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Sample records for bnip3 upregulation precedes

  1. Regulation of the mTOR Pathway by a Novel Rheb Binding Protein BNIP3

    National Research Council Canada - National Science Library

    Guan, Kun-Liang

    2008-01-01

    .... We demonstrate that BNIP3 plays a critical role in hypoxia-induced mTOR inhibition. Furthermore we found that BNIP3 itself has a growth inhibitory activity and inactivation of BNIP3 promotes cell growth...

  2. Hypoxia-Induced Autophagy Is Mediated through Hypoxia-Inducible Factor Induction of BNIP3 and BNIP3L via Their BH3 Domains▿ †

    OpenAIRE

    Bellot, Grégory; Garcia-Medina, Raquel; Gounon, Pierre; Chiche, Johanna; Roux, Danièle; Pouysségur, Jacques; Mazure, Nathalie M.

    2009-01-01

    While hypoxia-inducible factor (HIF) is a major actor in the cell survival response to hypoxia, HIF also is associated with cell death. Several studies implicate the HIF-induced putative BH3-only proapoptotic genes bnip3 and bnip3l in hypoxia-mediated cell death. We, like others, do not support this assertion. Here, we clearly demonstrate that the hypoxic microenvironment contributes to survival rather than cell death by inducing autophagy. The ablation of Beclin1, a major actor of autophagy,...

  3. Down-regulation of transcription of the proapoptotic gene BNip3 in cultured astrocytes by murine coronavirus infection

    International Nuclear Information System (INIS)

    Cai Yingyun; Liu Yin; Yu Dongdong; Zhang Xuming

    2003-01-01

    Murine coronavirus mouse hepatitis virus (MHV) causes encephalitis and demyelination in the central nervous system of susceptible rodents. Astrocytes are the major target for MHV persistence. However, the mechanisms by which astrocytes survive MHV infection and permit viral persistence are not known. Here we performed DNA microarray analysis on differential gene expression in astrocyte DBT cells by MHV infection and found that the mRNA of the proapoptotic gene BNip3 was significantly decreased following MHV infection. This finding was further confirmed by quantitative reverse transcription-polymerase chain reaction, Western blot analysis, and BNip3-promoter-luciferase reporter system. Interestingly, infection with live and ultraviolet light-inactivated viruses equally repressed BNip3 expression, indicating that the down-regulation of BNip3 expression does not require virus replication and is mediated during cell entry. Furthermore, treatment of cells with chloroquine, which blocks the acidification of endosomes, significantly inhibited the repression of the BNip3 promoter activity induced by the acidic pH-dependent MHV mutant OBLV60, which enters cells via endocytosis, indicating that the down-regulation of BNip3 expression is mediated by fusion between viral envelope and cell membranes during entry. Deletion analysis showed that the sequence between nucleotides 262 and 550 of the 588-base-pair BNip3 promoter is necessary and sufficient for driving the BNip3 expression and that it contains signals that are responsible for MHV-induced down-regulation of BNip3 expression in DBT cells. These results may provide insights into the mechanisms by which MHV evades host antiviral defense and promotes cell survival, thereby allowing its persistence in the host astrocytes

  4. Autophagy capacity and sub-mitochondrial heterogeneity shape Bnip3-induced mitophagy regulation of apoptosis.

    Science.gov (United States)

    Choe, Sehyo Charley; Hamacher-Brady, Anne; Brady, Nathan Ryan

    2015-08-08

    Mitochondria are key regulators of apoptosis. In response to stress, BH3-only proteins activate pro-apoptotic Bcl2 family proteins Bax and Bak, which induce mitochondrial outer membrane permeabilization (MOMP). While the large-scale mitochondrial release of pro-apoptotic proteins activates caspase-dependent cell death, a limited release results in sub-lethal caspase activation which promotes tumorigenesis. Mitochondrial autophagy (mitophagy) targets dysfunctional mitochondria for degradation by lysosomes, and undergoes extensive crosstalk with apoptosis signaling, but its influence on apoptosis remains undetermined. The BH3-only protein Bnip3 integrates apoptosis and mitophagy signaling at different signaling domains. Bnip3 inhibits pro-survival Bcl2 members via its BH3 domain and activates mitophagy through its LC3 Interacting Region (LIR), which is responsible for binding to autophagosomes. Previously, we have shown that Bnip3-activated mitophagy prior to apoptosis induction can reduce mitochondrial activation of caspases, suggesting that a reduction to mitochondrial levels may be pro-survival. An outstanding question is whether organelle dynamics and/or recently discovered subcellular variations of protein levels responsible for both MOMP sensitivity and crosstalk between apoptosis and mitophagy can influence the cellular apoptosis decision event. To that end, here we undertook a systems biology analysis of mitophagy-apoptosis crosstalk at the level of cellular mitochondrial populations. Based on experimental findings, we developed a multi-scale, hybrid model with an individually adaptive mitochondrial population, whose actions are determined by protein levels, embedded in an agent-based model (ABM) for simulating subcellular dynamics and local feedback via reactive oxygen species signaling. Our model, supported by experimental evidence, identified an emergent regulatory structure within canonical apoptosis signaling. We show that the extent of mitophagy is

  5. Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3

    Directory of Open Access Journals (Sweden)

    Li S

    2016-02-01

    Full Text Available Sainan Li, Yujing Xia, Kan Chen, Jingjing Li, Tong Liu, Fan Wang, Jie Lu, Yingqun Zhou, Chuanyong Guo Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Background: Epigallocatechin-3-gallate (EGCG is the most effective compound in green tea, and possesses a wide range of beneficial effects, including anti-inflammatory, antioxidant, antiobesity, and anticancer effects. In this study, we investigated the protective effects of EGCG in concanavalin A (ConA-induced hepatitis in mice and explored the possible mechanisms involved in these effects.Methods: Balb/C mice were injected with ConA (25 mg/kg to induce acute autoimmune hepatitis, and EGCG (10 or 30 mg/kg was administered orally twice daily for 10 days before ConA injection. Serum liver enzymes, proinflammatory cytokines, and other marker proteins were determined 2, 8, and 24 hours after the ConA administration.Results: BNIP3 mediated cell apoptosis and autophagy in ConA-induced hepatitis. EGCG decreased the immunoreaction and pathological damage by reducing inflammatory factors, such as TNF-α, IL-6, IFN-γ, and IL-1β. EGCG also exhibited an antiapoptotic and antiautophagic effect by inhibiting BNIP3 via the IL-6/JAKs/STAT3 pathway.Conclusion: EGCG attenuated liver injury in ConA-induced hepatitis by downregulating IL-6/JAKs/STAT3/BNIP3-mediated apoptosis and autophagy. Keywords: concanavalin A, hepatitis, EGCG, autophagy, apoptosis, BNIP3, STAT3, JAKs, IL-6

  6. Blockade of epidermal growth factor receptors chemosensitizes breast cancer cells through up-regulation of Bnip3L

    NARCIS (Netherlands)

    Real, PJ; Benito, A; Cuevas, J; Berciano, MT; de Juan, A; Coffer, P; Gomez-Roman, J; Lafarga, M; Lopez-Vega, JM; Fernandez-Luna, JL

    2005-01-01

    Epidermal growth factor receptor-1 (EGFR) and EGFR-2 (HER2) have become major targets for cancer treatment. Blocking antibodies and small-molecule inhibitors are being used to silence the activity of these receptors in different tumors with varying efficacy. Thus, a better knowledge on the signaling

  7. Expression of apoptosis-related genes in the mouse skin during the first postnatal catagen stage, focused on localization of Bnip3L and caspase-12

    Czech Academy of Sciences Publication Activity Database

    Veselá, Barbora; Matalová, Eva

    2015-01-01

    Roč. 56, č. 4 (2015), s. 326-335 ISSN 0300-8207 Grant - others:GA ČR(CZ) GAP502/12/1285 Program:GA Institutional support: RVO:67985904 Keywords : apoptosis * Bnip3L * caspase-12 Subject RIV: ED - Physiology Impact factor: 1.411, year: 2015

  8. MiR-30c regulates cisplatin-induced apoptosis of renal tubular epithelial cells by targeting Bnip3L and Hspa5.

    Science.gov (United States)

    Du, Bin; Dai, Xiao-Meng; Li, Shuang; Qi, Guo-Long; Cao, Guang-Xu; Zhong, Ying; Yin, Pei-di; Yang, Xue-Song

    2017-08-10

    As a common anticancer drug, cisplatin has been widely used for treating tumors in the clinic. However, its side effects, especially its nephrotoxicity, noticeably restrict the application of cisplatin. Therefore, it is imperative to investigate the mechanism of renal injury and explore the corresponding remedies. In this study, we showed the phenotypes of the renal tubules and epithelial cell death as well as elevated cleaved-caspase3- and TUNEL-positive cells in rats intraperitoneally injected with cisplatin. Similar cisplatin-induced cell apoptosis was found in HK-2 and NRK-52E cells exposed to cisplatin as well. In both models of cisplatin-induced apoptosis in vivo and in vitro, quantitative PCR data displayed reductions in miR-30a-e expression levels, indicating that miR-30 might be involved in regulating cisplatin-induced cell apoptosis. This was further confirmed when the effects of cisplatin-induced cell apoptosis were found to be closely correlated with alterations in miR-30c expression, which were manipulated by transfection of either the miR-30c mimic or miR-30c inhibitor in HK-2 and NRK-52E cells. Using bioinformatics tools, including TargetScan and a gene expression database (Gene Expression Omnibus), Adrb1, Bnip3L, Hspa5 and MAP3K12 were predicted to be putative target genes of miR-30c in cisplatin-induced apoptosis. Subsequently, Bnip3L and Hspa5 were confirmed to be the target genes after determining the expression of these putative genes following manipulation of miR-30c expression levels in HK-2 cells. Taken together, our current experiments reveal that miR-30c is certainly involved in regulating the renal tubular cell apoptosis induced by cisplatin, which might supply a new strategy to minimize cisplatin-induced nephrotoxicity.

  9. FGF-2 Transcriptionally Down-Regulates the Expression of BNIP3L via PI3K/Akt/FoxO3a Signaling and Inhibits Necrosis and Mitochondrial Dysfunction Induced by High Concentrations of Hydrogen Peroxide in H9c2 Cells

    Directory of Open Access Journals (Sweden)

    Qian Chen

    2016-12-01

    Full Text Available Background/Aims: Cardiovascular disease is a growing major global public health problem. Necrosis is one of the main forms of cardiomyocyte death in heart disease. Oxidative stress is regarded as one of the key regulators of cardiac necrosis, which eventually leads to cardiovascular disease. Many pharmacological and in vitro studies have suggested that FGF-2 can act directly on cardiomyocytes to maintain the integrity and function of the myocardium and prevent damage during oxidative stress. However, the mechanisms by which FGF-2 rescues the myocardium from oxidative stress damage in cardiovascular disease remain unclear. The present study explored the protective effects of FGF-2 in the H2O2-induced necrosis of H9C2 cardiomyocytes as well as the possible signaling pathways involved. Methods: Necrosis of H9c2 cardiomyocytes was induced by H2O2 and assessed using a Cell Counting Kit-8 (CCK8 assay and flow cytometry analysis. The cells were pretreated with the PI3K/Akt inhibitor Wortmannin to investigate the possible involvement of the PI3K/Akt pathway in the protection by FGF-2. The levels of Akt, p-Akt, FoxO3a, p-FoxO3a, and BNIP3L were detected by Western blot. Chromatin immuno-precipitation (ChIP analysis was used to test whether FoxO3a binds directly to the BNIP3L promoter region. A luciferase assay was used to study the effects of FoxO3a on BNIP3L gene promoter activity. Mitochondrial ΔΨM was quantified using tetramethylrhodamine methyl ester perchlorate (TMRM. The mitochondrial oxygen consumption rate (OCR was assessed with a Seahorse XF24 Analyzer. Results: Treatment with H2O2 decreased the phosphorylation of Akt and FoxO3a, and it induced the nuclear localization of FoxO3a and the necrosis of H9c2 cells. These effects of H2O2 were abrogated by pretreatment with FGF-2. Furthermore, the protective effects of FGF-2 were abolished by the PI3K/Akt inhibitor Wortmannin. ChIP analyses indicated that FoxO3a binds directly to the BNIP3L promoter

  10. Coordinated Upregulation of Mitochondrial Biogenesis and Autophagy in Breast Cancer Cells: The Role of Dynamin Related Protein-1 and Implication for Breast Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Peng Zou

    2016-01-01

    Full Text Available Overactive mitochondrial fission was shown to promote cell transformation and tumor growth. It remains elusive how mitochondrial quality is regulated in such conditions. Here, we show that upregulation of mitochondrial fission protein, dynamin related protein-1 (Drp1, was accompanied with increased mitochondrial biogenesis markers (PGC1α, NRF1, and Tfam in breast cancer cells. However, mitochondrial number was reduced, which was associated with lower mitochondrial oxidative capacity in breast cancer cells. This contrast might be owing to enhanced mitochondrial turnover through autophagy, because an increased population of autophagic vacuoles engulfing mitochondria was observed in the cancer cells. Consistently, BNIP3 (a mitochondrial autophagy marker and autophagic flux were significantly upregulated, indicative of augmented mitochondrial autophagy (mitophagy. The upregulation of Drp1 and BNIP3 was also observed in vivo (human breast carcinomas. Importantly, inhibition of Drp1 significantly suppressed mitochondrial autophagy, metabolic reprogramming, and cancer cell viability. Together, this study reveals coordinated increase of mitochondrial biogenesis and mitophagy in which Drp1 plays a central role regulating breast cancer cell metabolism and survival. Given the emerging evidence of PGC1α contributing to tumor growth, it will be of critical importance to target both mitochondrial biogenesis and mitophagy for effective cancer therapeutics.

  11. Information, Precedent, and Statute

    NARCIS (Netherlands)

    O. Yalnazov (Orlin)

    2017-01-01

    textabstractI compare precedent and statute in cost-effectiveness terms. To make laws, a lawmaker needs information. Information has a cost. That cost is sensitive to the choice of law production technology. The orthodoxy is that the courts acquire information more cheaply. Litigants volunteer it in

  12. Conditions precedent and indemnities

    International Nuclear Information System (INIS)

    Nielsen, A.D.

    1999-01-01

    The use of certain conditions which allow purchase and sale agreements to be voided without any liability to either the vendor or purchaser are discussed. The drafting issues that arise when preparing these conditions are described and some common types of conditions precedent found in oil and gas purchase and sale transactions are explained. A 'conditions precedent' was defined as being something which must happen before an interest can vest or grow or before an obligation can be performed. Vendors and purchasers use conditions precedent to provide protection against having to conclude a transaction in circumstances that are not acceptable to them. The manner in which indemnity provisions in an oil and gas purchase and sale agreement work, is also explained. These usually relate to breaches of the contract by either vendors or purchasers. Indemnity clauses are used to allocate risk between the vendor and the purchaser and to set out the mechanics by which either party may make a claim against the other. Ways in which to prepare indemnity clauses are described. 2 refs

  13. PRECEDENCE AS A PSYCHOLINGUISTIC CATEGORY

    Directory of Open Access Journals (Sweden)

    Panarina Nadezhda Sergeevna

    2015-06-01

    Full Text Available The use of particular linguistic units by representatives of a linguacultural community as the most preferable verbal actions is not necessary to be a case of verbal operations with some culturally specific knowledge. The analysis of a psychosocial mechanism used for generation and verbalization of such a knowledge allows to define the nature of precedence as a characteristic of meaning that is being effected in a speech act. The development of precedent meaning indispensably assumes not only generation of the definition component, but also entry into a structure of a culturological component meaning. The culturological component reflects a relationship between a subject-concept component of the meaning and the other elements of a speech situation – the relationship, which is notional for a person. Importance of the relationship consists in fact that definition of its content represents to a person their social identity. Until a person understands the content of relationship, which is represented by the culturological component, the use of corresponding linguistic units to nominate new objects of reality is a supraliminal appeal to the precedent knowledge, a speech act. But for new acts of usage the main thing is definitely quality of relationship as a characteristic of the cultural group stability, and the linguistic unit usage derives a new function. When the culturological component of the meaning is not included into generalization, since it is irrelevant one, and the core of meaning is composed of new and more relevant for the usage features, you can no more realize the inner form of the precedent meaning. The outer form is still relevant, since it is kept in mind by the representatives of linguaculture as the one which is preferable for usage. In this case the linguistic unit is just a tool not related to verbal representation of socially significant attitude, and its usage is a speech operation, a way to perform different speech acts

  14. Precedent Phenomena in Quebecois Linguistic World View

    Directory of Open Access Journals (Sweden)

    Ксения Эдуардовна Болотина

    2016-12-01

    Full Text Available This article is devoted to the linguocultural analysis of precedent phenomena as parts of Quebecois’ cognitive base. Precedent phenomena being cultural facts are one of the key issues in modern linguistic and cognitive studies. By precedent phenomena we mean, according to Y.E. Prohorov, such entities when verbalized in discourse that refer to a certain cultural fact behind them. In the article the precedent phenomena such as precedent text, precedent situation, precedent utterance, and precedent name are analyzed. The main theses of the precedence theory given in the article (Y.N. Karaulov, Y.E. Prohorov, V.V. Krasnyh, D.B. Gudkov are at the heart of precedence studies on the basis of different languages. However, a complex analysis of precedent phenomena in the Quebec national variant of French is new to Russian linguistics. The study of precedent phenomena enables us to elicit features of their functioning in ethnospecific discourse and determine cultural dominants existing in Quebecois’ linguistic world view. Given the fact that the size of the article is limited, we undertooke the analysis of eight phenomena precedent of the bearers of Quebec linguoculture. The choice of phenomena is determined by the frequency of their use in discourse. The facts analyzed are of national character, i.e. known to all members of the linguocultural community. A certain cultural fact is at the very core of each precedent phenomenon given in the article. To get the whole picture we analysed historic, political, and cultural context connected to the precedent phenomena in question. The study enables us to elicit distinctive features that are at the core of each phenomenon. The results are backed with the supportive material drawn from analysis of different types of discourse. The analysis of precedent phenomena undertaken in this article allows us to reconstruct, to a certain extent, Quebec cultural space and is a stepping stone to the reconstruction of the

  15. Precedent Names of Chinese National Culture

    Directory of Open Access Journals (Sweden)

    Валентина Алексеевна Ленинцева

    2015-12-01

    Full Text Available The article presents an analysis of precedent names as symbols of precedent phenomena in the material and spiritual culture of the Chinese. An evaluation of daily events and the attitude of the Chinese towards the world are reflected in the vocabulary of their language. The symbols of precedent phenomena can be proper names (anthroponomy, names of places, the date, as well as figurative and expressive means of language (idioms, sayings. Precedent names as symbols of precedent phenomena vividly and accurately capture the above-mentioned points, and encompass almost all spheres of life, history and spiritual development. The subject of our study are national precedent phenomena that define the ethno-cultural specificity, reflecting the history and culture of the Chinese people and their national character. Representatives of different cultures have different perceptions of the same precedent phenomena. Inadequate understanding of national invariants of precedent phenomena is often the source of communication failures. The aim of this paper is to highlight precedent names as a symbol of precedent phenomena in the discourse of the Chinese linguocultural community. For this purpose a classification of precedent names in Chinese was carried out. Precedent names which play an important role in shaping the Chinese national consciousness were taken from the Chinese-Russian Dictionary.

  16. Syntactic Idioms and Precedent Phenomena: Intersection Zones

    Directory of Open Access Journals (Sweden)

    Hanna Sytar

    2016-08-01

    Full Text Available Background: One examined mainly structural and semantic features of syntactic idioms so far. The pragmatic dimension of these original units that are on the verge of syntax and phraseology, has not been highlighted properly in the scientific literature, so it needs theoretical understanding. The combination of syntactic idiom and phraseological phenomenon refers to the communication techniques impacting on message recipient. Purpose: to analyze the intersection zones of syntactic idioms and precedent phenomena. Results: Analysis of the collected factual material allows to distinguish two areas of interpenetration of syntactic idioms and precedent units: 1 construction of expression according to the phraseologized model, within which the position of variable component is filled by the precedent name or precedent expression; 2 the model of sentence itself is precedent, and lexical content does not comply with generally known one that does not affect on understanding of model content by recipient. With a combination of syntactic idiom and precedent phenomena speakers provide drawing of recipients’ attention, carry out a hidden influence on them, express their own attitude to the realities, so that perform phatic, manipulative and expressive-evaluative functions. The modifications and transformations of precedent expressions and names appeared to be regular in such interpenetrations. Discussion: The obtained results reflect the general trend towards transform (transformation, modification, variation, etc. of precedent, as well as phraseological units, and can be used for the analysis of patterns of their formation and modifications. Further research phase implies tracing patterns of syntactic idioms combination with other means of expressive syntax.

  17. Mandatory Vaccinations: Precedent and Current Laws

    National Research Council Canada - National Science Library

    Welborn, Angie A

    2005-01-01

    This report discusses the history legal precedent for mandatory vaccination laws and provides a brief overview of state laws that require certain individuals or populations to be vaccinated against...

  18. INTEGRATED APPROACH TO GENERATION OF PRECEDENCE RELATIONS AND PRECEDENCE GRAPHS FOR ASSEMBLY SEQUENCE PLANNING

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    An integrated approach to generation of precedence relations and precedence graphs for assembly sequence planning is presented, which contains more assembly flexibility. The approach involves two stages. Based on the assembly model, the components in the assembly can be divided into partially constrained components and completely constrained components in the first stage, and then geometric precedence relation for every component is generated automatically. According to the result of the first stage, the second stage determines and constructs all precedence graphs. The algorithms of these two stages proposed are verified by two assembly examples.

  19. Page JUDICIAL PRECEDENT IN THE NIGERIAN LEGAL SYSTEM

    African Journals Online (AJOL)

    Fr. Ikenga

    Judicial precedent is a basic principle of the administration of justice in .... precedent assume a natural position that is not different from any other ... L. Alexander, Precedent in a Companion to Philosophy of Law and Legal Theory 503-513,.

  20. Cochlear contributions to the precedence effect

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Bianchi, Federica; Dau, Torsten

    2013-01-01

    will overlap in time, giving rise to complex interactions that have not been fully understood in the human cochlea. The perceptual consequences of these BM IR interactions are of interest as lead-lag click pairs are often used to study localization and the precedence effect. The present study aimed...... at characterizing perceptual consequences of BM IR interactions in individual listeners based on click-evoked otoacoustic emissions (CEOAEs) and auditory brainstem responses (ABRs). Lag suppression, denoting the level difference between the CEOAE or wave-V response amplitude evoked by the first and the second...... of the precedence effect....

  1. Safe specification of operator precedence rules

    NARCIS (Netherlands)

    Afroozeh, A.; Brand, van den M.G.J.; Johnstone, A.; Scott, E.; Vinju, J.J.; Erwig, M.; Paige, R.F.; Van Wyk, E.

    2013-01-01

    In this paper we present an approach to specifying operator precedence based on declarative disambiguation constructs and an implementation mechanism based on grammar rewriting. We identify a problem with existing generalized context-free parsing and disambiguation technology: generating a correct

  2. Safe Specification of Operator Precedence Rules

    NARCIS (Netherlands)

    A. Afroozeh (Ali); M.G.J. van den Brand (Mark); A. Johnstone; E. Scott; J.J. Vinju (Jurgen); K. Czarnecki; G. Hedin

    2013-01-01

    htmlabstractIn this paper we present an approach to specifying opera- tor precedence based on declarative disambiguation constructs and an implementation mechanism based on grammar rewriting. We identify a problem with existing generalized context-free parsing and disambigua- tion technology:

  3. Oral lichen planus preceding concomitant lichen planopilaris.

    Science.gov (United States)

    Stoopler, Eric T; Alfaris, Sausan; Alomar, Dalal; Alawi, Faizan

    2016-09-01

    Lichen planus (LP) is an immune-mediated mucocutaneous disorder with a wide array of clinical presentations. Oral lichen planus (OLP) is characterized clinically by striae, desquamation, and/or ulceration. Lichen planopilaris (LPP), a variant of LP, affects the scalp, resulting in perifollicular erythema and scarring of cutaneous surfaces accompanied by hair loss. The association between OLP and LPP has been reported previously with scant information on concomitant or sequential disease presentation. We describe a patient with concomitant OLP and LPP, and to the best of our knowledge, this is the first report on OLP preceding the onset of LPP. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.

    Science.gov (United States)

    Sones, Jennifer L; Merriam, Audrey A; Seffens, Angelina; Brown-Grant, Dex-Ann; Butler, Scott D; Zhao, Anna M; Xu, Xinjing; Shawber, Carrie J; Grenier, Jennifer K; Douglas, Nataki C

    2018-05-01

    Preeclampsia (PE), a hypertensive disorder of pregnancy, is a leading cause of maternal and fetal morbidity and mortality. Although the etiology is unknown, PE is thought to be caused by defective implantation and decidualization in pregnancy. Pregnant blood pressure high (BPH)/5 mice spontaneously develop placentopathies and maternal features of human PE. We hypothesized that BPH/5 implantation sites have transcriptomic alterations. Next-generation RNA sequencing of implantation sites at peak decidualization, embryonic day (E)7.5, revealed complement gene up-regulation in BPH/5 vs. controls. In BPH/5, expression of complement factor 3 was increased around the decidual vasculature of E7.5 implantation sites and in the trophoblast giant cell layer of E10.5 placentae. Altered expression of VEGF pathway genes in E5.5 BPH/5 implantation sites preceded complement dysregulation, which correlated with abnormal vasculature and increased placental growth factor mRNA and VEGF 164 expression at E7.5. By E10.5, proangiogenic genes were down-regulated, whereas antiangiogenic sFlt-1 was up-regulated in BPH/5 placentae. We found that early local misexpression of VEGF genes and abnormal decidual vasculature preceded sFlt-1 overexpression and increased complement deposition in BPH/5 placentae. Our findings suggest that abnormal decidual angiogenesis precedes complement activation, which in turn contributes to the aberrant trophoblast invasion and poor placentation that underlie PE.-Sones, J. L., Merriam, A. A., Seffens, A., Brown-Grant, D.-A., Butler, S. D., Zhao, A. M., Xu, X., Shawber, C. J., Grenier, J. K., Douglas, N. C. Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.

  5. [Wide QRS tachycardia preceded by pacemaker spikes].

    Science.gov (United States)

    Romero, M; Aranda, A; Gómez, F J; Jurado, A

    2014-04-01

    The differential diagnosis and therapeutic management of wide QRS tachycardia preceded by pacemaker spike is presented. The pacemaker-mediated tachycardia, tachycardia fibrillo-flutter in patients with pacemakers, and runaway pacemakers, have a similar surface electrocardiogram, but respond to different therapeutic measures. The tachycardia response to the application of a magnet over the pacemaker could help in the differential diagnosis, and in some cases will be therapeutic, as in the case of a tachycardia-mediated pacemaker. Although these conditions are diagnosed and treated in hospitals with catheterization laboratories using the application programmer over the pacemaker, patients presenting in primary care clinic and emergency forced us to make a diagnosis and treat the haemodynamically unstable patient prior to referral. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  6. Segmentation precedes face categorization under suboptimal conditions

    Directory of Open Access Journals (Sweden)

    Carlijn eVan Den Boomen

    2015-05-01

    Full Text Available Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain, using electroencephalography (EEG. Surface segmentation and category content were both manipulated using texture-defined objects, including faces. This allowed us to study brain activity related to segmentation and to categorization. In the main experiment, participants viewed texture-defined objects for a duration of 800 ms. EEG results revealed that segmentation-related responses precede category-selective responses. Three additional experiments revealed that the presence and timing of categorization depends on stimulus properties and presentation duration. Photographic objects were presented for a long and short (92 ms duration and evoked fast category-selective responses in both cases. On the other hand, presentation of texture-defined objects for a short duration only evoked segmentation-related but no category-selective responses. Category-selective responses were much slower when evoked by texture-defined than by photographic objects. We suggest that in case of categorization of objects under suboptimal conditions, such as when low-level stimulus properties are not sufficient for fast object categorization, segmentation facilitates the slower categorization process.

  7. NEIGHBORHOOD TEST DESIGN BASED ON HISTORIC PRECEDENTS

    Directory of Open Access Journals (Sweden)

    Besim S. Hakim

    2012-07-01

    Full Text Available There have been various attempts to emulate traditional architecture and to experiment with the form and aesthetics of building design. However, learning from precedents of urban morphology is rare. This design study is a test at the neighborhood level using the pattern of traditional courtyard housing that is prevalent in the majority of historic towns and cities of North Africa and the Middle East. The study is undertaken at five levels of design enquiry: dwelling types, dwelling groups, neighborhood segment and community center. All of which are synthesized into a full prototype neighborhood comprising of 428 dwelling units covering an area that includes circulation and the community center, of 17.6 hectares. The test demonstrates that the traditional pattern of neighborhoods that are based on the typology of the courtyard dwelling as the initial generator of urban form may be used to develop a contemporary settlement pattern that is compatible with current necessities of lifestyle, vehicular circulation,  including parking and infrastructure achieving an attractive livable environment with an overall gross density, that includes a community center, of about 24 dwelling units per hectare.

  8. Segmentation precedes face categorization under suboptimal conditions.

    Science.gov (United States)

    Van Den Boomen, Carlijn; Fahrenfort, Johannes J; Snijders, Tineke M; Kemner, Chantal

    2015-01-01

    Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain, using electroencephalography (EEG). Surface segmentation and category content were both manipulated using texture-defined objects, including faces. This allowed us to study brain activity related to segmentation and to categorization. In the main experiment, participants viewed texture-defined objects for a duration of 800 ms. EEG results revealed that segmentation-related responses precede category-selective responses. Three additional experiments revealed that the presence and timing of categorization depends on stimulus properties and presentation duration. Photographic objects were presented for a long and short (92 ms) duration and evoked fast category-selective responses in both cases. On the other hand, presentation of texture-defined objects for a short duration only evoked segmentation-related but no category-selective responses. Category-selective responses were much slower when evoked by texture-defined than by photographic objects. We suggest that in case of categorization of objects under suboptimal conditions, such as when low-level stimulus properties are not sufficient for fast object categorization, segmentation facilitates the slower categorization process.

  9. Can monaural temporal masking explain the ongoing precedence effect?

    Science.gov (United States)

    Freyman, Richard L; Morse-Fortier, Charlotte; Griffin, Amanda M; Zurek, Patrick M

    2018-02-01

    The precedence effect for transient sounds has been proposed to be based primarily on monaural processes, manifested by asymmetric temporal masking. This study explored the potential for monaural explanations with longer ("ongoing") sounds exhibiting the precedence effect. Transient stimuli were single lead-lag noise burst pairs; ongoing stimuli were trains of 63 burst pairs. Unlike with transients, monaural masking data for ongoing sounds showed no advantage for the lead, and are inconsistent with asymmetric audibility as an explanation for ongoing precedence. This result, along with supplementary measurements of interaural time discrimination, suggests different explanations for transient and ongoing precedence.

  10. Grammar Engineering Support for Precedence Rule Recovery and Compatibility Checking

    NARCIS (Netherlands)

    Bouwers, E.; Bravenboer, M.; Visser, E.

    2007-01-01

    A wide range of parser generators are used to generate parsers for programming languages. The grammar formalisms that come with parser generators provide different approaches for defining operator precedence. Some generators (e.g. YACC) support precedence declarations, others require the grammar to

  11. Power Measures and Solutions for Games Under Precedence Constraints

    NARCIS (Netherlands)

    Algaba, Encarnación; van den Brink, René; Dietz, Chris

    2017-01-01

    Games under precedence constraints model situations, where players in a cooperative transferable utility game belong to some hierarchical structure, which is represented by an acyclic digraph (partial order). In this paper, we introduce the class of precedence power solutions for games under

  12. Complexity Analysis of Precedence Terminating Infinite Graph Rewrite Systems

    Directory of Open Access Journals (Sweden)

    Naohi Eguchi

    2015-05-01

    Full Text Available The general form of safe recursion (or ramified recurrence can be expressed by an infinite graph rewrite system including unfolding graph rewrite rules introduced by Dal Lago, Martini and Zorzi, in which the size of every normal form by innermost rewriting is polynomially bounded. Every unfolding graph rewrite rule is precedence terminating in the sense of Middeldorp, Ohsaki and Zantema. Although precedence terminating infinite rewrite systems cover all the primitive recursive functions, in this paper we consider graph rewrite systems precedence terminating with argument separation, which form a subclass of precedence terminating graph rewrite systems. We show that for any precedence terminating infinite graph rewrite system G with a specific argument separation, both the runtime complexity of G and the size of every normal form in G can be polynomially bounded. As a corollary, we obtain an alternative proof of the original result by Dal Lago et al.

  13. 10 CFR 205.11 - Order of precedence.

    Science.gov (United States)

    2010-01-01

    ... precedence. (a) If there is any conflict or inconsistency between the provisions of this part and any other... prenotification and reporting and subpart J of part 212 of this chapter shall control with respect to accounting...

  14. Routing Cooperating Vehicles to Perform Precedence-Linked Tasks

    National Research Council Canada - National Science Library

    Vakhutinsky, Andrew; Wu, Cynara

    2005-01-01

    The problem of scheduling cooperating vehicles is a generalization of the classical vehicle routing problem where certain tasks are linked by precedence constraints and vehicles have varying constrained resources...

  15. Ludic Function of Precedent-Related Phenomena in Media Discourse

    Directory of Open Access Journals (Sweden)

    Yu. M. Velykoroda

    2016-12-01

    Full Text Available The aim of this paper is to determine the ludic function of precedent-related phenomena as a type of intertextuality. The analysis is done on the basis of relevance theoretic approach, through which we aim to show the additional cognitive effect which is created by precedent-related phenomena in media discourse, and this comic effect serves as a foundation for the ludic function of these units.

  16. Cytosolic DNA Sensor Upregulation Accompanies DNA Electrotransfer in B16.F10 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Katarina Znidar

    2016-01-01

    Full Text Available In several preclinical tumor models, antitumor effects occur after intratumoral electroporation, also known as electrotransfer, of plasmid DNA devoid of a therapeutic gene. In mouse melanomas, these effects are preceded by significant elevation of several proinflammatory cytokines. These observations implicate the binding and activation of intracellular DNA-specific pattern recognition receptors or DNA sensors in response to DNA electrotransfer. In tumors, IFNβ mRNA and protein levels significantly increased. The mRNAs of several DNA sensors were detected, and DAI, DDX60, and p204 tended to be upregulated. These effects were accompanied with reduced tumor growth and increased tumor necrosis. In B16.F10 cells in culture, IFNβ mRNA and protein levels were significantly upregulated. The mRNAs for several DNA sensors were present in these cells; DNA-dependent activator of interferon regulatory factor (DAI, DEAD (Asp-Glu-Ala-Asp box polypeptide 60 (DDX60, and p204 were significantly upregulated while DDX60 protein levels were coordinately upregulated. Upregulation of DNA sensors in tumors could be masked by the lower transfection efficiency compared to in vitro or to dilution by other tumor cell types. Mirroring the observation of tumor necrosis, cells underwent a significant DNA concentration-dependent decrease in proliferation and survival. Taken together, these results indicate that DNA electrotransfer may cause the upregulation of several intracellular DNA sensors in B16.F10 cells, inducing effects in vitro and potentially in vivo.

  17. Moxibustion upregulates hippocampal progranulin expression

    Directory of Open Access Journals (Sweden)

    Tao Yi

    2016-01-01

    Full Text Available In China, moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome, but its mechanisms are largely unknown. More recently, the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome, and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis. In the present study, we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms. Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome. The acupoints Guanyuan (CV4 and Zusanli (ST36, bilateral were simultaneously administered moxibustion. Untreated chronic fatigue syndrome rats and normal rats were used as controls. Results from the forced swimming test, open field test, tail suspension test, real-time PCR, enzyme-linked immunosorbent assay, and western blot assay showed that moxibustion treatment decreased mRNA expression of corticotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone and corticosterone levels in plasma, and markedly increased progranulin mRNA and protein expression in the hippocampus. These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome, at least in part, by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.

  18. Preceding trauma in childhood hematogenous bone and joint infections.

    Science.gov (United States)

    Pääkkönen, Markus; Kallio, Markku J T; Lankinen, Petteri; Peltola, Heikki; Kallio, Pentti E

    2014-03-01

    Preceding trauma may play a role in the etiology and pathogenesis of hematogenous bone and joint infections. Among 345 children with an acute hematogenous bone and/or joint infection, 20% reported trauma during a 2-week period leading to infection. Blunt impact, bruises, or excoriations were commonly reported. The rate was similar to that in the general pediatric population obtained from the literature. In the study group, patients with and without trauma were similar in age, serum C-reactive protein and erythrocyte sedimentation rate, length of hospitalization, and late sequelae. Preceding minor trauma did not prove to be significant as an etiological or as a prognostic factor.

  19. Notes on the Altazor case (preceded by a theoretical drifting

    Directory of Open Access Journals (Sweden)

    Daniel Glaydson Ribeiro

    2012-06-01

    Full Text Available Precede by a brief theoretical drifting about the great poet and the conditions of its appearance (mythic and/or mythological - and also a differential hypothesis about the lyric and the epic -, this is an essay engaged in comprehending the narrative entitled Altazor, eighty years after its publication.

  20. Impact of preceding crop on alfalfa competitiveness with weeds

    Science.gov (United States)

    Organic producers would like to include no-till practices in their farming systems. We are seeking to develop a continuous no-till system for organic farming, based on a complex rotation that includes a 3-year sequence of alfalfa. In this study, we evaluated impact of preceding crop on weed infest...

  1. Solon of Athens as a precedent for Plutarch's authorial persona

    NARCIS (Netherlands)

    Klooster, Julia

    2018-01-01

    Solon is the subject of both a Plutarchan biography (Solon) and a philosophical dialogue (Convivium septem sapientium). In this article I argue that Plutarch creates a precedent for his authorial persona of wise but modest adviser of the ruling class under the Roman empire in the figure of the

  2. Metrical expectations from preceding prosody influence perception of lexical stress.

    Science.gov (United States)

    Brown, Meredith; Salverda, Anne Pier; Dilley, Laura C; Tanenhaus, Michael K

    2015-04-01

    Two visual-world experiments tested the hypothesis that expectations based on preceding prosody influence the perception of suprasegmental cues to lexical stress. The results demonstrate that listeners' consideration of competing alternatives with different stress patterns (e.g., 'jury/gi'raffe) can be influenced by the fundamental frequency and syllable timing patterns across material preceding a target word. When preceding stressed syllables distal to the target word shared pitch and timing characteristics with the first syllable of the target word, pictures of alternatives with primary lexical stress on the first syllable (e.g., jury) initially attracted more looks than alternatives with unstressed initial syllables (e.g., giraffe). This effect was modulated when preceding unstressed syllables had pitch and timing characteristics similar to the initial syllable of the target word, with more looks to alternatives with unstressed initial syllables (e.g., giraffe) than to those with stressed initial syllables (e.g., jury). These findings suggest that expectations about the acoustic realization of upcoming speech include information about metrical organization and lexical stress and that these expectations constrain the initial interpretation of suprasegmental stress cues. These distal prosody effects implicate online probabilistic inferences about the sources of acoustic-phonetic variation during spoken-word recognition. (c) 2015 APA, all rights reserved.

  3. Reasoning with Previous Decisions: Beyond the Doctrine of Precedent

    DEFF Research Database (Denmark)

    Komárek, Jan

    2013-01-01

    in different jurisdictions use previous judicial decisions in their argument, we need to move beyond the concept of precedent to a wider notion, which would embrace practices and theories in legal systems outside the Common law tradition. This article presents the concept of ‘reasoning with previous decisions...... law method’, but they are no less rational and intellectually sophisticated. The reason for the rather conceited attitude of some comparatists is in the dominance of the common law paradigm of precedent and the accompanying ‘case law method’. If we want to understand how courts and lawyers......’ as such an alternative and develops its basic models. The article first points out several shortcomings inherent in limiting the inquiry into reasoning with previous decisions by the common law paradigm (1). On the basis of numerous examples provided in section (1), I will present two basic models of reasoning...

  4. Motility precedes egress of malaria parasites from oocysts

    Science.gov (United States)

    Klug, Dennis; Frischknecht, Friedrich

    2017-01-01

    Malaria is transmitted when an infected Anopheles mosquito deposits Plasmodium sporozoites in the skin during a bite. Sporozoites are formed within oocysts at the mosquito midgut wall and are released into the hemolymph, from where they invade the salivary glands and are subsequently transmitted to the vertebrate host. We found that a thrombospondin-repeat containing sporozoite-specific protein named thrombospondin-releated protein 1 (TRP1) is important for oocyst egress and salivary gland invasion, and hence for the transmission of malaria. We imaged the release of sporozoites from oocysts in situ, which was preceded by active motility. Parasites lacking TRP1 failed to migrate within oocysts and did not egress, suggesting that TRP1 is a vital component of the events that precede intra-oocyst motility and subsequently sporozoite egress and salivary gland invasion. DOI: http://dx.doi.org/10.7554/eLife.19157.001 PMID:28115054

  5. Cardiac tamponade preceding skin involvement in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    L. Bozzola

    2011-09-01

    Full Text Available The frequency of pericardial involvement in Systemic Sclerosis (SSc is high on autoptic or echocardiographic studies, but the clinical recognition of pericarditis with or without effusion is rare. We describe a case of a 71-year-old female with no previous history of heart disease, who presented with a large pericardial effusion and tamponade that required pericardial drain. She had suffered from Raynaud’s phenomenon since 25 years. Six weeks after hospital discharge she complained of skin hardening on left leg. Pericardial tamponade is a very rare manifestation of SSc and occurs both early or late in the course of the disease, but in our case it preceded the recognition of scleroderma. We have only identified two other cases of pericardial effusion preceding cutaneous involvement in scleroderma.

  6. Extended precedence preservative crossover for job shop scheduling problems

    Science.gov (United States)

    Ong, Chung Sin; Moin, Noor Hasnah; Omar, Mohd

    2013-04-01

    Job shop scheduling problems (JSSP) is one of difficult combinatorial scheduling problems. A wide range of genetic algorithms based on the two parents crossover have been applied to solve the problem but multi parents (more than two parents) crossover in solving the JSSP is still lacking. This paper proposes the extended precedence preservative crossover (EPPX) which uses multi parents for recombination in the genetic algorithms. EPPX is a variation of the precedence preservative crossover (PPX) which is one of the crossovers that perform well to find the solutions for the JSSP. EPPX is based on a vector to determine the gene selected in recombination for the next generation. Legalization of children (offspring) can be eliminated due to the JSSP representation encoded by using permutation with repetition that guarantees the feasibility of chromosomes. The simulations are performed on a set of benchmarks from the literatures and the results are compared to ensure the sustainability of multi parents recombination in solving the JSSP.

  7. Explicit Precedence Constraints in Safety-Critical Java

    DEFF Research Database (Denmark)

    Puffitsch, Wolfgang; Noulard, Eric; Pagetti, Claire

    2013-01-01

    Safety-critical Java (SCJ) aims at making the amenities of Java available for the development of safety-critical applications. The multi-rate synchronous language Prelude facilitates the specification of the communication and timing requirements of complex real-time systems. This paper combines...... to provide explicit support for precedence constraints. We present the considerations behind the design of this extension and discuss our experiences with a first prototype implementation based on the SCJ implementation of the Java Optimized Processor....

  8. Experimental Evidence for a Cochlear Source of the Precedence Effect

    DEFF Research Database (Denmark)

    Bianchi, Federica; Verhulst, Sarah; Dau, Torsten

    2013-01-01

    The precedence effect (PE) refers to the dominance of directional information carried by a direct sound (lead) over the spatial information contained in its multiple reflections (lags) in sound localization. Although the processes underlying the PE have been largely investigated, the extent...... to which peripheral versus central auditory processes contribute to this perceptual phenomenon has remained unclear. The present study investigated the contribution of peripheral processing to the PE through a comparison of physiological and psychoacoustical data in the same human listeners...

  9. Radiation protection: precedents, principles and practices - a regulatory viewpoint

    International Nuclear Information System (INIS)

    Jennekens, J.H.

    1986-06-01

    Radiation protection in its broadest sense is a multidisciplinary human function exemplifying in all meaningful respects the innate ability of dedicated persons to apply with both general and specialized expertise knowledge derived from a great many scientific and technical fields. The aim of this address is to outline from a regulatory viewpoint the precedents, principles and practices of radiation protection, a very essential human function

  10. Money laundering: The question of precedent relevant criminal fact

    Directory of Open Access Journals (Sweden)

    Fernando ANDRADE FERNANDES

    2014-07-01

    Full Text Available The article aims to make a more detailed analysis on the problem of the autonomy of money laundering crime. The rationale for the study is the existence of an understanding that defends the autonomy of the money laundering crime, despite the linkages she has with the precedent crime, of which result the illicit assets. The issue of autonomy of money laundering crime is analyzed in the perspective of the Criminal Law and Criminal Procedure.

  11. Blood cell oxidative stress precedes hemolysis in whole blood-liver slice co-cultures of rat, dog, and human tissues

    International Nuclear Information System (INIS)

    Vickers, Alison E.M.; Sinclair, John R.; Fisher, Robyn L.; Morris, Stephen R.; Way, William

    2010-01-01

    A novel in vitro model to investigate time-dependent and concentration-dependent responses in blood cells and hemolytic events is studied for rat, dog, and human tissues. Whole blood is co-cultured with a precision-cut liver slice. Methimazole (MMI) was selected as a reference compound, since metabolism of its imidazole thione moiety is linked with hematologic disorders and hepatotoxicity. An oxidative stress response occurred in all three species, marked by a decline in blood GSH levels by 24 h that progressed, and preceded hemolysis, which occurred at high MMI concentrations in the presence of a liver slice with rat (≥ 1000 μM at 48 h) and human tissues (≥ 1000 μM at 48 h, ≥ 750 μM at 72 h) but not dog. Human blood-only cultures exhibited a decline of GSH levels but minimal to no hemolysis. The up-regulation of liver genes for heme degradation (Hmox1 and Prdx1), iron cellular transport (Slc40a1), and GSH synthesis and utilization (mGST1 and Gclc) were early markers of the oxidative stress response. The up-regulation of the Kupffer cell lectin Lgals3 gene expression indicated a response to damaged red blood cells, and Hp (haptoglobin) up-regulation is indicative of increased hemoglobin uptake. Up-regulation of liver IL-6 and IL-8 gene expression suggested an activation of an inflammatory response by liver endothelial cells. In summary, MMI exposure led to an oxidative stress response in blood cells, and an up-regulation of liver genes involved with oxidative stress and heme homeostasis, which was clearly separate and preceded frank hemolysis.

  12. Ceramide-induced TCR up-regulation

    DEFF Research Database (Denmark)

    Menné, C; Lauritsen, Jens Peter Holst; Dietrich, J

    2000-01-01

    to increase T cell responsiveness. The purpose of this study was to identify and characterize potential pathways for TCR up-regulation. We found that ceramide affected TCR recycling dynamics and induced TCR up-regulation in a concentration- and time-dependent manner. Experiments applying phosphatase......The TCR is a constitutively recycling receptor meaning that a constant fraction of TCR from the plasma membrane is transported inside the cell at the same time as a constant fraction of TCR from the intracellular pool is transported to the plasma membrane. TCR recycling is affected by protein...... kinase C activity. Thus, an increase in protein kinase C activity affects TCR recycling kinetics leading to a new TCR equilibrium with a reduced level of TCR expressed at the T cell surface. Down-regulation of TCR expression compromises T cell activation. Conversely, TCR up-regulation is expected...

  13. The precedence effect for lateralization at low sensation levels.

    Science.gov (United States)

    Goverts, S T; Houtgast, T; van Beek, H H

    2000-10-01

    Using dichotic signals presented by headphone, stimulus onset dominance (the precedence effect) for lateralization at low sensation levels was investigated for five normal hearing subjects. Stimuli were based on 2400-Hz low pass filtered 5-ms noise bursts. We used the paradigm, as described by Aoki and Houtgast (Hear. Res., 59 (1992) 25-30) and Houtgast and Aoki (Hear. Res., 72 (1994) 29-36), in which the stimulus is divided into a leading and a lagging part with opposite lateralization cues (i.e. an interaural time delay of 0.2 ms). The occurrence of onset dominance was investigated by measuring lateral perception of the stimulus, with fixed equal duration of leading and lagging part, while decreasing absolute signal level or adding a filtered white noise with the signal level set at 65 dBA. The dominance of the leading part was quantified by measuring the perceived lateral position of the stimulus as a function of the relative duration of the leading (and thus the lagging) part. This was done at about 45 dB SL without masking noise and also at a signal-to-noise ratio resulting in a sensation level of 10 dB. The occurrence and strength of the precedence effect was found to depend on sensation level, which was decreased either by lowering the signal level or by adding noise. With the present paradigm, besides a decreased lateralization accuracy, a decrease in the precedence effect was found for sensation levels below about 30-40 dB. In daily-life conditions, with a sensation level in noise of typically 10 dB, the onset dominance was still manifest, albeit degraded to some extent.

  14. USING PRECEDENTS FOR REDUCTION OF DECISION TREE BY GRAPH SEARCH

    Directory of Open Access Journals (Sweden)

    I. A. Bessmertny

    2015-01-01

    Full Text Available The paper considers the problem of mutual payment organization between business entities by means of clearing that is solved by search of graph paths. To reduce the decision tree complexity a method of precedents is proposed that consists in saving the intermediate solution during the moving along decision tree. An algorithm and example are presented demonstrating solution complexity coming close to a linear one. The tests carried out in civil aviation settlement system demonstrate approximately 30 percent shortage of real money transfer. The proposed algorithm is planned to be implemented also in other clearing organizations of the Russian Federation.

  15. Human behavior preceding dog bites to the face.

    Science.gov (United States)

    Rezac, P; Rezac, K; Slama, P

    2015-12-01

    Facial injuries caused by dog bites pose a serious problem. The aims of this study were to determine human behavior immediately preceding a dog bite to the face and to assess the effects of victim age and gender and dog sex and size on the location of the bite to the face and the need for medical treatment. Complete data on 132 incidents of bites to the face were analysed. A human bending over a dog, putting the face close to the dog's face, and gazing between victim and dog closely preceded a dog bite to the face in 76%, 19% and 5% of cases, respectively. More than half of the bites were directed towards the central area of the victim's face (nose, lips). More than two thirds of the victims were children, none of the victims was an adult dog owner and only adult dogs bit the face. Victim's age and gender and dog's sex and size did not affect the location of the bite on the face. People who were bitten by large dogs sought medical treatment more often than people who were bitten by small dogs (P face close to the dog's face and gazing between human and dog should be avoided, and children should be carefully and constantly supervised when in the presence of dogs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Hydroclimatic conditions preceding the March 2014 Oso landslide

    Science.gov (United States)

    Henn, Brian; Cao, Qian; Lettenmaier, Dennis P.; Magirl, Christopher S.; Mass, Clifford; Bower, J. Brent; St. Laurent, Michael; Mao, Yixin; Perica, Sanja

    2015-01-01

    The 22 March 2014 Oso landslide was one of the deadliest in U.S. history, resulting in 43 fatalities and the destruction of more than 40 structures. We examine synoptic conditions, precipitation records and soil moisture reconstructions in the days, months, and years preceding the landslide. Atmospheric reanalysis shows a period of enhanced moisture transport to the Pacific Northwest beginning on 11 February 2014. The 21- to 42-day periods prior to the landslide had anomalously high precipitation; we estimate that 300-400 mm of precipitation fell at Oso in the 21 days prior to the landslide. Relative only to historical periods ending on 22 March, the return periods of these precipitation accumulations are large (25-88 years). However, relative to the largest accumulations from any time of the year (annual maxima), return periods are more modest (2-6 years). In addition to the 21-42 days prior to the landslide, there is a secondary maximum in the precipitation return periods for the 4 years preceding the landslide. Reconstructed soil moisture was anomalously high prior to the landslide, with a return period that exceeded 40 years about a week before the event.

  17. Arterial stiffening precedes systolic hypertension in diet-induced obesity.

    Science.gov (United States)

    Weisbrod, Robert M; Shiang, Tina; Al Sayah, Leona; Fry, Jessica L; Bajpai, Saumendra; Reinhart-King, Cynthia A; Lob, Heinrich E; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A; Seta, Francesca

    2013-12-01

    Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as the heart, brain, and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension although the mechanisms underlying hypertension are unknown. Here, we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within 1 month of the initiation of the diet and precedes the development of hypertension by 5 months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss resulted in return of arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause rather than a consequence of hypertension.

  18. Revisiting Precede-Proceed: A Leading Model for Ecological and Ethical Health Promotion

    Science.gov (United States)

    Porter, Christine M.

    2016-01-01

    Background: The Precede-Proceed model has provided moral and practical guidance for the fields of health education and health promotion since Lawrence Green first developed Precede in 1974 and Green and Kreuter added Proceed in 1991. Precede-Proceed today remains the most comprehensive and one of the most used approaches to promoting health.…

  19. Self-potential variations preceding earthquakes in central california

    International Nuclear Information System (INIS)

    Corwin, R.F.; Morrison, H.G.

    1977-01-01

    Two earthquakes in central California were preceded by anomalous variations in the horizontal electric field (self-potential) of the earth. The first variation was an anomaly of 90 mV amplitude across electrode dipoles of 630 and 640 m, which began 55 days before an earthquake of M=5, located 37 km NW of the dipoles. The second variation had an amplitude of 4 mV across a 300 m dipole, and began 110 hours before an event of M=2.4 located on the San Andreas fault, 2.5 km from the dipole. Streaming potentials generated by the flow of groundwater into a dilatant zone are proposed as a possible mechanism for the observed variations

  20. Progression of disease preceding lower extremity amputation in Denmark

    DEFF Research Database (Denmark)

    Jensen, Pia Søe; Petersen, Janne; Kirketerp-Møller, Klaus

    2017-01-01

    OBJECTIVES: Patients with non-traumatic lower extremity amputation are characterised by high age, multi-morbidity and polypharmacy and long-term complications of atherosclerosis and diabetes. To ensure early identification of patients at risk of amputation, we need to gain knowledge about...... the progression of diseases related to lower extremity amputations during the years preceding the amputation. DESIGN: A retrospective population-based national registry study. SETTING: The study includes data on demographics, diagnoses, surgery, medications and healthcare services from five national registries....... Data were retrieved from 14 years before until 1 year after the amputation. Descriptive statistics were used to describe the progression of diseases and use of medication and healthcare services. PARTICIPANTS: An unselected cohort of patients (≥50 years; n=2883) subjected to a primary non...

  1. Cancer preceding Wegener's granulomatosis: a case-control study

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Mellemkjaer, Lene; Sorensen, Inge J

    2009-01-01

    OBJECTIVE: To investigate whether patients with WG have an increased risk of malignancies prior to and/or around the time of the vasculitis diagnosis, as suggested by previous studies. METHODS: A total of 293 WG patients were included in the study. Ten gender- and age-matched controls were selected.......4; 95% CI 1.1, 38) based on two patients, who developed testis cancer >10 years before WG. The overall prevalence of malignancies diagnosed time...... interval (OR 4.0; 95% CI 1.4, 12). CONCLUSIONS: We did not find clear evidence of an increased prevalence of preceding cancer in our WG cohort, indicating that shared risk factors are of minor importance for the excess of malignancies that occur in WG patients after the vasculitis diagnosis. Furthermore...

  2. Urinary Clusterin Is Upregulated in Nephropathia Epidemica

    Directory of Open Access Journals (Sweden)

    Ekaterina V. Martynova

    2018-01-01

    Full Text Available Kidney insufficiency is a hallmark of nephropathia epidemica (NE. Little is known about the mechanisms of the NE kidney pathology, with current knowledge mainly based on findings in postmortem tissue. We have analyzed kidney damage biomarkers in urine collected from early- and late-phase NE using Bio-Plex kidney toxicity panels 1 and 2. To determine the disease specificity, kidney damage biomarkers were also analyzed in urine samples from patients diagnosed with gout, type 2 diabetes, systemic lupus erythematosus, and chronic kidney insufficiency. Analysis of 12 biomarkers suggests damage to the kidney proximal tubule at the onset of NE. Also, upregulation of biomarkers of inflammation and leukocyte chemotaxis were detected in NE urine. Furthermore, increased clusterin levels were found in early- and late-phase NE urine. Comparative analysis revealed that clusterin is a biomarker, upregulated in NE urine.

  3. Gene Expression Profiling of Bronchoalveolar Lavage Cells Preceding a Clinical Diagnosis of Chronic Lung Allograft Dysfunction.

    Directory of Open Access Journals (Sweden)

    S Samuel Weigt

    Full Text Available Chronic Lung Allograft Dysfunction (CLAD is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects.In a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL fluid samples were obtained from incipient CLAD (n = 9 and CLAD free (n = 8 lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy. Transcription profiles in the BAL cell pellets were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix. Differential gene expression analysis, based on an absolute fold change (incipient CLAD vs no CLAD >2.0 and an unadjusted p-value ≤0.05, generated a candidate list containing 55 differentially expressed probe sets (51 up-regulated, 4 down-regulated.The cell pellets in incipient CLAD cases were skewed toward immune response pathways, dominated by genes related to recruitment, retention, activation and proliferation of cytotoxic lymphocytes (CD8+ T-cells and natural killer cells. Both hierarchical clustering and a supervised machine learning tool were able to correctly categorize most samples (82.3% and 94.1% respectively into incipient CLAD and CLAD-free categories.These findings suggest that a pathobiology, similar to AR, precedes a clinical diagnosis of CLAD. A larger prospective investigation of the BAL cell pellet transcriptome as a biomarker for CLAD risk stratification is warranted.

  4. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives.

    Science.gov (United States)

    Sapone, Anna; de Magistris, Laura; Pietzak, Michelle; Clemente, Maria G; Tripathi, Amit; Cucca, Francesco; Lampis, Rosanna; Kryszak, Deborah; Cartenì, Maria; Generoso, Maddalena; Iafusco, Dario; Prisco, Francesco; Laghi, Francesca; Riegler, Gabriele; Carratu, Romano; Counts, Debra; Fasano, Alessio

    2006-05-01

    Zonulin, a protein that modulates intestinal permeability, is upregulated in several autoimmune diseases and is involved in the pathogenesis of autoimmune diabetes in the BB/Wor animal model of the disease. To verify the association between serum zonulin levels and in vivo intestinal permeability in patients with type 1 diabetes, both parameters were investigated in different stages of the autoimmune process. Forty-two percent (141 of 339) of the patients had abnormal serum zonulin levels, as compared with age-matched control subjects. The increased zonulin levels correlated with increased intestinal permeability in vivo and changes in claudin-1, claudin-2, and myosin IXB genes expression, while no changes were detected in ZO1 and occludin genes expression. When tested in serum samples collected during the pre-type 1 diabetes phase, elevated serum zonulin was detected in 70% of subjects and preceded by 3.5 +/- 0.9 years the onset of the disease in those patients who went on to develop type 1 diabetes. Combined, these results suggest that zonulin upregulation is associated with increased intestinal permeability in a subgroup of type 1 diabetic patients. Zonulin upregulation seems to precede the onset of the disease, providing a possible link between increased intestinal permeability, environmental exposure to non-self antigens, and the development of autoimmunity in genetically susceptible individuals.

  5. Precedents For Authorization Of Contents Using Dose Rate Measurements

    International Nuclear Information System (INIS)

    Abramczyk, G.; Bellamy, S.; Nathan, S.; Loftin, B.

    2012-01-01

    For the transportation of Radioactive Material (RAM) packages, the requirements for the maximum allowed dose rate at the package surface and in its vicinity are given in Title 10 of the Code of Federal Regulations, Section 71.47. The regulations are based on the acceptable dose rates to which the public, workers, and the environment may be exposed. As such, the regulations specify dose rates, rather than quantity of radioactive isotopes and require monitoring to confirm the requirements are met. 10CFR71.47 requires that each package of radioactive materials offered for transportation must be designed and prepared for shipment so that under conditions normally incident to transportation the radiation level does not exceed 2 mSv/h (200 mrem/h) at any point on the external Surface of the package, and the transport index does not exceed 10. Before shipment, the dose rate of the package is determined by measurement, ensuring that it conforms to the regulatory limits, regardless of any analyses. This is the requirement for all certified packagings. This paper discusses the requirements for establishing the dose rates when shipping RAM packages and the precedents for meeting these requirements by measurement.

  6. The Kosovo Precedent in the Secession and Recognition of Crimea

    Directory of Open Access Journals (Sweden)

    Dr.Sc. Elvina Jusufaj

    2015-06-01

    Full Text Available Crimea’s secession from Ukraine and its annexation to the Russian Federation invoked Kosovo precedent, in its declaration of independence, as an argument for secession. The territorial referendum in the Autonomous Republic of Crimea, only five days after the declaration of independence, was an attempt to justify the secession based on the right to selfdetermination of the people of Crimea. It is overwhelmingly considered illegal and its outcome has not been accepted and recognized by states, regional and international organizations. The comparative elements of statehood and secession between Kosovo and Crimea are reflected through analyzing the declarations of independence, international recognition and Russia’s role as a third-state factor in external selfdetermination. Essential distinctions are highlighted. Kosovo is widely acknowledged and accepted a sui generis case. Its declaration of independence came as result of a long monitored comprehensive process; not to legitimize the right for self-determination but as the final option for stability and peace in the region. Crimea seceded in violation of international law through the use of force. While Kosovo is a democratic, multi-ethnic new state and recognized by 107 states, the secession of Crimea and its annexation to the Russian Federation is considered illegal and endangers the existing international order.

