are less well understood than public-sector sources, especially in urban environments. This article explores the role that drug shops and pharmacies play in the provision of contraceptive methods in selected urban areas of Nigeria and Kenya as well as factors associated with women's choice of where to obtain these methods. Using data collected in 2010/2011 from representative samples of women in selected urban areas of Nigeria and Kenya as well as a census of pharmacies and drug shops audited in 2011, we examine the role of drug shops and pharmacies in the provision of short-acting contraceptive methods and factors associated with a women's choice of family planning source. In urban Nigeria and Kenya, drug shops and pharmacies were the major source for the family planning methods of oral contraceptive pills, emergency contraceptives, and condoms. The majority of injectable users obtained their method from public facilities in both countries, but 14% of women in Nigeria and 6% in Kenya obtained injectables from drug shops or pharmacies. Harder-to-reach populations were the most likely to choose these outlets to obtain their short-acting methods. For example, among users of these methods in Nigeria, younger women (family planning users who had never been married were significantly more likely than married users to obtain these methods from a drug shop or a pharmacy than from a public-sector health facility. Low levels of family planning-related training (57% of providers in Kenya and 41% in Nigeria had received training) and lack of family planning promotional activities in pharmacies and drug shops in both countries indicate the need for additional support from family planning programs to leverage this important access point. Drug shops and pharmacies offer an important

  20. A Multi-Compartment Hybrid Computational Model Predicts Key Roles for Dendritic Cells in Tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Simeone Marino

    2016-10-01

    Full Text Available Tuberculosis (TB is a world-wide health problem with approximately 2 billion people infected with Mycobacterium tuberculosis (Mtb, the causative bacterium of TB. The pathologic hallmark of Mtb infection in humans and Non-Human Primates (NHPs is the formation of spherical structures, primarily in lungs, called granulomas. Infection occurs after inhalation of bacteria into lungs, where resident antigen-presenting cells (APCs, take up bacteria and initiate the immune response to Mtb infection. APCs traffic from the site of infection (lung to lung-draining lymph nodes (LNs where they prime T cells to recognize Mtb. These T cells, circulating back through blood, migrate back to lungs to perform their immune effector functions. We have previously developed a hybrid agent-based model (ABM, labeled GranSim describing in silico immune cell, bacterial (Mtb and molecular behaviors during tuberculosis infection and recently linked that model to operate across three physiological compartments: lung (infection site where granulomas form, lung draining lymph node (LN, site of generation of adaptive immunity and blood (a measurable compartment. Granuloma formation and function is captured by a spatio-temporal model (i.e., ABM, while LN and blood compartments represent temporal dynamics of the whole body in response to infection and are captured with ordinary differential equations (ODEs. In order to have a more mechanistic representation of APC trafficking from the lung to the lymph node, and to better capture antigen presentation in a draining LN, this current study incorporates the role of dendritic cells (DCs in a computational fashion into GranSim. Results: The model was calibrated using experimental data from the lungs and blood of NHPs. The addition of DCs allowed us to investigate in greater detail mechanisms of recruitment, trafficking and antigen presentation and their role in tuberculosis infection. Conclusion: The main conclusion of this study is

  1. 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.

  2. MAGNETIC GAMES BETWEEN A PLANET AND ITS HOST STAR: THE KEY ROLE OF TOPOLOGY

    International Nuclear Information System (INIS)

    Strugarek, A.; Brun, A. S.; Réville, V.; Matt, S. P.

    2015-01-01

    Magnetic interactions between a star and a close-in planet are postulated to be a source of enhanced emissions and to play a role in the secular evolution of the orbital system. Close-in planets generally orbit in the sub-alfvénic region of the stellar wind, which leads to efficient transfers of energy and angular momentum between the star and the planet. We model the magnetic interactions occurring in close-in star–planet systems with three-dimensional, global, compressible magnetohydrodynamic numerical simulations of a planet orbiting in a self-consistent stellar wind. We focus on the cases of magnetized planets and explore three representative magnetic configurations. The Poynting flux originating from the magnetic interactions is an energy source for enhanced emissions in star–planet systems. Our results suggest a simple geometrical explanation for ubiquitous on/off enhanced emissions associated with close-in planets, and confirm that the Poynting fluxes can reach powers of the order of 10 19 W. Close-in planets are also shown to migrate due to magnetic torques for sufficiently strong stellar wind magnetic fields. The topology of the interaction significantly modifies the shape of the magnetic obstacle that leads to magnetic torques. As a consequence, the torques can vary by at least an order of magnitude as the magnetic topology of the interaction varies

  3. Scaffolding as a key role for teaching assistants: Perceptions of their pedagogical strategies.

    Science.gov (United States)

    Bowles, David; Radford, Julie; Bakopoulou, Ioanna

    2017-11-19

    Inclusive education policies have led to a worldwide increase in the number of teaching assistants (TAs) working in mainstream schools. TAs have a large amount of responsibility for supporting children with special educational needs and disabilities (SEND), a role which by default has become instructional in practice, and for which training and preparation are rarely adequate. While there is some research into the nature of TAs' interactions with pupils and the strategies they use which are helpful for children's learning, TAs' perspectives on their own classroom practice have yet to be explored. To explore TAs' perceptions about their use of inclusive pedagogical strategies. The study involved eleven TAs in two mainstream primary schools. The TAs were interviewed face to face to explore their views about inclusive pedagogical strategies. The data were analysed using thematic analysis. TAs were clear about the strategies they use to offer emotional and relational support to children. There were some gaps, however, in their knowledge about how children learn, specifically in terms of transferring responsibility for learning onto children. The study advances understanding of scaffolding from a TA perspective and highlights the importance of training TAs in scaffolding theory. © 2017 The British Psychological Society.

  4. Swimming motility plays a key role in the stochastic dynamics of cell clumping

    International Nuclear Information System (INIS)

    Qi, Xianghong; Nellas, Ricky B; Byrn, Matthew W; Russell, Matthew H; Bible, Amber N; Alexandre, Gladys; Shen, Tongye

    2013-01-01

    Dynamic cell-to-cell interactions are a prerequisite to many biological processes, including development and biofilm formation. Flagellum induced motility has been shown to modulate the initial cell–cell or cell–surface interaction and to contribute to the emergence of macroscopic patterns. While the role of swimming motility in surface colonization has been analyzed in some detail, a quantitative physical analysis of transient interactions between motile cells is lacking. We examined the Brownian dynamics of swimming cells in a crowded environment using a model of motorized adhesive tandem particles. Focusing on the motility and geometry of an exemplary motile bacterium Azospirillum brasilense, which is capable of transient cell–cell association (clumping), we constructed a physical model with proper parameters for the computer simulation of the clumping dynamics. By modulating mechanical interaction (‘stickiness’) between cells and swimming speed, we investigated how equilibrium and active features affect the clumping dynamics. We found that the modulation of active motion is required for the initial aggregation of cells to occur at a realistic time scale. Slowing down the rotation of flagellar motors (and thus swimming speeds) is correlated to the degree of clumping, which is consistent with the experimental results obtained for A. brasilense. (paper)

  5. Nanomaterials towards fabrication of cholesterol biosensors: Key roles and design approaches.

    Science.gov (United States)

    Saxena, Urmila; Das, Asim Bikas

    2016-01-15

    Importance of cholesterol biosensors is already recognized in the clinical diagnosis of cardiac and brain vascular diseases as discernible from the enormous amount of research in this field. Nevertheless, the practical application of a majority of the fabricated cholesterol biosensors is ordinarily limited by their inadequate performance in terms of one or more analytical parameters including stability, sensitivity and detection limit. Nanoscale materials offer distinctive size tunable electronic, catalytic and optical properties which opened new opportunities for designing highly efficient biosensor devices. Incorporation of nanomaterials in biosensing devices has found to improve the electroactive surface, electronic conductivity and biocompatibility of the electrode surfaces which then improves the analytical performance of the biosensors. Here we have reviewed recent advances in nanomaterial-based cholesterol biosensors. Foremost, the diverse roles of nanomaterials in these sensor systems have been discussed. Later, we have exhaustively explored the strategies used for engineering cholesterol biosensors with nanotubes, nanoparticles and nanocomposites. Finally, this review concludes with future outlook signifying some challenges of these nanoengineered cholesterol sensors. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. MAGNETIC GAMES BETWEEN A PLANET AND ITS HOST STAR: THE KEY ROLE OF TOPOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    Strugarek, A. [Département de physique, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montréal, QC H3C 3J7 (Canada); Brun, A. S.; Réville, V. [Laboratoire AIM Paris-Saclay, CEA/Irfu Université Paris-Diderot CNRS/INSU, F-91191 Gif-sur-Yvette (France); Matt, S. P., E-mail: strugarek@astro.umontreal.ca [Astrophysics group, School of Physics, University of Exeter, Stocker Road, Exeter EX4 4QL (United Kingdom)

    2015-12-20

    Magnetic interactions between a star and a close-in planet are postulated to be a source of enhanced emissions and to play a role in the secular evolution of the orbital system. Close-in planets generally orbit in the sub-alfvénic region of the stellar wind, which leads to efficient transfers of energy and angular momentum between the star and the planet. We model the magnetic interactions occurring in close-in star–planet systems with three-dimensional, global, compressible magnetohydrodynamic numerical simulations of a planet orbiting in a self-consistent stellar wind. We focus on the cases of magnetized planets and explore three representative magnetic configurations. The Poynting flux originating from the magnetic interactions is an energy source for enhanced emissions in star–planet systems. Our results suggest a simple geometrical explanation for ubiquitous on/off enhanced emissions associated with close-in planets, and confirm that the Poynting fluxes can reach powers of the order of 10{sup 19} W. Close-in planets are also shown to migrate due to magnetic torques for sufficiently strong stellar wind magnetic fields. The topology of the interaction significantly modifies the shape of the magnetic obstacle that leads to magnetic torques. As a consequence, the torques can vary by at least an order of magnitude as the magnetic topology of the interaction varies.

  7. Global citizenship is key to securing global health: the role of higher education.

    Science.gov (United States)

    Stoner, Lee; Perry, Lane; Wadsworth, Daniel; Stoner, Krystina R; Tarrant, Michael A

    2014-07-01

    Despite growing public awareness, health systems are struggling under the escalating burden of non-communicable diseases. While personal responsibility is crucial, alone it is insufficient. We argue that one must place themselves within the broader/global context to begin to truly understand the health implications of personal choices. Global citizenship competency has become an integral part of the higher education discourse; this discourse can and should be extended to include global health. A global citizen is someone who is (1) aware of global issues, (2) socially responsible, and (3) civically engaged. From this perspective, personal health is not solely an individual, self-serving act; rather, the consequences of our lifestyle choices and behaviors have far-reaching implications. This paper will argue that, through consciously identifying global health within the constructs of global citizenship, institutions of higher education can play an instrumental role in fostering civically engaged students capable of driving social change. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Mitochondria as Key Targets of Cardioprotection in Cardiac Ischemic Disease: Role of Thyroid Hormone Triiodothyronine

    Directory of Open Access Journals (Sweden)

    Francesca Forini

    2015-03-01

    Full Text Available Ischemic heart disease is the major cause of mortality and morbidity worldwide. Early reperfusion after acute myocardial ischemia has reduced short-term mortality, but it is also responsible for additional myocardial damage, which in the long run favors adverse cardiac remodeling and heart failure evolution. A growing body of experimental and clinical evidence show that the mitochondrion is an essential end effector of ischemia/ reperfusion injury and a major trigger of cell death in the acute ischemic phase (up to 48–72 h after the insult, the subacute phase (from 72 h to 7–10 days and chronic stage (from 10–14 days to one month after the insult. As such, in recent years scientific efforts have focused on mitochondria as a target for cardioprotective strategies in ischemic heart disease and cardiomyopathy. The present review discusses recent advances in this field, with special emphasis on the emerging role of the biologically active thyroid hormone triiodothyronine (T3.

  9. How self-determined choice facilitates performance: a key role of the ventromedial prefrontal cortex.

    Science.gov (United States)

    Murayama, Kou; Matsumoto, Madoka; Izuma, Keise; Sugiura, Ayaka; Ryan, Richard M; Deci, Edward L; Matsumoto, Kenji

    2015-05-01

    Recent studies have documented that self-determined choice does indeed enhance performance. However, the precise neural mechanisms underlying this effect are not well understood. We examined the neural correlates of the facilitative effects of self-determined choice using functional magnetic resonance imaging (fMRI). Participants played a game-like task involving a stopwatch with either a stopwatch they selected (self-determined-choice condition) or one they were assigned without choice (forced-choice condition). Our results showed that self-determined choice enhanced performance on the stopwatch task, despite the fact that the choices were clearly irrelevant to task difficulty. Neuroimaging results showed that failure feedback, compared with success feedback, elicited a drop in the vmPFC activation in the forced-choice condition, but not in the self-determined-choice condition, indicating that negative reward value associated with the failure feedback vanished in the self-determined-choice condition. Moreover, the vmPFC resilience to failure in the self-determined-choice condition was significantly correlated with the increased performance. Striatal responses to failure and success feedback were not modulated by the choice condition, indicating the dissociation between the vmPFC and striatal activation pattern. These findings suggest that the vmPFC plays a unique and critical role in the facilitative effects of self-determined choice on performance. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Contextualising change through a common strategy: Lecturers' perceptions and key role in supporting academic reform

    Science.gov (United States)

    Kindelan, Paz; Martin, Ana

    2014-05-01

    European universities are currently going through a process of change in order to meet the common goals set for higher education by the European Commission. They are revising their educational models to adjust them to the guidelines of the "Bologna Process" and are devising an institutional strategy for its implementation. In practical terms, this means aligning former national degrees and diplomas to standard European Bachelor and Masters degrees and PhD doctorates, by creating acknowledged professional qualification benchmarks that also include adjusted course lengths and contents. This process, in the end, mostly affects academic staff members who have a fundamental role to play in carrying out the pedagogical reforms on the teaching front. Besides presenting a commentary on the institutional approach of one particular technical university in Spain, the purpose of this paper is to propose, from the authors' point of view as lecturers, a strategy which has the potential to create a favourable atmosphere for carrying out such a reform. The article's main objective is to highlight a series of action points which may serve to reinforce and advance the main institutional strategy by relying on the powerful influence of its academic staff members.

  11. The Key Role of Government in Addressing the Pandemic of Micronutrient Deficiency Conditions in Southeast Asia

    Directory of Open Access Journals (Sweden)

    Theodore H. Tulchinsky

    2015-04-01

    Full Text Available Micronutrient deficiency conditions are a major global public health problem. While the private sector has an important role in addressing this problem, the main responsibility lies with national governments, in cooperation with international agencies and donors. Mandatory fortification of basic foods provides a basic necessary intake for the majority and needs to be supported by provision of essential vitamin and mineral supplements for mothers and children and other high risk groups. Fortification by government mandate and regulation is essential with cooperation by private sector food manufacturers, and in the context of broader policies for poverty reduction, education and agricultural reform. Iron, iodine, vitamin A, vitamin B complex, folic acid, zinc, vitamin D and vitamin B12 are prime examples of international fortification experience achieved by proactive governmental nutrition policies. These are essential to achieve the Millennium Development Goals and their follow-up sustainable global health targets. National governmental policies for nutritional security and initiatives are essential to implement both food fortification and targeted supplementation policies to reduce the huge burden of micronutrient deficiency conditions in Southeast Asia and other parts of the world.

  12. How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin

    Directory of Open Access Journals (Sweden)

    Salvatore Giovanni Vitale

    2016-01-01

    Full Text Available Assisted reproductive technologies (ART have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment.

  13. Swimming motility plays a key role in the stochastic dynamics of cell clumping

    Science.gov (United States)

    Qi, Xianghong; Nellas, Ricky B.; Byrn, Matthew W.; Russell, Matthew H.; Bible, Amber N.; Alexandre, Gladys; Shen, Tongye

    2013-04-01

    Dynamic cell-to-cell interactions are a prerequisite to many biological processes, including development and biofilm formation. Flagellum induced motility has been shown to modulate the initial cell-cell or cell-surface interaction and to contribute to the emergence of macroscopic patterns. While the role of swimming motility in surface colonization has been analyzed in some detail, a quantitative physical analysis of transient interactions between motile cells is lacking. We examined the Brownian dynamics of swimming cells in a crowded environment using a model of motorized adhesive tandem particles. Focusing on the motility and geometry of an exemplary motile bacterium Azospirillum brasilense, which is capable of transient cell-cell association (clumping), we constructed a physical model with proper parameters for the computer simulation of the clumping dynamics. By modulating mechanical interaction (‘stickiness’) between cells and swimming speed, we investigated how equilibrium and active features affect the clumping dynamics. We found that the modulation of active motion is required for the initial aggregation of cells to occur at a realistic time scale. Slowing down the rotation of flagellar motors (and thus swimming speeds) is correlated to the degree of clumping, which is consistent with the experimental results obtained for A. brasilense.

  14. Breast cancers radiation-resistance: key role of the cancer stem cells marker CD24

    International Nuclear Information System (INIS)

    Bensimon, Julie

    2013-01-01

    This work focuses on the characterization of radiation-resistant breast cancer cells, responsible for relapse after radiotherapy. The 'Cancer Stem Cells' (CSC) theory describes a radiation-resistant cellular sub-population, with enhanced capacity to induce tumors and proliferate. In this work, we show that only the CSC marker CD24-/low defines a radiation resistant cell population, able to transmit the 'memory' of irradiation, expressed as long term genomic instability in the progeny of irradiated cells. We show that CD24 is not only a marker, but is an actor of radiation-response. So, CD24 expression controls cell proliferation in vitro and in vivo, and ROS level before and after irradiation. As a result, CD24-/low cells display enhanced radiation-resistance and genomic stability. For the first time, our results attribute a role to CD24-/low CSCs in the transmission of genomic instability. Moreover, by providing informations on tumor intrinsic radiation-sensitivity, CD24- marker could help to design new radiotherapy protocols. (author)

  15. Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

    Directory of Open Access Journals (Sweden)

    Couture Réjean

    2010-06-01

    Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

  16. 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

  17. Non-metastatic 2 (NME2)-mediated suppression of lung cancer metastasis involves transcriptional regulation of key cell adhesion factor vinculin

    Science.gov (United States)

    Thakur, Ram Krishna; Yadav, Vinod Kumar; Kumar, Akinchan; Singh, Ankita; Pal, Krishnendu; Hoeppner, Luke; Saha, Dhurjhoti; Purohit, Gunjan; Basundra, Richa; Kar, Anirban; Halder, Rashi; Kumar, Pankaj; Baral, Aradhita; Kumar, MJ Mahesh; Baldi, Alfonso; Vincenzi, Bruno; Lorenzon, Laura; Banerjee, Rajkumar; Kumar, Praveen; Shridhar, Viji; Mukhopadhyay, Debabrata; Chowdhury, Shantanu

    2014-01-01

    Tumor metastasis refers to spread of a tumor from site of its origin to distant organs and causes majority of cancer deaths. Although >30 metastasis suppressor genes (MSGs) that negatively regulate metastasis have been identified so far, two issues are poorly understood: first, which MSGs oppose metastasis in a tumor type, and second, which molecular function of MSG controls metastasis. Herein, integrative analyses of tumor-transcriptomes (n = 382), survival data (n = 530) and lymph node metastases (n = 100) in lung cancer patients identified non-metastatic 2 (NME2) as a key MSG from a pool of >30 metastasis suppressors. Subsequently, we generated a promoter-wide binding map for NME2 using chromatin immunoprecipitation with promoter microarrays (ChIP-chip), and transcriptome profiling. We discovered novel targets of NME2 which are involved in focal adhesion signaling. Importantly, we detected binding of NME2 in promoter of focal adhesion factor, vinculin. Reduced expression of NME2 led to enhanced transcription of vinculin. In comparison, NME1, a close homolog of NME2, did not bind to vinculin promoter nor regulate its expression. In line, enhanced metastasis of NME2-depleted lung cancer cells was found in zebrafish and nude mice tumor models. The metastatic potential of NME2-depleted cells was remarkably diminished upon selective RNA-i-mediated silencing of vinculin. Together, we demonstrate that reduced NME2 levels lead to transcriptional de-repression of vinculin and regulate lung cancer metastasis. PMID:25249619

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. The key role of exudative lesions and their encapsulation: lessons learned from the pathology of human pulmonary tuberculosis.

    Science.gov (United States)

    Cardona, Pere-Joan

    2015-01-01

    A review of the pathology of human pulmonary TB cases at different stages of evolution in the pre-antibiotic era suggests that neutrophils play an instrumental role in the progression toward active TB. This progression is determined by the type of lesion generated. Thus, exudative lesions, in which neutrophils are the major cell type, are both triggered by and induce local high bacillary load, and tend to enlarge and progress toward liquefaction and cavitation. In contrast, proliferative lesions are triggered by low bacillary loads, mainly comprise epithelioid cells and fibroblasts and tend to fibrose, encapsulate and calcify, thus controlling the infection. Infection of the upper lobes is key to the progression toward active TB for two main reasons, namely poor breathing amplitude, which allows local bacillary accumulation, and the high mechanical stress to which the interlobular septae (which enclose secondary lobes) are submitted, which hampers their ability to encapsulate lesions. Overall, progressing factors can be defined as internal (exudative lesion, local bronchogenous dissemination, coalescence of lesions), with lympho-hematological dissemination playing a very limited role, or external (exogenous reinfection). Abrogating factors include control of the bacillary load and the local encapsulation process, as directed by interlobular septae. The age and extent of disease depend on the quality and speed with which lesions liquefy and disseminate bronchially, the volume of the slough, and the amount and distribution of the sloughing debris dispersed.

  9. The role of Health Insurance Companies in optimising drug prescription in Primary Care; The example of acid suppressing drugs

    NARCIS (Netherlands)

    Smeets, H.M.

    2009-01-01

    The use of Acid-suppressing drugs (ASDs) in the Netherlands increases more than 10% annually and of the Dutch population 3.5% uses ASD on a daily basis. However, indications for long term use of ASDs for gastrointestinal complaints are often not evidence based and many patients might be able to stop

  10. 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.

  11. Striking Plasticity of CRISPR-Cas9 and Key Role of Non-target DNA, as Revealed by Molecular Simulations.

    Science.gov (United States)

    Palermo, Giulia; Miao, Yinglong; Walker, Ross C; Jinek, Martin; McCammon, J Andrew

    2016-10-26

    The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system recently emerged as a transformative genome-editing technology that is innovating basic bioscience and applied medicine and biotechnology. The endonuclease Cas9 associates with a guide RNA to match and cleave complementary sequences in double stranded DNA, forming an RNA:DNA hybrid and a displaced non-target DNA strand. Although extensive structural studies are ongoing, the conformational dynamics of Cas9 and its interplay with the nucleic acids during association and DNA cleavage are largely unclear. Here, by employing multi-microsecond time scale molecular dynamics, we reveal the conformational plasticity of Cas9 and identify key determinants that allow its large-scale conformational changes during nucleic acid binding and processing. We show how the "closure" of the protein, which accompanies nucleic acid binding, fundamentally relies on highly coupled and specific motions of the protein domains, collectively initiating the prominent conformational changes needed for nucleic acid association. We further reveal a key role of the non-target DNA during the process of activation of the nuclease HNH domain, showing how the nontarget DNA positioning triggers local conformational changes that favor the formation of a catalytically competent Cas9. Finally, a remarkable conformational plasticity is identified as an intrinsic property of the HNH domain, constituting a necessary element that allows for the HNH repositioning. These novel findings constitute a reference for future experimental studies aimed at a full characterization of the dynamic features of the CRISPR-Cas9 system, and-more importantly-call for novel structure engineering efforts that are of fundamental importance for the rational design of new genome-engineering applications.

  12. 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.

  13. 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

  14. 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

  15. Development of a questionnaire to measure the key attributes of the community palliative care specialist nurse role.

    Science.gov (United States)

    Cameron, Dee; Johnston, Bridget

    2015-02-01

    Recent worldwide economic events have forced an examination of the nurse's contribution to high-quality, effective, person-centred care. Since the role of specialist nurses is considered one of the least understood or valued developments in nursing, specialist nurses must demonstrate their contribution to quality, person-centred health care. To develop a questionnaire which aims to measure the quality of care provided by palliative care specialist nurses from the patients' perspective and to undertake initial validation. The process of questionnaire development involved six phases including systematic literature reviews, patient advisory groups and expert panel reviews, each of which contributed to the questionnaire face and content validity. Johnston's Expert Palliative Care Nurse Model (2002; 2005) provided an evidence-based framework for the development of the questionnaire, and enabled the identification of the key attributes of the palliative care specialist nurse role, thereby providing the themes on which to base the questionnaire. The Quality Measure for Palliative Nursing, a questionnaire, was developed. The themes identified in the questionnaire--personal characteristics, communication skills, knowledge, relationship with patient and providing comfort--aim to facilitate measurement of the quality of care provided by palliative care specialist nurses. Designed for use by palliative patients the Quality Measure for Palliative Nursing is a one-page questionnaire comprising of 15 questions. The Quality Measure for Palliative Nursing is unique since it aims to measure the quality of care provided by community palliative care specialist nurses, and could also be used to measure patient satisfaction with the quality of care provided. Further testing is recommended to ensure that this questionnaire can provide reliable and valid results.

  16. ADP-glucose pyrophosphorylase gene plays a key role in the quality of corm and yield of cormels in gladiolus

    International Nuclear Information System (INIS)

    Seng, Shanshan; Wu, Jian; Sui, Juanjuan; Wu, Chenyu; Zhong, Xionghui; Liu, Chen; Liu, Chao; Gong, Benhe; Zhang, Fengqin; He, Junna; Yi, Mingfang

    2016-01-01

    Starch is the main storage compound in underground organs like corms. ADP-glucose pyrophosphorylase (AGPase) plays a key role in regulating starch biosynthesis in storage organs and is likely one of the most important determinant of sink strength. Here, we identify an AGPase gene (GhAGPS1) from gladiolus. The highest transcriptional levels of GhAGPS1 were observed in cormels and corms. Transformation of GhAGPS1 into Arabidopsis rescued the phenotype of aps1 mutant. Silencing GhAGPS1 in gladiolus corms by virus-induced gene silencing (VIGS) decreased the transcriptional levels of two genes and starch content. Transmission electron microscopy analyses of leaf and corm sections confirmed that starch biosynthesis was inhibited. Corm weight and cormel number reduced significantly in the silenced plants. Taken together, these results indicate that inhibiting the expression of AGPase gene could impair starch synthesis, which results in the lowered corm quality and cormel yield in gladiolus. -- Highlights: •Cormel quantity was reduced significantly in silenced Gladiolus plants. •Corm quality was declined significantly in silenced Gladiolus plants. •Starch synthesis was inhibited in silenced Gladiolus plants.

  17. Mechanism of conformational coupling in SecA: Key role of hydrogen-bonding networks and water interactions.

    Science.gov (United States)

    Milenkovic, Stefan; Bondar, Ana-Nicoleta

    2016-02-01

    SecA uses the energy yielded by the binding and hydrolysis of adenosine triphosphate (ATP) to push secretory pre-proteins across the plasma membrane in bacteria. Hydrolysis of ATP occurs at the nucleotide-binding site, which contains the conserved carboxylate groups of the DEAD-box helicases. Although crystal structures provide valuable snapshots of SecA along its reaction cycle, the mechanism that ensures conformational coupling between the nucleotide-binding site and the other domains of SecA remains unclear. The observation that SecA contains numerous hydrogen-bonding groups raises important questions about the role of hydrogen-bonding networks and hydrogen-bond dynamics in long-distance conformational couplings. To address these questions, we explored the molecular dynamics of SecA from three different organisms, with and without bound nucleotide, in water. By computing two-dimensional hydrogen-bonding maps we identify networks of hydrogen bonds that connect the nucleotide-binding site to remote regions of the protein, and sites in the protein that respond to specific perturbations. We find that the nucleotide-binding site of ADP-bound SecA has a preferred geometry whereby the first two carboxylates of the DEAD motif bridge via hydrogen-bonding water. Simulations of a mutant with perturbed ATP hydrolysis highlight the water-bridged geometry as a key structural element of the reaction path. Copyright © 2015. Published by Elsevier B.V.

  18. The key role of the meat industry in transformation to a low-carbon, climate resilient, sustainable economy.

    Science.gov (United States)

    Rijsberman, Frank

    2017-10-01

    Climate change, air pollution and refugees have become key global challenges threatening sustainability of lifestyles, economies and ecosystems. Agri-food systems are the number one driver of environmental change. Livestock production is the world's largest land user, responsible for half of greenhouse gas emissions from agri-food systems, and the source of repeated health crises. Poor diets have become the number one cause of ill health. Recommendations for a healthy diet emphasize plant-based food. Rapidly falling costs in information technology, biotechnology, renewable energy and battery technology will disrupt current energy and transportation systems and offer opportunities for responsible meat production. Growing consumer interest in healthy food, combined with innovative information systems, offer opportunities to create value through quality control and consumer information in integrated value chains. Meat scientists have a major role to play in the necessary transformation of global agri-food systems towards a new model of green economic growth that is climate resilient, sustainable and provides green jobs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. ADP-glucose pyrophosphorylase gene plays a key role in the quality of corm and yield of cormels in gladiolus

    Energy Technology Data Exchange (ETDEWEB)

    Seng, Shanshan, E-mail: seshsh108@126.com [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Yuan Mingyuan Western Road 2#, Beijing 100193 (China); Wu, Jian [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Yuan Mingyuan Western Road 2#, Beijing 100193 (China); Sui, Juanjuan [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Yuan Mingyuan Western Road 2#, Beijing 100193 (China); College of Biology, Fuyang Normal College, Qinghe Western Road 100#, Fuyang 236037, Anhui (China); Wu, Chenyu; Zhong, Xionghui; Liu, Chen; Liu, Chao; Gong, Benhe; Zhang, Fengqin; He, Junna [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Yuan Mingyuan Western Road 2#, Beijing 100193 (China); Yi, Mingfang, E-mail: ymfang@cau.edu.cn [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Yuan Mingyuan Western Road 2#, Beijing 100193 (China)

    2016-05-20

    Starch is the main storage compound in underground organs like corms. ADP-glucose pyrophosphorylase (AGPase) plays a key role in regulating starch biosynthesis in storage organs and is likely one of the most important determinant of sink strength. Here, we identify an AGPase gene (GhAGPS1) from gladiolus. The highest transcriptional levels of GhAGPS1 were observed in cormels and corms. Transformation of GhAGPS1 into Arabidopsis rescued the phenotype of aps1 mutant. Silencing GhAGPS1 in gladiolus corms by virus-induced gene silencing (VIGS) decreased the transcriptional levels of two genes and starch content. Transmission electron microscopy analyses of leaf and corm sections confirmed that starch biosynthesis was inhibited. Corm weight and cormel number reduced significantly in the silenced plants. Taken together, these results indicate that inhibiting the expression of AGPase gene could impair starch synthesis, which results in the lowered corm quality and cormel yield in gladiolus. -- Highlights: •Cormel quantity was reduced significantly in silenced Gladiolus plants. •Corm quality was declined significantly in silenced Gladiolus plants. •Starch synthesis was inhibited in silenced Gladiolus plants.

  20. Nitric oxide synthase and oxidative-nitrosative stress play a key role in placental infection by Trypanosoma cruzi.

    Science.gov (United States)

    Triquell, María Fernanda; Díaz-Luján, Cintia; Romanini, María Cristina; Ramirez, Juan Carlos; Paglini-Oliva, Patricia; Schijman, Alejandro Gabriel; Fretes, Ricardo Emilio

    2018-03-25

    The innate immune response of the placenta may participate in the congenital transmission of Chagas disease through releasing reactive oxygen and nitrogen intermediates. Placental explants were cultured with 1 × 10 6 and 1 × 10 5 trypomastigotes of Tulahuen and Lucky strains and controls without parasites, and with the addition of nitric oxide synthase inhibitor Nω-Nitro-l-arginine methyl ester (l-NAME) and N-acetyl cysteine (NAC) as the reactive oxygen species (ROS) scavenger. Detachment of the syncytiotrophoblast (STB) was examined by histological analysis, and the nitric oxide synthase, endothelial (eNOS), and nitrotyrosine expressions were analyzed by immunohistochemistry, as well as the human chorionic gonadotrophin (hCG) levels in the culture supernatant through ELISA assays. Parasite load with qPCR using Taqman primers was quantified. The higher number of T. cruzi (10 6 ) increased placental infection, eNOS expression, nitrosative stress, and STB detachment, with the placental barrier being injured by oxidative stress. The higher number of parasites caused deleterious consequences to the placental barrier, and the inhibitors (l-NAME and NAC) prevented the damage caused by trypomastigotes in placental villi but not that of the infection. Moreover, trophoblast eNOS played a key role in placental infection with the highest inoculum of Lucky, demonstrating the importance of the enzyme and nitrosative-oxidative stress in Chagas congenital transmission. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Suppressed Belief

    Directory of Open Access Journals (Sweden)

    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.

  5. 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....

  6. Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling.

    Science.gov (United States)

    Singhal, Sharad S; Singh, Sharda P; Singhal, Preeti; Horne, David; Singhal, Jyotsana; Awasthi, Sanjay

    2015-12-15

    4-Hydroxy-2-trans-nonenal (4HNE), one of the major end products of lipid peroxidation (LPO), has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione-peroxidase activity and that these enzymes can also detoxify LPO end-products such as 4HNE. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that LPO products, particularly hydroperoxides and 4HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the alpha-class GSTs through the regulation of the intracellular concentrations of 4HNE. We demonstrate that 4HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase (JNK) and caspase-3 activation. Cells exposed to mild, transient heat or oxidative stress acquire the capacity to exclude intracellular 4HNE at a faster rate by inducing GSTA4-4 which conjugates 4HNE to glutathione (GSH), and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4HNE (GS-HNE). The balance between formation and exclusion promotes different cellular processes - higher concentrations of 4HNE promote apoptosis; whereas, lower concentrations promote proliferation. In this article, we provide a brief summary of the cellular effects of 4HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTA4-4. Taken together, 4HNE is a key signaling molecule and that GSTs being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article. Copyright © 2015 Elsevier Inc. All rights

  7. Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling

    International Nuclear Information System (INIS)

    Singhal, Sharad S.; Singh, Sharda P.; Singhal, Preeti; Horne, David; Singhal, Jyotsana; Awasthi, Sanjay

    2015-01-01

    4-Hydroxy-2-trans-nonenal (4HNE), one of the major end products of lipid peroxidation (LPO), has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione-peroxidase activity and that these enzymes can also detoxify LPO end-products such as 4HNE. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that LPO products, particularly hydroperoxides and 4HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the alpha-class GSTs through the regulation of the intracellular concentrations of 4HNE. We demonstrate that 4HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase (JNK) and caspase-3 activation. Cells exposed to mild, transient heat or oxidative stress acquire the capacity to exclude intracellular 4HNE at a faster rate by inducing GSTA4-4 which conjugates 4HNE to glutathione (GSH), and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4HNE (GS-HNE). The balance between formation and exclusion promotes different cellular processes — higher concentrations of 4HNE promote apoptosis; whereas, lower concentrations promote proliferation. In this article, we provide a brief summary of the cellular effects of 4HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTA4-4. Taken together, 4HNE is a key signaling molecule and that GSTs being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article. - Highlights: • GSTs are the major

  8. The agricultural heritage of Lampedusa (Pelagie Archipelago, South Italy and its key role for cultivar and wildlife conservation

    Directory of Open Access Journals (Sweden)

    Tommaso La Mantia

    2011-04-01

    Full Text Available As occurred on many other small Mediterranean islands, agricultural activity at Lampedusa (Strait of Sicily underwent a very strong decline in terms of surface area during the second half of the last century. In particular, cereal crops have ceased and horticulture is disappearing, while vineyards still occupy a reduced area but are quickly vanishing and currently survive thanks to a small number of old farmers. Here are presented the results of a research carried out by interviewing seven farmers in order to study not only the techniques and the germplasm used in local viticulture, but also the final use of grapes and an evaluation on the connection between traditional farming and agro-ecosystems plant species-richness. Vines were grown for wine, to produce fresh and sun-dried grapes, or to preserve them in alcohol. Several names of the local varieties suggest that they might have been introduced in Lampedusa from the neighbouring territories: being fishermen and farmers at the same time, local people had trade relationships with other Mediterranean areas such as Tunisia, Malta and Southern Italy. Furthermore, local farming plays a key role in plant conservation. In fact, the disappearance of agricultural systems is leading to the extinction of 43 plant species, some of them considered rare not only on the local level, but also on the regional and national one. Because of the small size of farmland and its fragmentation, local agriculture cannot be supported by the European Community. Therefore, in order to safeguard local viticulture, special systems of assistance and new managing policies - focused on rural development plans and showing which concrete actions are necessary and feasible to protect the agroecosystems - are needed.

  9. Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13–Suppressed Elastin in Airway Fibroblasts in Asthma

    Science.gov (United States)

    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. PMID:26074138

  10. Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13-Suppressed Elastin in Airway Fibroblasts in Asthma.

    Science.gov (United States)

    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.

  11. Reduction of conspicuous facial pores by topical fullerene: possible role in the suppression of PGE2 production in the skin.

    Science.gov (United States)

    Inui, Shigeki; Mori, Ayako; Ito, Masayuki; Hyodo, Sayuri; Itami, Satoshi

    2014-02-22

    Conspicuous facial pores are therapeutic targets for cosmeceuticals. Here we examine the effect of topical fullerene on conspicuous facial pores using a new image analyser called the VISIA® system. Ten healthy Japanese females participated in this study, and they received applications of 1% fullerene lotion to the face twice a day for 8 weeks. Fullerene lotion significantly decreased conspicuous pores by 17.6% (p facial pores after an 8-week treatment possibly through the suppression of PGE2 production in the epidermis.

  12. A Role of Base Plate Jerk Feedback Scheme for Suppression of the Self Vibration in a Pneumatic Positioning Stage

    Science.gov (United States)

    Wali, Mohebullah; Nakamura, Yukinori; Wakui, Shinji

    In this study, a positioning stage is considered, which is actuated by four pneumatic cylinders and vertically supported by four coil-type spring isolators. Previously, we realized the base plate jerk feedback (BPJFB) to be analogues to a Master-Slave system which can synchronize the motion of the stage as a Slave to the motion of the base plate as a Master. However, in the case of real positioning, the stage had slightly self oscillation with higher frequency due to the higher gains set to the outer feedback loop controller besides its oscillation due to the natural vibration of the base plate. The self oscillation of stage was misunderstood to be the natural vibration of base plate due to the reaction force. However, according to the experimental results, the BPJFB scheme was able to control both of the mentioned vibrations. Suppression of the self vibration of stage is an interesting phenomenon, which should be experimentally investigated. Therefore, the current study focuses on the suppression of the self vibration of stage by using the BPJFB scheme. The experimental results show that besides operating as a Master-Slave synchronizing system, the PBJFB scheme is able to increase the damping ratio and stiffness of stage against its self vibration. This newly recognized phenomenon contributes to further increase the proportional gain of the outer feedback loop controller. As a result, the positioning speed and stability can be improved.

  13. Blunted suppression of acyl-ghrelin in response to fructose ingestion in obese adolescents: the role of insulin resistance.

    Science.gov (United States)

    Van Name, Michelle; Giannini, Cosimo; Santoro, Nicola; Jastreboff, Ania M; Kubat, Jessica; Li, Fangyong; Kursawe, Romy; Savoye, Mary; Duran, Elvira; Dziura, James; Sinha, Rajita; Sherwin, Robert S; Cline, Gary; Caprio, Sonia

    2015-03-01

    Fructose consumption has risen alongside obesity and diabetes. Gut hormones involved in hunger and satiety (ghrelin and PYY) may respond differently to fructose compared with glucose ingestion. This study evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity. Adolescents were divided into lean (n = 14), obese insulin sensitive (n = 12) (OIS), and obese insulin resistant (n = 15) (OIR). In a double-blind, cross-over design, subjects drank 75 g of glucose or fructose in random order, serum was obtained every 10 minutes for 60 minutes. Baseline acyl-ghrelin was highest in lean and lowest in OIR (P = 0.02). After glucose ingestion, acyl-ghrelin decreased similarly in lean and OIS but was lower in OIR (vs. lean, P = 0.03). Suppression differences were more pronounced after fructose (lean vs. OIS, P = 0.008, lean vs. OIR, P < 0.001). OIS became significantly hungrier after fructose (P = 0.015). PYY was not significantly different at baseline, varied minimally after glucose, and rose after fructose. Compared with lean, OIS adolescents have impaired acyl-ghrelin responses to fructose but not glucose, whereas OIR adolescents have blunted responses to both. Diminished suppression of acyl-ghrelin in childhood obesity, particularly if accompanied by insulin resistance, may promote hunger and overeating. © 2015 The Obesity Society.

  14. 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...

  15. The key role of U{sub 28} in the aqueous self-assembly of uranyl peroxide nanocages

    Energy Technology Data Exchange (ETDEWEB)

    Falaise, Clement; Nyman, May [Energy Frontier Research Center, Materials Science of Actinides, Department of Chemistry, Oregon State University, Corvallis, OR (United States)

    2016-10-04

    For 11 years now, the structural diversity and aesthetic beauty of uranyl-peroxide capsules have fascinated researchers from the diverse fields of mineralogy, polyoxometalate chemistry, and nuclear fuel technologies. There is still much to be learned about the mechanisms of the self-assembly process, and the role of solution parameters including pH, alkali template, temperature, time, and others. Here we have exploited the high solubility of the UO{sub 2}{sup 2+}/H{sub 2}O{sub 2}/LiOH aqueous system to address the effect of the hydroxide concentration. Important techniques of this study are single-crystal X-ray diffraction, small-angle X-ray scattering, and Raman spectroscopy. Three key phases dominate the solution speciation as a function of time and the LiOH/UO{sub 2}{sup 2+} ratio: the uranyl-triperoxide monomer [UO{sub 2}(O{sub 2}){sub 3}]{sup 4-}and the two capsules [(UO{sub 2})(O{sub 2})(OH)]{sub 24}{sup 24-}(U{sub 24}) and [(UO{sub 2})(O{sub 2}){sub 1.5}]{sub 28}{sup 28-}(U{sub 28}). When the LiOH/U ratio is around three, U{sub 28} forms rapidly and this cluster can be isolated in high yield and purity. This result was most surprising and challenges the hypothesis that alkali templating is the most important determinant in the cluster geometry. Moreover, analogous experiments with KOH, NH{sub 4}OH, and TEAOH (TEA=tetraethylammonium) also rapidly yield U{sub 28}, which suggests that U{sub 28} is the kinetically favored species. Complete mapping of the pH-time phase space reveals only a narrow window of the U{sub 28} dominance, which is why it was previously overlooked as an important kinetic species in this chemical system, as well as others with different counterions. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  16. Key role of the endothelial TGF-β/ALK1/endoglin signaling pathway in humans and rodents pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Benoît Gore

    Full Text Available Mutations affecting transforming growth factor-beta (TGF-β superfamily receptors, activin receptor-like kinase (ALK-1, and endoglin (ENG occur in patients with pulmonary arterial hypertension (PAH. To determine whether the TGF-β/ALK1/ENG pathway was involved in PAH, we investigated pulmonary TGF-β, ALK1, ALK5, and ENG expressions in human lung tissue and cultured pulmonary-artery smooth-muscle-cells (PA-SMCs and pulmonary endothelial cells (PECs from 14 patients with idiopathic PAH (iPAH and 15 controls. Seeing that ENG was highly expressed in PEC, we assessed the effects of TGF-β on Smad1/5/8 and Smad2/3 activation and on growth factor production by the cells. Finally, we studied the consequence of ENG deficiency on the chronic hypoxic-PH development by measuring right ventricular (RV systolic pressure (RVSP, RV hypertrophy, and pulmonary arteriolar remodeling in ENG-deficient (Eng+/- and wild-type (Eng+/+ mice. We also evaluated the pulmonary blood vessel density, macrophage infiltration, and cytokine expression in the lungs of the animals. Compared to controls, iPAH patients had higher serum and pulmonary TGF-β levels and increased ALK1 and ENG expressions in lung tissue, predominantly in PECs. Incubation of the cells with TGF-β led to Smad1/5/8 phosphorylation and to a production of FGF2, PDGFb and endothelin-inducing PA-SMC growth. Endoglin deficiency protected mice from hypoxic PH. As compared to wild-type, Eng+/- mice had a lower pulmonary vessel density, and no change in macrophage infiltration after exposure to chronic hypoxia despite the higher pulmonary expressions of interleukin-6 and monocyte chemoattractant protein-1. The TGF-β/ALK1/ENG signaling pathway plays a key role in iPAH and experimental hypoxic PH via a direct effect on PECs leading to production of growth factors and inflammatory cytokines involved in the pathogenesis of PAH.

  17. Calcineurin plays key roles in the dimorphic transition and virulence of the human pathogenic zygomycete Mucor circinelloides.

    Science.gov (United States)

    Lee, Soo Chan; Li, Alicia; Calo, Silvia; Heitman, Joseph

    2013-01-01

    Many pathogenic fungi are dimorphic and switch between yeast and filamentous states. This switch alters host-microbe interactions and is critical for pathogenicity. However, in zygomycetes, whether dimorphism contributes to virulence is a central unanswered question. The pathogenic zygomycete Mucor circinelloides exhibits hyphal growth in aerobic conditions but switches to multi-budded yeast growth under anaerobic/high CO₂ conditions. We found that in the presence of the calcineurin inhibitor FK506, Mucor exhibits exclusively multi-budded yeast growth. We also found that M. circinelloides encodes three calcineurin catalytic A subunits (CnaA, CnaB, and CnaC) and one calcineurin regulatory B subunit (CnbR). Mutations in the latch region of CnbR and in the FKBP12-FK506 binding domain of CnaA result in hyphal growth of Mucor in the presence of FK506. Disruption of the cnbR gene encoding the sole calcineurin B subunit necessary for calcineurin activity yielded mutants locked in permanent yeast phase growth. These findings reveal that the calcineurin pathway plays key roles in the dimorphic transition from yeast to hyphae. The cnbR yeast-locked mutants are less virulent than the wild-type strain in a heterologous host system, providing evidence that hyphae or the yeast-hyphal transition are linked to virulence. Protein kinase A activity (PKA) is elevated during yeast growth under anaerobic conditions, in the presence of FK506, or in the yeast-locked cnbR mutants, suggesting a novel connection between PKA and calcineurin. cnaA mutants lacking the CnaA catalytic subunit are hypersensitive to calcineurin inhibitors, display a hyphal polarity defect, and produce a mixture of yeast and hyphae in aerobic culture. The cnaA mutants also produce spores that are larger than wild-type, and spore size is correlated with virulence potential. Our results demonstrate that the calcineurin pathway orchestrates the yeast-hyphal and spore size dimorphic transitions that contribute to

  18. Upregulation of NOXA by 10-Hydroxycamptothecin plays a key role in inducing fibroblasts apoptosis and reducing epidural fibrosis

    Directory of Open Access Journals (Sweden)

    Jihang Dai

    2017-01-01

    the first to demonstrate that upregulation of NOXA by HCPT plays a key role in inducing fibroblast apoptosis and in reducing epidural fibrosis. These findings might provide a potential therapeutic target for preventing epidural fibrosis following laminectomy.

  19. Regulation of Neph3 gene in podocytes - key roles of transcription factors NF-kappaB and Sp1

    LENUS (Irish Health Repository)

    Ristola, Mervi

    2009-08-24

    Abstract Background Neph3 (filtrin) is expressed in the glomerular podocytes where it localizes at the specialized cell adhesion structures of the foot processes called slit diaphragms which form the outermost layer of the glomerular filtration barrier. Neph3 protein shows homology and structural similarity to Neph1, Neph2 and nephrin, which all are crucial for maintaining the normal glomerular ultrafiltration function. The exact function of Neph3 in the kidney is not known but we have previously shown that the level of Neph3 mRNA is decreased in proteinuric diseases. This suggests that Neph3 may play a role in the pathogenesis of kidney damage, and emphasizes the need to analyze the regulatory mechanisms of Neph3 gene. In this study we investigated the transcriptional regulation of Neph3 gene by identifying transcription factors that control Neph3 expression. Results We cloned and characterized approximately 5 kb fragment upstream of the Neph3 gene. Neph3 proximal promoter near the transcription start site was found to be devoid of TATA and CAAT boxes, but to contain a highly GC-rich area. Using promoter reporter gene constructs, we localized the main activating regulatory region of Neph3 gene in its proximal promoter region from -105 to -57. Within this region, putative transcription factor binding sites for NF-κB and Sp1 were found by computational analysis. Mutational screening indicated that NF-κB and Sp1 response elements are essential for the basal transcriptional activity of the Neph3 promoter. Co-transfection studies further showed that NF-κB and Sp1 regulate Neph3 promoter activity. In addition, overexpression of NF-κB increased endogenous Neph3 gene expression. Chromatin immunoprecipitation assay using cultured human podocytes demonstrated that both NF-κB and Sp1 interact with the Neph3 promoter. Conclusion Our results show that NF-κB and Sp1 are key regulators of Neph3 expression at the basal level in podocytes, therefore providing new insight

  20. The role of ventromedial prefrontal cortex volume in the association of expressive suppression and externally oriented thinking.

    Science.gov (United States)

    Li, Xu; Lu, Jiamei; Li, Bingbing; Li, Haijiang; Jin, Li; Qiu, Jiang

    2017-11-01

    Studies have suggested that expressive suppression (ES) is linked to externally oriented thinking (EOT) through the ventromedial prefrontal cortex (vmPFC), and there are gender differences in their association. The present structural magnetic resonance imaging study was to investigate the neural bases of ES and EOT and their association in females versus males in a Chinese college sample. A total of 142 participants (83 females) were enrolled, and they completed the ES subscale of the Emotion Regulation Questionnaire, 20-item Toronto Alexithymia Scale, and anatomical scanning. Voxel-based morphometry, region of interest, and whole brain analyses with peak-level significance (family-wise error corrected at p design limited causal conclusions. The vmPFC may be the only neural base of ES and EOT and their association. In addition, these results were sex-specific. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. A crucial role of activin A-mediated growth hormone suppression in mouse and human heart failure.

    Directory of Open Access Journals (Sweden)

    Noritoshi Fukushima

    Full Text Available Infusion of bone marrow-derived mononuclear cells (BMMNC has been reported to ameliorate cardiac dysfunction after acute myocardial infarction. In this study, we investigated whether infusion of BMMNC is also effective for non-ischemic heart failure model mice and the underlying mechanisms. Intravenous infusion of BMMNC showed transient cardioprotective effects on animal models with dilated cardiomyopathy (DCM without their engraftment in heart, suggesting that BMMNC infusion improves cardiac function via humoral factors rather than their differentiation into cardiomyocytes. Using conditioned media from sorted BMMNC, we found that the cardioprotective effects were mediated by growth hormone (GH secreted from myeloid (Gr-1(+ cells and the effects was partially mediated by signal transducer and activator of transcription 3 in cardiomyocytes. On the other hand, the GH expression in Gr-1(+ cells was significantly downregulated in DCM mice compared with that in healthy control, suggesting that the environmental cue in heart failure might suppress the Gr-1(+ cells function. Activin A was upregulated in the serum of DCM models and induced downregulation of GH levels in Gr-1(+ cells and serum. Furthermore, humoral factors upregulated in heart failure including angiotensin II upregulated activin A in peripheral blood mononuclear cells (PBMNC via activation of NFκB. Similarly, serum activin A levels were also significantly higher in DCM patients with heart failure than in healthy subjects and the GH levels in conditioned medium from PBMNC of DCM patients were lower than that in healthy subjects. Inhibition of activin A increased serum GH levels and improved cardiac function of DCM model mice. These results suggest that activin A causes heart failure by suppressing GH activity and that inhibition of activin A might become a novel strategy for the treatment of heart failure.

  2. Role of fluconazole in the long-term suppressive therapy of fungal infections in patients with artificial implants.

    Science.gov (United States)

    Penk, A; Pittrow, L

    1999-12-01

    With the increased use of artificial implants the management of related infections has become an important challenge. Normally an infected implant would be removed. In many cases this might be contraindicated and drug treatment remains as the only alternative. As microbiological eradication is often impossible, especially in fungal infections at artificial implants (FIAI) long-term suppressive therapy might be required. The objective of this study was to determine the therapeutic value of fluconazole (F) in the management of FIAI. Clinical data of 56 patients (pts) with proven or suspected fungal infections and artificial implants (FIAI) subsequently treated with F were analyzed retrospectively. FIAI caused by species with intrinsic resistance to F have been excluded from the study. The following implants were involved: prosthetic valve endocarditis (PVE) 25 pts (44.6%), intraocular lenses (IL) 9 pts (16.1%), ventriculoperitoneal shunts (VPS) 6 pts (10.7%), knee prostheses (KP) 5 pts (8.9%), biliary stents (BS) 4 pts (7.1 %), venous access devices (VAS) 3 pts (5.4%), urinary stents (US) 2 pts (3.6%), breast implant and pacemaker 1 patient (1.8%) each. Underlying diseases were valve insufficiency (in PVE), cataract surgery (in IL), prematurity in newborns (in VPS), arthrosis (in KP), biliary obstruction (in BS), cystic fibrosis (in VAS), and obstructive renal calculi (in US). Candida species (C. spp.) were the most frequently detected causative agents with C. parapsilosis as the leading cause (n = 19; 33.9%). Furthermore C. albicans (n = 15; 26.8%), C. spp. and fungi not further specified (n = 8; 14.3%), C. tropicalis (n = 3; 5.4%), C. glabrata (n = 3; 5.4%), and C. lusitaniae (n = 1; 1.8%) were identified. Acremonium kiliense has been detected in 4 pts (7.1%), Cryptococcus neoformans in 2 pts (3.6 %). Histoplasma capsulatum was identified in 1 patient (1.8%). The maximum duration of treatment with F was lifelong with a maximum recorded duration of 4,5 years. The

  3. 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.

  4. Owl-inspired leading-edge serrations play a crucial role in aerodynamic force production and sound suppression.

    Science.gov (United States)

    Rao, Chen; Ikeda, Teruaki; Nakata, Toshiyuki; Liu, Hao

    2017-07-04

    Owls are widely known for silent flight, achieving remarkably low noise gliding and flapping flights owing to their unique wing morphologies, which are normally characterized by leading-edge serrations, trailing-edge fringes and velvet-like surfaces. How these morphological features affect aerodynamic force production and sound suppression or noise reduction, however, is still not well known. Here we address an integrated study of owl-inspired single feather wing models with and without leading-edge serrations by combining large-eddy simulations (LES) with particle-image velocimetry (PIV) and force measurements in a low-speed wind tunnel. With velocity and pressure spectra analysis, we demonstrate that leading-edge serrations can passively control the laminar-turbulent transition over the upper wing surface, i.e. the suction surface at all angles of attack (0°    15° where owl wings often reach in flight. Our results indicate that the owl-inspired leading-edge serrations may be a useful device for aero-acoustic control in biomimetic rotor designs for wind turbines, aircrafts, multi-rotor drones as well as other fluid machinery.

  5. A genetic approach to elucidate the genotoxic pathway of monomethylarsonous acid suggests a key role for catalase

    Science.gov (United States)

    Although it is widely known that arsenic-contaminated drinking water causes many diseases, arsenic's exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as an important key event in the toxic MOA of arsenic. Our studies are centered...

  6. A genetic approach to elucidate the genotoxic pathway of monomethylarsonousacid (MMAIII) suggests a key role for catalase

    Science.gov (United States)

    Arsenic-contaminated drinking water causes cancer, neuropathy, respiratory effects, diabetes, and cardiovascular disease. Its exact mode of action (MOA) is not fully understood. Oxidative stress has been proposed as a key event in the toxic MOA of arsenic. Our studies are centere...

  7. 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.

  8. 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

  9. 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.

  10. What are the key dimensions of the personal tutor role for nurse education today? A literature review.

    OpenAIRE

    Leddington, Susan

    2012-01-01

    Background. The accepted position of the personal tutor role from the background literature includes both pastoral care and academic support. Recent government led initiatives of widening access to higher education, the Dearing report (NCIHE, 1997) and the National Student Survey (HEFCE, 2006) have changed higher education and affected the personal tutor role. The implication of these initiatives for nurse education is unclear. Aim. The aim of this literature review is to explore the dimensio...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

    Directory of Open Access Journals (Sweden)

    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

  13. 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

  14. Novel Role for Na,K-ATPase in Phosphatidylinositol 3-Kinase Signaling and Suppression of Cell Motility

    OpenAIRE

    Barwe, Sonali P.; Anilkumar, Gopalakrishnapillai; Moon, Sun Y.; Zheng, Yi; Whitelegge, Julian P.; Rajasekaran, Sigrid A.; Rajasekaran, Ayyappan K.

    2005-01-01

    The Na,K-ATPase, consisting of α- and β-subunits, regulates intracellular ion homeostasis. Recent studies have demonstrated that Na,K-ATPase also regulates epithelial cell tight junction structure and functions. Consistent with an important role in the regulation of epithelial cell structure, both Na,K-ATPase enzyme activity and subunit levels are altered in carcinoma. Previously, we have shown that repletion of Na,K-ATPase β1-subunit (Na,K-β) in highly motile Moloney sarcoma virus-transforme...

  15. The key role of peltate glandular trichomes in symbiota comprising clavicipitaceous fungi of the genus periglandula and their host plants.

    Science.gov (United States)

    Steiner, Ulrike; Kucht, Sabine Hellwig neé; Ahimsa-Müller, Mahalia A; Grundmann, Nicola; Li, Shu-Ming; Drewke, Christel; Leistner, Eckhard

    2015-04-16

    Clavicipitaceous fungi producing ergot alkaloids were recently discovered to be epibiotically associated with peltate glandular trichomes of Ipomoea asarifolia and Turbina corymbosa, dicotyledonous plants of the family Convolvulaceae. Mediators of the close association between fungi and trichomes may be sesquiterpenes, main components in the volatile oil of different convolvulaceous plants. Molecular biological studies and microscopic investigations led to the observation that the trichomes do not only secrete sesquiterpenes and palmitic acid but also seem to absorb ergot alkaloids from the epibiotic fungal species of the genus Periglandula. Thus, the trichomes are likely to have a dual and key function in a metabolic dialogue between fungus and host plant.

  16. Work Stress and Depressive Symptoms in Fishermen With a Smoking Habit: A Mediator Role of Nicotine Dependence and Possible Moderator Role of Expressive Suppression and Cognitive Reappraisal.

    Science.gov (United States)

    Jiang, Hongjuan; Li, Sailan; Yang, Juan

    2018-01-01

    This study examined pathways of influence between work stress, depressive symptoms, nicotine dependence, expressive suppression, and cognitive reappraisal in fishermen with smoking habits in Qionghai, Hainan province, China (N = 1068). These fishermen responded to multiple assessments a week before leaving on a deep-sea fishing trip, including a Mental Stressor Investigation Questionnaire (MSIQ), the Center for Epidemiological Studies Depression Scale (CES-D), the Russell Reason for Smoking Questionnaire (RRSQ), and an Emotion Regulation Questionnaire (ERQ). Structural equation modeling (SEM) analyses of the collected data in Mplus 7 showed that work stress and nicotine dependence were independent predictors of depressive symptoms. The relationship between work stress and depressive symptoms was found to be partially mediated by nicotine dependence and be moderated by cognitive reappraisal. The evidence suggests it advantageous to examine the need of work stress, nicotine dependence, and cognitive reappraisal when attempting to understand depressive symptoms in fishermen with a smoking habit. These findings suggest that improving nicotine dependence through work stress management and training in cognitive reappraisal could be utilized as effective modalities for improving depressive symptoms.

  17. Females Are Protected From Iron-Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress.

    Science.gov (United States)

    Das, Subhash K; Patel, Vaibhav B; Basu, Ratnadeep; Wang, Wang; DesAulniers, Jessica; Kassiri, Zamaneh; Oudit, Gavin Y

    2017-01-23

    Sex-related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron-overload cardiomyopathy is poorly understood. Male and female wild-type and hemojuvelin-null mice were injected and fed with a high-iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis. Female mice were completely protected from iron-overload cardiomyopathy, whereas iron overload resulted in marked diastolic dysfunction in male iron-overloaded mice based on echocardiographic and invasive pressure-volume analyses. Female mice demonstrated a marked suppression of iron-mediated oxidative stress and a lack of myocardial fibrosis despite an equivalent degree of myocardial iron deposition. Ovariectomized female mice with iron overload exhibited essential pathophysiological features of iron-overload cardiomyopathy showing distinct diastolic and systolic dysfunction, severe myocardial fibrosis, increased myocardial oxidative stress, and increased expression of cardiac disease markers. Ovariectomy prevented iron-induced upregulation of ferritin, decreased myocardial SERCA2a levels, and increased NCX1 levels. 17β-Estradiol therapy rescued the iron-overload cardiomyopathy in male wild-type mice. The responses in wild-type and hemojuvelin-null female mice were remarkably similar, highlighting a conserved mechanism of sex-dependent protection from iron-overload-mediated cardiac injury. Male and female mice respond differently to iron-overload-mediated effects on heart structure and function, and females are markedly protected from iron-overload cardiomyopathy. Ovariectomy in female mice exacerbated iron-induced myocardial injury and precipitated severe cardiac dysfunction during iron-overload conditions, whereas 17β-estradiol therapy was protective in male iron-overloaded mice.

  18. Highly sensitive avoidance plays a key role in sensory adaptation to deep-sea hydrothermal vent environments.

    Directory of Open Access Journals (Sweden)

    Tetsuya Ogino

    Full Text Available The environments around deep-sea hydrothermal vents are very harsh conditions for organisms due to the possibility of exposure to highly toxic compounds and extremely hot venting there. Despite such extreme environments, some indigenous species have thrived there. Alvinellid worms (Annelida are among the organisms best adapted to high-temperature and oxidatively stressful venting regions. Although intensive studies of the adaptation of these worms to the environments of hydrothermal vents have been made, little is known about the worms' sensory adaptation to the severe chemical conditions there. To examine the sensitivity of the vent-endemic worm Paralvinella hessleri to low pH and oxidative stress, we determined the concentration of acetic acid and hydrogen peroxide that induced avoidance behavior of this worm, and compared these concentrations to those obtained for related species inhabiting intertidal zones, Thelepus sp. The concentrations of the chemicals that induced avoidance behavior of P. hessleri were 10-100 times lower than those for Thelepus sp. To identify the receptors for these chemicals, chemical avoidance tests were performed with the addition of ruthenium red, a blocker of transient receptor potential (TRP channels. This treatment suppressed the chemical avoidance behavior of P. hessleri, which suggests that TRP channels are involved in the chemical avoidance behavior of this species. Our results revealed for the first time hypersensitive detection systems for acid and for oxidative stress in the vent-endemic worm P. hessleri, possibly mediated by TRP channels, suggesting that such sensory systems may have facilitated the adaptation of this organism to harsh vent environments.

  19. The role of health informatics in clinical audit: part of the problem or key to the solution?

    Science.gov (United States)

    Georgiou, Andrew; Pearson, Michael

    2002-05-01

    The concepts of quality assurance (for which clinical audit is an essential part), evaluation and clinical governance each depend on the ability to derive and record measurements that describe clinical performance. Rapid IT developments have raised many new possibilities for managing health care. They have allowed for easier collection and processing of data in greater quantities. These developments have encouraged the growth of quality assurance as a key feature of health care delivery. In the past most of the emphasis has been on hospital information systems designed predominantly for the administration of patients and the management of financial performance. Large, hi-tech information system capacity does not guarantee quality information. The task of producing information that can be confidently used to monitor the quality of clinical care requires attention to key aspects of the design and operation of the audit. The Myocardial Infarction National Audit Project (MINAP) utilizes an IT-based system to collect and process data on large numbers of patients and make them readily available to contributing hospitals. The project shows that IT systems that employ rigorous health informatics methodologies can do much to improve the monitoring and provision of health care.

  20. A key role for arbuscular mycorrhiza in plant acquisition of P from sewage sludge recycled to soil

    DEFF Research Database (Denmark)

    Mackay, Jessica E.; Cavagnaro, Timothy R.; Müller-Stöver, Dorette Sophie

    2017-01-01

    Dried and incinerated sewage sludge (SS) have the potential to be used as phosphorus (P) fertilisers. Arbuscular mycorrhizal fungi (AMF) contribute to plant P uptake; however, their role in P uptake from SS has yet to be fully explored. A compartmented pot system with an isotope pool dilution...... approach was used to investigate wheat (Triticum aestivum L.) P uptake from soluble P, dried SS and incinerated SS, via roots and/or AMF hyphae. Wheat was sown into an inner compartment containing a 33P label with/without AMF (Rhizophagus irregularis) inoculum. An outer soil compartment contained the P...... access dried SS than when only roots could access dried SS. We discuss the results in terms of availability of P to roots and hyphae. We conclude that AMF play an important role in wheat P acquisition from dried SS and therefore can assist in the recycling of P in waste....

  1. What Role Does The Executive Officer Play In Ensuring Senior Officer Success Building An Organization Of Trust Is Key

    Science.gov (United States)

    2016-02-16

    AIR WAR COLLEGE AIR UNIVERSITY WHAT ROLE DOES THE EXECUTIVE OFFICER PLAY IN ENSURING SENIOR OFFICER SUCCESS? BUILDING AN ORGANIZATION OF...talk, demonstrate respect, create transparency, right wrongs, show loyalty , deliver results, get better, confront reality, clarify expectations...When speaking for the senior leader, the exec must ensure commander’s intent is conveyed clearly and accurately. It is for this reason that execs

  2. Role of pathogen-derived cell wall carbohydrates and prostaglandin E2 in immune response and suppression of fish immunity by the oomycete Saprolegnia parasitica.

    Science.gov (United States)

    Belmonte, Rodrigo; Wang, Tiehui; Duncan, Gary J; Skaar, Ida; Mélida, Hugo; Bulone, Vincent; van West, Pieter; Secombes, Christopher J

    2014-11-01

    Saprolegnia parasitica is a freshwater oomycete that is capable of infecting several species of fin fish. Saprolegniosis, the disease caused by this microbe, has a substantial impact on Atlantic salmon aquaculture. No sustainable treatment against saprolegniosis is available, and little is known regarding the host response. In this study, we examined the immune response of Atlantic salmon to S. parasitica infection and to its cell wall carbohydrates. Saprolegnia triggers a strong inflammatory response in its host (i.e., induction of interleukin-1β1 [IL-1β1], IL-6, and tumor necrosis factor alpha), while severely suppressing the expression of genes associated with adaptive immunity in fish, through downregulation of T-helper cell cytokines, antigen presentation machinery, and immunoglobulins. Oomycete cell wall carbohydrates were recognized by fish leukocytes, triggering upregulation of genes involved in the inflammatory response, similar to what is observed during infection. Our data suggest that S. parasitica is capable of producing prostaglandin [corrected] E2 (PGE2) in vitro, a metabolite not previously shown to be produced by oomycetes, and two proteins with homology to vertebrate enzymes known to play a role in prostaglandin biosynthesis have been identified in the oomycete genome. Exogenous PGE2 was shown to increase the inflammatory response in fish leukocytes incubated with cell wall carbohydrates while suppressing genes involved in cellular immunity (gamma interferon [IFN-γ] and the IFN-γ-inducible protein [γ-IP]). Inhibition of S. parasitica zoospore germination and mycelial growth by two cyclooxygenase inhibitors (aspirin and indomethacin) also suggests that prostaglandins may be involved in oomycete development. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  3. Rich biotin content in lignocellulose biomass plays the key role in determining cellulosic glutamic acid accumulation by Corynebacterium glutamicum.

    Science.gov (United States)

    Wen, Jingbai; Xiao, Yanqiu; Liu, Ting; Gao, Qiuqiang; Bao, Jie

    2018-01-01

    Lignocellulose is one of the most promising alternative feedstocks for glutamic acid production as commodity building block chemical, but the efforts by the dominant industrial fermentation strain Corynebacterium glutamicum failed for accumulating glutamic acid using lignocellulose feedstock. We identified the existence of surprisingly high biotin concentration in corn stover hydrolysate as the determining factor for the failure of glutamic acid accumulation by Corynebacterium glutamicum . Under excessive biotin content, induction by penicillin resulted in 41.7 ± 0.1 g/L of glutamic acid with the yield of 0.50 g glutamic acid/g glucose. Our further investigation revealed that corn stover contained 353 ± 16 μg of biotin per kg dry solids, approximately one order of magnitude greater than the biotin in corn grain. Most of the biotin remained stable during the biorefining chain and the rich biotin content in corn stover hydrolysate almost completely blocked the glutamic acid accumulation. This rich biotin existence was found to be a common phenomenon in the wide range of lignocellulose biomass and this may be the key reason why the previous studies failed in cellulosic glutamic acid fermentation from lignocellulose biomass. The extended recording of the complete members of all eight vitamin B compounds in lignocellulose biomass further reveals that the major vitamin B members were also under the high concentration levels even after harsh pretreatment. The high content of biotin in wide range of lignocellulose biomass feedstocks and the corresponding hydrolysates was discovered and it was found to be the key factor in determining the cellulosic glutamic acid accumulation. The highly reserved biotin and the high content of their other vitamin B compounds in biorefining process might act as the potential nutrients to biorefining fermentations. This study creates a new insight that lignocellulose biorefining not only generates inhibitors, but also keeps nutrients

  4. fMRI evidence for the role of recollection in suppressing misattribution errors: the illusory truth effect.