  7. Neurological evidence linguistic processes precede perceptual simulation in conceptual processing.

    Science.gov (United States)

    Louwerse, Max; Hutchinson, Sterling

    2012-01-01

    There is increasing evidence from response time experiments that language statistics and perceptual simulations both play a role in conceptual processing. In an EEG experiment we compared neural activity in cortical regions commonly associated with linguistic processing and visual perceptual processing to determine to what extent symbolic and embodied accounts of cognition applied. Participants were asked to determine the semantic relationship of word pairs (e.g., sky - ground) or to determine their iconic relationship (i.e., if the presentation of the pair matched their expected physical relationship). A linguistic bias was found toward the semantic judgment task and a perceptual bias was found toward the iconicity judgment task. More importantly, conceptual processing involved activation in brain regions associated with both linguistic and perceptual processes. When comparing the relative activation of linguistic cortical regions with perceptual cortical regions, the effect sizes for linguistic cortical regions were larger than those for the perceptual cortical regions early in a trial with the reverse being true later in a trial. These results map upon findings from other experimental literature and provide further evidence that processing of concept words relies both on language statistics and on perceptual simulations, whereby linguistic processes precede perceptual simulation processes.

  8. Oral Hygiene Behaviors and Caries Experience in Northwest PRECEDENT Patients

    Science.gov (United States)

    Rothen, Marilynn; Cunha-Cruz, Joana; Zhou, Lingmei; Mancl, Lloyd; Jones, Jackie S.; Berg, Joel

    2014-01-01

    Objectives To investigate the association between oral hygiene behaviors (toothbrushing, water rinsing after brushing, interproximal cleaning, and adjunctive use of fluoride products) and recent caries (past 24 months) in a random sample of patients in Northwest PRECEDENT practices. Methods Practitioner-members of Northwest PRECEDENT dental Practice-based Research Network (PBRN) conducted a longitudinal study on caries risk assessment. At baseline patients completed a questionnaire on oral self-care, snacking, health, and socio-demographics. A dental exam recorded readily-visible heavy plaque and DMFT; chart review captured new caries and treatments in the previous 24 months. Bivariate and multiple GEE log-linear regression models stratified by age groups were used to relate oral hygiene behaviors to the primary outcome of mean dental caries in the past 24 months on data from 1400 patients in 63 practices. The primary exposure of interest was fluoride toothbrushing frequency. Results Fluoride toothbrushing once per day or more by patients 9-17 was significantly associated with a 50% lower mean caries rate compared to fluoride toothbrushing less than once per day, after adjustment for age, gender, race, education, income, between-meal carbohydrate snacks, sugar-added beverages, alcohol consumption, smoking, BMI, exercise, stimulated salivary pH, number of teeth, and all other oral hygiene behaviors captured [Rate Ratio (RR)=0.5; 95% confidence interval (CI)=0.3-0.8]. After adjustment, for patients 18-64 fluoride toothbrushing two or more times per day was significantly associated with a 40% lower recent mean caries rate (RR=0.6; 95%CI=0.4-0.9); in patients 65+, twice a day or more fluoride toothbrushing was not associated with lower caries rates (RR=1.1; 95%CI=0.7-1.8). Of the other oral hygiene variables, after adjustment, patients 18-64 who rinsed with water after brushing had a 40% lower mean caries rate compared to no rinsing (RR=0.6; 95%CI=0.4-0.9) and the

  9. Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions.

    Science.gov (United States)

    Lee, Sun Ha; Moon, Sung Jin; Paeng, Jisun; Kang, Hye-Young; Nam, Bo Young; Kim, Seonghun; Kim, Chan Ho; Lee, Mi Jung; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2015-08-01

    Podocyte hypertrophy and apoptosis are two hallmarks of diabetic glomeruli, but the sequence in which these processes occur remains a matter of debate. Here we investigated the effects of inhibiting hypertrophy on apoptosis, and vice versa, in both podocytes and glomeruli, under diabetic conditions. Hypertrophy and apoptosis were inhibited using an epidermal growth factor receptor inhibitor (PKI 166) and a pan-caspase inhibitor (zAsp-DCB), respectively. We observed significant increases in the protein expression of p27, p21, phospho-eukaryotic elongation factor 4E-binding protein 1, and phospho-p70 S6 ribosomal protein kinase, in both cultured podocytes exposed to high-glucose (HG) medium, and streptozotocin-induced diabetes mellitus (DM) rat glomeruli. These increases were significantly inhibited by PKI 166, but not by zAsp-DCB. In addition, the amount of protein per cell, the relative cell size, and the glomerular volume were all significantly increased under diabetic conditions, and these changes were also blocked by treatment with PKI 166, but not zAsp-DCB. Increased protein expression of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, together with increased Bax/Bcl-2 ratios, were also observed in HG-stimulated podocytes and DM glomeruli. Treatment with either zAsp-DCB or PKI 166 resulted in a significant attenuation of these effects. Both PKI 166 and zAsp-DCB also inhibited the increase in number of apoptotic cells, as assessed by Hoechst 33342 staining and TUNEL assay. Under diabetic conditions, inhibition of podocyte hypertrophy results in attenuated apoptosis, whereas blocking apoptosis has no effect on podocyte hypertrophy, suggesting that podocyte hypertrophy precedes apoptosis.

  10. Integrated Vehicle Ground Vibration Testing of Manned Spacecraft: Historical Precedent

    Science.gov (United States)

    Lemke, Paul R.; Tuma, Margaret L.; Askins, Bruce R.

    2008-01-01

    For the first time in nearly 30 years, NASA is developing a new manned space flight launch system. The Ares I will carry crew and cargo to not only the International Space Station, but onward for the future exploration of the Moon and Mars. The Ares I control system and structural designs use complex computer models for their development. An Integrated Vehicle Ground Vibration Test (IVGVT) will validate the efficacy of these computer models. The IVGVT will reduce the technical risk of unexpected conditions that could place the vehicle or crew in jeopardy. The Ares Project Office's Flight and Integrated Test Office commissioned a study to determine how historical programs, such as Saturn and Space Shuttle, validated the structural dynamics of an integrated flight vehicle. The study methodology was to examine the historical record and seek out members of the engineering community who recall the development of historic manned launch vehicles. These records and interviews provided insight into the best practices and lessons learned from these historic development programs. The information that was gathered allowed the creation of timelines of the historic development programs. The timelines trace the programs from the development of test articles through test preparation, test operations, and test data reduction efforts. These timelines also demonstrate how the historical tests fit within their overall vehicle development programs. Finally, the study was able to quantify approximate staffing levels during historic development programs. Using this study, the Flight and Integrated Test Office was able to evaluate the Ares I Integrated Vehicle Ground Vibration Test schedule and workforce budgets in light of the historical precedents to determine if the test had schedule or cost risks associated with it.

  11. Upregulation of FOXM1 induces genomic instability in human epidermal keratinocytes

    Directory of Open Access Journals (Sweden)

    Philpott Michael P

    2010-02-01

    Full Text Available Abstract Background The human cell cycle transcription factor FOXM1 is known to play a key role in regulating timely mitotic progression and accurate chromosomal segregation during cell division. Deregulation of FOXM1 has been linked to a majority of human cancers. We previously showed that FOXM1 was upregulated in basal cell carcinoma and recently reported that upregulation of FOXM1 precedes malignancy in a number of solid human cancer types including oral, oesophagus, lung, breast, kidney, bladder and uterus. This indicates that upregulation of FOXM1 may be an early molecular signal required for aberrant cell cycle and cancer initiation. Results The present study investigated the putative early mechanism of UVB and FOXM1 in skin cancer initiation. We have demonstrated that UVB dose-dependently increased FOXM1 protein levels through protein stabilisation and accumulation rather than de novo mRNA expression in human epidermal keratinocytes. FOXM1 upregulation in primary human keratinocytes triggered pro-apoptotic/DNA-damage checkpoint response genes such as p21, p38 MAPK, p53 and PARP, however, without causing significant cell cycle arrest or cell death. Using a high-resolution Affymetrix genome-wide single nucleotide polymorphism (SNP mapping technique, we provided the evidence that FOXM1 upregulation in epidermal keratinocytes is sufficient to induce genomic instability, in the form of loss of heterozygosity (LOH and copy number variations (CNV. FOXM1-induced genomic instability was significantly enhanced and accumulated with increasing cell passage and this instability was increased even further upon exposure to UVB resulting in whole chromosomal gain (7p21.3-7q36.3 and segmental LOH (6q25.1-6q25.3. Conclusion We hypothesise that prolonged and repeated UVB exposure selects for skin cells bearing stable FOXM1 protein causes aberrant cell cycle checkpoint thereby allowing ectopic cell cycle entry and subsequent genomic instability. The aberrant

  12. Fluoxetin Upregulates Connexin 43 Expression in Astrocyte

    Directory of Open Access Journals (Sweden)

    Hossein Mostafavi

    2014-02-01

    Full Text Available Introduction: Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS. Molecular target therapy studies in MS have revealed that connexin-43 (Cx43 and Aquaporin-4 (AQP4 contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects. Some of fluoxetine effects were attributed to its capability of cAMP signaling pathway stimulation. This study aimed to investigate possible acute effects of fluoxetine on Cx43 and AQP4 expression in astrocyte.  Methods: Astrocytoma cells were treated for 24 hours with fluoxetine (10 and 20 &mug/ml with or without adenyl cyclase (AC and protein kinase A (PKA inhibition. Cx43 expression at both mRNA and protein levels and AQP4 expression at mRNA level were evaluated.  Results: Acquired results showed that fluoxetine with and without AC and PKA inhibition resulted in Cx43 up-regulation both in mRNA and protein levels, whereas AQP4 expression have not changed.  Discussion: In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients. It seems that cAMP involvement in fluoxetine effects need more researches.

  13. A critical period of progesterone withdrawal precedes menstruation in macaques

    Science.gov (United States)

    Slayden, Ov D; Brenner, Robert M

    2006-01-01

    Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12–24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked. PMID:17118170

  14. Precedent approach to the formation of programs for cyclic objects control

    Science.gov (United States)

    Kulakov, S. M.; Trofimov, V. B.; Dobrynin, A. S.; Taraborina, E. N.

    2018-05-01

    The idea and procedure for formalizing the precedent method of formation of complex control solutions (complex control programs) is discussed with respect to technological or organizational objects, the operation of which is organized cyclically. A typical functional structure of the system of precedent control by complex technological unit is developed, including a subsystem of retrospective optimization of actually implemented control programs. As an example, the problem of constructing replaceable planograms for the operation of the link of a heading-and-winning machine on the basis of precedents is considered.

  15. An improved car-following model accounting for the preceding car's taillight

    Science.gov (United States)

    Zhang, Jian; Tang, Tie-Qiao; Yu, Shao-Wei

    2018-02-01

    During the deceleration process, the preceding car's taillight may have influences on its following car's driving behavior. In this paper, we propose an extended car-following model with consideration of the preceding car's taillight. Two typical situations are used to simulate each car's movement and study the effects of the preceding car's taillight on the driving behavior. Meanwhile, sensitivity analysis of the model parameter is in detail discussed. The numerical results show that the proposed model can improve the stability of traffic flow and the traffic safety can be enhanced without a decrease of efficiency especially when cars pass through a signalized intersection.

  16. Upregulation of Leukotriene Receptors in Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Venerito, Marino [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Kuester, Doerthe [Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Harms, Caroline [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Schubert, Daniel [Department of General, Visceral and Vascular Surgery, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, Magdeburg 39120 (Germany); Wex, Thomas, E-mail: thomas.wex@med.ovgu.de; Malfertheiner, Peter [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany)

    2011-08-08

    Leukotrienes (LT) mediate allergic and inflammatory processes. Previously, we identified significant changes in the expression pattern of LT receptors in the gastric mucosa after eradication of Helicobacter pylori infection. The aim of the present study was to evaluate the expression of 5-lipoxygenase (5-LOX) and LT receptors in gastric cancer (GC). The expression of 5-LOX and receptors for LTB4 (BLT-1, BLT-2) and cysteinyl-LT (CysLT-1, CysLT-2) were analyzed by immunohistochemistry (IHC) in GC samples of 35 consecutive patients who underwent gastrectomy and in 29 tumor-free tissue specimens from gastric mucosa. Male-to-female ratio was 24:11. The median age was 70 years (range 34–91). Twenty-two patients had GC of intestinal, six of diffuse, six of mixed and one of undifferentiated type. The IHC analysis showed a nearly ubiquitous expression of studied proteins in GC (88–97%) and in tumor-free specimens as well (89–100%). An increase in the immunoreactive score of both BLT receptors and CysLT-1 was observed in GC compared to tumor-free gastric mucosa (p < 0.001 for BLT-1; p < 0.01 for BLT-2 and CysLT-1, Mann-Whitney U-test). No differences in the IHC expression of 5-LOX and CsyLT-2 were observed between GC and tumor-free mucosa. The expression of BLT-2, CysLT-1 and CysLT-2 was increased in GC of intestinal type when compared to the diffuse type (p < 0.05; Mann-Whitney U-test). LTB4 receptors and CysLT-1 are up-regulated in GC tissue implying a role in gastric carcinogenesis.

  17. Late onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation.

    Science.gov (United States)

    Pontikis, Charlie C; Cella, Claire V; Parihar, Nisha; Lim, Ming J; Chakrabarti, Shubhodeep; Mitchison, Hannah M; Mobley, William C; Rezaie, Payam; Pearce, David A; Cooper, Jonathan D

    2004-10-15

    Mouse models of neuronal ceroid lipofuscinosis (NCL) exhibit many features of the human disorder, with widespread regional atrophy and significant loss of GABAergic interneurons in the hippocampus and neocortex. Reactive gliosis is a characteristic of all forms of NCL, but it is unclear whether glial activation precedes or is triggered by neuronal loss. To explore this issue we undertook detailed morphological characterization of the Cln3 null mutant (Cln3(-/-)) mouse model of juvenile NCL (JNCL) that revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread loss of hippocampal interneurons that was first evident at 14 months of age. Quantitative image analysis demonstrated upregulation of markers of astrocytic and microglial activation in presymptomatic Cln3(-/-) mice at 5 months of age, many months before significant neuronal loss occurs. These data provide evidence for subtle glial responses early in JNCL pathogenesis.

  18. Exact and Heuristic Algorithms for Routing AGV on Path with Precedence Constraints

    Directory of Open Access Journals (Sweden)

    Liang Xu

    2016-01-01

    Full Text Available A new problem arises when an automated guided vehicle (AGV is dispatched to visit a set of customers, which are usually located along a fixed wire transmitting signal to navigate the AGV. An optimal visiting sequence is desired with the objective of minimizing the total travelling distance (or time. When precedence constraints are restricted on customers, the problem is referred to as traveling salesman problem on path with precedence constraints (TSPP-PC. Whether or not it is NP-complete has no answer in the literature. In this paper, we design dynamic programming for the TSPP-PC, which is the first polynomial-time exact algorithm when the number of precedence constraints is a constant. For the problem with number of precedence constraints, part of the input can be arbitrarily large, so we provide an efficient heuristic based on the exact algorithm.

  19. Preceding diagnoses to young adult bipolar disorder and schizophrenia in a nationwide study

    Science.gov (United States)

    2013-01-01

    Background The aim of this comparative study was to investigate the type and frequency of diagnoses preceding adult bipolar disorder (BD) and schizophrenia (SZ). Methods A follow-back study of all preceding diagnoses in all patients aged 21–34 years with a primary, first time diagnosis of BD (N = 784) or SZ (N = 1667) in 2008 to 2010. Data were taken from the Danish Psychiatric Central Research Register (DPCRR) including ICD-10 and ICD-8 diagnoses. Results The numbers of patients with any preceding diagnoses amounted to 69.3% in BD and 76.6% in SZ with affective disorders (excluding BD) being the most frequent preceding diagnosis (46.6 vs. 28.0%), followed by psychoses (PSY) other than SZ (14.2 vs. 41.5%, p adolescence. Overall patients with SZ had a minor but statistically significant earlier onset of any psychiatric disorder compared to BD (mean age: 23.3 vs. 22.5, p < .001). Regression analyses indicated that BD was associated with an increased risk of having experienced preceding affective disorders and ADHD, while SZ was associated with an increased risk of preceding substance use disorders, psychosis, anxiety disorders, and personality disorders. Conclusions Specific developmental trajectories of preceding disorders were delineated for BD and SZ with affective disorders being more specific for BD and both SUD and PSY more specific to SZ. There are different patterns of vulnerability in terms of preceding diagnosis in young adults with BD and SZ. PMID:24359146

  20. Jogando com os precedentes: regras, analogias, princípios Playing with precedents: rules, analogies, principles

    Directory of Open Access Journals (Sweden)

    Antonio Moreira Maués

    2012-12-01

    Full Text Available Este artigo analisa decisões recentes do STF envolvendo a aplicação de súmulas vinculantes à luz de três concepções de precedentes, desenvolvidas por F. Schauer (precedentes como regras, C. Sunstein (precedentes como analogias e R. Dworkin (precedentes como princípios. Após a exposição dos principais aspectos de cada uma dessas teorias baseadas, respectivamente, nos conceitos de generalizações enraizadas, acordos teóricos incompletos e romance em cadeia, e discute os fundamentos que elas podem oferecer para o uso de precedentes no direito brasileiro.This article analyses the use of binding precedents by the Brazilian Supreme Court in the light of three conceptions of precedents, which are developed by F. Schauer (precedents as rules, C. Sunstein (precedents as analogies and R. Dworkin (precedents as principles. After the exposition of the main aspects of each theory, based respectively on the concepts of entrenched generalizations, incompletely theorized agreements and chain novel, the article debates the arguments that they can provide for the use of precedents in Brazilian law.

  1. General contrast effects in speech perception: effect of preceding liquid on stop consonant identification.

    Science.gov (United States)

    Lotto, A J; Kluender, K R

    1998-05-01

    When members of a series of synthesized stop consonants varying acoustically in F3 characteristics and varying perceptually from /da/ to /ga/ are preceded by /al/, subjects report hearing more /ga/ syllables relative to when each member is preceded by /ar/ (Mann, 1980). It has been suggested that this result demonstrates the existence of a mechanism that compensates for coarticulation via tacit knowledge of articulatory dynamics and constraints, or through perceptual recovery of vocal-tract dynamics. The present study was designed to assess the degree to which these perceptual effects are specific to qualities of human articulatory sources. In three experiments, series of consonant-vowel (CV) stimuli varying in F3-onset frequency (/da/-/ga/) were preceded by speech versions or nonspeech analogues of /al/ and /ar/. The effect of liquid identity on stop consonant labeling remained when the preceding VC was produced by a female speaker and the CV syllable was modeled after a male speaker's productions. Labeling boundaries also shifted when the CV was preceded by a sine wave glide modeled after F3 characteristics of /al/ and /ar/. Identifications shifted even when the preceding sine wave was of constant frequency equal to the offset frequency of F3 from a natural production. These results suggest an explanation in terms of general auditory processes as opposed to recovery of or knowledge of specific articulatory dynamics.

  2. Effectiveness of the PRECEDE model in obese patients undergoing primary care nurses follow-up

    Directory of Open Access Journals (Sweden)

    Inés Maria Barrio Cantalejo

    2004-04-01

    Full Text Available Obesity is a serious problem in western modern countries. Primary care nurses has to follow up these patients but often with poor results. The PRECEDE model (Green L.W try to help patients to identify factors that predispose, make easier or reinforce their relationship with food and physical exercise. Objectives: To evaluate if PRECEDE makes easier the adherence of obese patients to a new style of feeding and exercise that reduces their BMI. Metodology: Experimental design, community randomised study. We analysed two samples of two different interventions: in one we applied the PRECEDE, in the other one the conventional advice about diet and exercise. Measures at 12 and 18 months. Both samples were homogeneous. The relationship between qualitative data has been studied through the Pearson x2 test and the comparison of quantitative data between two groups through the Student T test for independent samples. Results: a The PRECEDE intervention group lost more weigh than control at 12ª month, but this difference is almost null at 18º month. b The BMI difference has low clinical value because in both cases the final BMI is >30. Conclusions: a PRECEDE model shows a major capacity to reduce the BMI than the conventional model at short time. b To conclude that the PRECEDE weigh reduction is clinically effective we should have to extend our educational intervention longer time.

  3. Osmotic stress upregulates the transcription of thiamine (vitamin B1 ...

    African Journals Online (AJOL)

    Osmotic stress upregulates the transcription of thiamine (vitamin B1) ... Oil palm's responses in terms of the expression profiles of these two thiamine biosynthesis genes to an osmotic stress inducer, polyethylene glycol ... from 32 Countries:.

  4. No evidence of conpopulation sperm precedence between allopatric populations of house mice.

    Directory of Open Access Journals (Sweden)

    Renée C Firman

    Full Text Available Investigations into the evolution of reproductive barriers have traditionally focused on closely related species, and the prevalence of conspecific sperm precedence. The effectiveness of conspecific sperm precedence at limiting gene exchange between species suggests that gametic isolation is an important component of reproductive isolation. However, there is a paucity of tests for evidence of sperm precedence during the earlier stages of divergence, for example among isolated populations. Here, we sourced individuals from two allopatric populations of house mice (Mus domesticus and performed competitive in vitro fertilisation assays to test for conpopulation sperm precedence specifically at the gametic level. We found that ova population origin did not influence the outcome of the sperm competitions, and thus provide no evidence of conpopulation or heteropopulation sperm precedence. Instead, we found that males from a population that had evolved under a high level of postcopulatory sexual selection consistently outcompeted males from a population that had evolved under a relatively lower level of postcopulatory sexual selection. We standardised the number of motile sperm of each competitor across the replicate assays. Our data therefore show that competitive fertilizing success was directly attributable to differences in sperm fertilizing competence.

  5. No evidence of conpopulation sperm precedence between allopatric populations of house mice.

    Science.gov (United States)

    Firman, Renée C; Simmons, Leigh W

    2014-01-01

    Investigations into the evolution of reproductive barriers have traditionally focused on closely related species, and the prevalence of conspecific sperm precedence. The effectiveness of conspecific sperm precedence at limiting gene exchange between species suggests that gametic isolation is an important component of reproductive isolation. However, there is a paucity of tests for evidence of sperm precedence during the earlier stages of divergence, for example among isolated populations. Here, we sourced individuals from two allopatric populations of house mice (Mus domesticus) and performed competitive in vitro fertilisation assays to test for conpopulation sperm precedence specifically at the gametic level. We found that ova population origin did not influence the outcome of the sperm competitions, and thus provide no evidence of conpopulation or heteropopulation sperm precedence. Instead, we found that males from a population that had evolved under a high level of postcopulatory sexual selection consistently outcompeted males from a population that had evolved under a relatively lower level of postcopulatory sexual selection. We standardised the number of motile sperm of each competitor across the replicate assays. Our data therefore show that competitive fertilizing success was directly attributable to differences in sperm fertilizing competence.

  6. Study on Determination of Preceding Vehicle Motion State at the Traffic Lights Intersection

    Directory of Open Access Journals (Sweden)

    Cailin Wu

    2014-10-01

    Full Text Available In order to enhance the security of automotive safety systems and reduce traffic accidents in traffic lights intersection, In view of this, it is proposed to apply the distance measurement technology of binocular vision ranging in determination of preceding vehicle motion state at the traffic lights intersection, We study the determination of preceding vehicle motion state at the traffic lights intersection based on binocular vision. The system, which is divided into four steps, adopts the theory combining the binocular stereo vision principle and the triangulation principle. First of all, from different angles, image information with preceding vehicles and traffic lights, collected by two CCD cameras, is processed and positioned. Next, two pairs of corresponding feature matching points is obtained by using the stereo matching method. Furthermore, the distance between the cameras and the preceding vehicle, and the distance between the cameras and the traffic lights are determined, according to the camera calibration technique, the parallax disparity principle and the triangulation principle. Finally, the determination about the motion state of traffic lights intersection is determined according to the distance difference principle. Experimental results show that the design, with high measurement accuracy and application value, realize the determination of preceding vehicle’s motion state at traffic lights intersection.

  7. Hemodynamic deterioration precedes onset of ventricular tachyarrhythmia after Heartmate II implantation.

    Science.gov (United States)

    Yaksh, Ameeta; Kik, Charles; Knops, Paul; Zwiers, Korinne; van Ettinger, Maarten J B; Manintveld, Olivier C; de Wijs, Marcel C J; van der Kemp, Peter; Bogers, Ad J J C; de Groot, Natasja M S

    2016-07-08

    Early postoperative ventricular tachyarrhythmia (PoVT) after left ventricular assist device (LVAD) implantation are common and associated with higher mortality-rates. At present, there is no data on initiation of these PoVT and the role of alterations in cardiac hemodynamics. A LVAD was implanted in a patient with end-stage heart failure due to a ischemic cardiomyopathy. Alterations in cardiac rhythm and hemodynamics preceding PoVT-episodes during the first five postoperative days were examined by using continuous recordings of cardiac rhythm and various hemodynamic parameters. All PoVT (N=120) were monomorphic, most often preceded by short-long-short-sequences or regular SR and initiated by ventricular runs. Prior to PoVT, mean arterial pressure decreased; heart rate and ST-segments deviations increased. PoVT are caused by different underlying electrophysiological mechanisms. Yet, they are all monomorphic and preceded by hemodynamic deterioration due to myocardial ischemia.

  8. Global precedence effects account for individual differences in both face and object recognition performance.

    Science.gov (United States)

    Gerlach, Christian; Starrfelt, Randi

    2018-03-20

    There has been an increase in studies adopting an individual difference approach to examine visual cognition and in particular in studies trying to relate face recognition performance with measures of holistic processing (the face composite effect and the part-whole effect). In the present study we examine whether global precedence effects, measured by means of non-face stimuli in Navon's paradigm, can also account for individual differences in face recognition and, if so, whether the effect is of similar magnitude for faces and objects. We find evidence that global precedence effects facilitate both face and object recognition, and to a similar extent. Our results suggest that both face and object recognition are characterized by a coarse-to-fine temporal dynamic, where global shape information is derived prior to local shape information, and that the efficiency of face and object recognition is related to the magnitude of the global precedence effect.

  9. Diverticular colitis of the ascending colon preceding the onset of ulcerative colitis.

    Science.gov (United States)

    Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Tetsu; Fujita, Jiro

    2014-06-30

    We present a case of diverticular colitis of the ascending colon preceding the onset of ulcerative colitis. A 58-year-old man presented with positive faecal occult blood test. Colonoscopy disclosed diverticular colitis of the ascending colon. After a year's follow-up, typical ulcerative colitis developed and diverticular colitis improved. Diverticular colitis is a newly established disorder of chronic segmental mucosal inflammation affected by diverticular disease. There is increasing recognition of such cases with diverticular colitis preceding ulcerative colitis. There may be a possible pathogenic relationship between the two diseases. 2014 BMJ Publishing Group Ltd.

  10. Aplastic anaemia preceding acute lymphoblastic leukaemia in an adult with isolated deletion of chromosome 9q.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2008-12-01

    Aplastic anaemia (AA) can precede acute lymphoblastic leukaemia (ALL) in 2% of children but this is rarely reported to occur in adults. A 21-year-old male presented with bone marrow failure and bone marrow biopsy showed a profoundly hypocellular marrow. He recovered spontaneously but represented 2 months later when he was diagnosed with pre-B acute lymphoblastic leukaemia. Chromosomal examination revealed 46,XY,del(9)(q13q34). To the best of our knowledge this is the first case to be reported of aplasia preceding ALL with 9q minus as the sole chromosomal abnormality.

  11. Global precedence effects account for individual differences in both face and object recognition performance

    DEFF Research Database (Denmark)

    Gerlach, Christian; Starrfelt, Randi

    2018-01-01

    examine whether global precedence effects, measured by means of non-face stimuli in Navon's paradigm, can also account for individual differences in face recognition and, if so, whether the effect is of similar magnitude for faces and objects. We find evidence that global precedence effects facilitate...... both face and object recognition, and to a similar extent. Our results suggest that both face and object recognition are characterized by a coarse-to-fine temporal dynamic, where global shape information is derived prior to local shape information, and that the efficiency of face and object recognition...

  12. 48 CFR 11.101 - Order of precedence for requirements documents.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Order of precedence for... A-119, “Federal Participation in the Development and Use of Voluntary Consensus Standards and in... of 1995, Pub. L. 104-113 (15 U.S.C. 272 note), agencies must use voluntary consensus standards, when...

  13. Last mated male sperm precedence in doubly mated females is not ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 92; Issue 2. Last mated male sperm precedence in doubly mated females is not ubiquitous: evidence from sperm competition in laboratory populations of Drosophila nasuta nasuta and Drosophila nasuta albomicans. B. Shruthi S. R. Ramesh. Research Note Volume 92 Issue 2 ...

  14. In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication

    NARCIS (Netherlands)

    Baltus, Andrew E.; Menke, Douglas B.; Hu, Yueh-Chiang; Goodheart, Mary L.; Carpenter, Anne E.; de Rooij, Dirk G.; Page, David C.

    2006-01-01

    The transition from mitosis to meiosis is a defining juncture in the life cycle of sexually reproducing organisms. In yeast, the decision to enter meiosis is made before the single round of DNA replication that precedes the two meiotic divisions. We present genetic evidence of an analogous decision

  15. Contributions from eye movement potentials to stimulus preceding negativity during anticipation of auditory stimulation

    DEFF Research Database (Denmark)

    Engdahl, Lis; Bjerre, Vicky K; Christoffersen, Gert R J

    2007-01-01

    Cognitive anticipation of a stimulus has been associated with an ERP called "stimulus preceding negativity" (SPN). A new auditory delay task without stimulus-related motor activity demonstrated a prefrontal SPN, present during attentive anticipation of sounds with closed eyes, but absent during d...

  16. Dendritic calcium activity precedes inspiratory bursts in preBotzinger complex neurons

    DEFF Research Database (Denmark)

    Del Negro, Christopher A; Hayes, John A; Rekling, Jens C

    2011-01-01

    to evoke a Ca(2+)-activated inward current that contributes to inspiratory burst generation. We measured Ca(2+) transients by two-photon imaging dendrites while recording neuronal somata electrophysiologically. Dendritic Ca(2+) accumulation frequently precedes inspiratory bursts, particularly at recording...

  17. Tiered Auctions for Multi-Agent Coordination in Domains with Precedence Constraints

    National Research Council Canada - National Science Library

    Jones, E. G; Dias, M. B; Stentz, Anthony

    2008-01-01

    .... In this work we focus on precedence-constrained emergency response. In this domain a group of fire trucks agents attempt to navigate through a city in order to extinguish a set of fires that have occurred in the wake of a large...

  18. Onset of Bonding Plasmon Hybridization Preceded by Gap Modes in Dielectric Splitting of Metal Disks

    DEFF Research Database (Denmark)

    Frederiksen, Maj; Bochenkov, Vladimir; Ogaki, Ryosuke

    2013-01-01

    Dielectric splitting of nanoscale disks was studied experimentally and via finite-difference time-domain (FDTD) simulations through systematic introduction of multiple ultrathin dielectric layers. Tunable, hybridized dark bonding modes were seen with first-order gap modes preceding the appearance...

  19. Use and adaptation of precedents in architectural design. Toward an evolutionary design model

    NARCIS (Netherlands)

    Moraes Zarzar, K.

    2003-01-01

    For centuries, architects have re-used design precedents in the conception of new design solutions. Whether explicitly - as in the case of Le Corbusier, James Stirling and Jo Coenen - or implicitly - as with J.J.P. Oud, Aldo van Eyk, and Santiago Calatrava - this practice has led to very

  20. Strategy Precedes Operational Effectiveness: Aligning High Graduation Rankings with Competitive Graduation Grade Point Averages

    Science.gov (United States)

    Apprey, Maurice; Bassett, Kimberley C.; Preston-Grimes, Patrice; Lewis, Dion W.; Wood, Beverly

    2014-01-01

    Two pivotal and interconnected claims are addressed in this article. First, strategy precedes program effectiveness. Second, graduation rates and rankings are insufficient in any account of academic progress for African American students. In this article, graduation is regarded as the floor and not the ceiling, as it were. The ideal situation in…

  1. High Health Care Utilization Preceding Diagnosis of Systemic Lupus Erythematosus in Youth.

    Science.gov (United States)

    Chang, Joyce C; Mandell, David S; Knight, Andrea M

    2017-12-01

    Childhood-onset systemic lupus erythematosus (SLE) is associated with high risk for organ damage, which may be mitigated by early diagnosis and treatment. We characterized health care utilization for youth in the year preceding SLE diagnosis compared to controls. Using Clinformatics ™ DataMart (OptumInsight, Eden Prairie, MN) de-identified administrative data from 2000 to 2013, we identified 682 youth ages 10-24 years with new-onset SLE (≥3 International Classification of Diseases, Ninth Revision (ICD-9) codes for SLE 710.0, each >30 days apart), and 1,364 age and sex-matched healthy controls. We compared the incidence of ambulatory, emergency, and inpatient visits 12 months before SLE diagnosis, and frequency of primary diagnoses. We examined subject characteristics associated with utilization preceding SLE diagnosis. Youth with SLE had significantly more visits in the year preceding diagnosis than controls across ambulatory (incidence rate ratio (IRR) 2.48, p<0.001), emergency (IRR 3.42, p<0.001) and inpatient settings (IRR 3.02, p<0.001). The most frequent acute care diagnoses and median days to SLE diagnosis were: venous thromboembolism (313, interquartile range (IQR) 18-356), thrombocytopenia (278, IQR 39-354), chest pain (73, IQR 29.5-168), fever (52, IQR 17-166), and acute kidney failure (14, IQR 5-168). Having a psychiatric diagnosis prior to SLE diagnosis was strongly associated with increased utilization across all settings. Youth with SLE have high health care utilization throughout the year preceding SLE diagnosis. Examining variable diagnostic trajectories of youth presenting for acute care preceding SLE diagnosis, and increased attention to psychiatric morbidity may help improve care for youth with new-onset SLE. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Upregulation of Interleukin-33 in obstructive renal injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wei-Yu, E-mail: wychen624@cgmh.org.tw [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Chang, Ya-Jen [Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (China); Su, Chia-Hao [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Tsai, Tzu-Hsien [Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Chen, Shang-Der [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan (China); Hsing, Chung-Hsi [Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan (China); Yang, Jenq-Lin, E-mail: jyang@adm.cgmh.org.tw [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China)

    2016-05-13

    Interstitial fibrosis and loss of parenchymal tubular cells are the common outcomes of progressive renal diseases. Pro-inflammatory cytokines have been known contributing to the damage of tubular cells and fibrosis responses after renal injury. Interleukin (IL)-33 is a tissue-derived nucleus alarmin that drives inflammatory responses. The regulation and function of IL-33 in renal injury, however, is not well understood. To investigate the involvement of cytokines in the pathogenesis of renal injury and fibrosis, we performed the mouse renal injury model induced by unilateral urinary obstruction (UUO) and analyze the differentially upregulated genes between the obstructed and the contralateral unobstructed kidneys using RNA sequencing (RNAseq). Our RNAseq data identified IL33 and its receptor ST2 were upregulated in the UUO kidney. Quantitative analysis confirmed that transcripts of IL33 and ST2 were upregulated in the obstructed kidneys. Immunofluorescent staining revealed that IL-33 was upregulated in Vimentin- and alpha-SMA-positive interstitial cells. By using genetically knockout mice, deletion of IL33 reduced UUO-induced renal fibrosis. Moreover, in combination with BrdU labeling technique, we observed that the numbers of proliferating tubular epithelial cells were increased in the UUO kidneys from IL33-or ST2-deficient mice compared to wild type mice. Collectively, our study demonstrated the upregulation of IL-33/ST2 signaling in the obstructed kidney may promote tubular cell injury and interstitial fibrosis. IL-33 may serve as a biomarker to detect renal injury and that IL-33/ST2 signaling may represent a novel target for treating renal diseases. -- Highlights: •Interleukin (IL)-33 was upregulated in obstructed kidneys. •Interstitial myofibroblasts expressed IL-33 after UUO-induced renal injury. •Deficiency of IL33 reduced interstitial fibrosis and promoted tubular cell proliferation.

  3. Respiratory Syncytial Virus Nonstructural Proteins Upregulate SOCS1 and SOCS3 in the Different Manner from Endogenous IFN Signaling

    Directory of Open Access Journals (Sweden)

    Junwen Zheng

    2015-01-01

    Full Text Available Respiratory syncytial virus (RSV infection upregulates genes of the suppressor of cytokine signaling (SOCS family, which utilize a feedback loop to inhibit type I interferon dependent antiviral signaling pathway. Here, we reconstituted RSV nonstructural (NS protein expression plasmids (pNS1, pNS2, and pNS1/2 and tested whether NS1 or NS2 would trigger SOCS1 and SOCS3 protein expression. These NS proteins inhibited interferon- (IFN- α signaling through a mechanism involving the induction of SOCS1 and SOCS3, which appeared to be different from autocrine IFN dependent. NS1 induced both SOCS1 and SOCS3 upregulation, while NS2 only induced SOCS1 expression. The induced expression of SOCS1 and SOCS3 preceded endogenous IFN-signaling activation and inhibited the IFN-inducible antiviral response as well as chemokine induction. Treatments with INF-α and NS proteins both induced SOCS1 expression; however, they had opposing effects on IFN-α-dependent antiviral gene expression. Our results indicate that NS1 and NS2, which induce the expression of SOCS1 or SOCS3, might represent an independent pathway of stimulating endogenous IFN signaling.

  4. The DNA damage checkpoint precedes activation of ARF in response to escalating oncogenic stress during tumorigenesis

    DEFF Research Database (Denmark)

    Evangelou, K.; Bartkova, J.; Kotsinas, A.

    2013-01-01

    oncogenes showed that the delayed upregulation of ARF reflected a requirement for a higher, transcriptionally based threshold of oncogenic stress, elicited by at least two oncogenic 'hits', compared with lower activation threshold for DDR. We propose that relative to DDR activation, ARF provides...

  5. Anomalous transport in fluid field with random waiting time depending on the preceding jump length

    International Nuclear Information System (INIS)

    Zhang Hong; Li Guo-Hua

    2016-01-01

    Anomalous (or non-Fickian) transport behaviors of particles have been widely observed in complex porous media. To capture the energy-dependent characteristics of non-Fickian transport of a particle in flow fields, in the present paper a generalized continuous time random walk model whose waiting time probability distribution depends on the preceding jump length is introduced, and the corresponding master equation in Fourier–Laplace space for the distribution of particles is derived. As examples, two generalized advection-dispersion equations for Gaussian distribution and lévy flight with the probability density function of waiting time being quadratic dependent on the preceding jump length are obtained by applying the derived master equation. (paper)

  6. Anomalous transport in fluid field with random waiting time depending on the preceding jump length

    Science.gov (United States)

    Zhang, Hong; Li, Guo-Hua

    2016-11-01

    Anomalous (or non-Fickian) transport behaviors of particles have been widely observed in complex porous media. To capture the energy-dependent characteristics of non-Fickian transport of a particle in flow fields, in the present paper a generalized continuous time random walk model whose waiting time probability distribution depends on the preceding jump length is introduced, and the corresponding master equation in Fourier-Laplace space for the distribution of particles is derived. As examples, two generalized advection-dispersion equations for Gaussian distribution and lévy flight with the probability density function of waiting time being quadratic dependent on the preceding jump length are obtained by applying the derived master equation. Project supported by the Foundation for Young Key Teachers of Chengdu University of Technology, China (Grant No. KYGG201414) and the Opening Foundation of Geomathematics Key Laboratory of Sichuan Province, China (Grant No. scsxdz2013009).

  7. Validity and QOL of neck dissection preceding radiation therapy for hypopharyngeal cancer

    International Nuclear Information System (INIS)

    Uemura, Hirokazu; Yoshino, Kunitoshi; Fujii, Takashi; Suzuki, Motoyuki

    2009-01-01

    Thirty-one cases of hypopharyngeal cancer with neck dissection preceding radiation and 16 cases of hypopharyngeal cancer with neck dissection for locoregional recurrences after radiation were reviewed in order to make comparative evaluations of difficulty in surgical operation, postoperative complications, laryngeal preservation rate, and cause specific 5-year survival rate retrospectively. And quality of life (QOL) after neck dissection was additionally evaluated through the questionnaire. Since neck dissection preceding radiation for hypopharyngeal cancer may be superior to neck dissection for radiation failure, with easy surgical approach an non-lymphoid tissue preservation, that modality can be a reasonable choice of treatment for patients with nodal lesions, which are probably difficult to treat with radiation alone. Even though further investigation on QOL questionnaire is necessary, this modality can make a contribution to the neck and shoulder condition after neck dissection. (author)

  8. Will the judgment in the Hague trial constitute a precedent in international law

    Directory of Open Access Journals (Sweden)

    Bojanić Petar

    2006-01-01

    Full Text Available On the great crime (mala in se; scelus infandum and sovereignty In this text we are attempting to think the International Criminal Tribunal for the former Yugoslavia together, and always with its necessary connection to the International Court of Justice and International Criminal Court. By paraphrasing the title of another work, the long forgotten Hans Kelsen text from 1947 (today usually used by detractors of the Tribunal "Will the Judgment in the Nuremberg Trial constitute a Precedent in International Law?", I wish to distinguish between the two Tribunals (as well as The Treaty of Versaille,and in so doing treat international law as legislative history or judicial precedents (and their recognition.

  9. Influence of Sound Source Location on the Behavior and Physiology of the Precedence Effect in Cats

    OpenAIRE

    Dent, Micheal L.; Tollin, Daniel J.; Yin, Tom C. T.

    2009-01-01

    Psychophysical experiments on the precedence effect (PE) in cats have shown that they localize pairs of auditory stimuli presented from different locations in space based on the spatial position of the stimuli and the interstimulus delay (ISD) between the stimuli in a manner similar to humans. Cats exhibit localization dominance for pairs of transient stimuli with |ISDs| from ∼0.4 to 10 ms, summing localization for |ISDs| 10 ms, which is the appro...

  10. Legal precedents regarding use and defensibility of risk assessment in Federal transportation of SNF and HLW

    International Nuclear Information System (INIS)

    Bentz, E.J. Jr.; Bentz, C.B.; O'Hora, T.D.; Chen, S.Y.

    1997-01-01

    Risk assessment has become an increasingly important and essential tool in support of Federal decision-making regarding the handling, storage, disposal, and transportation of spent nuclear fuel (SNF) and high-level radioactive waste (HLW). This paper analyzes the current statutory and regulatory framework and related legal precedents with regard to SNF and HLW transportation. The authors identify key scientific and technical issues regarding the use and defensibility of risk assessment in Federal decision-making regarding anticipated shipments

  11. Organizational precedents for ownership and management of decentralized renewable-energy systems

    Energy Technology Data Exchange (ETDEWEB)

    Meunier, R.; Silversmith, J.A.

    1981-03-01

    Three existing organizational types that meet the decentralization criteria of local consumer ownership and control - cooperatives, Rural Electric Cooperatives, and municipal utilities - are examined. These three organizational precedents are analyzed in terms of their histories, structures, legal powers, sources of capital, and social and political aspects. Examples of related experiments with renewable energy technologies are given, and inferences are drawn regarding the organizations' suitability as vehicles for future implementation of decentralized renewable energy systems.

  12. Medical records documentation of constipation preceding Parkinson disease: A case-control study.

    Science.gov (United States)

    Savica, R; Carlin, J M; Grossardt, B R; Bower, J H; Ahlskog, J E; Maraganore, D M; Bharucha, A E; Rocca, W A

    2009-11-24

    Parkinson disease (PD) may affect the autonomic nervous system and may cause constipation; however, few studies have explored constipation preceding the motor onset of PD. We investigated constipation preceding PD using a case-control study design in a population-based sample. Using the medical records-linkage system of the Rochester Epidemiology Project, we identified 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records-linkage system to ascertain the occurrence of constipation preceding the onset of PD (or index year). Constipation preceding PD or the index year was more common in cases than in controls (odds ratio [OR] 2.48; 95% confidence interval [CI] 1.49 to 4.11; p = 0.0005). This association remained significant after adjusting for smoking and coffee consumption (ever vs never), and after excluding constipation possibly induced by drugs. In addition, the association remained significant in analyses restricted to constipation documented 20 or more years before the onset of motor symptoms of PD. Although the association was stronger in women than in men and in patients with PD with rest tremor compared with patients with PD without rest tremor, these differences were not significant. Our findings suggest that constipation occurring as early as 20 or more years before the onset of motor symptoms is associated with an increased risk of Parkinson disease.

  13. Diverticular colitis of the ascending colon preceding the onset of ulcerative colitis

    OpenAIRE

    Maeshiro, Tatsuji; Hokama, Akira; Kinjo, Tetsu; Fujita, Jiro

    2014-01-01

    We present a case of diverticular colitis of the ascending colon preceding the onset of ulcerative colitis. A 58-year-old man presented with positive faecal occult blood test. Colonoscopy disclosed diverticular colitis of the ascending colon. After a year's follow-up, typical ulcerative colitis developed and diverticular colitis improved. Diverticular colitis is a newly established disorder of chronic segmental mucosal inflammation affected by diverticular disease. There is increasing recogni...

  14. Designing a community engagement strategy for Limerick Smarter travel using focus groups and precedent studies

    OpenAIRE

    Cullinane, Kathleen Clair

    2012-01-01

    peer-reviewed This research aims to create a rational basis for designing and implementing a plan for Limerick Smarter Travel. This plan will pay particular attention to community engagement. This research establishes a rationale for a community engagement strategy. Precedent studies also provide direct guidance for this rationale. The objective of the plan is to develop a local culture of Smarter Travel in Limerick communities using best international practice, and thereby achieving behav...

  15. Quiet Periods in Edge Turbulence Preceding the L-H Transition in NSTX

    International Nuclear Information System (INIS)

    Zweben, S.; Maqueda, R.J.; Hager, R.; Hallatschek, K.; Kaye, S.M.; Munsat, T.; Poli, F.M.; Roquemore, A.L.; Sechrest, Y.; Stotler, D.P.

    2010-01-01

    This paper describes the first observations in NSTX of 'quiet periods' in the edge turbulence preceding the L-H transition, as diagnosed by the GPI diagnostic near the outer midplane separatrix. During these quiet periods the GPI D light emission pattern was transiently similar to that seen during Hmode, i.e. with a relatively small fraction of the GPI light emission located outside the separatrix. These quiet periods had a frequency of ∼3 kHz for at least 30 msec before the L-H transition, and were correlated with changes in the direction of the local poloidal velocity. The GPI turbulence images were also analyzed to obtain an estimate for the dimensionless poloidal shearing S =(dVp/dr)(Lr/Lp). The values of S were strongly modulated by the quiet periods, but not otherwise varying for at least 30 msec preceding the L-H transition. Since neither the quiet periods nor the shear flow increased significantly immediately preceding the L-H transition, neither of these appears to be the trigger for this transition, at least for these cases in NSTX.

  16. Factors preceding CRM readiness in small- and medium-sized tourism enterprises

    Directory of Open Access Journals (Sweden)

    Dinesh Vallabh

    2015-07-01

    Full Text Available Orientation: Customer relationship management (CRM is important to organisations striving for competitive advantage through building relationships with their customers. Research purpose: This study identified the factors preceding CRM and assessed selected South African small- and medium-sized tourism enterprises’ (SMTEs readiness for CRM. Motivation: CRM is likely to enhance SMTEs’ competitiveness. However, successful adoption and implementation of CRM is unlikely unless the organisation is ready for it. Research design, approach and method: A quantitative research approach and survey questionnaire yielded primary data from 332 respondent organisations selected by systematic sampling. Exploratory factor analysis was used to identify the latent factors preceding CRM readiness. Organisational CRM readiness was assessed based on CRM maturity in terms of data collection, use and sharing throughout the organisation. Main findings: Respondent-organisations performed well on the four factors preceding CRM readiness − business strategy, customer strategy, touch points and competencies, skills and technology and also on data collections and use, but not on data sharing. Practical/Managerial implications: CRM practice is believed to assist organisations in tailoring products and services to customers’ needs, providing customer satisfaction, enhancing customer retention and ultimately improving the organisation’s competitiveness and profitability. CRM might fail if SMTEs do not have CRM-enabling conditions in place and a CRM readiness audit should therefore be performed. Contribution: The study contributes to a largely under-researched area concerning CRM in SMTEs by providing an improved understanding of the factors that will enable SMTEs to engage in CRM activities.

  17. The value of auditing negative lower GI investigations preceding a final diagnosis of colorectal cancer.

    Science.gov (United States)

    Somasekar, A; James, L; Stephenson, B M; Thompson, I W; Vellacott, K D; Allison, M C

    2009-09-01

    To review all preceding 'negative' large bowel investigations in patients with a final diagnosis of colorectal cancer, and to examine whether delayed diagnosis was associated with worse outcome. Details were gathered on all patients with a new diagnosis of colorectal adenocarcinoma presenting over 4.5 years. For each patient the hospital's clinical workstation and radiology and endoscopy databases were interrogated for all flexible sigmoidoscopies, colonoscopies and barium enemas during the 5 years prior to diagnosis. Among the 570 patients, 28 (5%) had undergone colonoscopy and/or flexible sigmoidoscopy that had not shown colorectal cancer during the 5 years preceding final diagnosis, and a further 28 (5%) had undergone 'negative' barium enemas. Polyp surveillance might have missed four lesions destined to become malignant. Correspondingly there were three patients undergoing IBD surveillance found to have CRC, having had a negative complete colonoscopy within the preceding 5 years. Among patients undergoing de novo colonoscopy for diagnosis the true miss rate was only one patient per year. At August 2007, 29 (58%) of those with delayed diagnosis were still alive, compared with 216 (42%) of those diagnosed during initial investigation (chi2 = 5.04, P auditing the quality assurance of lower gastrointestinal diagnostic services. Despite the delay, late diagnosis was found to be associated with improved survival and a lower likelihood of metastatic disease.

  18. The Response of Durum Wheat to the Preceding Crop in a Mediterranean Environment

    Directory of Open Access Journals (Sweden)

    Laura Ercoli

    2014-01-01

    Full Text Available Crop sequence is an important management practice that may affect durum wheat (Triticum durum Desf. production. Field research was conducted in 2007-2008 and 2008-2009 seasons in a rain-fed cold Mediterranean environment to examine the impact of the preceding crops alfalfa (Medicago sativa L., maize (Zea mays L., sunflower (Helianthus annuus L., and bread wheat (Triticum aestivum L. on yield and N uptake of four durum wheat varieties. The response of grain yield of durum wheat to the preceding crop was high in 2007-2008 and was absent in the 2008-2009 season, because of the heavy rainfall that negatively impacted establishment, vegetative growth, and grain yield of durum wheat due to waterlogging. In the first season, durum wheat grain yield was highest following alfalfa, and was 33% lower following wheat. The yield increase of durum wheat following alfalfa was mainly due to an increased number of spikes per unit area and number of kernels per spike, while the yield decrease following wheat was mainly due to a reduction of spike number per unit area. Variety growth habit and performance did not affect the response to preceding crop and varieties ranked in the order Levante > Saragolla = Svevo > Normanno.

  19. Measuring Algorithm for the Distance to a Preceding Vehicle on Curve Road Using On-Board Monocular Camera

    Science.gov (United States)

    Yu, Guizhen; Zhou, Bin; Wang, Yunpeng; Wun, Xinkai; Wang, Pengcheng

    2015-12-01

    Due to more severe challenges of traffic safety problems, the Advanced Driver Assistance Systems (ADAS) has received widespread attention. Measuring the distance to a preceding vehicle is important for ADAS. However, the existing algorithm focuses more on straight road sections than on curve measurements. In this paper, we present a novel measuring algorithm for the distance to a preceding vehicle on a curve road using on-board monocular camera. Firstly, the characteristics of driving on the curve road is analyzed and the recognition of the preceding vehicle road area is proposed. Then, the vehicle detection and distance measuring algorithms are investigated. We have verified these algorithms on real road driving. The experimental results show that this method proposed in the paper can detect the preceding vehicle on curve roads and accurately calculate the longitudinal distance and horizontal distance to the preceding vehicle.

  20. PPARGC1A is upregulated and facilitates lung cancer metastasis.

    Science.gov (United States)

    Li, Jin-Dong; Feng, Qing-Chuan; Qi, Yu; Cui, Guanghui; Zhao, Song

    2017-10-15

    Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAI1), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis. Copyright © 2017. Published by Elsevier Inc.

  1. Upregulation of LYAR induces neuroblastoma cell proliferation and survival.

    Science.gov (United States)

    Sun, Yuting; Atmadibrata, Bernard; Yu, Denise; Wong, Matthew; Liu, Bing; Ho, Nicholas; Ling, Dora; Tee, Andrew E; Wang, Jenny; Mungrue, Imran N; Liu, Pei Y; Liu, Tao

    2017-09-01

    The N-Myc oncoprotein induces neuroblastoma by regulating gene transcription and consequently causing cell proliferation. Paradoxically, N-Myc is well known to induce apoptosis by upregulating pro-apoptosis genes, and it is not clear how N-Myc overexpressing neuroblastoma cells escape N-Myc-mediated apoptosis. The nuclear zinc finger protein LYAR has recently been shown to modulate gene expression by forming a protein complex with the protein arginine methyltransferase PRMT5. Here we showed that N-Myc upregulated LYAR gene expression by binding to its gene promoter. Genome-wide differential gene expression studies revealed that knocking down LYAR considerably upregulated the expression of oxidative stress genes including CHAC1, which depletes intracellular glutathione and induces oxidative stress. Although knocking down LYAR expression with siRNAs induced oxidative stress, neuroblastoma cell growth inhibition and apoptosis, co-treatment with the glutathione supplement N-acetyl-l-cysteine or co-transfection with CHAC1 siRNAs blocked the effect of LYAR siRNAs. Importantly, high levels of LYAR gene expression in human neuroblastoma tissues predicted poor event-free and overall survival in neuroblastoma patients, independent of the best current markers for poor prognosis. Taken together, our data suggest that LYAR induces proliferation and promotes survival of neuroblastoma cells by repressing the expression of oxidative stress genes such as CHAC1 and suppressing oxidative stress, and identify LYAR as a novel co-factor in N-Myc oncogenesis.

  2. Sentinel Events Preceding Youth Firearm Violence An Investigation of Administrative Data in Delaware

    Science.gov (United States)

    Sumner, Steven A.; Maenner, Matthew J.; Socias, Christina M.; Mercy, James A.; Silverman, Paul; Medinilla, Sandra P.; Martin, Steven S.; Xu, Likang; Hillis, Susan D.

    2018-01-01

    Introduction Accurately identifying youth at highest risk of firearm violence involvement could permit delivery of focused, comprehensive prevention services. This study explored whether readily available city and state administrative data covering life events before youth firearm violence could elucidate patterns preceding such violence. Methods Four hundred twenty-one individuals arrested for homicide, attempted homicide, aggravated assault, or robbery with a firearm committed in Wilmington, Delaware, from January 1, 2009 to May 21, 2014, were matched 1:3 to 1,259 Wilmington resident controls on birth year and sex. In 2015, descriptive statistics and a conditional logistic regression model using Delaware healthcare, child welfare, juvenile services, labor, and education administrative data examined associations between preceding life events and subsequent firearm violence. Results In a multivariable adjusted model, experiencing a prior gunshot wound injury (AOR=11.4, 95% CI=2.7, 48.1) and being subject to community probation (AOR=13.2, 95% CI=5.7, 30.3) were associated with the highest risk of subsequent firearm violence perpetration, though multiple other sentinel events were informative. The mean number of sentinel events experienced by youth committing firearm violence was 13.0 versus 1.9 among controls (pviolence. Conclusions Youth who commit firearm violence have preceding patterns of life events that markedly differ from youth not involved in firearm violence. This information is readily available from administrative data, demonstrating the potential of data sharing across city and state institutions to focus prevention strategies on those at greatest risk. PMID:27742157

  3. Behaviour of coconut mites preceding take-off to passive aerial dispersal.

    Science.gov (United States)

    Melo, J W S; Lima, D B; Sabelis, M W; Pallini, A; Gondim, M G C

    2014-12-01

    For more than three decades the coconut mite Aceria guerreronis Keifer is one of the most important pests of coconut palms and has recently spread to many coconut production areas worldwide. Colonization of coconut palms is thought to arise from mites dispersing aerially after take-off from other plants within the same plantation or other plantations. The underlying dispersal behaviour of the mite at take-off, in the airborne state and after landing is largely unknown and this is essential to understand how they spread from tree to tree. In this article we studied whether take-off to aerial dispersal of coconut mites is preceded by characteristic behaviour, whether there is a correlation between the body position preceding aerial dispersal and the direction of the wind, and whether the substrate (outer surface of coconut bracts or epidermis) and the wind speed matter to the decision to take-off. We found that take-off can sometimes be preceded by a raised body stance, but more frequently take-off occurs while the mite is walking or resting on its substrate. Coconut mites that become airborne assumed a body stance that had no relation to the wind direction. Take-off was suppressed on a substrate providing food to coconut mites, but occurred significantly more frequently on the outer surface of coconut bracts than on the surface of the fruit. For both substrates, take-off frequency increased with wind speed. We conclude that coconut mites have at least some degree of control over take-off for aerial dispersal and that there is as yet no reason to infer that a raised body stance is necessary to become airborne.

  4. Development of a Rheumatoid Arthritis Education Program using the PRECEDE_PROCEED Model

    Directory of Open Access Journals (Sweden)

    Kaveh Bahmanpour

    2011-12-01

    Full Text Available Background: In order to help rheumatoid arthritis (RA patients in carrying out and attaining relevant self-care behaviors and adaptation to the physical limitations of this disease and, conse-quently, promoting their level of health status, an education program based on the PRECEDE component of the PRECEDE–PROCEED model targeting patients with RA was developed. This paper describes the planning of a RA Patient Education Program (RAPEP designed to promote their quality of life.Methods: The development of the program began with a comprehensive review of the literature. This included a review of the signs and symptoms of RA, accompanying functional disabilities, previous educational programs and the effect of the disease on the patient’s quality of life. Be-sides, in order to help inform RAPEP program development, and organize the survey according to the factors identified in the PRECEDE model a cross-sectional survey was applied on a non-prob-ability sample of 181 outpatients in Yazd, center of Iran.Results: The quality of life (QOL problem identified was the considerable low role functioning, health perception and physical functioning due to chronic pain. One of the most significant modi-fiable behavioral factors impacting pain and functional limitations was self-care behaviors in RA patients. Higher level of knowledge, attitude, self-efficacy, enabling factors and social support is associated with better self-care behavior.Conclusions: The PRECEDE component of the PRECEDE–PROCEED model provided a com-prehensive conceptual framework for the development of RAPEP aiming at RA patients in Yazd. Further research to evaluate this educational program is suggested.

  5. Characteristics of Precedent : The Case Law of the European Court of Justice in Three Dimensions

    OpenAIRE

    Derlén, Mattias; Lindholm, Johan

    2015-01-01

    The case law of the Court of Justice of the European Union (CJEU) is one of the most important sources of European Union law. However, case law’s role in EU law is not uniform. By empirically studying how the Court uses its own case law as a source of law, we explore the correlation between, on the one hand, the characteristics of a CJEU case— type of action, actors involved, and area of law—and, on the other hand, the judgment’s “embeddedness” in previous case law and value as a precedent in...

  6. The Preceding Voltage Pulse and Separation Welding Mechanism of Electrical Contacts

    DEFF Research Database (Denmark)

    Yang, Xiao Cheng; Huang, Jiang; Li, Zhen Biao

    2016-01-01

    In order to obtain a better understanding of the welding mechanism in contact separation, electrical endurance tests were conducted with AgSnO2 and AgNi contacts on a simulation test device. Waveforms of contact displacement, contact voltage, and current were recorded with LabVIEW during the tests......, and changes in a contact gap and heights of pips with increases in operation cycles were observed through charge-coupled device cameras. The resultant test results show that welding in separation is accompanied with a preceding voltage pulse which represents arc rather than contact bounce arc....

  7. Urinary Tract Infection Associated with a Celiac Crisis: A Preceding or Precipitating Event?

    Science.gov (United States)

    Tiwari, Abhinav; Qamar, Khola; Sharma, Himani; Almadani, Sameh Bashar

    2017-01-01

    Celiac crisis is a rare life-threatening presentation of celiac disease that manifests as profuse diarrhea, hypoproteinemia, and severe metabolic disturbances. It may be precipitated by a general immune stimulus such as surgery, infection, or pregnancy. We report the case of a 26-year-old woman who presented with a celiac crisis, potentially triggered by a preceding urinary tract infection. Metabolic derangement is caused by malabsorption and profuse diarrhea, which can be unremitting unless the celiac crisis is recognized, and treatment with gluten restriction is initiated.