    Science.gov (United States)

    Mitchell, Jason P; Dodson, Chad S; Schacter, Daniel L

    2005-05-01

    Misattribution refers to the act of attributing a memory or idea to an incorrect source, such as successfully remembering a bit of information but linking it to an inappropriate person or time [Jacoby, L. L., Kelley, C., Brown, J., & Jasechko, J. (1989). Becoming famous overnight: Limits on the ability to avoid unconscious influences of the past. Journal of Personality and Social Psychology, 56, 326-338; Schacter, D. L. (1999). The seven sins of memory: Insights from psychology and cognitive neuroscience. American Psychologist, 54, 182-203; Schacter, D. L. (2001). The seven sins of memory: How the mind forgets and remembers. Boston: Houghton Mifflin]. Cognitive studies have suggested that misattribution errors may occur in the absence of recollection for the details of an initial encounter with a stimulus, but little is known about the neural basis of this memory phenomenon. Here we used functional magnetic resonance imaging (fMRI) to examine the hypothesized role of recollection in counteracting the illusory truth effect, a misattribution error whereby perceivers systematically overrate the truth of previously presented information. Imaging was conducted during the encoding and subsequent judgment of unfamiliar statements that were presented as true or false. Event-related fMRI analyses were conditionalized as a function of subsequent performance. Results demonstrated that encoding activation in regions previously associated with successful recollection--including the hippocampus and the ventrolateral prefrontal cortex (PFC)--correlated with the successful avoidance of misattribution errors, providing initial neuroimaging support for earlier cognitive accounts of misattribution.

  5. Evaluation of putative allelochemicals in rice root exudates for their role in the suppression of arrowhead root growth.

    Science.gov (United States)

    Seal, Alexa N; Haig, Terry; Pratley, James E

    2004-08-01

    In previous studies, 15 putative allelopathic compounds detected in rice root exudates were quantified by GC/MS/MS. In this study, multiple regression analysis on these compounds determined that five selected phenolics, namely caffeic, p-hydroxybenzoic, vanillic, syringic, and p-coumaric acids, from rice exudates were best correlated with the observed allelopathic effect on arrowhead (Sagittaria montevidensis) root growth. Despite this positive association, determination of the phenolic acid dose-response curve established that the amount quantified in the exudates was much lower than the required threshold concentration for arrowhead inhibition. A similar dose-response curve resulted from a combination of all 15 quantified compounds. Significant differences between the amounts of trans-ferulic acid, abietic acid, and an indole also existed between allelopathic and non-allelopathic rice cultivars. The potential roles of these three compounds in rice allelopathy were examined by chemoassay. Overall, neither the addition of trans-ferulic acid nor 5-hydroxyindole-3-acetic acid to the phenolic mix significantly contributed to phytotoxicity, although at higher concentrations, trans-ferulic acid appeared to act antagonistically to the phytotoxic effects of the phenolic mix. The addition of abietic acid also decreased the inhibitory effect of the phenolic mix. These studies indicate that the compounds quantified are not directly responsible for the observed allelopathic response. It is possible that the amount of phenolic acids may be indirectly related to the chemicals finally responsible for the observed allelopathic effect.

  6. 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

  7. α,β-Unsaturated aldehyde pollutant acrolein suppresses cardiomyocyte contractile function: Role of TRPV1 and oxidative stress.

    Science.gov (United States)

    Wu, Zhenbiao; He, Emily Y; Scott, Glenda I; Ren, Jun

    2015-01-01

    Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,β-unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90 ), fura-2 fluorescence intensity (FFI) and intracellular Ca(2+) decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca(2+) properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR90 and intracellular Ca(2+) decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, as well as apoptosis (as evidenced by Bcl-2, Bax, FasL, Caspase-3 and -8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,β-unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution-induced heart disease via a TRPV1- and oxidative stress-dependent mechanism. © 2013 Wiley Periodicals, Inc.

  8. Emotion and Exclusion: Key Ideas from Vygotsky to Review our Role in a School with a Cultural Diversity Setting

    Directory of Open Access Journals (Sweden)

    Enrique Riquelme MELLA

    Full Text Available ABSTRACT: Research demonstrates that minorities' children diagnosed with Emotional and Behavioural Disorders is overrepresented, being the ethnic minorities the most affected. The diagnostics have resulted in racism and discrimination. This article reflects upon the necessity to develop more integrated and dynamic models of inclusion for the schools. Based on Vygotsky´s ideas, a reflexion is done regarding the emotional education in schools, specifically about the need to include -in the teacher formation- the main role of the culture emotional rules in the dynamic of exclusion/inclusion of minorities. The article concludes with proposals to be considered for a culturally sensible vision on inclusion.

  9. How can core self-evaluations influence job burnout? The key roles of organizational commitment and job satisfaction.

    Science.gov (United States)

    Peng, Jiaxi; Li, Dongdong; Zhang, Zhenjiang; Tian, Yu; Miao, Danmin; Xiao, Wei; Zhang, Jiaxi

    2016-01-01

    This study aimed to explore how core self-evaluations influenced job burnout and mainly focused on the confirmation of the mediator roles of organizational commitment and job satisfaction. A total of 583 female nurses accomplished the Core Self-Evaluation Scale, Organizational Commitment Scale, Minnesota Satisfaction Questionnaire, and Maslach Burnout Inventory-General Survey. The results revealed that core self-evaluations, organizational commitment, job satisfaction, and job burnout were significantly correlated with each other. Structural equation modeling indicated that core self-evaluations can significantly influence job burnout and are completely mediated by organizational commitment and job satisfaction. © The Author(s) 2014.

  10. Searching for a Role of Nursing Personnel in Developing Landscape of Ehealth: Factors Determining Attitudes toward Key Patient Empowering Applications.

    Science.gov (United States)

    Duplaga, Mariusz

    2016-01-01

    Nurses may play an important role in the delivery of medical services based on the use of ehealth tools. Nevertheless, their taking an active role in an ehealth environment depends on their possessing the appropriate skills and mindset. The main objective of this paper was to assess nurses' opinions and to analyze the predictors of their acceptance of ehealth features relevant to patient empowerment with a strong focus on chronic care. A survey was conducted among nurses from hospital centers of south-eastern Poland based on a questionnaire designed to assess their attitudes toward the ehealth domain. The predictors of the nurses' acceptance of ehealth usage within specific contexts were assessed with uni- and multivariate logistic regression. An analysis was performed on data from 648 questionnaires retained after a quality check. The duration of Internet use was consistently related to higher acceptance of ehealth applications and more certainty regarding the reliability of health-related information available on the Internet. Nurses from urban medical centers were more skeptical about the use of specific ehealth solutions. Previous experience in using information technologies is the main factor influencing the acceptance of specific ehealth solutions relevant for care provided to patients suffering from chronic conditions.

  11. The Relation Between Emotion Understanding and Theory of Mind in Children Aged 3 to 8: The Key Role of Language

    Directory of Open Access Journals (Sweden)

    Ilaria Grazzani

    2018-05-01

    Full Text Available Although a significant body of research has investigated the relationships among children’s emotion understanding (EU, theory of mind (ToM, and language abilities. As far as we know, no study to date has been conducted with a sizeable sample of both preschool and school-age children exploring the direct effect of EU on ToM when the role of language was evaluated as a potential exogenous factor in a single comprehensive model. Participants in the current study were 389 children (age range: 37–97 months, M = 60.79 months; SD = 12.66, to whom a False-Belief understanding battery, the Test of Emotion Comprehension, and the Peabody Test were administered. Children’s EU, ToM, and language ability (receptive vocabulary were positively correlated. Furthermore, EU scores explained variability in ToM scores independently of participants’ age and gender. Finally, language was found to play a crucial role in both explaining variance in ToM scores and in mediating the relationship between EU and ToM. We discuss the theoretical and educational implications of these outcomes, particularly in relation to offering social and emotional learning programs through schools.

  12. The Relation Between Emotion Understanding and Theory of Mind in Children Aged 3 to 8: The Key Role of Language.

    Science.gov (United States)

    Grazzani, Ilaria; Ornaghi, Veronica; Conte, Elisabetta; Pepe, Alessandro; Caprin, Claudia

    2018-01-01

    Although a significant body of research has investigated the relationships among children's emotion understanding (EU), theory of mind (ToM), and language abilities. As far as we know, no study to date has been conducted with a sizeable sample of both preschool and school-age children exploring the direct effect of EU on ToM when the role of language was evaluated as a potential exogenous factor in a single comprehensive model. Participants in the current study were 389 children (age range: 37-97 months, M = 60.79 months; SD = 12.66), to whom a False-Belief understanding battery, the Test of Emotion Comprehension, and the Peabody Test were administered. Children's EU, ToM, and language ability (receptive vocabulary) were positively correlated. Furthermore, EU scores explained variability in ToM scores independently of participants' age and gender. Finally, language was found to play a crucial role in both explaining variance in ToM scores and in mediating the relationship between EU and ToM. We discuss the theoretical and educational implications of these outcomes, particularly in relation to offering social and emotional learning programs through schools.

  13. Disturbance of Oligodendrocyte Function Plays a Key Role in the Pathogenesis of Schizophrenia and Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Shingo Miyata

    2015-01-01

    Full Text Available The major psychiatric disorders such as schizophrenia (SZ and major depressive disorder (MDD are thought to be multifactorial diseases related to both genetic and environmental factors. However, the genes responsible and the molecular mechanisms underlying the pathogenesis of SZ and MDD remain unclear. We previously reported that abnormalities of disrupted-in-Schizophrenia-1 (DISC1 and DISC1 binding zinc finger (DBZ might cause major psychiatric disorders such as SZ. Interestingly, both DISC and DBZ have been further detected in oligodendrocytes and implicated in regulating oligodendrocyte differentiation. DISC1 negatively regulates the differentiation of oligodendrocytes, whereas DBZ plays a positive regulatory role in oligodendrocyte differentiation. We have reported that repeated stressful events, one of the major risk factors of MDD, can induce sustained upregulation of plasma corticosterone levels and serum/glucocorticoid regulated kinase 1 (Sgk1 mRNA expression in oligodendrocytes. Repeated stressful events can also activate the SGK1 cascade and cause excess arborization of oligodendrocyte processes, which is thought to be related to depressive-like symptoms. In this review, we discuss the expression of DISC1, DBZ, and SGK1 in oligodendrocytes, their roles in the regulation of oligodendrocyte function, possible interactions of DISC1 and DBZ in relation to SZ, and the activation of the SGK1 signaling cascade in relation to MDD.

  14. First clinical use of stereotaxy in humans: the key role of x-ray localization discovered by Gaston Contremoulins.

    Science.gov (United States)

    Bourdillon, Pierre; Apra, Caroline; Lévêque, Marc

    2018-03-01

    Although attempts to develop stereotactic approaches to intracranial surgery started in the late 19th century with Dittmar, Zernov, and more famously, Horsley and Clarke, widespread use of the technique for human brain surgery started in the second part of the 20th century. Remarkably, a significant similar surgical procedure had already been performed in the late 19th century by Gaston Contremoulins in France and has remained unknown. Contremoulins used the principles of modern stereotaxy in association with radiography for the first time, allowing the successful removal of intracranial bullets in 2 patients. This surgical premiere, greatly acknowledged in the popular French newspaper L'Illustration in 1897, received little scientific or governmental interest at the time, as it emanated from a young self-taught scientist without official medical education. This surgical innovation was only made possible financially by popular crowdfunding and, despite widespread military use during World War I, with 37,780 patients having benefited from this technique for intra- or extracranial foreign bodies, it never attracted academic or neurosurgical consideration. The authors of this paper describe the historical context of stereotactic developments and the personal history of Contremoulins, who worked in the department of experimental physiology of the French Academy of Sciences led by Étienne-Jules Marey in Paris, and later devoted himself to radiography and radioprotection. The authors also give precise information about his original stereotactic tool "the bullet finder" ("le chercheur de projectiles") and its key concepts.

  15. The Fatty Acid Biosynthesis Enzyme FabI Plays a Key Role In the Development of Liver Stage Malarial Parasites

    Science.gov (United States)

    Yu, Min; Santha Kumar, T. R.; Nkrumah, Louis J.; Coppi, Alida; Retzlaff, Silke; Li, Celeste D.; Kelly, Brendan J.; Moura, Pedro A.; Lakshmanan, Viswanathan; Freundlich, Joel S.; Valderramos, Juan-Carlos; Vilcheze, Catherine; Siedner, Mark; Tsai, Jennifer H.-C.; Falkard, Brie; Sidhu, Amar bir Singh; Purcell, Lisa A.; Gratraud, Paul; Kremer, Laurent; Waters, Andy P.; Schiehser, Guy; Jacobus, David P.; Janse, Chris J.; Ager, Arba; Jacobs, William R.; Sacchettini, James C.; Heussler, Volker; Sinnis, Photini; Fidock, David A.

    2008-01-01

    SUMMARY Fatty acid biosynthesis has been viewed as an important biological function of and therapeutic target for Plasmodium falciparum asexual blood stage infection. This apicoplast-resident type II pathway, distinct from the mammalian type I process, includes FabI. Here, we report synthetic chemistry and transfection studies concluding that Plasmodium FabI is not the target of the antimalarial activity of the bacterial FabI inhibitor triclosan. Disruption of fabI in P. falciparum or the rodent parasite P. berghei does not impede blood stage growth. In contrast, mosquito-derived fabI-deficient P. berghei sporozoites are markedly less infective for mice and typically fail to complete liver stage development in vitro. This is characterized by an inability to form intra-hepatic merosomes that normally initiate blood stage infections. These data illuminate key differences between liver and blood stage parasites in their requirements for host versus de novo synthesized fatty acids, and create new prospects for stage-specific antimalarial interventions. PMID:19064257

  16. Key Role of Nitrate in Phase Transitions of Urban Particles: Implications of Important Reactive Surfaces for Secondary Aerosol Formation

    Science.gov (United States)

    Sun, Jiaxing; Liu, Lei; Xu, Liang; Wang, Yuanyuan; Wu, Zhijun; Hu, Min; Shi, Zongbo; Li, Yongjie; Zhang, Xiaoye; Chen, Jianmin; Li, Weijun

    2018-01-01

    Ammonium sulfate (AS) and ammonium nitrate (AN) are key components of urban fine particles. Both field and model studies showed that heterogeneous reactions of SO2, NO2, and NH3 on wet aerosols accelerated the haze formation in northern China. However, little is known on phase transitions of AS-AN containing haze particles. Here hygroscopic properties of laboratory-generated AS-AN particles and individual particles collected during haze events in an urban site were investigated using an individual particle hygroscopicity system. AS-AN particles showed a two-stage deliquescence at mutual deliquescence relative humidity (MDRH) and full deliquescence relative humidity (DRH) and three physical states: solid before MDRH, solid-aqueous between MDRH and DRH, and aqueous after DRH. During hydration, urban haze particles displayed a solid core and aqueous shell at RH = 60-80% and aqueous phase at RH > 80%. Most particles were in aqueous phase at RH > 50% during dehydration. Our results show that AS content in individual particles determines their DRH and AN content determines their MDRH. AN content increase can reduce MDRH, which indicates occurrence of aqueous shell at lower RH. The humidity-dependent phase transitions of nitrate-abundant urban particles are important to provide reactive surfaces of secondary aerosol formation in the polluted air.

  17. Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages.

    Science.gov (United States)

    Maler, Mareike D; Nielsen, Peter J; Stichling, Nicole; Cohen, Idan; Ruzsics, Zsolt; Wood, Connor; Engelhard, Peggy; Suomalainen, Maarit; Gyory, Ildiko; Huber, Michael; Müller-Quernheim, Joachim; Schamel, Wolfgang W A; Gordon, Siamon; Jakob, Thilo; Martin, Stefan F; Jahnen-Dechent, Willi; Greber, Urs F; Freudenberg, Marina A; Fejer, György

    2017-08-01

    The scavenger receptor MARCO is expressed in several subsets of naive tissue-resident macrophages and has been shown to participate in the recognition of various bacterial pathogens. However, the role of MARCO in antiviral defense is largely unexplored. Here, we investigated whether MARCO might be involved in the innate sensing of infection with adenovirus and recombinant adenoviral vectors by macrophages, which elicit vigorous immune responses in vivo Using cells derived from mice, we show that adenovirus infection is significantly more efficient in MARCO-positive alveolar macrophages (AMs) and in AM-like primary macrophage lines (Max Planck Institute cells) than in MARCO-negative bone marrow-derived macrophages. Using antibodies blocking ligand binding to MARCO, as well as gene-deficient and MARCO-transfected cells, we show that MARCO mediates the rapid adenovirus transduction of macrophages. By enhancing adenovirus infection, MARCO contributes to efficient innate virus recognition through the cytoplasmic DNA sensor cGAS. This leads to strong proinflammatory responses, including the production of interleukin-6 (IL-6), alpha/beta interferon, and mature IL-1α. These findings contribute to the understanding of viral pathogenesis in macrophages and may open new possibilities for the development of tools to influence the outcome of infection with adenovirus or adenovirus vectors. IMPORTANCE Macrophages play crucial roles in inflammation and defense against infection. Several macrophage subtypes have been identified with differing abilities to respond to infection with both natural adenoviruses and recombinant adenoviral vectors. Adenoviruses are important respiratory pathogens that elicit vigorous innate responses in vitro and in vivo The cell surface receptors mediating macrophage type-specific adenovirus sensing are largely unknown. The scavenger receptor MARCO is expressed on some subsets of naive tissue-resident macrophages, including lung alveolar macrophages

  18. Sucrose in Cyanobacteria: From a Salt-Response Molecule to Play a Key Role in Nitrogen Fixation

    Directory of Open Access Journals (Sweden)

    María A. Kolman

    2015-01-01

    Full Text Available In the biosphere, sucrose is mainly synthesized in oxygenic photosynthetic organisms, such as cyanobacteria, green algae and land plants, as part of the carbon dioxide assimilation pathway. Even though its central position in the functional biology of plants is well documented, much less is known about the role of sucrose in cyanobacteria. In those prokaryotes, sucrose accumulation has been associated with salt acclimation, and considered as a compatible solute in low-salt tolerant strains. In the last years, functional characterizations of sucrose metabolizing enzymes, metabolic control analysis, cellular localization of gene expressions, and reverse genetic experiments have revealed that sucrose metabolism is crucial in the diazotrophic growth of heterocystic strains, and besides, that it can be connected to glycogen synthesis. This article briefly summarizes the current state of knowledge of sucrose physiological functions in modern cyanobacteria and how they might have evolved taking into account the phylogenetic analyses of sucrose enzymes.

  19. Glycogen metabolism has a key role in the cancer microenvironment and provides new targets for cancer therapy.

    Science.gov (United States)

    Zois, Christos E; Harris, Adrian L

    2016-02-01

    Metabolic reprogramming is a hallmark of cancer cells and contributes to their adaption within the tumour microenvironment and resistance to anticancer therapies. Recently, glycogen metabolism has become a recognised feature of cancer cells since it is upregulated in many tumour types, suggesting that it is an important aspect of cancer cell pathophysiology. Here, we provide an overview of glycogen metabolism and its regulation, with a focus on its role in metabolic reprogramming of cancer cells under stress conditions such as hypoxia, glucose deprivation and anticancer treatment. The various methods to detect glycogen in tumours in vivo as well as pharmacological modulators of glycogen metabolism are also reviewed. Finally, we discuss the therapeutic value of targeting glycogen metabolism as a strategy for combinational approaches in cancer treatment.

  20. The TvLEGU-1, a Legumain-Like Cysteine Proteinase, Plays a Key Role in Trichomonas vaginalis Cytoadherence

    Directory of Open Access Journals (Sweden)

    Francisco Javier Rendón-Gandarilla

    2013-01-01

    Full Text Available The goal of this paper was to characterize a Trichomonas vaginalis cysteine proteinase (CP legumain-1 (TvLEGU-1 and determine its potential role as a virulence factor during T. vaginalis infection. A 30-kDa band, which migrates in three protein spots (pI~6.3, ~6.5, and ~6.7 with a different type and level of phosphorylation, was identified as TvLEGU-1 by one- and two-dimensional Western blot (WB assays, using a protease-rich trichomonad extract and polyclonal antibodies produced against the recombinant TvLEGU-1 (anti-TvLEGU-1r. Its identification was confirmed by mass spectrometry. Immunofluorescence, cell binding, and WB assays showed that TvLEGU-1 is upregulated by iron at the protein level, localized on the trichomonad surface and in lysosomes and Golgi complex, bound to the surface of HeLa cells, and was found in vaginal secretions. Additionally, the IgG and Fab fractions of the anti-TvLEGU-1r antibody inhibited trichomonal cytoadherence up to 45%. Moreover, the Aza-Peptidyl Michael Acceptor that inhibited legumain proteolytic activity in live parasites also reduced levels of trichomonal cytoadherence up to 80%. In conclusion, our data show that the proteolytic activity of TvLEGU-1 is necessary for trichomonal adherence. Thus, TvLEGU-1 is a novel virulence factor upregulated by iron. This is the first report that a legumain-like CP plays a role in a pathogen cytoadherence.

  1. IgG receptor FcγRIIB plays a key role in obesity-induced hypertension.

    Science.gov (United States)

    Sundgren, Nathan C; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D; Tanigaki, Keiji; Yuhanna, Ivan S; Chambliss, Ken L; Mineo, Chieko; Shaul, Philip W

    2015-02-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that FcγRIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that FcγRIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas FcγRIIB(+/+) mice developed obesity-induced hypertension, FcγRIIB(-/-) mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; FcγRIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet-fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting FcγRIIB may potentially offer new means to treat hypertension in obese individuals. © 2014 American Heart Association, Inc.

  2. A molecular key for building hyphae aggregates: the role of the newly identified Streptomyces protein HyaS.

    Science.gov (United States)

    Koebsch, Ilona; Overbeck, Jens; Piepmeyer, Sophie; Meschke, Holger; Schrempf, Hildgund

    2009-05-01

    Streptomycetes produce many metabolites with medical and biotechnological applications. During fermentations, their hyphae build aggregates, a process in which the newly identified protein HyaS plays an important role. The corresponding hyaS gene is present within all investigated Streptomyces species. Reporter fusions indicate that transcription of hyaS occurs within substrate hyphae of the Streptomyces lividans wild type (WT). The HyaS protein is dominantly associated with the substrate hyphae. The WT strain forms cylindrically shaped clumps of densely packed substrate hyphae, often fusing to higher aggregates (pellets), which remain stably associated during shaking. Investigations by electron microscopy suggest that HyaS induces tight fusion-like contacts among substrate hyphae. In contrast, the pellets of the designed hyaS disruption mutant ΔH are irregular in shape, contain frequently outgrowing bunches of hyphae, and fuse less frequently. ΔH complemented with a plasmid carrying hyaS resembles the WT phenotype. Biochemical studies indicate that the C-terminal region of HyaS has amine oxidase activity. Investigations of ΔH transformants, each carrying a specifically mutated gene, lead to the conclusion that the in situ oxidase activity correlates with the pellet-inducing role of HyaS, and depends on the presence of certain histidine residues. Furthermore, the level of undecylprodigiosin, a red pigment with antibiotic activity, is influenced by the engineered hyaS subtype within a strain. These data present the first molecular basis for future manipulation of pellets, and concomitant production of secondary metabolites during biotechnological processes. © 2009 The Authors. Journal compilation © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd.

  3. IgG Receptor FcγRIIB Plays a Key Role in Obesity-Induced Hypertension

    Science.gov (United States)

    Sundgren, Nathan C.; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D.; Tanigaki, Keiji; Yuhanna, Ivan S.; Chambliss, Ken L.; Mineo, Chieko; Shaul, Philip W.

    2015-01-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that FcγRIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that FcγRIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas FcγRIIB+/+ mice developed obesity-induced hypertension, FcγRIIB−/− mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; FcγRIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet–fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting FcγRIIB may potentially offer new means to treat hypertension in obese individuals. PMID:25368023

  4. Systematic Analysis of White Pox Disease in Acropora palmata of the Florida Keys and Role of Serratia marcescens.

    Science.gov (United States)

    Joyner, Jessica L; Sutherland, Kathryn P; Kemp, Dustin W; Berry, Brett; Griffin, Ashton; Porter, James W; Amador, Molly H B; Noren, Hunter K G; Lipp, Erin K

    2015-07-01

    White pox disease (WPD) affects the threatened elkhorn coral, Acropora palmata. Owing in part to the lack of a rapid and simple diagnostic test, there have been few systematic assessments of the prevalence of acroporid serratiosis (caused specifically by Serratia marcescens) versus general WPD signs. Six reefs in the Florida Keys were surveyed between 2011 and 2013 to determine the disease status of A. palmata and the prevalence of S. marcescens. WPD was noted at four of the six reefs, with WPD lesions found on 8 to 40% of the colonies surveyed. S. marcescens was detected in 26.9% (7/26) of the WPD lesions and in mucus from apparently healthy colonies both during and outside of disease events (9%; 18/201). S. marcescens was detected with greater frequency in A. palmata than in the overlying water column, regardless of disease status (P = 0.0177). S. marcescens could not be cultured from A. palmata but was isolated from healthy colonies of other coral species and was identified as pathogenic pulsed-field gel electrophoresis type PDR60. WPD lesions were frequently observed on the reef, but unlike in prior outbreaks, no whole-colony death was observed. Pathogenic S. marcescens was circulating on the reef but did not appear to be the primary pathogen in these recent WPD episodes, suggesting that other pathogens or stressors may contribute to signs of WPD. Results highlight the critical importance of diagnostics in coral disease investigations, especially given that field manifestation of disease may be similar, regardless of the etiological agent. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Radical change of Zn speciation in pig slurry amended soil: Key role of nano-sized sulfide particles.

    Science.gov (United States)

    Formentini, Thiago Augusto; Legros, Samuel; Fernandes, Cristovão Vicente Scapulatempo; Pinheiro, Adilson; Le Bars, Maureen; Levard, Clément; Mallmann, Fábio Joel Kochem; da Veiga, Milton; Doelsch, Emmanuel

    2017-03-01

    Spreading livestock manure as fertilizer on farmlands is a widespread practice. It represents the major source of heavy metal(loid)s (HM) input in agricultural soils. Since zinc (Zn) is present at high concentrations in manure, it poses special environmental concerns related to phytotoxicity, groundwater contamination, and introduction in the food chain. Therefore, investigations on the fate and behavior of manure-borne Zn, when it enters the soil environment, are necessary to predict the environmental effects. Nevertheless, long-term field studies assessing Zn speciation in the organic waste matrix, as well as within the soil after manure application, are lacking. This study was designed to fill this gap. Using SEM-EDS and XAS analysis, we reported the following new results: (i) ZnS made up 100% of the Zn speciation in the pig slurry (the highest proportion of ZnS ever observed in organic waste); and (ii) ZnS aggregates were about 1-μm diameter (the smallest particle size ever reported in pig slurry). Moreover, the pig slurry containing ZnS was spread on the soil over an 11-year period, totaling 22 applications, and the resulting Zn speciation within the amended soil was analyzed. Surprisingly, ZnS, i.e. the only species responsible for a nearly 2-fold increase in the Zn concentration within the amended soil, was not detected in this soil. Based on SEM-EDS and XAS observations, we put forward the hypothesis that Zn in the pig slurry consisted of nano-sized ZnS crystallites that further aggregated. The low stability of ZnS nanoparticles within oxic and complex environments such as the studied soil was the key explanation for the radical change in pig slurry-borne Zn speciation after long-term amendments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The role of the general practitioner in the Australian approach to HIV care: interviews with 'key informants' from government, non-government and professional organisations.

    Science.gov (United States)

    Newman, Christy E; de Wit, John B F; Kippax, Susan C; Reynolds, Robert H; Canavan, Peter G; Kidd, Michael R

    2012-03-01

    HIV care is provided in a range of settings in Australia, but advances in HIV treatment and demographic and geographic changes in the affected population and general practitioner (GP) workforce are testing the sustainability of the special role for GPs. This paper explores how a group of 'key informants' described the role of the GP in the Australian approach to HIV care, and conceptualised the challenges currently inspiring debate around future models of care. A thematic analysis was conducted of semistructured interviews carried out in 2010 with 24 professionals holding senior roles in government, non-government and professional organisations that influence Australian HIV care policy. The strengths of the role of the GP were described as their community setting, collaborative partnership with other medical and health professions, and focus on patient needs. A number of associated challenges were also identified including the different needs of GPs with high and low HIV caseloads, the changing expectations of professional roles in general practice, and barriers to service accessibility for people living with HIV. While there are many advantages to delivering HIV services in primary care, GPs need flexible models of training and accreditation, support in strengthening relationships with other health and medical professionals, and assistance in achieving service accessibility. Consideration of how to support the GP workforce so that care can be made available in the broadest range of geographical and service settings is also critical if systems of HIV care delivery are to be realistic and cost-effective and meet consumer needs.

  7. 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).

  8. Elevated risk of type 2 diabetes for development of Alzheimer disease: a key role for oxidative stress in brain.

    Science.gov (United States)

    Butterfield, D Allan; Di Domenico, Fabio; Barone, Eugenio

    2014-09-01

    Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5 years after 65 years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggests that oxidative stress plays a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data interpreted from the point of view of oxidative stress with the aim of highlighting progresses in this field. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Alternative splicing: the pledge, the turn, and the prestige : The key role of alternative splicing in human biological systems.

    Science.gov (United States)

    Gallego-Paez, L M; Bordone, M C; Leote, A C; Saraiva-Agostinho, N; Ascensão-Ferreira, M; Barbosa-Morais, N L

    2017-09-01

    Alternative pre-mRNA splicing is a tightly controlled process conducted by the spliceosome, with the assistance of several regulators, resulting in the expression of different transcript isoforms from the same gene and increasing both transcriptome and proteome complexity. The differences between alternative isoforms may be subtle but enough to change the function or localization of the translated proteins. A fine control of the isoform balance is, therefore, needed throughout developmental stages and adult tissues or physiological conditions and it does not come as a surprise that several diseases are caused by its deregulation. In this review, we aim to bring the splicing machinery on stage and raise the curtain on its mechanisms and regulation throughout several systems and tissues of the human body, from neurodevelopment to the interactions with the human microbiome. We discuss, on one hand, the essential role of alternative splicing in assuring tissue function, diversity, and swiftness of response in these systems or tissues, and on the other hand, what goes wrong when its regulatory mechanisms fail. We also focus on the possibilities that splicing modulation therapies open for the future of personalized medicine, along with the leading techniques in this field. The final act of the spliceosome, however, is yet to be fully revealed, as more knowledge is needed regarding the complex regulatory network that coordinates alternative splicing and how its dysfunction leads to disease.

  10. The maternal nucleolus plays a key role in centromere satellite maintenance during the oocyte to embryo transition.

    Science.gov (United States)

    Fulka, Helena; Langerova, Alena

    2014-04-01

    The oocyte (maternal) nucleolus is essential for early embryonic development and embryos originating from enucleolated oocytes arrest at the 2-cell stage. The reason for this is unclear. Surprisingly, RNA polymerase I activity in nucleolus-less mouse embryos, as manifested by pre-rRNA synthesis, and pre-rRNA processing are not affected, indicating an unusual role of the nucleolus. We report here that the maternal nucleolus is indispensable for the regulation of major and minor satellite repeats soon after fertilisation. During the first embryonic cell cycle, absence of the nucleolus causes a significant reduction in major and minor satellite DNA by 12% and 18%, respectively. The expression of satellite transcripts is also affected, being reduced by more than half. Moreover, extensive chromosome bridging of the major and minor satellite sequences was observed during the first mitosis. Finally, we show that the absence of the maternal nucleolus alters S-phase dynamics and causes abnormal deposition of the H3.3 histone chaperone DAXX in pronuclei of nucleolus-less zygotes.

  11. The Preferential Infection of Astrocytes by Enterovirus 71 Plays a Key Role in the Viral Neurogenic Pathogenesis.

    Science.gov (United States)

    Feng, Min; Guo, Sujie; Fan, Shengtao; Zeng, Xiaofeng; Zhang, Ying; Liao, Yun; Wang, Jianbin; Zhao, Ting; Wang, Lichun; Che, Yanchun; Wang, Jingjing; Ma, Na; Liu, Longding; Yue, Lei; Li, Qihan

    2016-01-01

    The pathological manifestations of fatal cases of human hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) are characterized by inflammatory damage to the central nervous system (CNS). Here, the dynamic distribution of EV71 in the CNS and the subsequent pathological characteristics within different regions of neonatal rhesus macaque brain tissue were studied using a chimeric EV71 expressing green fluorescence protein. The results were compared with brain tissue obtained from the autopsies of deceased EV71-infected HFMD patients. These observations suggested that the virus was prevalent in areas around the blood vessels and nerve nuclei in the brain stem and showed a preference for astrocytes in the CNS. Interestingly, infected astrocytes within the in vivo and in vitro human and macaque systems exhibited increased expression of excitatory neurotransmitters and cytokines that also stimulated the neuronal secretion of the excitatory neurotransmitters noradrenalin and adrenalin, and this process most likely plays a role in the pathophysiological events that occur during EV71 infection.

  12. Quantitative Phospho-proteomic Analysis of TNFα/NFκB Signaling Reveals a Role for RIPK1 Phosphorylation in Suppressing Necrotic Cell Death.

    Science.gov (United States)

    Mohideen, Firaz; Paulo, Joao A; Ordureau, Alban; Gygi, Steve P; Harper, J Wade

    2017-07-01

    TNFα is a potent inducer of inflammation due to its ability to promote gene expression, in part via the NFκB pathway. Moreover, in some contexts, TNFα promotes Caspase-dependent apoptosis or RIPK1/RIPK3/MLKL-dependent necrosis. Engagement of the TNF Receptor Signaling Complex (TNF-RSC), which contains multiple kinase activities, promotes phosphorylation of several downstream components, including TAK1, IKKα/IKKβ, IκBα, and NFκB. However, immediate downstream phosphorylation events occurring in response to TNFα signaling are poorly understood at a proteome-wide level. Here we use Tandem Mass Tagging-based proteomics to quantitatively characterize acute TNFα-mediated alterations in the proteome and phosphoproteome with or without inhibition of the cIAP-dependent survival arm of the pathway with a SMAC mimetic. We identify and quantify over 8,000 phosphorylated peptides, among which are numerous known sites in the TNF-RSC, NFκB, and MAP kinase signaling systems, as well as numerous previously unrecognized phosphorylation events. Functional analysis of S320 phosphorylation in RIPK1 demonstrates a role for this event in suppressing its kinase activity, association with CASPASE-8 and FADD proteins, and subsequent necrotic cell death during inflammatory TNFα stimulation. This study provides a resource for further elucidation of TNFα-dependent signaling pathways. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Photoreduction of Hg(II) and photodemethylation of methylmercury: the key role of thiol sites on dissolved organic matter

    Science.gov (United States)

    Jeremiason, Jeffrey D.; Portner, Joshua C.; Aiken, George R.; Hiranaka, Amber J.; Dvorak, Michelle T.; Tran, Khuyen T.; Latch, Douglas E.

    2015-01-01

    This study examined the kinetics of photoreduction of Hg(II) and photodemethylation of methylmercury (MeHg+) attached to, or in the presence of, dissolved organic matter (DOM). Both Hg(II) and MeHg+ are principally bound to reduced sulfur groups associated with DOM in many freshwater systems. We propose that a direct photolysis mechanism is plausible for reduction of Hg(II) bound to reduced sulfur groups on DOM while an indirect mechanism is supported for photodemethylation of MeHg+ bound to DOM. UV spectra of Hg(II) and MeHg+ bound to thiol containing molecules demonstrate that the Hg(II)–S bond is capable of absorbing UV-light in the solar spectrum to a much greater extent than MeHg+–S bonds. Experiments with chemically distinct DOM isolates suggest that concentration of DOM matters little in the photochemistry if there are enough reduced S sites present to strongly bind MeHg+ and Hg(II); DOM concentration does not play a prominent role in photodemethylation other than to screen light, which was demonstrated in a field experiment in the highly colored St. Louis River where photodemethylation was not observed at depths ≥10 cm. Experiments with thiol ligands yielded slower photodegradation rates for MeHg+ than in experiments with DOM and thiols; rates in the presence of DOM alone were the fastest supporting an intra-DOM mechanism. Hg(II) photoreduction rates, however, were similar in experiments with only DOM, thiols plus DOM, or only thiols suggesting a direct photolysis mechanism. Quenching experiments also support the existence of an intra-DOM photodemethylation mechanism for MeHg+. Utilizing the difference in photodemethylation rates measured for MeHg+ attached to DOM or thiol ligands, the binding constant for MeHg+ attached to thiol groups on DOM was estimated to be 1016.7.

  14. Catalytic Ozonation of Toluene Using Chilean Natural Zeolite: The Key Role of Brønsted and Lewis Acid Sites

    Directory of Open Access Journals (Sweden)

    Serguei Alejandro-Martín

    2018-05-01

    Full Text Available The influence of surface physical-chemical characteristics of Chilean natural zeolite on the catalytic ozonation of toluene is presented in this article. Surface characteristics of natural zeolite were modified by acid treatment with hydrochloric acid and ion-exchange with ammonium sulphate. Prior to catalytic ozonation assays, natural and chemically modified zeolite samples were thermally treated at 623 and 823 K in order to enhance Brønsted and Lewis acid sites formation, respectively. Natural and modified zeolite samples were characterised by N2 adsorption at 77 K, elemental analysis, X-ray fluorescence, and Fourier transform infrared (FTIR spectroscopy, using pyridine as a probe molecule. The highest values of the reaction rate of toluene oxidation were observed when NH4Z1 and 2NH4Z1 zeolite samples were used. Those samples registered the highest density values of Lewis acid sites compared to other samples used here. Results indicate that the presence of strong Lewis acid sites at the 2NH4Z1 zeolite surface causes an increase in the reaction rate of toluene oxidation, confirming the role of Lewis acid sites during the catalytic ozonation of toluene at room temperature. Lewis acid sites decompose gaseous ozone into atomic oxygen, which reacts with the adsorbed toluene at Brønsted acid sites. On the other hand, no significant contribution of Brønsted acid sites on the reaction rate was registered when NH4Z1 and 2NH4Z1 zeolite samples were used.

  15. Key Role of Alphaproteobacteria and Cyanobacteria in the Formation of Stromatolites of Lake Dziani Dzaha (Mayotte, Western Indian Ocean

    Directory of Open Access Journals (Sweden)

    Emmanuelle Gérard

    2018-05-01

    , respectively. These results point out the role of phototrophic Alphaproteobacteria in the formation of stromatolites, which may open new perspective for the analysis of the fossil record.

  16. The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin plays a key role in adipocyte differentiation.

    Science.gov (United States)

    Chen, Weiqin; Yechoor, Vijay K; Chang, Benny Hung-Junn; Li, Ming V; March, Keith L; Chan, Lawrence

    2009-10-01

    Mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2) are the underlying defect in patients with congenital generalized lipodystrophy type 2. BSCL2 encodes a protein called seipin, whose function is largely unknown. In this study, we investigated the role of Bscl2 in the regulation of adipocyte differentiation. Bscl2 mRNA is highly up-regulated during standard hormone-induced adipogenesis in 3T3-L1 cells in vitro. However, this up-regulation does not occur during mesenchymal stem cell (C3H10T1/2 cells) commitment to the preadipocyte lineage. Knockdown of Bscl2 by short hairpin RNA in C3H10T1/2 cells has no effect on bone morphogenetic protein-4-induced preadipocyte commitment. However, knockdown in 3T3-L1 cells prevents adipogenesis induced by a standard hormone cocktail, but adipogenesis can be rescued by the addition of peroxisome proliferator-activated receptor-gamma agonist pioglitazone at an early stage of differentiation. Interestingly, pioglitazone-induced differentiation in the absence of standard hormone is not associated with up-regulated Bscl2 expression. On the other hand, short hairpin RNA-knockdown of Bscl2 largely blocks pioglitazone-induced adipose differentiation. These experiments suggest that Bscl2 may be essential for normal adipogenesis; it works upstream or at the level of peroxisome proliferator-activated receptor-gamma, enabling the latter to exert its full activity during adipogenesis. Loss of Bscl2 function thus interferes with the normal transcriptional cascade of adipogenesis during fat cell differentiation, resulting in near total loss of fat or lipodystrophy.

  17. RISC-Target Interaction: Cleavage and Translational Suppression

    Science.gov (United States)

    van den Berg, Arjen; Mols, Johann; Han, Jiahuai

    2008-01-01

    Summary Small RNA molecules have been known and utilized to suppress gene expression for more than a decade. The discovery that these small RNA molecules are endogenously expressed in many organisms and have a critical role in controlling gene expression have led to the arising of a whole new field of research. Termed small interfering RNA (siRNA) or microRNA (miRNA) these ~22 nt RNA molecules have the capability to suppress gene expression through various mechanisms once they are incorporated in the multi-protein RNA-Induced Silencing Complex (RISC) and interact with their target mRNA. This review introduces siRNAs and microRNAs in a historical perspective and focuses on the key molecules in RISC, structural properties and mechanisms underlying the process of small RNA regulated post-transcriptional suppression of gene expression. PMID:18692607

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

    Science.gov (United States)

    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.

  19. 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.

  20. Adaptation Mechanism of the Aspartate Receptor: Electrostatics of the Adaptation Subdomain Play a Key Role in Modulating Kinase Activity†

    Science.gov (United States)

    Starrett, Diane J.; Falke, Joseph J.

    2010-01-01

    The aspartate receptor of the Escherichia coli and Salmonella typhimurium chemotaxis pathway generates a transmembrane signal that regulates the activity of the cytoplasmic kinase CheA. Previous studies have identified a region of the cytoplasmic domain that is critical to receptor adaptation and kinase regulation. This region, termed the adaptation subdomain, contains a high density of acidic residues, including specific glutamate residues that serve as receptor adaptation sites. However, the mechanism of signal propagation through this region remains poorly understood. This study uses site-directed mutagenesis to neutralize each acidic residue within the subdomain to probe the hypothesis that electrostatics in this region play a significant role in the mechanism of kinase activation and modulation. Each point mutant was tested for its ability to regulate chemotaxis in vivo and kinase activity in vitro. Four point mutants (D273N, E281Q, D288N, and E477Q) were found to superactivate the kinase relative to the wild-type receptor, and all four of these kinase-activating substitutions are located along the same intersubunit interface as the adaptation sites. These activating substitutions retained the wild-type ability of the attractant-occupied receptor to inhibit kinase activity. When combined in a quadruple mutant (D273N/E281Q/D288N/E477Q), the four charge-neutralizing substitutions locked the receptor in a kinase-superactivating state that could not be fully inactivated by the attractant. Similar lock-on character was observed for a charge reversal substitution, D273R. Together, these results implicate the electrostatic interactions at the intersubunit interface as a major player in signal transduction and kinase regulation. The negative charge in this region destabilizes the local structure in a way that enhances conformational dynamics, as detected by disulfide trapping, and this effect is reversed by charge neutralization of the adaptation sites. Finally, two

  1. Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Qi Xu

    2016-01-01

    Full Text Available Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD. However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P<0.0001 upregulated ferroportin 1 expression and significantly (P<0.05 decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P<0.05 and DNA fragmentation by 29% (P=0.086 and increased cell viability by 22% (P<0.05. In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P<0.05 and intracellular iron by 28% (P<0.01, indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1.

  2. The physical and mental health of lesbian, gay male, and bisexual (LGB) older adults: the role of key health indicators and risk and protective factors.

    Science.gov (United States)

    Fredriksen-Goldsen, Karen I; Emlet, Charles A; Kim, Hyun-Jun; Muraco, Anna; Erosheva, Elena A; Goldsen, Jayn; Hoy-Ellis, Charles P

    2013-08-01

    Based on resilience theory, this paper investigates the influence of key health indicators and risk and protective factors on health outcomes (including general health, disability, and depression) among lesbian, gay male, and bisexual (LGB) older adults. A cross-sectional survey was conducted with LGB older adults, aged 50 and older (N = 2,439). Logistic regressions were conducted to examine the contributions of key health indicators (access to health care and health behaviors), risk factors (lifetime victimization, internalized stigma, and sexual identity concealment), and protective factors (social support and social network size) to health outcomes, when controlling for background characteristics. The findings revealed that lifetime victimization, financial barriers to health care, obesity, and limited physical activity independently and significantly accounted for poor general health, disability, and depression among LGB older adults. Internalized stigma was also a significant predictor of disability and depression. Social support and social network size served as protective factors, decreasing the odds of poor general health, disability, and depression. Some distinct differences by gender and sexual orientation were also observed. High levels of poor general health, disability, and depression among LGB older adults are of major concern. These findings highlight the important role of key risk and protective factors, which significantly influences health outcomes among LGB older adults. Tailored interventions must be developed to address the distinct health issues facing this historically disadvantaged population.

  3. Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs

    Directory of Open Access Journals (Sweden)

    David Juan

    2016-02-01

    Full Text Available Summary: Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity. Here, we propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in ESCs. The epigenetic communication network was inferred from genome-wide location data plus extensive manual annotation. Notably, we found that 5-hydroxymethylcytosine (5hmC is the most-influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency. Moreover, an evolutionary analysis revealed a central role of 5hmC in the co-evolution of chromatin-related proteins. Further analysis of regions where 5hmC co-localizes with specific interactors shows that each interaction points to chromatin remodeling, stemness, differentiation, or metabolism. Our results highlight the importance of cytosine modifications in the epigenetic communication of ESCs. : 5-hydroxymethylcytosine (5hmC plays a key role in the epigenomic communication network of embryonic stem cells. Juan et al. build a communication network based in co-localization of epigenomic data and literature. The analysis of the network and its components reveals that proteins reading and editing 5hmC co-evolve and serve as links between diverse molecular processes.

  4. 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

  5. Suppression of cholesterol synthesis in cultured fibroblasts from a patient with homozygous familial hypercholesterolemia by her own low density lipoprotein density fraction. A possible role of apolipoprotein E

    NARCIS (Netherlands)

    Havekes, L.; Vermeer, B.J.; Wit, E. de

    1980-01-01

    The suppression of cellular cholesterol synthesis by low density lipoprotein (LDL) from a normal and from a homozygous familial hypercholesterolemic subject was measured on normal fibroblasts and on fibroblasts derived from the same homozygous familial hypercholesterolemic patient. On normal

  6. Abscisic acid (ABA) and key proteins in its perception and signaling pathways are ancient, but their roles have changed through time.

    Science.gov (United States)

    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.

  7. Comparison is key.

    Science.gov (United States)

    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.

  8. Return of the pulmonary nodule: the radiologist's key role in implementing the 2015 BTS guidelines on the investigation and management of pulmonary nodules.

    Science.gov (United States)

    Graham, Richard N J; Baldwin, David R; Callister, Matthew E J; Gleeson, Fergus V

    2016-01-01

    The British Thoracic Society has published new comprehensive guidelines for the management of pulmonary nodules. These guidelines are significantly different from those previously published, as they use two malignancy prediction calculators to better characterize the risk of malignancy. There are recommendations for a higher nodule size threshold for follow-up (≥5 mm or ≥80 mm(3)) and a reduction of the follow-up period to 1 year for solid pulmonary nodules; both of these will reduce the number of follow-up CT scans. PET-CT plays a crucial role in characterization also, with an ordinal scale being recommended for reporting. Radiologists will be the key in implementing these guidelines, and routine use of volumetric image-analysis software will be required to manage patients with pulmonary nodules correctly.

  9. 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.

  10. Human CD134 (OX40) expressed on T cells plays a key role for human herpesvirus 6B replication after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Nagamata, Satoshi; Nagasaka, Miwako; Kawabata, Akiko; Kishimoto, Kenji; Hasegawa, Daiichiro; Kosaka, Yoshiyuki; Mori, Takeshi; Morioka, Ichiro; Nishimura, Noriyuki; Iijima, Kazumoto; Yamada, Hideto; Kawamoto, Shinichiro; Yakushijin, Kimikazu; Matsuoka, Hiroshi; Mori, Yasuko

    2018-05-01

    CD134 (OX40), which is a cellular receptor for human herpesvirus-6B (HHV-6B) and expresses on activated T cells, may play a key role for HHV-6B replication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, we examined the CD134 expression on T cells and HHV-6B replication after allo-HSCT, and analyzed the correlation between them. Twenty-three patients after allo-HSCT were enrolled. The percentages of CD134-positive cells within the CD4 + and CD8 + cell populations were measured by flow cytometry, and the viral copy number of HHV-6B was simultaneously quantified by real-time PCR. The correlation between CD134 and HHV-6B viral load was then statistically analyzed. HHV-6B reactivation occurred in 11 of 23 patients (47.8%). CD134 expression was seen on T cells and was coincident with the time of peak viral load. The percentage of CD134-positive cells decreased significantly when HHV-6B DNA disappeared (p = .005 in CD4 + T cells, p = .02 in CD8 + T cells). In the 4 patients who underwent umbilical cord blood transplantation (UCBT), the viral load varied with the percentage of CD134-positive cells. In the comparison between the HHV-6B reactivation group and non-reactivation group, maximum percentages of CD134-positive cells among CD4 + T cells in reactivation group were significantly higher than those in non-reactivation group (p = .04). This is the first study to show that a correlation of CD134 expression on T cells with HHV-6B replication after allo-HSCT, especially in UCBT. The results possibly indicate that CD134 on T cells plays a key role for HHV-6B replication after allo-HSCT. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. 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.

  12. The MqsRA Toxin-Antitoxin System from Xylella fastidiosa Plays a Key Role in Bacterial Fitness, Pathogenicity, and Persister Cell Formation

    Science.gov (United States)

    Merfa, Marcus V.; Niza, Bárbara; Takita, Marco A.; De Souza, Alessandra A.

    2016-01-01

    Through the formation of persister cells, bacteria exhibit tolerance to multidrug and other environmental stresses without undergoing genetic changes. The toxin-antitoxin (TA) systems are involved in the formation of persister cells because they are able to induce cell dormancy. Among the TA systems, the MqsRA system has been observed to be highly induced in persister cells of Xylella fastidiosa (causal agent of citrus variegated chlorosis—CVC) activated by copper stress, and has been described in Escherichia coli as related to the formation of persister cells and biofilms. Thus, we evaluated the role of this TA system in X. fastidiosa by overexpressing the MqsR toxin, and verified that the toxin positively regulated biofilm formation and negatively cell movement, resulting in reduced pathogenicity in citrus plants. The overexpression of MqsR also increased the formation of persister cells under copper stress. Analysis of the gene and protein expression showed that this system likely has an autoregulation mechanism to express the toxin and antitoxin in the most beneficial ratio for the cell to oppose stress. Our results suggest that this TA system plays a key role in the adaptation and survival of X. fastidiosa and reveal new insights into the physiology of phytopathogen-host interactions. PMID:27375608

  13. The RNA chaperone, Hfq, controls two luxR-type regulators and plays a key role in pathogenesis and production of antibiotics in Serratia sp. ATCC 39006.

    Science.gov (United States)

    Wilf, Nabil M; Williamson, Neil R; Ramsay, Joshua P; Poulter, Simon; Bandyra, Kasia J; Salmond, George P C

    2011-10-01

    Serratia sp. ATCC 39006 (S39006) is a Gram-negative bacterium that is virulent in plant (potato) and animal (Caenorhabditis elegans) models. It produces two secondary metabolite antibiotics, a prodigiosin and a carbapenem, and the exoenzymes, pectate lyase and cellulase. A complex regulatory network that includes quorum sensing (QS) controls production of prodigiosin. While many aspects of the regulation of the metabolites and exoenzymes are well understood, the potential role in this network of the RNA chaperone Hfq and dependent small regulatory RNAs has not been characterized. Hfq is an RNA chaperone involved in post-transcriptional regulation that plays a key role in stress response and virulence in diverse bacterial species. To explore whether Hfq-dependent processes might contribute to the regulation of antibiotic production we constructed an S39006 Δhfq mutant. Production of prodigiosin and carbapenem was abolished in this mutant strain, while production of the QS signalling molecule, butanoyl homoserine lactone (BHL), was unaffected. Using transcriptional fusions, we found that Hfq regulates the QS response regulators, SmaR and CarR. Additionally, exoenzyme production and swimming motility were decreased in a Δhfq mutant, and virulence was attenuated in potato and C. elegans models. These results suggest that an Hfq-dependent pathway is involved in the regulation of virulence and secondary metabolite production in S39006. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

  14. 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)

  15. Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in Protection of Hypoxic Neurons.

    Science.gov (United States)

    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.

  16. 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.

  17. The role of causal reasoning in understanding Simpson's paradox, Lord's paradox, and the suppression effect: covariate selection in the analysis of observational studies

    NARCIS (Netherlands)

    Arah, Onyebuchi A.

    2008-01-01

    ABSTRACT: Tu et al present an analysis of the equivalence of three paradoxes, namely, Simpson's, Lord's, and the suppression phenomena. They conclude that all three simply reiterate the occurrence of a change in the association of any two variables when a third variable is statistically controlled

  18. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kwang-Soo, E-mail: shinks@dju.kr [Division of Life Science, Daejeon University, Daejeon, 300-716 (Korea, Republic of); Kim, Young Hwan [Biomedical Omics Team, Korea Basic Science Institute (KBSI), Ohcang, 368-883 (Korea, Republic of); Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Department of Bio-Analytical Science, University of Science and Technology, Daejeon, 305-333 (Korea, Republic of); Yu, Jae-Hyuk, E-mail: jyu1@wisc.edu [Departments of Bacteriology and Genetics, The University of Wisconsin–Madison, Madison, WI, 53706 (United States)

    2015-07-31

    The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found that the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus. - Highlights: • Proteome analyses of WT and mutants reveal 13 differentially expressed proteins. • The GliT and GliM proteins are significantly down-regulated by ΔabaA and ΔbrlA. • Expression of other gliotoxin biosynthetic genes is lowered by ΔabaA and ΔbrlA. • Growth of ΔbrlA strain lacking GliT is completely inhibited by exogenous gliotoxin. • BrlA and AbaA play key roles in biogenesis of gliotoxin in Aspergillus fumigatus.

  19. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus

    International Nuclear Information System (INIS)

    Shin, Kwang-Soo; Kim, Young Hwan; Yu, Jae-Hyuk

    2015-01-01

    The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found that the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus. - Highlights: • Proteome analyses of WT and mutants reveal 13 differentially expressed proteins. • The GliT and GliM proteins are significantly down-regulated by ΔabaA and ΔbrlA. • Expression of other gliotoxin biosynthetic genes is lowered by ΔabaA and ΔbrlA. • Growth of ΔbrlA strain lacking GliT is completely inhibited by exogenous gliotoxin. • BrlA and AbaA play key roles in biogenesis of gliotoxin in Aspergillus fumigatus

  20. Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity.

    Science.gov (United States)

    Yeves, A M; Burgos, J I; Medina, A J; Villa-Abrille, M C; Ennis, I L

    2018-05-13

    Myocardial Na + /H + exchanger-1 (NHE-1) hyperactivity and oxidative stress are interrelated phenomena playing pivotal roles in the development of pathological cardiac hypertrophy and heart failure. Exercise training is effective to convert pathological into physiological hypertrophy in the spontaneously hypertensive rats (SHR), and IGF-1-key humoral mediator of exercise training-inhibits myocardial NHE-1, at least in normotensive rats. Therefore, we hypothesize that IGF-1 by hampering NHE-1 hyperactivity and oxidative stress should exert a cardioprotective effect in the SHR. NHE-1 activity [proton efflux (JH+) mmol L -1  min -1 ], expression and phosphorylation; H 2 O 2 production; superoxide dismutase (SOD) activity; contractility and calcium transients were measured in SHR hearts in the presence/absence of IGF-1. IGF-1 significantly decreased NHE-1 activity (JH+ at pH i 6.95: 1.39 ± 0.32, n = 9 vs C 3.27 ± 0.3, n = 20, P IGF-1 receptor (2.7 ± 0.4, n = 7); by the PI3K inhibitor wortmannin (3.14 ± 0.41, n = 7); and the AKT inhibitor MK2206 (3.37 ± 0.43, n = 14). Moreover, IGF-1 exerted an antioxidant effect revealed by a significant reduction in H 2 O 2 production accompanied by an increase in SOD activity. In addition, IGF-1 improved cardiomyocyte contractility as evidenced by an increase in sarcomere shortening and a decrease in the relaxation constant, underlined by an increase in the amplitude and rate of decay of the calcium transients. IGF-1 exerts a cardioprotective role on the hypertrophied hearts of the SHR, in which the inhibition of NHE-1 hyperactivity, as well as the positive inotropic and antioxidant effects, emerges as key players. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  1. Nitric Oxide Plays a Key Role in Ovariectomy-Induced Apoptosis in Anterior Pituitary: Interplay between Nitric Oxide Pathway and Estrogen

    Science.gov (United States)

    Quinteros, Fernanda A.; Duvilanski, Beatriz H.; Cabilla, Jimena P.

    2016-01-01

    Changes in the estrogenic status produce deep changes in pituitary physiology, mainly because estrogens (E2) are one of the main regulators of pituitary cell population. Also, E2 negatively regulate pituitary neuronal nitric oxide synthase (nNOS) activity and expression and may thereby modulate the production of nitric oxide (NO), an important regulator of cell death and survival. Little is known about how ovary ablation affects anterior pituitary cell remodelling and molecular mechanisms that regulate this process have not yet been elucidated. In this work we used freshly dispersed anterior pituitaries as well as cell cultures from ovariectomized female rats in order to study whether E2 deficiency induces apoptosis in the anterior pituitary cells, the role of NO in this process and effects of E2 on the NO pathway. Our results showed that cell activity gradually decreases after ovariectomy (OVX) as a consequence of cell death, which is completely prevented by a pan-caspase inhibitor. Furthermore, there is an increase of fragmented nuclei and DNA cleavage thereby presenting the first direct evidence of the existence of apoptosis in the anterior pituitary gland after OVX. NO production and soluble guanylyl cyclase (sGC) expression in anterior pituitary cells increased concomitantly to the apoptosis. Inhibition of both, NO synthase (NOS) and sGC activities prevented the drop of cell viability after OVX, showing for the first time that increased NO levels and sGC activity observed post-OVX play a key role in the induction of apoptosis. Conversely, E2 and prolactin treatments decreased nNOS expression and activity in pituitary cells from OVX rats in a time- and E2 receptor-dependent manner, thus suggesting interplay between NO and E2 pathways in anterior pituitary. PMID:27611913

  2. Nitric Oxide Plays a Key Role in Ovariectomy-Induced Apoptosis in Anterior Pituitary: Interplay between Nitric Oxide Pathway and Estrogen.

    Directory of Open Access Journals (Sweden)

    Sonia A Ronchetti

    Full Text Available Changes in the estrogenic status produce deep changes in pituitary physiology, mainly because estrogens (E2 are one of the main regulators of pituitary cell population. Also, E2 negatively regulate pituitary neuronal nitric oxide synthase (nNOS activity and expression and may thereby modulate the production of nitric oxide (NO, an important regulator of cell death and survival. Little is known about how ovary ablation affects anterior pituitary cell remodelling and molecular mechanisms that regulate this process have not yet been elucidated. In this work we used freshly dispersed anterior pituitaries as well as cell cultures from ovariectomized female rats in order to study whether E2 deficiency induces apoptosis in the anterior pituitary cells, the role of NO in this process and effects of E2 on the NO pathway. Our results showed that cell activity gradually decreases after ovariectomy (OVX as a consequence of cell death, which is completely prevented by a pan-caspase inhibitor. Furthermore, there is an increase of fragmented nuclei and DNA cleavage thereby presenting the first direct evidence of the existence of apoptosis in the anterior pituitary gland after OVX. NO production and soluble guanylyl cyclase (sGC expression in anterior pituitary cells increased concomitantly to the apoptosis. Inhibition of both, NO synthase (NOS and sGC activities prevented the drop of cell viability after OVX, showing for the first time that increased NO levels and sGC activity observed post-OVX play a key role in the induction of apoptosis. Conversely, E2 and prolactin treatments decreased nNOS expression and activity in pituitary cells from OVX rats in a time- and E2 receptor-dependent manner, thus suggesting interplay between NO and E2 pathways in anterior pituitary.

  3. Nitric Oxide Plays a Key Role in Ovariectomy-Induced Apoptosis in Anterior Pituitary: Interplay between Nitric Oxide Pathway and Estrogen.

    Science.gov (United States)

    Ronchetti, Sonia A; Machiavelli, Leticia I; Quinteros, Fernanda A; Duvilanski, Beatriz H; Cabilla, Jimena P

    2016-01-01

    Changes in the estrogenic status produce deep changes in pituitary physiology, mainly because estrogens (E2) are one of the main regulators of pituitary cell population. Also, E2 negatively regulate pituitary neuronal nitric oxide synthase (nNOS) activity and expression and may thereby modulate the production of nitric oxide (NO), an important regulator of cell death and survival. Little is known about how ovary ablation affects anterior pituitary cell remodelling and molecular mechanisms that regulate this process have not yet been elucidated. In this work we used freshly dispersed anterior pituitaries as well as cell cultures from ovariectomized female rats in order to study whether E2 deficiency induces apoptosis in the anterior pituitary cells, the role of NO in this process and effects of E2 on the NO pathway. Our results showed that cell activity gradually decreases after ovariectomy (OVX) as a consequence of cell death, which is completely prevented by a pan-caspase inhibitor. Furthermore, there is an increase of fragmented nuclei and DNA cleavage thereby presenting the first direct evidence of the existence of apoptosis in the anterior pituitary gland after OVX. NO production and soluble guanylyl cyclase (sGC) expression in anterior pituitary cells increased concomitantly to the apoptosis. Inhibition of both, NO synthase (NOS) and sGC activities prevented the drop of cell viability after OVX, showing for the first time that increased NO levels and sGC activity observed post-OVX play a key role in the induction of apoptosis. Conversely, E2 and prolactin treatments decreased nNOS expression and activity in pituitary cells from OVX rats in a time- and E2 receptor-dependent manner, thus suggesting interplay between NO and E2 pathways in anterior pituitary.

  4. Study of 'Redhaven' peach and its white-fleshed mutant suggests a key role of CCD4 carotenoid dioxygenase in carotenoid and norisoprenoid volatile metabolism

    Directory of Open Access Journals (Sweden)

    Tartarini Stefano

    2011-01-01

    Full Text Available Abstract Background Carotenoids are plant metabolites which are not only essential in photosynthesis but also important quality factors in determining the pigmentation and aroma of flowers and fruits. To investigate the regulation of carotenoid metabolism, as related to norisoprenoids and other volatile compounds in peach (Prunus persica L. Batsch., and the role of carotenoid dioxygenases in determining differences in flesh color phenotype and volatile composition, the expression patterns of relevant carotenoid genes and metabolites were studied during fruit development along with volatile compound content. Two contrasted cultivars, the yellow-fleshed 'Redhaven' (RH and its white-fleshed mutant 'Redhaven Bianca' (RHB were examined. Results The two genotypes displayed marked differences in the accumulation of carotenoid pigments in mesocarp tissues. Lower carotenoid levels and higher levels of norisoprenoid volatiles were observed in RHB, which might be explained by differential activity of carotenoid cleavage dioxygenase (CCD enzymes. In fact, the ccd4 transcript levels were dramatically higher at late ripening stages in RHB with respect to RH. The two genotypes also showed differences in the expression patterns of several carotenoid and isoprenoid transcripts, compatible with a feed-back regulation of these transcripts. Abamine SG - an inhibitor of CCD enzymes - decreased the levels of both isoprenoid and non-isoprenoid volatiles in RHB fruits, indicating a complex regulation of volatile production. Conclusions Differential expression of ccd4 is likely to be the major determinant in the accumulation of carotenoids and carotenoid-derived volatiles in peach fruit flesh. More in general, dioxygenases appear to be key factors controlling volatile composition in peach fruit, since abamine SG-treated 'Redhaven Bianca' fruits had strongly reduced levels of norisoprenoids and other volatile classes. Comparative functional studies of peach carotenoid

  5. Drought-induced defoliation and long periods of near-zero gas exchange play a key role in accentuating metabolic decline of Scots pine.

    Science.gov (United States)

    Poyatos, Rafael; Aguadé, David; Galiano, Lucía; Mencuccini, Maurizio; Martínez-Vilalta, Jordi

    2013-10-01

    Drought-induced defoliation has recently been associated with the depletion of carbon reserves and increased mortality risk in Scots pine (Pinus sylvestris). We hypothesize that defoliated individuals are more sensitive to drought, implying that potentially higher gas exchange (per unit of leaf area) during wet periods may not compensate for their reduced photosynthetic area. We measured sap flow, needle water potentials and whole-tree hydraulic conductance to analyse the drought responses of co-occurring defoliated and nondefoliated Scots pines in northeast Spain during typical (2010) and extreme (2011) drought conditions. Defoliated Scots pines showed higher sap flow per unit leaf area during spring, but were more sensitive to summer drought, relative to nondefoliated pines. This pattern was associated with a steeper decline in soil-to-leaf hydraulic conductance with drought and an enhanced sensitivity of canopy conductance to soil water availability. Near-homeostasis in midday water potentials was observed across years and defoliation classes, with minimum values of -2.5 MPa. Enhanced sensitivity to drought and prolonged periods of near-zero gas exchange were consistent with low levels of carbohydrate reserves in defoliated trees. Our results support the critical links between defoliation, water and carbon availability, and their key roles in determining tree survival and recovery under drought. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  6. Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation.

    Science.gov (United States)

    Revenu, Céline; Streichan, Sebastian; Donà, Erika; Lecaudey, Virginie; Hufnagel, Lars; Gilmour, Darren

    2014-03-01

    The directed migration of cell collectives drives the formation of complex organ systems. A characteristic feature of many migrating collectives is a 'tissue-scale' polarity, whereby 'leader' cells at the edge of the tissue guide trailing 'followers' that become assembled into polarised epithelial tissues en route. Here, we combine quantitative imaging and perturbation approaches to investigate epithelial cell state transitions during collective migration and organogenesis, using the zebrafish lateral line primordium as an in vivo model. A readout of three-dimensional cell polarity, based on centrosomal-nucleus axes, allows the transition from migrating leaders to assembled followers to be quantitatively resolved for the first time in vivo. Using live reporters and a novel fluorescent protein timer approach, we investigate changes in cell-cell adhesion underlying this transition by monitoring cadherin receptor localisation and stability. This reveals that while cadherin 2 is expressed across the entire tissue, functional apical junctions are first assembled in the transition zone and become progressively more stable across the leader-follower axis of the tissue. Perturbation experiments demonstrate that the formation of these apical adherens junctions requires dynamic microtubules. However, once stabilised, adherens junction maintenance is microtubule independent. Combined, these data identify a mechanism for regulating leader-to-follower transitions within migrating collectives, based on the relocation and stabilisation of cadherins, and reveal a key role for dynamic microtubules in this process.

  7. How educational innovations and attention to competencies in postgraduate medical education relate to preparedness for practice: the key role of the learning environment.

    Science.gov (United States)

    Dijkstra, Ids S; Pols, Jan; Remmelts, Pine; Rietzschel, Eric F; Cohen-Schotanus, Janke; Brand, Paul L P

    2015-12-01

    Many training programmes in postgraduate medical education (PGME) have introduced competency frameworks, but the effects of this change on preparedness for practice are unknown. Therefore, we explored how elements of competency-based programmes in PGME (educational innovations, attention to competencies and learning environment) were related to perceived preparedness for practice among new consultants. A questionnaire was distributed among 330 new consultants. Respondents rated how well their PGME training programme prepared them for practice, the extent to which educational innovations (portfolio, Mini-CEX) were implemented, and how much attention was paid to CanMEDS competencies during feedback and coaching, and they answered questions on the learning environment and general self-efficacy. Multiple regression and mediation analyses were used to analyze data. The response rate was 43 % (143/330). Controlling for self-efficacy and gender, the learning environment was the strongest predictor of preparedness for practice (B = 0.42, p competencies (B = 0.29, p competencies mediated the relationship between educational innovations and preparedness for practice. This mediation became stronger at higher learning environment values. The learning environment plays a key role in determining the degree to which competency-based PGME prepares trainees for independent practice.