  8. An Adaptive Evolutionary Algorithm for Traveling Salesman Problem with Precedence Constraints

    Directory of Open Access Journals (Sweden)

    Jinmo Sung

    2014-01-01

    Full Text Available Traveling sales man problem with precedence constraints is one of the most notorious problems in terms of the efficiency of its solution approach, even though it has very wide range of industrial applications. We propose a new evolutionary algorithm to efficiently obtain good solutions by improving the search process. Our genetic operators guarantee the feasibility of solutions over the generations of population, which significantly improves the computational efficiency even when it is combined with our flexible adaptive searching strategy. The efficiency of the algorithm is investigated by computational experiments.

  9. Preventive aspects in children's caries treatments preceding dental care under general anaesthesia.

    Science.gov (United States)

    Savanheimo, Nora; Vehkalahti, Miira M

    2008-03-01

    In Helsinki Public Dental Service (PDS) the Special Oral Health Care Unit (SOHCU) provides comprehensive dental treatments under general anaesthesia (GA). For the present study, all dental treatment given under GA for generally healthy children (n = 102) below 16 years of age (range 2.3-15.8) during a 1-year period and dental treatment and visits of these children in the preceding 2 years in Helsinki PDS was recorded in detail. These children were referred to the SOHCU because of serious difficulties in dental care due to large treatment needs or failures in psychological and chemical management, including sedation. To describe treatments given to generally healthy children under GA and to evaluate preventive aspects of their dental care in the preceding 2 years. The study was cross-sectional and retrospective. Data came from the patients' individual records. Treatments under GA included an average of 6.0 restorations (SD = 2.7, range 0-12) and 1.7 extractions (SD = 2.1, range 0-10). In the 2 preceding years, these children had visited dentist an average of 5.1 times (SD = 2.7, range 1-14) with an average of 2.4 restorations (SD = 1.9, range 0-12) and 0.5 extractions (SD = 1.4, range 0-10). Of the restorations made, 36% were temporary. Of all visits, those with an operative approach accounted for 35%, preventive for 37%, operative and preventive for 5%, and visits with total uncooperation for 23%. Of the children, 90% had at least one preventive visit. Children treated under conscious sedation in the preceding 2 years received less prevention (P = 0.02). Remaining without preventive measures was most likely for those children exhibiting visits with total uncooperation (odds ratio = 4.6; P = 0.004) and for those receiving numerous temporary fillings (odds ratio = 4.1; P = 0.0005). The uncooperative high-caries children pose a demanding challenge to PDS. The early identification of high-caries risk and efforts of intensive preventive care are in key position to

  10. Investigating the build-up of precedence effect using reflection masking

    DEFF Research Database (Denmark)

    Hartcher-O'Brien, Jessica; Buchholz, Jörg

    2006-01-01

    signal processing, such an approach represents a bottom-up approach to the buildup of precedence. Three conditioner configurations measuring a possible buildup of reflection suppression were compared to the baseline RMT for four reflection delays ranging from 2.5–15 ms. No buildup of reflection...... suppression was observed for any of the conditioner configurations. Buildup of template (decrease in RMT for two of the conditioners), on the other hand, was found to be delay dependent. For five of six listeners, with reflection delay=2.5 and 15 ms, RMT decreased relative to the baseline. For 5- and 10-ms...

  11. Solving a large-scale precedence constrained scheduling problem with elastic jobs using tabu search

    DEFF Research Database (Denmark)

    Pedersen, C.R.; Rasmussen, R.V.; Andersen, Kim Allan

    2007-01-01

    exploitation of the elastic jobs and solve the problem using a tabu search procedure. Finding an initial feasible solution is in general -complete, but the tabu search procedure includes a specialized heuristic for solving this problem. The solution method has proven to be very efficient and leads......This paper presents a solution method for minimizing makespan of a practical large-scale scheduling problem with elastic jobs. The jobs are processed on three servers and restricted by precedence constraints, time windows and capacity limitations. We derive a new method for approximating the server...... to a significant decrease in makespan compared to the strategy currently implemented....

  12. Solving a large-scale precedence constrained scheduling problem with elastic jobs using tabu search

    DEFF Research Database (Denmark)

    Pedersen, C.R.; Rasmussen, R.V.; Andersen, Kim Allan

    2007-01-01

    This paper presents a solution method for minimizing makespan of a practical large-scale scheduling problem with elastic jobs. The jobs are processed on three servers and restricted by precedence constraints, time windows and capacity limitations. We derive a new method for approximating the server...... exploitation of the elastic jobs and solve the problem using a tabu search procedure. Finding an initial feasible solution is in general -complete, but the tabu search procedure includes a specialized heuristic for solving this problem. The solution method has proven to be very efficient and leads...

  13. The upper spatial limit for perception of displacement is affected by preceding motion.

    Science.gov (United States)

    Stefanova, Miroslava; Mateeff, Stefan; Hohnsbein, Joachim

    2009-03-01

    The upper spatial limit D(max) for perception of apparent motion of a random dot pattern may be strongly affected by another, collinear, motion that precedes it [Mateeff, S., Stefanova, M., &. Hohnsbein, J. (2007). Perceived global direction of a compound of real and apparent motion. Vision Research, 47, 1455-1463]. In the present study this phenomenon was studied with two-dimensional motion stimuli. A random dot pattern moved alternately in the vertical and oblique direction (zig-zag motion). The vertical motion was of 1.04 degrees length; it was produced by three discrete spatial steps of the dots. Thereafter the dots were displaced by a single spatial step in oblique direction. Each motion lasted for 57ms. The upper spatial limit for perception of the oblique motion was measured under two conditions: the vertical component of the oblique motion and the vertical motion were either in the same or in opposite directions. It was found that the perception of the oblique motion was strongly influenced by the relative direction of the vertical motion that preceded it; in the "same" condition the upper spatial limit was much shorter than in the "opposite" condition. Decreasing the speed of the vertical motion reversed this effect. Interpretations based on networks of motion detectors and on Gestalt theory are discussed.

  14. Nonseizure SUDEP: Sudden unexpected death in epilepsy without preceding epileptic seizures.

    Science.gov (United States)

    Lhatoo, Samden D; Nei, Maromi; Raghavan, Manoj; Sperling, Michael; Zonjy, Bilal; Lacuey, Nuria; Devinsky, Orrin

    2016-07-01

    To describe the phenomenology of monitored sudden unexpected death in epilepsy (SUDEP) occurring in the interictal period where death occurs without a seizure preceding it. We report a case series of monitored definite and probable SUDEP where no electroclinical evidence of underlying seizures was found preceding death. Three patients (two definite and one probable) had SUDEP. They had a typical high SUDEP risk profile with longstanding intractable epilepsy and frequent generalized tonic-clonic seizures (GTCS). All patients had varying patterns of respiratory and bradyarrhythmic cardiac dysfunction with profound electroencephalography (EEG) suppression. In two patients, patterns of cardiorespiratory failure were similar to those seen in some patients in the Mortality in Epilepsy Monitoring Units Study (MORTEMUS). SUDEP almost always occur postictally, after GTCS and less commonly after a partial seizure. Monitored SUDEP or near-SUDEP cases without a seizure have not yet been reported in literature. When nonmonitored SUDEP occurs in an ambulatory setting without an overt seizure, the absence of EEG information prevents the exclusion of a subtle seizure. These cases confirm the existence of nonseizure SUDEP; such deaths may not be prevented by seizure detection-based devices. SUDEP risk in patients with epilepsy may constitute a spectrum of susceptibility wherein some are relatively immune, death occurs in others with frequent GTCS with one episode of seizure ultimately proving fatal, while in others still, death may occur even in the absence of a seizure. We emphasize the heterogeneity of SUDEP phenomena. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  15. Situational Factors of Influencing Drivers to Give Precedence to Jaywalking Pedestrians at Signalized Crosswalk

    Directory of Open Access Journals (Sweden)

    Xiaobei Jiang

    2011-12-01

    Full Text Available A large number of fatalities are caused by the vehicle-pedestrian accidents. Under a potential conflict between the vehicle and jaywalking pedestrian, giving precedence to the pedestrian will be a proper decision taken by the driver to avoid collision. Field traffic data has been collected by video recording and image processing at two signalized crosswalks. Vehicle speed performance in the single vehicle-pedestrian encounter and platoon vehicle-pedestrian encounter were analyzed for understanding the driver behavior in the conflict process. Binary logic model was proposed to estimate the drivers' giving precedence influenced by the situational factors and the model was validated to predict the drivers' choices accurately. The vehicle speed, pedestrian speed, pedestrian lateral distance and the vehicle longitudinal distance to the conflict point were proved to affect the drivers' choices in platoon driving. The research results would hopefully be helpful to the design of intelligent vehicles and pedestrian protection systems by the knowledge-based decision making process.

  16. Patterns of Life Events Preceding the Suicide in Rural Young Chinese: A Case Control Study1

    Science.gov (United States)

    Zhang, Jie; Ma, Zhenyu

    2012-01-01

    Background Previous studies on the Chinese suicide found some life events prior to the suicide different from those in the West, but there is a lack of summary of the Chinese life event patterns to better understand the effects of the social structure on Chinese suicide. Aim We tried to identify the life events that precede the Chinese rural youth suicides and compare them with what found in the West, so as to find the patterns that are particularly true in the Chinese culture contexts. Methods Suicide cases were investigated with a psychological autopsy study in rural China, and local community living controls were also interviewed with the same protocol. Results We collapsed 64 negative life events into six categories: (1) Marriage/Love, (2) Family/Home, (3) Work/Business, (4) Health/Hospital, (5) Law/Legal, (6) Friend/Relationship. About 92.3% of the suicides studied had experienced at least one type of negative life events. The three most common negative life events categories in the past one year were Family/Home (60.7%), Health/Hospital (53.8%) and Marriage/Love (51.3%) in the rural young suicide victims. Conclusions Among the negative life events, those related to family relations, love affairs, and marital issues were most likely to precede a suicide of rural suicides in China, and it is especially true of rural young women. Family is an important social institution in rural China for suicide prevention efforts. PMID:22595373

  17. HIGH-RESOLUTION SIMULATIONS OF CONVECTION PRECEDING IGNITION IN TYPE Ia SUPERNOVAE USING ADAPTIVE MESH REFINEMENT

    International Nuclear Information System (INIS)

    Nonaka, A.; Aspden, A. J.; Almgren, A. S.; Bell, J. B.; Zingale, M.; Woosley, S. E.

    2012-01-01

    We extend our previous three-dimensional, full-star simulations of the final hours of convection preceding ignition in Type Ia supernovae to higher resolution using the adaptive mesh refinement capability of our low Mach number code, MAESTRO. We report the statistics of the ignition of the first flame at an effective 4.34 km resolution and general flow field properties at an effective 2.17 km resolution. We find that off-center ignition is likely, with radius of 50 km most favored and a likely range of 40-75 km. This is consistent with our previous coarser (8.68 km resolution) simulations, implying that we have achieved sufficient resolution in our determination of likely ignition radii. The dynamics of the last few hot spots preceding ignition suggest that a multiple ignition scenario is not likely. With improved resolution, we can more clearly see the general flow pattern in the convective region, characterized by a strong outward plume with a lower speed recirculation. We show that the convective core is turbulent with a Kolmogorov spectrum and has a lower turbulent intensity and larger integral length scale than previously thought (on the order of 16 km s –1 and 200 km, respectively), and we discuss the potential consequences for the first flames.

  18. An fMRI investigation into the effect of preceding stimuli during visual oddball tasks.

    Science.gov (United States)

    Fajkus, Jiří; Mikl, Michal; Shaw, Daniel Joel; Brázdil, Milan

    2015-08-15

    This study investigates the modulatory effect of stimulus sequence on neural responses to novel stimuli. A group of 34 healthy volunteers underwent event-related functional magnetic resonance imaging while performing a three-stimulus visual oddball task, involving randomly presented frequent stimuli and two types of infrequent stimuli - targets and distractors. We developed a modified categorization of rare stimuli that incorporated the type of preceding rare stimulus, and analyzed the event-related functional data according to this sequence categorization; specifically, we explored hemodynamic response modulation associated with increasing rare-to-rare stimulus interval. For two consecutive targets, a modulation of brain function was evident throughout posterior midline and lateral temporal cortex, while responses to targets preceded by distractors were modulated in a widely distributed fronto-parietal system. As for distractors that follow targets, brain function was modulated throughout a set of posterior brain structures. For two successive distractors, however, no significant modulation was observed, which is consistent with previous studies and our primary hypothesis. The addition of the aforementioned technique extends the possibilities of conventional oddball task analysis, enabling researchers to explore the effects of the whole range of rare stimuli intervals. This methodology can be applied to study a wide range of associated cognitive mechanisms, such as decision making, expectancy and attention. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice

    International Nuclear Information System (INIS)

    Wang, Degui; Yu, Tianyu; Liu, Yongqiang; Yan, Jun; Guo, Yingli; Jing, Yuhong; Yang, Xuguang; Song, Yanfeng; Tian, Yingxia

    2016-01-01

    Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages. - Highlights: • This study explore contribution of DNA damage to neurodegeneration in Parkinson's disease mice. • A53T-α-Syn MEF cells show a prolonged DNA damage repair process and senescense phenotype. • DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice. • DNA damage decrease the number of nigrostriatal dopaminergic neurons. • Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages.

  20. Left ventricle expands maximally preceding end-diastole. Radionuclide ventriculography study

    International Nuclear Information System (INIS)

    Horinouchi, Osamu

    2002-01-01

    It has been considered that left ventricle (LV) expands maximally at the end-diastole. However, is it exactly coincident with this point? This study was aimed to determine whether the maximal expansion of LV coincides with the peak of R wave on electrocardiogram. Thirty-three angina pectoris patients with normal LV motion were examined using radionuclide ventriculography. Data were obtained from every 30 ms backward frame from the peak of R wave. All patients showed the time of maximal expansion preceded the peak of R wave. The intervals from the peak of R wave and the onset of P wave to maximal expansion of LV was 105±29 ms and 88±25 ms, respectively. This period corresponds to the timing of maximal excurtion of mitral valve by atrial contraction, and the centripetal motion of LV without losing its volume before end-diastole may be interpreted on account of the movement of mitral valve toward closure. These findings suggest that LV expands maximally between P and R wave after atrial contraction, preceding the peak of R wave thought conventionally as the end-diastole. (author)

  1. Stressful life events preceding the onset of depression in Asian patients with major depressive disorder.

    Science.gov (United States)

    Park, Subin; Hatim, Ahmad; Si, Tian-Mei; Jeon, Hong Jin; Srisurapanont, Manit; Bautista, Dianne; Liu, Shen-ing; Chua, Hong Choon; Hong, Jin Pyo

    2015-12-01

    Previous studies have identified the significant role of stressful life events in the onset of depressive episodes. However, there is a paucity of cross-national studies on stressful life events that precede depression. We aimed to compare types of stressful life events associated with the onset of depressive episodes in patients with major depressive disorder (MDD) in five Asian countries. A total of 507 outpatients with MDD were recruited in China (n = 114), South Korea (n = 101), Malaysia (n = 90), Thailand (n = 103) and Taiwan (n = 99). All patients were assessed with the Mini-International Neuropsychiatric Interview and the List of Threatening Experiences. The prevalence of each type of stressful life events was calculated and compared between each country. The type of stressful life event that preceded the onset of a depressive episode differed between patients in China and Taiwan and those in South Korea, Malaysia and Thailand. Patients in China and Taiwan were less likely to report interpersonal relationship problems and occupational/financial problems than patients in South Korea, Malaysia and Thailand. Understanding the nature and basis of culturally determined susceptibilities to specific stressful life events is critical for establishing a policy of depression prevention and providing effective counseling services for depressed patients. © The Author(s) 2015.

  2. A Legal Analysis of the Precedents of Medical Disputes in the Cosmetic Surgery Field.

    Science.gov (United States)

    Park, Bo Young; Kim, Min Ji; Kang, So Ra; Hong, Seung Eun

    2016-05-01

    Disputes regarding medical malpractice occur between practitioners and patients. As patients have become increasingly aware regarding medical care, an increase in the unexpected side effects of procedures has been observed, thereby leading to an increase in disputes regarding medical malpractice. In this study, we reviewed trends in precedents involving cosmetic surgery-related medical disputes, with the goal of helping to prevent unnecessary disputes in the future. We conducted a search of the judgments made in South Korean courts between 2000 and 2013 that were related to the field of plastic surgery. A total of 54 judgments were analyzed, and the selected precedents were reviewed and classified according to the kind of negligence involved. The claim amounts ranged from under 8 million KRW (6,991 USD) to 750 million KRW (629,995 USD). The most common ratio of the judgment amount to the claim amount was 20%-30%. The judgments were classified according to the following categories: violation of the duty of explanation in 17 cases (29%), violation of the duty of care in 10 cases (17%), violation of both duties in 20 cases (35%), and no violation of duty in six cases (10%). Cosmetic surgery-related suits require different approaches than general malpractice suits. The Supreme Court requires plastic surgeons to determine the type, timing, methods, and scope of their treatments when considering possible results. Therefore, practitioners should be educated on their rights and responsibilities to enable them to cope with any possible medical dispute that may arise.

  3. QUOTEchemo: a patient-centered instrument to measure quality of communication preceding chemotherapy treatment through the patient’s eyes

    NARCIS (Netherlands)

    van Weert, J.C.M.; Jansen, J.; de Bruijn, G.J.; Noordman, J.; van Dulmen, S.

    2009-01-01

    Background: Knowing patients’ needs is a prerequisite to ensure high quality cancer care. This study describes the development and psychometric properties of a patient-centred instrument to measure needs and actual experiences with communication preceding chemotherapy treatment: QUOTEchemo.

  4. QUOTEchemo: a patient-centered instrument to measure quality of communication preceding chemotherapy treatment through the patient's eyes.

    NARCIS (Netherlands)

    Weert, J.C.M. van; Jansen, J.; Bruijn, G.J. de; Noordman, J.; Dulmen, A.M. van; Bensing, J.M.

    2009-01-01

    Background: Knowing patients’ needs is a prerequisite to ensure high quality cancer care. This study describes the development and psychometric properties of a patient-centred instrument to measure needs and actual experiences with communication preceding chemotherapy treatment: QUOTEchemo.

  5. Anomalous high-frequency wave activity flux preceding anomalous changes in the Northern polar jet

    Science.gov (United States)

    Nakamura, Mototaka; Kadota, Minoru; Yamane, Shozo

    2010-05-01

    Anomalous forcing by quasi-geostrophic (QG) waves has been reported as an important forcing factor in the Northern Annular Mode (NAM) in recent literatures. In order to shed a light on the dynamics of the NAM from a different angle, we have examined anomalous behavior of the winter jets in the upper troposphere and stratosphere by focusing our diagnosis on not the anomalous geopotential height (Z) itself, but on the anomalous change in the Z (dZ) between two successive months and preceding transient QG wave activity flux during the cold season. We calculated EOFs of dZ between two successive months at 150hPa for a 46-year period, from 1958 to 2003, using the monthly mean NCEP reanalysis data. We then formed anomaly composites of changes in Z and the zonal velocity (U), as well as the preceding and following wave activity flux, Z, U, and temperature at various heights, for both positive and negative phases of the first EOF. For the wave forcing fields, we adopted the diagnostic system for the three-dimensional QG transient wave activity flux in the zonally-varying three-dimensional mean flow developed by Plumb (1986) with a slight modification in its application to the data. Our choice of the Plumb86 is based on the fact that the winter mean flow in the Northern Hemisphere is characterized by noticeable zonal asymmetry, and has a symbiotic relationship with waves in the extra-tropics. The Plumb86 flux was calculated for high-frequency (period of 2 to 7 days) and low-frequency (period of 10 to 20 days) waves with the ultra-low-frequency (period of 30 days or longer) flow as the reference state for each time frame of the 6 hourly NCEP reanalysis data from 1958 to 2003. By replacing the mean flow with the ultra-low-frequency flow in the application of the Plumb86 formula, the flux fields were calculated as time series at 6 hour intervals. The time series of the wave activity flux was then averaged for each month. The patterns of composited anomalous dZ and dU clearly

  6. Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Yeom, Chul-gon; Kim, Dong-il; Park, Min-jung; Choi, Joo-hee [College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Jeong, Jieun; Wi, Anjin; Park, Whoashig [Jeollanamdo Forest Resources Research Institute, Naju 520-833 (Korea, Republic of); Han, Ho-jae [College of Veterinary Medicine, Seoul National University, Seoul 151-741 (Korea, Republic of); Park, Soo-hyun, E-mail: parksh@chonnam.ac.kr [College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 (Korea, Republic of)

    2015-06-05

    Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expression in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation.

  7. Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

    International Nuclear Information System (INIS)

    Yeom, Chul-gon; Kim, Dong-il; Park, Min-jung; Choi, Joo-hee; Jeong, Jieun; Wi, Anjin; Park, Whoashig; Han, Ho-jae; Park, Soo-hyun

    2015-01-01

    Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expression in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

  8. Upregulated copper transporters in hypoxia-induced pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Adriana M Zimnicka

    Full Text Available Pulmonary vascular remodeling and increased arterial wall stiffness are two major causes for the elevated pulmonary vascular resistance and pulmonary arterial pressure in patients and animals with pulmonary hypertension. Cellular copper (Cu plays an important role in angiogenesis and extracellular matrix remodeling; increased Cu in vascular smooth muscle cells has been demonstrated to be associated with atherosclerosis and hypertension in animal experiments. In this study, we show that the Cu-uptake transporter 1, CTR1, and the Cu-efflux pump, ATP7A, were both upregulated in the lung tissues and pulmonary arteries of mice with hypoxia-induced pulmonary hypertension. Hypoxia also significantly increased expression and activity of lysyl oxidase (LOX, a Cu-dependent enzyme that causes crosslinks of collagen and elastin in the extracellular matrix. In vitro experiments show that exposure to hypoxia or treatment with cobalt (CoCl2 also increased protein expression of CTR1, ATP7A, and LOX in pulmonary arterial smooth muscle cells (PASMC. In PASMC exposed to hypoxia or treated with CoCl2, we also confirmed that the Cu transport is increased using 64Cu uptake assays. Furthermore, hypoxia increased both cell migration and proliferation in a Cu-dependent manner. Downregulation of hypoxia-inducible factor 1α (HIF-1α with siRNA significantly attenuated hypoxia-mediated upregulation of CTR1 mRNA. In summary, the data from this study indicate that increased Cu transportation due to upregulated CTR1 and ATP7A in pulmonary arteries and PASMC contributes to the development of hypoxia-induced pulmonary hypertension. The increased Cu uptake and elevated ATP7A also facilitate the increase in LOX activity and thus the increase in crosslink of extracellular matrix, and eventually leading to the increase in pulmonary arterial stiffness.

  9. Rottlerin upregulates DDX3 expression in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Zhong; Shen, Gen-Hai; Xie, Jia-Ming; Li, Bin; Gao, Quan-Gen

    2018-01-01

    Rottlerin has been reported to exert its anti-tumor activity in various types of human cancers. However, the underlying molecular mechanism has not been fully elucidated. In the current study, we explored whether rottlerin exhibits its tumor suppressive function in hepatocellular carcinoma cells. Our MTT assay results showed that rottlerin inhibited cell growth in hepatocellular carcinoma cells. Moreover, we found that rottlerin induced cell apoptosis and caused cell cycle arrest at G1 phase. Furthermore, our wound healing assay result demonstrated that rottlerin retarded cell migration in hepatocellular carcinoma cells. Additionally, rottlerin suppressed cell migration and invasion. Notably, we found that rottlerin upregulated DDX3 expression and subsequently downregulated Cyclin D1 expression and increased p21 level. Importantly, down-regulation of DDX3 abrogated the rottlerin-mediated tumor suppressive function, whereas overexpression of DDX3 promoted the anti-tumor activity of rottlerin. Our study suggests that rottlerin exhibits its anti-cancer activity partly due to upregulation of DDX3 in hepatocellular carcinoma cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase

    Directory of Open Access Journals (Sweden)

    Kao Ming-Ching

    2011-02-01

    Full Text Available Abstract Background Hyperbaric oxygen therapy (HBOT is a known adjuvant for treating ischemia-related inner ear diseases. Controversies still exist in the role of HBOT in cochlear diseases. Few studies to date have investigated the cellular changes that occur in inner ears after HBOT. Nitric oxide, which is synthesized by nitric oxide synthase (NOS, is an important signaling molecule in cochlear physiology and pathology. Here we investigated the effects of hyperbaric oxygen on eardrum morphology, cochlear function and expression of NOS isoforms in cochlear substructures after repetitive HBOT in guinea pigs. Results Minor changes in the eardrum were observed after repetitive HBOT, which did not result in a significant hearing threshold shift by tone burst auditory brainstem responses. A differential effect of HBOT on the expression of NOS isoforms was identified. Upregulation of constitutive NOS (nNOS and eNOS was found in the substructures of the cochlea after HBOT, but inducible NOS was not found in normal or HBOT animals, as shown by immunohistochemistry. There was no obvious DNA fragmentation present in this HBOT animal model. Conclusions The present evidence indicates that the customary HBOT protocol may increase constitutive NOS expression but such upregulation did not cause cell death in the treated cochlea. The cochlear morphology and auditory function are consequently not changed through the protocol.

  11. Involvement of Prohibitin Upregulation in Abrin-Triggered Apoptosis

    Directory of Open Access Journals (Sweden)

    Yu-Huei Liu

    2012-01-01

    Full Text Available Abrin (ABR, a protein purified from the seeds of Abrus precatorius, induces apoptosis in various types of cancer cells. However, the detailed mechanism remains largely uncharacterized. By using a cDNA microarray platform, we determined that prohibitin (PHB, a tumor suppressor protein, is significantly upregulated in ABR-triggered apoptosis. ABR-induced upregulation of PHB is mediated by the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK pathway, as demonstrated by chemical inhibitors. In addition, ABR significantly induced the expression of Bax as well as the activation of caspase-3 and poly(ADP-ribose polymerase (PARP in Jurkat T cells, whereas the reduction of PHB by specific RNA interference delayed ABR-triggered apoptosis through the proapoptotic genes examined. Moreover, our results also indicated that nuclear translocation of the PHB-p53 complex may play a role in the transcription of Bax. Collectively, our data show that PHB plays a role in ABR-induced apoptosis, which may be helpful for the development of diagnostic or therapeutic agents.

  12. Hypoxia upregulates neutrophil degranulation and potential for tissue injury

    Science.gov (United States)

    Hoenderdos, Kim; Lodge, Katharine M; Hirst, Robert A; Chen, Cheng; Palazzo, Stefano G C; Emerenciana, Annette; Summers, Charlotte; Angyal, Adri; Porter, Linsey; Juss, Jatinder K; O'Callaghan, Christopher; Chilvers, Edwin R

    2016-01-01

    Background The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown. Methods and results Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents. Neutrophil supernatants derived under hypoxic but not normoxic conditions induced extensive airway epithelial cell detachment and death, which was prevented by coincubation with the antiprotease α-1 antitrypsin; both normoxic and hypoxic supernatants impaired ciliary function. Surprisingly, the hypoxic upregulation of neutrophil degranulation was not dependent on hypoxia-inducible factor (HIF), nor was it fully reversed by inhibition of phospholipase C signalling. Hypoxia augmented the resting and cytokine-stimulated phosphorylation of AKT, and inhibition of phosphoinositide 3-kinase (PI3K)γ (but not other PI3K isoforms) prevented the hypoxic upregulation of neutrophil elastase release. Conclusion Hypoxia augments neutrophil degranulation and confers enhanced potential for damage to respiratory airway epithelial cells in a HIF-independent but PI3Kγ-dependent fashion. PMID:27581620

  13. Upregulation of Relaxin after Experimental Subarachnoid Hemorrhage in Rabbits

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    Yuichiro Kikkawa

    2014-01-01

    Full Text Available Background. Although relaxin causes vasodilatation in systemic arteries, little is known about its role in cerebral arteries. We investigated the expression and role of relaxin in basilar arteries after subarachnoid hemorrhage (SAH in rabbits. Methods. Microarray analysis with rabbit basilar artery RNA was performed. Messenger RNA expression of relaxin-1 and relaxin/insulin-like family peptide receptor 1 (RXFP1 was investigated with quantitative RT-PCR. RXFP1 expression in the basilar artery was investigated with immunohistochemistry. Relaxin concentrations in cerebrospinal fluid (CSF and serum were investigated with an enzyme-linked immunosorbent assay. Using human brain vascular smooth muscle cells (HBVSMC preincubated with relaxin, myosin light chain phosphorylation (MLC was investigated with immunoblotting after endothelin-1 stimulation. Results. After SAH, RXFP1 mRNA and protein were significantly downregulated on day 3, whereas relaxin-1 mRNA was significantly upregulated on day 7. The relaxin concentration in CSF was significantly elevated on days 5 and 7. Pretreatment with relaxin reduced sustained MLC phosphorylation induced by endothelin-1 in HBVSMC. Conclusion. Upregulation of relaxin and downregulation of RXFP1 after SAH may participate in development of cerebral vasospasm. Downregulation of RXFP1 may induce a functional decrease in relaxin activity during vasospasm. Understanding the role of relaxin may provide further insight into the mechanisms of cerebral vasospasm.

  14. Constitutive upregulation of chaperone-mediated autophagy in Huntington's disease.

    Science.gov (United States)

    Koga, Hiroshi; Martinez-Vicente, Marta; Arias, Esperanza; Kaushik, Susmita; Sulzer, David; Cuervo, Ana Maria

    2011-12-14

    Autophagy contributes to the removal of prone-to-aggregate proteins, but in several instances these pathogenic proteins have been shown to interfere with autophagic activity. In the case of Huntington's disease (HD), a congenital neurodegenerative disorder resulting from mutation in the huntingtin protein, we have previously described that the mutant protein interferes with the ability of autophagic vacuoles to recognize cytosolic cargo. Growing evidence supports the existence of cross talk among autophagic pathways, suggesting the possibility of functional compensation when one of them is compromised. In this study, we have identified a compensatory upregulation of chaperone-mediated autophagy (CMA) in different cellular and mouse models of HD. Components of CMA, namely the lysosome-associated membrane protein type 2A (LAMP-2A) and lysosomal-hsc70, are markedly increased in HD models. The increase in LAMP-2A is achieved through both an increase in the stability of this protein at the lysosomal membrane and transcriptional upregulation of this splice variant of the lamp-2 gene. We propose that CMA activity increases in response to macroautophagic dysfunction in the early stages of HD, but that the efficiency of this compensatory mechanism may decrease with age and so contribute to cellular failure and the onset of pathological manifestations.

  15. Upregulation of decorin by FXR in vascular smooth muscle cells

    International Nuclear Information System (INIS)

    He Fengtian; Zhang Qiuhong; Kuruba, Ramalinga; Gao Xiang; Li Jiang; Li Yong; Gong Wei; Jiang, Yu; Xie Wen; Li Song

    2008-01-01

    Decorin is a member of the family of small leucine-rich proteoglycans that are present in blood vessels and synthesized by vascular smooth muscle cells (VSMCs). Decorin plays complex roles in both normal vascular physiology and the pathogenesis of various types of vascular disorders. However, the mechanisms of regulation of decorin expression in vasculature are not clearly understood. Particularly little information is available about a role of nuclear receptors in the regulation of decorin expression. In the present study, we report that activation of vascular FXR by a specific ligand resulted in upregulation of decorin at the levels of both mRNA and protein. FXR appears to induce decorin expression at a transcriptional level because (1) upregulation of decorin mRNA expression was abolished by the treatment of a transcription inhibitor, actinomycin D; and (2) decorin promoter activity was significantly increased by activation of FXR. Functional analysis of human decorin promoter identified an imperfect inverted repeat DNA motif, IR8 (-2313TGGTCAtagtgtcaTGACCT-2294), as a likely FXR-responsive element that is involved in decorin regulation

  16. Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells

    Directory of Open Access Journals (Sweden)

    Ana Paula Santin Bertoni

    2015-01-01

    Full Text Available Thyroid cancer and thyroid nodules are more prevalent in women than men, so female sex hormones may have an etiological role in these conditions. There are no data about direct effects of progesterone on thyroid cells, so the aim of the present study was to evaluate progesterone effects in the sodium-iodide symporter NIS, thyroglobulin TG, thyroperoxidase TPO, and KI-67 genes expression, in normal thyroid follicular cells, derived from human tissue. NIS, TG, TPO, and KI-67 mRNA expression increased significantly after TSH 20 μUI/mL, respectively: 2.08 times, P<0.0001; 2.39 times, P=0.01; 1.58 times, P=0.0003; and 1.87 times, P<0.0001. In thyroid cells treated with 20 μUI/mL TSH plus 10 nM progesterone, RNA expression of NIS, TG, and KI-67 genes increased, respectively: 1.78 times, P<0.0001; 1.75 times, P=0.037; and 1.95 times, P<0.0001, and TPO mRNA expression also increased, though not significantly (1.77 times, P=0.069. These effects were abolished by mifepristone, an antagonist of progesterone receptor, suggesting that genes involved in thyroid cell function and proliferation are upregulated by progesterone. This work provides evidence that progesterone has a direct effect on thyroid cells, upregulating genes involved in thyroid function and growth.

  17. Precedent Research on Compact Laser-plasma based Gantry for Cancer Therapy

    International Nuclear Information System (INIS)

    Hee, Park Seong; Jeong, Young Uk; Lee, Ki Tae; Kim, Kyung Nam; Cha, Young Ho

    2012-03-01

    This is the precedent R and D to develop the technology of next generation compact particle cancer treatment system based on laser-plasma interaction and to deduce a big project. The subject of this project are the survey of application technology of laser-plasma based particle beam and the design of compact laser-plasma based gantry. The survey of characteristic of particle beam for cancer therapy and present status can be adapted to develop new system. The comparison between particle beams from the existing system and new one based on laser-plasma acceleration will be important to new design and design optimization. The project includes design of multi-dimensional laser transfer beamline, minimization of laser-plasma acceleration chamber, design of effective energy separation/selection system, and radiation safety and local shielding

  18. Preceding bronchial cutting for exposure of the pulmonary artery buried in scar tissue after chemoradiotherapy.

    Science.gov (United States)

    Nomori, Hiroaki; Cong, Yue; Sugimura, Hiroshi

    2017-01-01

    It is often difficult to expose the pulmonary artery buried in a scar tissue, especially in lung cancer patients that responded well to neoadjuvant chemoradiotherapy. Difficulty to access pulmonary artery branches may lead to potentially unnecessary pneumonectomy. To complete lobectomy in such cases, a technique with preceding bronchial cutting for exposure of the pulmonary artery is presented. After dissecting the pulmonary vein, the lobar bronchus is cut from the opposite side of the pulmonary artery with scissors. The back wall of the lobar bronchus is cut using a surgical knife from the luminal face, which can expose the pulmonary artery behind the bronchial stump and then complete lobectomy. Fourteen patients have been treated using the present technique, enabling complete resection by lobectomy (including sleeve lobectomy in 3 patients) without major bleeding. The present procedure can expose pulmonary artery buried in scar tissue, resulting in making the lobectomy safer.

  19. The effect of a preceding cue on the conflict solving mechanism.

    Science.gov (United States)

    Goldfarb, Liat; Henik, Avishai

    2013-01-01

    In everyday life cues and signs are used in order to improve our performance and to modify and control our behavior. This study examines whether cues can improve the performance of the mental mechanism in charge of solving conflicts when the nature of the irrelevant task remains constant. In two experiments participants performed the Stroop task in which they were asked to name the color of a stimulus while ignoring its meaning. Half the trials were preceded by a conflict-cue containing information about an upcoming conflict. In addition, conflict trial proportions were manipulated. We found that only when the probability of conflict is low can cues alter the conflict solving mechanism. These findings are discussed in the context of the nature of the control mechanism and its tendency to minimize the cost of mental resources.

  20. Body size shifts and early warning signals precede the historic collapse of whale stocks.

    Science.gov (United States)

    Clements, Christopher F; Blanchard, Julia L; Nash, Kirsty L; Hindell, Mark A; Ozgul, Arpat

    2017-06-22

    Predicting population declines is a key challenge in the face of global environmental change. Abundance-based early warning signals have been shown to precede population collapses; however, such signals are sensitive to the low reliability of abundance estimates. Here, using historical data on whales harvested during the 20th century, we demonstrate that early warning signals can be present not only in the abundance data, but also in the more reliable body size data of wild populations. We show that during the period of commercial whaling, the mean body size of caught whales declined dramatically (by up to 4 m over a 70-year period), leading to early warning signals being detectable up to 40 years before the global collapse of whale stocks. Combining abundance and body size data can reduce the length of the time series required to predict collapse, and decrease the chances of false positive early warning signals.

  1. Brain Musics: History, Precedents, and Commentary on Whalley, Mavros and Furniss

    Directory of Open Access Journals (Sweden)

    Miguel Ortiz

    2015-05-01

    Full Text Available Whalley, Mavros and Furniss explore questions of agency, control and interaction, as well as the embodied nature of musical performance in relation to the use of human-computer interaction through the work Clasp Together (beta for small ensemble and live electronics. The underlying concept of the piece focuses on direct mapping of a human neural network (embodied by a performer within the ensemble to an artificial neural network running on a computer. With our commentary, we contextualize the work within the field of Music Neuroscience. Specifically, we point at precedents in EEG-based musical practice as well as ongoing research in the field. We hope to more clearly situate Clasp Together (beta in the broad area of Brain Computer Musical Interfaces and discuss the challenges and opportunities that these technologies offer for composers.

  2. Temporal Precedence Checking for Switched Models and its Application to a Parallel Landing Protocol

    Science.gov (United States)

    Duggirala, Parasara Sridhar; Wang, Le; Mitra, Sayan; Viswanathan, Mahesh; Munoz, Cesar A.

    2014-01-01

    This paper presents an algorithm for checking temporal precedence properties of nonlinear switched systems. This class of properties subsume bounded safety and capture requirements about visiting a sequence of predicates within given time intervals. The algorithm handles nonlinear predicates that arise from dynamics-based predictions used in alerting protocols for state-of-the-art transportation systems. It is sound and complete for nonlinear switch systems that robustly satisfy the given property. The algorithm is implemented in the Compare Execute Check Engine (C2E2) using validated simulations. As a case study, a simplified model of an alerting system for closely spaced parallel runways is considered. The proposed approach is applied to this model to check safety properties of the alerting logic for different operating conditions such as initial velocities, bank angles, aircraft longitudinal separation, and runway separation.

  3. A Hybrid Genetic Algorithm to Minimize Total Tardiness for Unrelated Parallel Machine Scheduling with Precedence Constraints

    Directory of Open Access Journals (Sweden)

    Chunfeng Liu

    2013-01-01

    Full Text Available The paper presents a novel hybrid genetic algorithm (HGA for a deterministic scheduling problem where multiple jobs with arbitrary precedence constraints are processed on multiple unrelated parallel machines. The objective is to minimize total tardiness, since delays of the jobs may lead to punishment cost or cancellation of orders by the clients in many situations. A priority rule-based heuristic algorithm, which schedules a prior job on a prior machine according to the priority rule at each iteration, is suggested and embedded to the HGA for initial feasible schedules that can be improved in further stages. Computational experiments are conducted to show that the proposed HGA performs well with respect to accuracy and efficiency of solution for small-sized problems and gets better results than the conventional genetic algorithm within the same runtime for large-sized problems.

  4. Electric current precedes emergence of a lateral root in higher plants.

    Science.gov (United States)

    Hamada, S; Ezaki, S; Hayashi, K; Toko, K; Yamafuji, K

    1992-10-01

    Stable electrochemical patterns appear spontaneously around roots of higher plants and are closely related to growth. An electric potential pattern accompanied by lateral root emergence was measured along the surface of the primary root of adzuki bean (Phaseolus angularis) over 21 h using a microelectrode manipulated by a newly developed apparatus. The electric potential became lower at the point where a lateral root emerged. This change preceded the emergence of the lateral root by about 10 h. A theory is presented for calculating two-dimensional patterns of electric potential and electric current density around the primary root (and a lateral root) using only data on the one-dimensional electric potential measured near the surface of the primary root. The development of the lateral root inside the primary root is associated with the influx of electric current of about 0.7 muA.cm(-2) at the surface.

  5. DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice.

    Science.gov (United States)

    Wang, Degui; Yu, Tianyu; Liu, Yongqiang; Yan, Jun; Guo, Yingli; Jing, Yuhong; Yang, Xuguang; Song, Yanfeng; Tian, Yingxia

    2016-12-02

    Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The market for precedent: shifting visions of the role of clinical negligence claims and trials.

    Science.gov (United States)

    Mulcahy, Linda

    2014-01-01

    This article considers the interface between the standard setting activity of the NHS Litigation Authority, and the courts and uses the clinical negligence action as a prism through which to examine it. It is suggested that despite its many disadvantages, the clinical negligence action remains an important safety valve when internal regulatory systems fail or are insufficiently transparent to gain full legitimacy. More specifically, it explores the ways in which attitudes about the usefulness of the data contained in claims against the NHS have changed in the aftermath of a number of high profile inquiries which have focused on issues of poor performance. The article concludes that while much greater use is now been made of the data contained in claims when setting standards, strategies for prompting judicial precedent as an alternative way of mobilising standard setting behaviour remain under developed. © The Author 2014. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Possible deep fault slip preceding the 2004 Parkfield earthquake, inferred from detailed observations of tectonic tremor

    Science.gov (United States)

    Shelly, David R.

    2009-01-01

    Earthquake predictability depends, in part, on the degree to which sudden slip is preceded by slow aseismic slip. Recently, observations of deep tremor have enabled inferences of deep slow slip even when detection by other means is not possible, but these data are limited to certain areas and mostly the last decade. The region near Parkfield, California, provides a unique convergence of several years of high-quality tremor data bracketing a moderate earthquake, the 2004 magnitude 6.0 event. Here, I present detailed observations of tectonic tremor from mid-2001 through 2008 that indicate deep fault slip both before and after the Parkfield earthquake that cannot be detected with surface geodetic instruments. While there is no obvious short-term precursor, I find unidirectional tremor migration accompanied by elevated tremor rates in the 3 months prior to the earthquake, which suggests accelerated creep on the fault ∼16 km beneath the eventual earthquake hypocenter.

  8. Foreshock patterns preceding large earthquakes in the subduction zone of Chile

    Science.gov (United States)

    Minadakis, George; Papadopoulos, Gerassimos A.

    2016-04-01

    Some of the largest earthquakes in the globe occur in the subduction zone of Chile. Therefore, it is of particular interest to investigate foreshock patterns preceding such earthquakes. Foreshocks in Chile were recognized as early as 1960. In fact, the giant (Mw9.5) earthquake of 22 May 1960, which was the largest ever instrumentally recorded, was preceded by 45 foreshocks in a time period of 33h before the mainshock, while 250 aftershocks were recorded in a 33h time period after the mainshock. Four foreshocks were bigger than magnitude 7.0, including a magnitude 7.9 on May 21 that caused severe damage in the Concepcion area. More recently, Brodsky and Lay (2014) and Bedford et al. (2015) reported on foreshock activity before the 1 April 2014 large earthquake (Mw8.2). However, 3-D foreshock patterns in space, time and size were not studied in depth so far. Since such studies require for good seismic catalogues to be available, we have investigated 3-D foreshock patterns only before the recent, very large mainshocks occurring on 27 February 2010 (Mw 8.8), 1 April 2014 (Mw8.2) and 16 September 2015 (Mw8.4). Although our analysis does not depend on a priori definition of short-term foreshocks, our interest focuses in the short-term time frame, that is in the last 5-6 months before the mainshock. The analysis of the 2014 event showed an excellent foreshock sequence consisting by an early-weak foreshock stage lasting for about 1.8 months and by a main-strong precursory foreshock stage that was evolved in the last 18 days before the mainshock. During the strong foreshock period the seismicity concentrated around the mainshock epicenter in a critical area of about 65 km mainly along the trench domain to the south of the mainshock epicenter. At the same time, the activity rate increased dramatically, the b-value dropped and the mean magnitude increased significantly, while the level of seismic energy released also increased. In view of these highly significant seismicity

  9. Static Scheduling of Periodic Hardware Tasks with Precedence and Deadline Constraints on Reconfigurable Hardware Devices

    Directory of Open Access Journals (Sweden)

    Ikbel Belaid

    2011-01-01

    Full Text Available Task graph scheduling for reconfigurable hardware devices can be defined as finding a schedule for a set of periodic tasks with precedence, dependence, and deadline constraints as well as their optimal allocations on the available heterogeneous hardware resources. This paper proposes a new methodology comprising three main stages. Using these three main stages, dynamic partial reconfiguration and mixed integer programming, pipelined scheduling and efficient placement are achieved and enable parallel computing of the task graph on the reconfigurable devices by optimizing placement/scheduling quality. Experiments on an application of heterogeneous hardware tasks demonstrate an improvement of resource utilization of 12.45% of the available reconfigurable resources corresponding to a resource gain of 17.3% compared to a static design. The configuration overhead is reduced to 2% of the total running time. Due to pipelined scheduling, the task graph spanning is minimized by 4% compared to sequential execution of the graph.

  10. Blood-brain barrier hyperpermeability precedes demyelination in the cuprizone model.

    Science.gov (United States)

    Berghoff, Stefan A; Düking, Tim; Spieth, Lena; Winchenbach, Jan; Stumpf, Sina K; Gerndt, Nina; Kusch, Kathrin; Ruhwedel, Torben; Möbius, Wiebke; Saher, Gesine

    2017-12-01

    In neuroinflammatory disorders such as multiple sclerosis, the physiological function of the blood-brain barrier (BBB) is perturbed, particularly in demyelinating lesions and supposedly secondary to acute demyelinating pathology. Using the toxic non-inflammatory cuprizone model of demyelination, we demonstrate, however, that the onset of persistent BBB impairment precedes demyelination. In addition to a direct effect of cuprizone on endothelial cells, a plethora of inflammatory mediators, which are mainly of astroglial origin during the initial disease phase, likely contribute to the destabilization of endothelial barrier function in vivo. Our study reveals that, at different time points of pathology and in different CNS regions, the level of gliosis correlates with the extent of BBB hyperpermeability and edema. Furthermore, in mutant mice with abolished type 3 CXC chemokine receptor (CXCR3) signaling, inflammatory responses are dampened and BBB dysfunction ameliorated. Together, these data have implications for understanding the role of BBB permeability in the pathogenesis of demyelinating disease.

  11. Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans

    Science.gov (United States)

    Magnin, Michel; Rey, Marc; Bastuji, Hélène; Guillemant, Philippe; Mauguière, François; Garcia-Larrea, Luis

    2010-01-01

    Thalamic and cortical activities are assumed to be time-locked throughout all vigilance states. Using simultaneous intracortical and intrathalamic recordings, we demonstrate here that the thalamic deactivation occurring at sleep onset most often precedes that of the cortex by several minutes, whereas reactivation of both structures during awakening is synchronized. Delays between thalamus and cortex deactivations can vary from one subject to another when a similar cortical region is considered. In addition, heterogeneity in activity levels throughout the cortical mantle is larger than previously thought during the descent into sleep. Thus, asynchronous thalamo-cortical deactivation while falling asleep probably explains the production of hypnagogic hallucinations by a still-activated cortex and the common self-overestimation of the time needed to fall asleep. PMID:20142493

  12. Patterns of life events preceding the suicide in rural young Chinese: a case control study.

    Science.gov (United States)

    Zhang, Jie; Ma, Zhenyu

    2012-10-01

    Previous studies on the Chinese suicide found some life events prior to the suicide different from those in the West, but there is a lack of summary of the Chinese life event patterns to better understand the effects of the social structure on Chinese suicide. We tried to identify the life events that precede the Chinese rural youth suicides and compare them with what are found in the West, so as to find the patterns that are particularly true in the Chinese culture contexts. Suicide cases were investigated with a psychological autopsy study in rural China, and local community living controls were also interviewed with the same protocol. We collapsed 64 negative life events into six categories: (1) Marriage/Love, (2) Family/Home, (3) Work/Business, (4) Health/Hospital, (5) Law/Legal, (6) Friend/Relationship. About 92.3% of the suicides studied had experienced at least one type of negative life events. The three most common negative life events categories in the past one year were Family/Home (60.7%), Health/Hospital (53.8%) and Marriage/Love (51.3%) in the rural young suicide victims. Among the negative life events, those related to family relations, love affairs, and marital issues were most likely to precede a suicide of rural suicides in China, and it is especially true of rural young women. Family is an important social institution in rural China for suicide prevention efforts. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Diseases that precede disability among latter-stage elderly individuals in Japan.

    Science.gov (United States)

    Naruse, Takashi; Sakai, Mahiro; Matsumoto, Hiroshige; Nagata, Satoko

    2015-08-01

    Understanding causes of disability among elderly individuals is an important public health issue, particularly because of the increasing rate of disabled elderly individuals and the social costs in a rapidly aging society. Accordingly, we aimed to describe the diseases that precede disability and investigate the types of diseases that are related to severe disability among Japanese elderly individuals aged over 75 years. Using claim data from the latter-stage elderly healthcare system and long-term care insurance system, we identified 76,265 elderly individuals over 75 years old who did not qualify as disabled on April 1, 2011. Among them, 3,715 elderly individuals who had been newly qualified as disabled between April 1, 2011 and March 31, 2012 were selected. Disease codes from the medical claim data in the 6 months prior to disability were collected. All descriptions were developed separately for six groups divided by gender and disability level (low, middle, and high). The results of the ordinal logistic analysis including sex and age revealed that men tended to have significantly higher levels of disability (β = 0.417, p disability level groups. In low-level disability groups, cancer in men (12.8%) and arthropathy and fracture in women (11.9% and 13.5%, respectively) were as common as cerebrovascular disorder (12.2% and 9.7%, in men and women, respectively). Stroke was the most common disease for all genders and disability levels. The diseases preceding low-level disability differed by gender. This study demonstrated the need to consider arthropathy and fracture as well as CVD in order to prevent disability.

  14. Impairment of adolescent hippocampal plasticity in a mouse model for Alzheimer's disease precedes disease phenotype.

    Directory of Open Access Journals (Sweden)

    Daniela Hartl

    Full Text Available The amyloid precursor protein (APP was assumed to be an important neuron-morphoregulatory protein and plays a central role in Alzheimer's disease (AD pathology. In the study presented here, we analyzed the APP-transgenic mouse model APP23 using 2-dimensional gel electrophoresis technology in combination with DIGE and mass spectrometry. We investigated cortex and hippocampus of transgenic and wildtype mice at 1, 2, 7 and 15 months of age. Furthermore, cortices of 16 days old embryos were analyzed. When comparing the protein patterns of APP23 with wildtype mice, we detected a relatively large number of altered protein spots at all age stages and brain regions examined which largely preceded the occurrence of amyloid plaques. Interestingly, in hippocampus of adolescent, two-month old mice, a considerable peak in the number of protein changes was observed. Moreover, when protein patterns were compared longitudinally between age stages, we found that a large number of proteins were altered in wildtype mice. Those alterations were largely absent in hippocampus of APP23 mice at two months of age although not in other stages compared. Apparently, the large difference in the hippocampal protein patterns between two-month old APP23 and wildtype mice was caused by the absence of distinct developmental changes in the hippocampal proteome of APP23 mice. In summary, the absence of developmental proteome alterations as well as a down-regulation of proteins related to plasticity suggest the disturption of a normally occurring peak of hippocampal plasticity during adolescence in APP23 mice. Our findings are in line with the observation that AD is preceded by a clinically silent period of several years to decades. We also demonstrate that it is of utmost importance to analyze different brain regions and different age stages to obtain information about disease-causing mechanisms.

  15. Creating an inclusive mall environment with the PRECEDE-PROCEED model: a living lab case study.

    Science.gov (United States)

    Ahmed, Sara; Swaine, Bonnie; Milot, Marc; Gaudet, Caroline; Poldma, Tiiu; Bartlett, Gillian; Mazer, Barbara; Le Dorze, Guylaine; Barbic, Skye; Rodriguez, Ana Maria; Lefebvre, Hélène; Archambault, Philippe; Kairy, Dahlia; Fung, Joyce; Labbé, Delphine; Lamontagne, Anouk; Kehayia, Eva

    2017-10-01

    Although public environments provide opportunities for participation and social inclusion, they are not always inclusive spaces and may not accommodate the wide diversity of people. The Rehabilitation Living Lab in the Mall is a unique, interdisciplinary, and multi-sectoral research project with an aim to transform a shopping complex in Montreal, Canada, into an inclusive environment optimizing the participation and social inclusion of all people. The PRECEDE-PROCEDE Model (PPM), a community-oriented and participatory planning model, was applied as a framework. The PPM is comprised of nine steps divided between planning, implementation, and evaluation. The PPM is well suited as a framework for the development of an inclusive mall. Its ecological approach considers the environment, as well as the social and individual factors relating to mall users' needs and expectations. Transforming a mall to be more inclusive is a complex process involving many stakeholders. The PPM allows the synthesis of several sources of information, as well as the identification and prioritization of key issues to address. The PPM also helps to frame and drive the implementation and evaluate the components of the project. This knowledge can help others interested in using the PPM to create similar enabling and inclusive environments world-wide. Implication for rehabilitation While public environments provide opportunities for participation and social inclusion, they are not always inclusive spaces and may not accommodate the wide diversity of people. The PRECEDE PROCEDE Model (PPM) is well suited as a framework for the development, implementation, and evaluation of an inclusive mall. Environmental barriers can negatively impact the rehabilitation process by impeding the restoration and augmentation of function. Removing barriers to social participation and independent living by improving inclusivity in the mall and other environments positively impacts the lives of people with disabilities.

  16. A Legal Analysis of the Precedents of Medical Disputes in the Cosmetic Surgery Field

    Directory of Open Access Journals (Sweden)

    Bo Young Park

    2016-05-01

    Full Text Available BackgroundDisputes regarding medical malpractice occur between practitioners and patients. As patients have become increasingly aware regarding medical care, an increase in the unexpected side effects of procedures has been observed, thereby leading to an increase in disputes regarding medical malpractice. In this study, we reviewed trends in precedents involving cosmetic surgery-related medical disputes, with the goal of helping to prevent unnecessary disputes in the future.MethodsWe conducted a search of the judgments made in South Korean courts between 2000 and 2013 that were related to the field of plastic surgery. A total of 54 judgments were analyzed, and the selected precedents were reviewed and classified according to the kind of negligence involved.ResultsThe claim amounts ranged from under 8 million KRW (6,991 USD to 750 million KRW (629,995 USD. The most common ratio of the judgment amount to the claim amount was 20%–30%. The judgments were classified according to the following categories: violation of the duty of explanation in 17 cases (29%, violation of the duty of care in 10 cases (17%, violation of both duties in 20 cases (35%, and no violation of duty in six cases (10%.ConclusionsCosmetic surgery-related suits require different approaches than general malpractice suits. The Supreme Court requires plastic surgeons to determine the type, timing, methods, and scope of their treatments when considering possible results. Therefore, practitioners should be educated on their rights and responsibilities to enable them to cope with any possible medical dispute that may arise.

  17. Up-regulation of reciprocal inhibition by explosive strength training

    DEFF Research Database (Denmark)

    Geertsen, Svend Sparre; Jensen, Jesper Lundbye; Nielsen, Jens Bo

    of 26 ± 7 years strength trained the ankle dorsiflexor muscles 3 times a week for 4 weeks. Each training session consisted of 4 sets of 16 isometric dorsiflexions with the aim of increasing force as rapidly as possible, separated by 4min rest periods. Test sessions were conducted before, immediately...... in the ankle plantarflexors at the onset of dorsiflexion is larger the quicker the movement, we hypothesized that DRI may be up-regulated when subjects are trained to perform dorsiflexion movements as quickly as possible.   For this purpose, 15 healthy human subjects (7 male, 8 female) with an average age...... after and 2 weeks after the training period. The rate of dorsiflexion force development measured within 30, 50, 100 and 200ms after onset of voluntary explosive isometric dorsiflexion increased by 20-30% (p

  18. A multi-stage process including transient polyploidization and EMT precedes the emergence of chemoresistent ovarian carcinoma cells with a dedifferentiated and pro-inflammatory secretory phenotype.

    Science.gov (United States)

    Rohnalter, Verena; Roth, Katrin; Finkernagel, Florian; Adhikary, Till; Obert, Julia; Dorzweiler, Kristina; Bensberg, Maike; Müller-Brüsselbach, Sabine; Müller, Rolf

    2015-11-24

    DNA-damaging drugs induce a plethora of molecular and cellular alterations in tumor cells, but their interrelationship is largely obscure. Here, we show that carboplatin treatment of human ovarian carcinoma SKOV3 cells triggers an ordered sequence of events, which precedes the emergence of mitotic chemoresistant cells. The initial phase of cell death after initiation of carboplatin treatment is followed around day 14 by the emergence of a mixed cell population consisting of cycling, cell cycle-arrested and senescent cells. At this stage, giant cells make up >80% of the cell population, p21 (CDKN1A) in strongly induced, and cell numbers remain nearly static. Subsequently, cell death decreases, p21 expression drops to a low level and cell divisions increase, including regular mitoses of giant cells and depolyploidization by multi-daughter divisions. These events are accompanied by the upregulation of stemness markers and a pro-inflammatory secretory phenotype, peaking after approximately 14 days of treatment. At the same time the cells initiate epithelial to mesenchymal transition, which over the subsequent weeks continuously increases, concomitantly with the emergence of highly proliferative, migratory, dedifferentiated, pro-inflammatory and chemoresistant cells (SKOV3-R). These cells are anchorage-independent and grow in a 3D collagen matrix, while cells on day 14 do not survive under these conditions, indicating that SKOV3-R cells were generated thereafter by the multi-stage process described above. This process was essentially recapitulated with the ovarian carcinoma cell line IGROV-1. Our observations suggest that transitory cells characterized by polyploidy, features of stemness and a pro-inflammatory secretory phenotype contribute to the acquisition of chemoresistance.

  19. Arginase up-regulation and eNOS uncoupling contribute to impaired endothelium-dependent vasodilation in a rat model of intrauterine growth restriction.

    Science.gov (United States)

    Grandvuillemin, Isabelle; Buffat, Christophe; Boubred, Farid; Lamy, Edouard; Fromonot, Julien; Charpiot, Philippe; Simoncini, Stephanie; Sabatier, Florence; Dignat-George, Françoise; Peyter, Anne-Christine; Simeoni, Umberto; Yzydorczyk, Catherine

    2018-05-09

    Individuals born after intrauterine growth restriction (IUGR) are at increased risk of developing cardiovascular diseases in adulthood, notably hypertension (HTN). Alterations in the vascular system, particularly impaired endothelium-dependent vasodilation, may play an important role in long-term effects of IUGR. Whether such vascular dysfunction precedes HTN has not been fully established in individuals born after IUGR. Moreover, the intimate mechanisms of altered endothelium-dependent vasodilation remain incompletely elucidated. We therefore investigated, using a rat model of IUGR, whether impaired endothelium-dependent relaxation precedes the development of HTN and whether key components of the L-Arginine-nitric oxide (NO) pathway are involved in its pathogenesis. Pregnant rats were fed with a control (CTRL, 23% casein) or low-protein diet (LP, 9% casein) to induce IUGR. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography in 5- and 8-week-old male offspring. Aortic rings were isolated to investigate relaxation to acetylcholine, NO production, eNOS protein content, arginase activity, and superoxide anion production. SBP was not different at 5 weeks, but significantly increased in 8-week-old LP vs. CRTL offspring. In 5-week-old LP vs. CRTL males, endothelium-dependent vasorelaxation was significantly impaired, but restored by pre-incubation with L-Arginine or the arginase inhibitor BEC; NO production was significantly reduced, but restored by L-Arginine pretreatment; total eNOS protein, dimer/monomer ratio, and arginase activity were significantly increased; superoxide anion production was significantly enhanced, but normalized by pretreatment with the NOS inhibitor L-NNA. In this model, IUGR leads to early-impaired endothelium-dependent vasorelaxation, resulting from arginase up-regulation and eNOS uncoupling, which precedes the development of HTN.

  20. The association between preceding drought occurrence and heat waves in the Mediterranean

    Science.gov (United States)

    Russo, Ana; Gouveia, Célia M.; Ramos, Alexandre M.; Páscoa, Patricia; Trigo, Ricardo M.