  8. A Key Role for NF-κB Transcription Factor c-Rel in T-Lymphocyte-Differentiation and Effector Functions

    Directory of Open Access Journals (Sweden)

    Alexander Visekruna

    2012-01-01

    Full Text Available The transcription factors of the Rel/NF-κB family function as key regulators of innate and adoptive immunity. Tightly and temporally controlled activation of NF-κB-signalling pathways ensures prevention of harmful immune cell dysregulation, whereas a loss of control leads to pathological conditions such as severe inflammation, autoimmune disease, and inflammation-associated oncogenesis. Five family members have been identified in mammals: RelA (p65, c-Rel, RelB, and the precursor proteins NF-κB1 (p105 and NF-κB2 (p100, that are processed into p50 and p52, respectively. While RelA-containing dimers are present in most cell types, c-Rel complexes are predominately found in cells of hematopoietic origin. In T-cell lymphocytes, certain genes essential for immune function such as Il2 and Foxp3 are directly regulated by c-Rel. Additionally, c-Rel-dependent IL-12 and IL-23 transcription by macrophages and dendritic cells is crucial for T-cell differentiation and effector functions. Accordingly, c-Rel expression in T cells and antigen-presenting cells (APCs controls a delicate balance between tolerance and immunity. This review gives a selective overview on recent progress in understanding of diverse roles of c-Rel in regulating adaptive immunity.

  9. Role of aryl hydrocarbon receptor polymorphisms on TCDD-mediated CYP1B1 induction and IgM suppression by human B cells

    Energy Technology Data Exchange (ETDEWEB)

    Kovalova, Natalia, E-mail: kovalova@msu.edu [Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Manzan, Maria, E-mail: ale.manzan@gmail.com [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Crawford, Robert, E-mail: crawfo28@msu.edu [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Kaminski, Norbert, E-mail: kamins11@msu.edu [Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States)

    2016-10-15

    Previous studies have demonstrated that most of the intraspecies variation in sensitivity to the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), including suppression of antibody responses, in murine models is due to single nucleotide polymorphisms (SNPs) within the aryl hydrocarbon receptor (AhR) gene. The underlying reason for variation in sensitivity to TCDD-induced suppression of IgM responses among humans is not well understood, but is thought, in part, to be a result of different polymorphic forms of the AhR expressed by different individuals. In this study, the functional properties of six (P517S, R554K, V570I, V570I + P517S, R554K + V570I and P517S + R554K + V570I) human AhR variants were examined in the human B cell line, SKW 6.4. TCDD-induced Cyp1B1 and Cyp1A2 mRNA expression levels and Cyp1B1-regulated reporter gene activity, used for comparative purposes, were markedly lower in SKW cells containing the R554K SNP than in SKW-AHR{sup +} (control AhR) cells. Furthermore, all AhR variants were able to mediate TCDD-induced suppression of the IgM response; however, a combined P517S + R554K + V570I variant partially reduced sensitivity to TCDD-mediated suppression of IgM secretion. Collectively, our findings show that the R554K human AhR SNP alone altered sensitivity of human B cells to TCDD-mediated induction of Cyp1B1 and Cyp1A2. By contrast, attenuation of TCDD-induced IgM suppression required a combination of all three SNPs P517S, R554K, and V570I. - Highlights: • Mouse, rat and SKW-AHR{sup +} B cells have a similar window of sensitivity to TCDD. • R554K AhR SNP alters B cell sensitivity to TCDD-mediated Cyp1B1 and Cyp1A2 induction. • Combination of P517S, R554K, and V570I SNPs attenuates TCDD-induced IgM suppression.

  10. Chk1 suppressed cell death

    Directory of Open Access Journals (Sweden)

    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.

  11. Ursodeoxycholic Acid Suppresses Lipogenesis in Mouse Liver: Possible Role of the Decrease in β-Muricholic Acid, a Farnesoid X Receptor Antagonist.

    Science.gov (United States)

    Fujita, Kyosuke; Iguchi, Yusuke; Une, Mizuho; Watanabe, Shiro

    2017-04-01

    The farnesoid X receptor (FXR) is a major nuclear receptor of bile acids; its activation suppresses sterol regulatory element-binding protein 1c (SREBP1c)-mediated lipogenesis and decreases the lipid contents in the liver. There are many reports showing that the administration of ursodeoxycholic acid (UDCA) suppresses lipogenesis and reduces the lipid contents in the liver of experimental animals. Since UDCA is not recognized as an FXR agonist, these effects of UDCA cannot be readily explained by its direct activation of FXR. We observed that the dietary administration of UDCA in mice decreased the expression levels of SREBP1c and its target lipogenic genes. Alpha- and β-muricholic acids (MCA) and cholic acid (CA) were the major bile acids in the mouse liver but their contents decreased upon UDCA administration. The hepatic contents of chenodeoxycholic acid and deoxycholic acid (DCA) were relatively low but were not changed by UDCA. UDCA did not show FXR agonistic or antagonistic potency in in vitro FXR transactivation assay. Taking these together, we deduced that the above-mentioned change in hepatic bile acid composition induced upon UDCA administration might cause the relative increase in the FXR activity in the liver, mainly by the reduction in the content of β-MCA, a farnesoid X receptor antagonist, which suggests a mechanism by which UDCA suppresses lipogenesis and decreases the lipid contents in the mouse liver.

  12. 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...

  13. Key Decision Points in the Careers of Geoscientists: The Role of the YES Network in Facilitating Successful Career Transitions for Early Career Geoscientists (Invited)

    Science.gov (United States)

    Venus, J. H.; Gonzales, L. M.; Yes Network

    2010-12-01

    The external influences on the decisions that geoscientists make pertaining to their careers are often assumed but not quantified. The YES Network is conducting an international study to determine the Key Decision points in the career pathways of early career geoscientists. The study aims to identify factors contributing to individual career decisions and to monitor these over a ten year period. The Initial phase of the study is now underway enabling preliminary conclusions to be drawn and will identify a group of individuals that will be tracked over the 10 year programme. The Survey will highlight reoccurring areas where Early Career Geoscientists are experiencing progression difficulties and, importantly, provide respondents with an opportunity to suggest solutions whilst also allowing general resource needs to be identified from the results as a whole. Early results show an overwhelming majority expressing job satisfaction most or all of the time (only 2 candidates reporting none). Respondents rate job satisfaction and respect highly, returning more responses than good salaries. A general frustration with administration, paper work and bureaucracy is particularly evident in those employed by government organisations. Early Career geoscientists express a frustration concerning a lack of involvement in decision making processes; interestingly several later career respondents also acknowledge a need to properly train, nurture and encourage new recruits to retain good graduates who may otherwise become disillusioned and leave the profession. The role of family in career choices has been highlighted both in survey and general feedback responses particularly by female geoscientists and those working in jobs with high levels of fieldwork; we aim to determine, to some extent, to what point these decisions are controlled by family as opposed to normal career progression. Flexible working conditions and agreed time away from field duty have been independently suggested

  14. 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.

  15. Key issues

    International Nuclear Information System (INIS)

    Cook, N.G.W.

    1980-01-01

    Successful modeling of the thermo-mechanical and hydrochemical behavior of radioactive waste repositories in hard rock is possible in principle. Because such predictions lie outside the realm of experience, their adequacy depends entirely upon a thorough understanding of three fundamental questions: an understanding of the chemical and physical processess that determine the behavior of rock and all its complexities; accurate and realistic numerical models of the geologic media within which a repository may be built; and sufficient in-situ data covering the entire geologic region affected by, or effecting the behavior of a repository. At present sufficient is known to be able to identify most of those areas which require further attention. These areas extend all the way from a complete understanding of the chemical and physical processes determining the behavior of rock through to the exploration mapping and testing that must be done during the development of any potential repository. Many of the techniques, laboratory equipment, field instrumentation, and numerical methods needed to accomplish this do not exist at present. Therefore it is necessary to accept that a major investment in scientific research is required to generate this information over the next few years. The spectrum of scientific and engineering activities is wide extending from laboratory measurements through the development of numerical models to the measurement of data in-situ, but there is every prospect that sufficient can be done to resolve these key issues. However, to do so requires overt recognition of the many gaps which exist in our knowledge and abilities today, and of the need to bridge these gaps and of the significant costs involved in doing so

  16. RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

    Directory of Open Access Journals (Sweden)

    Elias Abdou

    2017-05-01

    Full Text Available For aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original “in vitro model of persistence” consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ΔregA strains to identify the RegA-regulon potentially involved in the set-up of persistence. Consecutive to oxygen consumption resulting in growth arrest, 12% of the genes in B. suis were potentially controlled directly or indirectly by RegA, among which numerous transcriptional regulators were up-regulated. In contrast, genes or proteins involved in envelope biogenesis and in cellular division were repressed, suggesting a possible role for RegA in the set-up of a non-proliferative persistence state. Importantly, the greatest number of the RegA-repressed genes and proteins, including aceA encoding the functional IsoCitrate Lyase (ICL, were involved in energy production. A potential consequence of this RegA impact may be the slowing-down of the central metabolism as B. suis progressively enters into persistence. Moreover, ICL is an essential determinant of pathogenesis and long-term interactions with the host, as demonstrated by the strict dependence of B. suis on ICL activity for multiplication and persistence during in vivo infection. RegA regulates gene or protein expression of all functional groups, which is why RegA is a key regulator of B. suis in adaptation to oxygen depletion. This function may contribute to the constraint of bacterial growth, typical of chronic infection. Oxygen-dependent activation of two-component systems that control persistence regulons, shared by several aerobic human pathogens, has not been studied in Brucella sp. before. This work

  17. The extracytoplasmic function sigma factor SigV plays a key role in the original model of lysozyme resistance and virulence of Enterococcus faecalis.

    Directory of Open Access Journals (Sweden)

    André Le Jeune

    Full Text Available BACKGROUND: Enterococcus faecalis is one of the leading agents of nosocomial infections. To cause diseases, pathogens or opportunistic bacteria have to adapt and survive to the defense systems encountered in the host. One of the most important compounds of the host innate defense response against invading microorganisms is lysozyme. It is found in a wide variety of body fluids, as well as in cells of the innate immune system. Lysozyme could act either as a muramidase and/or as a cationic antimicrobial peptide. Like Staphylococcus aureus, E. faecalis is one of the few bacteria that are completely lysozyme resistant. RESULTS: This study revealed that oatA (O-acetyl transferase and dlt (D-Alanylation of lipoteicoic acids genes contribute only partly to the lysozyme resistance of E. faecalis and that a specific transcriptional regulator, the extracytoplasmic function SigV sigma factor plays a key role in this event. Indeed, the sigV single mutant is as sensitive as the oatA/dltA double mutant, and the sigV/oatA/dltA triple mutant displays the highest level of lysozyme sensitivity suggesting synergistic effects of these genes. In S. aureus, mutation of both oatA and dlt genes abolishes completely the lysozyme resistance, whereas this is not the case in E. faecalis. Interestingly SigV does not control neither oatA nor dlt genes. Moreover, the sigV mutants clearly showed a reduced capacity to colonize host tissues, as they are significantly less recovered than the parental JH2-2 strain from organs of mice subjected to intravenous or urinary tract infections. CONCLUSIONS: This work led to the discovery of an original model of lysozyme resistance mechanism which is obviously more complex than those described for other Gram positive pathogens. Moreover, our data provide evidences for a direct link between lysozyme resistance and virulence of E. faecalis.

  18. Aerosol Liquid Water Driven by Anthropogenic inorganic salts: Playing a key role in the winter haze formation over North China Plain

    Science.gov (United States)

    Wu, Z.; Liu, Y.; Tan, T.; Wang, Y.; Shang, D.; Xiao, Y.; Li, M.; Zeng, L.; Hu, M.

    2017-12-01

    Aerosol liquid water influences ambient particulate matter mass concentrations and aerosol optical properties, and can serve as a reactor for multiphase reactions that perturb local photochemistry1. Our observations revealed that ambient relative humidity, inorganic fraction (sulfate, ammonium, nitrate), and PM2.5 mass concentration generally simultaneously elevated during haze episodes, resulting in the abundant anthropogenic aerosol water in the atmosphere of Beijing. The enrichment of aerosol liquid water may significantly affect the particle phase, which plays a key role in determining the reactive uptake, gas-particle partitioning, and heterogeneous chemical reactivity2. A newly-built three-arm impactor was used to detect the particle rebound fraction. The observations showed the increased RH and inorganic-rich particulate matter led to an increased aerosol liquid water content, and thus a liquid phase state during haze episode during wintertime. Here, we proposed that the transition to a liquid phase state marked the beginning of the haze episode and kicked off a positive feedback loop, wherein the liquid particles readily uptake pollutants that could react to form inorganics which could then uptake more water. The strict controlling strategy of sulfur emissions in China might lead to a decreased sulfate fraction and increased nitrate fraction in PM1. As a result, due to the lower deliquescence RH of nitrate, the feedback loop proposed could start at an even lower RH in the future. Reference1 Herrmann, H., T. Schaefer, A. Tilgner, S. A. Styler, C. Weller, M. Teich, and T. Otto (2015), Tropospheric Aqueous-Phase Chemistry: Kinetics, Mechanisms, and Its Coupling to a Changing Gas Phase, Chemical Reviews, 115(10), 4259-4334.2 M. Kuwata, S. T. Martin (2012), Phase of atmospheric secondary organic material affects its reactivity, Proceedings of the National Academy of Sciences of the United States of America, 109(43):17354-17359

  19. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus.

    Science.gov (United States)

    Shin, Kwang-Soo; Kim, Young Hwan; Yu, Jae-Hyuk

    2015-07-31

    The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found that the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Calcium plays a key role in paraoxon-induced apoptosis in EL4 cells by regulating both endoplasmic reticulum- and mitochondria-associated pathways.

    Science.gov (United States)

    Li, Lan; Du, Yi; Ju, Furong; Ma, Shunxiang; Zhang, Shengxiang

    2016-01-01

    Paraoxon (POX) is one of the most toxic organophosphorus pesticides, but its toxic mechanisms associated with apoptosis remain unclear. The aim of this study was to investigate calcium-associated mechanisms in POX-induced apoptosis in EL4 cells. EL4 cells were exposed to POX for 0-16 h. EGTA was used to chelate Ca(2+ ) in extracellular medium, and heparin and procaine were used to inhibit Ca(2+ )efflux from the endoplasmic reticulum (ER). Z-ATAD-FMK was used to inhibit caspase-12 activity. The apoptotic rate assay, western blotting and immunocytochemistry (ICC) were used to reveal the mechanisms of POX-induced apoptosis. POX significantly increased the expression and activation of caspase-12 and caspase-3, enhanced expression of calpain 1 and calpain 2, and induced the release of cyt c, but did not change the expression of Grp 78. Inhibiting caspase-12 activity alleviated POX-induced upregulation of calpain 1 and caspase-3, promoted POX-induced upregulation of calpain 2, and reduced POX-induced cyt c release, suggesting that there was a cross-talk between the ER-associated pathway and mitochondria-associated apoptotic signals. Attenuating intracellular calcium concentration with EGTA, heparin or procaine decreased POX-induced upregulation of calpain 1, calpain 2, caspase-12 and caspase-3, and reduced POX-induced cyt c release. After pretreatment with EGTA or procaine, POX significantly promoted expression of Grp 78. Calcium played a key role in POX-induced apoptosis in EL4 cells by regulating both ER- and mitochondria-associated pathways. The cross-talk of ER- and mitochondria-associated pathways was accomplished through calcium signal.

  1. Extracellular Zn2+ Influx into Nigral Dopaminergic Neurons Plays a Key Role for Pathogenesis of 6-Hydroxydopamine-Induced Parkinson's Disease in Rats.

    Science.gov (United States)

    Tamano, Haruna; Nishio, Ryusuke; Morioka, Hiroki; Takeda, Atsushi

    2018-04-29

    Parkinson's disease (PD) is a progressive neurological disease characterized by a selective loss of nigrostriatal dopaminergic neurons. The exact cause of the neuronal loss remains unclear. Here, we report a unique mechanism of nigrostriatal dopaminergic neurodegeneration, in which extracellular Zn 2+ influx plays a key role for PD pathogenesis induced with 6-hydroxydopamine (6-OHDA) in rats. 6-OHDA rapidly increased intracellular Zn 2+ only in the substantia nigra pars compacta (SNpc) of brain slices and this increase was blocked in the presence of CaEDTA, an extracellular Zn 2+ chelator, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, indicating that 6-OHDA rapidly increases extracellular Zn 2+ influx via AMPA receptor activation in the SNpc. Extracellular Zn 2+ concentration was decreased under in vivo SNpc perfusion with 6-OHDA and this decrease was blocked by co-perfusion with CNQX, supporting 6-OHDA-induced Zn 2+ influx via AMPA receptor activation in the SNpc. Interestingly, both 6-OHDA-induced loss of nigrostriatal dopaminergic neurons and turning behavior to apomorphine were ameliorated by co-injection of intracellular Zn 2+ chelators, i.e., ZnAF-2DA and N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). Co-injection of TPEN into the SNpc blocked 6-OHDA-induced increase in intracellular Zn 2+ but not in intracellular Ca 2+ . These results suggest that the rapid influx of extracellular Zn 2+ into dopaminergic neurons via AMPA receptor activation in the SNpc induces nigrostriatal dopaminergic neurodegeneration, resulting in 6-OHDA-induced PD in rats.

  2. Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis.

    Directory of Open Access Journals (Sweden)

    Xingxing Kong

    2010-07-01

    Full Text Available Sirtuin 3 (SIRT3 is one of the seven mammalian sirtuins, which are homologs of the yeast Sir2 gene. SIRT3 is the only sirtuin with a reported association with the human life span. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha plays important roles in adaptive thermogenesis, gluconeogenesis, mitochondrial biogenesis and respiration. PGC-1alpha induces several key reactive oxygen species (ROS-detoxifying enzymes, but the molecular mechanism underlying this is not well understood.Here we show that PGC-1alpha strongly stimulated mouse Sirt3 gene expression in muscle cells and hepatocytes. Knockdown of PGC-1alpha led to decreased Sirt3 gene expression. PGC-1alpha activated the mouse SIRT3 promoter, which was mediated by an estrogen-related receptor (ERR binding element (ERRE (-407/-399 mapped to the promoter region. Chromatin immunoprecipitation and electrophoretic mobility shift assays confirmed that ERRalpha bound to the identified ERRE and PGC-1alpha co-localized with ERRalpha in the mSirt3 promoter. Knockdown of ERRalpha reduced the induction of Sirt3 by PGC-1alpha in C(2C(12 myotubes. Furthermore, Sirt3 was essential for PGC-1alpha-dependent induction of ROS-detoxifying enzymes and several components of the respiratory chain, including glutathione peroxidase-1, superoxide dismutase 2, ATP synthase 5c, and cytochrome c. Overexpression of SIRT3 or PGC-1alpha in C(2C(12 myotubes decreased basal ROS level. In contrast, knockdown of mSIRT3 increased basal ROS level and blocked the inhibitory effect of PGC-1alpha on cellular ROS production. Finally, SIRT3 stimulated mitochondrial biogenesis, and SIRT3 knockdown decreased the stimulatory effect of PGC-1alpha on mitochondrial biogenesis in C(2C(12 myotubes.Our results indicate that Sirt3 functions as a downstream target gene of PGC-1alpha and mediates the PGC-1alpha effects on cellular ROS production and mitochondrial biogenesis. Thus, SIRT3 integrates cellular energy

  3. DSP30 enhances the immunosuppressive properties of mesenchymal stromal cells and protects their suppressive potential from lipopolysaccharide effects: A potential role of adenosine.

    Science.gov (United States)

    Sangiorgi, Bruno; De Freitas, Helder Teixeira; Schiavinato, Josiane Lilian Dos Santos; Leão, Vitor; Haddad, Rodrigo; Orellana, Maristela Delgado; Faça, Vitor Marcel; Ferreira, Germano Aguiar; Covas, Dimas Tadeu; Zago, Marco Antônio; Panepucci, Rodrigo Alexandre

    2016-07-01

    Multipotent mesenchymal stromal cells (MSC) are imbued with an immunosuppressive phenotype that extends to several immune system cells. In this study, we evaluated how distinct Toll-like receptor (TLR) agonists impact immunosuppressive properties of bone marrow (BM)-MSC and explored the potential mechanisms involved. We show that TLR4 stimulation by lipopolysaccharide (LPS) restricted the ability of MSC to suppress the proliferation of T lymphocytes, increasing the gene expression of interleukin (IL)-1β and IL-6. In contrast, stimulation of TLR9 by DSP30 induced proliferation and the suppressive potential of BM-MSC, coinciding with reducing tumor necrosis factor (TNF)-α expression, increased expression of transforming growth factor (TGF)-β1, increased percentages of BM-MSC double positive for the ectonucleotidases CD39+CD73+ and adenosine levels. Importantly, following simultaneous stimulation with LPS and DSP30, BM-MSC's ability to suppress T lymphocyte proliferation was comparable with that of non-stimulated BM-MSC levels. Moreover, stimulation of BM-MSC with LPS reduced significantly the gene expression levels, on co-cultured T lymphocyte, of IL-10 and interferon (IFN)γ, a cytokine with potential to enhance the immunosuppression mediated by MSC and ameliorate the clinical outcome of patients with graft-versus-host disease (GVHD). Altogether, our findings reiterate the harmful effects of LPS on MSC immunosuppression, besides indicating that DSP30 could provide a protective effect against LPS circulating in the blood of GVHD patients who receive BM-MSC infusions, ensuring a more predictable immunosuppressive effect. The novel effects and potential mechanisms following the stimulation of BM-MSC by DSP30 might impact their clinical use, by allowing the derivation of optimal "licensing" protocols for obtaining therapeutically efficient MSC. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  4. 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 ...

  5. 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

  6. 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...

  7. 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.

  8. 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

  9. 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

  10. Role of the Ah locus in suppression of cytotoxic T lymphocyte activity by halogenated aromatic hydrocarbons (PCBs and TCDD): Structure-activity relationships and effects in C57Bl/6 mice congenic at the Ah locus

    International Nuclear Information System (INIS)

    Kerkvliet, N.I.; Baecher-Steppan, L.; Smith, B.B.; Youngberg, J.A.; Henderson, M.C.; Buhler, D.R.

    1990-01-01

    Previous studies have shown that the generation of cytotoxic T lymphocytes (CTL) following allogeneic tumor challenge is suppressed in Ah-responsive C57Bl/6 mice treated with a single oral dose of the toxic, Ah receptor-binding 3,4,5,3',4',5'-hexachlorobiphenyl (HxCB). The present studies have examined the specific role of the Ah receptor in this immunotoxic response by utilizing HxCB isomers of known, varied affinity for the Ah receptor as well as by comparing effects of high-affinity Ah receptor ligands (3,4,5,3',4',5'-HxCB and 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]) on the CTL response of mice that differ only at the Ah locus, that is, Ah-responsive (Ahbb) and Ah-nonresponsive (Ahdd) congenic C57Bl/6 mice. Correlative changes in thymic weight, serum corticosterone (CS) levels, and spleen cellularity were also measured. The potency of HxCB congeners (3,4,5,3',4',5'-; 2,3,4,5,3',4'-; 2,4,5,2',4',5'-) and 2,3,7,8-TCDD to suppress the CTL response, to reduce spleen cellularity, to cause thymic atrophy, and to elevate serum CS levels was directly correlated with the binding affinity of the congener for the Ah receptor. Furthermore, these parameters of immunotoxicity in Ahdd C57Bl/6 mice were significantly more resistant to alterations induced by either 3,4,5,3',4',5'-HxCB or 2,3,7,8-TCDD as compared to Ahbb C57Bl/6 mice. These results strongly support an Ah receptor-dependent immunotoxic mechanism in suppression of the CTL response following acute exposure to halogenated aromatic hydrocarbons

  11. 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’.

  12. Effective suppression of efficiency droop in GaN-based light-emitting diodes: role of significant reduction of carrier density and built-in field

    Science.gov (United States)

    Yoo, Yang-Seok; Na, Jong-Ho; Son, Sung Jin; Cho, Yong-Hoon

    2016-10-01

    A critical issue in GaN-based high power light-emitting diodes (LEDs) is how to suppress the efficiency droop problem occurred at high current injection while improving overall quantum efficiency, especially in conventional c-plane InGaN/GaN quantum well (QW), without using complicated bandgap engineering or unconventional materials and structures. Although increasing thickness of each QW may decrease carrier density in QWs, formation of additional strain and defects as well as increased built-in field effect due to enlarged QW thickness are unavoidable. Here, we propose a facile and effective method for not only reducing efficiency droop but also improving quantum efficiency by utilizing c-plane InGaN/GaN QWs having thinner barriers and increased QW number while keeping the same single well thickness and total active layer thickness. As the barrier thickness decreases and the QW number increases, both internal electric field and carrier density within QWs are simultaneously reduced without degradation of material quality. Furthermore, we found overall improved efficiency and reduced efficiency droop, which was attributed to the decrease of the built-in field and to less influence by non-radiative recombination processes at high carrier density. This simple and effective approach can be extended further for high power ultraviolet, green, and red LEDs.

  13. The Entomopathogenic Fungi Isaria fumosorosea Plays a Vital Role in Suppressing the Immune System of Plutella xylostella: RNA-Seq and DGE Analysis of Immunity-Related Genes.

    Science.gov (United States)

    Xu, Jin; Xu, Xiaoxia; Shakeel, Muhammad; Li, Shuzhong; Wang, Shuang; Zhou, Xianqiang; Yu, Jialin; Xu, Xiaojing; Yu, Xiaoqiang; Jin, Fengliang

    2017-01-01

    Most, if not all, entomopathogenic fungi have been used as alternative control agents to decrease the insect resistance and harmful effects of the insecticides on the environment. Among them, Isaria fumosorosea has also shown great potential to control different insect pests. In the present study, we explored the immune response of P. xylostella to the infection of I. fumosorosea at different time points by using RNA-Sequencing and differential gene expression technology at the genomic level. To gain insight into the host-pathogen interaction at the genomic level, five libraries of P. xylostella larvae at 12, 18, 24, and 36 h post-infection and a control were constructed. In total, 161 immunity-related genes were identified and grouped into four categories; immune recognition families, toll and Imd pathway, melanization, and antimicrobial peptides (AMPs). The results of differentially expressed immunity-related genes depicted that 15, 13, 53, and 14 up-regulated and 38, 51, 56, and 49 were down-regulated in P. xylostella at 12, 18, 24, and 36 h post-treatment, respectively. RNA-Seq results of immunity-related genes revealed that the expression of AMPs was reduced after treatment with I. fumosorosea . To validate RNA-Seq results by RT-qPCR, 22 immunity-related genes were randomly selected. In conclusion, our results demonstrate that I. fumosorosea has the potential to suppress the immune response of P. xylostella and can become a potential biopesticide for controlling P. xylostella .

  14. The Entomopathogenic Fungi Isaria fumosorosea Plays a Vital Role in Suppressing the Immune System of Plutella xylostella: RNA-Seq and DGE Analysis of Immunity-Related Genes

    Directory of Open Access Journals (Sweden)

    Jin Xu

    2017-07-01

    Full Text Available Most, if not all, entomopathogenic fungi have been used as alternative control agents to decrease the insect resistance and harmful effects of the insecticides on the environment. Among them, Isaria fumosorosea has also shown great potential to control different insect pests. In the present study, we explored the immune response of P. xylostella to the infection of I. fumosorosea at different time points by using RNA-Sequencing and differential gene expression technology at the genomic level. To gain insight into the host-pathogen interaction at the genomic level, five libraries of P. xylostella larvae at 12, 18, 24, and 36 h post-infection and a control were constructed. In total, 161 immunity-related genes were identified and grouped into four categories; immune recognition families, toll and Imd pathway, melanization, and antimicrobial peptides (AMPs. The results of differentially expressed immunity-related genes depicted that 15, 13, 53, and 14 up-regulated and 38, 51, 56, and 49 were down-regulated in P. xylostella at 12, 18, 24, and 36 h post-treatment, respectively. RNA-Seq results of immunity-related genes revealed that the expression of AMPs was reduced after treatment with I. fumosorosea. To validate RNA-Seq results by RT-qPCR, 22 immunity-related genes were randomly selected. In conclusion, our results demonstrate that I. fumosorosea has the potential to suppress the immune response of P. xylostella and can become a potential biopesticide for controlling P. xylostella.

  15. The role of causal reasoning in understanding Simpson's paradox, Lord's paradox, and the suppression effect: covariate selection in the analysis of observational studies

    Directory of Open Access Journals (Sweden)

    Arah Onyebuchi A

    2008-02-01

    Full Text Available Abstract Tu et al present an analysis of the equivalence of three paradoxes, namely, Simpson's, Lord's, and the suppression phenomena. They conclude that all three simply reiterate the occurrence of a change in the association of any two variables when a third variable is statistically controlled for. This is not surprising because reversal or change in magnitude is common in conditional analysis. At the heart of the phenomenon of change in magnitude, with or without reversal of effect estimate, is the question of which to use: the unadjusted (combined table or adjusted (sub-table estimate. Hence, Simpson's paradox and related phenomena are a problem of covariate selection and adjustment (when to adjust or not in the causal analysis of non-experimental data. It cannot be overemphasized that although these paradoxes reveal the perils of using statistical criteria to guide causal analysis, they hold neither the explanations of the phenomenon they depict nor the pointers on how to avoid them. The explanations and solutions lie in causal reasoning which relies on background knowledge, not statistical criteria.

  16. Role of perfluoropolyether-based electrolytes in lithium metal batteries: Implication for suppressed Al current collector corrosion and the stability of Li metal/electrolytes interfaces

    Science.gov (United States)

    Cong, Lina; Liu, Jia; Armand, Michel; Mauger, Alain; Julien, Christian M.; Xie, Haiming; Sun, Liqun

    2018-03-01

    The development of safe and high performance lithium metal batteries represents a major technological challenge for this new century. Historically, intrinsic instabilities of conventional liquid organic electrolytes induced battery failures and safety issues that hinder the practical utilization of advanced rechargeable lithium metal batteries. Herein, we report a multifunctional perfluoropolyether-based liquid polymer electrolyte (PFPE-MC/LiTFSI), presenting a unique "anion-solvent" interaction. This interaction optimizes the interfacial chemistry of lithium metal batteries, which effectively inhibits the corrosion of aluminum current collectors, suppresses lithium dendrite growth, and also facilitates the formation of a thin and stable SEI layer on Li anode. Even at a high current density of 0.7 mA cm-2, the lithium dendrites do not form after 1360 h of continuous operation. The LiFePO4|PFPE-MC/LiTFSI|Li cell delivers a stable cycling performance with over 99.9% columbic efficiency either at ambient temperature or high temperature, which is significantly superior to those using traditional carbonate electrolytes. In addition, PFPE-MC/LiTFSI electrolyte also possesses eye-catching properties, such as being non-flammable, non-volatile, non-hygroscopic, and existing in the liquid state between -90 °C and 200 °C, which further ensures the high safety of the lithium metal batteries, making this electrolyte promising for the development of high energy lithium metal batteries.

  17. Catalase Has a Key Role in Protecting Cells from the Genotoxic Effects of Monomethylarsonous Acid, a Highly Active Metabolite of Arsenic

    Science.gov (United States)

    ABSTRACT Although it is widely known that arsenic-contaminated drinking water causes many diseases, arsenic’s exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as an important key event in the toxic MOA of arsenic. The author's...

  18. 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.

  19. The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans.

    Science.gov (United States)

    Shao, Jing; Zhang, MengXiang; Wang, TianMing; Li, Yue; Wang, ChangZhong

    2016-01-01

    Fungal infections caused by fluconazole-resistant Candida albicans are an intractable clinical problem, calling for new efficient antifungal drugs. Kaempferol, an active flavonoid, has been considered a potential candidate against Candida species. This work investigates the resistance reversion of kaempferol in fluconazole-resistant C. albicans and the underlying mechanism. The antifungal activities of fluconazole and/or kaempferol were assessed by a series of standard procedures including broth microdilution method, checkerboard assay and time-kill (T-K) test in nine clinical strains as well as a standard reference isolate of C. albicans. Subsequently, the morphological changes, the efflux of rhodamine 6G, and the expressions of CDR 1, CDR 2, and MDR 1 were analysed by scanning electron microscope (SEM), inverted fluorescence microscope and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in C. albicans z2003. For all the tested C. albicans strains, the minimum inhibitory concentrations (MICs) of fluconazole and kaempferol ranged 0.25-32 and 128-256 μg/mL with a range of fractional inhibitory concentration index of 0.257-0.531. In C. albicans z2003, the expression of both CDR 1 and CDR 2 were decreased after exposure to kaempferol alone with negligible rhodamine 6G accumulation, while the expression of CDR 1, CDR 2 and MDR 1 were all decreased when fluconazole and kaempferol were used concomitantly with notable fluorescence of rhodamine 6G observed. Kaempferol-induced reversion in fluconazole-resistant C. albicans might be likely due to the suppression of the expression of CDR1, CDR2 and MDR1.

  20. Heterotypic contact reveals a COX-2-mediated suppression of osteoblast differentiation by endothelial cells: A negative modulatory role for prostanoids in VEGF-mediated cell: cell communication?

    International Nuclear Information System (INIS)

    Clarkin, Claire E.; Garonna, Elena; Pitsillides, Andrew A.; Wheeler-Jones, Caroline P.D.