    2017-04-01

    A large number of weather driven extreme events has occurred worldwide in the last decade, namely in Europe that has been struck by record breaking extreme events with unprecedented socio-economic impacts, including the mega-heatwaves of 2003 in Europe and 2010 in Russia, and the large droughts in southwestern Europe in 2005 and 2012. The last IPCC report on extreme events points that a changing climate can lead to changes in the frequency, intensity, spatial extent, duration, and timing of weather and climate extremes. These, combined with larger exposure, can result in unprecedented risk to humans and ecosystems. In this context it is becoming increasingly relevant to improve the early identification and predictability of such events, as they negatively affect several socio-economic activities. Moreover, recent diagnostic and modelling experiments have confirmed that hot extremes are often preceded by surface moisture deficits in some regions throughout the world. In this study we analyze if the occurrence of hot extreme months is enhanced by the occurrence of preceding drought events throughout the Mediterranean area. In order to achieve this purpose, the number of hot days in the regions' hottest month will be associated with a drought indicator. The evolution and characterization of drought was analyzed using both the Standardized Precipitation Evaporation Index (SPEI) and the Standardized Precipitation Index (SPI), as obtained from CRU TS3.23 database for the period 1950-2014. We have used both SPI and SPEI for different time scales between 3 and 9 months with a spatial resolution of 0.5°. The number of hot days and nights per month (NHD and NHN) was determined using the ECAD-EOBS daily dataset for the same period and spatial resolution (dataset v14). The NHD and NHN were computed, respectively, as the number of days with a maximum or minimum temperature exceeding the 90th percentile. Results show that the most frequent hottest months for the Mediterranean

  1. Rethinking 'flexibilities' in the international drug control system-Potential, precedents and models for reforms.

    Science.gov (United States)

    Collins, John

    2017-01-24

    Much international drug policy debate centres on, what policies are permissible under the international drug treaties, whether member states are openly 'breaching' these treaties by changing national regulatory frameworks and shifting priorities away from a 'war on drugs' approach, and what 'flexibility' exists for policy reform and experimentation at national and local levels. Orthodox interpretations hold that the current system is a US-led 'prohibition regime' that was constructed in an extremely repressive and restrictive manner with almost no flexibility for significant national deviations. This paper challenges these orthodox interpretive frameworks and suggests no absolute and clear dichotomy between strict adherence and 'breaches' of the international treaties. This paper uses historical analysis to highlight the flaws in orthodox policy analyses, which assume a uniform interpretation, implementation and set of policy trajectories towards a 'prohibition regime' in the 20th century. It challenges some existing legal interpretations of the treaties through recourse to historical precedents of flexible interpretation and policy prioritisation. It then examines the legal justifications currently being formulated by member states to explain a shift towards policies which, until recently, have been viewed as outside the permissible scope of the conventions. It then examines a functionalist framework for understanding the likely contours of drug diplomacy in the post-UN General Assembly Special Session (UNGASS) 2016 era. The paper highlights that, contrary to current policy discourses, the international control system has always been implemented in a 'flexible' manner. It demonstrates that drug control goals were repeatedly subsumed to security, development, political stability and population welfare imperatives, or what we might now refer to under the umbrella of 'development issues.' The paper further demonstrates that policy prioritisation, inherent treaty

  2. Coordinated Ramping of Dorsal Striatal Pathways preceding Food Approach and Consumption.

    Science.gov (United States)

    London, Tanisha D; Licholai, Julia A; Szczot, Ilona; Ali, Mohamed A; LeBlanc, Kimberly H; Fobbs, Wambura C; Kravitz, Alexxai V

    2018-04-04

    The striatum controls food-related actions and consumption and is linked to feeding disorders, including obesity and anorexia nervosa. Two populations of neurons project from the striatum: direct pathway medium spiny neurons and indirect pathway medium spiny neurons. The selective contribution of direct pathway medium spiny neurons and indirect pathway medium spiny neurons to food-related actions and consumption remains unknown. Here, we used in vivo electrophysiology and fiber photometry in mice (of both sexes) to record both spiking activity and pathway-specific calcium activity of dorsal striatal neurons during approach to and consumption of food pellets. While electrophysiology revealed complex task-related dynamics across neurons, population calcium was enhanced during approach and inhibited during consumption in both pathways. We also observed ramping changes in activity that preceded both pellet-directed actions and spontaneous movements. These signals were heterogeneous in the spiking units, with neurons exhibiting either increasing or decreasing ramps. In contrast, the population calcium signals were homogeneous, with both pathways having increasing ramps of activity for several seconds before actions were initiated. An analysis comparing population firing rates to population calcium signals also revealed stronger ramping dynamics in the calcium signals than in the spiking data. In a second experiment, we trained the mice to perform an action sequence to evaluate when the ramping signals terminated. We found that the ramping signals terminated at the beginning of the action sequence, suggesting they may reflect upcoming actions and not preconsumption activity. Plasticity of such mechanisms may underlie disorders that alter action selection, such as drug addiction or obesity. SIGNIFICANCE STATEMENT Alterations in striatal function have been linked to pathological consumption in disorders, such as obesity and drug addiction. We recorded spiking and

  3. THE BRAZILIAN SUPREME COURT'S PRECEDENTS AND THE CURIOUS TAXING DIFFERENCE ON THE AIR AND INLAND PASSENGER TRANSPORT

    Directory of Open Access Journals (Sweden)

    Marciano Seabra de Godoi

    2016-07-01

    Full Text Available The study aims to the taxing of transport service provision, particularly the passenger transport, as well as the odd difference of treatment created directly by the Brazilian Supreme Court’s precedents, applying distinguished regimes for air passenger and inland. It discusses the evolution of legislation on the subject and, specially, it examines critically how the Supreme Court’s case law stood on the issue, through the judgment of many direct actions of unconstitutionality (ADI. The study considers legally inconsistent these precedents, in which is unconstitutional the tax collection over the air transport, but constitutional over the inland one.

  4. Resting-state functional connectivity remains unaffected by preceding exposure to aversive visual stimuli.

    Science.gov (United States)

    Geissmann, Léonie; Gschwind, Leo; Schicktanz, Nathalie; Deuring, Gunnar; Rosburg, Timm; Schwegler, Kyrill; Gerhards, Christiane; Milnik, Annette; Pflueger, Marlon O; Mager, Ralph; de Quervain, Dominique J F; Coynel, David

    2018-02-15

    While much is known about immediate brain activity changes induced by the confrontation with emotional stimuli, the subsequent temporal unfolding of emotions has yet to be explored. To investigate whether exposure to emotionally aversive pictures affects subsequent resting-state networks differently from exposure to neutral pictures, a resting-state fMRI study implementing a two-group repeated-measures design in healthy young adults (N = 34) was conducted. We focused on investigating (i) patterns of amygdala whole-brain and hippocampus connectivity in both a seed-to-voxel and seed-to-seed approach, (ii) whole-brain resting-state networks with an independent component analysis coupled with dual regression, and (iii) the amygdala's fractional amplitude of low frequency fluctuations, all while EEG recording potential fluctuations in vigilance. In spite of the successful emotion induction, as demonstrated by stimuli rating and a memory-facilitating effect of negative emotionality, none of the resting-state measures was differentially affected by picture valence. In conclusion, resting-state networks connectivity as well as the amygdala's low frequency oscillations appear to be unaffected by preceding exposure to widely used emotionally aversive visual stimuli in healthy young adults. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Autopsy case of acute myelocytic leukemia preceded by hemopoietic dysplasia found in an atomic bomb survivor

    Energy Technology Data Exchange (ETDEWEB)

    Sonoda, Y; Edagawa, J; Taniwaki, M; Ide, T; Misawa, S [Kyoto Prefectural Univ. of Medicine (Japan)

    1981-03-01

    An autopsy case of acute myelocytic leukemia preceded by hemopoietic dysplasia, presumably on a sequela to the atomic bomb in Hiroshima is reported. On admission, severe anemia and thrombocytosis were found and the bone marrow aspiration showed myeloid hyperplasia without definite maturation arrest. Mild to moderate eosinophilia and basophilia continued during the course of the disease, accompaning mild monocytosis 2 years later. Furthermore, he had the radical operation for the early gastric cancer in this preleukemic stage. After the administration of methenolone acetate (25 mg/day), severe anemia has dramatically improved, but leukocytosis with profound monocytosis persisted, and subsequently acute myelocytic leukemia developed. He died from an intracerebral bleeding due to an accidental trauma on the head. Autopsy findings disclosed the systemic leukemic infiltration. Repeated chromosome analyses revealed the mosaic karyotype of 46, XY/45, XY, -16 on admission, but it was 46, XY/46, XY, del (8) (p 12) in the overt leukemic phase. The granulopoietic colony forming capacity of bone marrow cells was already low one year before the onset of overt leukemia. This finding suggested that the existence of an abnormal clone could be predictable. In addition, the possible causative effect of the exposure to the atomic bomb in leukemogenesis in this case is discussed.

  6. Subchondral Bone Plate Thickening Precedes Chondrocyte Apoptosis and Cartilage Degradation in Spontaneous Animal Models of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Zaitunnatakhin Zamli

    2014-01-01

    Full Text Available Osteoarthritis (OA is the most common joint disorder characterised by bone remodelling and cartilage degradation and associated with chondrocyte apoptosis. These processes were investigated at 10, 16, 24, and 30 weeks in Dunkin Hartley (DH and Bristol Strain 2 (BS2 guinea pigs that develop OA spontaneously. Both strains had a more pronounced chondrocyte apoptosis, cartilage degradation, and subchondral bone changes in the medial than the lateral side of the tibia, and between strains, the changes were always greater and faster in DH than BS2. In the medial side, a significant increase of chondrocyte apoptosis and cartilage degradation was observed in DH between 24 and 30 weeks of age preceded by a progressive thickening and stiffening of subchondral bone plate (Sbp. The Sbp thickness consistently increased over the 30-week study period but the bone mineral density (BMD of the Sbp gradually decreased after 16 weeks. The absence of these changes in the medial side of BS2 may indicate that the Sbp of DH was undergoing remodelling. Chondrocyte apoptosis was largely confined to the deep zone of articular cartilage and correlated with thickness of the subchondral bone plate suggesting that cartilage degradation and chondrocyte apoptosis may be a consequence of continuous bone remodelling during the development of OA in these animal models of OA.

  7. Influence of sound source location on the behavior and physiology of the precedence effect in cats.

    Science.gov (United States)

    Dent, Micheal L; Tollin, Daniel J; Yin, Tom C T

    2009-08-01

    Psychophysical experiments on the precedence effect (PE) in cats have shown that they localize pairs of auditory stimuli presented from different locations in space based on the spatial position of the stimuli and the interstimulus delay (ISD) between the stimuli in a manner similar to humans. Cats exhibit localization dominance for pairs of transient stimuli with |ISDs| from approximately 0.4 to 10 ms, summing localization for |ISDs| 10 ms, which is the approximate echo threshold. The neural correlates to the PE have been described in both anesthetized and unanesthetized animals at many levels from auditory nerve to cortex. Single-unit recordings from the inferior colliculus (IC) and auditory cortex of cats demonstrate that neurons respond to both lead and lag sounds at ISDs above behavioral echo thresholds, but the response to the lag is reduced at shorter ISDs, consistent with localization dominance. Here the influence of the relative locations of the leading and lagging sources on the PE was measured behaviorally in a psychophysical task and physiologically in the IC of awake behaving cats. At all configurations of lead-lag stimulus locations, the cats behaviorally exhibited summing localization, localization dominance, and breakdown of fusion. Recordings from the IC of awake behaving cats show neural responses paralleling behavioral measurements. Both behavioral and physiological results suggest systematically shorter echo thresholds when stimuli are further apart in space.

  8. Barriers to Effective Doctor-Patient Relationship Based on PRECEDE PROCEED Model

    Science.gov (United States)

    Ghaffarifar, Saeideh; Ghofranipour, Fazlollah; Ahmadi, Fazlollah; Khoshbaten, Manouchehr

    2015-01-01

    Objective: This study intends to investigate interns and faculty members’ insights into constructing relationship between physicians and patients at 3 more accredited Iranian universities of medical sciences. Method: Applying PRECEDE PROCEED model, semi-structured interviews were completed with 7 interns and 14 faculty members and two themes were emerged from directed content analysis. The meaning units of the first theme, barriers to effective doctor-patient relationship, are discussed in this paper. Results: According to the participants, building doctor-patient relationship is influenced by many contextual and regulatory factors as well as content, process and perceptual skills of physicians. Conclusions: Faculty and curriculum development, as well as foundation of the department of communication skills at medical schools are recommended to eliminate the impact of poor communication on patients’ satisfaction and physicians’ self-efficacy specific to their communication skills. Practice Implications: Applying theories and models of health education and health promotion, researchers and educators can use the most predictive constructs of theories to design and implement effective interventions. PMID:26153160

  9. Cost estimation for solid waste management in industrialising regions – Precedents, problems and prospects

    International Nuclear Information System (INIS)

    Parthan, Shantha R.; Milke, Mark W.; Wilson, David C.; Cocks, John H.

    2012-01-01

    Highlights: ► We review cost estimation approaches for solid waste management. ► Unit cost method and benchmarking techniques used in industrialising regions (IR). ► Variety in scope, quality and stakeholders makes cost estimation challenging in IR. ► Integrate waste flow and cost models using cost functions to improve cost planning. - Abstract: The importance of cost planning for solid waste management (SWM) in industrialising regions (IR) is not well recognised. The approaches used to estimate costs of SWM can broadly be classified into three categories – the unit cost method, benchmarking techniques and developing cost models using sub-approaches such as cost and production function analysis. These methods have been developed into computer programmes with varying functionality and utility. IR mostly use the unit cost and benchmarking approach to estimate their SWM costs. The models for cost estimation, on the other hand, are used at times in industrialised countries, but not in IR. Taken together, these approaches could be viewed as precedents that can be modified appropriately to suit waste management systems in IR. The main challenges (or problems) one might face while attempting to do so are a lack of cost data, and a lack of quality for what data do exist. There are practical benefits to planners in IR where solid waste problems are critical and budgets are limited.

  10. Ten-year weight gain is associated with elevated fasting insulin levels and precedes glucose elevation.

    Science.gov (United States)

    Pennings, Nicholas; Jaber, Johnny; Ahiawodzi, Peter

    2018-05-01

    Numerous studies have examined the relationship between endogenous insulin and weight change with mixed results. This study examined the relationship between fasting insulin levels, insulin resistance (IR), and 10-year weight change by glycaemic stage. Using data from the US National Health and Nutrition Examination Survey 2011-2014, 3840 participants were divided into 6 groups based on fasting glucose and fasting insulin levels. Fasting insulin concentrations were dichotomized into <25th percentile (normal) and ≥25th percentile (elevated). Ten-year weight change associated with fasting insulin was assessed by glycaemic stage. Average weight change over a 10-year period was higher in individuals with elevated insulin levels compared to the first quartile (1.40 lbs. vs 11.12 lbs, P < .0001). Across all groups, a 1 μU increase in fasting insulin levels resulted in a 0.52-pound increase in weight (P < .0001). Similarly, an increase in HOMA-IR was associated with increase in weight (1.32 lbs per IR unit, P < .0001). Marginal increases in weight were most pronounced in the normal insulin groups compared to elevated insulin groups and diminished as glycaemic stage progressed. Elevated fasting insulin level was positively associated with weight gain. The impact of fasting insulin and IR on weight gain preceded hyperglycaemia and diminished as glycaemic stage progressed. Copyright © 2018 John Wiley & Sons, Ltd.

  11. Problems in neoadjuvant chemoradiotherapy preceding surgery for advanced squamous cell carcinoma of the thoracic esophagus

    International Nuclear Information System (INIS)

    Ishida, Kaoru; Koeda, Keisuke; Sato, Nobuhiro

    1999-01-01

    The adverse effect of neoadjuvant chemoradiotherapy on the postoperative course in esophageal cancer was studied in 9 patients undergoing neoadjuvant chemoradiotherapy preceding surgery for thoracic esophageal carcinoma possibly involving adjacent organs (neoadjuvant group), and 13 patients undergoing surgery without neoadjuvant therapy for same disease (control group). The two groups were compared for volume of intraoperative hemorrhage, surgical duration, frequency of postoperative morbidity, and for postoperative changes in blood platelet counts, and serum thrombopoietin and interleukin-6 levels. Mean intraoperative blood loss was 1121 g (580-1,662 g) in the neoadjuvant group and 546.5 g (274.7-778.3 g) in controls group (Student's T test: p<0.01). No significant difference was seen found between the two groups in the degree of postoperative deterioration in cardiopulmonary function or in interleukin-6 levels. Blood platelet counts decreased in both groups until postoperative day 7, but recovery on postoperative day 14 was significantly depressed in the neoadjuvant group compared to controls. Serum thrombopoietin levels were higher in the neoadjuvant group than in controls (Mann-Whitney U-test: p<0.05). We found that neoadjuvant chemoradiotherapy induces latent postoperative myelosuppression and may lead to intractable infection. (author)

  12. Precedents, Patterns and Puzzles: Feminist Reflections on the First Women Lawyers

    Directory of Open Access Journals (Sweden)

    Mary Jane Mossman

    2016-10-01

    Full Text Available This paper initially examines the historical precedents established by some of the first women who entered the “gentleman’s profession” of law in different jurisdictions, as well as the biographical patterns that shaped some women’s ambitions to enter the legal professions. The paper then uses feminist methods and theories to interpret “puzzles that remain unsolved” about early women lawyers, focusing especially on two issues. One puzzle is the repeated claims on the part of many of these early women lawyers that they were “lawyers”, and not “women lawyers”, even as they experienced exclusionary practices and discrimination on the part of male lawyers and judges—a puzzle that suggests how professional culture required women lawyers to conform to existing patterns in order to succeed. A second puzzle relates to the public voices of early women lawyers, which tended to suppress disappointments, difficulties and discriminatory practices. In this context, feminist theories suggest a need to be attentive to the “silences” in women’s stories, including the stories of the lives of early women lawyers. Moreover, these insights may have continuing relevance for contemporary women lawyers because it is at least arguable that, while there have been changes in women’s experiences, there has been very little transformation in their work status in relation to men.

  13. Engineering Codes of Ethics and the Duty to Set a Moral Precedent.

    Science.gov (United States)

    Schlossberger, Eugene

    2016-10-01

    Each of the major engineering societies has its own code of ethics. Seven "common core" clauses and several code-specific clauses can be identified. The paper articulates objections to and rationales for two clauses that raise controversy: do engineers have a duty (a) to provide pro bono services and/or speak out on major issues, and (b) to associate only with reputable individuals and organizations? This latter "association clause" can be justified by the "proclamative principle," an alternative to Kant's universalizability requirement. At the heart of engineering codes of ethics, and implicit in what it is to be a moral agent, the "proclamative principle" asserts that one's life should proclaim one's moral stances (one's values, principles, perceptions, etc.). More specifically, it directs engineers to strive to insure that their actions, thoughts, and relationships be fit to offer to their communities as part of the body of moral precedents for how to be an engineer. Understanding codes of ethics as reflections of this principle casts light both on how to apply the codes and on the distinction between private and professional morality.

  14. Community health needs assessment with precede-proceed model: a mixed methods study

    Directory of Open Access Journals (Sweden)

    Wang Yang

    2009-10-01

    Full Text Available Abstract Background Community health services in China have developed over the last few decades. In order to use limited health resources more effectively, we conducted a community health needs assessment. This aimed to provide an understanding of the community's health problems and the range of potential factors affecting risk behaviours for the priority health problems. Methods We used the precede-proceed model for the needs assessment. Triangulation of data, methods and researchers were employed in data collection. Results Main findings include: cardiovascular diseases (CVDs were identified as the priority health problems in the study communities; risk factors associated with CVDs included smoking, physical inactivity and unhealthy eating behaviours, particularly amongst male residents with low education level; factors negatively affecting behaviours were classified into predisposing factors (limited knowledge, beliefs and lack of perceived needs, enabling factors (limited access to health promotion activities, unawareness of health promotion, lack of work-site and school health promotion, absence of health promotion related policy and reinforcing factors (culture. Policies and organization were not perfect; there were limited staff skilled in providing health promotion in the community. Conclusion CVDs were identified by the communities as priority health problems. Future health programs should focus on smoking, physical inactivity and unhealthy eating behaviours. Behaviour change strategies should take predisposing factors, enabling factors and reinforcing factors into consideration. Policies, organization and human resource need strengthening.

  15. A New Car-Following Model considering Driving Characteristics and Preceding Vehicle’s Acceleration

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2017-01-01

    Full Text Available In the past decades, many improved car-following models based on the full velocity difference (FVD model have been developed. But these models do not consider the acceleration of leading vehicle. Some of them consider individual anticipation behavior of drivers, but they either do not quantitatively determine the types of driving or artificially divide the driving types rather than deriving them from actual traffic data. In this paper, driver’s driving styles are firstly categorized based on actual traffic data via data mining and clustering algorithm. Secondly, a new car-following model based on FVD model is developed, taking into account individual anticipation effects and the acceleration of leading vehicle. The effect of driving characteristics and leading vehicle’s acceleration on car-following behavior is further analyzed via numerical simulation. The results show that considering the acceleration of preceding vehicle in the model improves the stability of traffic flow and different driving characteristics have different influence on the stability of traffic flow.

  16. A polycomb-mediated epigenetic field defect precedes invasive cervical carcinoma.

    Science.gov (United States)

    Wijetunga, Neil Ari; Ben-Dayan, Miriam; Tozour, Jessica; Burk, Robert D; Schlecht, Nicolas F; Einstein, Mark H; Greally, John M

    2016-09-20

    Human papillomavirus (HPV)-associated cervical carcinoma is preceded by stages of cervical intra-epithelial neoplasia (CIN) that can variably progress to malignancy. Understanding the different molecular processes involved in the progression of pre-malignant CIN is critical to the development of improved predictive and interventional capabilities. We tested the role of regulators of transcription in both the development and the progression of HPV-associated CIN, performing the most comprehensive genomic survey to date of DNA methylation in HPV-associated cervical neoplasia, testing ~2 million loci throughout the human genome in biopsies from 78 HPV+ women, identifying changes starting in early CIN and maintained through carcinogenesis. We identified loci at which DNA methylation is consistently altered, beginning early in the course of neoplastic disease and progressing with disease advancement. While the loss of DNA methylation occurs mostly at intergenic regions, acquisition of DNA methylation is at sites involved in transcriptional regulation, with strong enrichment for targets of polycomb repression. Using an independent cohort from The Cancer Genome Atlas, we validated the loci with increased DNA methylation and found that these regulatory changes were associated with locally decreased gene expression. Secondary validation using immunohistochemistry showed that the progression of neoplasia was associated with increasing polycomb protein expression specifically in the cervical epithelium. We find that perturbations of genomic regulatory processes occur early and persist in cervical carcinoma. The results indicate a polycomb-mediated epigenetic field defect in cervical neoplasia that may represent a target for early, topical interventions using polycomb inhibitors.

  17. Menstrual irregularities and lactation failure may precede thyroid dysfunction or goitre.

    Directory of Open Access Journals (Sweden)

    Joshi J

    1993-07-01

    Full Text Available Menstrual and reproductive history of 178 women referred to the thyroid clinic was compared with 49 healthy controls. Cases were classified as euthyroid, hypothyroid or hyperthyroid after clinical examination and after serum T3, T4, TSH measurements. Reproductive history was related chronologically to symptoms and signs of thyroid dysfunction. Only 31.8% of hypothyroid and 35.3% of hyperthyroid women had normal menstrual pattern in contrast with 56.3% of Euthyroid and 87.8% of healthy controls (p < 0.001. Reproductive failure (infertility, pregnancy wastage, failure of lactation occurred in 37.5% of hypothyroid and 36.5% of hyperthyroid cases against 16.3% of euthyroid and 16.7% of healthy controls (p < 0.05. Interestingly, in 45% of cases with menstrual abnormality, the anomaly was antecedent to other clinical features by a variable period of two months to ten years. Reproductive failure and lactation failure also preceded thyroid dysfunction or goitre. Reproductive dysfunction may therefore be considered as one of the presenting symptoms of thyroid disorders in women, keeping in mind both menstrual irregularities and lactation failure may also arise from other common or idiopathic origins. Especially in women with menstrual irregularities in the perimenopausal age if thyroid dysfunction is detected, pharmacotherapy may be a superior alternative to surgical interventions like hysterectomy.

  18. Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    James, N D; Apperley, J F; Kam, K C; Mackinnon, S; Goldman, J M; Goolden, A W.G.; Sikora, K [Royal Postgraduate Medical School, London (UK)

    1989-03-01

    Between August 1985 and October 1987 35 patients with chronic myeloid leukaemia (CML) were treated by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n=31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n=35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. TLI did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. It is concluded that addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This is not associated with significantly increased toxicity. (author).

  19. Future climate forcing potentially without precedent in the last 420 million years.

    Science.gov (United States)

    Foster, Gavin L; Royer, Dana L; Lunt, Daniel J

    2017-04-04

    The evolution of Earth's climate on geological timescales is largely driven by variations in the magnitude of total solar irradiance (TSI) and changes in the greenhouse gas content of the atmosphere. Here we show that the slow ∼50 Wm -2 increase in TSI over the last ∼420 million years (an increase of ∼9 Wm -2 of radiative forcing) was almost completely negated by a long-term decline in atmospheric CO 2 . This was likely due to the silicate weathering-negative feedback and the expansion of land plants that together ensured Earth's long-term habitability. Humanity's fossil-fuel use, if unabated, risks taking us, by the middle of the twenty-first century, to values of CO 2 not seen since the early Eocene (50 million years ago). If CO 2 continues to rise further into the twenty-third century, then the associated large increase in radiative forcing, and how the Earth system would respond, would likely be without geological precedent in the last half a billion years.

  20. The first film presentation of REM sleep behavior disorder precedes its scientific debut by 35 years

    Directory of Open Access Journals (Sweden)

    Janković Slavko M.

    2006-01-01

    Full Text Available The perplexing and tantalizing disease of rapid eye movement (REM sleep behavior disorder (RBD is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats [1]. In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepressant medication [2], and Tachibana et al., in 1975, the preservation of muscle tone during REM sleep in the acute psychosis induced by alcohol and meprobamate abuse [3]. However, the first formal description of RBD in humans as new parasomnia was made by Schenck et al in 1986 [4-7]. Subsequently, in 1990, the International Classification of Sleep Disorders definitely recognized RBD as new parasomnia [8]. To our knowledge, arts and literature do not mention RBD. Except for the quotation, made by Schenck et al [6] in 2002, of Don Quixote de la Mancha whose behavior in sleep strongly suggested that Miguel de Servantes actually described RBD, no other artistic work has portrayed this disorder. Only recently we become aware of the cinematic presentation of RBD which by decades precedes the first scientific description. The first presentation of RBD on film was made prior to the era of advanced electroencephalography and polysomnography, and even before the discovery of REM sleep by Aserinsky and Kleitman in 1953. [9]. The artistic and intuitive presentation of RBD was produced in Technicolor in a famous film "Cinderella" created by Walt Disney in 1950, some 35 years prior to its original publication in the journal "Sleep" [2]. Since there is an earlier version of the film initially produced in 1920, presumably containing this similar scene, we can only speculate that the first cinematic presentation of RBD might precede its scientific debut by 65 years. In a scene

  1. Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction.

    Science.gov (United States)

    Stanyer, Lee; Jorgensen, Wenche; Hori, Osamu; Clark, John B; Heales, Simon J R

    2008-09-01

    The accumulation of oxidatively modified proteins has been shown to be a characteristic feature of many neurodegenerative disorders and its regulation requires efficient proteolytic processing. One component of the mitochondrial proteolytic system is Lon, an ATP-dependent protease that has been shown to degrade oxidatively modified aconitase in vitro and may thus play a role in defending against the accumulation of oxidized matrix proteins in mitochondria. Using an assay system that allowed us to distinguish between basal and ATP-stimulated Lon protease activity, we have shown in isolated non-synaptic rat brain mitochondria that Lon protease is highly susceptible to oxidative inactivation by peroxynitrite (ONOO(-)). This susceptibility was more pronounced with regard to ATP-stimulated activity, which was inhibited by 75% in the presence of a bolus addition of 1mM ONOO(-), whereas basal unstimulated activity was inhibited by 45%. Treatment of mitochondria with a range of peroxynitrite concentrations (10-1000 microM) revealed that a decline in Lon protease activity preceded electron transport chain (ETC) dysfunction (complex I, II-III and IV) and that ATP-stimulated activity was approximately fivefold more sensitive than basal Lon protease activity. Furthermore, supplementation of mitochondrial matrix extracts with reduced glutathione, following ONOO(-) exposure, resulted in partial restoration of basal and ATP-stimulated activity, thus suggesting possible redox regulation of this enzyme complex. Taken together these findings suggest that Lon protease may be particularly vulnerable to inactivation in conditions associated with GSH depletion and elevated oxidative stress.

  2. Bilirubin exposure is associated with neonatal sepsis in the eight days preceding symptoms: a retrospective study.

    Science.gov (United States)

    Raimondi, Francesco; Borrelli, Angela Carla; Ferrara, Teresa; Giannattasio, Antonietta; Capasso, Letizia

    2017-09-01

    To compare levels of bilirubin (using the area under the curve, AUC) in preterm infants before the onset of sepsis with healthy matched-controls. Preterm infants born between January 2011 and December 2015 with late-onset sepsis were enrolled in our retrospective study and were matched with healthy controls (sex, birth weight and gestational age). Levels of bilirubin were registered in the eight days preceding the onset of sepsis and the AUC was calculated for both groups. Eighty-eight neonates (44 cases) were studied. GA and BW did not differ between cases and controls. In cases, we found a higher value of AUC (30.7 versus 22.5; p = 0.021). In our retrospective cohort, we found that the levels of bilirubin and the AUC in the first eight days before the onset of sepsis in preterm infants were significantly higher than the healthy controls. These data suggest that the prolonged exposition to high levels of bilirubin could increase the infection susceptibility in preterm infants.

  3. Stromal cell migration precedes hemopoietic repopulation of the bone marrow after irradiation

    International Nuclear Information System (INIS)

    Werts, E.D.; Gibson, D.P.; Knapp, S.A.; DeGowin, R.L.

    1980-01-01

    Circulation of hemopoietic stem cells into an irradiated site has been thoroughly documented, but migration of stromal cells to repair radiation damage has not. We determined the radiosensitivity of mouse bone marrow stroma and evaluated stromal and hemopoietic repopulation in x-irradiated marrow. The D 0 for growth of colonies of marrow stromal cells (MSC) was 215 to 230 rad. Total-body irradiation (TB) obliterated marrow stromal and hemopoietic cells within 3 days. In contrast, 1 day after 1000 rad leg irradiation (LI), MSC rose to 80% of normal, but fell to 34% by 3 days and recovered to 72% by 30 days. However, femoral nucleated cells diminished to 20% by 3 days and recovered to 74% of normal by 30 days. Likewise, differentiated marrow cells and hemopoietic stem cells were initially depleted. With 1000 rad LI followed 3 h later by 1000 rad to the body while shielding the leg, MSC and femoral nucleated cells recovered to values intermediate between 1000 rad TB and 1000 rad LI. We concluded that: (1) the D 0 for MSC was 215 to 230 rad, (2) stromal repopulation preceded hemopoietic recovery, and (3) immigration of stromal cells from an unirradiated sanctuary facilitated hemopoietic repopulation of a heavily irradiated site

  4. How are topics born? Understanding the research dynamics preceding the emergence of new areas

    Directory of Open Access Journals (Sweden)

    Angelo A. Salatino

    2017-06-01

    Full Text Available The ability to promptly recognise new research trends is strategic for many stakeholders, including universities, institutional funding bodies, academic publishers and companies. While the literature describes several approaches which aim to identify the emergence of new research topics early in their lifecycle, these rely on the assumption that the topic in question is already associated with a number of publications and consistently referred to by a community of researchers. Hence, detecting the emergence of a new research area at an embryonic stage, i.e., before the topic has been consistently labelled by a community of researchers and associated with a number of publications, is still an open challenge. In this paper, we begin to address this challenge by performing a study of the dynamics preceding the creation of new topics. This study indicates that the emergence of a new topic is anticipated by a significant increase in the pace of collaboration between relevant research areas, which can be seen as the ‘parents’ of the new topic. These initial findings (i confirm our hypothesis that it is possible in principle to detect the emergence of a new topic at the embryonic stage, (ii provide new empirical evidence supporting relevant theories in Philosophy of Science, and also (iii suggest that new topics tend to emerge in an environment in which weakly interconnected research areas begin to cross-fertilise.

  5. Bell’s Palsy: Symptoms Preceding and Accompanying the Facial Paresis

    Directory of Open Access Journals (Sweden)

    Daniele De Seta

    2014-01-01

    Full Text Available This individual prospective cohort study aims to report and analyze the symptoms preceding and accompanying the facial paresis in Bell’s palsy (BP. Two hundred sixty-nine patients affected by BP with a maximum delay of 48 hours from the onset were enrolled in the study. The evolution of the facial paresis expressed as House-Brackmann grade in the first 10 days and its correlation with symptoms were analyzed. At the onset, 136 patients presented postauricular pain, 114 were affected by dry eye, and 94 reported dysgeusia. Dry mouth was present in 54 patients (19.7%, facial pain, hyperlacrimation, aural fullness, and hyperacusis represented a smaller percentage of the reported symptoms. After 10 days, 39.9% of the group had a severe paresis while 10.2% reached a complete recovery. Dry mouth at the onset was correlated with severe grade of palsy and was prognostic for poor recovery in the early period. These outcomes lead to the deduction that the nervus intermedius plays an important role in the presentation of the BP and it might be responsible for most of the accompanying symptomatology of the paresis. Our findings could be of important interest to early address a BP patient to further examinations and subsequent therapy.

  6. Presentations and Preceding factors of Drug Overdose amongst adolescents admitted to a Large Regional Hospital.

    LENUS (Irish Health Repository)

    Maduemem, KE

    2018-04-01

    Suicide is the third most common cause of death among adolescents globally, and poisoning is the leading method of attempted suicide. Survival after self-poisoning or drug overdose (OD) is common, providing an opportunity for secondary prevention. The aim of this study was to highlight pattern of presentations and preceding factors of OD in an adolescent population. We retrospectively evaluated the data of 85 adolescents presenting to a large regional hospital with OD over a 3-year period. The female-to-male ratio was 4.3:1. The median age of adolescents was 15.83 (range: 11.32 – 16.98) years. History of deliberate self-harm (DSH) was documented in 44.7%. Twenty-eight (33%) patients had been under the care of the CAMHS prior to index admission. Acetaminophen was the commonest drug used. Depression was the most common cause of mental illness in the study group. Substance abuse and conduct disorder were significantly commoner in males (p<0.05). Self-poisoning including OD in adolescence is a strong predictor of suicide; understanding the probable triggers can be significant in establishing appropriate prevention strategies.

  7. Smoking, alcohol, and coffee consumption preceding Parkinson's disease: a case-control study.

    Science.gov (United States)

    Benedetti, M D; Bower, J H; Maraganore, D M; McDonnell, S K; Peterson, B J; Ahlskog, J E; Schaid, D J; Rocca, W A

    2000-11-14

    To study the association of PD with preceding smoking, alcohol, and coffee consumption using a case-control design. The authors used the medical records linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, MN, during the years 1976 to 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control subject. The authors reviewed the complete medical records of cases and control subjects to abstract exposure information. For coffee consumption, the authors found an OR of 0.35 (95% CI = 0.16 to 0.78, p = 0.01), a dose-effect trend (p = 0.003), and a later age at PD onset in cases who drank coffee compared with those who never did (median 72 versus 64 years; p = 0.0002). The inverse association with coffee remained significant after adjustment for education, smoking, and alcohol drinking and was restricted to PD cases with onset at age coffee drinking and PD; however, this association does not imply that coffee has a direct protective effect against PD. Alternative explanations for the association should be considered.

  8. Cognitive declines precede and predict functional declines in aging and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Laura B Zahodne

    Full Text Available To investigate the temporal ordering of cognitive and functional declines separately in older adults with or without Alzheimer's disease (AD.A community-based longitudinal study of aging and dementia in Northern Manhattan (Washington Heights/Hamilton Heights Inwood Columbia Aging Project and a multicenter, clinic-based longitudinal study of prevalent AD at Columbia University Medical Center, Johns Hopkins School of Medicine, Massachusetts General Hospital, and the Hôpital de la Salpêtrière in Paris, France (the Predictors Study.3,443 initially non-demented older adults (612 with eventual incident dementia and 517 patients with AD.Cognitive measures included the modified Mini-Mental State Exam and composite scores of memory and language derived from a standardized neuropsychological battery. Function was measured with the Blessed Dementia Rating Scale, completed by the participant (in the sample of non-demented older adults or an informant (in the sample of prevalent AD patients. Data were analyzed with autoregressive cross-lagged panel analysis.Cognitive scores more consistently predicted subsequent functional abilities than vice versa in non-demented older adults, participants with eventual incident dementia, and patients with prevalent AD.Cognitive declines appear to precede and cause functional declines prior to and following dementia diagnosis. Standardized neuropsychological tests are valid predictors of later functional changes in both non-demented and demented older adults.

  9. Calcium release-dependent inactivation precedes formation of the tubular system in developing rat cardiac myocytes.

    Science.gov (United States)

    Macková, Katarina; Zahradníková, Alexandra; Hoťka, Matej; Hoffmannová, Barbora; Zahradník, Ivan; Zahradníková, Alexandra

    2017-12-01

    Developing cardiac myocytes undergo substantial structural and functional changes transforming the mechanism of excitation-contraction coupling from the embryonic form, based on calcium influx through sarcolemmal DHPR calcium channels, to the adult form, relying on local calcium release through RYR calcium channels of sarcoplasmic reticulum stimulated by calcium influx. We characterized day-by-day the postnatal development of the structure of sarcolemma, using techniques of confocal fluorescence microscopy, and the development of the calcium current, measured by the whole-cell patch-clamp in isolated rat ventricular myocytes. We characterized the appearance and expansion of the t-tubule system and compared it with the appearance and progress of the calcium current inactivation induced by the release of calcium ions from sarcoplasmic reticulum as structural and functional measures of direct DHPR-RYR interaction. The release-dependent inactivation of calcium current preceded the development of the t-tubular system by several days, indicating formation of the first DHPR-RYR couplons at the surface sarcolemma and their later spreading close to contractile myofibrils with the growing t-tubules. Large variability of both of the measured parameters among individual myocytes indicates uneven maturation of myocytes within the growing myocardium.

  10. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus.

    Science.gov (United States)

    Sohn, Elliott H; van Dijk, Hille W; Jiao, Chunhua; Kok, Pauline H B; Jeong, Woojin; Demirkaya, Nazli; Garmager, Allison; Wit, Ferdinand; Kucukevcilioglu, Murat; van Velthoven, Mirjam E J; DeVries, J Hans; Mullins, Robert F; Kuehn, Markus H; Schlingemann, Reinier Otto; Sonka, Milan; Verbraak, Frank D; Abràmoff, Michael David

    2016-05-10

    Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.

  11. Nucleus basalis of Meynert degeneration precedes and predicts cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Schulz, Jonathan; Pagano, Gennaro; Fernández Bonfante, Juan Alberto; Wilson, Heather; Politis, Marios

    2018-05-01

    Currently, no reliable predictors of cognitive impairment in Parkinson's disease exist. We hypothesized that microstructural changes at grey matter T1-weighted MRI and diffusion tensor imaging in the cholinergic system nuclei and associated limbic pathways underlie cognitive impairment in Parkinson's disease. We performed a cross-sectional comparison between patients with Parkinson's disease with and without cognitive impairment. We also performed a longitudinal 36-month follow-up study of cognitively intact Parkinson's disease patients, comparing patients who remained cognitively intact to those who developed cognitive impairment. Patients with Parkinson's disease with cognitive impairment showed lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert, compared to patients with Parkinson's disease without cognitive impairment. These results were confirmed both with region of interest and voxel-based analyses, and after partial volume correction. Lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert was predictive for developing cognitive impairment in cognitively intact patients with Parkinson's disease, independent of other clinical and non-clinical markers of the disease. Structural and microstructural alterations in entorhinal cortex, amygdala, hippocampus, insula, and thalamus were not predictive for developing cognitive impairment in Parkinson's disease. Our findings provide evidence that degeneration of the nucleus basalis of Meynert precedes and predicts the onset of cognitive impairment, and might be used in a clinical setting as a reliable biomarker to stratify patients at higher risk of cognitive decline.

  12. Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia

    International Nuclear Information System (INIS)

    James, N.D.; Apperley, J.F.; Kam, K.C.; Mackinnon, S.; Goldman, J.M.; Goolden, A.W.G.; Sikora, K.

    1989-01-01

    Between August 1985 and October 1987 35 patients with chronic myeloid leukaemia (CML) were treated by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n=31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n=35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. TLI did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. It is concluded that addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This is not associated with significantly increased toxicity. (author)

  13. Genetic architecture of conspecific sperm precedence in Allonemobius fasciatus and A. socius.

    Science.gov (United States)

    Britch, Seth C; Swartout, Emma J; Hampton, Daniel D; Draney, Michael L; Chu, Jiming; Marshall, Jeremy L; Howard, Daniel J

    2007-06-01

    The evolution of barriers to gene exchange is centrally important to speciation. We used the crickets Allonemobius fasciatus and A. socius to investigate the genetic architecture of conspecific sperm precedence (CSP), a postinsemination prezygotic reproductive barrier. With amplified fragment-length polymorphism (AFLP) markers and controlled crosses we constructed linkage maps and estimated positions of QTL associated with CSP. The majority of QTL have low to moderate effects, although a few QTL exist in A. socius with large effects, and the numbers of QTL are comparable to numbers of genes accounting for species differences in other studies. The QTL are spread across many unlinked markers, yet QTL placed with linked markers are on a small number of linkage groups that could reflect the role of the large Allonemobius sex chromosome in prezygotic isolation. Although many QTL had positive effects on conspecific sperm utilization several QTL also exerted negative effects, which could be explained by intraspecific sexual conflict, sperm competition, or epistasis of introgressed genes on novel backgrounds. One unexpected outcome was that A. socius CSP alleles have a stronger effect than those from A. fasciatus in hybrid females, causing hybrids to behave like A. socius with regard to sperm utilization. Implications of this asymmetry in the Allonemobius hybrid zone are discussed.

  14. Temporal changes in stress preceding the 2004-2008 eruption of Mount St. Helens, Washington

    Science.gov (United States)

    Lehto, H.L.; Roman, D.C.; Moran, S.C.

    2010-01-01

    The 2004-2008 eruption of Mount St. Helens (MSH), Washington, was preceded by a swarm of shallow volcano-tectonic earthquakes (VTs) that began on September 23, 2004. We calculated locations and fault-plane solutions (FPS) for shallow VTs recorded during a background period (January 1999 to July 2004) and during the early vent-clearing phase (September 23 to 29, 2004) of the 2004-2008 eruption. FPS show normal and strike-slip faulting during the background period and on September 23; strike-slip and reverse faulting on September 24; and a mixture of strike-slip, reverse, and normal faulting on September 25-29. The orientation of ??1 beneath MSH, as estimated from stress tensor inversions, was found to be sub-horizontal for all periods and oriented NE-SW during the background period, NW-SE on September 24, and NE-SW on September 25-29. We suggest that the ephemeral ~90?? change in ??1 orientation was due to intrusion and inflation of a NE-SW-oriented dike in the shallow crust prior to the eruption onset. ?? 2010 Elsevier B.V.

  15. [The first film presentation of REM sleep behavior disorder precedes its scientific debut by 35 years].

    Science.gov (United States)

    Janković, Slavko M; Sokić, Dragoslav V; Vojvodić, Nikola M; Ristić, Aleksandar J

    2006-01-01

    The perplexing and tantalizing disease of rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats. In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepressant medication, and Tachibana et al., in 1975, the preservation of muscle tone during REM sleep in the acute psychosis induced by alcohol and meprobamate abuse. wever, the first formal description of RBD in humans as new parasomnia was made by Schenck et al in 1986. Subsequently, in 1990, the International Classification of Sleep Disorders definitely recognized RBD as new parasomnia. To our knowledge, arts and literature do not mention RBD. Except for the quotation, made by Schenck et al [n 2002, of Don Quixote de la Mancha whose behavior in sleep strongly suggested that Miguel de Servantes actually described RBD, no other artistic work has portrayed this disorder. Only recently we become aware of the cinematic presentation of RBD which by decades precedes the first scientific description. The first presentation of RBD on film was made prior to the era of advanced electroencephalography and polysomnography, and even before the discovery of REM sleep by Aserinsky and Kleitman in 1953. The artistic and intuitive presentation of RBD was produced in Technicolor in a famous film "Cinderella" created by Walt Disney in 1950, some 35 years prior to its original publication in the journal "Sleep". Since there is an earlier version of the film initially produced in 1920, presumably containing this similar scene, we can only speculate that the first cinematic presentation of RBD might precede its scientific debut by 65 years. In a scene in a barn, clumsy and goofy dog Bruno is, as dogs

  16. Understanding suicide among indigenous adolescents: a review using the PRECEDE model.

    Science.gov (United States)

    Clarke, V A; Frankish, C J; Green, L W

    1997-06-01

    To use the available literature to identify the causes of suicide among indigenous adolescents. The PRECEDE model provided a framework to organize the material and identify the areas where relatively little research had been reported. The epidemiological diagnosis showed that suicide was greater in indigenous than non-indigenous populations and particularly high among adolescent males. Environments of native persons are characterized by remoteness, poverty, cultural displacement, and family disintegration. The educational and organizational diagnosis identified predisposing factors reflecting the social environments previously identified, the enabling factors of televised suicides, and firearm and alcohol availability, in conjunction with an absence of positive expectations. Finally the administrative and policy diagnosis identified a piecemeal, short term perspective, often lacking cultural sensitivity. Although there was more literature from the United States than from Canada, Australia or New Zealand, the pictures emerging were consistent, with problems being identified across continents. Literature was more abundant in relation to the epidemiological, environmental, and educational/ organizational diagnoses than in relation to policy and administration. The increased suicide rates among indigenous adolescents were not a product of their native origins, but of the social milieu in which these people generally found themselves.

  17. "Facilitated" amino acid transport is upregulated in brain tumors.

    Science.gov (United States)

    Miyagawa, T; Oku, T; Uehara, H; Desai, R; Beattie, B; Tjuvajev, J; Blasberg, R

    1998-05-01

    The goal of this study was to determine the magnitude of "facilitated" amino acid transport across tumor and brain capillaries and to evaluate whether amino acid transporter expression is "upregulated" in tumor vessels compared to capillaries in contralateral brain tissue. Aminocyclopentane carboxylic acid (ACPC), a non-metabolized [14C]-labeled amino acid, and a reference molecule for passive vascular permeability, [67Ga]-gallium-diethylenetriaminepentaacetic acid (Ga-DTPA), were used in these studies. Two experimental rat gliomas were studied (C6 and RG2). Brain tissue was rapidly processed for double label quantitative autoradiography 10 minutes after intravenous injection of ACPC and Ga-DTPA. Parametric images of blood-to-brain transport (K1ACPC and K1Ga-DTPA, microL/min/g) produced from the autoradiograms and the histology were obtained from the same tissue section. These three images were registered in an image array processor; regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images to obtain mean values. The facilitated component of ACPC transport (deltaK1ACPC) was calculated from the K1ACPC and K1Ga-DTPA data, and paired comparisons between tumor and contralateral brain were performed. ACPC flux, K1ACPC, across normal brain capillaries (22.6 +/- 8.1 microL/g/min) was >200-fold greater than that of Ga-DTPA (0.09 +/- 0.04 microL/g/min), and this difference was largely (approximately 90%) due to facilitated ACPC transport. Substantially higher K1ACPC values compared to corresponding K1DTPA values were also measured in C6 and RG2 gliomas. The deltaK1ACPC values for C6 glioma were more than twice that of contralateral brain cortex. K1ACPC and deltaK1ACPC values for RG2 gliomas was not significantly higher than that of contralateral cortex, although a approximately 2-fold difference in facilitated transport is obtained after normalization for differences in capillary

  18. The usability of a 15-gene hypoxia classifier as a universal hypoxia profile in various cancer cell types

    DEFF Research Database (Denmark)

    Sørensen, Brita Singers; Knudsen, Anders Bisgård; Wittrup, Catja Foged

    2015-01-01

    genes, with BNIP3 not being upregulated at hypoxic conditions in 3 out of 6 colon cancer cell lines, and ALDOA in OE21 and FAM162A and SLC2A1 in SW116 only showing limited hypoxia induction. Furthermore, in the esophagus cell lines, the normoxic and hypoxic expression levels of LOX and BNIP3 were below...... the tissue type dependency of hypoxia induced genes included in a 15-gene hypoxic profile in carcinoma cell lines from prostate, colon, and esophagus cancer, and demonstrated that in vitro, with minor fluctuations, the genes in the hypoxic profile are hypoxia inducible, and the hypoxia profile may......BACKGROUND AND PURPOSE: A 15-gene hypoxia profile has previously demonstrated to have both prognostic and predictive impact for hypoxic modification in squamous cell carcinoma of the head and neck. This gene expression profile may also have a prognostic value in other histological cancer types...

  19. Up-regulation of melanin synthesis by the antidepressant fluoxetine.

    Science.gov (United States)

    Liao, Sha; Shang, Jing; Tian, Xiaoli; Fan, Xueqi; Shi, Xiupu; Pei, Siran; Wang, Qian; Yu, Boyang

    2012-08-01

    Fluoxetine, a member of the class of selective serotonin reuptake inhibitors, is a potent antidepressant commonly used in clinical practice. Here, we report that fluoxetine increases cellular tyrosinase (TYR) activity, enhances the protein levels of microphthalmia-associated transcription factor (MITF), TYR and tyrosinase-related protein-1 (TRP-1) and eventually leads to a dramatic increase in melanin production in both murine B16F10 melanoma cells and normal human melanocytes (NHMCs). In well-characterized C57BL/6 mouse models, systemic application of fluoxetine increased hair pigmentation by up-regulating hair follicular MITF, TYR, TRP-1 and tyrosinase-related protein-2 (TRP-2) protein levels. Using a serotonin 1A receptor (SR1A) antagonist and RNA interference (RNAi) technique, we revealed that SR1A appears to be one of the involved pathways in the fluoxetine-induced melanogenesis in B16F10 cells. These results suggest that fluoxetine may hold a significant therapeutic potential for treating skin hypopigmentation disorders, and SR1A may serve as a novel target in modulating melanogenesis. © 2012 John Wiley & Sons A/S.

  20. Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells

    Directory of Open Access Journals (Sweden)

    Iva eBozic

    2015-09-01

    Full Text Available Chronic microglial activation and resulting sustained neuroinflammatory reaction are generally associated with neurodegeneration. Activated microglia acquires proinflammatory cellular profile that generates oxidative burst. Their persistent activation exacerbates inflammation, which damages healthy neurons via cytotoxic mediators, such as superoxide radical anion and nitric oxide. In our recent study, we have shown that benfotiamine (S-benzoylthiamine O-monophosphate possesses anti-inflammatory effects. Here, the effects of benfotiamine on the pro-oxidative component of activity of LPS-stimulated BV-2 cells were investigated. The activation of microglia was accompanied by upregulation of intracellular antioxidative defense, which was further promoted in the presence of benfotiamine. Namely, activated microglia exposed to non-cytotoxic doses of benfotiamine showed increased levels and activities of hydrogen peroxide- and superoxide-removing enzymes – catalase and glutathione system, and superoxide dismutase. In addition, benfotiamine showed the capacity to directly scavenge superoxide radical anion. As a consequence, benfotiamine suppressed the activation of microglia and provoked a decrease in NO and •O2- production and lipid peroxidation. In conclusion, benfotiamine might silence pro-oxidative activity of microglia to alleviate/prevent oxidative damage of neighboring CNS cells.

  1. Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells.

    Science.gov (United States)

    Bozic, Iva; Savic, Danijela; Stevanovic, Ivana; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

    2015-01-01

    Chronic microglial activation and resulting sustained neuroinflammatory reaction are generally associated with neurodegeneration. Activated microglia acquires proinflammatory cellular profile that generates oxidative burst. Their persistent activation exacerbates inflammation, which damages healthy neurons via cytotoxic mediators, such as superoxide radical anion and nitric oxide. In our recent study, we have shown that benfotiamine (S-benzoylthiamine O-monophosphate) possesses anti-inflammatory effects. Here, the effects of benfotiamine on the pro-oxidative component of activity of LPS-stimulated BV-2 cells were investigated. The activation of microglia was accompanied by upregulation of intracellular antioxidative defense, which was further promoted in the presence of benfotiamine. Namely, activated microglia exposed to non-cytotoxic doses of benfotiamine showed increased levels and activities of hydrogen peroxide- and superoxide-removing enzymes-catalase and glutathione system, and superoxide dismutase. In addition, benfotiamine showed the capacity to directly scavenge superoxide radical anion. As a consequence, benfotiamine suppressed the activation of microglia and provoked a decrease in NO and (·)O(-) 2 production and lipid peroxidation. In conclusion, benfotiamine might silence pro-oxidative activity of microglia to alleviate/prevent oxidative damage of neighboring CNS cells.

  2. The Effect of an Education Program Utilising PRECEDE Model on the Quality of Life in Patients with Type 2 Diabetes

    Science.gov (United States)

    Taghdisi, M. H.; Borhani, M.; Solhi, M.; Afkari, M. E.; Hosseini, F.

    2012-01-01

    Background and objective: The problems caused by diabetes have direct and indirect impacts on the quality of life of diabetic patients. An increase of these problems means a decrease in a patient's quality of life. This study was conducted to assess the effect of the educational programme based on the precede model in promoting quality of life of…

  3. Magnetic resonance imaging findings of mumps meningoencephalitis with bilateral hippocampal lesions without preceding acute parotitis: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Ah Reum; Lee, Ha Young; Lim, Myung Kwan; Kang, Young Hye; Cho, Soon Gu; Choi, Seong Hye; Baek, Ji Hyeon [Inha University School of Medicine, Incheon (Korea, Republic of)

    2017-04-15

    Meningitis is a common central nervous system (CNS) complication of the mumps, a viral infection, but encephalitis and meningoencephalitis are less common in mumps. We describe magnetic resonance imaging findings of acute mumps meningoencephalitis in a 32-year-old male who showed bilateral hippocampal lesions without preceding parotitis. Although it is rare, hippocampal involvement should be considered a CNS complication of mumps infection.

  4. Self-verification strivings in children holding negative self-views: the mitigating effects of a preceding success experience

    NARCIS (Netherlands)

    Reijntjes, A.; Thomaes, S.; Kamphuis, J.H.; Orobio de Castro, B.; Telch, M.J.

    2010-01-01

    Research among adults has consistently shown that people holding negative self-views prefer negative over positive feedback. The present study tested the hypothesis that this preference is less robust among pre-adolescents, such that it will be mitigated by a preceding positive event.

  5. Different Fear-Regulation Behaviors in Toddlerhood: Relations to Preceding Infant Negative Emotionality, Maternal Depression, and Sensitivity

    Science.gov (United States)

    Gloggler, Bettina; Pauli-Pott, Ursula

    2008-01-01

    In the study presented, the development of different fear regulation behaviors and their associations with preceding maternal sensitivity and depression is addressed. A sample of 64 mother-child pairs was examined at the children's ages of 4, 12, and 30 months. Four-month negative reactivity and 12- and 30- month behavioral inhibition and fear…

  6. First sale doctrine on computer programs in the European Union. reiteration of the precedent or jurisprudential change?

    Directory of Open Access Journals (Sweden)

    Sergio Raúl Cardoso González

    2017-08-01

    Full Text Available Comparative analysis of rulings C-128/11 (UsedSoft of July 3, 2012 and C-166/15 (Ranks and Vasiļevičs of October 12, 2016 by the Court of Justice of the European Union, concerning first sale doctrine on computer programs. Reiteration of the precedent or jurisprudential change?

  7. Number and sequence of preceding miscarriages and maternal age for the prediction of antiphospholipid syndrome in women with recurrent miscarriage.

    NARCIS (Netherlands)

    Boogaard, E. van den; Cohn, D.M.; Korevaar, J.C.; Dawood, F.; Vissenberg, R.; Middeldorp, S.; Goddijn, M.; Farquharson, R.G.

    2013-01-01

    Objective: To investigate the relationship between the number and sequence of preceding miscarriages and antiphospholipid syndrome (APS). Design: Retrospective cohort study. Setting: Recurrent miscarriage (RM) clinic. Patient(s): Women who attended the RM clinic from 1988 to 2006. Intervention(s):

  8. Suicide and general elections in Austria: do preceding regional suicide rate differentials foreshadow subsequent voting behavior swings?

    Science.gov (United States)

    Voracek, Martin; Formann, Anton K; Fülöp, Gerhard; Sonneck, Gernot

    2003-05-01

    Suicide-epidemiological research on short-term effects of elections on national/regional suicide and parasuicide incidence has yielded contradictory evidence. Reversing the cause-effect relationship of this line of research we investigated whether preceding regional suicide rates are related to subsequent election results. For Austria's 121 districts, we regressed averaged standardized suicide rates for the preceding period (1988-1994) on political parties' subsequent electoral gains/losses (1999-to-1995) while controlling for a set of 12 domain-relevant psychosocial/economic indices. Stepwise weighted multiple regression led to a significant model. The 1999-to-1995 electoral gains/losses of two opposition parties, together with the population variation caused by migration balance and by births/deaths balance, accounted for a substantial part (30%) of the variability in preceding district-level suicide rates. Various other social indices failed to contribute further substantial increments to this model. This finding suggests that variations in preceding regional suicide incidence might be mirrored in subsequent changes in voting behavior. A speculative post hoc explanation for the finding is offered: on a community level, suicide's aftermath might produce socially and politically alienated survivors of suicide who co-shape swings towards opposition parties in subsequent general elections. The finding calls for more research on suicide's long-term aftermath. Within-country replicability and cross-national generalizability await further investigation. At present, the factor/mechanism accounting for this finding is neither well-established nor has been directly tested.

  9. “Caint na ndaoine”. The Irish Language as a Precedent for Standardisation

    Directory of Open Access Journals (Sweden)

    Carlo James Waskowski Ritchie

    2016-12-01

    Full Text Available “Caint na ndaoine”. The Irish Language as a Precedent for Standardisation Critics of the standardisation of the Irish language argue that the “modernisation” of the Irish orthography has been detrimental to the preservation of the various dialects that form native spoken Irish. The effects of standardisation on Irish consequently form an important precedent for language standardisation. The potential alienation of a language’s native speakers is an outcome of standardisation that is obviously destructive for a language community that exists in a minority. The issues that surround the movement for a standardised Plattdeutsch are similar to those faced in the standardisation of Modern Irish. Since the recognition by the European Union of Low German (Plattdeutsch as a regional language in 1998, there has been newfound momentum in the movement for its reestablishment as a unified language of Northern Germany. One of the great difficulties of this movement however is the lack of any universal orthography due to the separate nature of the language’s dialects. Given the sociolinguistic similarities of these two (albeit unrelated languages, a study of the effects of the standardisation of Irish is useful for an assessment of the possibility of a standardised Plattdeutsch.   “Caint na ndaoine”. Język irlandzki jako precedens standaryzacji Krytycy procesu standaryzacji języka irlandzkiego uważają, że „modernizacja” irlandzkiej ortografii zaszkodziła ochronie wielu dialektów składających się na oralny język natywnych Irlandczyków. Skutki standaryzacji irlandzkiego stanowią więc ważny precedens standaryzacji języków. Możliwe wyobcowanie natywnych użytkowników języka jest w oczywisty sposób destrukcyjnym dla trwania wspólnoty mniejszościowej rezultatem procesu standaryzacji. Zagadnienia towarzyszące ruchowi na rzecz standaryzacji języka dolnoniemieckiego są podobne do problemów standaryzacji, wobec kt

  10. Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

    International Nuclear Information System (INIS)

    Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell'Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto; Pellegrino, Teresa; Petretta, Mario; Riccio, Eleonora; Pisani, Antonio

    2017-01-01

    Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by 123 I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by 123 I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r 2 = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, 123 I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

  11. Optimally growing boundary layer disturbances in a convergent nozzle preceded by a circular pipe

    Science.gov (United States)

    Uzun, Ali; Davis, Timothy B.; Alvi, Farrukh S.; Hussaini, M. Yousuff

    2017-06-01

    We report the findings from a theoretical analysis of optimally growing disturbances in an initially turbulent boundary layer. The motivation behind this study originates from the desire to generate organized structures in an initially turbulent boundary layer via excitation by disturbances that are tailored to be preferentially amplified. Such optimally growing disturbances are of interest for implementation in an active flow control strategy that is investigated for effective jet noise control. Details of the optimal perturbation theory implemented in this study are discussed. The relevant stability equations are derived using both the standard decomposition and the triple decomposition. The chosen test case geometry contains a convergent nozzle, which generates a Mach 0.9 round jet, preceded by a circular pipe. Optimally growing disturbances are introduced at various stations within the circular pipe section to facilitate disturbance energy amplification upstream of the favorable pressure gradient zone within the convergent nozzle, which has a stabilizing effect on disturbance growth. Effects of temporal frequency, disturbance input and output plane locations as well as separation distance between output and input planes are investigated. The results indicate that optimally growing disturbances appear in the form of longitudinal counter-rotating vortex pairs, whose size can be on the order of several times the input plane mean boundary layer thickness. The azimuthal wavenumber, which represents the number of counter-rotating vortex pairs, is found to generally decrease with increasing separation distance. Compared to the standard decomposition, the triple decomposition analysis generally predicts relatively lower azimuthal wavenumbers and significantly reduced energy amplification ratios for the optimal disturbances.