    2008-01-01

    In bone, angiogenesis must be initiated appropriately, but limited once remodelling or repair is complete. Our recent findings have supported a role for prostaglandins (PG), known modulators of osteoblast (OB) and endothelial cell (EC) behaviour, in facilitating VEGF-mediated paracrine communication from OBs to 'remotely located' ECs, but the mechanism(s) regulating OB:EC crosstalk when these cells are closely opposed are undefined. In this study we have examined: (i) the effects of exogenous PGE 2 on VEGF-driven events in ECs, and (ii) the role of endogenous COX-2-derived prostanoids in mediating communication between intimately opposed OBs and ECs in direct contact. Exposure of ECs to PGE 2 increased ERK1/2 phosphorylation, COX-2 induction, 6-keto-PGF 1α release and EC proliferation. In contrast, PGE 2 attenuated VEGF 165 -induced VEGFR2/Flk1 phosphorylation, ERK1/2 activation and proliferation of ECs, suggesting that exogenous PGE 2 restricts the actions of VEGF. However, the COX-2-selective inhibitor, NS398, also attenuated VEGF-induced proliferation, implying a distinct role for endogenous COX-2 activity in regulating EC behaviour. To examine the effect of OB:EC proximity and the role of COX-2 products further, we used a confrontational co-culture model. These studies showed that COX-2 blockade with NS398 enhanced EC-dependent increases in OB differentiation, that this effect was reversed by exogenous PGH 2 (immediate COX-2 product), and that exogenous VEGF did not influence EC-dependent OB differentiation under these conditions. Our findings indicate that locally produced prostanoids may serve distinct roles depending on OB:EC proximity and negatively modulate VEGF-mediated changes in EC behaviour when these cells are closely opposed to control angiogenesis during bone (re)modelling

  1. Key factors for a high-quality peritoneal dialysis program--the role of the PD team and continuous quality improvement.

    Science.gov (United States)

    Fang, Wei; Ni, Zhaohui; Qian, Jiaqi

    2014-06-01

    The proportion of end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) has increased very fast in China over the last decade. Renji Hospital, affiliated with Shanghai Jiaotong University School of Medicine, is a recognized high-quality PD unit with a high PD utilization rate, excellent patient and technique survival (1-year and 5-year patient survival rate of 93% and 71%, and 1-year and 5-year technique survival of 96% and 82%, respectively), low peritonitis rate and a well-documented good quality of life of the treated patients. We believe that a dedicated and experienced PD team, a structured patient training program, continuous patient support, establishing and utilizing standardized protocols, starting PD with low dialysis dose, monitoring key performance indicators (KPIs), and continuous quality improvement (CQI) are the key factors underlying this successful PD program. Copyright © 2014 International Society for Peritoneal Dialysis.

  2. 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.

  3. The key role of proinflammatory cytokines, matrix proteins, RANKL/OPG and Wnt/β-catenin in bone healing of hip arthroplasty patients.

    Science.gov (United States)

    Cassuto, Jean; Folestad, Agnetha; Göthlin, Jan; Malchau, Henrik; Kärrholm, Johan

    2018-02-01

    We still lack understanding of why some implants fail while most remain stable after decades of use. Proinflammatory cytokines, matrix proteins and bone regulating cytokines of the RANKL/OPG (receptor activator of nuclear factor kappa B ligand/osteoprotegerin) and Wnt/β-catenin pathways are mandatory for normal bone repair but their spatial and temporal role in the healing of primary total hip arthroplasties (THA) has not been previously shown. Twenty-four osteoarthritis patients with one-sided well-fixed primary THA were prospectively monitored during 18years (18Y) with repeated blood samples, clinical variables and radiographs. Eighty-one healthy donors divided in three age- and gender-matched groups and twenty osteoarthritis patients awaiting THA and serving as control of the validity of stored plasma in THA patients, were included. Plasma was analyzed for C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-1β, tumor necrosis factor (TNF)-α, osteopontin (OPN), secreted protein acidic and rich in cysteine (SPARC/osteonectin), osteocalcin (OC), bone specific alkaline phosphatase (BALP), N-terminal propeptide of collagen type I (P1NP), RANKL, OPG, the Wnt agonistic ligands (Wnt)-1 and Wnt-3a, and the Wnt antagonists sclerostin, Dickkopf (Dkk)-1, Dkk-3, Dkk-4, secreted frizzled related protein (sFRP)-1, sFRP-3 and Wnt inhibitory factor-1 (Wif-1). Inflammatory mediators in arthroplasty patients (CRP, IL-6, OPN) increased significantly on day one after surgery vs preoperative value (PR) and healthy subjects and returned to baseline at 6W. TNF-α did not change relative preoperative level or healthy subjects. SPARC and OC increased in a biphasic fashion with the primary phase beginning shortly after surgery and lasting 3M (SPARC) and 2Y (OC) while the secondary phase peaked at 1Y (SPARC) and 13Y (OC), with both returning to basal level at 15Y. BALP peaked at 3M after surgery with a return to basal level at 2Y followed by a continuous increase from 5Y until 18Y. P

  4. The Relationship Between Coronary Heart Disease (CHD and Major Depressive Disorder (MDD: Key Mechanisms and the Role of Quality of Life

    Directory of Open Access Journals (Sweden)

    Adrienne O’Neil

    2013-02-01

    Full Text Available Various trials have been conducted evaluating depression management programs for patients with Coronary Heart Disease (CHD. However, to date, the most effective way to manage this co-morbidity in the real world setting remains unclear. To better understand the past successes and failures of previous trials and subsequently develop suitable interventions that target key components of health related quality of life (HRQOL such as mental, physical and vocational functioning, we first need to understand the mechanisms underpinning the relationship between the two conditions. This paper will draw on the key literature in this field as identified by psychiatric, medical and social sciences databases (Cochrane Central Register of Controlled Trials, PubMed, OVID, Medline available up to January 2012, with the aim to conduct a narrative review which explores: the aetiological relationship between depression and CHD; its association with HRQOL; the relationship between CHD, depression and vocational functioning; and the impact of depression treatment on these outcomes. Key recommendations are made regarding the management of this prevalent co-morbidity in clinical settings.

  5. Clinical evidence of the role of the cerebellum in the suppression of overt articulatory movements during reading. A study of reading in children and adolescents treated for cerebellar pilocytic astrocytoma.

    Science.gov (United States)

    Ait Khelifa-Gallois, N; Puget, S; Longaud, A; Laroussinie, F; Soria, C; Sainte-Rose, C; Dellatolas, G

    2015-04-01

    It has been suggested that the cerebellum is involved in reading acquisition and in particular in the progression from automatic grapheme-phoneme conversion to the internalization of speech required for silent reading. This idea is in line with clinical and neuroimaging data showing a cerebellar role in subvocal rehearsal for printed verbalizable material and with computational "internal models" of the cerebellum suggesting its role in inner speech (i.e. covert speech without mouthing the words). However, studies examining a possible cerebellar role in the suppression of articulatory movements during silent reading acquisition in children are lacking. Here, we report clinical evidence that the cerebellum plays a part in this transition. Reading performances were compared between a group of 17 paediatric patients treated for benign cerebellar tumours and a group of controls matched for age, gender, and parental socio-educational level. The patients scored significantly lower on all reading, but the most striking difference concerned silent reading, perfectly acquired by almost all controls, contrasting with 41 % of the patients who were unable to read any item silently. Silent reading was correlated with the Working Memory Index. The present findings converge with previous reports on an implication of the cerebellum in inner speech and in the automatization of reading. This cerebellar implication is probably not specific to reading, as it also seems to affect non-reading tasks such as counting.

  6. Targeting Oxidative Stress, Cytokines and Serotonin Interactions Via Indoleamine 2, 3 Dioxygenase by Coenzyme Q10: Role in Suppressing Depressive Like Behavior in Rats.

    Science.gov (United States)

    Abuelezz, Sally A; Hendawy, Nevien; Magdy, Yosra

    2017-06-01

    Depression is a major health problem in which oxidative stress and inflammation are inextricably connected in its pathophysiology. Coenzyme Q10 (CoQ10) is an important anti-oxidant compound with anti-inflammatory and neuro-protective properties. This study was designed to investigate the hypothesis that CoQ10 by its anti-oxidant and anti-inflammatory potentials can alleviate depressive- like behavior by restoring the balance of the tryptophan catabolites kynurenine/serotonin toward the serotonin pathway by down-regulation of hippocampal indoleamine 2,3-dioxygenase 1 (IDO-1). Depressive-like behavior was induced by chronic unpredictable mild stress (CUMS) protocol including food or water deprivation, cage tilting, reversed light cycle etc. Male Wistar rats were randomly divided into five groups; Control, CUMS, CUMS and CoQ10 (50,100 and 200 mg/kg/day i.p. respectively) groups. CoQ10 effects on different behavioral and biochemical tests were analyzed. CoQ10 showed significant antidepressant efficacy, as evidenced by significantly decreased stress induced changes to forced swimming challenge and open field test, as well as attenuating raised corticosterone level and adrenal glands weight. The anti-oxidant effect of CoQ10 was exhibited by its ability to significantly reduce hippocampal elevated malondialdehyde and 4-hydroxynonenal levels and elevate the reduced glutathione and catalase levels. CoQ10 significantly reduced different pro-inflammatory cytokines levels including interleukin (IL)-1β, IL-2, IL-6 and tumor necrosis factor-α. It suppressed hippocampal IDO-1 and subsequent production of kynurenine and enhanced the hippocampal contents of tryptophan and serotonin. Immunohistochemical analysis revealed that CoQ10 was able to attenuate the elevated microglial CD68 and elevate the astrocyte glial fibrillary acidic protein compared to CUMS group. CoQ10 exhibited antidepressant-like effects on rats exposed to CUMS. This could be attributed to its ability to reduce

  7. What¿s the deal with the web/blogs/the next big technology: a key role for information science in e-social science research?

    NARCIS (Netherlands)

    Thelwall, M.; Wouters, P.

    2005-01-01

    Since many nations have provided substantial funding for new e-social science and humanities investigations, there is now an opportunity for information scientists to adopt an enabling role for this new kind of research. Logically, a more information-centred environment should be more conducive to

  8. Plasminogen activator inhibitor-1 released from activated platelets plays a key role in thrombolysis resistance. Studies with thrombi generated in the Chandler loop

    NARCIS (Netherlands)

    Stringer, H. A.; van Swieten, P.; Heijnen, H. F.; Sixma, J. J.; Pannekoek, H.

    1994-01-01

    To investigate the potential role of plasminogen activator inhibitor-1 (PAI-1), which is released from the alpha-granules of activated platelets, in thrombolysis resistance, we employed a model (the "Chandler loop") that mimics the formation of arterial thrombi in vivo and that can be manipulated in

  9. CLMP Is Essential for Intestinal Development, but Does Not Play a Key Role in Cellular Processes Involved in Intestinal Epithelial Development

    NARCIS (Netherlands)

    van der Werf, Christine S.; Hsiao, Nai-Hua; Conroy, Siobhan; Paredes, Joana; Ribeiro, Ana S.; Sribudiani, Yunia; Seruca, Raquel; Hofstra, Robert M. W.; Westers, Helga; van IJzendoorn, Sven C. D.

    2013-01-01

    Loss-of-function mutations in CLMP have been found in patients with Congenital Short Bowel Syndrome (CSBS), suggesting that its encoded protein plays a major role in intestinal development. CLMP is a membrane protein that co-localizes with tight junction proteins, but its function is largely

  10. Hyperosmotic stress induces Rho/Rho kinase/LIM kinase-mediated cofilin phosphorylation in tubular cells: key role in the osmotically triggered F-actin response

    DEFF Research Database (Denmark)

    Thirone, Ana C P; Speight, Pam; Zulys, Matthew

    2009-01-01

    Hyperosmotic stress induces cytoskeleton reorganization and a net increase in cellular F-actin, but the underlying mechanisms are incompletely understood. While de novo F-actin polymerization likely contributes to the actin response, the role of F-actin severing is unknown. To address this proble...

  11. Promoting or suppressing resilience to mental health outcomes in at risk young people: The role of parental and peer attachment and school connectedness.

    Science.gov (United States)

    Oldfield, Jeremy; Stevenson, Andrew; Ortiz, Emily; Haley, Bethany

    2018-04-01

    Adolescent attachment relationships formed with parents are salient predictors of mental health. Few studies, however, have demonstrated whether peer attachment or school connectedness can predict resilience to mental health difficulties when a young person is at risk due to poor parental attachment. Ninety adolescents (44 females and 46 males) living in economically disadvantaged areas and attending informal schooling projects in and around Guatemala City participated. Participants completed self-report measures of parental and peer attachment, school connectedness and mental health. Resilience to mental health difficulties was predicted by more secure school connectedness but lower levels of secure peer attachment. School connectedness may provide a role in promoting resilience for mental health for adolescents living in risk, whereas the potential negative influence that secure attachments to peers exerts, in context of poor parental attachment, needs to be explored further. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  12. JHR Project: a future Material Testing Reactor working as an International user Facility: The key-role of instrumentation in support to the development of modern experimental capacity

    Energy Technology Data Exchange (ETDEWEB)

    Bignan, G. [CEA, DEN, DER, JHR user Facility Interface Manager' , Cadarache, F-13108 St-Paul-Lez-Durance (France); Gonnier, C. [CEA, DEN, DER, SRJH Jules Horowitz Reactor Service, Cadarache, F-13108 St-Paul-Lez-Durance (France); Lyoussi, A.; Villard, J.F.; Destouches, C. [CEA, DEN, DER, Instrumentation Sensors and Dosimetry Laboratory, Cadarache, F-13108 St-Paul-Lez-Durance (France); Chauvin, J.P. [CEA,DEN, DER, SPEX, Experimental Physics Service, Cadarache, F-13108 St-Paul-Lez-Durance (France); Maugard, B. [CEA, DEN, DER, Reactor Department Studies, Cadarache, F-13108 St-Paul-Lez-Durance (France)

    2015-07-01

    Research and development on fuel and material behaviour under irradiation is a key issue for sustainable nuclear energy in order to meet specific needs by keeping the best level of safety. These needs mainly deal with a constant improvement of performances and safety in order to optimize the fuel cycle and hence to reach nuclear energy sustainable objectives. A sustainable nuclear energy requires a high level of performances in order to meet specific needs such as: - Pursuing improvement of the performances and safety of present and coming water cooled reactor technologies. This will require a continuous R and D support following a long-term trend driven by the plant life management, safety demonstration, flexibility and economics improvement. Experimental irradiations of structure materials are necessary to anticipate these material behaviours and will contribute to their optimisation. - Upgrading continuously nuclear fuel technology in present and future nuclear power plants to achieve better performances and to optimise the fuel cycle keeping the best level of safety. Fuel evolution for generation II, III and III+ is a key stake requiring developments, qualification tests and safety experiments to ensure the competitiveness and safety: experimental tests exploring the full range of fuel behaviour determine fuel stability limits and safety margins, as a major input for the fuel reliability analysis. To perform such accurate and innovative progress and developments, specific and ad hoc instrumentation, irradiation devices, measurement methods are necessary to be set up inside or beside the material testing reactor (MTR) core. These experiments require beforehand in situ and on line sophisticated measurements to accurately determine different key parameters such as thermal and fast neutron fluxes and nuclear heating in order to precisely monitor and control the conducted assays. The new Material Testing Reactor JHR (Jules Horowitz Reactor) currently under

  13. Old Yellow Enzyme from Trypanosoma cruzi Exhibits In Vivo Prostaglandin F2α Synthase Activity and Has a Key Role in Parasite Infection and Drug Susceptibility

    Directory of Open Access Journals (Sweden)

    Florencia Díaz-Viraqué

    2018-03-01

    Full Text Available The discovery that trypanosomatids, unicellular organisms of the order Kinetoplastida, are capable of synthesizing prostaglandins raised questions about the role of these molecules during parasitic infections. Multiple studies indicate that prostaglandins could be related to the infection processes and pathogenesis in trypanosomatids. This work aimed to unveil the role of the prostaglandin F2α synthase TcOYE in the establishment of Trypanosoma cruzi infection, the causative agent of Chagas disease. This chronic disease affects several million people in Latin America causing high morbidity and mortality. Here, we propose a prokaryotic evolutionary origin for TcOYE, and then we used in vitro and in vivo experiments to show that T. cruzi prostaglandin F2α synthase plays an important role in modulating the infection process. TcOYE overexpressing parasites were less able to complete the infective cycle in cell culture infections and increased cardiac tissue parasitic load in infected mice. Additionally, parasites overexpressing the enzyme increased PGF2α synthesis from arachidonic acid. Finally, an increase in benznidazole and nifurtimox susceptibility in TcOYE overexpressing parasites showed its participation in activating the currently anti-chagasic drugs, which added to its observed ability to confer resistance to hydrogen peroxide, highlights the relevance of this enzyme in multiple events including host–parasite interaction.

  14. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    Science.gov (United States)

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

  15. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    International Nuclear Information System (INIS)

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA

  16. The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses in human fibroblasts induced by α-irradiated keratinocytes

    International Nuclear Information System (INIS)

    Tian, Wenqian; Yin, Xiaoming; Wang, Longxiao; Wang, Jingdong; Zhu, Wei; Cao, Jianping; Yang, Hongying

    2015-01-01

    Highlights: • After co-culture with α-irradiated HaCaT cells, WS1 cells displayed oxidative stress and DNA damage. • Increased miR-21 expression in bystander cells was critical to the occurrence of RIBEs. • SOD2 of bystander cells played an important role in bystander responses. • miR-21 mediated bystander effects through its regulation on SOD2. - Abstract: Radiation-induced bystander effect (RIBE) is well accepted in the radiation research field by now, but the underlying molecular mechanisms for better understanding this phenomenon caused by intercellular communication and intracellular signal transduction are still incomplete. Although our previous study has demonstrated an important role of miR-21 of unirradiated bystander cells in RIBEs, the direct evidence for the hypothesis that RIBE is epigenetically regulated is still limited and how miR-21 mediates RIBEs is unknown. Reactive oxygen species (ROS) have been demonstrated to be involved in RIBEs, however, the roles of anti-oxidative stress system of cells in RIBEs are unclear. Using transwell insert co-culture system, we investigated medium-mediated bystander responses in WS1 human fibroblasts after co-culture with HaCaT keratinocytes traversed by α-particles. Results showed that the ROS levels in unirradiated bystander WS1 cells were significantly elevated after 30 min of co-culture, and 53BP1 foci, a surrogate marker of DNA damage, were obviously induced after 3 h of co-culture. This indicates the occurrence of oxidative stress and DNA damage in bystander WS1 cells after co-culture with irradiated keratinocytes. Furthermore, the expression of miR-21 was increased in bystander WS1 cells, downregulation of miR-21 eliminated the bystander responses, overexpression of miR-21 alone could induce bystander-like oxidative stress and DNA damage in WS1 cells. These data indicate an important mediating role of miR-21 in RIBEs. In addition, MnSOD or SOD2 in WS1 cells was involved in the bystander effects

  17. The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses in human fibroblasts induced by α-irradiated keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Wenqian; Yin, Xiaoming; Wang, Longxiao; Wang, Jingdong; Zhu, Wei; Cao, Jianping [School of Radiation Medicine and Protection, Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123 (China); Yang, Hongying, E-mail: yanghongying@suda.edu.cn [School of Radiation Medicine and Protection, Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123 (China); Institute of Radiotherapy & Oncology, Soochow University (China)

    2015-10-15

    Highlights: • After co-culture with α-irradiated HaCaT cells, WS1 cells displayed oxidative stress and DNA damage. • Increased miR-21 expression in bystander cells was critical to the occurrence of RIBEs. • SOD2 of bystander cells played an important role in bystander responses. • miR-21 mediated bystander effects through its regulation on SOD2. - Abstract: Radiation-induced bystander effect (RIBE) is well accepted in the radiation research field by now, but the underlying molecular mechanisms for better understanding this phenomenon caused by intercellular communication and intracellular signal transduction are still incomplete. Although our previous study has demonstrated an important role of miR-21 of unirradiated bystander cells in RIBEs, the direct evidence for the hypothesis that RIBE is epigenetically regulated is still limited and how miR-21 mediates RIBEs is unknown. Reactive oxygen species (ROS) have been demonstrated to be involved in RIBEs, however, the roles of anti-oxidative stress system of cells in RIBEs are unclear. Using transwell insert co-culture system, we investigated medium-mediated bystander responses in WS1 human fibroblasts after co-culture with HaCaT keratinocytes traversed by α-particles. Results showed that the ROS levels in unirradiated bystander WS1 cells were significantly elevated after 30 min of co-culture, and 53BP1 foci, a surrogate marker of DNA damage, were obviously induced after 3 h of co-culture. This indicates the occurrence of oxidative stress and DNA damage in bystander WS1 cells after co-culture with irradiated keratinocytes. Furthermore, the expression of miR-21 was increased in bystander WS1 cells, downregulation of miR-21 eliminated the bystander responses, overexpression of miR-21 alone could induce bystander-like oxidative stress and DNA damage in WS1 cells. These data indicate an important mediating role of miR-21 in RIBEs. In addition, MnSOD or SOD2 in WS1 cells was involved in the bystander effects

  18. 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.

  19. Thirst is associated with suppression of LHB outputs and active stress coping: Is there a role for a non-canonical vasopressin-glutamate pathway?

    Directory of Open Access Journals (Sweden)

    Limei eZhang

    2016-03-01

    Full Text Available Water-homeostasis is a fundamental physiological process for terrestrial life. In vertebrates, thirst drives water intake, but the neuronal circuits that connect the physiology of water regulation with emotional context are poorly understood. Vasopressin (VP is a prominent messenger in this circuit, as well as L-glutamate. We have investigated the role of a VP circuit and interaction between thirst and motivational behaviors evoked by life-threatening stimuli in rats. We demonstrate a direct pathway from hypothalamic paraventricular VP-expressing, glutamatergic magnocellular neurons to the medial division of lateral habenula (LHbM, a region containing GABAergic neurons. In vivo recording and juxtacellular labeling revealed that GABAergic neurons in the LHbM had locally branching axons, and received VP-positive axon terminal contacts on their dendrites. Water deprivation significantly reduced freezing and immobility behaviors evoked by innate fear and behavioral despair respectively, accompanied by decreased Fos expression in the lateral habenula. Our results reveal a novel VP-expressing hypothalamus to the LHbM circuit that is likely to evoke GABA-mediated inhibition in the LHbM, which promotes escape behavior during stress coping.

  20. Selective reduction of nitric oxide over Cu/ZSM-5: The role of oxygen in suppressing catalyst deactivation by carbonaceous deposits

    Energy Technology Data Exchange (ETDEWEB)

    d' Itri, Julie L; Sachtler, Wolfgang M.H. [V.N. Ipatieff Laboratory, Center for Catalysis and Surface Science, Departments of Chemical Engineering and Chemistry, Northwestern University, Evanston, IL (United States)

    1993-06-15

    The role of oxygen in the selective reduction of nitrogen monoxide by either propane or propene over 'excessively' ion-exchanged Cu/ZSM-5 has been studied. In a wide temperature region and in the absence of additives such as steam, propane is a more effective reductant than propene; with propane and in the presence of oxygen reduction of nitric oxide to nitrogen approaches 100% above 600 K. The difference in effectiveness is due to the different degree of catalyst deactivation by carbonaceous deposits: more carbonaceous material is deposited from propene than from propane. Temperature-programmed oxidation shows that above 600 K the rate of oxidation of carbonaceous deposits by oxygen is significant. The amount of such carbonaceous deposits is, therefore, lower when catalytic tests above 600 K are done in the presence of oxygen. At very high temperatures, the in situ volatilization of the deposits by reaction with oxygen keeps the catalyst surface clean in the steady state of nitric oxide reduction.

  1. Cytokine-mediated FOXO3a phosphorylation suppresses FasL expression in hemopoietic cell lines: investigations of the role of Fas in apoptosis due to cytokine starvation.

    Science.gov (United States)

    Behzad, Hayedeh; Jamil, Sarwat; Denny, Trisha A; Duronio, Vincent

    2007-05-01

    We have investigated phosphatidylinositol 3-kinase (PI3K)-dependent survival signalling pathways using several cytokines in three different hemopoietic cell lines, MC/9, FDC-P1, and TF-1. Cytokines caused PI3K- and PKB-dependent phosphorylation of FOXO3a (previously known as FKHRL1) at three distinct sites. Following cytokine withdrawal or PI3K inhibition, both of which are known to lead to apoptosis, there was a loss of FOXO3a phosphorylation, and a resulting increase in forkhead transcriptional activity, along with increased expression of Fas Ligand (FasL), which could be detected at the cell surface. Concurrently, an increase in cell surface expression of Fas was also detected. Despite the presence of both FasL and Fas, there was no detectable evidence that activation of Fas-mediated apoptotic events was contributing to apoptosis resulting from cytokine starvation or inhibition of PI3K activity. Thus, inhibition of FOXO3a activity is mediated by the PI3K-PKB pathway, but regulation of FasL is not the primary means by which cell survival is regulated in cytokine-dependent hemopoietic cells. We were also able to confirm increased expression of known FOXO3a targets, Bim and p27kip1. Together, these results support the conclusion that mitochondrial-mediated signals play the major role in apoptosis of hemopoietic cells due to loss of cytokine signalling.

  2. Mechanisms of Mitochondrial Holocytochrome c Synthase and the Key Roles Played by Cysteines and Histidine of the Heme Attachment Site, Cys-XX-Cys-His*

    Science.gov (United States)

    Babbitt, Shalon E.; San Francisco, Brian; Mendez, Deanna L.; Lukat-Rodgers, Gudrun S.; Rodgers, Kenton R.; Bretsnyder, Eric C.; Kranz, Robert G.

    2014-01-01

    Mitochondrial cytochrome c assembly requires the covalent attachment of heme by thioether bonds between heme vinyl groups and a conserved CXXCH motif of cytochrome c/c1. The enzyme holocytochrome c synthase (HCCS) binds heme and apocytochrome c substrate to catalyze this attachment, subsequently releasing holocytochrome c for proper folding to its native structure. We address mechanisms of assembly using a functional Escherichia coli recombinant system expressing human HCCS. Human cytochrome c variants with individual cysteine, histidine, double cysteine, and triple cysteine/histidine substitutions (of CXXCH) were co-purified with HCCS. Single and double mutants form a complex with HCCS but not the triple mutant. Resonance Raman and UV-visible spectroscopy support the proposal that heme puckering induced by both thioether bonds facilitate release of holocytochrome c from the complex. His-19 (of CXXCH) supplies the second axial ligand to heme in the complex, the first axial ligand was previously shown to be from HCCS residue His-154. Substitutions of His-19 in cytochrome c to seven other residues (Gly, Ala, Met, Arg, Lys, Cys, and Tyr) were used with various approaches to establish other roles played by His-19. Three roles for His-19 in HCCS-mediated assembly are suggested: (i) to provide the second axial ligand to the heme iron in preparation for covalent attachment; (ii) to spatially position the two cysteinyl sulfurs adjacent to the two heme vinyl groups for thioether formation; and (iii) to aid in release of the holocytochrome c from the HCCS active site. Only H19M is able to carry out these three roles, albeit at lower efficiencies than the natural His-19. PMID:25170082

  3. Mechanisms of mitochondrial holocytochrome c synthase and the key roles played by cysteines and histidine of the heme attachment site, Cys-XX-Cys-His.

    Science.gov (United States)

    Babbitt, Shalon E; San Francisco, Brian; Mendez, Deanna L; Lukat-Rodgers, Gudrun S; Rodgers, Kenton R; Bretsnyder, Eric C; Kranz, Robert G

    2014-10-17

    Mitochondrial cytochrome c assembly requires the covalent attachment of heme by thioether bonds between heme vinyl groups and a conserved CXXCH motif of cytochrome c/c1. The enzyme holocytochrome c synthase (HCCS) binds heme and apocytochrome c substrate to catalyze this attachment, subsequently releasing holocytochrome c for proper folding to its native structure. We address mechanisms of assembly using a functional Escherichia coli recombinant system expressing human HCCS. Human cytochrome c variants with individual cysteine, histidine, double cysteine, and triple cysteine/histidine substitutions (of CXXCH) were co-purified with HCCS. Single and double mutants form a complex with HCCS but not the triple mutant. Resonance Raman and UV-visible spectroscopy support the proposal that heme puckering induced by both thioether bonds facilitate release of holocytochrome c from the complex. His-19 (of CXXCH) supplies the second axial ligand to heme in the complex, the first axial ligand was previously shown to be from HCCS residue His-154. Substitutions of His-19 in cytochrome c to seven other residues (Gly, Ala, Met, Arg, Lys, Cys, and Tyr) were used with various approaches to establish other roles played by His-19. Three roles for His-19 in HCCS-mediated assembly are suggested: (i) to provide the second axial ligand to the heme iron in preparation for covalent attachment; (ii) to spatially position the two cysteinyl sulfurs adjacent to the two heme vinyl groups for thioether formation; and (iii) to aid in release of the holocytochrome c from the HCCS active site. Only H19M is able to carry out these three roles, albeit at lower efficiencies than the natural His-19. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses in human fibroblasts induced by α-irradiated keratinocytes.

    Science.gov (United States)

    Tian, Wenqian; Yin, Xiaoming; Wang, Longxiao; Wang, Jingdong; Zhu, Wei; Cao, Jianping; Yang, Hongying

    2015-10-01

    Radiation-induced bystander effect (RIBE) is well accepted in the radiation research field by now, but the underlying molecular mechanisms for better understanding this phenomenon caused by intercellular communication and intracellular signal transduction are still incomplete. Although our previous study has demonstrated an important role of miR-21 of unirradiated bystander cells in RIBEs, the direct evidence for the hypothesis that RIBE is epigenetically regulated is still limited and how miR-21 mediates RIBEs is unknown. Reactive oxygen species (ROS) have been demonstrated to be involved in RIBEs, however, the roles of anti-oxidative stress system of cells in RIBEs are unclear. Using transwell insert co-culture system, we investigated medium-mediated bystander responses in WS1 human fibroblasts after co-culture with HaCaT keratinocytes traversed by α-particles. Results showed that the ROS levels in unirradiated bystander WS1 cells were significantly elevated after 30min of co-culture, and 53BP1 foci, a surrogate marker of DNA damage, were obviously induced after 3h of co-culture. This indicates the occurrence of oxidative stress and DNA damage in bystander WS1 cells after co-culture with irradiated keratinocytes. Furthermore, the expression of miR-21 was increased in bystander WS1 cells, downregulation of miR-21 eliminated the bystander responses, overexpression of miR-21 alone could induce bystander-like oxidative stress and DNA damage in WS1 cells. These data indicate an important mediating role of miR-21 in RIBEs. In addition, MnSOD or SOD2 in WS1 cells was involved in the bystander effects, overexpression of SOD2 abolished the bystander oxidative stress and DNA damage, indicating that SOD2 was critical to the induction of RIBEs. Moreover, we found that miR-21 regulated SOD2, suggesting that miR-21 might mediate bystander responses through its regulation on SOD2. In conclusion, this study revealed a profound role of miR-21-regulated SOD2 of unirradiated WS1

  5. 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.

  6. Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chi-Chen [Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan (China); Institute of Biomedical Science, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taiwan (China); Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan (China); Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan (China); Chen, Jing-Ting [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Lin, Meng-Wei [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); Chan, Chia-Hao [Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital, Hsinchu 30071, Taiwan (China); Wen, Yueh-Feng [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan (China); Wu, Shin-Bei [Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); Chung, Ting-Wen [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Lyu, Kevin W. [Lutheran Medical Center, Brooklyn, NY (United States); Global Scholars Program, St. George' s University/Northumbria University, Newcastle upon Tyne (United Kingdom); Chou, Hsiu-Chuan, E-mail: chouhc@mail.nhcue.edu.tw [Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); and others

    2015-11-01

    Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However, most patients eventually develop drug resistance after 12–18 months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated with the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC. - Highlights: • 164 proteins associated with gefitinib resistance were identified through proteomic analysis. • In this study, a lung adenocarcinoma and its gefitinib resistant partner were established. • mPR and PCNT proteins have evidenced to play important roles in gefitinib resistance.

  7. Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance

    International Nuclear Information System (INIS)

    Lin, Chi-Chen; Chen, Jing-Ting; Lin, Meng-Wei; Chan, Chia-Hao; Wen, Yueh-Feng; Wu, Shin-Bei; Chung, Ting-Wen; Lyu, Kevin W.; Chou, Hsiu-Chuan

    2015-01-01

    Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However, most patients eventually develop drug resistance after 12–18 months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated with the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC. - Highlights: • 164 proteins associated with gefitinib resistance were identified through proteomic analysis. • In this study, a lung adenocarcinoma and its gefitinib resistant partner were established. • mPR and PCNT proteins have evidenced to play important roles in gefitinib resistance.

  8. Deleted in breast cancer 1 limits adipose tissue fat accumulation and plays a key role in the development of metabolic syndrome phenotype.

    Science.gov (United States)

    Escande, Carlos; Nin, Veronica; Pirtskhalava, Tamar; Chini, Claudia C S; Tchkonia, Tamar; Kirkland, James L; Chini, Eduardo N

    2015-01-01

    Obesity is often regarded as the primary cause of metabolic syndrome. However, many lines of evidence suggest that obesity may develop as a protective mechanism against tissue damage during caloric surplus and that it is only when the maximum fat accumulation capacity is reached and fatty acid spillover occurs into to peripheral tissues that metabolic diseases develop. In this regard, identifying the molecular mechanisms that modulate adipocyte fat accumulation and fatty acid spillover is imperative. Here we identify the deleted in breast cancer 1 (DBC1) protein as a key regulator of fat storage capacity of adipocytes. We found that knockout (KO) of DBC1 facilitated fat cell differentiation and lipid accumulation and increased fat storage capacity of adipocytes in vitro and in vivo. This effect resulted in a "healthy obesity" phenotype. DBC1 KO mice fed a high-fat diet, although obese, remained insulin sensitive, had lower free fatty acid in plasma, were protected against atherosclerosis and liver steatosis, and lived longer. We propose that DBC1 is part of the molecular machinery that regulates fat storage capacity in adipocytes and participates in the "turn-off" switch that limits adipocyte fat accumulation and leads to fat spillover into peripheral tissues, leading to the deleterious effects of caloric surplus. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  9. The ZntA-like NpunR4017 plays a key role in maintaining homeostatic levels of zinc in Nostoc punctiforme.

    Science.gov (United States)

    Hudek, L; Bräu, L; Michalczyk, A A; Neilan, B A; Meeks, J C; Ackland, M L

    2015-12-01

    Analysis of cellular response to zinc exposure provides insights into how organisms maintain homeostatic levels of zinc that are essential, while avoiding potentially toxic cytosolic levels. Using the cyanobacterium Nostoc punctiforme as a model, qRT-PCR analyses established a profile of the changes in relative mRNA levels of the ZntA-like zinc efflux transporter NpunR4017 in response to extracellular zinc. In cells treated with 18 μM of zinc for 1 h, NpunR4017 mRNA levels increased by up to 1300 % above basal levels. The accumulation and retention of radiolabelled (65)Zn by NpunR4107-deficient and overexpressing strains were compared to wild-type levels. Disruption of NpunR4017 resulted in a significant increase in zinc accumulation up to 24 % greater than the wild type, while cells overexpressing NpunR4107 accumulated 22 % less than the wild type. Accumulation of (65)Zn in ZntA(-) Escherichia coli overexpressing NpunR4017 was reduced by up to 21 %, indicating the capacity for NpunR4017 to compensate for the loss of ZntA. These findings establish the newly identified NpunR4017 as a zinc efflux transporter and a key transporter for maintaining zinc homeostasis in N. punctiforme.

  10. The fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites.

    Science.gov (United States)

    Yu, Min; Kumar, T R Santha; Nkrumah, Louis J; Coppi, Alida; Retzlaff, Silke; Li, Celeste D; Kelly, Brendan J; Moura, Pedro A; Lakshmanan, Viswanathan; Freundlich, Joel S; Valderramos, Juan-Carlos; Vilcheze, Catherine; Siedner, Mark; Tsai, Jennifer H-C; Falkard, Brie; Sidhu, Amar Bir Singh; Purcell, Lisa A; Gratraud, Paul; Kremer, Laurent; Waters, Andrew P; Schiehser, Guy; Jacobus, David P; Janse, Chris J; Ager, Arba; Jacobs, William R; Sacchettini, James C; Heussler, Volker; Sinnis, Photini; Fidock, David A

    2008-12-11

    The fatty acid synthesis type II pathway has received considerable interest as a candidate therapeutic target in Plasmodium falciparum asexual blood-stage infections. This apicoplast-resident pathway, distinct from the mammalian type I process, includes FabI. Here, we report synthetic chemistry and transfection studies concluding that Plasmodium FabI is not the target of the antimalarial activity of triclosan, an inhibitor of bacterial FabI. Disruption of fabI in P. falciparum or the rodent parasite P. berghei does not impede blood-stage growth. In contrast, mosquito-derived, FabI-deficient P. berghei sporozoites are markedly less infective for mice and typically fail to complete liver-stage development in vitro. This defect is characterized by an inability to form intrahepatic merosomes that normally initiate blood-stage infections. These data illuminate key differences between liver- and blood-stage parasites in their requirements for host versus de novo synthesized fatty acids, and create new prospects for stage-specific antimalarial interventions.

  11. A key role of the prefrontal cortex in the maintenance of chronic tinnitus: An fMRI study using a Stroop task.

    Science.gov (United States)

    Araneda, Rodrigo; Renier, Laurent; Dricot, Laurence; Decat, Monique; Ebner-Karestinos, Daniela; Deggouj, Naïma; De Volder, Anne G

    2018-01-01

    Since we recently showed in behavioural tasks that the top-down cognitive control was specifically altered in tinnitus sufferers, here we wanted to establish the link between this impaired executive function and brain alterations in the frontal cortex in tinnitus patients. Using functional magnetic resonance imaging (fMRI), we monitored the brain activity changes in sixteen tinnitus patients (TP) and their control subjects (CS) while they were performing a spatial Stroop task, both in audition and vision. We observed that TP differed from CS in their functional recruitment of the dorsolateral prefrontal cortex (dlPFC, BA46), the cingulate gyrus and the ventromedial prefrontal cortex (vmPFC, BA10). This recruitment was higher during interference conditions in tinnitus participants than in controls, whatever the sensory modality. Furthermore, the brain activity level in the right dlPFC and vmPFC correlated with the performance in the Stroop task in TP. Due to the direct link between poor executive functions and prefrontal cortex alterations in TP, we postulate that a lack of inhibitory modulation following an impaired top-down cognitive control may maintain tinnitus by hampering habituation mechanisms. This deficit in executive functions caused by prefrontal cortex alterations would be a key-factor in the generation and persistence of tinnitus.

  12. The communication of endogenous biomolecules (RNA, DNA, protein, hormone) via graft union might play key roles in the new traits formation of graft hybrids

    International Nuclear Information System (INIS)

    Khan, I.A.; Ghazal, L.; Arsalan, M.H.; Siddiqui, M.F.

    2018-01-01

    Plant graft hybridization is a fact of a sexual hybridization in which heritable changes trigger by grafting, it can produce hereditable variation types desired by breeders and can be used as a new method for germplasm innovation. This paper aimed to discuss new phenotypic variations such as phenotypic diversity and polyploidy formation discovered in recent years, new evidence supporting genetic material exchange between the rootstock and scion, and the timeliness, direction, and genetic stability of trait formation induced by graft hybridization. The unresolved mechanisms of trait variation were also discussed, and the relationship with exchange of chloroplast DNA (cpDNA) genetic information, horizontal gene transfer events of chloroplast and mitochondria, miRNA-mediated post-transcriptional regulation, and pressure-driven trait variations from graft hybridization were performed to clarify the relevant questions. Finally, the future research trend and key questions of graft hybridization were identified. Three clear conclusions for graft hybridization are presented: the new traits of graft hybrids have stable genetic characteristics and can be controlled via selection different genetic plant by grafting, and the products of graft hybrids were safer than those of transgenic plants. (author)

  13. 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)

  14. 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)

  15. In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

    Directory of Open Access Journals (Sweden)

    Henrique Borges da Silva

    2015-02-01

    Full Text Available Dendritic cells (DCs are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip, with Plasmodium chabaudi AS (Pc parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.

  16. In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

    Science.gov (United States)

    Borges da Silva, Henrique; Fonseca, Raíssa; Cassado, Alexandra Dos Anjos; Machado de Salles, Érika; de Menezes, Maria Nogueira; Langhorne, Jean; Perez, Katia Regina; Cuccovia, Iolanda Midea; Ryffel, Bernhard; Barreto, Vasco M; Marinho, Cláudio Romero Farias; Boscardin, Silvia Beatriz; Álvarez, José Maria; D'Império-Lima, Maria Regina; Tadokoro, Carlos Eduardo

    2015-02-01

    Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.

  17. 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.

  18. 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.

  19. Assessing the herbivore role of the sea-urchin Echinometra viridis: Keys to determine the structure of communities in disturbed coral reefs.

    Science.gov (United States)

    Sangil, Carlos; Guzman, Hector M

    2016-09-01

    Echinometra viridis previously was considered a cryptic species unable to control the development and growth of macroalgae on coral reefs. Its role as a herbivore was seen as minor compared to other grazers present on the reef. However, the present disturbed state of some reefs has highlighted the role played by this sea-urchin. Combining field data with experiments on the Caribbean coast of Panama, we demonstrate that the current community organization on disturbed coral reefs in the Mesoamerican Caribbean is largely due to the action of E. viridis. It is the most abundant sea-urchin species, together with two others (Diadema antillarum and Echinometra lucunter). Field data also indicate that the relationship between its density and the abundance of macroalgae is stronger and it is more negative in impact than those of the other two. However, the niche this urchin exploits most efficiently is confined to leeward reefs with low levels of sedimentation. Outside these habitats, their populations are not decisive in controlling macroalgal growth. Grazing experiments showed that E. viridis consumes more fresh macroalgae per day and per weight of sea-urchin, and is a more effective grazer than D. antillarum or E. lucunter. E. viridis showed food preferences for early-successional turf macroalgae (Acanthophora spicifera), avoiding the less palatable late-successional and fleshy macroalgae (Lobophora variegata, Halimeda opuntia). However, it becomes a generalist herbivore feeding on all varieties of macroalgae when resources are scarce. H. opuntia is the macroalga that most resists E. viridis activity, which may explain its wide distribution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Conformational differences between the methoxy groups of QA and QB site ubisemiquinones in bacterial reaction centers: a key role for methoxy group orientation in modulating ubiquinone redox potential.

    Science.gov (United States)

    Taguchi, Alexander T; O'Malley, Patrick J; Wraight, Colin A; Dikanov, Sergei A

    2013-07-09

    Ubiquinone is an almost universal, membrane-associated redox mediator. Its ability to accept either one or two electrons allows it to function in critical roles in biological electron transport. The redox properties of ubiquinone in vivo are determined by its environment in the binding sites of proteins and by the dihedral angle of each methoxy group relative to the ring plane. This is an attribute unique to ubiquinone among natural quinones and could account for its widespread function with many different redox complexes. In this work, we use the photosynthetic reaction center as a model system for understanding the role of methoxy conformations in determining the redox potential of the ubiquinone/semiquinone couple. Despite the abundance of X-ray crystal structures for the reaction center, quinone site resolution has thus far been too low to provide a reliable measure of the methoxy dihedral angles of the primary and secondary quinones, QA and QB. We performed 2D ESEEM (HYSCORE) on isolated reaction centers with ubiquinones (13)C-labeled at the headgroup methyl and methoxy substituents, and have measured the (13)C isotropic and anisotropic components of the hyperfine tensors. Hyperfine couplings were compared to those derived by DFT calculations as a function of methoxy torsional angle allowing estimation of the methoxy dihedral angles for the semiquinones in the QA and QB sites. Based on this analysis, the orientation of the 2-methoxy groups are distinct in the two sites, with QB more out of plane by 20-25°. This corresponds to an ≈50 meV larger electron affinity for the QB quinone, indicating a substantial contribution to the experimental difference in redox potentials (60-75 mV) of the two quinones. The methods developed here can be readily extended to ubiquinone-binding sites in other protein complexes.

  1. Atherogenicity of amino acids in the lipid-laden macrophage model system in vitro and in atherosclerotic mice: a key role for triglyceride metabolism.

    Science.gov (United States)

    Rom, Oren; Grajeda-Iglesias, Claudia; Najjar, Mahmoud; Abu-Saleh, Niroz; Volkova, Nina; Dar, Dalit Esther; Hayek, Tony; Aviram, Michael

    2017-07-01

    Atherosclerosis-related research has focused mainly on the effects of lipids on macrophage foam cell formation and atherogenesis, whereas the role of amino acids (AAs) was understudied. The current study aimed to identify anti- or pro-atherogenic AA in the macrophage model system and to elucidate the underlying metabolic and molecular mechanisms. J774A.1 cultured macrophages were treated with increasing concentrations of each 1 of the 20 AAs. Macrophage atherogenicity was assessed in terms of cellular toxicity, generation of reactive oxygen species (ROS) and cellular cholesterol or triglyceride content. At nontoxic concentrations (up to 1 mM), modest effects on ROS generation or cholesterol content were noted, but six specific AAs significantly affected macrophage triglyceride content. Glycine, cysteine, alanine and leucine significantly decreased macrophage triglyceride content (by 24%-38%), through attenuated uptake of triglyceride-rich very low-density lipoprotein (VLDL) by macrophages. In contrast, glutamate and glutamine caused a marked triglyceride accumulation in macrophages (by 107% and 129%, respectively), via a diacylglycerol acyltransferase-1 (DGAT1)-dependent increase in triglyceride biosynthesis rate with a concurrent maturation of the sterol regulatory element-binding protein-1 (SREBP1). Supplementation of apolipoprotein E-deficient (apoE -/- ) mice with glycine for 40 days significantly decreased the triglyceride levels in serum and in peritoneal macrophages (MPMs) isolated from the mice (by 19%). In contrast, glutamine supplementation significantly increased MPM ROS generation and the accumulation of cholesterol and that of triglycerides (by 48%), via enhanced uptake of LDL and VLDL. Altogether, the present findings reveal some novel roles for specific AA in macrophage atherogenicity, mainly through modulation of cellular triglyceride metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. C9orf72 poly GA RAN-translated protein plays a key role in amyotrophic lateral sclerosis via aggregation and toxicity.

    Science.gov (United States)

    Lee, Youn-Bok; Baskaran, Pranetha; Gomez-Deza, Jorge; Chen, Han-Jou; Nishimura, Agnes L; Smith, Bradley N; Troakes, Claire; Adachi, Yoshitsugu; Stepto, Alan; Petrucelli, Leonard; Gallo, Jean-Marc; Hirth, Frank; Rogelj, Boris; Guthrie, Sarah; Shaw, Christopher E

    2017-12-15

    An intronic GGGGCC (G4C2) hexanucleotide repeat expansion inC9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of G4C2 RNA can result in five different dipeptide repeat proteins (DPR: poly GA, poly GP, poly GR, poly PA, and poly PR), which aggregate into neuronal cytoplasmic and nuclear inclusions in affected patients, however their contribution to disease pathogenesis remains controversial. We show that among the DPR proteins, expression of poly GA in a cell culture model activates programmed cell death and TDP-43 cleavage in a dose-dependent manner. Dual expression of poly GA together with other DPRs revealed that poly GP and poly PA are sequestered by poly GA, whereas poly GR and poly PR are rarely co-localised with poly GA. Dual expression of poly GA and poly PA ameliorated poly GA toxicity by inhibiting poly GA aggregation both in vitro and in vivo in the chick embryonic spinal cord. Expression of alternative codon-derived DPRs in chick embryonic spinal cord confirmed in vitro data, revealing that each of the dipeptides caused toxicity, with poly GA being the most toxic. Further, in vivo expression of G4C2 repeats of varying length caused apoptotic cell death, but failed to generate DPRs. Together, these data demonstrate that C9-related toxicity can be mediated by either RNA or DPRs. Moreover, our findings provide evidence that poly GA is a key mediator of cytotoxicity and that cross-talk between DPR proteins likely modifies their pathogenic status in C9ALS/FTD. © The Author 2017. Published by Oxford University Press.

  3. Exceptionally tight membrane-binding may explain the key role of the synaptotagmin-7 C 2 A domain in asynchronous neurotransmitter release

    Energy Technology Data Exchange (ETDEWEB)

    Voleti, Rashmi; Tomchick, Diana R.; Südhof, Thomas C.; Rizo, Josep

    2017-09-18

    Synaptotagmins (Syts) act as Ca2+ sensors in neurotransmitter release by virtue of Ca2+-binding to their two C2 domains, but their mechanisms of action remain unclear. Puzzlingly, Ca2+-binding to the C2B domain appears to dominate Syt1 function in synchronous release, whereas Ca2+-binding to the C2A domain mediates Syt7 function in asynchronous release. Here we show that crystal structures of the Syt7 C2A domain and C2AB region, and analyses of intrinsic Ca2+-binding to the Syt7 C2 domains using isothermal titration calorimetry, did not reveal major differences that could explain functional differentiation between Syt7 and Syt1. However, using liposome titrations under Ca2+ saturating conditions, we show that the Syt7 C2A domain has a very high membrane affinity and dominates phospholipid binding to Syt7 in the presence or absence of L-α-phosphatidylinositol 4,5-diphosphate (PIP2). For Syt1, the two Ca2+-saturated C2 domains have similar affinities for membranes lacking PIP2, but the C2B domain dominates binding to PIP2-containing membranes. Mutagenesis revealed that the dramatic differences in membrane affinity between the Syt1 and Syt7 C2A domains arise in part from apparently conservative residue substitutions, showing how striking biochemical and functional differences can result from the cumulative effects of subtle residue substitutions. Viewed together, our results suggest that membrane affinity may be a key determinant of the functions of Syt C2 domains in neurotransmitter release.

  4. The intracellular redox stress caused by hexavalent chromium is selective for proteins that have key roles in cell survival and thiol redox control

    International Nuclear Information System (INIS)

    Myers, Judith M.; Antholine, William E.; Myers, Charles R.

    2011-01-01

    Hexavalent chromium [Cr(VI)] compounds (e.g. chromates) are strong oxidants that readily enter cells where they are reduced to reactive Cr intermediates that can directly oxidize some cell components and can promote the generation of reactive oxygen and nitrogen species. Inhalation is a major route of exposure which directly exposes the bronchial epithelium. Previous studies with non-cancerous human bronchial epithelial cells (BEAS-2B) demonstrated that Cr(VI) treatment results in the irreversible inhibition of thioredoxin reductase (TrxR) and the oxidation of thioredoxins (Trx) and peroxiredoxins (Prx). The mitochondrial Trx/Prx system is somewhat more sensitive to Cr(VI) than the cytosolic Trx/Prx system, and other redox-sensitive mitochondrial functions are subsequently affected including electron transport complexes I and II. Studies reported here show that Cr(VI) does not cause indiscriminant thiol oxidation, and that the Trx/Prx system is among the most sensitive of cellular protein thiols. Trx/Prx oxidation is not unique to BEAS-2B cells, as it was also observed in primary human bronchial epithelial cells. Increasing the intracellular levels of ascorbate, an endogenous Cr(VI) reductant, did not alter the effects on TrxR, Trx, or Prx. The peroxynitrite scavenger MnTBAP did not protect TrxR, Trx, Prx, or the electron transport chain from the effects of Cr(VI), implying that peroxynitrite is not required for these effects. Nitration of tyrosine residues of TrxR was not observed following Cr(VI) treatment, further ruling out peroxynitrite as a significant contributor to the irreversible inhibition of TrxR. Cr(VI) treatments that disrupt the TrxR/Trx/Prx system did not cause detectable mitochondrial DNA damage. Overall, the redox stress that results from Cr(VI) exposure shows selectivity for key proteins which are known to be important for redox signaling, antioxidant defense, and cell survival.

  5. The key role of {sup 99m}Tc-MIBI SPECT/CT in the diagnosis of parathyroid adenoma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qing; Pan, Jiemin; Luo, Quanyong; Wang, Yan; Bao, Yuqian; Jia, Weiping, E-mail: wpjia@sjtu.edu.cn, E-mail: wpjia@yahoo.com [Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai (China)

    2015-06-15

    The concomitant occurrence of primary hyperparathyroidism (PHPT) due to parathyroid adenoma and papillary thyroid carcinoma (PTC) is not common. The co-occurrence of parathyroid tumors and thyroid diseases can lead to misdiagnosis owing to mutual interference of imaging in the early period of disease. The most commonly used imaging techniques for the preoperative localization of parathyroid and thyroid adenomas are technetium-99m sestamibi ({sup 99m}Tc-MIBI) scintigraphy and ultrasonography of the neck. Recently, {sup 99m}Tc-MIBI single-photon emission computed tomography associated with computed tomography scintigraphy (SPECT/CT) has been used to detect PHPT, and its diagnostic value is being evaluated. Herein, we report a patient with an unusual co-occurrence of parathyroid adenoma and multiple thyroid diseases, including papillary thyroid carcinoma, thyroid adenoma and lymphocytic thyroiditis, which were localized with {sup 99}mTc-MIBI SPECT/CT and confirmed surgically. We suggest that {sup 99m}Tc-MIBI SPECT/CT can play an important role in the diagnosis of parathyroid and thyroid lesions. (author)

  6. The transcription factors CREB and c-Fos play key roles in NCAM-mediated neuritogenesis in PC12-E2 cells

    DEFF Research Database (Denmark)

    Jessen, U; Novitskaya, V; Pedersen, N

    2001-01-01

    The neural cell adhesion molecule (NCAM) stimulates axonal outgrowth by activation of the Ras-mitogen activated protein kinase (MAPK) pathway and by generation of arachidonic acid. We investigated whether the transcription factors, cyclic-AMP response-element binding protein (CREB) and c-Fos play...... roles in this process by estimating NCAM-dependent neurite outgrowth from PC12-E2 cells grown in co-culture with NCAM-negative or NCAM-positive fibroblasts. PC12-E2 cells were transiently transfected with expression plasmids encoding wild-type or dominant negative forms of CREB and c-Fos or an activated...... form of the MAPK kinase, MEK2. Alternatively, PC12-E2 cells were treated with arachidonic acid, the cAMP analogue dBcAMP, or protein kinase A (PKA) inhibitors. The negative forms of CREB and c-Fos inhibited neurite outgrowth mediated by NCAM, arachidonic acid, dBcAMP, or MEK2. Neither CREB nor c...

  7. Diversity: A key aspect of 21st century faculty roles as implemented in the Robert Wood Johnson Foundation Nurse Faculty Scholars program.

    Science.gov (United States)

    Adams, Linda Thompson; Campbell, Jacquelyn; Deming, Katie

    Academic nursing faculty play a vital role in recruiting a diverse student body to increase the diversity of the profession and educate students to provide culturally sensitive care to expand equitable health care. The purpose of the study is to present the Robert Wood Johnson Foundation Nurse Faculty Scholars program diversity initiatives and outcomes. Data on the diversity of the 90 scholars and their diversity-related leadership positions were compiled. Although the program was designed with selection criteria to encourage racial/ethnic and gender diversity, it was not until a diversity strategic plan was designed and implemented that sufficient diversity in the applicant pool and consistent diversity among the scholars was achieved. The program also included highly evaluated leadership content in diversity and inclusion. Lessons learned from the program are important for the assurance of continued diversity among tenure-track nursing faculty, commitment to diversity in the nursing workforce among all faculty, and support in nursing education on providing culturally sensitive nursing care and nursing research that addresses health inequities. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. ATP-binding motifs play key roles in Krp1p, kinesin-related protein 1, function for bi-polar growth control in fission yeast

    International Nuclear Information System (INIS)

    Rhee, Dong Keun; Cho, Bon A; Kim, Hyong Bai

    2005-01-01

    Kinesin is a microtubule-based motor protein with various functions related to the cell growth and division. It has been reported that Krp1p, kinesin-related protein 1, which belongs to the kinesin heavy chain superfamily, localizes on microtubules and may play an important role in cytokinesis. However, the function of Krp1p has not been fully elucidated. In this study, we overexpressed an intact form and three different mutant forms of Krp1p in fission yeast constructed by site-directed mutagenesis in two ATP-binding motifs or by truncation of the leucine zipper-like motif (LZiP). We observed hyper-extended microtubules and the aberrant nuclear shape in Krp1p-overexpressed fission yeast. As a functional consequence, a point mutation of ATP-binding domain 1 (G89E) in Krp1p reversed the effect of Krp1p overexpression in fission yeast, whereas the specific mutation in ATP-binding domain 2 (G238E) resulted in the altered cell polarity. Additionally, truncation of the leucine zipper-like domain (LZiP) at the C-terminal of Krp1p showed a normal nuclear division. Taken together, we suggest that krp1p is involved in regulation of cell-polarized growth through ATP-binding motifs in fission yeast

  9. Key role of group v secreted phospholipase A2 in Th2 cytokine and dendritic cell-driven airway hyperresponsiveness and remodeling.

    Directory of Open Access Journals (Sweden)

    William R Henderson

    Full Text Available Previous work has shown that disruption of the gene for group X secreted phospholipase A2 (sPLA2-X markedly diminishes airway hyperresponsiveness and remodeling in a mouse asthma model. With the large number of additional sPLA2s in the mammalian genome, the involvement of other sPLA2s in the asthma model is possible - in particular, the group V sPLA2 (sPLA2-V that like sPLA2-X is highly active at hydrolyzing membranes of mammalian cells.The allergen-driven asthma phenotype was significantly reduced in sPLA2-V-deficient mice but to a lesser extent than observed previously in sPLA2-X-deficient mice. The most striking difference observed between the sPLA2-V and sPLA2-X knockouts was the significant impairment of the primary immune response to the allergen ovalbumin (OVA in the sPLA2-V(-/- mice. The impairment in eicosanoid generation and dendritic cell activation in sPLA2-V(-/- mice diminishes Th2 cytokine responses in the airways.This paper illustrates the diverse roles of sPLA2s in the immunopathogenesis of the asthma phenotype and directs attention to developing specific inhibitors of sPLA2-V as a potential new therapy to treat asthma and other allergic disorders.

  10. A Key Role of Xanthophylls That Are Not Embedded in Proteins in Regulation of the Photosynthetic Antenna Function in Plants, Revealed by Monomolecular Layer Studies.

    Science.gov (United States)

    Welc, Renata; Luchowski, Rafal; Grudzinski, Wojciech; Puzio, Michal; Sowinski, Karol; Gruszecki, Wieslaw I

    2016-12-29

    The main physiological function of LHCII (light-harvesting pigment-protein complex of photosystem II), the largest photosynthetic antenna complex of plants, is absorption of light quanta and transfer of excitation energy toward the reaction centers, to drive photosynthesis. However, under strong illumination, the photosynthetic apparatus faces the danger of photodegradation and therefore excitations in LHCII have to be down-regulated, e.g., via thermal energy dissipation. One of the elements of the regulatory system, operating in the photosynthetic apparatus under light stress conditions, is a conversion of violaxanthin, the xanthophyll present under low light, to zeaxanthin, accumulated under strong light. In the present study, an effect of violaxanthin and zeaxanthin on the molecular organization and the photophysical properties of LHCII was studied in a monomolecular layer system with application of molecular imaging (atomic force microscopy, fluorescence lifetime imaging microscopy) and spectroscopy (UV-Vis absorption, FTIR, fluorescence spectroscopy) techniques. The results of the experiments show that violaxanthin promotes the formation of supramolecular LHCII structures preventing dissipative excitation quenching while zeaxanthin is involved in the formation of excitonic energy states able to quench chlorophyll excitations in both the higher (B states) and lower (Q states) energy levels. The results point to a strategic role of xanthophylls that are not embedded in a protein environment, in regulation of the photosynthetic light harvesting activity in plants.

  11. OsLEA3-2, an abiotic stress induced gene of rice plays a key role in salt and drought tolerance.

    Directory of Open Access Journals (Sweden)

    Jianli Duan

    Full Text Available Late embryogenesis abundant (LEA proteins are involved in tolerance to drought, cold and high salinity in many different organisms. In this report, a LEA protein producing full-length gene OsLEA3-2 was identified in rice (Oryza sativa using the Rapid Amplification of cDNA Ends (RACE method. OsLEA3-2 was found to be only expressed in the embryo and can be induced by abiotic stresses. The coding protein localizes to the nucleus and overexpression of OsLEA3-2 in yeast improved growth performance compared with control under salt- and osmotic-stress conditions. OsLEA3-2 was also inserted into pHB vector and overexpressed in Arabidopsis and rice. The transgenic Arabidopsis seedlings showed better growth on MS media supplemented with 150 mM mannitol or 100 mM NaCl as compared with wild type plants. The transgenic rice also showed significantly stronger growth performance than control under salinity or osmotic stress conditions and were able to recover after 20 days of drought stress. In vitro analysis showed that OsLEA3-2 was able to protect LDH from aggregation on freezing and inactivation on desiccation. These results indicated that OsLEA3-2 plays an important role in tolerance to abiotic stresses.

  12. Dissecting the functional role of key residues in triheme cytochrome PpcA: a path to rational design of G. sulfurreducens strains with enhanced electron transfer capabilities.

    Directory of Open Access Journals (Sweden)

    Leonor Morgado

    Full Text Available PpcA is the most abundant member of a family of five triheme cytochromes c7 in the bacterium Geobacter sulfurreducens (Gs and is the most likely carrier of electrons destined for outer surface during respiration on solid metal oxides, a process that requires extracellular electron transfer. This cytochrome has the highest content of lysine residues (24% among the family, and it was suggested to be involved in e-/H(+ energy transduction processes. In the present work, we investigated the functional role of lysine residues strategically located in the vicinity of each heme group. Each lysine was replaced by glutamine or glutamic acid to evaluate the effects of a neutral or negatively charged residue in each position. The results showed that replacing Lys9 (located near heme IV, Lys18 (near heme I or Lys22 (between hemes I and III has essentially no effect on the redox properties of the heme groups and are probably involved in redox partner recognition. On the other hand, Lys43 (near heme IV, Lys52 (between hemes III and IV and Lys60 (near heme III are crucial in the regulation of the functional mechanism of PpcA, namely in the selection of microstates that allow the protein to establish preferential e-/H(+ transfer pathways. The results showed that the preferred e-/H(+ transfer pathways are only established when heme III is the last heme to oxidize, a feature reinforced by a higher difference between its reduction potential and that of its predecessor in the order of oxidation. We also showed that K43 and K52 mutants keep the mechanistic features of PpcA by establishing preferential e-/H+ transfer pathways at lower reduction potential values than the wild-type protein, a property that can enable rational design of Gs strains with optimized extracellular electron transfer capabilities.

  13. When bad guys become good ones: the key role of reactive oxygen species and nitric oxide in the plant responses to abiotic stress

    Directory of Open Access Journals (Sweden)

    Fernanda Dos Santos Farnese

    2016-04-01

    Full Text Available The natural environment of plants is composed of a complex set of abiotic stresses and their ability to respond to these stresses is highly flexible and finely balanced through the interaction between signaling molecules. In this review, we highlight the integrated action between reactive oxygen species (ROS and reactive nitrogen species (RNS, particularly nitric oxide (NO, involved in the acclimation to different abiotic stresses. Under stressful conditions, the biosynthesis transport and the metabolism of ROS and NO influence plant response mechanisms. The enzymes involved in ROS and NO synthesis and scavenging can be found in different cells compartments and their temporal and spatial locations are determinant for signaling mechanisms. Both ROS and NO are involved in long distances signaling (ROS wave and GSNO transport, promoting an acquired systemic acclimation to abiotic stresses. The mechanisms of abiotic stresses response triggered by ROS and NO involve some general steps, as the enhancement of antioxidant systems, but also stress-specific mechanisms, according to the stress type (drought, hypoxia, heavy metals, etc, and demand the interaction with other signaling molecules, such as MAPK, plant hormones and calcium. The transduction of ROS and NO bioactivity involves post-translational modifications of proteins, particularly S-glutathionylation for ROS, and S-nitrosylation for NO. These changes may alter the activity, stability, and interaction with other molecules or subcellular location of proteins, changing the entire cell dynamics and contributing to the maintenance of homeostasis. However, despite the recent advances about the roles of ROS and NO in signaling cascades, many challenges remain, and future studies focusing on the signaling of these molecules in planta are still necessary.

  14. Reasons for living, meaning in life, and suicide ideation: investigating the roles of key positive psychological factors in reducing suicide risk in community-residing older adults.

    Science.gov (United States)

    Heisel, Marnin J; Neufeld, Eva; Flett, Gordon L

    2016-01-01

    To investigate the roles of reasons for living (RFL) and meaning in life (MIL) in potentially promoting mental health and well-being and protecting against suicide ideation among community-residing older adults and to investigate the psychometric properties of the Reasons for Living Scale-Older Adult version (RFL-OA). Of 173 older adults initially recruited into a longitudinal study on late-life suicide ideation, 109 completed the RFL-OA and measures of cognitive and physical functioning and positive and negative psychological factors at a two-year follow-up assessment. We tested a model in which RFL and MIL protect against suicide ideation, controlling for demographic and clinical factors. We also assessed the psychometric properties of the RFL-OA in community-residing older adults, investigating its internal consistency and its convergent (MIL, perceived social support, and life satisfaction), divergent (loneliness, depressive symptom severity, and suicide ideation), and discriminant validity (cognitive and physical functioning). RFL-OA scores explained significant variance in suicide ideation, controlling for age, sex, depressive symptom severity, and loneliness. MIL explained significant unique variance in suicide ideation, controlling for these factors and RFL, and MIL significantly mediated the association between RFL and suicide ideation. Psychometric analyses indicated strong internal consistency (α = .94), convergent, divergent, and discriminant validity for the RFL-OA relative to positive and negative psychological factors and cognitive and physical functioning. These findings add to a growing body of literature suggesting merit in investigating positive psychological factors together with negative factors when assessing suicide risk and planning psychological services for older adults.

  15. Conserved Epigenetic Mechanisms Could Play a Key Role in Regulation of Photosynthesis and Development-Related Genes during Needle Development of Pinus radiata.

    Science.gov (United States)

    Valledor, Luis; Pascual, Jesús; Meijón, Mónica; Escandón, Mónica; Cañal, María Jesús

    2015-01-01

    Needle maturation is a complex process that involves cell growth, differentiation and tissue remodelling towards the acquisition of full physiological competence. Leaf induction mechanisms are well known; however, those underlying the acquisition of physiological competence are still poorly understood, especially in conifers. We studied the specific epigenetic regulation of genes defining organ function (PrRBCS and PrRBCA) and competence and stress response (PrCSDP2 and PrSHMT4) during three stages of needle development and one de-differentiated control. Gene-specific changes in DNA methylation and histone were analysed by bisulfite sequencing and chromatin immunoprecipitation (ChIP). The expression of PrRBCA and PrRBCS increased during needle maturation and was associated with the progressive loss of H3K9me3, H3K27me3 and the increase in AcH4. The maturation-related silencing of PrSHMT4 was correlated with increased H3K9me3 levels, and the repression of PrCSDP2, to the interplay between AcH4, H3K27me3, H3K9me3 and specific DNA methylation. The employ of HAT and HDAC inhibitors led to a further determination of the role of histone acetylation in the regulation of our target genes. The integration of these results with high-throughput analyses in Arabidopsis thaliana and Populus trichocarpa suggests that the specific epigenetic mechanisms that regulate photosynthetic genes are conserved between the analysed species.

  16. Conserved Epigenetic Mechanisms Could Play a Key Role in Regulation of Photosynthesis and Development-Related Genes during Needle Development of Pinus radiata.

    Directory of Open Access Journals (Sweden)

    Luis Valledor

    Full Text Available Needle maturation is a complex process that involves cell growth, differentiation and tissue remodelling towards the acquisition of full physiological competence. Leaf induction mechanisms are well known; however, those underlying the acquisition of physiological competence are still poorly understood, especially in conifers. We studied the specific epigenetic regulation of genes defining organ function (PrRBCS and PrRBCA and competence and stress response (PrCSDP2 and PrSHMT4 during three stages of needle development and one de-differentiated control. Gene-specific changes in DNA methylation and histone were analysed by bisulfite sequencing and chromatin immunoprecipitation (ChIP. The expression of PrRBCA and PrRBCS increased during needle maturation and was associated with the progressive loss of H3K9me3, H3K27me3 and the increase in AcH4. The maturation-related silencing of PrSHMT4 was correlated with increased H3K9me3 levels, and the repression of PrCSDP2, to the interplay between AcH4, H3K27me3, H3K9me3 and specific DNA methylation. The employ of HAT and HDAC inhibitors led to a further determination of the role of histone acetylation in the regulation of our target genes. The integration of these results with high-throughput analyses in Arabidopsis thaliana and Populus trichocarpa suggests that the specific epigenetic mechanisms that regulate photosynthetic genes are conserved between the analysed species.