  12. Predictive Physiological Anticipation Preceding Seemingly Unpredictable Stimuli:A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Julia eMossbridge

    2012-10-01

    Full Text Available This meta-analysis of 26 reports published between 1978 and 2010 tests an unusal hypothesis: for stimuli of two or more types that are presented in an order designed to be unpredictable and that produce different post-stimulus physiological activity, the direction of pre-stimulus physiological activity reflects the direction of post-stimulus physiological activity, resulting in an unexplained anticipatory effect. The reports we examined used one of two paradigms: 1 randomly presented arousing vs. neutral stimuli, or 2 guessing tasks with feedback (correct vs. incorrect. Dependent variables included: electrodermal activity, heart rate, blood volume, pupil dilation, electroencephalographic activity (EEG, and blood oxygenation level dependent (BOLD activity. To avoid including data hand-picked from multiple different analyses, no post-hoc experiments are considered. The results reveal a significant overall effect with a small effect size (random effects: overall [weighted] ES=0.21, 95%CI=0.13-0.29, z=5.3, p<5.7x10-8; fixed effects: overall ES=0.21, 95%CI=0.15-0.27, z=6.9, p<2.7x10-12. Higher quality experiments produce a quantitately larger effect size and a greater level of significance than lower quality studies. The number of contrary unpublished reports that would be necessary to reduce the level of significance to chance (p>0.05 was conservatively calculated to be 87 reports. We explore alternative explanations and examine the potential linkage between this unexplained anticipatory activity and other results demonstrating meaningful pre-stimulus activity preceding behaviourally relevant events. Multiple replications arising from different laboratories using the same methods are necessary to further examine this currently unexplained anticipatory activity. The cause of this anticipatory activity, which undoubtedly lies within the realm of natural physical processes (as opposed to supernatural or paranormal ones, remains to be determined.

  13. Observations of increased tropical rainfall preceded by air passage over forests.

    Science.gov (United States)

    Spracklen, D V; Arnold, S R; Taylor, C M

    2012-09-13

    Vegetation affects precipitation patterns by mediating moisture, energy and trace-gas fluxes between the surface and atmosphere. When forests are replaced by pasture or crops, evapotranspiration of moisture from soil and vegetation is often diminished, leading to reduced atmospheric humidity and potentially suppressing precipitation. Climate models predict that large-scale tropical deforestation causes reduced regional precipitation, although the magnitude of the effect is model and resolution dependent. In contrast, observational studies have linked deforestation to increased precipitation locally but have been unable to explore the impact of large-scale deforestation. Here we use satellite remote-sensing data of tropical precipitation and vegetation, combined with simulated atmospheric transport patterns, to assess the pan-tropical effect of forests on tropical rainfall. We find that for more than 60 per cent of the tropical land surface (latitudes 30 degrees south to 30 degrees north), air that has passed over extensive vegetation in the preceding few days produces at least twice as much rain as air that has passed over little vegetation. We demonstrate that this empirical correlation is consistent with evapotranspiration maintaining atmospheric moisture in air that passes over extensive vegetation. We combine these empirical relationships with current trends of Amazonian deforestation to estimate reductions of 12 and 21 per cent in wet-season and dry-season precipitation respectively across the Amazon basin by 2050, due to less-efficient moisture recycling. Our observation-based results complement similar estimates from climate models, in which the physical mechanisms and feedbacks at work could be explored in more detail.

  14. Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph-Ephrin Signaling

    Directory of Open Access Journals (Sweden)

    Cecilie Linneberg

    2015-09-01

    Full Text Available In the central nervous system, myelination of axons is required to ensure fast saltatory conduction and for survival of neurons. However, not all axons are myelinated, and the molecular mechanisms involved in guiding the oligodendrocyte processes toward the axons to be myelinated are not well understood. Only a few negative or positive guidance clues that are involved in regulating axo-glia interaction prior to myelination have been identified. One example is laminin, known to be required for early axo-glia interaction, which functions through α6β1 integrin. Here, we identify the Eph-ephrin family of guidance receptors as novel regulators of the initial axo-glia interaction, preceding myelination. We demonstrate that so-called forward and reverse signaling, mediated by members of both Eph and ephrin subfamilies, has distinct and opposing effects on processes extension and myelin sheet formation. EphA forward signaling inhibits oligodendrocyte process extension and myelin sheet formation, and blocking of bidirectional signaling through this receptor enhances myelination. Similarly, EphB forward signaling also reduces myelin membrane formation, but in contrast to EphA forward signaling, this occurs in an integrin-dependent manner, which can be reversed by overexpression of a constitutive active β1-integrin. Furthermore, ephrin-B reverse signaling induced by EphA4 or EphB1 enhances myelin sheet formation. Combined, this suggests that the Eph-ephrin receptors are important mediators of bidirectional signaling between axons and oligodendrocytes. It further implies that balancing Eph-ephrin forward and reverse signaling is important in the selection process of axons to be myelinated.

  15. Enhanced canopy growth precedes senescence in 2005 and 2010 Amazonian droughts

    KAUST Repository

    Liu, Yi Y.

    2018-04-09

    preceding drought-induced senescence should be taken into account when interpreting the ecological impacts of Amazonian droughts.

  16. Effect of preceding exercise on cerebral and splanchnic vascular responses to mental task

    Directory of Open Access Journals (Sweden)

    Someya Nami

    2012-06-01

    Full Text Available Abstract Background To investigate the effect of preceding acute exercise on the peripheral vascular response to a mental task, we measured splanchnic and cerebral blood flow responses to performing a mental task after exercise and resting. Methods In the exercise trial, 11 males exercised for 30 min on a cycle ergometer with a workload set at 70% of the age-predicted maximal heart rate for each individual. After a 15-min recovery period, the subjects rested for 5 min for pre-task baseline measurement and then performed mental arithmetic for 5 min followed by 5 min of post-task measurement. In the resting trial, they rested for 45 min and pre-task baseline data was obtained for 5 min. Then mental arithmetic was performed for 5 min followed by post-task measurement. We measured the mean blood velocity in the middle cerebral artery and superior mesenteric artery and the mean arterial pressure. Results Mean arterial pressure and mean blood velocity in the middle cerebral artery were significantly higher than the baseline during mental arithmetic in both exercise and resting trials. Mean blood velocity in the middle cerebral artery during mental arithmetic was greater in the control trial than the exercise trial. Mean blood velocity in the superior mesenteric artery showed no significant change during mental arithmetic from baseline in both trials. Conclusion These results suggest that acute exercise can moderate the increase in cerebral blood flow induced by a mental task.

  17. A polycomb-mediated epigenetic field defect precedes invasive cervical carcinoma

    Science.gov (United States)

    Wijetunga, Neil Ari; Ben-Dayan, Miriam; Tozour, Jessica; Burk, Robert D.; Schlecht, Nicolas F.; Einstein, Mark H.; Greally, John M.

    2016-01-01

    Human papillomavirus (HPV)-associated cervical carcinoma is preceded by stages of cervical intra-epithelial neoplasia (CIN) that can variably progress to malignancy. Understanding the different molecular processes involved in the progression of pre-malignant CIN is critical to the development of improved predictive and interventional capabilities. We tested the role of regulators of transcription in both the development and the progression of HPV-associated CIN, performing the most comprehensive genomic survey to date of DNA methylation in HPV-associated cervical neoplasia, testing ~2 million loci throughout the human genome in biopsies from 78 HPV+ women, identifying changes starting in early CIN and maintained through carcinogenesis. We identified loci at which DNA methylation is consistently altered, beginning early in the course of neoplastic disease and progressing with disease advancement. While the loss of DNA methylation occurs mostly at intergenic regions, acquisition of DNA methylation is at sites involved in transcriptional regulation, with strong enrichment for targets of polycomb repression. Using an independent cohort from The Cancer Genome Atlas, we validated the loci with increased DNA methylation and found that these regulatory changes were associated with locally decreased gene expression. Secondary validation using immunohistochemistry showed that the progression of neoplasia was associated with increasing polycomb protein expression specifically in the cervical epithelium. We find that perturbations of genomic regulatory processes occur early and persist in cervical carcinoma. The results indicate a polycomb-mediated epigenetic field defect in cervical neoplasia that may represent a target for early, topical interventions using polycomb inhibitors. PMID:27557505

  18. Severe hyponatremia as the initial sign preceding Guillain-Barré syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Abhishek Wankar

    2014-01-01

    Full Text Available Diagnosis of Guillain-Barrι syndrome (GBS is established clinically and is supported by nerve conduction studies and cerebrospinal fluid examination. Renal function is usually not affected, but recent case reports have established a link between GBS and hyponatremia. A 60-year-old woman presenting with lower back ache since 3 days, became drowsy the next day and developed paraparesis and bulbar symptoms. Her sensorium and power deteriorated progressively over the next 2 days and she was brought to hospital in a drowsy state. She was found to have severe hyponatremia (Na + at 113 and nerve conduction study (NCS was son of AMAN. The patient was started on intravenous immunoglobulin and her sodium levels were corrected, and the patient recovered completely. The occurrence of hyponatremia in patients diagnosed with GBS is well described. However, there have been only two prior case reports in which hyponatremia had been observed before the manifestation of neuromuscular deficits. Our patient case is unique in that severe hyponatremia occurred simultaneously with neurologic symptoms and the diagnosis of GBS. In most cases reported in the literature, hyponatremia was noted after a diagnosis of GBS was established. The mean period of onset of syndrome of inappropriate antidiuretic hormone (SIADH was 8.8 days after the onset of symptoms of GBS. In Conclusion , this presentation raises the possibility that early changes in the autonomic nervous system triggered by GBS might lead to alterations in water and sodium balance that can precede symptomatic changes in the peripheral nervous system. Although rarely, but both GBS and its treatment, intravenous immunoglobulin, should be considered in the differential diagnosis of hyponatremia.

  19. Increased diagnostic activity in general practice during the year preceding colorectal cancer diagnosis.

    Science.gov (United States)

    Hansen, Pernille Libach; Hjertholm, Peter; Vedsted, Peter

    2015-08-01

    Accurate diagnostic activity in general practice before colorectal cancer (CRC) diagnosis is crucial for an early detection of CRC. This study aimed to investigate the rates of daytime consultations, hemoglobin (Hb) measurements and medicine prescriptions for hemorrhoids in general practice in the year preceding CRC diagnosis. Using Danish registries, we conducted a population-based matched cohort study including CRC patients aged 40-80 years (n = 19,209) and matched references (n = 192,090). We calculated odds ratios (ORs) using a conditional logistical regression model and incidence rate ratios (IRRs) using a negative binomial regression model. The CRC patients had significantly more consultations from 9 months before diagnosis and significantly increased rates of Hb measurements from up to 17 months before diagnosis compared with references. Furthermore, up to 18 months before diagnosis, CRC patients had significantly higher rates of prescriptions for hemorrhoids; and 2 months before diagnosis, the IRR was 12.24 (95% confidence interval (CI): 10.29-14.55) for men. The positive predictive value (PPV) of CRC for having a first-time prescription for hemorrhoids was highest among men aged 70-80 years [PPV = 3.2% (95% CI: 2.8-3.7)]. High prescription rates were predominantly seen among rectal cancer patients, whereas colon cancer patients had higher rates of consultations and Hb measurements. This study revealed a significant increase in healthcare seeking and diagnostic activity in general practice in the year prior to CRC diagnosis, which indicates the presence of a "diagnostic time window" and a potential for earlier diagnosis of CRC based on clinical signs and symptoms. © 2015 UICC.

  20. Enhanced canopy growth precedes senescence in 2005 and 2010 Amazonian droughts

    KAUST Repository

    Liu, Yi Y.; van Dijk, Albert I.J.M.; Miralles, Diego G.; McCabe, Matthew; Evans, Jason P.; de Jeu, Richard A.M.; Gentine, Pierre; Huete, Alfredo; Parinussa, Robert M.; Wang, Lixin; Guan, Kaiyu; Berry, Joe; Restrepo-Coupe, Natalia

    2018-01-01

    preceding drought-induced senescence should be taken into account when interpreting the ecological impacts of Amazonian droughts.

  1. Growth perturbations in a phenotype with rapid fetal growth preceding preterm labor and term birth.

    Science.gov (United States)

    Lampl, Michelle; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Espinoza, Jimmy; Goncalves, Luis; Lee, Wesley; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A; Romero, Roberto

    2009-01-01

    The variability in fetal growth rates and gestation duration in humans is not well understood. Of interest are women presenting with an episode of preterm labor and subsequently delivering a term neonate, who is small relative to peers of similar gestational age. To further understand these relationships, fetal growth patterns predating an episode of preterm labor were investigated. Retrospective analysis of fetal biometry assessed by serial ultrasound in a prospectively studied sample of pregnancies in Santiago, Chile, tested the hypothesis that fetal growth patterns among uncomplicated pregnancies (n = 3,706) and those with an episode of preterm labor followed by term delivery (n = 184) were identical across the time intervals 16-22 weeks, 22-28 weeks, and 28-34 weeks in a multilevel mixed-effects regression. The hypothesis was not supported. Fetal weight growth rate was faster from 16 weeks among pregnancies with an episode of preterm labor (P < 0.05), declined across midgestation (22-28 weeks, P < 0.05), and rebounded between 28 and 34 weeks (P = 0.06). This was associated with perturbations in abdominal circumference growth and proportionately larger biparietal diameter from 22 gestational weeks (P = 0.03), greater femur (P = 0.01), biparietal diameter (P = 0.001) and head circumference (P = 0.02) dimensions relative to abdominal circumference across midgestation (22-28 weeks), followed by proportionately smaller femur diaphyseal length (P = 0.02) and biparietal diameter (P = 0.03) subsequently. A distinctive rapid growth phenotype characterized fetal growth preceding an episode of preterm labor among this sample of term-delivered neonates. Perturbations in abdominal circumference growth and patterns of proportionality suggest an altered growth strategy pre-dating the preterm labor episode.

  2. A case-control study on cigarette, alcohol, and coffee consumption preceding Parkinson's disease.

    Science.gov (United States)

    Ragonese, P; Salemi, G; Morgante, L; Aridon, P; Epifanio, A; Buffa, D; Scoppa, F; Savettieri, G

    2003-01-01

    To investigate the association between cigarette smoking, alcohol drinking, coffee consumption and Parkinson's disease (PD). We selected subjects affected by idiopathic PD, with a Mini-Mental State Examination of > or =24, and controls matched 1 to 1 with cases by age (+/- 2 years) and sex. Controls were randomly selected from the resident list of the same municipality of residence of the cases. We assessed cigarette smoking, alcohol drinking, and coffee consumption preceding the onset of PD or the corresponding time for controls using a structured questionnaire, which also evaluated the duration and dose of exposure. Using conditional logistic regression analysis, we calculated adjusted OR and 95% CI. We interviewed 150 PD patients and 150 matched controls. Cigarette smoking (ever vs. never smokers OR = 0.66, 95% CI = 0.41-1.05, p = 0.08) did not show a statistically significant association with PD. We observed an inverse association between alcohol drinking (ever vs. never OR = 0.61, 95% CI = 0.39-0.97, p = 0.037) and coffee consumption (ever vs. never OR = 0.16, 95% CI 0.05-0.46, p = 0.0001) and PD. These associations remained significant after adjustment for other covariates: OR for ever vs. never alcohol consumption was 0.62 (95% CI = 0.43-0.89, p = 0.009) and that for coffee drinking 0.19 (95% CI = 0.07-0.52, p = 0.001). Heavy coffee consumption confirmed the inverse association between coffee and PD (more than 81 cup/year vs. none: OR = 0.20, 95% CI = 0.08-0.47, p coffee drinking, alcohol consumption and PD. The multiple inverse association observed may indicate a complex interaction between genetic and environmental factors. Copyright 2003 S. Karger AG, Basel

  3. Dentate gyrus network dysfunctions precede the symptomatic phase in a genetic mouse model of seizures

    Directory of Open Access Journals (Sweden)

    Oana eToader

    2013-08-01

    Full Text Available Neuronal circuit disturbances that lead to hyperexcitability in the cortico-hippocampal network are one of the landmarks of temporal lobe epilepsy. The dentate gyrus (DG network plays an important role in regulating the excitability of the entire hippocampus by filtering and integrating information received via the perforant path. Here, we investigated possible epileptogenic abnormalities in the function of the DG neuronal network in the Synapsin II (Syn II knockout mouse (Syn II-/-, a genetic mouse model of epilepsy. Syn II is a presynaptic protein whose deletion in mice reproducibly leads to generalized seizures starting at the age of two months. We made use of a high-resolution microelectrode array (4096 electrodes and patch-clamp recordings, and found that in acute hippocampal slices of young pre-symptomatic (3-6 weeks-old Syn II-/- mice excitatory synaptic output of the mossy fibers is reduced. Moreover, we showed that the main excitatory neurons present in the polymorphic layer of the DG, hilar mossy cells, display a reduced excitability. We also provide evidence of a predominantly inhibitory regulatory output from mossy cells to granule cells, through feed-forward inhibition, and show that the excitatory-inhibitory ratio is increased in both pre-symptomatic and symptomatic Syn II-/- mice. These results support the key role of the hilar mossy neurons in maintaining the normal excitability of the hippocampal network and show that the late epileptic phenotype of the Syn II-/- mice is preceded by neuronal circuitry dysfunctions. Our data provide new insights into the mechanisms of epileptogenesis in the Syn II-/- mice and open the possibility for early diagnosis and therapeutic interventions.

  4. Preoperative biliary decompression preceding pancreaticoduodenectomy with plastic or self-expandable metallic stent.

    Science.gov (United States)

    Haapamäki, C; Seppänen, H; Udd, M; Juuti, A; Halttunen, J; Kiviluoto, T; Sirén, J; Mustonen, H; Kylänpää, L

    2015-06-01

    The rainage (PBD) prior to pancreaticoduodenectomy (PD) is controversial. If PBD is required, large bore self-expandable metallic stents (SEMS) are thought to maintain better drainage and have fewer postoperative complications than plastic stents. The confirming evidence is scarce. The aim of the study was to compare outcomes of surgery in patients who underwent PBD with SEMS or plastic stents deployed at endoscopic retrograde cholangiopancreatography (ERCP). This is a retrospective study of 366 patients having had PD during 2000-2009. Preceding endoscopic PBD was performed in 191 patients and nine had had percutaneous transhepatic drainage (PTD). At the time of operation, 163 patients had a plastic stent and 28 had SEMS. Due to stent exchanges, 176 plastic stents and 29 SEMS were placed in all. The stent failure rate was 7.4% for plastic stents and 3.4% for SEMS (p = 0.697). A bilirubin level under 50 µmol/L was reached by 80% of the patients with plastic stents and by 61% of the patients with SEMS (p = 0.058). A postoperative infection complication and/or a pancreatic fistula was found in 26% while using plastic stents and in 25% using SEMS (p = 1.000). In unstented patients with biliary obstruction, the bile juice was sterile significantly more often than in endoscopically stented patients (100% vs 1%, p stented and unstented patients were compared regarding postoperative infection complications, there was no significant difference between the groups (p = 0.365). Plastic stents did not differ from SEMS regarding the stent failure rate, bilirubin level decrease, amount of bacteria in the bile juice, or postoperative complications when used for PBD. The significantly higher price of SEMS suggests their use in selected cases only. © The Finnish Surgical Society 2014.

  5. Mismatch repair deficiency commonly precedes adenoma formation in Lynch Syndrome-Associated colorectal tumorigenesis.

    Science.gov (United States)

    Sekine, Shigeki; Mori, Taisuke; Ogawa, Reiko; Tanaka, Masahiro; Yoshida, Hiroshi; Taniguchi, Hirokazu; Nakajima, Takeshi; Sugano, Kokichi; Yoshida, Teruhiko; Kato, Mamoru; Furukawa, Eisaku; Ochiai, Atsushi; Hiraoka, Nobuyoshi

    2017-08-01

    Lynch syndrome is a cancer predisposition syndrome caused by germline mutations in mismatch repair (MMR) genes. MMR deficiency is a ubiquitous feature of Lynch syndrome-associated colorectal adenocarcinomas; however, it remains unclear when the MMR-deficient phenotype is acquired during tumorigenesis. To probe this issue, the present study examined genetic alterations and MMR statuses in Lynch syndrome-associated colorectal adenomas and adenocarcinomas, in comparison with sporadic adenomas. Among the Lynch syndrome-associated colorectal tumors, 68 of 86 adenomas (79%) and all adenocarcinomas were MMR-deficient, whereas all the sporadic adenomas were MMR-proficient, as determined by microsatellite instability testing and immunohistochemistry for MMR proteins. Sequencing analyses identified APC or CTNNB1 mutations in the majority of sporadic adenomas (58/84, 69%) and MMR-proficient Lynch syndrome-associated adenomas (13/18, 72%). However, MMR-deficient Lynch syndrome-associated adenomas had less APC or CTNNB1 mutations (25/68, 37%) and frequent frameshift RNF43 mutations involving mononucleotide repeats (45/68, 66%). Furthermore, frameshift mutations affecting repeat sequences constituted 14 of 26 APC mutations (54%) in MMR-deficient adenomas whereas these frameshift mutations were rare in MMR-proficient adenomas in patients with Lynch syndrome (1/12, 8%) and in sporadic adenomas (3/52, 6%). Lynch syndrome-associated adenocarcinomas exhibited mutation profiles similar to those of MMR-deficient adenomas. Considering that WNT pathway activation sufficiently drives colorectal adenoma formation, the distinct mutation profiles of WNT pathway genes in Lynch syndrome-associated adenomas suggest that MMR deficiency commonly precedes adenoma formation.

  6. Identification of Aging-Associated Gene Expression Signatures That Precede Intestinal Tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Yoshihisa Okuchi

    Full Text Available Aging-associated alterations of cellular functions have been implicated in various disorders including cancers. Due to difficulties in identifying aging cells in living tissues, most studies have focused on aging-associated changes in whole tissues or certain cell pools. Thus, it remains unclear what kinds of alterations accumulate in each cell during aging. While analyzing several mouse lines expressing fluorescent proteins (FPs, we found that expression of FPs is gradually silenced in the intestinal epithelium during aging in units of single crypt composed of clonal stem cell progeny. The cells with low FP expression retained the wild-type Apc allele and the tissues composed of them did not exhibit any histological abnormality. Notably, the silencing of FPs was also observed in intestinal adenomas and the surrounding normal mucosae of Apc-mutant mice, and mediated by DNA methylation of the upstream promoter. Our genome-wide analysis then showed that the silencing of FPs reflects specific gene expression alterations during aging, and that these alterations occur in not only mouse adenomas but also human sporadic and hereditary (familial adenomatous polyposis adenomas. Importantly, pharmacological inhibition of DNA methylation, which suppresses adenoma development in Apc-mutant mice, reverted the aging-associated silencing of FPs and gene expression alterations. These results identify aging-associated gene expression signatures that are heterogeneously induced by DNA methylation and precede intestinal tumorigenesis triggered by Apc inactivation, and suggest that pharmacological inhibition of the signature genes could be a novel strategy for the prevention and treatment of intestinal tumors.

  7. Influence of preceding diagnostic and therapeutic procedures on the radioiodine therapy of benign thyroid diseases

    International Nuclear Information System (INIS)

    Rendl, J.; Boerner, W.

    1991-01-01

    Before and until 3 weeks after application of nonionic CA iodine and the 20-min-technetium-thyroid-uptake was measured in serum and urine in 23 euthyroid patients, which were given intravenously nonionic CA during heart catheterization. Concerning the possible influence of iodine contamination on a subsequent radioiodine therapy the following aspects result from the study: the time interval between application of CA and therapy has to be at least 4-6 weeks to avoid dilution of the radioiodine by iodine being released from the contrast agents. The thyroid-uptake of Technetium or Iodine after administration of CA is not constant over time but reaches its original value only in a gradual way (60% of the initial value 3 weeks after the CA were given); that means, the iodine-uptake during, radioiodine therapy can be higher than it was at the time the dose was calculated. Concerning the possible influence of preceding therapeutic procedures on the therapy with radioiodine the pretreatment with antithyroid drugs plays the most important role. Antithyroid drugs of the thiourylene group have been shown by many study groups to have a radioprotective effect. Other large studies however could not demonstrate any effect of antithyroid medication on the results of radioiodine therapy. All studies so far existing have in common that they are not strongly randomized with regard to the patient groups, because generally only in severe cases of hyperthyroidism additional antithyroid drug treatment has been employed, therefore it might be the case that the radioprotective effect of antithyroid drugs may be caused only by selection artifacts. The contradictory results of the different studies justify the practical way in so far as there are no reasonable objections against the pretreatment with antithyroid drugs to restore euthyroidism before starting the therapy with radioiodine. (orig./MG) [de

  8. Seagrass proliferation precedes mortality during hypo-salinity events: a stress-induced morphometric response.

    Directory of Open Access Journals (Sweden)

    Catherine J Collier

    Full Text Available Halophytes, such as seagrasses, predominantly form habitats in coastal and estuarine areas. These habitats can be seasonally exposed to hypo-salinity events during watershed runoff exposing them to dramatic salinity shifts and osmotic shock. The manifestation of this osmotic shock on seagrass morphology and phenology was tested in three Indo-Pacific seagrass species, Halophila ovalis, Halodule uninervis and Zostera muelleri, to hypo-salinity ranging from 3 to 36 PSU at 3 PSU increments for 10 weeks. All three species had broad salinity tolerance but demonstrated a moderate hypo-salinity stress response--analogous to a stress induced morphometric response (SIMR. Shoot proliferation occurred at salinities <30 PSU, with the largest increases, up to 400% increase in shoot density, occurring at the sub-lethal salinities <15 PSU, with the specific salinity associated with peak shoot density being variable among species. Resources were not diverted away from leaf growth or shoot development to support the new shoot production. However, at sub-lethal salinities where shoots proliferated, flowering was severely reduced for H. ovalis, the only species to flower during this experiment, demonstrating a diversion of resources away from sexual reproduction to support the investment in new shoots. This SIMR response preceded mortality, which occurred at 3 PSU for H. ovalis and 6 PSU for H. uninervis, while complete mortality was not reached for Z. muelleri. This is the first study to identify a SIMR in seagrasses, being detectable due to the fine resolution of salinity treatments tested. The detection of SIMR demonstrates the need for caution in interpreting in-situ changes in shoot density as shoot proliferation could be interpreted as a healthy or positive plant response to environmental conditions, when in fact it could signal pre-mortality stress.

  9. Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice

    Science.gov (United States)

    Angelis, Katia De; Senador, Danielle D.; Mostarda, Cristiano; Irigoyen, Maria C.

    2012-01-01

    Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease. PMID:22319048

  10. Alterations of carotid arterial mechanics preceding the wall thickening in patients with hypertension.

    Science.gov (United States)

    Kim, Sung-Ai; Park, Sun-Hee; Jo, Sang-Ho; Park, Kyoung-Ha; Kim, Hyun-Sook; Han, Sang-Jin; Park, Woo-Jung; Ha, Jong-Won

    2016-05-01

    Carotid intima-media thickness (cIMT) is an established surrogate marker of atherosclerosis. However, cIMT may not reflect the whole arterial changes occurring in various pathologic conditions, such as hypertension. The aim of this study was to evaluate whether vascular properties of carotid artery (CA) in patients with hypertension differ from those of patients with diabetes and controls before the progression of cIMT. Vascular properties of CA were assessed in 402 consecutive asymptomatic subjects who have normal cIMT (131 with hypertension, 151 with diabetes mellitus, and 120 controls). Conventional carotid stiffness indices calculated from vessel diameter and blood pressure, and parameters from velocity-vector imaging (VVI), including vessel area, fractional area change (FAC), radial velocity, circumferential strain, and strain rate were measured to assess the differences between the groups. In univariate analysis, both patients with hypertension and diabetes showed higher elastic modulus, lower distensibility coefficients and FAC of VVI than those of controls. However, when adjusting for baseline covariates, only FAC (odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.70-0.97, p = 0.025) and vessel area (OR = 2.84, 95% CI = 1.64-4.91, p hypertension from those of controls. Also, patients with hypertension showed larger vessel area than diabetes (OR = 2.58, 95% CI = 1.75-3.80, p hypertensive patients was stiffer than those of controls and positive remodeling preceded the wall thickening independent of baseline covariates. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell' Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy); Riccio, Eleonora; Pisani, Antonio [University of Naples Federico II, Department of Public Health, Naples (Italy)

    2017-12-15

    Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by {sup 123}I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by {sup 123}I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r{sup 2} = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, {sup 123}I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

  12. The effects of an educational program based on PRECEDE model on depression levels in patients with coronary artery bypass grafting

    Directory of Open Access Journals (Sweden)

    Sayyed Mohammad Mahdi Hazavei

    2012-06-01

    Full Text Available    BACKGROUND: Depression is among the most important barriers to proper treatment of cardiac patients. It causes failure in accepting their conditions, decreases their motivation in following the therapeutic recommendations, and thus negatively affects their functionality and quality of life. The present study aimed to investigate the effects of an educational program based on Predisposing, Reinforcing, Enabling Constructs in Educational Diagnosis and Evaluation (PRECEDE model on depression level in coronary artery bypass grafting (CABG surgery patients.    METHODS: This was a quasi-experimental study in which 54 post-bypass surgery patients of Isfahan Cardiovascular Research Center were investigated. The patients were randomly divided into two groups of intervention and control. The data was collected using two questionnaires. Primarily, the cardiac depression scale was used to measure the degree of depression followed by PRECEDE model-based educational questionnaire to identify the role of the educational intervention on patients. The PRECEDE model-based intervention composed of 9 educational sessions per week (60-90 minutes each. The patients were followed up for two months post-intervention.    RESULTS: Following the educational intervention, mean scores of predisposing, enabling, and reinforcing factors, and self-helping behaviors significantly increased in the intervention group compared to the control group (P < 0.001. In addition, a significant difference in mean scores of depression was observed between the two groups following the educational intervention (P < 0.001.    CONCLUSION: The findings of the current study confirmed the practicability and effectiveness of the PRECEDE model-based educational programs on preventing or decreasing depression levels in CABG patients.         Keywords: Educational Program, PRECEDE Model, Depression, Coronary Artery Bypass Surgery.  

  13. Legal Sentience and the Problem of the Instant: A Critical Assessment of the Temporal Structure of Precedent and its Implications for Legal Authority

    OpenAIRE

    Wargan, Pawel

    2015-01-01

    This paper assesses the authority of precedent from a phenomenological standpoint. Phenomenology distinguishes between two temporal models. One describes time in an idealised form, as a divisible chain of instants or events. The other looks at lived temporality as fluid and indivisible duration. In the system of precedent, we witness an interaction of both models. The legal order is constructed from slices in time that become the building blocks of future judgments. Precedents are binding for...

  14. Upregulation of cognitive control networks in older adults’ speech comprehension

    Directory of Open Access Journals (Sweden)

    Julia eErb

    2013-12-01

    Full Text Available Speech comprehension abilities decline with age and with age-related hearing loss, but it is unclear how this decline expresses in terms of central neural mechanisms. The current study examined neural speech processing in a group of older adults (aged 56–77, n=16, with varying degrees of sensorineural hearing loss, and compared them to a cohort of young adults (aged 22–31, n=30, self-reported normal hearing. In an fMRI experiment, listeners heard and repeated back degraded sentences (4-band vocoding, which preserves the temporal envelope of the acoustic signal, while substantially degrading spectral information. Behaviourally, older adults adapted to degraded speech at the same rate as young listeners, although their overall comprehension of degraded speech was lower. Neurally, both older and young adults relied on the left anterior insula for degraded more than clear speech perception. However, anterior insula engagement in older adults was dependent on hearing acuity. Young adults additionally employed the anterior cingulate cortex (ACC. Interestingly, this age group × degradation interaction was driven by a reduced dynamic range in older adults, who displayed elevated levels of ACC activity in both conditions, consistent with a persistent upregulation in cognitive control irrespective of task difficulty. For correct speech comprehension, older adults recruited the middle frontal gyrus in addition to a core speech comprehension network on which young adults relied, suggestive of a compensatory mechanism. Taken together, the results indicate that older adults increasingly recruit cognitive control networks, even under optimal listening conditions, at the expense of these systems’ dynamic range.

  15. Oxidative stress upregulates the NMDA receptor on cerebrovascular endothelium.

    Science.gov (United States)

    Betzen, Christian; White, Robin; Zehendner, Christoph M; Pietrowski, Eweline; Bender, Bianca; Luhmann, Heiko J; Kuhlmann, Christoph R W

    2009-10-15

    N-methyl-d-aspartate receptor (NMDA-R)-mediated oxidative stress has been implicated in blood-brain barrier (BBB) disruption in a variety of neuropathological diseases. Although some interactions between both phenomena have been elucidated, possible influences of reactive oxygen species (ROS) on the NMDA-R itself have so far been neglected. The objective of this study was to examine how the cerebroendothelial NMDA-R is affected by exposure to oxidative stress and to assess possible influences on BBB integrity. RT-PCR confirmed several NMDA-R subunits (NR1, NR2B-D) expressed in the bEnd3 cell line (murine cerebrovascular endothelial cells). NR1 protein expression after exposure to ROS was observed via in-cell Western. The functionality of the expressed NMDA-R was determined by measuring DiBAC fluorescence in ROS-preexposed cells upon stimulation with the specific agonist NMDA. Finally, the effects on barrier integrity were evaluated using the ECIS system to detect changes in monolayer impedance upon NMDA-R stimulation after exposure to ROS. The expression of NR1 significantly (p<0.001) increased 72 h after 30 min exposure to superoxide (+33.8+/-7.5%), peroxynitrite (+84.9+/-10.7%), or hydrogen peroxide (+92.8+/-7.6%), resulting in increased cellular response to NMDA-R stimulation and diminished monolayer impedance. We conclude that oxidative stress upregulates NMDA-R on cerebrovascular endothelium and thus heightens susceptibility to glutamate-induced BBB disruption.

  16. Cerebral adenosine A₁ receptors are upregulated in rodent encephalitis.

    Science.gov (United States)

    Paul, Soumen; Khanapur, Shivashankar; Boersma, Wytske; Sijbesma, Jurgen W; Ishiwata, Kiichi; Elsinga, Philip H; Meerlo, Peter; Doorduin, Janine; Dierckx, Rudi A; van Waarde, Aren

    2014-05-15

    Adenosine A1 receptors (A1Rs) are implied in the modulation of neuroinflammation. Activation of cerebral A1Rs acts as a brake on the microglial response after traumatic brain injury and has neuroprotective properties in animal models of Parkinson's disease and multiple sclerosis. Neuroinflammatory processes in turn may affect the expression of A1Rs, but the available data is limited and inconsistent. Here, we applied an animal model of encephalitis to assess how neuroinflammation affects the expression of A1Rs. Two groups of animals were studied: Infected rats (n=7) were intranasally inoculated with herpes simplex virus-1 (HSV-1, 1 × 10(7) plaque forming units), sham-infected rats (n=6) received only phosphate-buffered saline. Six or seven days later, microPET scans (60 min with arterial blood sampling) were made using the tracer 8-dicyclopropyl-1-(11)C-methyl-3-propyl-xanthine ((11)C-MPDX). Tracer clearance from plasma and partition coefficient (K₁/k₂ estimated from a 2-tissue compartment model fit) were not significantly altered after virus infection. PET tracer distribution volume calculated from a Logan plot was significantly increased in the hippocampus (+37%) and medulla (+27%) of virus infected rats. Tracer binding potential (k₃/k₄ estimated from the model fit) was significantly increased in the cerebellum (+87%) and the medulla (+148%) which may indicate increased A1R expression. This was confirmed by immunohistochemical analysis showing a strong increase of A1R immunoreactivity in the cerebellum of HSV-1-infected rats. Both the quantitative PET data and immunohistochemical analysis indicate that A1Rs are upregulated in brain areas where active virus is present. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Celecoxib prevents colitis associated colon carcinogenesis: an upregulation of apoptosis.

    Science.gov (United States)

    Setia, Shruti; Nehru, Bimla; Sanyal, Sankar N

    2014-12-01

    Uncontrolled cell proliferation and suppressed apoptosis are the critical events transforming a normal cell to a cancerous one wherein the inflammatory microenvironment supports this oncogenic transformation. The process of colon carcinogenesis may be aggravated in chronic inflammatory conditions such as ulcerative colitis where non-steroidal anti-inflammatory drugs (NSAIDs) may effectively prevent the cellular and molecular events. Western blots and immunofluorescent analysis of DNA mismatch repair enzymes, cell cycle regulators and pro- and anti-apoptotic proteins were performed in dextran sulfate sodium (DSS)-induced ulcerative colitis and 1,2-dimethyl benz(a)anthracene (DMH)-induced colon cancer. Also, apoptotic studies were done in isolated colonocytes using fluorescent staining and in paraffin sections using TUNEL assay. An upregulation of cell cycle regulators: cyclin D1/cdk4 and cyclin E/cdk2 and anti-apoptotic Bcl-2, along with the suppression of DNA repair enzymes: MLH1 and MSH2; tumour suppressors: p53, p21and Rb and pro-apoptotic proteins: Bax and Bad were observed in the DSS, DMH and DSS+DMH groups. Proliferating cell nuclear antigen (PCNA) was also overexpressed in these groups. The ultimate executioner of the apoptotic pathway; caspase-3, was suppressed in these groups. Apoptotic studies in colonocytes and paraffin sections revealed suppressed apoptosis in these groups. These effects were corrected with the administration of a second generation NSAID, celecoxib along with the treatment of DSS and DMH. The chemopreventive action of celecoxib in colitis mediated colon carcinogenesis may include the regulation of DNA mismatch repair enzymes, cell cycle check points, cell proliferation and apoptosis. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. TRPA1 receptor is upregulated in human oral lichen planus.

    Science.gov (United States)

    Kun, J; Perkecz, A; Knie, L; Sétáló, G; Tornóczki, T; Pintér, E; Bán, Á

    2017-03-01

    Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology with antigen-specific and non-specific mechanisms. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel activated by noxious stimuli such as oxidative stress products evoking pain and release of proinflammatory mediators from sensory nerve endings culminating in neurogenic inflammation. Extraneuronal TRPA1s, for example, on immune cells possess yet unknown functions. We studied the buccal mRNA expression (qPCR) and protein localization (immunohistochemistry) of TRPA1 receptors and key OLP mediator transcripts in oral mucosa samples of healthy volunteers (n = 9), OLP patients (n = 43), and OLP-like hyperkeratotic patients (n = 12). We measured 27.7- and 25.5-fold TRPA1 mRNA increase in OLP and OLP-like hyperkeratotic patients compared to healthy controls. TRPA1 transcripts elevated 2.4-fold in hypertensive OLP but not in hyperkeratotic patients compared to counterparts, reduced by 1.6-fold by angiotensin-convertase inhibitor intake. TRPA1 messenger RNA was more coexpressed with transcripts of tumor necrosis factor α than with interferon γ. Keratinocytes, macrophages but not T cells expressed TRPA1. We provided evidence for the extraneuronal presence and upregulation of the proinflammatory TRPA1 receptor in buccal samples of patients with OLP. This may implicate the ion channel in the pathomechanism of OLP. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Lack of upregulation of epidermal fatty acid binding protein in dithranol induced irritation.

    NARCIS (Netherlands)

    Kucharekova, M.; Vissers, W.H.P.M.; Schalkwijk, J.; Kerkhof, P.C.M. van de; Valk, P.G.M. van der

    2003-01-01

    The exact role of epidermal fatty acid binding protein (E-FABP) in skin is unknown. A restoration of the barrier function may be associated with an upregulation of E-FABP. Moreover, E-FABP is upregulated in a variety of cells in response to oxidative stress. A recent observation that dithranol

  20. Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain

    Directory of Open Access Journals (Sweden)

    Sarah L. DeVos

    2018-04-01

    Full Text Available Alzheimer's disease (AD is defined by the presence of intraneuronal neurofibrillary tangles (NFTs composed of hyperphosphorylated tau aggregates as well as extracellular amyloid-beta plaques. The presence and spread of tau pathology through the brain is classified by Braak stages and thought to correlate with the progression of AD. Several in vitro and in vivo studies have examined the ability of tau pathology to move from one neuron to the next, suggesting a “prion-like” spread of tau aggregates may be an underlying cause of Braak tau staging in AD. Using the HEK293 TauRD-P301S-CFP/YFP expressing biosensor cells as a highly sensitive and specific tool to identify the presence of seed competent aggregated tau in brain lysate—i.e., tau aggregates that are capable of recruiting and misfolding monomeric tau—, we detected substantial tau seeding levels in the entorhinal cortex from human cases with only very rare NFTs, suggesting that soluble tau aggregates can exist prior to the development of overt tau pathology. We next looked at tau seeding levels in human brains of varying Braak stages along six regions of the Braak Tau Pathway. Tau seeding levels were detected not only in the brain regions impacted by pathology, but also in the subsequent non-pathology containing region along the Braak pathway. These data imply that pathogenic tau aggregates precede overt tau pathology in a manner that is consistent with transneuronal spread of tau aggregates. We then detected tau seeding in frontal white matter tracts and the optic nerve, two brain regions comprised of axons that contain little to no neuronal cell bodies, implying that tau aggregates can indeed traverse along axons. Finally, we isolated cytosolic and synaptosome fractions along the Braak Tau Pathway from brains of varying Braak stages. Phosphorylated and seed competent tau was significantly enriched in the synaptic fraction of brain regions that did not have extensive cellular tau

  1. A case of Meigs' syndrome with preceding pericardial effusion in advance of pleural effusion.

    Science.gov (United States)

    Okuda, Kenichi; Noguchi, Satoshi; Narumoto, Osamu; Ikemura, Masako; Yamauchi, Yasuhiro; Tanaka, Goh; Takai, Daiya; Fukayama, Masashi; Nagase, Takahide

    2016-05-10

    Meigs' syndrome is defined as the presence of a benign ovarian tumor with pleural effusion and ascites that resolve after removal of the tumor. The pathogenesis of the production of ascites and pleural effusion in this syndrome remains unknown. Aside from pleural effusion and ascites, pericardial effusion is rarely observed in Meigs' syndrome. Here, we report the first case of Meigs' syndrome with preceding pericardial effusion in advance of pleural effusion. An 84-year-old Japanese non-smoking woman with a history of lung cancer, treated by surgery, was admitted due to gradual worsening of dyspnea that had occurred over the previous month. She had asymptomatic and unchanging pericardial effusion and a pelvic mass, which had been detected 3 and 11 years previously, respectively. The patient was radiologically followed-up without the need for treatment. Two months before admission, the patient underwent a right upper lobectomy for localized lung adenocarcinoma and intraoperative pericardial fenestration confirmed that the pericardial effusion was not malignant. However, she began to experience dyspnea on exertion leading to admission. A chest, abdomen, and pelvis computed tomography scan confirmed the presence of right-sided pleural and pericardial effusion and ascites with a left ovarian mass. Repeated thoracentesis produced cultures that were negative for any microorganism and no malignant cells were detected in the pleural effusions. Pleural fluid accumulation persisted despite a tube thoracostomy for pleural effusion drainage. With a suspicion of Meigs' syndrome, the patient underwent surgical resection of the ovarian mass and histopathological examination of the resected mass showed ovarian fibroma. Pleural and pericardial effusion as well as ascites resolved after tumor resection, confirming a diagnosis of Meigs' syndrome. This clinical course suggests a strong association between pericardial effusion and ovarian fibroma, as well as pleural and peritoneal

  2. Effects of Preceding Ethanol Intake on Glucose Response to Low-Dose Glucagon in Individuals With Type 1 Diabetes

    DEFF Research Database (Denmark)

    Ranjan, Ajenthen; Nørgaard, Kirsten; Tetzschner, Rikke

    2018-01-01

    OBJECTIVE: This study investigated whether preceding ethanol intake impairs glucose response to low-dose glucagon in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a randomized, crossover, placebo-controlled study in 12 insulin pump-treated individuals (median...... ethanol compared with placebo. The second glucagon bolus had similar responses between visits, but PG remained 1.8 ± 0.7 mmol/L lower after ethanol compared with placebo. CONCLUSIONS: The ability of low-dose glucagon to treat mild hypoglycemia persisted with preceding ethanol intake, although it tended...... to be metabolized, and a subcutaneous (s.c.) insulin bolus was given to induce mild hypoglycemia. When plasma glucose (PG) was ≤3.9 mmol/L, 100 µg glucagon was given s.c., followed by another s.c. 100 µg glucagon 2 h later. Primary end point was incremental peak PG induced by the first glucagon bolus. RESULTS...

  3. Gender and age differences among youth, in utilization of mental health services in the year preceding suicide in Taiwan.

    Science.gov (United States)

    Chang, Hsiu-Ju; Lai, Yuen-Liang; Chang, Chia-Ming; Kao, Ching-Chiu; Shyu, Meei-Ling; Lee, Ming-Been

    2012-12-01

    The primary objective of this study was to explore gender and age differences in the use of medical services during the year preceding suicide. Data were obtained from the mortality dataset of Department of Health and National Health Insurance Database. Included in the sample were 862 persons aged 12-24 years who committed suicide in Taiwan between 2001 and 2004. We compared the records of medical service utilization of adolescents (ages 12-18 years) with young adults (ages 19-24 years). Persons in both age groups contacted general practitioners more often than other types of medical providers in the year preceding suicide, with the exception of the month before suicide. Females made greater use of medical services than males in both age groups. Suicide prevention strategies should increase the emphasis in training non-psychiatric medical practitioners to identify and treat young persons at suicide risk.

  4. Left in limbo – Experiences and needs among postmenopausal women newly diagnosed with osteoporosis without preceding osteoporotic fractures

    DEFF Research Database (Denmark)

    Jakobsen, Pernille Ravn; Hermann, Anne Pernille; Søndergaard, Jens

    2018-01-01

    to participate in treatment decision-making and (3) needs of being able to take care of bone health. Conclusion and implications In general the women experienced as been left ‘in limbo’, and they requested targeted and tailored information about osteoporosis. In particular, they want information about dual...... more attention on the benefits of detecting early stage osteoporosis. The study highlights the call for new approaches to postmenopausal women newly diagnosed with osteoporosis without preceding fractures....

  5. Network topology and functional connectivity disturbances precede the onset of Huntington's disease.

    Science.gov (United States)

    Harrington, Deborah L; Rubinov, Mikail; Durgerian, Sally; Mourany, Lyla; Reece, Christine; Koenig, Katherine; Bullmore, Ed; Long, Jeffrey D; Paulsen, Jane S; Rao, Stephen M

    2015-08-01

    Cognitive, motor and psychiatric changes in prodromal Huntington's disease have nurtured the emergent need for early interventions. Preventive clinical trials for Huntington's disease, however, are limited by a shortage of suitable measures that could serve as surrogate outcomes. Measures of intrinsic functional connectivity from resting-state functional magnetic resonance imaging are of keen interest. Yet recent studies suggest circumscribed abnormalities in resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease, despite the spectrum of behavioural changes preceding a manifest diagnosis. The present study used two complementary analytical approaches to examine whole-brain resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease. Network topology was studied using graph theory and simple functional connectivity amongst brain regions was explored using the network-based statistic. Participants consisted of gene-negative controls (n = 16) and prodromal Huntington's disease individuals (n = 48) with various stages of disease progression to examine the influence of disease burden on intrinsic connectivity. Graph theory analyses showed that global network interconnectivity approximated a random network topology as proximity to diagnosis neared and this was associated with decreased connectivity amongst highly-connected rich-club network hubs, which integrate processing from diverse brain regions. However, functional segregation within the global network (average clustering) was preserved. Functional segregation was also largely maintained at the local level, except for the notable decrease in the diversity of anterior insula intermodular-interconnections (participation coefficient), irrespective of disease burden. In contrast, network-based statistic analyses revealed patterns of weakened frontostriatal connections and strengthened frontal-posterior connections that evolved as disease

  6. Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes

    Science.gov (United States)

    2012-01-01

    Action potentials at the neurons and graded signals at the synapses are primary codes in the brain. In terms of their functional interaction, the studies were focused on the influence of presynaptic spike patterns on synaptic activities. How the synapse dynamics quantitatively regulates the encoding of postsynaptic digital spikes remains unclear. We investigated this question at unitary glutamatergic synapses on cortical GABAergic neurons, especially the quantitative influences of release probability on synapse dynamics and neuronal encoding. Glutamate release probability and synaptic strength are proportionally upregulated by presynaptic sequential spikes. The upregulation of release probability and the efficiency of probability-driven synaptic facilitation are strengthened by elevating presynaptic spike frequency and Ca2+. The upregulation of release probability improves spike capacity and timing precision at postsynaptic neuron. These results suggest that the upregulation of presynaptic glutamate release facilitates a conversion of synaptic analogue signals into digital spikes in postsynaptic neurons, i.e., a functional compatibility between presynaptic and postsynaptic partners. PMID:22852823

  7. Low-grade disease activity in early life precedes childhood asthma and allergy.

    Science.gov (United States)

    Chawes, Bo Lund Krogsgaard

    2016-08-01

    particular, metabolomic analyses of serum, urine, and airway lining fluid from neonates as well as neonatal VOC profiling of exhaled breath may facilitate a broader understanding of the early low-grade disease activity preceding clinical symptoms. Disentangling the introductory pathophysiological mechanisms and underlying endotypes of disease is paramount for generating successful preventive measures to alleviate the major global burden of asthma, allergy, and other NCDs of modern time.

  8. DMPD: Mechanism of age-associated up-regulation in macrophage PGE2 synthesis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15331118 Mechanism of age-associated up-regulation in macrophage PGE2 synthesis. Wu...e-associated up-regulation in macrophage PGE2 synthesis. PubmedID 15331118 Title Mechanism of age-associated... up-regulation in macrophage PGE2 synthesis. Authors Wu D, Meydani SN. Publicatio

  9. Increased antigen presentation but impaired T cells priming after upregulation of interferon-beta induced by lipopolysaccharides is mediated by upregulation of B7H1 and GITRL.

    Directory of Open Access Journals (Sweden)

    Fang Wang

    Full Text Available Dendritic cells are able to present Ag-derived peptides on MHC class I and II molecules and induce T cells priming. Lipopolysaccharides (LPS, an activator of Toll-like 4 receptor (TLR4 signaling, has been demonstrated to facilitate Ag-presentation, up-regulate surface molecules expression but impair T cells priming. In this study, we investigated the effect of LPS on nicotine-enhanced DCs-dependent T cells priming and the mechanisms of LPS orchestrating the immunosuppressive program. We could demonstrate that the treatment with LPS resulted in increased surface molecules expression, enhanced Ag-presentation, up-regulated release of TGF-beta, TNF-alpha, IL-6, and IFN-beta. Concomititantly, the upregulation of IFN-beta in DCs induces the up-regulation of coinhibitory molecules B7H1 and GITRL, which cause an impaired activation of naïve Ag-specific T cells and the induction of T cell tolerance by enhancing B7H1-PD-1 interactions and promoting GITRL-GITL facilitated Treg generation, respectively. These data provide a mechanistic basis for the immunomodulatory action of IFN-beta which might open new possibilities in the development of therapeutic approaches aimed at the control of excessive immune response and persistent infection.

  10. Upregulation of NLRP3 Inflammasome in the Tears and Ocular Surface of Dry Eye Patients.

    Directory of Open Access Journals (Sweden)

    Liangliang Niu

    Full Text Available To evaluate the mRNA and protein expressions of NLRP3 inflammasome and its downstream inflammatory factors in human dry eye.We recruited 54 patients with Sjögren's syndrome dry eye (SSDE, 50 patients with non-Sjögren's syndrome dry eye (NSSDE, and 46 healthy controls. Tear film breakup time (TBUT, Schirmer I test, and fluorescein staining (FL were performed on all subjects. Tear samples were obtained to analyze the inflammatory cytokine levels of IL-1β and IL-18 via enzyme-linked immunosorbent (ELISA. Conjunctival impression cytology (CIC specimens were collected to detect the mRNA expression of NLRP3, caspase-1, IL-1β, and IL-18 using quantitative RT-PCR, and the protein expression of NLRP3 and caspase-1 by Western blotting.NLRP3 mRNA expression showed higher levels in both dry eye groups compared with controls, with a comparably significant elevation in the SSDE group (relative 2.47-fold upregulation, p<0.05. NLRP3 protein expression was also increased in SSDE group (relative1.94-fold upregulation compared with the controls. mRNA expression of caspase-1 was significantly upregulated in both SSDE (relative 1.44-fold upregulation, p<0.05 and NSSDE (relative 1.32-fold upregulation, p<0.05. Procaspase-1 protein level was increased in SSDE (relative 1.84-fold upregulation and NSSDE (relative 1.12-fold upregulation versus controls; and caspase-1 protein expression was also increased in SSDE (relative 1.49-fold upregulation and NSSDE (relative 1.17-fold upregulation compared with the controls. The patients with SSDE and NSSDE had higher IL-1β and IL-18 mRNA values and protein expressions than the controls did. The relative mRNA expression of IL-1β upregulated 3.59-fold (p<0.001 in SSDE and 2.13-fold (p<0.01 in NSSDE compared with the controls. IL-1β protein level also showed significant upregulation in SSDE (p=0.01; vs. controls groups. IL-18 mRNA expression levels were significantly upregulated in the SSDE (relative 2.97-fold upregulation, p

  11. FEMALE CONTROL OF SPERM TRANSFER AND INTRASPECIFIC VARIATION IN SPERM PRECEDENCE: ANTECEDENTS TO THE EVOLUTION OF A COURTSHIP FOOD GIFT.

    Science.gov (United States)

    Sakaluk, Scott K; Eggert, Anne-Katrin

    1996-04-01

    Manipulation of ejaculates is believed to be an important avenue of female choice throughout the animal kingdom, but evidence of its importance to sexual selection remains scarce. In crickets, such manipulation is manifest in the premature removal of the externally attached spermatophore, which may afford females an important means of postcopulatory mate choice. We tested the hypothesis that premature spermatophore removal contributes significantly to intraspecific variation in sperm precedence by (1) experimentally manipulating spermatophore attachment durations of competing male Gryllodes sigillatus and (2) employing protein electrophoresis to determine the paternity of doubly mated females. The relative spermatophore attachment durations of competing males had a significant influence on male paternity, but the pattern of sperm precedence deviated significantly from the predictions of an ideal lottery. Instead, paternity data and morphological evidence accorded best with a model of partial sperm displacement derived here. Our model is similar to a displacement model of Parker et al. in that sperm of the second male mixes instantaneously with that of the first throughout the displacement process, but the novel feature of our model is that the number of sperm displaced is only a fraction of the number of sperm transferred by the second male. Regardless of the underlying mechanism, female G. sigillatus can clearly alter the paternity of their offspring through their spermatophore-removal behavior, and employ such cryptic choice in favoring larger males and those providing larger courtship food gifts. We discuss how female control of sperm transfer and intraspecific variation in sperm precedence may be important precursors to the evolution of gift giving in insects. © 1996 The Society for the Study of Evolution.

  12. Minimizing total weighted tardiness for the single machine scheduling problem with dependent setup time and precedence constraints

    Directory of Open Access Journals (Sweden)

    Hamidreza Haddad

    2012-04-01

    Full Text Available This paper tackles the single machine scheduling problem with dependent setup time and precedence constraints. The primary objective of this paper is minimization of total weighted tardiness. Since the complexity of the resulted problem is NP-hard we use metaheuristics method to solve the resulted model. The proposed model of this paper uses genetic algorithm to solve the problem in reasonable amount of time. Because of high sensitivity of GA to its initial values of parameters, a Taguchi approach is presented to calibrate its parameters. Computational experiments validate the effectiveness and capability of proposed method.

  13. EL PRECEDENTE EN LA DIMENSIÓN DE LA SEGURIDAD JURÍDICA THE PRECEDENT IN THE LEGAL CERTAINTY DIMENSION

    Directory of Open Access Journals (Sweden)

    Luiz Guilherme Marinon

    2012-01-01

    Full Text Available El estudio aquí presentado se destina a introducir a la comunidad jurídica latinoamericana la importancia del precedente vinculante como forma de tutela del valor constitucional seguridad jurídica. En ese sentido, es a través del precedente que obtiene importancia este valor constitucional pues, al constituirse en derecho fundamental para los ciudadanos, requiere de un medio de protección por estar consagrado en la Constitución, siendo este, el precedente vinculante. Asimismo, son presentados fundamentos para la construcción no sólo de una tutela de la seguridad jurídica, sino, de la confianza del ciudadano respecto a las decisiones del órgano jurisdiccional. Finalmente, el estudio intenta teorizar el apartamiento que existe entre la cosa juzgada y la calidad de estabilidad de las decisiones judiciales, siendo la primera la garantía que tiene el ciudadano de que su caso fue decidido y lo decidido no será variado, mientras que a través de la estabilidad propia del precedente, se contempla el derecho a obtener una decisión respetando la igualdad respecto de casos similares anteriormente decididos.The study given in this essay aims to introduce to the Latin-American legal community and academia the importance of the judicial precedent as a way to protect the constitutional value of legal certainty. In this respect, it is through the judicial precedent that the constitutional value of legal certainty could obtain the judicial protection because once it is constituted as a fundamental and constitutional right to the whole citizenship, this right claims an adequate protection, and this could be achieved by means of the judicial precedent. Also, not only foundations and basis to the protection of judicial certainty are presented here, but also reasons to theorize that by means of the judicial precedent, it could also be achieved the protection of the trust of the citizenship among the judicial decisions of diverse courts. Finally, this

  14. A dynamical model of car-following with the consideration of the multiple information of preceding cars

    International Nuclear Information System (INIS)

    Peng, G.H.; Sun, D.H.

    2010-01-01

    An improved multiple car-following (MCF) model is proposed, based on the full velocity difference (FVD) model, but taking into consideration multiple information inputs from preceding vehicles. The linear stability condition of the model is obtained by using the linear stability theory. Through nonlinear analysis, the modified Korteweg-de Vries (mKdV) equation is derived to describe the traffic behavior near the critical point. Numerical simulation shows that the proposed model is theoretically an improvement over others, while retaining many strong points in the previous ones by adjusting the information of the multiple leading vehicles.

  15. FOXM1 upregulation is an early event in human squamous cell carcinoma and it is enhanced by nicotine during malignant transformation.

    Directory of Open Access Journals (Sweden)

    Emilios Gemenetzidis

    Full Text Available Cancer associated with smoking and drinking remains a serious health problem worldwide. The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC.FOXM1 mRNA and protein expressions were investigated in four independent cohorts (total 75 patients consisting of normal, premalignant and HNSCC tissues and cells using quantitative PCR (qPCR, expression microarray, immunohistochemistry and immunocytochemistry. Effect of putative oral carcinogens on FOXM1 transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblotting and short-hairpin RNA interference. Genome-wide single nucleotide polymorphism (SNP array was used to 'trace' the genomic instability signature pattern in 8 clonal lines of FOXM1-induced malignant human oral keratinocytes. Furthermore, acute FOXM1 upregulation in primary oral keratinocytes directly induced genomic instability. We have shown for the first time that overexpression of FOXM1 precedes HNSCC malignancy. Screening putative carcinogens in human oral keratinocytes surprisingly showed that nicotine, which is not perceived to be a human carcinogen, directly induced FOXM1 mRNA, protein stabilisation and transcriptional activity at concentrations relevant to tobacco chewers. Importantly, nicotine also augmented FOXM1-induced transformation of human oral keratinocytes. A centrosomal protein CEP55 and a DNA helicase/putative stem cell marker HELLS, both located within a consensus loci (10q23, were found to be novel targets of FOXM1 and their expression correlated tightly with HNSCC progression.This study cautions the potential co-carcinogenic effect of nicotine in tobacco replacement therapies. We hypothesise that aberrant upregulation of FOXM1 may be inducing genomic instability through a

  16. Patterns and sources of alcohol consumption preceding alcohol-affected attendances to a New Zealand hospital emergency department.

    Science.gov (United States)

    Das, Manidipa; Stewart, Rebecca; Ardagh, Michael; Deely, Joanne M; Dodd, Stuart; Bartholomew, Nadia V; Pearson, Scott; Spearing, Ruth; Williams, Tracey; Than, Martin

    2014-08-29

    To perform a descriptive study of the drinking behaviour (amounts, types, sources of alcohol consumed) preceding alcohol-affected presentations to Christchurch Hospital Emergency Department (ED). Over 336 hours in the ED, patients with recent alcohol consumption or alcohol-related attendances were identified, classified as alcohol-affected or alcohol- unaffected, and invited to consent to answering questions on types, amounts and sources of alcohol consumed in the drinking session preceding or implicated in their ED attendance. Demographic information and level of intoxication were also recorded. Data were summarised descriptively. Alcohol-affected patients were more frequently young (16-25 years) and male. Median alcohol consumption was 14 (range 1 to 71) standard drinks. Beer was the most popular beverage (34%), but spirits (23%), ready-to-drink mixes (21%) and wine (20%) were also popular. Liquor stores (45%) were the most popular source of alcohol, followed by on-licence premises (25%), and supermarkets (21%). The popularity of different types of beverages and their source varied according to patient age and gender. Consumption of large amounts, as well as allegedly 'safe' amounts, of a range of alcoholic beverages, most commonly from an off-licence source, contributed to alcohol-affected presentations to the ED. Beverage and source popularity varied by age and gender.

  17. When practice precedes theory - A mixed methods evaluation of students' learning experiences in an undergraduate study program in nursing.

    Science.gov (United States)

    Falk, Kristin; Falk, Hanna; Jakobsson Ung, Eva

    2016-01-01

    A key area for consideration is determining how optimal conditions for learning can be created. Higher education in nursing aims to prepare students to develop their capabilities to become independent professionals. The aim of this study was to evaluate the effects of sequencing clinical practice prior to theoretical studies on student's experiences of self-directed learning readiness and students' approach to learning in the second year of a three-year undergraduate study program in nursing. 123 nursing students was included in the study and divided in two groups. In group A (n = 60) clinical practice preceded theoretical studies. In group (n = 63) theoretical studies preceded clinical practice. Learning readiness was measured using the Directed Learning Readiness Scale for Nursing Education (SDLRSNE), and learning process was measured using the revised two-factor version of the Study Process Questionnaire (R-SPQ-2F). Students were also asked to write down their personal reflections throughout the course. By using a mixed method design, the qualitative component focused on the students' personal experiences in relation to the sequencing of theoretical studies and clinical practice. The quantitative component provided information about learning readiness before and after the intervention. Our findings confirm that students are sensitive and adaptable to their learning contexts, and that the sequencing of courses is subordinate to a pedagogical style enhancing students' deep learning approaches, which needs to be incorporated in the development of undergraduate nursing programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. U.S. Case Law and Legal Precedent Affirming the Due Process Rights of Immigrants Fleeing Persecution.

    Science.gov (United States)

    Sidhu, Shawn S; Boodoo, Ramnarine

    2017-09-01

    The political discourse on domestic immigration policy has shifted rapidly in recent years, mirrored by similar shifts in the geopolitical climate worldwide. However, a nuanced assessment of the legal basis backing such rhetoric is sorely lacking. This article examines the historical, legal, and case law precedent as it pertains specifically to immigrants who are fleeing persecution and residing within the United States. Due process rights emerged from the Fifth, Sixth, and Fourteenth Constitutional Amendments and have been expanded to include this population through several sequential United States Supreme Court Cases. We review the 1951 Convention Related to the Status of Refugees and 1967 Protocol Relating to the Status of Refugees and examine subsequent case law and legal precedent. We then present evidence documenting widespread violations of due process rights for immigrants fleeing persecution. Specifically, we address the right to a fair hearing for individuals fearing for their lives upon return to their home country, the right against wrongful detainment, and the right to apply for asylum regardless of religion or country of origin. We conclude by addressing potential counterarguments to our thesis, future directions, and the role of forensic psychiatrists. © 2017 American Academy of Psychiatry and the Law.

  19. Comparative analysis of insect succession data from Victoria (Australia) using summary statistics versus preceding mean ambient temperature models.

    Science.gov (United States)

    Archer, Mel

    2014-03-01

    Minimum postmortem interval (mPMI) can be estimated with preceding mean ambient temperature models that predict carrion taxon pre-appearance interval. But accuracy has not been compared with using summary statistics (mean ± SD of taxon arrival/departure day, range, 95% CI). This study collected succession data from ten experimental and five control (infrequently sampled) pig carcasses over two summers (n = 2 experimental, n = 1 control per placement date). Linear and exponential preceding mean ambient temperature models for appearance and departure times were constructed for 17 taxa/developmental stages. There was minimal difference in linear or exponential model success, although arrival models were more often significant: 65% of linear arrival (r2 = 0.09–0.79) and exponential arrival models (r2 = 0.05–81.0) were significant, and 35% of linear departure (r2 = 0.0–0.71) and exponential departure models (r2 = 0.0–0.72) were significant. Performance of models and summary statistics for estimating mPMI was compared in two forensic cases. Only summary statistics produced accurate mPMI estimates.

  20. The effect of intervention using the PRECEDE-PROCEED model based on quality of life in diabetic patients.

    Science.gov (United States)

    Azar, Farbod Ebadifard; Solhi, Mahnaz; Nejhaddadgar, Nazila; Amani, Firoz

    2017-08-01

    Poor quality of life is common among diabetic patients, and educational intervention is one of the most effective strategies to improve the quality of life for chronic patients. To determine the effect of an educational intervention based on PRECEDE-PROCEED in quality of life of diabetic patients, in 2016. In this quasi-experimental study, 86 patients referred to diabetic centers of Ardabil participated. We used the components PRECEDE-PROCEED model for planning, implementation and evaluation of the program. Data collection tools were Diabetes Quality of Life questionnaire (DQOL) and a researcher-made questionnaire. Eight training sessions were conducted for the intervention group for self-efficiency, self- management, attitude, knowledge, and enabling reinforcing factors. Quality of life was followed one and three months after intervention. Data were analyzed through SPSS 16 software using descriptive and analytical tests. The mean age of patients was 55.88 (±12.1) years. The result showed that before intervention, no significant difference was observed among the mean scores of quality of life, self-management, knowledge, attitude, enabling and reinforcing factors, and self-efficiency in two groups. But one and three months after intervention a significant difference was observed (pmodel improved the diabetic patient's quality of life.

  1. Applying an Educational-participatory Program based on the PRECEDE Model for Promoting Self-esteem and Mental Health of Students in Iran

    Directory of Open Access Journals (Sweden)

    Mahdi Moshki

    2012-01-01

    Conclusion: Health promotion planning by using life skills training based on the PRECEDE model can result in participation and empowerment, in order to promote the self-esteem and mental health of the students.

  2. Mechanisms of Hypoxic Up-Regulation of Versican Gene Expression in Macrophages.

    Directory of Open Access Journals (Sweden)

    Fattah Sotoodehnejadnematalahi

    Full Text Available Hypoxia is a hallmark of many pathological tissues. Macrophages accumulate in hypoxic sites and up-regulate a range of hypoxia-inducible genes. The matrix proteoglycan versican has been identified as one such gene, but the mechanisms responsible for hypoxic induction are not fully characterised. Here we investigate the up-regulation of versican by hypoxia in primary human monocyte-derived macrophages (HMDM, and, intriguingly, show that versican mRNA is up-regulated much more highly (>600 fold by long term hypoxia (5 days than by 1 day of hypoxia (48 fold. We report that versican mRNA decay rates are not affected by hypoxia, demonstrating that hypoxic induction of versican mRNA is mediated by increased transcription. Deletion analysis of the promoter identified two regions required for high level promoter activity of luciferase reporter constructs in human macrophages. The hypoxia-inducible transcription factor HIF-1 has previously been implicated as a key potential regulator of versican expression in hypoxia, however our data suggest that HIF-1 up-regulation is unlikely to be principally responsible for the high levels of induction observed in HMDM. Treatment of HMDM with two distinct specific inhibitors of Phosphoinositide 3-kinase (PI3K, LY290042 and wortmannin, significantly reduced induction of versican mRNA by hypoxia and provides evidence of a role for PI3K in hypoxic up-regulation of versican expression.

  3. Pim kinases are upregulated during Epstein-Barr virus infection and enhance EBNA2 activity

    International Nuclear Information System (INIS)

    Rainio, Eeva-Marja; Ahlfors, Helena; Carter, Kara L.; Ruuska, Marja; Matikainen, Sampsa; Kieff, Elliott; Koskinen, Paeivi J.

    2005-01-01

    Latent Epstein-Barr virus (EBV) infection is strongly associated with B-cell proliferative diseases such as Burkitt's lymphoma. Here we show that the oncogenic serine/threonine kinases Pim-1 and Pim-2 enhance the activity of the viral transcriptional activator EBNA2. During EBV infection of primary B-lymphocytes, the mRNA expression levels of pim genes, especially of pim-2, are upregulated and remain elevated in latently infected B-cell lines. Thus, EBV-induced upregulation of Pim kinases and Pim-stimulated EBNA2 transcriptional activity may contribute to the ability of EBV to immortalize B-cells and predispose them to malignant growth

  4. Peripheral blood changes preceding the development of leukemia in atomic bomb survivors: Hiroshima and Nagasaki, 1947--1962

    Energy Technology Data Exchange (ETDEWEB)

    Hoshino, T; Finch, S C; Lamphere, J P; Ishimaru, T

    1975-01-01

    The peripheral blood changes in 44 patients who died of either acute leukemia or chronic granulocytic leukemia were evaluated during the preleukemic phase of their clinical illnesses at the time of routine health examination. The most striking finding was the presence of increased numbers of atypical and abnormal lymphocytes in the peripheral blood for periods of 3 to 4 years prior to establishment of the clinical diagnosis of both acute and chronic leukemia. Moderate leukocytosis with left-shifted myeloid cells and basophilia preceded the diagnosis of chronic granulocytic leukemia by 1 or 2 years. Basophilia did not occur in the absence of leukocytosis. The lymphocyte changes suggest the possibility that the host response to underlying clones of leukemic cells may exist for several years prior to the emergence of clinical leukemia. None of the preleukemic hematologic changes which previously have been defined in the preleukemic syndrome for acute leukemia was observed in any of the patients.

  5. Histopathological insights into hair loss in Cronkhite-Canada syndrome: diffuse anagen-telogen conversion precedes clinical hair loss progression.

    Science.gov (United States)

    Watanabe-Okada, Emiko; Inazumi, Toyoko; Matsukawa, Hidehiko; Ohyama, Manabu

    2014-05-01

    Cronkhite-Canada syndrome (CCS) is a rare disorder characterised by gastrointestinal polyposis and ectodermal changes, represented by extensive alopecia. Detailed histopathological investigations of alopecic lesions in two female CCS patients with severe hair loss revealed a marked increase in telogen hair follicles with no sign of loss or of the minaturisation or atrophy of hair follicle structures and the absence of inflammatory change, despite severe inflammation in the gastrointestinal tract. These findings suggested that hair regrowth can be expected without systemic corticosteroids, if they are not necessary for treatment of the gastrointestinal tract, and that anagen-telogen transition is an early event preceding clinical hair loss in CCS. © 2013 The Authors. Australasian Journal of Dermatology © 2013 The Australasian College of Dermatologists.

  6. Crystal structure of a Na+-bound Na+,K+-ATPase preceding the E1P state.

    Science.gov (United States)

    Kanai, Ryuta; Ogawa, Haruo; Vilsen, Bente; Cornelius, Flemming; Toyoshima, Chikashi

    2013-10-10

    Na(+),K(+)-ATPase pumps three Na(+) ions out of cells in exchange for two K(+) taken up from the extracellular medium per ATP molecule hydrolysed, thereby establishing Na(+) and K(+) gradients across the membrane in all animal cells. These ion gradients are used in many fundamental processes, notably excitation of nerve cells. Here we describe 2.8 Å-resolution crystal structures of this ATPase from pig kidney with bound Na(+), ADP and aluminium fluoride, a stable phosphate analogue, with and without oligomycin that promotes Na(+) occlusion. These crystal structures represent a transition state preceding the phosphorylated intermediate (E1P) in which three Na(+) ions are occluded. Details of the Na(+)-binding sites show how this ATPase functions as a Na(+)-specific pump, rejecting K(+) and Ca(2+), even though its affinity for Na(+) is low (millimolar dissociation constant). A mechanism for sequential, cooperative Na(+) binding can now be formulated in atomic detail.

  7. A case of AML with preceding hypoplastic stage after oophoro-hysterectomy and 60Co-irradiation

    International Nuclear Information System (INIS)

    Yoshida, Takashi; Nakamura, Shinobu; Hattori, Kenichi; Tanimoto, Kazuo.

    1975-01-01

    A case of AML (preceded by a hypoplastic stage) which developed after oophoro-hysterectomy and 60 Co-irradiation is presented, and related literature concerning irradiation-induced leukemia and the early diagnosis of leukemia and/or preleukemia are discussed. The patient, a 47 year old female had had surgery and irradiation with a subsequent normachromic anemia necessitating transfusions 11 years prior to her presenting herself at our hospital because of anemia. Her pancytopenic peripheral blood picture combined with a relatively hypererythroid marron led to a diagnosis of atypical hypoplastic anemia. Two years after this she suddenly developed a high fever, general fatigue and a severe anemia. Hematological studies revealed acute myeloblastic leukemia. A combination therapy consisting of DM, 6MP, prednisolon and blood transfusions was given with no effect and 3 months after the onset, the patient died of asphyxia resulting from gross hemoptysis. Autopsy revealed pulmonary hemorrhage secondary to the leukemia. (J. Evans)

  8. Elevated Eosinophil Protein X in Urine from Healthy Neonates Precedes Development of Atopy in the First 6 Years of Life

    DEFF Research Database (Denmark)

    Chawes, Bo Lund Krogsgaard; Bønnelykke, Klaus; Bisgaard, Hans

    2011-01-01

    -prostaglandin-F2a was associated with any of the atopic phenotypes. Conclusion Eosinophil protein-X in urine from asymptomatic neonates is a biomarker significantly associated with later development of allergic sensitization, nasal eosinophilia and eczema during the first 6 years of life. These findings suggest...... D2 metabolite) assessed in urine from healthy at-risk neonates precede development of atopic disease during the first 6 years of life. Methods We measured eosinophil protein-X (N=369), leukotriene-C4/D4/E4 (N=367), and 11ß-prostaglandin-F2a (N=366) in urine from 1-month-old children participating...... untill age 6 years. Associations between urinary biomarkers and development of atopic traits were investigated using general estimating equations, logistic regression and Cox regression. Measurements and Main Results Eosinophil protein-X in the urine of the asymptomatic 1-month-old neonates...

  9. Application of high resolution x-ray spectrometry preceded by neutron activation for elemental analysis of soil samples

    International Nuclear Information System (INIS)

    Hernandez Rivero, A.; Capote Rodriguez, G.; Padilla Alvarez, R.; Herrera Peraza, E.

    1997-01-01

    Utilization of High Resolution X-Ray Spectrometry preceded by activation of the samples by irradiation with neutron fluxes (NAA-RX) is a relatively modern trend in application of nuclear techniques. This method may complement advantageously the usual Neutron Activation Analysis by means of Gamma Spectrometry (NAA-G). In this work results obtained by the application of NAA-RX for non-destructive analysis of Cuban soil samples are discussed. The samples were irradiated with reactor neutron fluxes and the induced characteristic X-rays were measured by using Si(Li)-detector. Concentrations of Fe, Zn and Eu as determined by NAA-RX are compared with both NAA-G and XRF data. For the elaboration of X-Ray and Gamma Spectra the computer programs AXIL and ACTAN were used respectively. (author) [es

  10. The Precedent 443 of the Superior Labor Court and Judicial Activism: The Defense of a Non Selective Constitutional Hermeneutics

    Directory of Open Access Journals (Sweden)

    Humberto Lima de Lucena Filho

    2015-12-01

    Full Text Available This paper is dedicated to the analysis of the Precedent 443 of the Superior Labor Court, which deals with the discriminatory dismissal presumption of those labor with social stigma diseases from the perspective of judicial activism in the brazilian labor law and its objective influence on law and labor procedure law from the from the perspective of a not univocal constitutional hermeneutics. It aims, also, to conceptualize the stability institute in order to configure the dangers and misconceptions arising from it. Therefore, it concludes that the analogy that embodied the repeated judicial position was excessive. The research points out the logical-deductive method operated by the aid of the literature review, case law and positioning applicable law.

  11. Self-Verification Strivings in Children Holding Negative Self-Views: The Mitigating Effects of a Preceding Success Experience.

    Science.gov (United States)

    Reijntjes, Albert; Thomaes, Sander; Kamphuis, Jan Henk; de Castro, Bram Orobio; Telch, Michael J

    2010-12-01

    Research among adults has consistently shown that people holding negative self-views prefer negative over positive feedback. The present study tested the hypothesis that this preference is less robust among pre-adolescents, such that it will be mitigated by a preceding positive event. Pre-adolescents (n = 75) holding positive or negative global self-esteem were randomized to a favorable or unfavorable peer evaluation outcome. Next, preferences for positive versus negative feedback were assessed using an unobtrusive behavioral viewing time measure. As expected, results showed that after being faced with the success outcome children holding negative self-views were as likely as their peers holding positive self-views to display a significant preference for positive feedback. In contrast, children holding negative self-views displayed a stronger preference for negative feedback after being faced with the unfavorable outcome that matched their pre-existing self-views.

  12. Application of high resolution x-ray spectrometry preceded by neutron activation for elemental analysis of soil samples

    International Nuclear Information System (INIS)

    Hernandez Rivero, A.; Capote Rodriguez, G.; Herrera Peraza, E.

    1996-01-01

    Utilization of High Resolution X-Ray Spectrometry preceded by activation of the samples by irradiation with neutron fluxes (NAA R X) is a relatively modern trend in application of nuclear techniques. This method may complement advantageously the usual Neutron Activation Analysis by means of Gamma Spectrometry (NAA-G) In this work results obtained by the application of NAA-RX for non-destructive analysis of Cuban soil samples are discussed. The samples were irradiated with reactor neutron fluxes and the induced characteristic X-rays were measured by using Si(li)-detector. Concentrations of Fe, Zn and Eu as determined by NAA-RX are compared with both NAA-G and XRF data. For the elaboration of X-ray and Gamma Spectra the computer programs AXIL and ACTAN were used respectively

  13. Characteristics of claims in the management of septic arthritis in Japan: Retrospective analyses of judicial precedents and closed claims.

    Science.gov (United States)

    Otaki, Yasuhiro; DaSilva, Makiko Ishida; Saito, Yuichi; Oyama, Yasuaki; Oiso, Giichiro; Yoshida, Tomohiko; Fukuhara, Masakazu; Moriyama, Mitsuru

    2018-03-01

    Septic arthritis (SA) cases can result in claims or litigation because of poor prognosis even if it is unavoidable. Although these claims or litigation are useful for understanding causes and background factors of medical errors, the characteristics of malpractice claims associated with SA remain undetermined in Japan. This study aimed to increase our understanding of malpractice claims in the clinical management of SA. We analyzed 6 civil precedents and 16 closed claims of SA from 8530 malpractice claims processed between July 2004 and June 2014 by the Tokyo office of Sompo Japan Nipponkoa Insurance, Incorporated. We also studied 5 accident and 21 incident reports of SA based on project data compiled by the Japan Council for Quality Health Care. The rate of negligence was 83.3% in the precedents and 75.0% in closed claims. Two main malpractice claim patterns were revealed: SA in a lower extremity joint following sepsis caused by methicillin-resistant Staphylococcus aureus in newborns and SA in an injection site following joint injection. These two patterns accounted for 83.3% and 56.3% of judicial cases and closed claim cases, respectively. Breakdowns in care process of accident and incident reports were clearly differentiated from judicial cases or closed claim cases (Fisher's exact test, p < 0.001). It is important to pay particular attention to SA following sepsis in newborns and to monitor for any signs of SA after joint injection to ensure early diagnosis. Analysis of both malpractice claims and accident and incident reports is essential to ensure a full understanding of the situation in Japan. Copyright © 2017. Published by Elsevier Taiwan LLC.

  14. Peak lean tissue mass accrual precedes changes in bone strength indices at the proximal femur during the pubertal growth spurt.

    Science.gov (United States)

    Jackowski, Stefan A; Faulkner, Robert A; Farthing, Jonathan P; Kontulainen, Saija A; Beck, Thomas J; Baxter-Jones, Adam D G

    2009-06-01

    We examined the timing of the age and the magnitude of peak lean tissue mass accrual (PLTV) relative to the age and magnitude of two variables of bone strength [peak cross sectional area velocity (PCSAV), and peak section modulus velocity, (PZV)] at the proximal femur in males and females during the adolescent growth spurt. We hypothesized that the age of PLTV would precede the ages of PCSAV and PZV and that there is a positive relationship between the magnitude of PLTV and both PCSAV and PZV in both genders. 41 males and 42 females aged 8-18 years were selected from the Saskatchewan Pediatric Bone Mineral Accrual Study (1991-2005). Participants' total body lean tissue mass was assessed annually for 6 consecutive years using DXA. Narrow neck and femoral shaft cross sectional areas (CSA) and section modulus (Z) were determined using the hip structural analysis (HSA) program. Participants were aligned by maturational age (years from peak height velocity). Lean tissue mass, CSA, and Z were converted into whole year velocities and the maturational age of peak tissue velocities was determined using a cubic spline curve fitting procedure. A 2 x 3 (gender x tissue) factorial MANOVA with repeated measures was used to test for differences between age of PLTV and the ages of PCSAV and PZV between genders. Multiple regression analyses were used to examine the relationship between PLTV and both PCSAV and PZV. There were no sex differences in the ages at which tissue peaks occurred when aligned by maturational age. There were significant differences between the age of PLTV and both PCSAV and PZV at the narrow neck (p=0.001) and femoral shaft (p=0.03), where the age of PLTV preceded both PCSAV and PZV when pooled by gender. PLTV was a significant predictor of the magnitude of both PCSAV and PZV at all sites (ptheory that muscle development is an important factor in affecting bone strength.

  15. SELF and VLF electromagnetic emissions that preceded the M6.2 Central Italy earthquake occurred on August 24, 2016

    Science.gov (United States)

    Cataldi, Daniele; Cataldi, Gabriele; Straser, Valentino

    2017-04-01

    On August 24, 2016 at 01:36:32 UTC a destructive earthquake hit Central Italy with a magnitude of M6.2. The authors of this study have recorded some electromagnetic signals that have preceded this strong earthquake. These signals were recorded through two electromagnetic monitoring stations realized by Gabriele Cataldi and Daniele Cataldi, located near the town of Albano Laziale (Rome, Italy) and near the city of Lariano (Rome, Italy) and can monitor the radio spectrum 24h7 between 0.001 Hz and 96 kHz (SELF-LF band). The electromagnetic monitoring allowed to identify two interesting types of electromagnetic anomalies: the first electromagnetic anomaly was recorded on August 18, 2016 between 02:47 UTC and 06:21 UTC, in the VLF band prevalently between 18kHz and 26kHz; the second electromagnetic anomaly was registered between 08:00 UTC on August 23, 2016 and 05:00 UTC on August 24, 2016, prevalently between 0.01 and 0.7Hz: the most intense signals were recorded at 08:50 UTC on August 23, 2016 and approximately 1 hour before the strong earthquake. The Earth's electromagnetic background monitoring in the SELF-VLF band (0HzM6+ earthquakes that occur on a global scale are always preceded by an increase of the solar wind proton density near Earth, the solar and geomagnetic activity monitoring is a seismic prediction method that has proven reliable for understanding when we can expect a recovery of the M6+ global seismic activity and could be used internationally as an indicator of seismic risk in the countries where there are potentially destructive earthquakes and tsunamis.

  16. Dissociable neural effects of stimulus valence and preceding context during the inhibition of responses to emotional faces.

    Science.gov (United States)

    Schulz, Kurt P; Clerkin, Suzanne M; Halperin, Jeffrey M; Newcorn, Jeffrey H; Tang, Cheuk Y; Fan, Jin

    2009-09-01

    Socially appropriate behavior requires the concurrent inhibition of actions that are inappropriate in the context. This self-regulatory function requires an interaction of inhibitory and emotional processes that recruits brain regions beyond those engaged by either processes alone. In this study, we isolated brain activity associated with response inhibition and emotional processing in 24 healthy adults using event-related functional magnetic resonance imaging (fMRI) and a go/no-go task that independently manipulated the context preceding no-go trials (ie, number of go trials) and the valence (ie, happy, sad, and neutral) of the face stimuli used as trial cues. Parallel quadratic trends were seen in correct inhibitions on no-go trials preceded by increasing numbers of go trials and associated activation for correct no-go trials in inferior frontal gyrus pars opercularis, pars triangularis, and pars orbitalis, temporoparietal junction, superior parietal lobule, and temporal sensory association cortices. Conversely, the comparison of happy versus neutral faces and sad versus neutral faces revealed valence-dependent activation in the amygdala, anterior insula cortex, and posterior midcingulate cortex. Further, an interaction between inhibition and emotion was seen in valence-dependent variations in the quadratic trend in no-go activation in the right inferior frontal gyrus and left posterior insula cortex. These results suggest that the inhibition of response to emotional cues involves the interaction of partly dissociable limbic and frontoparietal networks that encode emotional cues and use these cues to exert inhibitory control over the motor, attention, and sensory functions needed to perform the task, respectively. 2008 Wiley-Liss, Inc.

  17. Examining the impact of migrant status on ethnic differences in mental health service use preceding a first diagnosis of schizophrenia.

    Science.gov (United States)

    Anderson, Kelly K; McKenzie, Kwame J; Kurdyak, Paul

    2017-08-01

    Some ethnic groups have more negative contacts with health services for first-episode psychosis, likely arising from a complex interaction between ethnicity, socio-economic factors, and immigration status. Using population-based health administrative data, we sought to examine the effects of ethnic group and migrant status on patterns of health service use preceding a first diagnosis of schizophrenia or schizoaffective disorder among people aged 14-35 over a 10-year period. We compared access to care and intensity of service use for first-generation ethnic minority groups to the general population of Ontario. To control for migrant status, we restricted the sample to first-generation migrants and compared service use indicators for ethnic minority groups to the European migrant group. Our cohort included 18,080 people with a first diagnosis of schizophrenia or schizoaffective disorder, of whom 14.4% (n = 2607) were the first-generation migrants. Our findings suggest that the magnitude of ethnic differences in health service use is reduced and no longer statistically significant when the sample is restricted to first-generation migrants. Of exception, nearly, all migrant groups have lower intensity of primary care use, and Caribbean migrants are consistently less likely to use psychiatric services. We observed fewer ethnic differences in health service use preceding the first diagnosis of psychosis when patterns are compared among first-generation migrants, rather than to the general population, suggesting that the choice of reference group influences ethnic patterning of health service use. We need a comprehensive understanding of the mechanisms behind observed differences for minority groups to adequately address disparities in access to care.

  18. Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression

    DEFF Research Database (Denmark)

    Xu, Cang-Bao; Zheng, Jian-Pu; Zhang, Wei

    2014-01-01

    Vasoconstrictive endothelin type B (ET(B)) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ET(B) receptor expression and if extracellular signal...

  19. Functional aspects of dexamethasone upregulated nicotinic acetylcholine receptors in C2C12 myotubes

    NARCIS (Netherlands)

    Maestrone, E; Lagostena, L; Henning, RH; DenHertog, A; Nobile, M

    Three days of treatment with the glucocorticoid dexamethasone (1 nM-mu M) induced a concentration-dependent up-regulation of muscle nicotinic acetylcholine receptor (nAChR) in C2C12 mouse myotubes (EC(50)=10+/-7.3 nM), as assessed by [H-3]alpha-BuTx binding. The maximum increase in binding amounted

  20. Early events triggering delayed vasoconstrictor receptor upregulation and cerebral ischemia after subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Povlsen, Gro Klitgaard; Johansson, Sara Ellinor; Larsen, Carl Christian

    2013-01-01

    shown to be mediated by intracellular signalling via the mitogen activated protein kinase kinase (MEK1/2)--extracellular regulated kinase 1/2 (ERK1/2) pathway. However, it is not known what event(s) that trigger MEK-ERK1/2 activation and vasoconstrictor receptor upregulation after SAH.We hypothesise...

  1. Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries

    DEFF Research Database (Denmark)

    Ahnstedt, Hilda; Cao, Lei; Krause, Diana N

    2013-01-01

    Male-female differences may significantly impact stroke prevention and treatment in men and women, however underlying mechanisms for sexual dimorphism in stroke are not understood. We previously found in males that cerebral ischemia upregulates contractile receptors in cerebral arteries, which...

  2. Cisplatin upregulates mitochondrial nitric oxide synthase and peroxynitrite formation to promote renal injury

    International Nuclear Information System (INIS)

    Jung, Michaela; Hotter, Georgina; Vinas, Jose Luis; Sola, Anna

    2009-01-01

    The mitochondria are a critical target for cisplatin-associated nephrotoxicity. Though nitric oxide formation has been implicated in the toxicity of cisplatin, this formation has not so far been related to a possible activation of mitochondrial nitric oxide synthase (mNOS). We show here that the upregulation of oxide mNOS and peroxynitrite formation in cisplatin treatment are key events that influence the development of the harmful parameters described in cisplatin-associated kidney failure. We confirm this by isolating the mitochondrial fraction of the kidney and across different access routes such as the use of a specific inhibitor of neuronal NOS, L-NPA, a peroxynitrite scavenger, FeTMPyP, and a peroxynitrite donor, SIN-1. The in vitro studies corroborated the information obtained in the in vivo experiments. The administration of cisplatin reveals a clear upregulation in the transcription of neuronal NOS and an increase in the levels of nitrites in the mitochondrial fractions of the kidneys. The upregulated transcription directly affects the cytoskeleton structure and the apoptosis. The inhibition of neuronal NOS reduces the levels of nitrites, cell death, and cytoskeleton derangement. Peroxynitrite is involved in the mechanism promoting the NOS transcription. In addition, in controls SIN-1 imitates the effects of cisplatin. In summary, we demonstrate that upregulation of mNOS in cisplatin treatment is a key component in both the initiation and the spread of cisplatin-associated damage in the kidney. Furthermore, peroxynitrite formation is directly involved in this process

  3. The emerging role of m-TOR up-regulation in brain Astrocytoma.

    Science.gov (United States)

    Ryskalin, Larisa; Limanaqi, Fiona; Biagioni, Francesca; Frati, Alessandro; Esposito, Vincenzo; Calierno, Maria Teresa; Lenzi, Paola; Fornai, Francesco

    2017-05-01

    The present manuscript is an overview of various effects of mTOR up-regulation in astrocytoma with an emphasis on its deleterious effects on the proliferation of Glioblastoma Multiforme. The manuscript reports consistent evidence indicating the occurrence of mTOR up-regulation both in experimental and human astrocytoma. The grading of human astrocytoma is discussed in relationship with mTOR up-regulation. In the second part of the manuscript, the biochemical pathways under the influence of mTOR are translated to cell phenotypes which are generated by mTOR up-regulation and reverted by its inhibition. A special section is dedicated to the prominent role of autophagy in mediating the effects of mTOR in glioblastoma. In detail, autophagy inhibition produced by mTOR up-regulation determines the fate of cancer stem cells. On the other hand, biochemical findings disclose the remarkable effects of autophagy activators as powerful inducers of cell differentiation with a strong prevalence towards neuronal phenotypes. Thus, mTOR modulation acts on the neurobiology of glioblastoma just like it operates in vivo at the level of brain stem cell niches by altering autophagy-dependent cell differentiation. In the light of such a critical role of autophagy we analyzed the ubiquitin proteasome system. The merging between autophagy and proteasome generates a novel organelle, named autophagoproteasome which is strongly induced by mTOR inhibitors in glioblastoma cells. Remarkably, when mTOR is maximally inhibited the proteasome component selectively moves within autophagy vacuoles, thus making the proteasome activity dependent on the entry within autophagy compartment.

  4. Up-regulation of the Neuronal Nicotinic Receptor α7 by HIV Glycoprotein 120

    Science.gov (United States)

    Ballester, Leomar Y.; Capó-Vélez, Coral M.; García-Beltrán, Wilfredo F.; Ramos, Félix M.; Vázquez-Rosa, Edwin; Ríos, Raymond; Mercado, José R.; Meléndez, Roberto I.; Lasalde-Dominicci, José A.

    2012-01-01

    Approximately 30–50% of the >30 million HIV-infected subjects develop neurological complications ranging from mild symptoms to dementia. HIV does not infect neurons, and the molecular mechanisms behind HIV-associated neurocognitive decline are not understood. There are several hypotheses to explain the development of dementia in HIV+ individuals, including neuroinflammation mediated by infected microglia and neuronal toxicity by HIV proteins. A key protein associated with the neurological complications of HIV, gp120, forms part of the viral envelope and can be found in the CSF of infected individuals. HIV-1-gp120 interacts with several receptors including CD4, CCR5, CXCR4, and nicotinic acetylcholine receptors (nAChRs). However, the role of nAChRs in HIV-associated neurocognitive disorder has not been investigated. We studied the effects of gp120IIIB on the expression and function of the nicotinic receptor α7 (α7-nAChR). Our results show that gp120, through activation of the CXCR4 chemokine receptor, induces a functional up-regulation of α7-nAChRs. Because α7-nAChRs have a high permeability to Ca2+, we performed TUNEL staining to investigate the effects of receptor up-regulation on cell viability. Our data revealed an increase in cell death, which was blocked by the selective antagonist α-bungarotoxin. The in vitro data are supported by RT-PCR and Western blot analysis, confirming a remarkable up-regulation of the α7-nAChR in gp120-transgenic mice brains. Specifically, α7-nAChR up-regulation is observed in mouse striatum, a region severely affected in HIV+ patients. In summary, CXCR4 activation induces up-regulation of α7-nAChR, causing cell death, suggesting that α7-nAChR is a previously unrecognized contributor to the neurotoxicity associated with HIV infection. PMID:22084248

  5. Mycobacterium tuberculosis, but not vaccine BCG, specifically upregulates matrix metalloproteinase-1.

    Science.gov (United States)

    Elkington, Paul T G; Nuttall, Robert K; Boyle, Joseph J; O'Kane, Cecilia M; Horncastle, Donna E; Edwards, Dylan R; Friedland, Jon S

    2005-12-15

    Pulmonary cavitation is fundamental to the global success of Mycobacterium tuberculosis. However, the mechanisms of this lung destruction are poorly understood. The biochemistry of lung matrix predicts matrix metalloproteinase (MMP) involvement in immunopathology. We investigated gene expression of all MMPs, proteins with a disintegrin and metalloproteinase domain, and tissue inhibitors of metalloproteinases in M. tuberculosis-infected human macrophages by real-time polymerase chain reaction. MMP secretion was measured by zymography and Western analysis, and expression in patients with pulmonary tuberculosis was localized by immunohistochemistry. MMP-1 and MMP-7 gene expression and secretion are potently upregulated by M. tuberculosis, and no increase in tissue inhibitor of metalloproteinase expression occurs to oppose their activity. Dexamethasone completely suppresses MMP-1 but not MMP-7 gene expression and secretion. In patients with active tuberculosis, macrophages express MMP-1 and MMP-7 adjacent to areas of tissue destruction. MMP-1 but not MMP-7 expression and secretion are relatively M. tuberculosis specific, are not upregulated by tuberculosis-associated cytokines, and are prostaglandin dependent. In contrast, the vaccine M. bovis bacillus Calmette-Guérin (BCG) does not stimulate MMP-1 secretion from human macrophages, although M. tuberculosis and BCG do upregulate MMP-7 equally. BCG-infected macrophages secrete reduced prostaglandin E2 concentrations compared with M. tuberculosis-infected macrophages, and prostaglandin pathway supplementation augments MMP-1 secretion from BCG-infected cells. M. tuberculosis specifically upregulates MMP-1 in a cellular model of human infection and in patients with tuberculosis. In contrast, vaccine BCG, which does not cause lung cavitation, does not upregulate prostaglandin E2-dependent MMP-1 secretion.

  6. Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries.

    Directory of Open Access Journals (Sweden)

    Hilda Ahnstedt

    Full Text Available BACKGROUND AND PURPOSE: Male-female differences may significantly impact stroke prevention and treatment in men and women, however underlying mechanisms for sexual dimorphism in stroke are not understood. We previously found in males that cerebral ischemia upregulates contractile receptors in cerebral arteries, which is associated with lower blood flow. The present study investigates if cerebral arteries from men and women differ in cerebrovascular receptor upregulation. EXPERIMENTAL APPROACH: Freshly obtained human cerebral arteries were placed in organ culture, an established model for studying receptor upregulation. 5-hydroxtryptamine type 1B (5-HT1B, angiotensin II type 1 (AT1 and endothelin-1 type A and B (ETA and ETB receptors were evaluated using wire myograph for contractile responses, real-time PCR for mRNA and immunohistochemistry for receptor expression. KEY RESULTS: Vascular sensitivity to angiotensin II and endothelin-1 was markedly lower in cultured cerebral arteries from women as compared to men. ETB receptor-mediated contraction occurred in male but not female arteries. Interestingly, there were similar upregulation in mRNA and expression of 5-HT1B, AT1, and ETB receptors and in local expression of Ang II after organ culture. CONCLUSIONS AND IMPLICATIONS: In spite of receptor upregulation after organ culture in both sexes, cerebral arteries from women were significantly less responsive to vasoconstrictors angiotensin II and endothelin-1 as compared to arteries from men. This suggests receptor coupling and/or signal transduction mechanisms involved in cerebrovascular contractility may be suppressed in females. This is the first study to demonstrate sex differences in the vascular function of human brain arteries.

  7. Designing with precedents

    NARCIS (Netherlands)

    Pasman, G.

    2003-01-01

    Every year designers are challenged to generate new and unique product forms. Often, the design and form of previous products constitutes a basis for the generation of new ones. What role then do existing products play in the generation and development of new product forms? How can this role be

  8. The Effect of Preceding Crops on the Chemical Fractions of Copper (Cu in the Rhizosphere and the Bulk Soil and its Relationship with Copper Uptake by Wheat

    Directory of Open Access Journals (Sweden)

    shahrzad kabirinejad

    2017-02-01

    Full Text Available Introduction: Preceding crops as a source of organic matter are an important source of micronutrient and can play an important role in the soil fertility and the micronutrients cycle of soil. In addition to the role of the organic matter in increasing the concentration of micronutrients in soil solution, attention also should be paid to the role of the kind and the quantity of the root’s exudates that are released in response to the incorporation of different plant residues in the rhizosphere. Present research was conducted with the objective of studying the effect of the kind of preceding crops: Trifolium (Trifolium pretense L, Sofflower (Carthamus tinectirus L, Sorghum (Sorghum bicolor L, Sunflower (Heliantus annus L and control (fallow on the chemical forms of copper in the wheat rhizosphere and the bulk soil and Cu uptake by wheat and also investigating the correlation between the fractions of Cu in soil and Cu uptake in wheat. Materials and Methods: The present research was conducted as split plot in a Randomized Complete Block design (RCBD with 3 replications and 5 treatments, in field conditions. In the beginning, the preceding crops were cultivated in the experimental plots and after ending growth, preceding crops were harvested. Then the wheat was cultivated in the experimental plots. Finally, after harvesting the wheat, soil samples were collected from the two parts of the root zone (the wheat rhizosphere and the bulk soil. The soil samples were air dried ground and passed through a 2-mm sieve and stored for chemical analysis. Soil pH (in the soil saturation extract and organic matter (Walkley–Black wet digestion were measured in standard methods (1. The Total Organic Carbon (TOC was measured by Analyzer (Primacs SLC TOC Analyzer (CS22, Netherlands. The available Cu in soil was extracted by DTPA and determined using atomic absorption spectroscopy (2. The fractionation of soil Cu was carried out using the MSEP method (3. Results and

  9. On the Reflection in the Solar Radio Emission of Processes in the Chromosphere and the lower Corona preceded CMEs Registration

    Science.gov (United States)

    Durasova, M. S.; Tikhomirov, Yu. V.; Fridman, V. M.; Sheiner, O. A.

    The phenomena preceding the Coronal Mass Ejections (CMEs) and observed in the radio-frequency band represent a lot of sporadic components of the emission, that cover the wide frequency range. The study of these phenomena composes the new, prevailing for the last ten years direction. This is caused by the fact that solar radioastronomy possesses the developed network of observant tools, by the sensitive methods of observations. It makes possible in a number of cases to obtain information from the layers of solar atmosphere, inaccessible for the studies by other methods of observations. The purpose of this work is analysis of information about the CMEs preceding radio-events and their dynamics in the centimeter and decimeter radio emission in 1998. We use the data of the worldwide network of solar observatories in the radio-frequency band, the data about the CMEs phenomena and the characteristics are taken from Internet: http://sdaw.gsfc.nasa.gov./CME_list}. From great number of the CMEs we select only such, before which there were no more recorded events in the time interval of 8 hours, and before which sporadic radio emission was observed on 2-hours interval. The selection of this interval was caused by available study about the mean lifetime of precursors before CMEs and powerful flares, as a rule, accompanying CMEs, in the optical, X-ray and radio emissions. It constitutes, on the average, about 30 min. The total volume of data composed 68 analyzed events of CMEs in 1998. The analysis of the spectral- temporary characteristics of sporadic radio emission in the dependence on the CMEs parameters is carried out. The nature of processes at the stage of formation and initial propagation of CMEs, such as floating up of new magnetic fluxes, the development of instabilities, the characteristic scales of phenomena, that have an effect upon the observed radio emission is analyzed. The work is carried out with the support of Russian Fund of Basic Research (grant 03

  10. Similar and Contrasting Response of Rifting and Transtension in the Gulf of California and Walker Lane to Preceding Arc Magmatism

    Science.gov (United States)

    Henry, C. D.; Faulds, J. E.

    2006-12-01

    The Gulf of California (GC) and Walker Lane (WL) have undergone strikingly similar development with strike- slip faulting following initial extension. They differ significantly in the amount of Pacific-North American plate motion taken up by each: essentially all relative motion in the GC and ~25% in the WL. In both areas, ancestral arc magmatism preceded and probably focused deformation, perhaps because heating and/or hydration weakened the lithosphere. However, differences in migration of the Rivera (RTJ) and Mendocino triple junctions (MTJ) related to differences in the orientation of plate boundaries determined how strike-slip faulting developed. Abrupt southward jumps in the RTJ led to abrupt cessation of magmatism over arc lengths of as much as 1000 km and initiation of east-northeast extension within the future GC. The best known jump was at ~13 Ma, but an earlier jump occurred at ~18 Ma. Arc magmatism has been best documented in Baja California, Sonora, and Nayarit, although Baja constituted the most-trenchward fringe of the ancestral arc. New and published data indicate that Sinaloa underwent a similar history of arc magmatism. The greatest volume of the arc immediately preceding RTJ jumps was probably in mainland Mexico. Arc magmatism shut off following these jumps, extension began in the future GC, and strike-slip faulting either followed or accompanied extension in the GC. In contrast, the MTJ migrated progressively northward. New and published data indicate magmatism generally shut off coincident with this retreat, but distinct nodes or zones of magmatism, presumably unrelated to subduction, persisted or initiated after arc activity ceased. We have suggested that the WL has grown progressively northward, following the retreating arc, and that the northern WL is its youngest part. However, the timing of initiation of strike-slip faulting in most of the WL is poorly known and controversial. Testing our hypothesis requires determining initiation and

  11. Hydrometeorological conditions preceding wildfire, and the subsequent burning of a fen watershed in Fort McMurray, Alberta, Canada

    Science.gov (United States)

    Elmes, Matthew C.; Thompson, Dan K.; Sherwood, James H.; Price, Jonathan S.

    2018-01-01

    The destructive nature of the ˜ 590 000 ha Horse river wildfire in the Western Boreal Plain (WBP), northern Alberta, in May of 2016 motivated the investigation of the hydrometeorological conditions that preceded the fire. Historical climate and field hydrometeorological data from a moderate-rich fen watershed were used to (a) identify whether the spring 2016 conditions were outside the range of natural variability for WBP climate cycles, (b) explain the observed patterns in burn severity across the watershed, and (c) identify whether fall and winter moisture signals observed in peatlands and lowland forests in the region are indicative of wildfire. Field hydrometeorological data from the fen watershed confirmed the presence of cumulative moisture deficits prior to the fire. Hydrogeological investigations highlighted the susceptibility of fen and upland areas to water table and soil moisture decline over rain-free periods (including winter), due to the watershed's reliance on supply from localized flow systems originating in topographic highs. Subtle changes in topographic position led to large changes in groundwater connectivity, leading to greater organic soil consumption by fire in wetland margins and at high elevations. The 2016 spring moisture conditions measured prior to the ignition of the fen watershed were not illustrated well by the Drought Code (DC) when standard overwintering procedures were applied. However, close agreement was found when default assumptions were replaced with measured duff soil moisture recharge and incorporated into the overwintering DC procedure. We conclude that accumulated moisture deficits dating back to the summer of 2015 led to the dry conditions that preceded the fire. The infrequent coinciding of several hydrometeorological conditions, including low autumn soil moisture, a modest snowpack, lack of spring precipitation, and high spring air temperatures and winds, ultimately led to the Horse river wildfire spreading widely and

  12. Zika Virus Escapes NK Cell Detection by Upregulating Major Histocompatibility Complex Class I Molecules.

    Science.gov (United States)

    Glasner, Ariella; Oiknine-Djian, Esther; Weisblum, Yiska; Diab, Mohammad; Panet, Amos; Wolf, Dana G; Mandelboim, Ofer

    2017-11-15

    NK cells are innate lymphocytes that participate in many immune processes encompassing cancer, bacterial and fungal infection, autoimmunity, and even pregnancy and that specialize in antiviral defense. NK cells express inhibitory and activating receptors and kill their targets when activating signals overpower inhibitory signals. The NK cell inhibitory receptors include a uniquely diverse array of proteins named killer cell immunoglobulin-like receptors (KIRs), the CD94 family, and the leukocyte immunoglobulin-like receptor (LIR) family. The NK cell inhibitory receptors recognize mostly major histocompatibility complex (MHC) class I (MHC-I) proteins. Zika virus has recently emerged as a major threat due to its association with birth defects and its pandemic potential. How Zika virus interacts with the immune system, and especially with NK cells, is unclear. Here we show that Zika virus infection is barely sensed by NK cells, since little or no increase in the expression of activating NK cell ligands was observed following Zika infection. In contrast, we demonstrate that Zika virus infection leads to the upregulation of MHC class I proteins and consequently to the inhibition of NK cell killing. Mechanistically, we show that MHC class I proteins are upregulated via the RIGI-IRF3 pathway and that this upregulation is mediated via beta interferon (IFN-β). Potentially, countering MHC class I upregulation during Zika virus infection could be used as a prophylactic treatment against Zika virus. IMPORTANCE NK cells are innate lymphocytes that recognize and eliminate various pathogens and are known mostly for their role in controlling viral infections. NK cells express inhibitory and activating receptors, and they kill or spare their targets based on the integration of inhibitory and activating signals. Zika virus has recently emerged as a major threat to humans due to its pandemic potential and its association with birth defects. The role of NK cells in Zika virus

  13. An autopsy case of acute myelocytic leukemia preceded by hemopoietic dysplasia found in an atomic bomb survivor

    International Nuclear Information System (INIS)

    Sonoda, Yoshiaki; Edagawa, Junichi; Taniwaki, Masafumi; Ide, Tohru; Misawa, Shinichi

    1981-01-01

    An autopsy case of acute myelocytic leukemia preceded by hemopoietic dysplasia, presumably on a sequela to the atomic bomb in Hiroshima is reported. On admission, severe anemia and thrombocytosis were found and the bone marrow aspiration showed myeloid hyperplasia without definite maturation arrest. Mild to moderate eosinophilia and basophilia continued during the course of the disease, accompaning mild monocytosis 2 years later. Furthermore, he had the radical operation for the early gastric cancer in this preleukemic stage. After the administration of methenolone acetate (25 mg/day), severe anemia has dramatically improved, but leukocytosis with profound monocytosis persisted, and subsequently acute myelocytic leukemia developed. He died from an intracerebral bleeding due to an accidental trauma on the head. Autopsy findings disclosed the systemic leukemic infiltration. Repeated chromosome analyses revealed the mosaic karyotype of 46, XY/45, XY, -16 on admission, but it was 46, XY/46, XY, del (8) (p 12) in the overt leukemic phase. The granulopoietic colony forming capacity of bone marrow cells was already low one year before the onset of overt leukemia. This finding suggested that the existence of an abnormal clone could be predictable. In addition, the possible causative effect of the exposure to the atomic bomb in leukemogenesis in this case is discussed. (author)

  14. Single-cell analysis of pyroptosis dynamics reveals conserved GSDMD-mediated subcellular events that precede plasma membrane rupture.

    Science.gov (United States)

    de Vasconcelos, Nathalia M; Van Opdenbosch, Nina; Van Gorp, Hanne; Parthoens, Eef; Lamkanfi, Mohamed

    2018-04-17

    Pyroptosis is rapidly emerging as a mechanism of anti-microbial host defense, and of extracellular release of the inflammasome-dependent cytokines interleukin (IL)-1β and IL-18, which contributes to autoinflammatory pathology. Caspases 1, 4, 5 and 11 trigger this regulated form of necrosis by cleaving the pyroptosis effector gasdermin D (GSDMD), causing its pore-forming amino-terminal domain to oligomerize and perforate the plasma membrane. However, the subcellular events that precede pyroptotic cell lysis are ill defined. In this study, we triggered primary macrophages to undergo pyroptosis from three inflammasome types and recorded their dynamics and morphology using high-resolution live-cell spinning disk confocal laser microscopy. Based on quantitative analysis of single-cell subcellular events, we propose a model of pyroptotic cell disintegration that is initiated by opening of GSDMD-dependent ion channels or pores that are more restrictive than recently proposed GSDMD pores, followed by osmotic cell swelling, commitment of mitochondria and other membrane-bound organelles prior to sudden rupture of the plasma membrane and full permeability to intracellular proteins. This study provides a dynamic framework for understanding cellular changes that occur during pyroptosis, and charts a chronological sequence of GSDMD-mediated subcellular events that define pyroptotic cell death at the single-cell level.

  15. Application of Behavioral Analysis Phase of PRECEDE Model on Women’s Psychological Well-being in the Menopausal Period

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    Mahdi Moshki

    2015-08-01

    Full Text Available Background and Aims Positive psychology introduce mental health as a positive psychological functioning and represent it as wellbeing psychology and having positive characteristics such as self-esteem, positive social relationships, and life satisfaction. The purpose of this study was to investigate the psychological wellbeing of postmenopausal women based on the behavioral analysis phase of PRECEDE model. Materials and Methods This study is a cross-sectional survey and carried out through random sampling in the case of 110 postmenopausal women at Ferdows city, Iran in 2014. The psychological wellbeing variable was studied by Ryff test, including 84 questions and six components containing autonomy, purposeful in life, dominance on environment, personal development, positive relationships with others, and self-acceptance. The collected data were analyzed by SPSS v.20 using descriptive statistics and analytic statistics through correlation and ANOVA. Results The mean age of participants and the average number of their children were 51.62 ± 4.26 and 3.42 ± 1.38, respectively. 61.80 percent of participants had primary education. Pearson correlation test indicated a positive and significant relationship between psychological wellbeing and predisposing factors (knowledge, attitude toward menopause, environmentalbehavioral factors, enabling factors and reinforcing factors (P < 0.01. Conclusion The results indicated that increasing awareness, creating positive attitude and promoting healthy behaviors are the effective steps to improve the psychological wellbeing in postmenopausal women. * Corresponding Author: Gonabad University of Medical Sciences, Faculty of Public Health. Email: Fpf357@gmail.com

  16. Changes in myonuclear domain size do not precede muscle hypertrophy during prolonged resistance-type exercise training.

    Science.gov (United States)

    Snijders, T; Smeets, J S J; van Kranenburg, J; Kies, A K; van Loon, L J C; Verdijk, L B

    2016-02-01

    Muscle fibre hypertrophy is accompanied by an increase in myonuclear number, an increase in myonuclear domain size or both. It has been suggested that increases in myonuclear domain size precede myonuclear accretion and subsequent muscle fibre hypertrophy during prolonged exercise training. In this study, we assessed the changes in muscle fibre size, myonuclear and satellite cell content throughout 12 weeks of resistance-type exercise training in young men. Twenty-two young men (23 ± 1 year) were assigned to a progressive, 12-weeks resistance-type exercise training programme (3 sessions per week). Muscle biopsies from the vastus lateralis muscle were taken before and after 2, 4, 8 and 12 weeks of exercise training. Muscle fibre size, myonuclear content, myonuclear domain size and satellite cell content were assessed by immunohistochemistry. Type I and type II muscle fibre size increased gradually throughout the 12 weeks of training (type I: 18 ± 5%, type II: 41 ± 6%, P muscle fibres. No changes in type I and type II myonuclear domain size were observed at any time point throughout the intervention. Satellite cell content increased significantly over time in both type I and type II muscle fibres (P muscle fibre hypertrophy during prolonged resistance-type exercise training in vivo in humans. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  17. Preceding Vehicle Detection and Tracking Adaptive to Illumination Variation in Night Traffic Scenes Based on Relevance Analysis

    Science.gov (United States)

    Guo, Junbin; Wang, Jianqiang; Guo, Xiaosong; Yu, Chuanqiang; Sun, Xiaoyan

    2014-01-01

    Preceding vehicle detection and tracking at nighttime are challenging problems due to the disturbance of other extraneous illuminant sources coexisting with the vehicle lights. To improve the detection accuracy and robustness of vehicle detection, a novel method for vehicle detection and tracking at nighttime is proposed in this paper. The characteristics of taillights in the gray level are applied to determine the lower boundary of the threshold for taillights segmentation, and the optimal threshold for taillight segmentation is calculated using the OTSU algorithm between the lower boundary and the highest grayscale of the region of interest. The candidate taillight pairs are extracted based on the similarity between left and right taillights, and the non-vehicle taillight pairs are removed based on the relevance analysis of vehicle location between frames. To reduce the false negative rate of vehicle detection, a vehicle tracking method based on taillights estimation is applied. The taillight spot candidate is sought in the region predicted by Kalman filtering, and the disturbed taillight is estimated based on the symmetry and location of the other taillight of the same vehicle. Vehicle tracking is completed after estimating its location according to the two taillight spots. The results of experiments on a vehicle platform indicate that the proposed method could detect vehicles quickly, correctly and robustly in the actual traffic environments with illumination variation. PMID:25195855

  18. Necessity of mycorrhizal re-inoculation in the transplantation of banana in areas with precedent of inoculated canavalia with AMF

    Directory of Open Access Journals (Sweden)

    Jaime Enrique Simó González

    2016-07-01

    Full Text Available From being the banana, a mycotrophic crop and previous results on the potential of green manure inoculated as a way to mycorrhizal economic crops, this work was developed in order to assess whether a precedent Canavalia ensiformis cultivation, inoculated with efficient strains of arbuscular mycorrhizal fungi (AMF inoculation, it is necessary the banana inoculation, ‘FHIA-18’ (AAAB cultivar in the transplant field. Four treatments were evaluated: a control without application of fertilizers and other organic-mineral fertilizers (100% FOM, both without canavalia and two other treatments that are used above canavalia inoculated AMF and half also received organic-mineral fertilizer applications: (50% FOM, one of which, the banana was reinoculated in the transplant field and the other one not. The experimental design used, was randomized blocks, with four replications. The experiment ended after three productive cycles (mother plant, stems 1 and 2. Canavalia inoculated treatments and 50 % of FOM, guaranteed high yields and satisfactory nutritional content similar to that received 100 % of FOM and significantly higher than those obtained with the control treatment. This together with the values of colonization percentages and pores at both high and inoculated treatments were no significant differences between them, indicated not only the effectiveness of mycorrhizal inoculation but rather green manure inoculation was successful to inoculate bananas and re-inoculation of the same was not needed on the transplant.

  19. Effectiveness of a Training Program based in PRECEDE Model on Fruit and Vegetable Consumption among Female Students

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    Ali Khani Jeihooni

    2017-10-01

    Full Text Available Background Fruit and vegetable consumption increases students' health and growth and strengthens their mental activities. The present study aimed to investigates a training program based on PRECEDE model on fruit and vegetable consumption by female students in high schools of Fasa, Iran. Materials and Methods This is a quasi –experimental study. The research sample includes 100 female high school students in Fasa city, Fars Province, Iran, who were randomly assigned to two groups of control (n=50 and experimental (n=50 groups. Data collection instrument was a questionnaire that included items on demographic characteristics and the PERCEDE model components (knowledge, attitude, enabling and reinforcing factors and performance. Educational intervention for the experimental group was carried out in four sessions which each lasting 55 to 60 minutes, and subjects were followed for 2 months. The questionnaires were administered to both groups before and 3 months after the intervention. The collected data was analyzed by SPSS version 18.0 statistical software. Results The average performance score of experimental and control groups regarding fruits and vegetables consumption was 15.15±2.44 and 14.96±2.12 (before the intervention and 28.22±2.22 and 16.1±11.32 (after the intervention. Mean scores of predisposing (knowledge and attitude, reinforcing, and enabling factors showed a significant difference in the experimental group in comparison the control group (P

  20. Land surface anomalies preceding the 2010 Russian heat wave and a link to the North Atlantic oscillation

    International Nuclear Information System (INIS)

    Wright, Christopher K; Henebry, Geoffrey M; De Beurs, Kirsten M

    2014-01-01

    The Eurasian wheat belt (EWB) spans a region across Eastern Ukraine, Southern Russia, and Northern Kazakhstan; accounting for nearly 15% of global wheat production. We assessed land surface conditions across the EWB during the early growing season (April–May–June; AMJ) leading up to the 2010 Russian heat wave, and over a longer-term period from 2000 to 2010. A substantial reduction in early season values of the normalized difference vegetation index occurred prior to the Russian heat wave, continuing a decadal decline in early season primary production in the region. In 2010, an anomalously cold winter followed by an abrupt shift to a warmer-than-normal early growing season was consistent with a persistently negative phase of the North Atlantic oscillation (NAO). Regression analyses showed that early season vegetation productivity in the EWB is a function of both the winter (December–January–February; DJF) and AMJ phases of the NAO. Land surface anomalies preceding the heat wave were thus consistent with highly negative values of both the DJF NAO and AMJ NAO in 2010. (letter)

  1. Altered growth pattern, not altered growth per se, is the hallmark of early lesions preceding cancer development.

    Science.gov (United States)

    Doratiotto, S; Marongiu, F; Faedda, S; Pani, P; Laconi, E

    2009-01-01

    Many human solid cancers arise from focal proliferative lesions that long precede the overt clinical appearance of the disease. The available evidence supports the notion that cancer precursor lesions are clonal in origin, and this notion forms the basis for most of the current theories on the pathogenesis of neoplastic disease. In contrast, far less attention has been devoted to the analysis of the phenotypic property that serves to define these focal lesions, i.e. their altered growth pattern. In fact, the latter is often considered a mere morphological by-product of clonal growth, with no specific relevance in the process. In the following study, evidence will be presented to support the concept that focal growth pattern is an inherent property of altered cells, independent of clonal growth; furthermore, it will be discussed how such a property, far from being merely descriptive, might indeed play a fundamental role in the sequence of events leading to the development of cancer. Within this paradigm, the earliest steps of neoplasia should be considered and analysed as defects in the mechanisms of tissue pattern formation.

  2. Reduced translocation of current photosynthate precedes changes in gas exchange for Quercus rubra seedlings under flooding stress.

    Science.gov (United States)

    Sloan, Joshua L; Islam, M Anisul; Jacobs, Douglass F

    2016-01-01

    Northern red oak (Quercus rubra L.) seedlings are frequently planted on suboptimal sites in their native range in North America, subjecting them to environmental stresses, such as flooding, for which they may not be well adapted. Members of the genus Quercus exhibit a wide range of responses to flooding, and responses of northern red oak to flooding remain inadequately described. To better understand the physiological effects of root system inundation in post-transplant northern red oak seedlings and the effects of flooding on endogenous patterns of resource allocation within the plant, we observed the effects of short-term flooding initiated at the linear shoot growth stage on net photosynthetic rates, dark respiration, chlorophyll fluorescence (Fv/Fm) and translocation of (13)C-labeled current photosynthate. Downward translocation of current photosynthate declined after 4 days of flooding and was the first measured physiological response to flooding; net photosynthetic rates decreased and dark respiration rates increased after 7 days of flooding. Short-term flooding did not affect maximal potential efficiency of photosystem II (Fv/Fm). The finding that decreased downward translocation of (13)C-labeled current photosynthate preceded reduced net photosynthesis and increased dark respiration during flooding suggests the occurrence of sink-limited photosynthesis under these conditions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. A PRECEDE-PROCEED based educational intervention in quality of life of women-headed households in Iran.

    Science.gov (United States)

    Solhi, Mahnaz; Shabani Hamedan, Marziyeh; Salehi, Masoud

    2016-01-01

    Background: Women-headed households are more exposed to social damages than other women. Such condition remarkably influences the women's health-related life quality. The present study is aimed to investigate the effect of an educational intervention in quality of life of women-headed households under protection of Tehran Welfare Organization, in 2015. Methods: In this quasi-experimental study with control group, 180 women-headed households participated. Sampling method was random allocation. Data collection tools were Life Quality standard questionnaire (WHOQOL-BREF) and a researcher-made questionnaire about structures of ecological and educational diagnosis phase of PRECEDE-PROCEED model. Validity and reliability of the questionnaire approved in a primary study. Based on the results obtained from the primary study, the intervention was performed in the case group only. Participants were followed one and three months after intervention. Data were analyzed through SPSS v. 15 software using descriptive and analytical tests. Results: Before intervention no significant difference was observed among the mean scores of life quality, behavioral factors, and knowledge, enabling, and reinforcing factors in the two groups. But, one month and three months after intervention a significant difference was observed between the mean scores of these variables (in five instances pquality of life. The innovation of this study is using such intervention on quality of life in women-headed households for the first time.