  17. Edaphic, structural and physiological contrasts across Amazon Basin forest–savanna ecotones suggest a role for potassium as a key modulator of tropical woody vegetation structure and function

    Directory of Open Access Journals (Sweden)

    J. Lloyd

    2015-11-01

    C / N ratios than nearby forest plots. These soil differences were also reflected in canopy averaged leaf traits with savanna trees typically having higher leaf mass per unit area but lower mass-based nitrogen (Nm and potassium (Km. Both Nm and Km also increased with declining mean annual precipitation (PA, but most area-based leaf traits such as leaf photosynthetic capacity showed no systematic variation with PA or vegetation type. Despite this invariance, when taken in conjunction with other measures such as mean canopy height, area-based soil exchangeable potassium content, [K]sa , proved to be an excellent predictor of several photosynthetic properties (including 13C isotope discrimination. Moreover, when considered in a multivariate context with PA and soil plant available water storage capacity (θP as covariates, [K]sa also proved to be an excellent predictor of stand-level canopy area, providing drastically improved fits as compared to models considering just PA and/or θP. Neither calcium, nor magnesium, nor soil pH could substitute for potassium when tested as alternative model predictors (ΔAIC > 10. Nor for any model could simple soil texture metrics such as sand or clay content substitute for either [K]sa or θP. Taken in conjunction with recent work in Africa and the forests of the Amazon Basin, this suggests – in combination with some newly conceptualised interacting effects of PA and θP also presented here – a critical role for potassium as a modulator of tropical vegetation structure and function.

  18. Dissecting a QTL into Candidate Genes Highlighted the Key Role of Pectinesterases in Regulating the Ascorbic Acid Content in Tomato Fruit

    Directory of Open Access Journals (Sweden)

    Valentino Ruggieri

    2015-07-01

    Full Text Available Tomato ( is a crucial component of the human diet because of its high nutritional value and the antioxidant content of its fruit. As a member of the Solanaceae family, it is considered a model species for genomic studies in this family, especially since its genome has been completely sequenced. Among genomic resources available, introgression lines represent a valuable tool to mine the genetic diversity present in wild species. One introgression line, IL12-4, was previously selected for high ascorbic acid (AsA content, and a transcriptomic analysis indicated the involvement of genes controlling pectin degradation in AsA accumulation. In this study the integration of data from different “omics” platforms has been exploited to identify candidate genes that increase AsA belonging to the wild region 12-4. Thirty-two genes potentially involved in pathways controlling AsA levels were analyzed with bioinformatic tools. Two hundred-fifty nonsynonymous polymorphisms were detected in their coding regions, and 11.6% revealed deleterious effects on predicted protein function. To reduce the number of genes that had to be functionally validated, introgression sublines of the region 12–4 were selected using species-specific polymorphic markers between the two species. Four sublines were obtained and we demonstrated that a subregion of around 1 Mbp includes 12 candidate genes potentially involved in AsA accumulation. Among these, only five exhibited structural deleterious variants, and one of the 12 was differentially expressed between the two species. We have highlighted the role of three polymorphic pectinesterases and inhibitors of pectinesterases that merit further investigation.

  19. Planktonic stages of small pelagic fishes (Sardinella aurita and Engraulis encrasicolus) in the central Mediterranean Sea: The key role of physical forcings and implications for fisheries management

    Science.gov (United States)

    Torri, Marco; Corrado, Raffaele; Falcini, Federico; Cuttitta, Angela; Palatella, Luigi; Lacorata, Guglielmo; Patti, Bernardo; Arculeo, Marco; Mifsud, Roberta; Mazzola, Salvatore; Santoleri, Rosalia

    2018-03-01

    Multidisciplinary studies are recently aiming to define diagnostic tools for fishery sustainability by coupling ichthyoplanktonic datasets, physical and bio-geochemical oceanographic measurements, and ocean modelling. The main goal of these efforts is to understand those processes that control the dispersion and fate of fish larvae and eggs, and thus tuning the inter-annual variability of the biomass of small pelagic fish species. In this paper we analyse the distribution of eggs and larvae as well as the biological features of the two species of pelagic fish, Engraulis encrasicolus and Sardinella aurita in the north-eastern sector of the Sicily Channel (Mediterranean Sea) from ichthyoplanktonic data collected during the 2010 and 2011 summer cruises. We use Lagrangian simulations and satellite data (i.e., sea surface temperature, wind, and chlorophyll-a concentration) to recognize the main oceanographic patterns that mark eggs and larvae transport processes. We provide a mechanistic explanation of a cross-shore transport process by using a potential vorticity (PV) model that takes into account the role of wind stress in generating cold filaments. Our results show that the strong offshore transport towards Malta occurred in 2010 was likely due to a persistent Mistral wind forcing that generated high-PV cold filaments. This phenomenon was not found in the 2011 analysis, which indeed showed an along-shore transport towards the retention area of Capo Passero. Since, for the first time, we describe the spatial distribution of the early life stage of Sardinella aurita in the northern part of the Sicily Channel and we clarify the link between the ocean dynamics and the fate of small pelagic fish larvae, this work provides a useful, diagnostic tool for the sustainable management of fishery resources.

  20. STOP-EVENT-RELATED POTENTIALS FROM INTRACRANIAL ELECTRODES REVEAL A KEY ROLE OF PREMOTOR AND MOTOR CORTICES IN STOPPING ONGOING MOVEMENTS

    Directory of Open Access Journals (Sweden)

    Maurizio eMattia

    2012-06-01

    Full Text Available In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal–basal ganglia–thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus. These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e. premotor (PMA and primary motor (M1 cortices. Electroencephalographic (EEG studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA and Brodmann's area (BA 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times. These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal–basal ganglia–thalamic network.

  1. When Bad Guys Become Good Ones: The Key Role of Reactive Oxygen Species and Nitric Oxide in the Plant Responses to Abiotic Stress.

    Science.gov (United States)

    Farnese, Fernanda S; Menezes-Silva, Paulo E; Gusman, Grasielle S; Oliveira, Juraci A

    2016-01-01

    The natural environment of plants is composed of a complex set of abiotic stresses and their ability to respond to these stresses is highly flexible and finely balanced through the interaction between signaling molecules. In this review, we highlight the integrated action between reactive oxygen species (ROS) and reactive nitrogen species (RNS), particularly nitric oxide (NO), involved in the acclimation to different abiotic stresses. Under stressful conditions, the biosynthesis transport and the metabolism of ROS and NO influence plant response mechanisms. The enzymes involved in ROS and NO synthesis and scavenging can be found in different cells compartments and their temporal and spatial locations are determinant for signaling mechanisms. Both ROS and NO are involved in long distances signaling (ROS wave and GSNO transport), promoting an acquired systemic acclimation to abiotic stresses. The mechanisms of abiotic stresses response triggered by ROS and NO involve some general steps, as the enhancement of antioxidant systems, but also stress-specific mechanisms, according to the stress type (drought, hypoxia, heavy metals, etc.), and demand the interaction with other signaling molecules, such as MAPK, plant hormones, and calcium. The transduction of ROS and NO bioactivity involves post-translational modifications of proteins, particularly S-glutathionylation for ROS, and S-nitrosylation for NO. These changes may alter the activity, stability, and interaction with other molecules or subcellular location of proteins, changing the entire cell dynamics and contributing to the maintenance of homeostasis. However, despite the recent advances about the roles of ROS and NO in signaling cascades, many challenges remain, and future studies focusing on the signaling of these molecules in planta are still necessary.

  2. 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)

  3. 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.

  4. Methylmercury production in soil in the water-level-fluctuating zone of the Three Gorges Reservoir, China: The key role of low-molecular-weight organic acids.

    Science.gov (United States)

    Yin, Deliang; Wang, Yongmin; Jiang, Tao; Qin, Caiqing; Xiang, Yuping; Chen, Qiuyu; Xue, Jinping; Wang, Dingyong

    2018-04-01

    As important parts of dissolved organic matter, low-molecular-weight organic acids (LMWOAs) typically play important roles in desorbing Hg(II) from the soil solid-phase, which may directly or indirectly impact methylmercury (MeHg) production. However, the mechanism of these processes remains unclear. To better understand the effects of LMWOAs on Hg methylation in the soil, a field study was conducted to investigate the distribution of LMWOAs and their relationship with soil MeHg in a seasonally inundated area in the Three Gorges Reservoir (TGR), China. Meanwhile, laboratory simulation experiments were performed to determine the potential mechanism of LMWOAs in Hg methylation. The field investigation detected considerable amounts of LMWOAs in soil, among which tartaric acid and oxalic acid were dominant components. Among which, tartaric acid and oxalic acid were dominant components. Also, a seasonally and spatially heterogeneous distribution of LMWOAs in soil was observed. Notably, a significant positive relationship was found between MeHg concentrations and LMWOA pools in soil (r = 0.969, p < .01), implying that LMWOAs could promote soil MeHg production. The simulation experiments confirmed that the MeHg levels in soil were largely elevated with the addition of LMWOAs, which occurred mainly in oxygen-deficient environment and was mediated by biotic factors. The soluble Hg-LMWOA complexes, which were formed by the enhanced desorption of Hg(II) from solid-phase, were mostly responsible for the elevated MeHg production in soil. Moreover, those LMWOAs with more carboxylic groups were believed to enhance the net production of MeHg. The generated MeHg in sediment could diffuse into the overlying water, which thus poses a potential threat to the aquatic food web. Therefore, the enhanced Hg methylation caused by LMWOAs should be given more attention, especially in a seasonally inundated ecosystem, where the MeHg exposure is usually related to fishery activities

  5. miR-218 is involved in the negative regulation of osteoclastogenesis and bone resorption by partial suppression of p38MAPK-c-Fos-NFATc1 signaling: Potential role for osteopenic diseases.

    Science.gov (United States)

    Qu, Bo; Xia, Xun; Yan, Ming; Gong, Kai; Deng, Shaolin; Huang, Gang; Ma, Zehui; Pan, Xianming

    2015-10-15

    The increased osteoclastic activity accounts for pathological bone loss in diseases including osteoporosis. MicroRNAs are widely accepted to be involved in the regulation of osteopenic diseases. Recently, the low expression of miR-218 was demonstrated in CD14(+) peripheral blood mononuclear cells (PBMCs) from patients with postmenopausal osteoporosis. However, its role and the underlying mechanism in osteoporosis are still undefined. Here, an obvious decrease in miR-218 expression was observed during osteoclastogenesis under receptor activator of nuclear factor κB ligand (RANKL) stimulation, in both osteoclast precursors of bone marrow macrophages (BMMs) and RAW 264.7. Further analysis confirmed that overexpression of miR-218 obviously attenuated the formation of multinuclear mature osteoclasts, concomitant with the decrease in Trap and Cathepsin K levels, both the master regulators of osteoclastogenesis. Moreover, miR-218 up-regulation dramatically inhibited osteoclast precursor migration, actin ring formation and bone resorption. Mechanism assay demonstrated that miR-218 overexpression attenuated the expression of p38MAPK, c-Fos and NFATc1 signaling molecules. Following preconditioning with P79350, an agonist of p38MAPK, the inhibitor effect of miR-218 on osteoclastogenesis and bone-resorbing activity was strikingly ameliorated. Together, this study revealed a crucial role of miR-218 as a negative regulator for osteoclastogenesis and bone resorption by suppressing the p38MAPK-c-Fos-NFATc1 pathway. Accordingly, this research will provide a promising therapeutic agent against osteopenic diseases including osteoporosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. 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.)

  7. 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.)

  8. Quantum key management

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, Richard John; Thrasher, James Thomas; Nordholt, Jane Elizabeth

    2016-11-29

    Innovations for quantum key management harness quantum communications to form a cryptography system within a public key infrastructure framework. In example implementations, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a Merkle signature scheme (using Winternitz one-time digital signatures or other one-time digital signatures, and Merkle hash trees) to constitute a cryptography system. More generally, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a hash-based signature scheme. This provides a secure way to identify, authenticate, verify, and exchange secret cryptographic keys. Features of the quantum key management innovations further include secure enrollment of users with a registration authority, as well as credential checking and revocation with a certificate authority, where the registration authority and/or certificate authority can be part of the same system as a trusted authority for quantum key distribution.

  9. Group key management

    Energy Technology Data Exchange (ETDEWEB)

    Dunigan, T.; Cao, C.

    1997-08-01

    This report describes an architecture and implementation for doing group key management over a data communications network. The architecture describes a protocol for establishing a shared encryption key among an authenticated and authorized collection of network entities. Group access requires one or more authorization certificates. The implementation includes a simple public key and certificate infrastructure. Multicast is used for some of the key management messages. An application programming interface multiplexes key management and user application messages. An implementation using the new IP security protocols is postulated. The architecture is compared with other group key management proposals, and the performance and the limitations of the implementation are described.

  10. Modular Connector Keying Concept

    Science.gov (United States)

    Ishman, Scott; Dukes, Scott; Warnica, Gary; Conrad, Guy; Senigla, Steven

    2013-01-01

    For panel-mount-type connectors, keying is usually "built-in" to the connector body, necessitating different part numbers for each key arrangement. This is costly for jobs that require small quantities. This invention was driven to provide a cost savings and to reduce documentation of individual parts. The keys are removable and configurable in up to 16 combinations. Since the key parts are separate from the connector body, a common design can be used for the plug, receptacle, and key parts. The keying can then be set at the next higher assembly.

  11. 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.

  12. China's key role in climate protection

    International Nuclear Information System (INIS)

    Bach, W.; Fiebig, S.

    1998-01-01

    China is in the process of becoming the fourth main global player in the world economy, together with the US, the EU, and Japan. Due to an energy mix with 75% dependence on coal, a high energy intensity and low energy prices, it is, after the US, the world's second largest emitter of CO 2 . China's recoverable fossil fuel reserves have a CO 2 emission potential of some 225 Gt (the current global CO 2 emission is about 22 Gt/yr). Under a business-as-usual (BAU) scenario, all of it would be released to the atmosphere by 2040. This emission may cause a significant disruption of the climate system, resulting in severe adverse climatic and ecological impacts on China and the world. To avoid this outcome, an equitable climate-protection strategy is introduced to explore an alternative energy/climate future. Using a macroeconomic approach, it is shown that under BAU conditions, the year 2100 emissions of CO 2 will increase above 1990 levels by 370 and 96% for China and the US, respectively. In contrast, for the climate-protection conditions required by the Climate Convention, CO 2 emissions must decrease by 36% for China and by 90% for the US below 1990 levels. Using a macroeconomic-engineering approach, the total CO 2 reduction potential is found to be about 4600 Mt for 13 specific measures over a 10-yr period. The incremental costs range from US$ 0.09 to 18.55 per ton of CO 2 reduction for coal-saving stoves and solar cookers, respectively. The total reduction costs for China would be about US$ 2 billion per year or ∼ 0.4% of the 1994 GDP of China. This estimate does not allow for benefits from saved resources and avoided damages. We conclude with a discussion of various avenues for obtaining needed technological and financial support for China. (author)

  13. Moderate takes key science role in Congress

    CERN Multimedia

    MacIlwain, C

    2001-01-01

    Sherry Boehlert has been named as chair of the Science committee in the US House of Representatives. Described as a moderate Republican with a keen interest in environmental and energy issues, it is seen as a good appointment by scientists (1/2 page)

  14. Biometry, the safe key

    Directory of Open Access Journals (Sweden)

    María Fraile-Hurtado

    2010-12-01

    Full Text Available Biometry is the next step in authentication, why do not we take this stepforward in our communication security systems? Keys are the main disadvantage in the cryptography, what if we were our own key?

  15. Financial Key Ratios

    OpenAIRE

    Tănase Alin-Eliodor

    2014-01-01

    This article focuses on computing techniques starting from trial balance data regarding financial key ratios. There are presented activity, liquidity, solvency and profitability financial key ratios. It is presented a computing methodology in three steps based on a trial balance.

  16. Public Key Cryptography.

    Science.gov (United States)

    Tapson, Frank

    1996-01-01

    Describes public key cryptography, also known as RSA, which is a system using two keys, one used to put a message into cipher and another used to decipher the message. Presents examples using small prime numbers. (MKR)

  17. Key Management Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Provides a secure environment to research and develop advanced electronic key management and networked key distribution technologies for the Navy and DoD....

  18. Public Key Infrastructure Study

    National Research Council Canada - National Science Library

    Berkovits, Shimshon

    1994-01-01

    The National Institute of Standards and Technology (NIST) has tasked The MITRE Corporation to study the alternatives for automated management of public keys and of the associated public key certificates for the Federal Government...

  19. 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...

  20. J/Ψ suppression

    International Nuclear Information System (INIS)

    Giubellino, P.; Abreu, M.C.; Alessandro, B.; Alexa, C.; Arnaldi, R.; Astruc, J.; Atayan, M.; Baglin, C.; Baldit, A.; Bedjidian, M.; Bellaiche, F.; Beole, S.; Boldea, V.; Bordalo, P.; Bussiere, A.; Capony, V.; Casagrande, L.; Castor, J.; Chambon, T.; Chaurand, B.; Chevrot, I.; Cheynis, B.; Chiavassa, E.; Cicalo, C.; Comets, M.P.; Constantinescu, S.; Cruz, J.; De Falco, A.; De Marco, N.; Dellacasa, G.; Devaux, A.; Dita, S.; Drapier, O.; Espagnon, B.; Fargeix, J.; Filippov, S.N.; Fleuret, F.; Force, P.; Gallio, M.; Gavrilov, Y.K.; Gerschel, C.; Giubellino, P.; Golubeva, M.B.; Gonin, M.; Grigorian, A.A.; Grossiord, J.Y.; Guber, F.F.; Guichard, A.; Gulkaninan, H.; Hakobyan, R.; Haroutunian, R.; Idzik, M.; Jouan, D.; Karavitcheva, T.L.; Kluberg, L.; Kurepin, A.B.; Le Bornec, Y.; Lourenco, C.; Mac Cormick, M.; Macciotta, P.; Marzari-Chiesa, A.; Masera, M.; Masoni, A.; Mehrabyan, S.; Mourgues, S.; Musso, A.; Ohlsson-Malek, F.; Petiau, P.; Piccotti, A.; Pizzi, J.R.; Prado da Silva, W.L.; Puddu, G.; Quintans, C.; Racca, C.; Ramello, L.; Ramos, S.; Rato-Mendes, P.; Riccati, L.; Romana, A.; Sartori, S.; Saturnini, P.; Scomparin, E.; Serci, S.; Shahoyan, R.; Silva, S.; Soave, C.; Sonderegger, P.; Tarrago, X.; Temnikov, P.; Topilskaya, N.S.; Usai, G.; Vale, C.; Vercellin, E.; Willis, N.

    1999-01-01

    The cross section for J/Ψ production in Pb-Pb interactions at 158 GeV per nucleon is measured at the CERN SPS by the NA50 experiment. The final results from the 1995 run are presented here together with preliminary ones from the high-statistics 1996 run. An anomalous J/Ψ suppression is observed in Pb-Pb collisions as compared to extrapolations of the previous results obtained by the NA38 experiment with proton and lighter ion beams. The results of the two runs are in good agreement. The results from the 1996 run allow the study of the onset of the anomalous suppression within the same set of data, showing evidence of a sharp change of behaviour around a value of neutral transverse energy, as measured by our electromagnetic calorimeter, of about 50 GeV

  1. P-glycoprotein binds to ezrin at amino acid residues 149-242 in the FERM domain and plays a key role in the multidrug resistance of human osteosarcoma.

    Science.gov (United States)

    Brambilla, Daria; Zamboni, Silvia; Federici, Cristina; Lugini, Luana; Lozupone, Francesco; De Milito, Angelo; Cecchetti, Serena; Cianfriglia, Maurizio; Fais, Stefano

    2012-06-15

    Overexpression of the mdr1 gene encoding P-glycoprotein (Pgp) exerts a major role in reducing the effectiveness of cytotoxic therapy in osteosarcoma. The interaction between actin and Pgp has been shown to be instrumental in the establishment of multidrug resistance (MDR) in human tumor cells. The cytoskeleton linker ezrin exerts a pivotal role in maintaining the functional connection between actin and Pgp. We investigated the role of ezrin in a human multidrug-resistant osteosarcoma cell line overexpressing Pgp and compared it to its counterpart that overexpresses an ezrin deletion mutant. The results showed that Pgp binds at amino acid residues 149-242 of the N-terminal domain of ezrin. The interaction between ezrin and Pgp occurs in the plasma membrane of MDR cells, where they also co-localize with the ganglioside G(M1) located in lipid rafts. The overexpression of the ezrin deletion mutant entirely restored drug susceptibility of osteosarcoma cells, consistent with Pgp dislocation to cytoplasmic compartments and abrogation of G(M1) /Pgp co-localization at the plasma membrane. Our study provides evidence that ezrin exerts a key role in MDR of human osteosarcoma cells through a Pgp-ezrin-actin connection that is instrumental for the permanence of Pgp into plasma membrane lipid rafts. We also show for the first time that Pgp-binding site is localized to amino acid residues 149-242 of the ezrin Band 4.1, Ezrin/Radixin/Moesin (FERM) domain, thus proposing a specific target for future molecular therapy aimed at counteracting MDR in osteosarcoma patients. Copyright © 2011 UICC.

  2. Structural and Biochemical Characterization of a Copper-Binding Mutant of the Organomercurial Lyase MerB: Insight into the Key Role of the Active Site Aspartic Acid in Hg-Carbon Bond Cleavage and Metal Binding Specificity.

    Science.gov (United States)

    Wahba, Haytham M; Lecoq, Lauriane; Stevenson, Michael; Mansour, Ahmed; Cappadocia, Laurent; Lafrance-Vanasse, Julien; Wilkinson, Kevin J; Sygusch, Jurgen; Wilcox, Dean E; Omichinski, James G

    2016-02-23

    In bacterial resistance to mercury, the organomercurial lyase (MerB) plays a key role in the detoxification pathway through its ability to cleave Hg-carbon bonds. Two cysteines (C96 and C159; Escherichia coli MerB numbering) and an aspartic acid (D99) have been identified as the key catalytic residues, and these three residues are conserved in all but four known MerB variants, where the aspartic acid is replaced with a serine. To understand the role of the active site serine, we characterized the structure and metal binding properties of an E. coli MerB mutant with a serine substituted for D99 (MerB D99S) as well as one of the native MerB variants containing a serine residue in the active site (Bacillus megaterium MerB2). Surprisingly, the MerB D99S protein copurified with a bound metal that was determined to be Cu(II) from UV-vis absorption, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, and electron paramagnetic resonance studies. X-ray structural studies revealed that the Cu(II) is bound to the active site cysteine residues of MerB D99S, but that it is displaced following the addition of either an organomercurial substrate or an ionic mercury product. In contrast, the B. megaterium MerB2 protein does not copurify with copper, but the structure of the B. megaterium MerB2-Hg complex is highly similar to the structure of the MerB D99S-Hg complexes. These results demonstrate that the active site aspartic acid is crucial for both the enzymatic activity and metal binding specificity of MerB proteins and suggest a possible functional relationship between MerB and its only known structural homologue, the copper-binding protein NosL.

  3. The Key Lake project

    International Nuclear Information System (INIS)

    1991-01-01

    Key Lake is located in the Athabasca sand stone basin, 640 kilometers north of Saskatoon, Saskatchewan, Canada. The three sources of ore at Key Lake contain 70 100 tonnes of uranium. Features of the Key Lake Project were described under the key headings: work force, mining, mill process, tailings storage, permanent camp, environmental features, worker health and safety, and economic benefits. Appendices covering the historical background, construction projects, comparisons of western world mines, mining statistics, Northern Saskatchewan surface lease, and Key Lake development and regulatory agencies were included

  4. LOCKS AND KEYS SERVICE

    CERN Multimedia

    Locks and Keys Service

    2002-01-01

    The Locks and Keys service (ST/FM) will move from building 55 to building 570 from the 2nd August to the 9th August 2002 included. During this period the service will be closed. Only in case of extreme urgency please call the 164550. Starting from Monday, 12th August, the Locks and Keys Service will continue to follow the activities related to office keys (keys and locks) and will provide the keys for furniture. The service is open from 8h30 to 12h00 and from 13h00 to 17h30. We remind you that your divisional correspondents can help you in the execution of the procedures. We thank you for your comprehension and we remain at your service to help you in solving all the matters related to keys for offices and furniture. Locks and Keys Service - ST Division - FM Group

  5. Antibody-mediated suppression of grafted lymphoma. III. Evaluation of the role of thymic function, non-thymus-derived lymphocytes, macrophages, platelets, and polymorphonuclear leukocytes in syngeneic and allogeneic hosts

    International Nuclear Information System (INIS)

    Shin, H.S.; Hayden, M.; Langley, S.; Kaliss, N.; Smith, M.R.

    1975-01-01

    Syngeneic or allogeneic mice pretreated with sublethal whole-body irradiation were rendered incapable of suppressing the growth of grafted tumor cells sensitized with alloantibody. The growth of sensitized tumor cells was suppressed when they were mixed with donor effector cells from mice syngeneic or allogeneic to the recipients and then were inoculated in irradiated recipients. Three donor-host combinations were used to study the suppression of the murine lymphoma 6C3HED indigenous to C3H mice. These were C3H donor cells in C3H recipients, C57BL/6 donor cells in C3H recipients, or C57BL/6 donor cells in C57BL/6 recipients. In all three combinations, macrophages obtained from an inflammatory exudate, exudate lymphocytes not bearing theta antigen, and platelets were, in descending order of effectiveness, consistently active in restoring antibody-mediated suppression of tumor growth in irradiated hosts. Prior irradiation of the transferred lymphocytes somewhat diminished their effectiveness. Freeze-thawed or heat-killed macrophages (but not freeze-thawed platelets or lymphocytes) were effective in restoration. Peripheral blood mononuclear leukocytes and splenic lymphoid cells were not active in the recipients syngeneic to the donor cells but were active in recipients allogeneic to the donor cells. Polymorphonuclear leukocytes isolated from peripheral blood or an inflammatory exudate were not active. Intact thymic function seems unimportant since antibody-mediated suppression took place as effectively in thymectomized mice as in normal controls. (U.S.)

  6. Quantum dense key distribution

    International Nuclear Information System (INIS)

    Degiovanni, I.P.; Ruo Berchera, I.; Castelletto, S.; Rastello, M.L.; Bovino, F.A.; Colla, A.M.; Castagnoli, G.

    2004-01-01

    This paper proposes a protocol for quantum dense key distribution. This protocol embeds the benefits of a quantum dense coding and a quantum key distribution and is able to generate shared secret keys four times more efficiently than the Bennet-Brassard 1984 protocol. We hereinafter prove the security of this scheme against individual eavesdropping attacks, and we present preliminary experimental results, showing its feasibility

  7. 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.

  8. 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.

  9. 4-1BB Signaling in Conventional T Cells Drives IL-2 Production That Overcomes CD4+CD25+FoxP3+ T Regulatory Cell Suppression.

    Directory of Open Access Journals (Sweden)

    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.

  10. Radiation effluent suppression system

    International Nuclear Information System (INIS)

    Watanabe, Atsushi.

    1992-01-01

    In a radiation release suppression system upon accident, an electromotive valve, a pneumatic operation valve or a manual operation valve is disposed to gas ventilation pipelines which are extended from both of a dry well and a wet well of a reactor container to a stuck. In addition, a combination filter of a metal fiber filter made of stainless steel etc. and an activated carbon fiber filter is disposed in the midway of pipelines in a reactor building. With such a constitution, the inside of the container can be depressurized (prevention of ruptures) and the amount of radioactive substances released to circumstances is remarkably suppressed by the effect of radioactive substance capturing effect of the metal fiber filter made of stainless steel etc. disposed in the vent pipe in the container and a radioactive substance capturing effect by the combination filter of the metal fiber filter made of stainless steel, etc. and the activated carbon fiber filter disposed in the gas ventilation pipelines even upon occurrence of an accident exceeding design basis. Systems can be simplified and minimized, and cost down can also be attained. (N.H.)

  11. Planck-suppressed operators

    International Nuclear Information System (INIS)

    Assassi, Valentin; Baumann, Daniel; Green, Daniel; McAllister, Liam

    2014-01-01

    We show that the recent Planck limits on primordial non-Gaussianity impose strong constraints on light hidden sector fields coupled to the inflaton via operators suppressed by a high mass scale Λ. We study a simple effective field theory in which a hidden sector field is coupled to a shift-symmetric inflaton via arbitrary operators up to dimension five. Self-interactions in the hidden sector lead to non-Gaussianity in the curvature perturbations. To be consistent with the Planck limit on local non-Gaussianity, the coupling to any hidden sector with light fields and natural cubic couplings must be suppressed by a very high scale Λ > 10 5 H. Even if the hidden sector has Gaussian correlations, nonlinearities in the mixing with the inflaton still lead to non-Gaussian curvature perturbations. In this case, the non-Gaussianity is of the equilateral or orthogonal type, and the Planck data requires Λ > 10 2 H

  12. Genome-Wide Bimolecular Fluorescence Complementation-Based Proteomic Analysis of Toxoplasma gondii ROP18’s Human Interactome Shows Its Key Role in Regulation of Cell Immunity and Apoptosis

    Directory of Open Access Journals (Sweden)

    Jing Xia

    2018-02-01

    Full Text Available Toxoplasma gondii rhoptry protein ROP18 (TgROP18 is a key virulence factor secreted into the host cell during invasion, where it modulates the host cell response by interacting with its host targets. However, only a few TgROP18 targets have been identified. In this study, we applied a high-throughput protein–protein interaction (PPI screening in human cells using bimolecular fluorescence complementation (BiFC to identify the targets of Type I strain ROP18 (ROP18I and Type II strain ROP18 (ROP18II. From a pool of more than 18,000 human proteins, 492 and 141 proteins were identified as the targets of ROP18I and ROP18II, respectively. Gene ontology, search tool for the retrieval of interacting genes/proteins PPI network, and Ingenuity pathway analyses revealed that the majority of these proteins were associated with immune response and apoptosis. This indicates a key role of TgROP18 in manipulating host’s immunity and cell apoptosis, which might contribute to the immune escape and successful parasitism of the parasite. Among the proteins identified, the immunity-related proteins N-myc and STAT interactor, IL20RB, IL21, ubiquitin C, and vimentin and the apoptosis-related protein P2RX1 were further verified as ROP18I targets by sensitized emission-fluorescence resonance energy transfer (SE-FRET and co-immunoprecipitation. Our study substantially contributes to the current limited knowledge on human targets of TgROP18 and provides a novel tool to investigate the function of parasite effectors in human cells.

  13. 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.

  14. Key improvements to XTR

    NARCIS (Netherlands)

    Lenstra, A.K.; Verheul, E.R.; Okamoto, T.

    2000-01-01

    This paper describes improved methods for XTR key representation and parameter generation (cf. [4]). If the field characteristic is properly chosen, the size of the XTR public key for signature applications can be reduced by a factor of three at the cost of a small one time computation for the

  15. 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.

  16. Key Principles of Superfund Remedy Selection

    Science.gov (United States)

    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.

  17. Acetyltransferases and tumour suppression

    International Nuclear Information System (INIS)

    Phillips, A C; Vousden, Karen H

    2000-01-01

    The acetyltransferase p300 was first identified associated with the adenoviral transforming protein E1A, suggesting a potential role for p300 in the regulation of cell proliferation. Direct evidence demonstrating a role for p300 in human tumours was lacking until the recentl publication by Gayther et al, which strongly supports a role for p300 as a tumour suppressor. The authors identify truncating mutations associated with the loss or mutation of the second allele in both tumour samples and cell lines, suggesting that loss of p300 may play a role in the development of a subset of human cancers

  18. Key to Language Learning Success

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. 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.

  1. Key Facts about Tularemia

    Science.gov (United States)

    ... Submit What's this? Submit Button Key Facts About Tularemia Recommend on Facebook Tweet Share Compartir This fact ... and Prevention (CDC) Tularemia Web site . What is Tularemia? Tularemia is a potentially serious illness that occurs ...

  2. Key technologies book

    International Nuclear Information System (INIS)

    1997-01-01

    In this book can be found all the useful information on the French industry key technologies of the years 2000-2005. 136 technologies at the junction of the science advances and of the markets expectations are divided into 9 sectors. Among them, only 4 are interesting here: the environment, the transports, the materials and the energy. In 1995, the secretary's office of State for industry has published a first synthesis book on these key technologies. This 1997 new key technologies book extends and completes the initial study. For each key technology, an encyclopedic sheet is given. Each sheet combines thus some exact and practical information on: advance state of the technology, market characteristics, development forecasts, occupation and involved sectors, technology acquisition cost, research programs but also contacts of the main concerned efficiency poles. (O.M.)

  3. The Key Lake project

    International Nuclear Information System (INIS)

    Glattes, G.

    1985-01-01

    Aspects of project financing for the share of the Canadian subsidiary of Uranerzbergbau-GmbH, Bonn, in the uranium mining and milling facility at Key Lake, Saskatchewan, by a Canadian bank syndicate. (orig.) [de

  4. 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

  5. Key drivers of airline loyalty.

    Science.gov (United States)

    Dolnicar, Sara; Grabler, Klaus; Grün, Bettina; Kulnig, Anna

    2011-10-01

    This study investigates drivers of airline loyalty. It contributes to the body of knowledge in the area by investigating loyalty for a number of a priori market segments identified by airline management and by using a method which accounts for the multi-step nature of the airline choice process. The study is based on responses from 687 passengers. Results indicate that, at aggregate level, frequent flyer membership, price, the status of being a national carrier and the reputation of the airline as perceived by friends are the variables which best discriminate between travellers loyal to the airline and those who are not. Differences in drivers of airline loyalty for a number of segments were identified. For example, loyalty programs play a key role for business travellers whereas airline loyalty of leisure travellers is difficult to trace back to single factors. For none of the calculated models satisfaction emerged as a key driver of airline loyalty.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Pressure suppression device

    International Nuclear Information System (INIS)

    Yoshida, Toyokazu.

    1976-01-01

    Purpose: To provide a pressure suppression device for a gas cooled reactor wherein the coolant is discharged in a reactor building by a loss-of-coolant accident or the like, the increase in the pressure and temperature is controlled and thermal energy of the discharged coolant of high temperature and high pressure can be absorbed. Constitution: A low heat source unit is provided at the upper part in an inner space of a reactor building provided around the reactor, and at the upper part of the low heat source unit a stirring fan for mixing gas within the building, and a low heat source circulating the low heat source through a pipe is connected to the low heat source unit. The low heat source unit is provided with the pipe arranged in a spiral shape at the upper part of the space of the unit, and a large number of fins are provided at the outer surface of the pipe for increasing the transmission area and improve the heat exchange. When the coolant of high temperature and high pressure has been lost in the building, the thermal energy of the coolant is absorbed by the low heat source unit. (Aizawa, K.)

  11. 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