  4. Anticipatory kinematics and muscle activity preceding transitions from level-ground walking to stair ascent and descent.

    Science.gov (United States)

    Peng, Joshua; Fey, Nicholas P; Kuiken, Todd A; Hargrove, Levi J

    2016-02-29

    The majority of fall-related accidents are during stair ambulation-occurring commonly at the top and bottom stairs of each flight, locations in which individuals are transitioning to stairs. Little is known about how individuals adjust their biomechanics in anticipation of walking-stair transitions. We identified the anticipatory stride mechanics of nine able-bodied individuals as they approached transitions from level ground walking to stair ascent and descent. Unlike prior investigations of stair ambulation, we analyzed two consecutive "anticipation" strides preceding the transitions strides to stairs, and tested a comprehensive set of kinematic and electromyographic (EMG) data from both the leading and trailing legs. Subjects completed ten trials of baseline overground walking and ten trials of walking to stair ascent and descent. Deviations relative to baseline were assessed. Significant changes in mechanics and EMG occurred in the earliest anticipation strides analyzed for both ascent and descent transitions. For stair descent, these changes were consistent with observed reductions in walking speed, which occurred in all anticipation strides tested. For stair ascent, subjects maintained their speed until the swing phase of the latest anticipation stride, and changes were found that would normally be observed for decreasing speed. Given the timing and nature of the observed changes, this study has implications for enhancing intent recognition systems and evaluating fall-prone or disabled individuals, by testing their abilities to sense upcoming transitions and decelerate during locomotion. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. TET-Catalyzed 5-Hydroxymethylation Precedes HNF4A Promoter Choice during Differentiation of Bipotent Liver Progenitors

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    Pierre-Benoit Ancey

    2017-07-01

    Full Text Available Understanding the processes that govern liver progenitor cell differentiation has important implications for the design of strategies targeting chronic liver diseases, whereby regeneration of liver tissue is critical. Although DNA methylation (5mC and hydroxymethylation (5hmC are highly dynamic during early embryonic development, less is known about their roles at later stages of differentiation. Using an in vitro model of hepatocyte differentiation, we show here that 5hmC precedes the expression of promoter 1 (P1-dependent isoforms of HNF4A, a master transcription factor of hepatocyte identity. 5hmC and HNF4A expression from P1 are dependent on ten-eleven translocation (TET dioxygenases. In turn, the liver pioneer factor FOXA2 is necessary for TET1 binding to the P1 locus. Both FOXA2 and TETs are required for the 5hmC-related switch in HNF4A expression. The epigenetic event identified here may be a key step for the establishment of the hepatocyte program by HNF4A.

  6. The role of stressful life events preceding death by suicide: Evidence from two samples of suicide decedents.

    Science.gov (United States)

    Buchman-Schmitt, Jennifer M; Chu, Carol; Michaels, Matthew S; Hames, Jennifer L; Silva, Caroline; Hagan, Christopher R; Ribeiro, Jessica D; Selby, Edward A; Joiner, Thomas E

    2017-10-01

    Stressful life events (SLEs) are associated with increased risk for suicidal behavior. Less is known regarding the intensity of SLEs and how this may vary as a function of suicide attempt history. As a large percentage of suicide decedents do not have a history of suicidal behavior, SLEs precipitating suicide may help characterize suicidality in this understudied population. This paper examines the intensity, number, and accumulation of SLEs preceding death by suicide among decedents with varying suicide attempt histories. Suicide attempts, SLEs, and suicide methods were examined in two samples: 62 prison-based and 117 community-based suicide decedents. Regression was used to compare the level of stressor precipitating death by suicide in decedents who died on a first attempt versus multiple previous attempts. A non-significant trend was observed in the prison population which was supported by significant findings in the community-based sample. Decedents who died on a first attempt experienced a stressor of a lower magnitude when compared to decedents with multiple previous suicide attempts. We discuss the implications of these findings in relation to the stress-diathesis model for suicide. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Effect of age on upregulation of the cardiac adrenergic beta receptors

    International Nuclear Information System (INIS)

    Tumer, N.; Houck, W.T.; Roberts, J.

    1990-01-01

    Radioligand binding studies were performed to determine whether upregulation of postjunctional beta receptors occurs in sympathectomized hearts of aged animals. Fischer 344 rats 6, 12, and 24 months of age (n = 10) were used in these experiments. To produce sympathectomy, rats were injected with 6-hydroxydopamine hydrobromide (6-OHDA; 2 x 50 mg/kg iv) on days 1 and 8; the animals were decapitated on day 15. The depletion of norepinephrine in the heart was about 86% in each age group. 125I-Iodopindolol (IPIN), a beta adrenergic receptor antagonist, was employed to determine the affinity and total number of beta adrenergic receptors in the ventricles of the rat heart. The maximal number of binding sites (Bmax) was significantly elevated by 37%, 48%, and 50% in hearts from sympathectomized 6-, 12-, and 24-month-old rats, respectively. These results indicate that beta receptor mechanisms in older hearts can respond to procedures that cause upregulation of the beta adrenergic receptors

  8. Prickly pear induces upregulation of liver LDL binding in familial heterozygous hypercholesterolemia

    International Nuclear Information System (INIS)

    Palumbo, B.; Palumbo, R.; Efthimiou, Y.; Stamatopoulos, J.; Sinzinger, H.; Oguogho, A.; Budinsky, A.; Sinzinger, H.

    2003-01-01

    The hypoglycemic effect of prickly pear is well known by native local Indian population since a long time. Beside the beneficial effects on lipid metabolism, oxidation injury and platelet function has been claimed in experimental animals. We recently found an upregulation of apo-B/E receptor. We therefore examined 10 patients with isolated heterozygous familial hypercholesterolemia (FH) being enrolled in a dietary run-in phase of 6 weeks after dietary counselling and a further 6 weeks of prickly pear addition. Uptake of autologous 123 I-radiolabeled LDL was determined at entry as well as after 6 weeks of daily prickly pear ingestion. We found a significant (p 176.4 mg/dl; p 123 I-LDL binding by prickly pear in FH-patients in vivo and indicate that prickly pear exerts a significant hypolipidemic action via receptor upregulation. (author)

  9. Triazophos up-regulated gene expression in the female brown planthopper, Nilaparvata lugens.

    Science.gov (United States)

    Bao, Yan-Yuan; Li, Bao-Ling; Liu, Zhao-Bu; Xue, Jian; Zhu, Zeng-Rong; Cheng, Jia-An; Zhang, Chuan-Xi

    2010-09-01

    The widespread use of insecticides has caused the resurgence of the brown planthopper, Nilaparvata lugens, in Asia. In this study, we investigated an organo-phosphorous insecticide, triazophos, and its ability to induce gene expression variation in female N. lugens nymphs just before emergence. By using the suppression subtractive hybridization method, a triazophos-induced cDNA library was constructed. In total, 402 differentially expressed cDNA clones were obtained. Real-time qPCR analysis confirmed that triazophos up-regulated the expression of six candidate genes at the transcript level in nymphs on day 3 of the 5th instar. These genes encode N. lugens vitellogenin, bystin, multidrug resistance protein (MRP), purine nucleoside phosphorylase (PNP), pyrroline-5-carboxylate reductase (P5CR) and carboxylesterase. Our results imply that the up-regulation of these genes may be involved in the induction of N. lugens female reproduction or resistance to insecticides.

  10. Gene up-regulation in response to predator kairomones in the water flea, Daphnia pulex

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    Okada Yasukazu

    2010-04-01

    Full Text Available Abstract Background Numerous cases of predator-induced polyphenisms, in which alternate phenotypes are produced in response to extrinsic stimuli, have been reported in aquatic taxa to date. The genus Daphnia (Branchiopoda, Cladocera provides a model experimental system for the study of the developmental mechanisms and evolutionary processes associated with predator-induced polyphenisms. In D. pulex, juveniles form neckteeth in response to predatory kairomones released by Chaoborus larvae (Insecta, Diptera. Results Previous studies suggest that the timing of the sensitivity to kairomones in D. pulex can generally be divided into the embryonic and postembryonic developmental periods. We therefore examined which of the genes in the embryonic and first-instar juvenile stages exhibit different expression levels in the presence or absence of predator kairomones. Employing a candidate gene approach and identifying differentially-expressed genes revealed that the morphogenetic factors, Hox3, extradenticle and escargot, were up-regulated by kairomones in the postembryonic stage and may potentially be responsible for defense morph formation. In addition, the juvenile hormone pathway genes, JHAMT and Met, and the insulin signaling pathway genes, InR and IRS-1, were up-regulated in the first-instar stage. It is well known that these hormonal pathways are involved in physiological regulation following morphogenesis in many insect species. During the embryonic stage when morphotypes were determined, one of the novel genes identified by differential display was up-regulated, suggesting that this gene may be related to morphotype determination. Biological functions of the up-regulated genes are discussed in the context of defense morph formation. Conclusions It is suggested that, following the reception of kairomone signals, the identified genes are involved in a series of defensive phenotypic alterations and the production of a defensive phenotype.

  11. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

    2016-04-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  12. Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn.

    Science.gov (United States)

    Sei, Hiroo; Oshima, Tadayuki; Shan, Jing; Wu, Liping; Yamasaki, Takahisa; Okugawa, Takuya; Kondo, Takashi; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

    2016-01-01

    Interleukin-33 (IL-33) is a tissue-derived cytokine that is constitutively expressed in epithelial cells of tissues exposed to the environment and plays a role in sensing damage caused by inflammatory diseases. IL-33 acts as both a traditional cytokine and as a chromatin-associated nuclear factor in both innate and adaptive immunity. We recently showed that IL-33 in esophageal mucosa is upregulated in reflux esophagitis. However, IL-33 expression in patients with heartburn without mucosal injury and its relationship with intercellular space (ICS) have never been examined. We therefore examined the expression of cytokines and ICS in patients with heartburn. The expression of IL-33 in the middle and distal esophageal mucosa of patients with heartburn without mucosal break and control samples was examined using real-time RT-PCR and immunofluorescence. The mRNA expression of IL-6, IL-8, MCP-1, and RANTES, and ICS was also analyzed. IL-33 expression and the mean ICS were significantly increased in the mucosa of patients with heartburn compared to that of the control. IL-33 and ICS were not different between the patients who were taking a PPI and those who were not. The upregulated IL-33 expression in the heartburn group was located in the nuclei of the basal cell layer. Although IL-6, IL-8, MCP-1 and RANTES levels were not different between control and patients with heartburn samples, IL-33 mRNA levels were still significantly correlated with IL-6, IL-8, or MCP-1 mRNA levels. Nuclear IL-33 is upregulated in patients with heartburn. Upregulated IL-33 in heartburn patients is related to the symptoms.

  13. Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn.

    Directory of Open Access Journals (Sweden)

    Hiroo Sei

    Full Text Available Interleukin-33 (IL-33 is a tissue-derived cytokine that is constitutively expressed in epithelial cells of tissues exposed to the environment and plays a role in sensing damage caused by inflammatory diseases. IL-33 acts as both a traditional cytokine and as a chromatin-associated nuclear factor in both innate and adaptive immunity. We recently showed that IL-33 in esophageal mucosa is upregulated in reflux esophagitis. However, IL-33 expression in patients with heartburn without mucosal injury and its relationship with intercellular space (ICS have never been examined. We therefore examined the expression of cytokines and ICS in patients with heartburn.The expression of IL-33 in the middle and distal esophageal mucosa of patients with heartburn without mucosal break and control samples was examined using real-time RT-PCR and immunofluorescence. The mRNA expression of IL-6, IL-8, MCP-1, and RANTES, and ICS was also analyzed.IL-33 expression and the mean ICS were significantly increased in the mucosa of patients with heartburn compared to that of the control. IL-33 and ICS were not different between the patients who were taking a PPI and those who were not. The upregulated IL-33 expression in the heartburn group was located in the nuclei of the basal cell layer. Although IL-6, IL-8, MCP-1 and RANTES levels were not different between control and patients with heartburn samples, IL-33 mRNA levels were still significantly correlated with IL-6, IL-8, or MCP-1 mRNA levels.Nuclear IL-33 is upregulated in patients with heartburn. Upregulated IL-33 in heartburn patients is related to the symptoms.

  14. Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy

    OpenAIRE

    Zabirnyk, Olga; Liu, Wei; Khalil, Shadi; Sharma, Anit; Phang, James M.

    2009-01-01

    Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible ...

  15. Catalase activity prevents exercise-induced up-regulation of vasoprotective proteins in venous tissue.

    Science.gov (United States)

    Dao, Vu Thao-Vi; Floeren, Melanie; Kumpf, Stephanie; Both, Charlotte; Peter, Bärbel; Balz, Vera; Suvorava, Tatsiana; Kojda, Georg

    2011-11-01

    Physical activity induces favourable changes of arterial gene expression and protein activity, although little is known about its effect in venous tissue. Although our understanding of the initiating molecular signals is still incomplete, increased expression of endothelial nitric oxide synthase (eNOS) is considered a key event. This study sought to investigate the effects of two different training protocols on the expression of eNOS and extracellular superoxide dismutase (ecSOD) in venous and lung tissue and to evaluate the underlying molecular mechanisms. C57Bl/6 mice underwent voluntary exercise or forced physical activity. Changes of vascular mRNA and protein levels and activity of eNOS, ecSOD and catalase were determined in aorta, heart, lung and vena cava. Both training protocols similarly increased relative heart weight and resulted in up-regulation of aortic and myocardial eNOS. In striking contrast, eNOS expression in vena cava and lung remained unchanged. Likewise, exercise up-regulated ecSOD in the aorta and in left ventricular tissue but remained unchanged in lung tissue. Catalase expression in lung tissue and vena cava of exercised mice exceeded that in aorta by 6.9- and 10-fold, respectively, suggesting a lack of stimulatory effects of hydrogen peroxide. In accordance, treatment of mice with the catalase inhibitor aminotriazole for 6 weeks resulted in significant up-regulation of eNOS and ecSOD in vena cava. These data suggest that physiological venous catalase activity prevents exercise-induced up-regulation of eNOS and ecSOD. Furthermore, therapeutic inhibition of vascular catalase might improve pulmonary rehabilitation. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  16. Fenofibrate suppressed proliferation and migration of human neuroblastoma cells via oxidative stress dependent of TXNIP upregulation

    Energy Technology Data Exchange (ETDEWEB)

    Su, Cunjin; Shi, Aiming; Cao, Guowen [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Tao, Tao [Department of Urology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009 (China); Chen, Ruidong [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Hu, Zhanhong; Shen, Zhu; Tao, Hong; Cao, Bin [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Hu, Duanmin, E-mail: hudmsdfey@sina.com [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Bao, Junjie, E-mail: baojjsdfey@sina.com [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China)

    2015-05-15

    There are no appropriate drugs for metastatic neuroblastoma (NB), which is the most common extra-cranial solid tumor for childhood. Thioredoxin binding protein (TXNIP), the endogenous inhibitor of ROS elimination, has been identified as a tumor suppressor in various solid tumors. It reported that fenofibrate exerts anti-tumor effects in several human cancer cell lines. However, its detail mechanisms remain unclear. The present study assessed the effects of fenofibrate on NB cells and investigated TXNIP role in its anti-tumor mechanisms. We used MTT assay to detect cells proliferation, starch wound test to investigate cells migration, H{sub 2}DCF-DA to detect intracellular ROS, siRNA to interfere TXNIP and peroxisome proliferator-androgen receptor-alpha (PPAR-α) expression, western blot to determine protein levels, flow cytometry to analyze apoptosis. Fenofibrate suppressed proliferation and migration of NB cells, remarkably increased intracellular ROS, upregulated TXNIP expression, promoted cell apoptosis. Furthermore, inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. Our results indicated the anti-tumor role of fenofibrate on NB cells by exacerbating oxidative stress and inducing apoptosis was dependent on the upregulation of TXNIP. - Highlights: • We found that fenofibrate suppressed proliferation and migration of NB cells. • We found that fenofibrate remarkably increased intracellular ROS, upregulated TXNIP expression, and promoted cell apoptosis. • Inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. • Our results indicated the anti-tumor role of fenofibrate on NB cells was dependent on the upregulation of TXNIP.

  17. Generation of a mouse model for studying the role of upregulated RTEL1 activity in tumorigenesis

    OpenAIRE

    Wu, Xiaoli; Sandhu, Sumit; Nabi, Zinnatun; Ding, Hao

    2012-01-01

    Regulator of telomere length 1 (RTEL1) is a DNA helicase protein that has been demonstrated to be required for the maintenance of telomere length and genomic stability. It has also been found to be essential for DNA homologous recombination during DNA repairing. Human RTEL1 genomic locus (20q13.3) is frequently amplified in multiple types of human cancers, including hepatocellular carcinoma and gastrointestinal tract tumors, indicating that upregulated RTEL1 activity could be important for tu...

  18. Appendix 1:Upregulated genes in gene expression profile (P<0.05 ...

    Indian Academy of Sciences (India)

    lazi

    Appendix 1: Upregulated genes in gene expression profile«P2). Probe_s. Gene_Symbol pvalues foldchange. Probe_S. et_ID. Gene_Symbol pvalues foldchange. et_ID. 1370355. 1393751. Scd1. 1.35E-04. 25.77. Loc1009122508.06E-03. 2.55. -at at. 1398250. 1370870. Acot1. 2.43E-02. 12.18. Me1.

  19. LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma.

    Science.gov (United States)

    Yun-Bo, Feng; Xiao-Po, Liu; Xiao-Li, Li; Guo-Long, Cao; Pei, Zhang; Fa-Ming, Tian

    2016-01-01

    To examine the expression and function of long non-coding RNA taurine up-regulated 1 ( TUG1 ) in human osteosarcoma cells. Real-time quantitive PCR was used to detect the transcription level of TUG1 in a series of osteosarcoma cell lines. Knockdown of TUG1 in U2OS cells was carried out by transient transfection of siRNAs. MTT assay was performed to access the cell growth rates. Afterwards, RNA and protein of these cells were extracted to analyze the transfection efficient as well as the expression of other molecules. Compared to the normal cell line, TUG1 exhibited a significant upregulation in osteosarcoma cells. Phenotyping analysis showed the growth-promotion activity of TUG1 , since knockdown of TUG1 resulted in declined proliferation. We also found that AKT phosphorylation was impaired after TUG1 was inhibited, suggesting that the AKT pathway was involved in the regulation of TUG1 in U2OS cells. Our data provided evidence that TUG1 was upregulated and acted as a possible oncogene via positively regulating cell proliferation in osteosarcoma cells.

  20. Short-term mastication after weaning upregulates GABAergic signalling and reduces dendritic spine in thalamus.

    Science.gov (United States)

    Ogawa, Mana; Nagai, Toshitada; Saito, Yoshikazu; Miyaguchi, Hitonari; Kumakura, Kei; Abe, Keiko; Asakura, Tomiko

    2018-04-06

    Mastication enhances brain function and mental health, but little is known about the molecular mechanisms underlying the effects of mastication on neural development in early childhood. Therefore, we analysed the gene expression in juvenile neural circuits in rats fed with a soft or chow diet immediately after weaning. We observed that the gene expression patterns in the thalamus varied depending on the diet. Furthermore, gene ontology analysis revealed that two terms were significantly enhanced: chemical synaptic transmission and positive regulation of dendritic spine morphogenesis. With respect to chemical synaptic transmission, glutamate decarboxylase and GABA receptors were upregulated in the chow diet group. The related genes, including vesicular GABA transporter, were also upregulated, suggesting that mastication activates GABAergic signalling. With respect to dendritic spine morphogenesis, Ingenuity Pathway Analysis predicted fewer extension of neurites and neurons and fewer number of branches in the chow diet group. The numbers of spines in the ventral posterolateral and posteromedial regions were significantly decreased. These results suggest that mastication in the early developing period upregulates GABAergic signalling genes, with a decrease of spines in the thalamus. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein

    Directory of Open Access Journals (Sweden)

    Rui-Xin Yang

    2017-06-01

    Full Text Available Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB, against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro. SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

  2. Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein.

    Science.gov (United States)

    Yang, Rui-Xin; Lei, Jie; Wang, Bo-Dong; Feng, Da-Yun; Huang, Lu; Li, Yu-Qian; Li, Tao; Zhu, Gang; Li, Chen; Lu, Fang-Fang; Nie, Tie-Jian; Gao, Guo-Dong; Gao, Li

    2017-01-01

    Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R) injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB), against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro . SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

  3. Six1 promotes proliferation of pancreatic cancer cells via upregulation of cyclin D1 expression.

    Directory of Open Access Journals (Sweden)

    Zhaoming Li

    Full Text Available Six1 is one of the transcription factors that act as master regulators of development and are frequently dysregulated in cancers. However, the role of Six1 in pancreatic cancer is not clear. Here we show that the relative expression of Six1 mRNA is increased in pancreatic cancer and correlated with advanced tumor stage. In vitro functional assays demonstrate that forced overexpression of Six1 significantly enhances the growth rate and proliferation ability of pancreatic cancer cells. Knockdown of endogenous Six1 decreases the proliferation of these cells dramatically. Furthermore, Six1 promotes the growth of pancreatic cancer cells in a xenograft assay. We also show that the gene encoding cyclin D1 is a direct transcriptional target of Six1 in pancreatic cancer cells. Overexpression of Six1 upregulates cyclin D1 mRNA and protein, and significantly enhances the activity of the cyclin D1 promoter in PANC-1 cells. We demonstrate that Six1 promotes cell cycle progression and proliferation by upregulation of cyclin D1. These data suggest that Six1 is overexpressed in pancreatic cancer and may contribute to the increased cell proliferation through upregulation of cyclin D1.

  4. P53-dependent upregulation of neutral sphingomyelinase-2: role in doxorubicin-induced growth arrest.

    Science.gov (United States)

    Shamseddine, A A; Clarke, C J; Carroll, B; Airola, M V; Mohammed, S; Rella, A; Obeid, L M; Hannun, Y A

    2015-10-29

    Neutral sphingomyelinase-2 (nSMase2) is a ceramide-generating enzyme that has been implicated in growth arrest, apoptosis and exosome secretion. Although previous studies have reported transcriptional upregulation of nSMase2 in response to daunorubicin, through Sp1 and Sp3 transcription factors, the role of the DNA damage pathway in regulating nSMase2 remains unclear. In this study, we show that doxorubicin induces a dose-dependent induction of nSMase2 mRNA and protein with concomitant increases in nSMase activity and ceramide levels. Upregulation of nSMase2 was dependent on ATR, Chk1 and p53, thus placing it downstream of the DNA damage pathway. Moreover, overexpression of p53 was sufficient to transcriptionally induce nSMase2, without the need for DNA damage. DNA-binding mutants as well as acetylation mutants of p53 were unable to induce nSMase2, suggesting a role of nSMase2 in growth arrest. Moreover, knockdown of nSMase2 prevented doxorubicin-induced growth arrest. Finally, p53-induced nSMase2 upregulation appears to occur via a novel transcription start site upstream of exon 3. These results identify nSMase2 as a novel p53 target gene, regulated by the DNA damage pathway to induce cell growth arrest.

  5. HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

    Science.gov (United States)

    Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

    2017-08-01

    Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

  6. Fluoride Stimulates the Proliferation of Osteoclasts in vitro by Upregulating MCM3

    Directory of Open Access Journals (Sweden)

    Shengbin Bai

    2016-06-01

    Full Text Available We have previously shown that the expression of the minichromosome maintenance protein 3 (MCM3 gene was upregulated in lymphocytes of patients with skeletal fluorosis. We speculated that increased MCM3 expression may be contribute to osteopathy in patients with skeletal fluorosis. Here, we investigated the effect of fluoride on the proliferation of osteoclasts derived from RAW264.7 cells and the involvement of MCM3. Our MTT assays showed that 0.25 mM NaF markedly stimulated the proliferation of RAW264.7 cells. The RT-PCR and immunoblotting assays revealed that 0.25 mM NaF upregulated MCM3 expression in RAW264.7 cells. The MTT assays additionally demonstrated that stimulation with MCM3 potentiated the effect of fluorine on the proliferation of RAW264.7 cells. These results demonstrated that fluoride at clinical relevant concentration upregulates MCM3 expression in osteoclasts in vitro. We are currently conducting a series of experiments to examine whether increased MCM3 in osteoclasts indeed contributes to osteopathy in skeletal fluorosis.

  7. Lysophosphatidic Acid Upregulates Laminin-332 Expression during A431 Cell Colony Dispersal

    Directory of Open Access Journals (Sweden)

    Hironobu Yamashita

    2010-01-01

    Full Text Available Lysophosphatidic acid (LPA is a bioactive phospholipid that affects various biological functions, such as cell proliferation, migration, survival, wound healing, and tumor invasion through LPA receptors. Previously, we reported that LPA induces A431 colony dispersal, accompanied by disruption of cell-cell contacts and cell migration. However, it remains unclear how LPA affects cell migration and gene expression during A431 colony dispersal. In this paper, we performed cDNA microarray analysis to investigate this question by comparing gene expression between untreated and LPA-treated A431 cells. Interestingly, these results revealed that LPA treatment upregulates several TGF-β1 target genes, including laminin-332 (Ln-332 components (α3, β3, and γ2 chains. Western blot analysis also showed that LPA increased phosphorylation of Smad2, an event that is carried out by TGF-β1 interactions. Among the genes upregulated, we further addressed the role of Ln-332. Real-time PCR analysis confirmed the transcriptional upregulation of all α3, β3, and γ2 chains of Ln-332 by LPA, corresponding to the protein level increases revealed by western blot. Further, the addition of anti-Ln-332 antibody prevented LPA-treated A431 colonies from dispersing. Taken together, our results suggest that LPA-induced Ln-332 plays a significant role in migration of individual cells from A431 colonies.

  8. Atomistic mechanism of microRNA translation upregulation via molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Wei Ye

    Full Text Available MicroRNAs are endogenous 23-25 nt RNAs that play important gene-regulatory roles in animals and plants. Recently, miR369-3 was found to upregulate translation of TNFα mRNA in quiescent (G0 mammalian cell lines. Knock down and immunofluorescence experiments suggest that microRNA-protein complexes (with FXR1 and AGO2 are necessary for the translation upregulation. However the molecular mechanism of microRNA translation activation is poorly understood. In this study we constructed the microRNA-mRNA-AGO2-FXR1 quadruple complex by bioinformatics and molecular modeling, followed with all atom molecular dynamics simulations in explicit solvent to investigate the interaction mechanisms for the complex. A combined analysis of experimental and computational data suggests that AGO2-FXR1 complex relocalize microRNA:mRNA duplex to polysomes in G0. The two strands of dsRNA are then separated upon binding of AGO2 and FXR1. Finally, polysomes may improve the translation efficiency of mRNA. The mutation research confirms the stability of microRNA-mRNA-FXR1 and illustrates importance of key residue of Ile304. This possible mechanism can shed more light on the microRNA-dependent upregulation of translation.

  9. LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma

    Directory of Open Access Journals (Sweden)

    Yun-Bo Feng

    2016-01-01

    Full Text Available Objective: To examine the expression and function of long non-coding RNA taurine up-regulated 1 (TUG1 in human osteosarcoma cells. Methods: Real-time quantitive PCR was used to detect the transcription level of TUG1 in a series of osteosarcoma cell lines. Knockdown of TUG1 in U2OS cells was carried out by transient transfection of siRNAs. MTT assay was performed to access the cell growth rates. Afterwards, RNA and protein of these cells were extracted to analyze the transfection efficient as well as the expression of other molecules. Results: Compared to the normal cell line, TUG1 exhibited a significant upregulation in osteosarcoma cells. Phenotyping analysis showed the growth-promotion activity of TUG1, since knockdown of TUG1 resulted in declined proliferation. We also found that AKT phosphorylation was impaired after TUG1 was inhibited, suggesting that the AKT pathway was involved in the regulation of TUG1 in U2OS cells. Conclusion: Our data provided evidence that TUG1 was upregulated and acted as a possible oncogene via positively regulating cell proliferation in osteosarcoma cells.

  10. N-Cadherin Upregulation Promotes the Neurogenic Differentiation of Menstrual Blood-Derived Endometrial Stem Cells.

    Science.gov (United States)

    Liu, Yanli; Yang, Fen; Liang, Shengying; Liu, Qing; Fu, Sulei; Wang, Zhenyu; Yang, Ciqing; Lin, Juntang

    2018-01-01

    Peripheral nerve injuries are typically caused by either trauma or medical disorders, and recently, stem cell-based therapies have provided a promising treatment approach. Menstrual blood-derived endometrial stem cells (MenSCs) are considered an ideal therapeutic option for peripheral nerve repair due to a noninvasive collection procedure and their high proliferation rate and immunological tolerance. Here, we successfully isolated MenSCs and examined their biological characteristics including their morphology, multipotency, and immunophenotype. Subsequent in vitro studies demonstrated that MenSCs express high levels of neurotrophic factors, such as NT3, NT4, BDNF, and NGF, and are capable of transdifferentiating into glial-like cells under conventional induction conditions. Moreover, upregulation of N-cadherin (N-cad) mRNA and protein expression was observed after neurogenic differentiation. In vivo studies clearly showed that N-cad knockdown via in utero electroporation perturbed the migration and maturation of mouse neural precursor cells (NPCs). Finally, a further transfection assay also confirmed that N-cad upregulation in MenSCs results in the expression of S100. Collectively, our results confirmed the paracrine effect of MenSCs on neuroprotection as well as their potential for transdifferentiation into glial-like cells and demonstrated that N-cad upregulation promotes the neurogenic differentiation of MenSCs, thereby providing support for transgenic MenSC-based therapy for peripheral nerve injury.

  11. 20-hydroxyecdysone upregulates Atg genes to induce autophagy in the Bombyx fat body

    Science.gov (United States)

    Tian, Ling; Ma, Li; Guo, Enen; Deng, Xiaojuan; Ma, Sanyuan; Xia, Qingyou; Cao, Yang; Li, Sheng

    2013-01-01

    Autophagy is finely regulated at multiple levels and plays crucial roles in development and disease. In the fat body of the silkworm, Bombyx mori, autophagy occurs and Atg gene expression peaks during the nonfeeding molting and pupation stages when the steroid hormone (20-hydroxyecdysone; 20E) is high. Injection of 20E into the feeding larvae upregulated Atg genes and reduced TORC1 activity resulting in autophagy induction in the fat body. Conversely, RNAi knockdown of the 20E receptor partner (USP) or targeted overexpression of a dominant negative mutant of the 20E receptor (EcRDN) in the larval fat body reduced autophagy and downregulated the Atg genes, confirming the importance of 20E-induction of Atg gene expression during pupation. Moreover, in vitro treatments of the larval fat body with 20E upregulated the Atg genes. Five Atg genes were potentially 20E primary-responsive, and a 20E response element was identified in the Atg1 (ortholog of human ULK1) promoter region. Furthermore, RNAi knockdown of 4 key genes (namely Br-C, E74, HR3 and βftz-F1) in the 20E-triggered transcriptional cascade reduced autophagy and downregulated Atg genes to different levels. Taken together, we conclude that in addition to blocking TORC1 activity for autophagosome initiation, 20E upregulates Atg genes to induce autophagy in the Bombyx fat body. PMID:23674061

  12. Prdx6 Upregulation by Curcumin Attenuates Ischemic Oxidative Damage via SP1 in Rats after Stroke

    Directory of Open Access Journals (Sweden)

    Gongwei Jia

    2017-01-01

    Full Text Available Background. The role of Peroxiredoxin 6 (Prdx6 in brain ischemia remains unclear. Curcumin (Cur treatment elicits neuroprotective effects against cerebral ischemic injury, and the associated mechanisms may involve Prdx6. In this study, we investigated whether Prdx6 and the transcription factor specific protein 1 (SP1 were involved in the antioxidant effect of Cur after stoke. Methods. Focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 2 hours in male Sprague-Dawley rats treated with or without Prdx6 siRNA. Expression of Prdx6 in the penumbra was assessed by Real-Time PCR (RT-PCR, Western blot analysis, and immunoflourescent staining. In addition, infarct volume, neurological deficit score, and oxidative stress were evaluated. Prdx6 levels were also determined in the presence and absence of SP1 antagonist mithramycin A (MTM-A. Results. Cur treatment upregulated Prdx6 protein expression and the number of Prdx6-positive neuronal cells 24 hours after reperfusion. Cur treatment also attenuated oxidative stress and induced neuroprotective effects against ischemic damage, whereas the beneficial effects of Cur treatment were lost in animals treated with Prdx6-siRNA. Prdx6 upregulation by Cur treatment was abolished by SP1 antagonists MTM. Conclusions. Prdx6 upregulation by Cur treatment attenuates ischemic oxidative damage through SP1 induction in rats after stroke. This represents a novel mechanism of Cur-induced neuroprotection against cerebral ischemia.

  13. Apoptosis inhibitor 5 (API-5; AAC-11; FIF) is upregulated in human carcinomas in vivo.

    Science.gov (United States)

    Koci, Lenka; Chlebova, Katarina; Hyzdalova, Martina; Hofmanova, Jirina; Jira, Miroslav; Kysela, Petr; Kozubik, Alois; Kala, Zdenek; Krejci, Pavel

    2012-04-01

    Apoptosis inhibitor 5 (API-5) is a 55 kDa nuclear protein with potent anti-apoptotic signaling in tumor cells in vitro. In this study, we analyzed the expression of the API-5 protein in vivo in a broad spectrum of human carcinomas, including those of the colon, lung, liver, kidney, pancreas, stomach and esophagus using tumor tissues obtained during tumor resection. The results showed significant upregulation of API-5 expression in biopsies of lung (23%, n=13) and colorectal tumors (33%, n=27) in comparison with biopsies from the adjacent normal tissue. Colon cancer biopsies were used to study the cell populations with an upregulated level of expression of API-5 more closely. Using a magnetic bead-based selection for the epithelial cell marker EpCAM, we purified epithelial cells from the tumor and control tissues and analyzed these cells for API-5 expression by western immunoblotting. We observed that EpCAM-positive tumor cells expressed API-5 in all three colorectal cancer cases tested, in contrast to the control EpCAM-positive and EpCAM-negative cells isolated from the control or tumor tissues. These data suggest that the expression of the API-5 protein is upregulated in tumor epithelial cells and may serve as a prognostic marker in colorectal cancer.

  14. The Influence of Emotion Upregulation on the Expectation of Sexual Reward.

    Science.gov (United States)

    Brom, Mirte; Laan, Ellen; Everaerd, Walter; Spinhoven, Philip; Trimbos, Baptist; Both, Stephanie

    2016-01-01

    Emotion regulation research has shown successful altering of unwanted aversive emotional reactions. Cognitive strategies can also downregulate expectations of reward arising from conditioned stimuli, including sexual stimuli. However, little is known about whether such strategies can also efficiently upregulate expectations of sexual reward arising from conditioned stimuli, and possible gender differences therein. The present study examined whether a cognitive upregulatory strategy could successfully upregulate sexual arousal elicited by sexual reward-conditioned cues in men and women. Men (n = 40) and women (n = 53) participated in a study using a differential conditioning paradigm, with genital vibrostimulation as unconditioned stimulus (US) and sexually relevant pictures as conditional stimuli. Penile circumference and vaginal pulse amplitude were assessed and ratings of US expectancy, affective value, and sexual arousal value were obtained. Also a stimulus response compatibility task was included to assess automatic approach and avoidance tendencies. Evidence was found for emotion upregulation to increase genital arousal response in the acquisition phase in both sexes, and to enhance resistance to extinction of conditioned genital responding in women. In men, the emotion upregulatory strategy resulted in increased conditioned positive affect. The findings support that top-down modulation may indeed influence conditioned sexual responses. This knowledge may have implications for treating disturbances in sexual appetitive responses, such as low sexual arousal and desire. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  15. Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

    NARCIS (Netherlands)

    Hempenius, R.A.; Lina, B.A.R.; Haggitt, R.C.

    2000-01-01

    Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm,

  16. Mycoplasma pneumoniae preceding Lemierre's syndrome due to Fusobacterium nucleatum complicated by acute Epstein-Barr virus (EBV) infectious mononucleosis in an immunocompetent host.

    Science.gov (United States)

    Klein, Natalie C; Petelin, Andrew; Cunha, Burke A

    2013-01-01

    We report an unusual case of Lemierre's syndrome due to a rare species of Fusobacterium, that is, Fusobacterium nucleatum preceded by Mycoplasma pneumoniae pharyngitis and followed later by Epstein-Barr virus infectious mononucleosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. The effect of the training program on the quality of life in patients with asthma based on the Precede model in Ahvaz, Iran.

    Science.gov (United States)

    Nejad, Mina Motaghi; Nejad, Ghodratollah Shakeri; Tavakol, Heshmatollah; Cheraghi, Maria

    2017-06-01

    The aim of the study was to determine the effect of the training program based on the Precede model and its main components on improving the quality of life in patients with asthma. It was a randomized quasi-experimental study done on 120 patients with asthma who were referred to the Imam Khomeini hospital in Ahvaz who were selected using the convenience sampling method and were randomly divided into intervention and control groups. The data collection tool consisted of two questionnaires. The first questionnaire evaluated the quality of life in patients with asthma and the other one was developed by the researcher based on the structures of the Precede model. Training intervention was conducted during four sessions twice a week and each session was carried out for an hour based on the structures of the Precede model. In order to achieve the results, SPSS software, even t -test, and χ 2 were used. The results showed that after the training intervention in the experimental group, the mean scores of predisposing factors ( p quality of life in two groups after the intervention ( p quality of life of patients in the experimental group was improved after the training intervention. The design and implementation of the training program based on the Precede model can have a positive effect on the improvement of quality of life in patients with asthma.

  18. Integration of sensory information precedes the sensation of vection: a combined behavioral and event-related brain potential (ERP) study.

    Science.gov (United States)

    Keshavarz, Behrang; Berti, Stefan

    2014-02-01

    Illusory self-motion (known as vection) describes the sensation of ego-motion in the absence of physical movement. Vection typically occurs in stationary observers being exposed to visual information that suggest self-motion (e.g. simulators, virtual reality). In the present study, we tested whether sensory integration of visual information triggers vection: participants (N=13) perceived patterns of moving altered black-and-white vertical stripes on a screen that was divided into a central and a surrounding peripheral visual field. In both fields the pattern was either moving or stationary, resulting in four combinations of central and peripheral motions: (1) central and peripheral stripes moved into the same direction, (2) central and peripheral stripes moved in opposite directions, or (3) either the central or (4) the peripheral stripes were stable while the other stripes were in motion. This stimulation induced vection: Results showed significantly higher vection ratings when the stationary center of the pattern was surrounded by a moving periphery. Event-related potentials mirrored this finding: The occipital N2 was largest with stationary central and moving peripheral stripes. Our findings suggest that sensory integration of peripheral and central visual information triggers the perception of vection. Furthermore, we found evidence that neural processes precede the subjective perception of vection strength prior to the actual onset of vection. We will discuss our findings with respect to the role of stimulus eccentricity, stimulus' depth, and neural correlates involved during the genesis of vection. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Elevations in the Fasting Serum Proinsulin–to–C-Peptide Ratio Precede the Onset of Type 1 Diabetes

    Science.gov (United States)

    Sims, Emily K.; Chaudhry, Zunaira; Watkins, Renecia; Syed, Farooq; Blum, Janice; Ouyang, Fangqian; Perkins, Susan M.; Mirmira, Raghavendra G.; Sosenko, Jay; DiMeglio, Linda A.

    2016-01-01

    OBJECTIVE We tested whether an elevation in the serum proinsulin–to–C-peptide ratio (PI:C), a biomarker of β-cell endoplasmic reticulum (ER) dysfunction, was associated with progression to type 1 diabetes. RESEARCH DESIGN AND METHODS Fasting total PI and C levels were measured in banked serum samples obtained from TrialNet Pathway to Prevention (PTP) participants, a cohort of autoantibody-positive relatives without diabetes of individuals with type 1 diabetes. Samples were obtained ∼12 months before diabetes onset from PTP progressors in whom diabetes developed (n = 60), and were compared with age-, sex-, and BMI-matched nonprogressors who remained normoglycemic (n = 58). PI:C ratios were calculated as molar ratios and were multiplied by 100% to obtain PI levels as a percentage of C levels. RESULTS Although absolute PI levels did not differ between groups, PI:C ratios were significantly increased in antibody-positive subjects in whom there was progression to diabetes compared with nonprogressors (median 1.81% vs. 1.17%, P = 0.03). The difference between groups was most pronounced in subjects who were ≤10 years old, where the median progressor PI:C ratio was nearly triple that of nonprogressors; 90.0% of subjects in this age group within the upper PI:C quartile progressed to the development of diabetes. Logistic regression analysis, adjusted for age and BMI, demonstrated increased odds of progression for higher natural log PI:C ratio values (odds ratio 1.44, 95% CI 1.02, 2.05). CONCLUSIONS These data suggest that β-cell ER dysfunction precedes type 1 diabetes onset, especially in younger children. Elevations in the serum PI:C ratio may have utility in predicting the onset of type 1 diabetes in the presymptomatic phase. PMID:27385327

  20. Elevations in the Fasting Serum Proinsulin-to-C-Peptide Ratio Precede the Onset of Type 1 Diabetes.

    Science.gov (United States)

    Sims, Emily K; Chaudhry, Zunaira; Watkins, Renecia; Syed, Farooq; Blum, Janice; Ouyang, Fangqian; Perkins, Susan M; Mirmira, Raghavendra G; Sosenko, Jay; DiMeglio, Linda A; Evans-Molina, Carmella

    2016-09-01

    We tested whether an elevation in the serum proinsulin-to-C-peptide ratio (PI:C), a biomarker of β-cell endoplasmic reticulum (ER) dysfunction, was associated with progression to type 1 diabetes. Fasting total PI and C levels were measured in banked serum samples obtained from TrialNet Pathway to Prevention (PTP) participants, a cohort of autoantibody-positive relatives without diabetes of individuals with type 1 diabetes. Samples were obtained ∼12 months before diabetes onset from PTP progressors in whom diabetes developed (n = 60), and were compared with age-, sex-, and BMI-matched nonprogressors who remained normoglycemic (n = 58). PI:C ratios were calculated as molar ratios and were multiplied by 100% to obtain PI levels as a percentage of C levels. Although absolute PI levels did not differ between groups, PI:C ratios were significantly increased in antibody-positive subjects in whom there was progression to diabetes compared with nonprogressors (median 1.81% vs. 1.17%, P = 0.03). The difference between groups was most pronounced in subjects who were ≤10 years old, where the median progressor PI:C ratio was nearly triple that of nonprogressors; 90.0% of subjects in this age group within the upper PI:C quartile progressed to the development of diabetes. Logistic regression analysis, adjusted for age and BMI, demonstrated increased odds of progression for higher natural log PI:C ratio values (odds ratio 1.44, 95% CI 1.02, 2.05). These data suggest that β-cell ER dysfunction precedes type 1 diabetes onset, especially in younger children. Elevations in the serum PI:C ratio may have utility in predicting the onset of type 1 diabetes in the presymptomatic phase. © 2016 by the American Diabetes Association.

  1. Evaporation of impact water droplets in interception processes: Historical precedence of the hypothesis and a brief literature overview

    Science.gov (United States)

    Dunkerley, David L.

    2009-10-01

    SummaryIntra-storm evaporation depths exceed post-storm evaporation depths in the interception of rainfall on plant canopies. An important fraction of the intra-storm evaporation may involve the small impact (or splash) droplets produced when raindrops, and perhaps gravity drops (drips released from plant parts), collide with wet plant surfaces. This idea has been presented as a new conception by Murakami [Murakami, S., 2006. A proposal for a new forest canopy interception mechanism: splash droplet evaporation. Journal of Hydrology 319, 72-82; Murakami, S., 2007a. Application of three canopy interception models to a young stand of Japanese cypress and interpretation in terms of interception mechanism. Journal of Hydrology 342, 305-319; Murakami, S., 2007b. A follow-up for the splash droplet evaporation hypothesis of canopy interception and remaining problems: why is humidity unsaturated during rainfall? In: Proceedings of the 20th Annual Conference. Japan Society of Hydrology and Water Resources (in Japanese). ] but was in fact advanced by Dunin [Dunin, F.X., O'Loughlin, E.M., Reyenga, W., 1988. Interception loss from eucalypt forest: lysimeter determination of hourly rates for long term evaluation. Hydrological Processes 2, 315-329] more than 20 years ago. In addition, Dunin et al. considered that canopy ventilation might be enhanced in intense rain. This note draws attention to the historical precedence of the work of Dunin et al. and also presents a short review of literature on impact droplet production, highlighting areas where data are still required for the full exploration of the role of droplet evaporation in canopy interception. Droplet production needs to be properly parameterised and included in models of interception processes and landsurface-atmosphere interactions.

  2. Discovering the impact of preceding units' characteristics on the wait time of cardiac surgery unit from statistic data.

    Science.gov (United States)

    Liu, Jiming; Tao, Li; Xiao, Bo

    2011-01-01

    Prior research shows that clinical demand and supplier capacity significantly affect the throughput and the wait time within an isolated unit. However, it is doubtful whether characteristics (i.e., demand, capacity, throughput, and wait time) of one unit would affect the wait time of subsequent units on the patient flow process. Focusing on cardiac care, this paper aims to examine the impact of characteristics of the catheterization unit (CU) on the wait time of cardiac surgery unit (SU). This study integrates published data from several sources on characteristics of the CU and SU units in 11 hospitals in Ontario, Canada between 2005 and 2008. It proposes a two-layer wait time model (with each layer representing one unit) to examine the impact of CU's characteristics on the wait time of SU and test the hypotheses using the Partial Least Squares-based Structural Equation Modeling analysis tool. Results show that: (i) wait time of CU has a direct positive impact on wait time of SU (β = 0.330, p relationships among different characteristics (except for the effect of throughput on wait time in SU). Characteristics of CU have direct and indirect impacts on wait time of SU. Specifically, demand and wait time of preceding unit are good predictors for wait time of subsequent units. This suggests that considering such cross-unit effects is necessary when alleviating wait time in a health care system. Further, different patient risk profiles may affect wait time in different ways (e.g., positive or negative effects) within SU. This implies that the wait time management should carefully consider the relationship between priority triage and risk stratification, especially for cardiac surgery.

  3. Adolescent idiopathic scoliosis screening for school, community, and clinical health promotion practice utilizing the PRECEDE-PROCEED model

    Directory of Open Access Journals (Sweden)

    Wyatt Lawrence A

    2005-11-01

    Full Text Available Abstract Background Screening for adolescent idiopathic scoliosis (AIS is a commonly performed procedure for school children during the high risk years. The PRECEDE-PROCEDE (PP model is a health promotion planning model that has not been utilized for the clinical diagnosis of AIS. The purpose of this research is to study AIS in the school age population using the PP model and its relevance for community, school, and clinical health promotion. Methods MEDLINE was utilized to locate AIS data. Studies were screened for relevance and applicability under the auspices of the PP model. Where data was unavailable, expert opinion was utilized based on consensus. Results The social assessment of quality of life is limited with few studies approaching the long-term effects of AIS. Epidemiologically, AIS is the most common form of scoliosis and leading orthopedic problem in children. Behavioral/environmental studies focus on discovering etiologic relationships yet this data is confounded because AIS is not a behavioral. Illness and parenting health behaviors can be appreciated. The educational diagnosis is confounded because AIS is an orthopedic disorder and not behavioral. The administration/policy diagnosis is hindered in that scoliosis screening programs are not considered cost-effective. Policies are determined in some schools because 26 states mandate school scoliosis screening. There exists potential error with the Adam's test. The most widely used measure in the PP model, the Health Belief Model, has not been utilized in any AIS research. Conclusion The PP model is a useful tool for a comprehensive study of a particular health concern. This research showed where gaps in AIS research exist suggesting that there may be problems to the implementation of school screening. Until research disparities are filled, implementation of AIS screening by school, community, and clinical health promotion will be compromised. Lack of data and perceived importance by

  4. QUOTEchemo: a patient-centred instrument to measure quality of communication preceding chemotherapy treatment through the patient's eyes.

    Science.gov (United States)

    van Weert, Julia C M; Jansen, Jesse; de Bruijn, Gert-Jan; Noordman, Janneke; van Dulmen, Sandra; Bensing, Jozien M

    2009-11-01

    Knowing patients' needs is a prerequisite to ensure high quality cancer care. This study describes the development and psychometric properties of a patient-centred instrument to measure needs and actual experiences with communication preceding chemotherapy treatment: QUOTE(chemo). QUOTE-questionnaires (Quality Of care Through the patients' Eyes) are widely used to gain insight into unmet needs, but no validated, standardised questionnaire combining patients' needs and experiences surrounding chemotherapy treatment is available yet. To evaluate the psychometric properties of the QUOTE(chemo), content validity, internal structure and convergent validity were investigated amongst 345 cancer patients, new to chemotherapy, from 10 different hospitals. Literature study, focus group discussions and a categorisation procedure of 67 relevant topics revealed seven main themes: Treatment-related information, Prognosis information, Rehabilitation information, Coping information, Interpersonal communication, Tailored communication and Affective communication. Confirmatory factor analysis using structural equation modelling indicated that the measurement model provided good fit to the data with factor loadings ranging from .43 to .77. The seven QUOTE(chemo) dimensions captured relevant issues of concern with good internal consistency (alpha .72-.92), satisfactory item-total correlations (.35-.79) and satisfactory convergent validity. Affective communication, Treatment-related information and Rehabilitation information were perceived most important by patients. The instrument also appeared to be able to determine which aspects need improvement to ensure high quality care. The highest need for improvement was found for communicating Prognosis information and Rehabilitation information and for Interpersonal communication. These findings provide preliminary evidence of the reliability and validity of the QUOTE(chemo) for use in cancer care surrounding chemotherapy treatment

  5. Identification of Characteristic Motor Patterns Preceding Freezing of Gait in Parkinson’s Disease Using Wearable Sensors

    Directory of Open Access Journals (Sweden)

    Luca Palmerini

    2017-08-01

    Full Text Available Freezing of gait (FOG is a disabling symptom that is common among patients with advanced Parkinson’s disease (PD. External cues such as rhythmic auditory stimulation can help PD patients experiencing freezing to resume walking. Wearable systems for automatic freezing detection have been recently developed. However, these systems detect a FOG episode after it has happened. Instead, in this study, a new approach for the prediction of FOG (before it actually happens is presented. Prediction of FOG might enable preventive cueing, reducing the likelihood that FOG will occur. Moreover, understanding the causes and circumstances of FOG is still an open research problem. Hence, a quantitative characterization of movement patterns just before FOG (the pre-FOG phase is of great importance. In this study, wearable inertial sensors were used to identify and quantify the characteristics of gait during the pre-FOG phase and compare them with the characteristics of gait that do not precede FOG. The hypothesis of this study is based on the threshold-based model of FOG, which suggests that before FOG occurs, there is a degradation of the gait pattern. Eleven PD subjects were analyzed. Six features extracted from movement signals recorded by inertial sensors showed significant differences between gait and pre-FOG. A classification algorithm was developed in order to test if it is feasible to predict FOG (i.e., detect it before it happens. The aim of the classification procedure was to identify the pre-FOG phase. Results confirm that there is a degradation of gait occurring before freezing. Results also provide preliminary evidence on the feasibility of creating an automatic algorithm to predict FOG. Although some limitations are present, this study shows promising findings for characterizing and identifying pre-FOG patterns, another step toward a better understanding, prediction, and prevention of this disabling symptom.

  6. Structural brain alterations associated with schizophrenia preceded by conduct disorder: a common and distinct subtype of schizophrenia?

    Science.gov (United States)

    Schiffer, Boris; Leygraf, Norbert; Müller, Bernhard W; Scherbaum, Norbert; Forsting, Michael; Wiltfang, Jens; Gizewski, Elke R; Hodgins, Sheilagh

    2013-09-01

    Conduct disorder (CD) prior to age 15 is a precursor of schizophrenia in a minority of cases and is associated with violent behavior through adulthood, after taking account of substance misuse. The present study used structural magnetic imaging to examine gray matter (GM) volumes among 27 men with schizophrenia preceded by CD (SZ+CD), 23 men with schizophrenia but without CD (SZ-CD), 27 men with CD only (CD), and 25 healthy (H) men. The groups with schizophrenia were similar in terms of age of onset and duration of illness, levels of psychotic symptoms, and medication. The 2 groups with CD were similar as to number of CD symptoms, lifelong aggressive behavior, and number of criminal convictions. Men with SZ+CD, relative to those with SZ-CD, displayed (1) increased GM volumes in the hypothalamus, the left putamen, the right cuneus/precuneus, and the right inferior parietal cortex after controlling for age, alcohol, and drug misuse and (2) decreased GM volumes in the inferior frontal region. Men with SZ+CD (relative to the SZ-CD group) and CD (relative to the H group) displayed increased GM volumes of the hypothalamus and the inferior and superior parietal lobes, which were not associated with substance misuse. Aggressive behavior, both prior to age 15 and lifetime tendency, was positively correlated with the GM volume of the hypothalamus. Thus, among males, SZ+CD represents a distinct subtype of schizophrenia. Although differences in behavior emerge in childhood and remain stable through adulthood, further research is needed to determine whether the differences in GM volumes result from abnormal neural development distinct from that of other males developing schizophrenia.

  7. The role of information technology in translating educational interventions into practice: an analysis using the PRECEDE/PROCEED model.

    Science.gov (United States)

    Weir, Charlene; McLeskey, Nanci; Brunker, Cherie; Brooks, Denise; Supiano, Mark A

    2011-01-01

    The evidence base for information technology (IT) has been criticized, especially with the current emphasis on translational science. The purpose of this paper is to present an analysis of the role of IT in the implementation of a geriatric education and quality improvement (QI) intervention. A mixed-method three-group comparative design was used. The PRECEDE/PROCEED implementation model was used to qualitatively identify key factors in the implementation process. These results were further explored in a quantitative analysis. Thirty-three primary care clinics at three institutions (Intermountain Healthcare, VA Salt Lake City Health Care System, and University of Utah) participated. The program consisted of an onsite, didactic session, QI planning and 6 months of intense implementation support. Completion rate was 82% with an average improvement rate of 21%. Important predisposing factors for success included an established electronic record and a culture of quality. The reinforcing and enabling factors included free continuing medical education credits, feedback, IT access, and flexible support. The relationship between IT and QI emerged as a central factor. Quantitative analysis found significant differences between institutions for pre-post changes even after the number and category of implementation strategies had been controlled for. The analysis illustrates the complex dependence between IT interventions, institutional characteristics, and implementation practices. Access to IT tools and data by individual clinicians may be a key factor for the success of QI projects. Institutions vary widely in the degree of access to IT tools and support. This article suggests that more attention be paid to the QI and IT department relationship.

  8. Spatial and Temporal Characteristics of the Microseismicity Preceding the 2016 M L 6.6 Meinong Earthquake in Southern Taiwan

    Science.gov (United States)

    Pu, Hsin-Chieh

    2018-02-01

    Before the M L 6.6 Meinong earthquake in 2016, intermediate-term quiescence (Q i), foreshocks, and short-term quiescence (Q s) were extracted from a comprehensive earthquake catalog. In practice, these behaviors are thought to be the seismic indicators of an earthquake precursor, and their spatiotemporal characteristics may be associated with location, magnitude, and occurrence time of the following main shock. Hence, detailed examinations were carried out to derive the spatiotemporal characteristics of these meaningful seismic behaviors. First, the spatial range of the Q i that occurred for 96 days was revealed in and around the Meinong earthquake. Second, a series of foreshocks was present for 1 day, clustered at the southeastern end of the Meinong earthquake. Third, Q s was present for 3 days and was pronounced after the foreshocks. Although these behaviors were recorded difficultly because the Q i was characterized by microseismicity at the lower cut-off magnitude, between M L 1.2 and 1.6, and most of the foreshocks were comprised of earthquakes with a magnitude lower than 1.8, they carried meaningful precursory indicators preceding the Meinong earthquake. These indicators provide the information of (1) the hypocenter, which was indicated by the area including the Q i, foreshocks, and Q s; (2) the magnitude, which could be associated to the spatial range of the Q i; (3) the asperity locations, which might be related to the areas of extraordinary low seismicity; and (4) a short-term warning leading of 3 days, which could have been announced based on the occurrence of the Q s. Particularly, Q i also appeared before strong inland earthquakes so that Q i might be an anticipative phenomenon before a strong earthquake in Taiwan.

  9. Molecular changes preceding endometrial and ovarian cancer: a study of consecutive endometrial specimens from Lynch syndrome surveillance.

    Science.gov (United States)

    Niskakoski, Anni; Pasanen, Annukka; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

    2018-03-27

    Molecular alterations preceding endometrial and ovarian cancer and the sequence of events are unknown. Consecutive specimens from lifelong surveillance for Lynch syndrome provides a natural setting to address such questions. To molecularly define the multistep gynecological tumorigenesis, DNA mismatch repair gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nation-wide registry and endometrial biopsy specimens taken from these individuals during 20 years of screening were collected. A total of 213 endometrial and ovarian specimens from Lynch syndrome individuals and 197 histology-matched (non-serous) samples from sporadic cases were available for this investigation. The specimens were profiled for markers linked to endometrial and ovarian tumorigenesis, including ARID1A protein expression, mismatch repair status, and tumor suppressor gene promoter methylation. In Lynch syndrome-associated endometrial and ovarian carcinomas, ARID1A protein was lost in 61-100% and mismatch repair was deficient in 97-100%, compared to 0-17% and 14-44% in sporadic cases (P = 0.000). ARID1A loss appeared in complex hyperplasia and deficient mismatch repair and tumor suppressor gene promoter methylation in histologically normal endometrium. Despite quantitative differences between Lynch syndrome and sporadic cases, ARID1A expression, mismatch repair, and tumor suppressor gene promoter methylation divided endometrial samples from both patient groups into three categories of increasing abnormality, comprising normal endometrium and simple hyperplasia (I), complex hyperplasia with or without atypia (II), and endometrial cancer (III). Complex hyperplasias without vs. with atypia were molecularly indistinguishable. In conclusion, surveillance specimens from Lynch syndrome identify mismatch repair deficiency, tumor suppressor gene promoter methylation, and ARID1A loss as early changes in tumor development. Our findings are

  10. Isoform-Specific Na,K-ATPase Alterations Precede Disuse-Induced Atrophy of Rat Soleus Muscle

    Directory of Open Access Journals (Sweden)

    Violetta V. Kravtsova

    2015-01-01

    Full Text Available This study examines the isoform-specific effects of short-term hindlimb suspension (HS on the Na,K-ATPase in rat soleus muscle. Rats were exposed to 24–72 h of HS and we analyzed the consequences on soleus muscle mass and contractile parameters; excitability and the resting membrane potential (RMP of muscle fibers; the electrogenic activity, protein, and mRNA content of the α1 and α2 Na,K-ATPase; the functional activity and plasma membrane localization of the α2 Na,K-ATPase. Our results indicate that 24–72 h of HS specifically decreases the electrogenic activity of the Na,K-ATPase α2 isozyme and the RMP of soleus muscle fibers. This decrease occurs prior to muscle atrophy or any change in contractile parameters. The α2 mRNA and protein content increased after 24 h of HS and returned to initial levels at 72 h; however, even the increased content was not able to restore α2 enzyme activity in the disused soleus muscle. There was no change in the membrane localization of α2 Na,K-ATPase. The α1 Na,K-ATPase electrogenic activity, protein and mRNA content did not change. Our findings suggest that skeletal muscle use is absolutely required for α2 Na,K-ATPase transport activity and provide the first evidence that Na,K-ATPase alterations precede HS-induced muscle atrophy.

  11. Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge.

    Science.gov (United States)

    Norden, Diana M; Trojanowski, Paige J; Villanueva, Emmanuel; Navarro, Elisa; Godbout, Jonathan P

    2016-02-01

    Activation of the peripheral immune system elicits a coordinated response from the central nervous system. Key to this immune to brain communication is that glia, microglia, and astrocytes, interpret and propagate inflammatory signals in the brain that influence physiological and behavioral responses. One issue in glial biology is that morphological analysis alone is used to report on glial activation state. Therefore, our objective was to compare behavioral responses after in vivo immune (lipopolysaccharide, LPS) challenge to glial specific mRNA and morphological profiles. Here, LPS challenge induced an immediate but transient sickness response with decreased locomotion and social interaction. Corresponding with active sickness behavior (2-12 h), inflammatory cytokine mRNA expression was elevated in enriched microglia and astrocytes. Although proinflammatory cytokine expression in microglia peaked 2-4 h after LPS, astrocyte cytokine, and chemokine induction was delayed and peaked at 12 h. Morphological alterations in microglia (Iba-1(+)) and astrocytes (GFAP(+)), however, were undetected during this 2-12 h timeframe. Increased Iba-1 immunoreactivity and de-ramified microglia were evident 24 and 48 h after LPS but corresponded to the resolution phase of activation. Morphological alterations in astrocytes were undetected after LPS. Additionally, glial cytokine expression did not correlate with morphology after four repeated LPS injections. In fact, repeated LPS challenge was associated with immune and behavioral tolerance and a less inflammatory microglial profile compared with acute LPS challenge. Overall, induction of glial cytokine expression was sequential, aligned with active sickness behavior, and preceded increased Iba-1 or GFAP immunoreactivity after LPS challenge. © 2015 Wiley Periodicals, Inc.

  12. Discovering the impact of preceding units' characteristics on the wait time of cardiac surgery unit from statistic data.

    Directory of Open Access Journals (Sweden)

    Jiming Liu

    Full Text Available INTRODUCTION: Prior research shows that clinical demand and supplier capacity significantly affect the throughput and the wait time within an isolated unit. However, it is doubtful whether characteristics (i.e., demand, capacity, throughput, and wait time of one unit would affect the wait time of subsequent units on the patient flow process. Focusing on cardiac care, this paper aims to examine the impact of characteristics of the catheterization unit (CU on the wait time of cardiac surgery unit (SU. METHODS: This study integrates published data from several sources on characteristics of the CU and SU units in 11 hospitals in Ontario, Canada between 2005 and 2008. It proposes a two-layer wait time model (with each layer representing one unit to examine the impact of CU's characteristics on the wait time of SU and test the hypotheses using the Partial Least Squares-based Structural Equation Modeling analysis tool. RESULTS: Results show that: (i wait time of CU has a direct positive impact on wait time of SU (β = 0.330, p < 0.01; (ii capacity of CU has a direct positive impact on demand of SU (β = 0.644, p < 0.01; (iii within each unit, there exist significant relationships among different characteristics (except for the effect of throughput on wait time in SU. CONCLUSION: Characteristics of CU have direct and indirect impacts on wait time of SU. Specifically, demand and wait time of preceding unit are good predictors for wait time of subsequent units. This suggests that considering such cross-unit effects is necessary when alleviating wait time in a health care system. Further, different patient risk profiles may affect wait time in different ways (e.g., positive or negative effects within SU. This implies that the wait time management should carefully consider the relationship between priority triage and risk stratification, especially for cardiac surgery.

  13. Metformin normalizes the structural changes in glycogen preceding prediabetes in mice overexpressing neuropeptide Y in noradrenergic neurons.

    Science.gov (United States)

    Ailanen, Liisa; Bezborodkina, Natalia N; Virtanen, Laura; Ruohonen, Suvi T; Malova, Anastasia V; Okovityi, Sergey V; Chistyakova, Elizaveta Y; Savontaus, Eriika

    2018-04-01

    Hepatic insulin resistance and increased gluconeogenesis are known therapeutic targets of metformin, but the role of hepatic glycogen in the pathogenesis of diabetes is less clear. Mouse model of neuropeptide Y (NPY) overexpression in noradrenergic neurons (OE-NPY D βH ) with a phenotype of late onset obesity, hepatosteatosis, and prediabetes was used to study early changes in glycogen structure and metabolism preceding prediabetes. Furthermore, the effect of the anti-hyperglycemic agent, metformin (300 mg/kg/day/4 weeks in drinking water), was assessed on changes in glycogen metabolism, body weight, fat mass, and glucose tolerance. Glycogen structure was characterized by cytofluorometric analysis in isolated hepatocytes and mRNA expression of key enzymes by qPCR. OE-NPY D βH mice displayed decreased labile glycogen fraction relative to stabile fraction (the intermediate form of glycogen) suggesting enhanced glycogen cycling. This was supported by decreased filling of glucose residues in the 10th outer tier of the glycogen molecule, which suggests accelerated glycogen phosphorylation. Metformin reduced fat mass gain in both genotypes, but glucose tolerance was improved mostly in wild-type mice. However, metformin inhibited glycogen accumulation and normalized the ratio between glycogen structures in OE-NPY D βH mice indicating decreased glycogen synthesis. Furthermore, the presence of glucose residues in the 11th tier together with decreased glycogen phosphorylase expression suggested inhibition of glycogen degradation. In conclusion, structural changes in glycogen of OE-NPY D βH mice point to increased glycogen metabolism, which may predispose them to prediabetes. Metformin treatment normalizes these changes and suppresses both glycogen synthesis and phosphorylation, which may contribute to its preventive effect on the onset of diabetes.

  14. Mutations in BALB mitochondrial DNA induce CCL20 up-regulation promoting tumorigenic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Sligh, James [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Janda, Jaroslav [University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Jandova, Jana, E-mail: jjandova@email.arizona.edu [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States)

    2014-11-15

    Highlights: • Alterations in mitochondrial DNA are commonly found in various human cancers. • Mutations in BALB mitochondrial DNA induce up-regulation of chemokine CCL20. • Increased growth and motility of mtBALB cells is associated with CCL20 levels. • mtDNA changes in BALB induce in vivo tumor growth through CCL20 up-regulation. • Mutations in mitochondrial DNA play important roles in keratinocyte neoplasia. - Abstract: mtDNA mutations are common in human cancers and are thought to contribute to the process of neoplasia. We examined the role of mtDNA mutations in skin cancer by generating fibroblast cybrids harboring a mutation in the gene encoding the mitochondrial tRNA for arginine. This somatic mutation (9821insA) was previously reported in UV-induced hyperkeratotic skin tumors in hairless mice and confers specific tumorigenic phenotypes to mutant cybrids. Microarray analysis revealed and RT-PCR along with Western blot analysis confirmed the up-regulation of CCL20 and its receptor CCR6 in mtBALB haplotype containing the mt-Tr 9821insA allele compared to wild type mtB6 haplotype. Based on reported role of CCL20 in cancer progression we examined whether the hyper-proliferation and enhanced motility of mtBALB haplotype would be associated with CCL20 levels. Treatment of both genotypes with recombinant CCL20 (rmCCL20) resulted in enhanced growth and motility of mtB6 cybrids. Furthermore, the acquired somatic alteration increased the in vivo tumor growth of mtBALB cybrids through the up-regulation of CCL20 since neutralizing antibody significantly decreased in vivo tumor growth of these cells; and tumors from anti-CCL20 treated mice injected with mtBALB cybrids showed significantly decreased CCL20 levels. When rmCCL20 or mtBALB cybrids were used as chemotactic stimuli, mtB6 cybrids showed increased motility while anti-CCL20 antibody decreased the migration and in vivo tumor growth of mtBALB cybrids. Moreover, the inhibitors of MAPK signaling and NF

  15. Airborne fine particulate matter induces an upregulation of endothelin receptors on rat bronchi

    International Nuclear Information System (INIS)

    Wang, Rong; Xiao, Xue; Cao, Lei; Shen, Zhen-xing; Lei, Ying; Cao, Yong-xiao

    2016-01-01

    Airborne fine particulate matter (PM2.5) is a risk factor for respiratory diseases. However, little is known about the effects of PM2.5 on bronchi. The present study investigated the effect of airborne PM2.5 on rat bronchi and the underlying mechanisms. Isolated rat bronchial segments were cultured for 24 h. Endothelin (ET) receptor-mediated contractile responses were recorded using a wire myograph. The mRNA and protein expression levels of ET receptors were studied using quantitative real-time PCR, Western blotting, and immunohistochemistry. The results demonstrated that ET A and ET B receptor agonists induced remarkable contractile responses on fresh and cultured bronchial segments. PM2.5 (1.0 or 3.0 μg/ml) significantly enhanced ET A and ET B receptor-mediated contractile responses in bronchi with a markedly increased maximal contraction compared to the DMSO or fresh groups. PM2.5 increased the mRNA and protein expression levels of ET A and ET B receptors. U0126 (a MEK1/2 inhibitor) and SB203580 (a p38 inhibitor) significantly suppressed PM2.5-induced increases in ET B receptor-mediated contractile responses, mRNA and protein levels. SP600125 (a JNK inhibitor) and SB203580 significantly abrogated the PM2.5-induced enhancement of ET A receptor-mediated contraction and receptor expression. In conclusion, PM2.5 upregulates ET receptors in bronchi. ET B receptor upregulation is associated with MEK1/2 and p38 pathways, and the upregulation of ET A receptor is involved in JNK and p38 pathways. - Highlights: • Airborne PM2.5 induces bronchial hyperreactivity mediated with endothelin ET B and ET A receptors in rats. • PM2.5 increases mRNA and protein expressions of endothelin ET B and ET A receptors in bronchi. • The upregulation of ET B receptor is associated with MEK1/2 and p38 pathways. • The upregulation of ET A receptor is involved in JNK and p38 pathways. • The research provides novel understanding for PM2.5-associated respiratory diseases.

  16. Reduction of the CD16(-CD56bright NK cell subset precedes NK cell dysfunction in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Kyo Chul Koo

    Full Text Available BACKGROUND: Natural cytotoxicity, mediated by natural killer (NK cells plays an important role in the inhibition and elimination of malignant tumor cells. To investigate the immunoregulatory role of NK cells and their potential as diagnostic markers, NK cell activity (NKA was analyzed in prostate cancer (PCa patients with particular focus on NK cell subset distribution. METHODS: Prospective data of NKA and NK cell subset distribution patterns were measured from 51 patients initially diagnosed with PCa and 54 healthy controls. NKA was represented by IFN-γ levels after stimulation of the peripheral blood with Promoca®. To determine the distribution of NK cell subsets, PBMCs were stained with fluorochrome-conjugated monoclonal antibodies. Then, CD16(+CD56(dim and CD16(-CD56(bright cells gated on CD56(+CD3(- cells were analyzed using a flow-cytometer. RESULTS: NKA and the proportion of CD56(bright cells were significantly lower in PCa patients compared to controls (430.9 pg/ml vs. 975.2 pg/ml and 2.3% vs. 3.8%, respectively; p<0.001. Both tended to gradually decrease according to cancer stage progression (p for trend = 0.001. A significantly higher CD56(dim-to-CD56(bright cell ratio was observed in PCa patients (41.8 vs. 30.3; p<0.001 along with a gradual increase according to cancer stage progression (p for trend = 0.001, implying a significant reduction of CD56(bright cells in relation to the alteration of CD56(dim cells. The sensitivity and the specificity of NKA regarding PCa detection were 72% and 74%, respectively (best cut-off value at 530.9 pg/ml, AUC = 0.786. CONCLUSIONS: Reduction of CD56(bright cells may precede NK cell dysfunction, leading to impaired cytotoxicity against PCa cells. These observations may explain one of the mechanisms behind NK cell dysfunction observed in PCa microenvironment and lend support to the development of future cancer immunotherapeutic strategies.

  17. SU-E-J-58: Comparison of Conformal Tracking Methods Using Initial, Adaptive and Preceding Image Frames for Image Registration

    Energy Technology Data Exchange (ETDEWEB)

    Teo, P; Guo, K; Alayoubi, N; Kehler, K; Pistorius, S [CancerCare Manitoba, Winnipeg, MB (Canada)

    2015-06-15

    Purpose: Accounting for tumor motion during radiation therapy is important to ensure that the tumor receives the prescribed dose. Increasing the field size to account for this motion exposes the surrounding healthy tissues to unnecessary radiation. In contrast to using motion-encompassing techniques to treat moving tumors, conformal radiation therapy (RT) uses a smaller field to track the tumor and adapts the beam aperture according to the motion detected. This work investigates and compares the performance of three markerless, EPID based, optical flow methods to track tumor motion with conformal RT. Methods: Three techniques were used to track the motions of a 3D printed lung tumor programmed to move according to the tumor of seven lung cancer patients. These techniques utilized a multi-resolution optical flow algorithm as the core computation for image registration. The first method (DIR) registers the incoming images with an initial reference frame, while the second method (RFSF) uses an adaptive reference frame and the third method (CU) uses preceding image frames for registration. The patient traces and errors were evaluated for the seven patients. Results: The average position errors for all patient traces were 0.12 ± 0.33 mm, −0.05 ± 0.04 mm and −0.28 ± 0.44 mm for CU, DIR and RFSF method respectively. The position errors distributed within 1 standard deviation are 0.74 mm, 0.37 mm and 0.96 mm respectively. The CU and RFSF algorithms are sensitive to the characteristics of the patient trace and produce a wider distribution of errors amongst patients. Although the mean error for the DIR method is negatively biased (−0.05 mm) for all patients, it has the narrowest distribution of position error, which can be corrected using an offset calibration. Conclusion: Three techniques of image registration and position update were studied. Using direct comparison with an initial frame yields the best performance. The authors would like to thank Dr.YeLin Suh for

  18. Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer's disease.

    Science.gov (United States)

    Streit, Wolfgang J; Braak, Heiko; Xue, Qing-Shan; Bechmann, Ingo

    2009-10-01

    The role of microglial cells in the pathogenesis of Alzheimer's disease (AD) neurodegeneration is unknown. Although several works suggest that chronic neuroinflammation caused by activated microglia contributes to neurofibrillary degeneration, anti-inflammatory drugs do not prevent or reverse neuronal tau pathology. This raises the question if indeed microglial activation occurs in the human brain at sites of neurofibrillary degeneration. In view of the recent work demonstrating presence of dystrophic (senescent) microglia in aged human brain, the purpose of this study was to investigate microglial cells in situ and at high resolution in the immediate vicinity of tau-positive structures in order to determine conclusively whether degenerating neuronal structures are associated with activated or with dystrophic microglia. We used a newly optimized immunohistochemical method for visualizing microglial cells in human archival brain together with Braak staging of neurofibrillary pathology to ascertain the morphology of microglia in the vicinity of tau-positive structures. We now report histopathological findings from 19 humans covering the spectrum from none to severe AD pathology, including patients with Down's syndrome, showing that degenerating neuronal structures positive for tau (neuropil threads, neurofibrillary tangles, neuritic plaques) are invariably colocalized with severely dystrophic (fragmented) rather than with activated microglial cells. Using Braak staging of Alzheimer neuropathology we demonstrate that microglial dystrophy precedes the spread of tau pathology. Deposits of amyloid-beta protein (Abeta) devoid of tau-positive structures were found to be colocalized with non-activated, ramified microglia, suggesting that Abeta does not trigger microglial activation. Our findings also indicate that when microglial activation does occur in the absence of an identifiable acute central nervous system insult, it is likely to be the result of systemic infectious

  19. Induction of IL-17A precedes development of airway hyperresponsiveness during diet induced obesity and correlates with complement factor D

    Directory of Open Access Journals (Sweden)

    Joel A. Mathews, Phd

    2014-09-01

    Full Text Available Obesity is a risk factor for the development of asthma. Obese mice exhibit innate airway hyperresponsiveness (AHR, a characteristic feature of asthma, and IL-17A is required for development of AHR in obese mice. The purpose of this study was to examine the temporal association between the onset of AHR and changes in IL-17A during the development of obesity by high fat feeding in mice. At weaning, C57BL/6J mice were placed either on mouse chow or on a high fat diet (HFD and examined 9, 12, 15, 18, or 24 weeks later. Airway responsiveness to aerosolized methacholine (assessed via the forced oscillation technique was greater in mice fed HFD versus chow for 24 weeks, but not at earlier time points. Bronchoalveolar lavage and serum IL-17A were not affected by either the type or duration of diet, but increased pulmonary IL17a mRNA abundance was observed in HFD versus chow fed mice after both 18 and 24 weeks. Flow cytometry also confirmed an increase in IL-17A+ gd T cells and IL-17A+ CD4+ T (Th17 cells in lungs of HFD versus chow fed mice. Pulmonary expression of Cfd (complement factor D, adipsin, a gene whose expression can be reduced by IL-17A, decreased after both 18 and 24 weeks in HFD versus chow fed mice. Furthermore, pulmonary Cfd mRNA abundance correlated with elevations in pulmonary Il17a mRNA expression and with AHR. Serum levels of TNFa, MIP-1a and MIP-1b, classical markers of systemic inflammation of obesity, were significantly greater in HFD than chow fed mice after 24 weeks, but not earlier. In conclusion, our data indicate that pulmonary rather than systemic IL-17A is important for obesity-related AHR and suggest that changes in pulmonary Cfd expression contribute to these effects of IL-17A. Further, the observation that increases in Il17a preceded the development of AHR by several weeks suggests that IL-17A interacts with other factors to promote AHR. The observation that the onset of the systemic inflammation of obesity coincided

  20. Early cytoskeletal protein modifications precede overt structural degeneration in the DBA/2J mouse model of glaucoma

    Directory of Open Access Journals (Sweden)

    Gina Nicole Wilson

    2016-11-01

    Full Text Available Axonal transport deficits precede structural loss in glaucoma and other neurodegenerations. Impairments in structural support, including modified cytoskeletal proteins and microtubule-destabilizing elements, could be initiating factors in glaucoma pathogenesis. We investigated the time course of changes in protein levels and post-translational modifications in the DBA/2J mouse model of glaucoma. Using anterograde tract tracing of the retinal projection, we assessed major cytoskeletal and transported elements as a function of transport integrity in different stages of pathological progression. Using capillary-based electrophoresis, single- and multiplex immunosorbent assays, and immunofluorescence, we quantified hyperphosphorylated neurofilament-heavy chain, phosphorylated tau (ptau, calpain-mediated spectrin breakdown product (145/150kDa, β –tubulin, and amyloid-β42 proteins based on age and transport outcome to the superior colliculus (SC, the main retinal target in mice. Phosphorylated neurofilament-heavy chain (pNF-H was elevated within the optic nerve (ON and SC of 8-10 month-old DBA/2J mice, but was not evident in the retina until 12-15 months, suggesting that cytoskeletal modifications first appear in the distal retinal projection. As expected, higher pNF-H levels in the SC and retina were correlated with axonal transport deficits. Elevations in hyperphosphorylated tau (ptau occurred in ON and SC between 3-8 month of age while retinal ptau accumulations occurred at 12-15 months in DBA/2J mice. In vitro co-immunoprecipitation experiments suggested increased affinity of ptau for the retrograde motor complex protein, dynactin. We observed a transport-related decrease of β-tubulin in ON of 10-12 month-old DBA/2J mice, suggesting destabilized microtubule array. Elevations in calpain-mediated spectrin breakdown product were seen in ON and SC at the earliest age examined, well before axonal transport loss is evident. Finally, transport

  1. Intestinal Metagenomes and Metabolomes in Healthy Young Males: Inactivity and Hypoxia Generated Negative Physiological Symptoms Precede Microbial Dysbiosis

    Directory of Open Access Journals (Sweden)

    Robert Šket

    2018-03-01

    Full Text Available We explored the metagenomic, metabolomic and trace metal makeup of intestinal microbiota and environment in healthy male participants during the run-in (5 day and the following three 21-day interventions: normoxic bedrest (NBR, hypoxic bedrest (HBR and hypoxic ambulation (HAmb which were carried out within a controlled laboratory environment (circadian rhythm, fluid and dietary intakes, microbial bioburden, oxygen level, exercise. The fraction of inspired O2 (FiO2 and partial pressure of inspired O2 (PiO2 were 0.209 and 133.1 ± 0.3 mmHg for the NBR and 0.141 ± 0.004 and 90.0 ± 0.4 mmHg (~4,000 m simulated altitude for HBR and HAmb interventions, respectively. Shotgun metagenomes were analyzed at various taxonomic and functional levels, 1H- and 13C -metabolomes were processed using standard quantitative and human expert approaches, whereas metals were assessed using X-ray fluorescence spectrometry. Inactivity and hypoxia resulted in a significant increase in the genus Bacteroides in HBR, in genes coding for proteins involved in iron acquisition and metabolism, cell wall, capsule, virulence, defense and mucin degradation, such as beta-galactosidase (EC3.2.1.23, α-L-fucosidase (EC3.2.1.51, Sialidase (EC3.2.1.18, and α-N-acetylglucosaminidase (EC3.2.1.50. In contrast, the microbial metabolomes, intestinal element and metal profiles, the diversity of bacterial, archaeal and fungal microbial communities were not significantly affected. The observed progressive decrease in defecation frequency and concomitant increase in the electrical conductivity (EC preceded or took place in absence of significant changes at the taxonomic, functional gene, metabolome and intestinal metal profile levels. The fact that the genus Bacteroides and proteins involved in iron acquisition and metabolism, cell wall, capsule, virulence and mucin degradation were enriched at the end of HBR suggest that both constipation and EC decreased intestinal metal availability

  2. SU-E-J-58: Comparison of Conformal Tracking Methods Using Initial, Adaptive and Preceding Image Frames for Image Registration

    International Nuclear Information System (INIS)

    Teo, P; Guo, K; Alayoubi, N; Kehler, K; Pistorius, S

    2015-01-01

    Purpose: Accounting for tumor motion during radiation therapy is important to ensure that the tumor receives the prescribed dose. Increasing the field size to account for this motion exposes the surrounding healthy tissues to unnecessary radiation. In contrast to using motion-encompassing techniques to treat moving tumors, conformal radiation therapy (RT) uses a smaller field to track the tumor and adapts the beam aperture according to the motion detected. This work investigates and compares the performance of three markerless, EPID based, optical flow methods to track tumor motion with conformal RT. Methods: Three techniques were used to track the motions of a 3D printed lung tumor programmed to move according to the tumor of seven lung cancer patients. These techniques utilized a multi-resolution optical flow algorithm as the core computation for image registration. The first method (DIR) registers the incoming images with an initial reference frame, while the second method (RFSF) uses an adaptive reference frame and the third method (CU) uses preceding image frames for registration. The patient traces and errors were evaluated for the seven patients. Results: The average position errors for all patient traces were 0.12 ± 0.33 mm, −0.05 ± 0.04 mm and −0.28 ± 0.44 mm for CU, DIR and RFSF method respectively. The position errors distributed within 1 standard deviation are 0.74 mm, 0.37 mm and 0.96 mm respectively. The CU and RFSF algorithms are sensitive to the characteristics of the patient trace and produce a wider distribution of errors amongst patients. Although the mean error for the DIR method is negatively biased (−0.05 mm) for all patients, it has the narrowest distribution of position error, which can be corrected using an offset calibration. Conclusion: Three techniques of image registration and position update were studied. Using direct comparison with an initial frame yields the best performance. The authors would like to thank Dr.YeLin Suh for

  3. Genes Involved in Human Ribosome Biogenesis areTranscriptionally Upregulated in Colorectal Cancer

    DEFF Research Database (Denmark)

    Mansilla, Francisco; Lamy, Philippe; Ørntoft, Torben Falck

    2009-01-01

    Microarray gene expression profiling comprising 168 colorectal adenocarcinomas and 10 normal mucosas showed that over 79% of the genes involved in human ribosome biogenesis are significantly upregulated (log2>0.5, p<10-3) when compared to normal mucosa. Overexpression was independent of microsate......Microarray gene expression profiling comprising 168 colorectal adenocarcinomas and 10 normal mucosas showed that over 79% of the genes involved in human ribosome biogenesis are significantly upregulated (log2>0.5, p... of microsatellite status. The promoters of the genes studied showed a significant enrichment for several transcription factor binding sites. There was a significant correlation between the number of binding site targets for these transcription factors and the observed gene transcript upregulation. The upregulation...

  4. Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis.

    Science.gov (United States)

    Schwartz, Erica S; Xie, Amy; La, Jun-Ho; Gebhart, G F

    2015-08-01

    Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue) from the prostate revealed that thoracolumbar and lumbosacral DRG are the principal sources of somata of prostate afferents. Nociceptive markers (eg, transient receptor potential, TREK, and P2X channels) were upregulated in fast blue-labeled thoracolumbar and lumbosacral somata for up to four weeks after inflaming the prostate (intraprostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21, and 28 days after zymosan injection. Interleukin 10 and NGF were also significantly upregulated in the prostate throughout the 4 weeks of inflammation. Open-field pain-related behaviors (eg, rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase, and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for the study of mechanisms underlying pain in chronic prostatitis.

  5. Urban air pollution produces up-regulation of myocardial inflammatory genes and dark chocolate provides cardioprotection.

    Science.gov (United States)

    Villarreal-Calderon, Rodolfo; Reed, William; Palacios-Moreno, Juan; Keefe, Sheyla; Herritt, Lou; Brooks, Diane; Torres-Jardón, Ricardo; Calderón-Garcidueñas, Lilian

    2012-05-01

    Air pollution is a serious environmental problem. Elderly subjects show increased cardiac morbidity and mortality associated with air pollution exposure. Mexico City (MC) residents are chronically exposed to high concentrations of fine particulate matter (PM(2.5)) and PM-associated lipopolysaccharides (PM-LPS). To test the hypothesis that chronic exposure to urban pollution produces myocardial inflammation, female Balb-c mice age 4 weeks were exposed for 16 months to two distinctly different polluted areas within MC: southwest (SW) and northwest (NW). SW mice were given either no treatment or chocolate 2g/9.5 mg polyphenols/3 times per week. Results were compared to mice kept in clean air. Key inflammatory mediator genes: cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the LPS receptor CD14 (cluster of differentiation antigen 14) were measured by real-time polymerase chain reaction. Also explored were target NFκB (nuclear factor κB), oxidative stress and antioxidant defense genes. TNF-α, IL-6, and COX-2 were significantly increased in both NW and SWMC mice (p=0.0001). CD14 was up-regulated in SW mice in keeping with the high exposures to particulate matter associated endotoxin. Chocolate administration resulted in a significant down-regulation of TNF-α (p<0.0001), IL-6 (p=0.01), and IL-1β (p=0.02). The up-regulation of antioxidant enzymes and the down-regulation of potent oxidases, toll-like receptors, and pro-apoptotic signaling genes completed the protective profile. Exposure to air pollution produces up-regulation of inflammatory myocardial genes and endotoxin plays a key role in the inflammatory response. Regular consumption of dark chocolate may reduce myocardial inflammation and have cardioprotective properties in the setting of air pollution exposures. Copyright © 2010 Elsevier GmbH. All rights reserved.

  6. Identification of a conserved set of upregulated genes in mouse skeletal muscle hypertrophy and regrowth.

    Science.gov (United States)

    Chaillou, Thomas; Jackson, Janna R; England, Jonathan H; Kirby, Tyler J; Richards-White, Jena; Esser, Karyn A; Dupont-Versteegden, Esther E; McCarthy, John J

    2015-01-01

    The purpose of this study was to compare the gene expression profile of mouse skeletal muscle undergoing two forms of growth (hypertrophy and regrowth) with the goal of identifying a conserved set of differentially expressed genes. Expression profiling by microarray was performed on the plantaris muscle subjected to 1, 3, 5, 7, 10, and 14 days of hypertrophy or regrowth following 2 wk of hind-limb suspension. We identified 97 differentially expressed genes (≥2-fold increase or ≥50% decrease compared with control muscle) that were conserved during the two forms of muscle growth. The vast majority (∼90%) of the differentially expressed genes was upregulated and occurred at a single time point (64 out of 86 genes), which most often was on the first day of the time course. Microarray analysis from the conserved upregulated genes showed a set of genes related to contractile apparatus and stress response at day 1, including three genes involved in mechanotransduction and four genes encoding heat shock proteins. Our analysis further identified three cell cycle-related genes at day and several genes associated with extracellular matrix (ECM) at both days 3 and 10. In conclusion, we have identified a core set of genes commonly upregulated in two forms of muscle growth that could play a role in the maintenance of sarcomere stability, ECM remodeling, cell proliferation, fast-to-slow fiber type transition, and the regulation of skeletal muscle growth. These findings suggest conserved regulatory mechanisms involved in the adaptation of skeletal muscle to increased mechanical loading. Copyright © 2015 the American Physiological Society.

  7. Portland cement induces human periodontal ligament cells to differentiate by upregulating miR-146a

    Directory of Open Access Journals (Sweden)

    Min-Ching Wang

    2018-04-01

    Full Text Available Background/Purpose: Bioaggregates such as Portland cement (PC can be an economical alternative for mineral trioxide aggregate (MTA with additional benefit of less discoloration. MTA has been known to induce differentiations of several dental cells. MicroRNAs are important regulators of biological processes, including differentiation, physiologic homeostasis, and disease progression. This study is to explore how PC enhances the differentiation of periodontal ligament (PDL cells in microRNAs level. Methods: PDL cells were cultured in a regular PC- or MTA-conditioned medium or an osteoinduction medium (OIM. Alizarin red staining was used to evaluate the extent of mineralization. Transfection of microRNA mimics induced exogenous miR-31 and miR-146a expression. The expression of microRNAs and differentiation markers was assayed using reverse-transcriptase polymerase chain reaction. Results: PC enhanced the mineralization of PDL cells in a dose-dependent manner in the OIM. Exogenous miR-31 and miR-146a expression upregulated alkaline phosphatase (ALP, bone morphogenic protein (BMP, and dentin matrix protein 1 (DMP1 expression. However, miR-31 and miR-146a modulates cementum protein 1 (CEMP1 expression in different ways. PC also enhanced ALP and BMP but attenuated CEMP1 in the OIM. Although the OIM or PC treatment upregulated miR-21, miR-29b, and miR-146a, only miR-146a was able to be induced by PC in combination with OIM. Conclusion: This study demonstrated that PC enhances the differentiation of PDL cells, especially osteogenic through miR-146a upregulation. In order to control the ankylosis after regenerative endodontics with the usage of bioaggregates, further investigations to explore these differentiation mechanisms in the miRNA level may be needed. Keywords: Portland cement, Bioaggregate, miR-146a, Osteogenic differentiation, Periodontal ligament (PDL

  8. Nestin upregulation characterizes vascular remodeling secondary to hypertension in the rat.

    Science.gov (United States)

    Tardif, Kim; Hertig, Vanessa; Duquette, Natacha; Villeneuve, Louis; El-Hamamsy, Ismail; Tanguay, Jean-François; Calderone, Angelino

    2015-05-15

    Proliferation and hypertrophy of vascular smooth muscle cells represent hallmark features of vessel remodeling secondary to hypertension. The intermediate filament protein nestin was recently identified in vascular smooth muscle cells and in other cell types directly participated in proliferation. The present study tested the hypothesis that vessel remodeling secondary to hypertension was characterized by nestin upregulation in vascular smooth muscle cells. Two weeks after suprarenal abdominal aorta constriction of adult male Sprague-Dawley rats, elevated mean arterial pressure increased the media area and thickness of the carotid artery and aorta and concomitantly upregulated nestin protein levels. In the normal adult rat carotid artery, nestin immunoreactivity was observed in a subpopulation of vascular smooth muscle cells, and the density significantly increased following suprarenal abdominal aorta constriction. Filamentous nestin was detected in cultured rat carotid artery- and aorta-derived vascular smooth muscle cells and an analogous paradigm observed in human aorta-derived vascular smooth muscle cells. ANG II and EGF treatment of vascular smooth muscle cells stimulated DNA and protein synthesis and increased nestin protein levels. Lentiviral short-hairpin RNA-mediated nestin depletion of carotid artery-derived vascular smooth muscle cells inhibited peptide growth factor-stimulated DNA synthesis, whereas protein synthesis remained intact. These data have demonstrated that vessel remodeling secondary to hypertension was characterized in part by nestin upregulation in vascular smooth muscle cells. The selective role of nestin in peptide growth factor-stimulated DNA synthesis has revealed that the proliferative and hypertrophic responses of vascular smooth muscle cells were mediated by divergent signaling events. Copyright © 2015 the American Physiological Society.

  9. Upregulation of CREB-mediated transcription enhances both short- and long-term memory.

    Science.gov (United States)

    Suzuki, Akinobu; Fukushima, Hotaka; Mukawa, Takuya; Toyoda, Hiroki; Wu, Long-Jun; Zhao, Ming-Gao; Xu, Hui; Shang, Yuze; Endoh, Kengo; Iwamoto, Taku; Mamiya, Nori; Okano, Emiko; Hasegawa, Shunsuke; Mercaldo, Valentina; Zhang, Yue; Maeda, Ryouta; Ohta, Miho; Josselyn, Sheena A; Zhuo, Min; Kida, Satoshi

    2011-06-15

    Unraveling the mechanisms by which the molecular manipulation of genes of interest enhances cognitive function is important to establish genetic therapies for cognitive disorders. Although CREB is thought to positively regulate formation of long-term memory (LTM), gain-of-function effects of CREB remain poorly understood, especially at the behavioral level. To address this, we generated four lines of transgenic mice expressing dominant active CREB mutants (CREB-Y134F or CREB-DIEDML) in the forebrain that exhibited moderate upregulation of CREB activity. These transgenic lines improved not only LTM but also long-lasting long-term potentiation in the CA1 area in the hippocampus. However, we also observed enhanced short-term memory (STM) in contextual fear-conditioning and social recognition tasks. Enhanced LTM and STM could be dissociated behaviorally in these four lines of transgenic mice, suggesting that the underlying mechanism for enhanced STM and LTM are distinct. LTM enhancement seems to be attributable to the improvement of memory consolidation by the upregulation of CREB transcriptional activity, whereas higher basal levels of BDNF, a CREB target gene, predicted enhanced shorter-term memory. The importance of BDNF in STM was verified by microinfusing BDNF or BDNF inhibitors into the hippocampus of wild-type or transgenic mice. Additionally, increasing BDNF further enhanced LTM in one of the lines of transgenic mice that displayed a normal BDNF level but enhanced LTM, suggesting that upregulation of BDNF and CREB activity cooperatively enhances LTM formation. Our findings suggest that CREB positively regulates memory consolidation and affects memory performance by regulating BDNF expression.

  10. Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

    LENUS (Irish Health Repository)

    Cronin, Patricia A

    2010-05-21

    Abstract Background Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α. Methods Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability. Results CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-α in vitro. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness. Conclusions CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.

  11. Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival

    International Nuclear Information System (INIS)

    Eftang, Lars L; Esbensen, Ying; Tannæs, Tone M; Blom, Gustav P; Bukholm, Ida RK; Bukholm, Geir

    2013-01-01

    The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastric adenocarcinomas from a Norwegian selection, compared to matched normal mucosa, and we have related our findings to prognosis, survival and chronic Helicobacter pylori infection. Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 20 patients immediately following surgical resection of the tumor. Whole genome, cDNA microarray analysis was performed on the RNA isolated from the sample pairs to compare the gene expression profiles between the tumor against matched mucosa. The samples were microscopically examined to classify gastritis. The presence of H. pylori was examined using microscopy and immunohistochemistry. 130 genes showed differential regulation above a predefined cut-off level. Interleukin-8 (IL-8) and Claudin-1 (CLDN1) were the most consistently up-regulated genes in the tumors. Very high CLDN1 expression in the tumor was identified as an independent and significant predictor gene of reduced post-operative survival. There were distinctly different expression profiles between the tumor group and the control mucosa group, and the histological subsets of mixed type, diffuse type and intestinal type cancer demonstrated further sub-clustering. Up-regulated genes were mapped to cell-adhesion, collagen-related processes and angiogenesis, whereas normal intestinal functions such as digestion and excretion were associated with down-regulated genes. We relate the current findings to our previous study on the gene response of gastric epithelial cells to H. pylori infection. CLDN1 was highly up-regulated in gastric cancer, and CLDN1 expression was independently associated with a poor post-operative prognosis, and may have important prognostic

  12. Reciprocal upregulation of Notch signaling molecules in hematopoietic progenitor and mesenchymal stromal cells

    Directory of Open Access Journals (Sweden)

    Kikuchi Y

    2011-01-01

    Full Text Available Although mesenchymal stem cells (MSCs play pivotal supportive roles in hematopoiesis, how they interact with hematopoietic stem cells (HSCs is not well understood. We investigated the interaction between HSCs and surrogate MSCs (C3H10T1/2 stromal cells, focusing on the molecular events induced by cell contact of these bipartite populations. C3H10T1/2 is a mesenchymal stromal cell line that can be induced to differentiate into preadipocytes (A54 and myoblasts (M1601. The stromal cell derivatives were cocultured with murine HSCs (Lineage-Sca1+, and gene expression profiles in stromal cells and HSCs were compared before and after the coculture. HSCs gave rise to cobblestone areas only on A54 cells, with ninefold more progenitors than on M1601 or undifferentiated C3H10T1/2 cells. Microarray-based screening and a quantitative reverse transcriptase directed-polymerase chain reaction showed that the levels of Notch ligands (Jagged1 and Delta-like 3 were increased in A54 cells upon interaction with HSCs. On the other hand, the expression of Notch1 and Hes1 was upregulated in the HSCs cocultured with A54 cells. A transwell assay revealed that the reciprocal upregulation was dependent on cell-to-cell contact. The result suggested that in the hematopoietic niche, HSCs help MSCs to produce Notch ligands, and in turn, MSCs help HSCs to express Notch receptor. Such a reciprocal upregulation would reinforce the downstream signaling to determine the fate of hematopoietic cell lineage. Clarification of the initiating events on cell contact should lead to the identification of specific molecular targets to facilitate HSC engraftment in transplantation therapy.

  13. Myostatin signaling is up-regulated in female patients with advanced heart failure.

    Science.gov (United States)

    Ishida, Junichi; Konishi, Masaaki; Saitoh, Masakazu; Anker, Markus; Anker, Stefan D; Springer, Jochen

    2017-07-01

    Myostatin, a negative regulator of skeletal muscle mass, is up-regulated in the myocardium of heart failure (HF) and increased myostatin is associated with weight loss in animal models with HF. Although there are disparities in pathophysiology and epidemiology between male and female patients with HF, it remains unclear whether there is gender difference in myostatin expression and whether it is associated with weight loss in HF patients. Heart tissue samples were collected from patients with advanced heart failure (n=31, female n=5) as well as healthy control donors (n=14, female n=6). Expression levels of myostatin and its related proteins in the heart were evaluated by western blotting analysis. Body mass index was significantly lower in female HF patients than in male counterparts (20.0±4.2 in female vs 25.2±3.8 in male, p=0.04). In female HF patients, both mature myostatin and pSmad2 were significantly up-regulated by 1.9 fold (p=0.05) and 2.5 fold (pmyostatin was not. There was no significant difference in protein expression related to myostatin signaling between male and female patients. In this study, myostatin and pSmad2 were significantly up-regulated in the failing heart of female patients, but not male patients, and female patients displayed lower body mass index. Enhanced myostatin signaling in female failing heart may causally contribute to pathogenesis of HF and cardiac cachexia. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. KSHV encoded LANA upregulates Pim-1 and is a substrate for its kinase activity

    International Nuclear Information System (INIS)

    Bajaj, Bharat G.; Verma, Subhash C.; Lan, Ke; Cotter, Murray A.; Woodman, Zenda L.; Robertson, Erle S.

    2006-01-01

    Pim kinases are proto-oncogenes that are upregulated in a number of B cell cancers, including Epstein-Barr Virus (EBV) associated Burkitt's lymphoma. They have also been shown to be upregulated in Kaposi sarcoma-associated herpes virus (KSHV) infected primary B cells. Most cells in KSHV-associated tumors are latently infected and express only a small subset of viral genes, with KSHV latency associated nuclear antigen (LANA) being constitutively expressed. LANA regulates the transcription of a large number of cellular and viral genes. Here, we show that LANA upregulates transcription from the Pim-1 promoter (pPim-1) and map this activation to a region in the promoter located within the sequence (-681 to +37). We show that LANA expressing cells can proliferate faster and are better protected from drug induced apoptosis. Since transition through cell cycle check points and anti-apoptosis are functions associated with Pim-1, it is likely that higher Pim-1 expression in cells expressing LANA is responsible, at least in part, for this effect. A Pim-1 phosphorylation site was also identified within the amino-terminal domain of LANA. Using in vitro kinase assays, we confirmed that LANA was indeed a Pim-1 substrate, and the failure of Pim-1 to phosphorylate LANA mutated at SS205/6RR identified this site as the specific serine residues phosphorylated by Pim-1. This report provides valuable insight into yet another cellular signaling pathway subverted by KSHV LANA and suggests a contribution to KSHV related oncogenesis

  15. Up-regulation of the chemokine CCL21 in the skin of subjects exposed to irritants

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    Kuznitzky Raquel

    2004-04-01

    Full Text Available Abstract Background Expression of murine CCL21 by dermal lymphatic endothelial cells (LEC has been demonstrated to be one of the most important steps in Langerhans cell emigration from skin. Previously, our group and others have found that this chemokine is up-regulated in different human inflammatory skin diseases mediated by diverse specific immune responses. This study was carried out to investigate the involvement of CCL21 in human skin after challenge with irritant agents responsible for inducing Irritant Contact Dermatitis (ICD. Results Eleven normal individuals were challenged with different chemical or physical irritants. Two patients with Allergic Contact Dermatitis (ACD were also challenged with the relevant antigen in order to have a positive control for CCL21 expression. Macroscopic as well as microscopic responses were evaluated. We observed typical ICD responses with mostly mononuclear cells in perivascular areas, but a predominance of polymorphonuclear cells away from the inflamed blood vessels and in the epidermis at 24 hours. Immunohistochemical studies showed up-regulation of CCL21 by lymphatic endothelial cells in all the biopsies taken from ICD and ACD lesions compared to normal skin. Kinetic study at 10, 48, 96 and 168 hours after contact with a classical irritant (sodium lauryl sulphate showed that the expression of CCL21 was increased in lymphatic vessels at 10 hours, peaked at 48 hours, and then gradually declined. There was a strong correlation between CCL21 expression and the macroscopic response (r = 0.69; p = 0.0008, but not between CCL21 and the number of infiltrating cells in the lesions. Conclusions These results provide new evidence for the role of CCL21 in inflammatory processes. Since the up-regulation of this chemokine was observed in ICD and ACD, it is tempting to speculate that this mechanism operates independently of the type of dermal insult, facilitating the emigration of CCR7+ cells.

  16. Upregulation of gene expression in reward-modulatory striatal opioid systems by sleep loss.

    Science.gov (United States)

    Baldo, Brian A; Hanlon, Erin C; Obermeyer, William; Bremer, Quentin; Paletz, Elliott; Benca, Ruth M

    2013-12-01

    Epidemiological studies have shown a link between sleep loss and the obesity 'epidemic,' and several observations indicate that sleep curtailment engenders positive energy balance via increased palatable-food 'snacking.' These effects suggest alterations in reward-modulatory brain systems. We explored the effects of 10 days of sleep deprivation in rats on the expression of striatal opioid peptide (OP) genes that subserve food motivation and hedonic reward, and compared effects with those seen in hypothalamic energy balance-regulatory systems. Sleep-deprived (Sleep-Dep) rats were compared with yoked forced-locomotion apparatus controls (App-Controls), food-restricted rats (Food-Restrict), and unmanipulated controls (Home-Cage). Detection of mRNA levels with in situ hybridization revealed a subregion-specific upregulation of striatal preproenkephalin and prodynorhin gene expression in the Sleep-Dep group relative to all other groups. Neuropeptide Y (NPY) gene expression in the hippocampal dentate gyrus and throughout neocortex was also robustly upregulated selectively in the Sleep-Dep group. In contrast, parallel gene expression changes were observed in the Sleep-Dep and Food-Restrict groups in hypothalamic energy-sensing systems (arcuate nucleus NPY was upregulated, and cocaine- and amphetamine-regulated transcript was downregulated), in alignment with leptin suppression in both groups. Together, these results reveal a novel set of sleep deprivation-induced transcriptional changes in reward-modulatory peptide systems, which are dissociable from the energy-balance perturbations of sleep loss or the potentially stressful effects of the forced-locomotion procedure. The recruitment of telencephalic food-reward systems may provide a feeding drive highly resistant to feedback control, which could engender obesity through the enhancement of palatable feeding.

  17. Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

    Science.gov (United States)

    Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

    2015-10-01

    Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness. © 2014 Wiley Periodicals, Inc.

  18. PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Shuang, E-mail: luoshuangsch@163.com [Department of Obstetrics and Gynecology, Suining Central Hospital, Suining (China); Wang, Jidong [Department of Gynecology and Obsterics, Jinan Central Hospital, Jinan (China); Ma, Ying [Department of Otorhinolaryngolgy, Suining Central Hospital, Suining (China); Yao, Zhenwei [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Pan, Hongjuan [Department of Gynecology and Obsterics, Zhongshan Hospital, Wuhan (China)

    2015-06-26

    miR-125b has essential roles in coordinating tumor proliferation, angiogenesis, invasiveness, metastasis and chemotherapy recurrence. In ovarian cancer miR-125b has been shown to be downregulated and acts as a tumor suppressor by targeting proto-oncogene BCL3. PPARγ, a multiple functional transcription factor, has been reported to have anti-tumor effects through inhibition of proliferation and induction of differentiation and apoptosis by targeting the tumor related genes. However, it is unclear whether miR-125b is regulated by PPARγ in ovarian cancer. In this study, we demonstrated that the miR-125b downregulated in ovarian cancer tissues and cell lines. Ligands-activated PPARγ suppressed proliferation of ovarian cancer cells and this PPARγ-induced growth inhibition is mediated by the upregulation of miR-125b. PPARγ promoted the expression of miR-125b by directly binding to the responsive element in miR-125b gene promoter region. Thus, our results suggest that PPARγ can induce growth suppression of ovarian cancer by upregulating miR-125b which inhibition of proto-oncogene BCL3. These findings will extend our understanding of the function of PPARγ in tumorigenesis and miR-125b may be a therapeutic intervention of ovarian cancer. - Highlights: • miR-125b is down-regulated in ovarian cancer tissues and cells. • PPARγ upregulates miR-125b and downregulates its target gene BCL3 expression. • Silence of miR-125b attenuates PPARγ-mediated growth suppression of ovarian cancer cells. • PPARγ promotes the transcription of miR-125b via binding to PPARE in miR-125b gene promoter region.

  19. The Natural Antimicrobial Enzyme Lysozyme is Up-Regulated in Gastrointestinal Inflammatory Conditions

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    Carlos A. Rubio

    2014-01-01

    Full Text Available The cells that line the mucosa of the human gastrointestinal tract (GI, that is, oral cavity, oesophagus, stomach, small intestine, large intestine, and rectum are constantly challenged by adverse micro-environmental factors, such as different pH, enzymes, and bacterial flora. With exception of the oral cavity, these microenvironments also contain remnant cocktails of secreted enzymes and bacteria from upper organs along the tract. The density of the GI bacteria varies, from 103/mL near the gastric outlet, to 1010/mL at the ileocecal valve, to 1011 to 1012/mL in the colon. The total microbial population (ca. 1014 exceeds the total number of cells in the tract. It is, therefore, remarkable that despite the prima facie inauspicious mixture of harmful secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To counteract the hostile microenvironment, the GI epithelia react by speeding cell exfoliation (the GI mucosa has a turnover time of two to three days, by increasing peristalsis, by eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial compounds, such as defensin-5 and lysozyme. Only recently, lysozyme was found up-regulated in Barrett’s oesophagitis, chronic gastritis, gluten-induced atrophic duodenitis (coeliac disease, collagenous colitis, lymphocytic colitis, and Crohn’s colitis. This up-regulation is a response directed to the special types of bacteria recently detected in these diseases. The aim of lysozyme up-regulation is to protect individual mucosal segments to chronic inflammation. The molecular mechanisms connected to the crosstalk between the intraluminal bacterial flora and the production of lysozyme released by the GI mucosae, are discussed. Bacterial resistance continues to exhaust our supply of commercial antibiotics. The potential use of lysozyme to treat infectious diseases is receiving much attention.

  20. LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma

    OpenAIRE

    Yun-Bo, Feng; Xiao-Po, Liu; Xiao-Li, Li; Guo-Long, Cao; Pei, Zhang; Fa-Ming, Tian

    2016-01-01

    Abstract Objective: To examine the expression and function of long non-coding RNA taurine up-regulated 1 (TUG1) in human osteosarcoma cells. Methods: Real-time quantitive PCR was used to detect the transcription level of TUG1 in a series of osteosarcoma cell lines. Knockdown of TUG1 in U2OS cells was carried out by transient transfection of siRNAs. MTT assay was performed to access the cell growth rates. Afterwards, RNA and protein of these cells were extracted to analyze the transfection eff...

  1. Severe energy deficit upregulates leptin receptors, leptin signaling, and PTP1B in human skeletal muscle.

    Science.gov (United States)

    Perez-Suarez, Ismael; Ponce-González, Jesús Gustavo; de La Calle-Herrero, Jaime; Losa-Reyna, Jose; Martin-Rincon, Marcos; Morales-Alamo, David; Santana, Alfredo; Holmberg, Hans-Christer; Calbet, Jose A L

    2017-11-01

    In obesity, leptin receptors (OBR) and leptin signaling in skeletal muscle are downregulated. To determine whether OBR and leptin signaling are upregulated with a severe energy deficit, 15 overweight men were assessed before the intervention (PRE), after 4 days of caloric restriction (3.2 kcal·kg body wt -1 ·day -1 ) in combination with prolonged exercise (CRE; 8 h walking + 45 min single-arm cranking/day) to induce an energy deficit of ~5,500 kcal/day, and following 3 days of control diet (isoenergetic) and reduced exercise (CD). During CRE, the diet consisted solely of whey protein ( n = 8) or sucrose ( n = 7; 0.8 g·kg body wt -1 ·day -1 ). Muscle biopsies were obtained from the exercised and the nonexercised deltoid muscles and from the vastus lateralis. From PRE to CRE, serum glucose, insulin, and leptin were reduced. OBR expression was augmented in all examined muscles associated with increased maximal fat oxidation. Compared with PRE, after CD, phospho-Tyr 1141 OBR, phospho-Tyr 985 OBR, JAK2, and phospho-Tyr 1007/1008 JAK2 protein expression were increased in all muscles, whereas STAT3 and phospho-Tyr 705 STAT3 were increased only in the arms. The expression of protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle was increased by 18 and 45% after CRE and CD, respectively ( P < 0.05). Suppressor of cytokine signaling 3 (SOCS3) tended to increase in the legs and decrease in the arm muscles (ANOVA interaction: P < 0.05). Myosin heavy chain I isoform was associated with OBR protein expression ( r  = -0.75), phospho-Tyr 985 OBR ( r  = 0.88), and phospho-Tyr 705 STAT3/STAT3 ( r = 0.74). In summary, despite increased PTP1B expression, skeletal muscle OBR and signaling are upregulated by a severe energy deficit with greater response in the arm than in the legs likely due to SOCS3 upregulation in the leg muscles. NEW & NOTEWORTHY This study shows that the skeletal muscle leptin receptors and their corresponding signaling cascade are upregulated in

  2. Up-regulation of ALG-2 in hepatomas and lung cancer tissue

    DEFF Research Database (Denmark)

    la Cour, Jonas Marstrand; Mollerup, Jens; Winding, Pernille

    2003-01-01

    , a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our...... using Western blot analysis and immunohistochemistry. Western blot analysis of 15 different adult mouse tissues demonstrated that ALG-2 is ubiquitously expressed. We found that ALG-2 was more than threefold overexpressed in rat liver hepatoma compared to normal rat liver using Western blot analysis...

  3. Insecticide-Mediated Up-Regulation of Cytochrome P450 Genes in the Red Flour Beetle (Tribolium castaneum

    Directory of Open Access Journals (Sweden)

    Xiao Liang

    2015-01-01

    Full Text Available Some cytochrome P450 (CYP genes are known for their rapid up-regulation in response to insecticide exposures in insects. To date, however, limited information is available with respect to the relationships among the insecticide type, insecticide concentration, exposure duration and the up-regulated CYP genes. In this study, we examined the transcriptional response of eight selected CYP genes, including CYP4G7, CYP4Q4, CYP4BR3, CYP12H1, CYP6BK11, CYP9D4, CYP9Z5 and CYP345A1, to each of four insecticides in the red flour beetle, Tribolium castaneum. Reverse transcription quantitative PCR (RT-qPCR revealed that CYP4G7 and CYP345A1 can be significantly up-regulated by cypermethrin (1.97- and 2.06-fold, respectively, permethrin (2.00- and 2.03-fold and lambda-cyhalothrin (1.73- and 1.81-fold, whereas CYP4BR3 and CYP345A1 can be significantly up-regulated by imidacloprid (1.99- and 1.83-fold when 20-day larvae were exposed to each of these insecticides at the concentration of LC20 for 24 h. Our studies also showed that similar levels of up-regulation can be achieved for CYP4G7, CYP4BR3 and CYP345A1 by cypermethrin, permethrin, lambda-cyhalothrin or imidacloprid with approximately one fourth of LC20 in 6 h. Our study demonstrated that up-regulation of these CYP genes was rapid and only required low concentrations of insecticides, and the up-regulation not only depended on the CYP genes but also the type of insecticides. Our results along with those from previous studies also indicated that there were no specific patterns for predicting the up-regulation of specific CYP gene families based on the insecticide classification.

  4. Dysregulation of mitotic machinery genes precedes genome instability during spontaneous pre-malignant transformation of mouse ovarian surface epithelial cells

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    Ulises Urzúa

    2016-10-01

    Full Text Available Abstract Background Based in epidemiological evidence, repetitive ovulation has been proposed to play a role in the origin of ovarian cancer by inducing an aberrant wound rupture-repair process of the ovarian surface epithelium (OSE. Accordingly, long term cultures of isolated OSE cells undergo in vitro spontaneous transformation thus developing tumorigenic capacity upon extensive subcultivation. In this work, C57BL/6 mouse OSE (MOSE cells were cultured up to passage 28 and their RNA and DNA copy number profiles obtained at passages 2, 5, 7, 10, 14, 18, 23, 25 and 28 by means of DNA microarrays. Gene ontology, pathway and network analyses were focused in passages earlier than 20, which is a hallmark of malignancy in this model. Results At passage 14, 101 genes were up-regulated in absence of significant DNA copy number changes. Among these, the top-3 enriched functions (>30 fold, adj p < 0.05 comprised 7 genes coding for centralspindlin, chromosome passenger and minichromosome maintenance protein complexes. The genes Ccnb1 (Cyclin B1, Birc5 (Survivin, Nusap1 and Kif23 were the most recurrent in over a dozen GO terms related to the mitotic process. On the other hand, Pten plus the large non-coding RNAs Malat1 and Neat1 were among the 80 down-regulated genes with mRNA processing, nuclear bodies, ER-stress response and tumor suppression as relevant terms. Interestingly, the earliest discrete segmental aneuploidies arose by passage 18 in chromosomes 7, 10, 11, 13, 15, 17 and 19. By passage 23, when MOSE cells express the malignant phenotype, the dysregulated gene expression repertoire expanded, DNA imbalances enlarged in size and covered additional loci. Conclusion Prior to early aneuploidies, overexpression of genes coding for the mitotic apparatus in passage-14 pre-malignant MOSE cells indicate an increased proliferation rate suggestive of replicative stress. Concomitant down-regulation of nuclear bodies and RNA processing related genes

  5. The Effect of Educational Intervention Based on PRECEDE-PROCEED Model on Promoting Traffic Safety Behaviors in Primary Schools Students of Tabriz in 2014

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    Saeed Omidi

    2016-03-01

    Full Text Available Background and Objectives: Pedestrian injuries are a public health problem and one of the major victims of road traffic injuries are children. Education is one of the most important strategies to solve traffic problems. To achieve effective results, education should be defined on the basis of theories and models. The aim of this study was to evaluate the effect of PRECEDE-PROCEED based intervention for promoting traffic safety behaviors in elementary schools students of Tabriz. Materials and Methods: This study was a randomized controlled trial. The sample included 75 elementary students who were randomly selected from two different schools. Data was collected using a questionnaire including the PRECEDE-PROCEED model constructs and demographic variables. Participants completed questionnaires before and one month after intervention. The intervention consisted of six sessions and was conducted in experimental group schools. The data were analyzed with fisher’s exact test, chi square, t-test and paired t-test, using SPSS-18 software. Results: The average age of participants was 10.11 ± 0.68 years. There was no significant differences in demographic variables between the two groups before the intervention (P>0.05. The findings showed that after the educational intervention, significant differences were observed in knowledge, attitude, enabling factors, reinforcing factors and behavior scores in the experimental group compared to the control group. Conclusions: An educational intervention based on the PRECEDE-PROCEED model could promote students’ traffic safety behaviors.

  6. Some anomalous behaviour of vertebrates and insects preceding M5+ earthquakes in the North Western Apennines (Italy)

    Science.gov (United States)

    Straser, Valentino

    2013-04-01

    Earthquakes with a magnitude greater than M5+ are an unusual event in the seismic area of the Frignano District and the areas surrounding Parma in the North Western Apennines (Italy). Only two seismic events have occurred in the last four years: on 23 December 2008 (M5.1) and on 27 January 2012 (M5.4). The earthquake of 23 December 2008 allowed the verification of unusual behaviour in man and animals in the run-up to the main shock, in addition to anomalies of an electromagnetic type. An initial study showed that there are elements of coincidence between the seismic events and the number of admissions to hospitals around the epicentre: in the month of December 2008, the days with the greatest number of admissions coincided with seismic shocks. A half hour before the main event of 23 December, recorded at 16:24:21 local time (see: INGV), a slowworm (Anguis fragilis) left its hibernation site and died shortly afterwards from the cold on a road, as did a viper (Vipera aspis) found near some dwellings in an area around twenty kilometres from the epicentre. The investigation proceeded in 2009, but this time based on the number of daily admissions to the hospital A&E department, between June and December 2009. During the six months of the investigation, the maximum number of emergencies was 9 per day, while the earthquakes were in line with the usual number and magnitude for the Frignano seismic district. The earthquakes from June to December 2009 numbered 10, with a magnitude from M2.5 to M3.6. In 8 cases, in the 48 hours preceding the occurrence of the seism, there was a greater number of hospital emergencies. The subsequent occasion to check on a possible relationship between anomalous behaviour in animals and a seism occurred on 27 January 2012 (see: INGV), when an earthquake with a magnitude of M5.4 shook the North Western Apennines, thankfully without resulting in victims. Like 2008, in an area around fifteen kilometres from the epicentre, a grass snake (Zamenis

  7. Diastolic And Systolic Right Ventricular Dysfunction Precedes Left Ventricular Dysfunction In Patients Paced From Right Ventricular Apex

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    Dwivedi SK

    2006-07-01

    .05 without any significant change in the resting cardiac output. Conclusion: The present study shows that dysfunction of right ventricle is the first abnormality that occurs in VVI paced patients, which manifests by 1 week followed by LV dysfunction which starts appearing by 1 month and the diastolic dysfunctions precede the systolic dysfunction in both ventricles.

  8. The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina.

    Science.gov (United States)

    Young, T L; Matsuda, T; Cepko, C L

    2005-03-29

    With the advent of genome-wide analyses, it is becoming evident that a large number of noncoding RNAs (ncRNAs) are expressed in vertebrates. However, of the thousands of ncRNAs identified, the functions of relatively few have been established. In a screen for genes upregulated by taurine in developing retinal cells, we identified a gene that appears to be a ncRNA. Taurine Upregulated Gene 1 (TUG1) is a spliced, polyadenylated RNA that does not encode any open reading frame greater than 82 amino acids in its full-length, 6.7 kilobase (kb) RNA sequence. Analyses of Northern blots and in situ hybridization revealed that TUG1 is expressed in the developing retina and brain, as well as in adult tissues. In the newborn retina, knockdown of TUG1 with RNA interference (RNAi) resulted in malformed or nonexistent outer segments of transfected photoreceptors. Immunofluorescent staining and microarray analyses suggested that this loss of proper photoreceptor differentiation is a result of the disregulation of photoreceptor gene expression. A function for a newly identified ncRNA, TUG1, has been established. TUG1 is necessary for the proper formation of photoreceptors in the developing rodent retina.

  9. Upregulation of long noncoding RNA TUG1 promotes cervical cancer cell proliferation and migration.

    Science.gov (United States)

    Hu, Yingying; Sun, Xiangwei; Mao, Chenchen; Guo, Gangqiang; Ye, Sisi; Xu, Jianfeng; Zou, Ruanmin; Chen, Jun; Wang, Ledan; Duan, Ping; Xue, Xiangyang

    2017-02-01

    Long noncoding RNAs (lncRNAs), a novel class of transcripts that have critical roles in carcinogenesis and progression, have emerged as important gene expression modulators. Recent evidence indicates that lncRNA taurine-upregulated gene 1 (TUG1) functions as an oncogene in numerous types of human cancers. However, its function in the development of cervical cancer remains unknown. The aim of this research was to investigate the clinical significance and biological functions of TUG1 in cervical cancer. TUG1 was found to be significantly upregulated in cervical cancer tissues and four cervical cancer cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Elevated TUG1 expression was correlated with larger tumor size, advanced international federation of gynecology and obstetrics (FIGO) stage, poor differentiation, and lymph node metastasis. Furthermore, knockdown of TUG1 suppressed cell proliferation with activation of apoptosis, in part by regulating the expression of Bcl-2 and caspase-3. Silencing of TUG1 inhibited cell migration and invasion via the progression of epithelial-mesenchymal transition (EMT). Taken together, our findings indicate that TUG1 acts as an oncogene in cervical cancer and may represent a novel therapeutic target. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  10. IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance.

    Science.gov (United States)

    Tsai, Pei-Yun; Zhang, Bingkun; He, Wei-Qi; Zha, Juan-Min; Odenwald, Matthew A; Singh, Gurminder; Tamura, Atsushi; Shen, Le; Sailer, Anne; Yeruva, Sunil; Kuo, Wei-Ting; Fu, Yang-Xin; Tsukita, Sachiko; Turner, Jerrold R

    2017-06-14

    Diarrhea is a host response to enteric pathogens, but its impact on pathogenesis remains poorly defined. By infecting mice with the attaching and effacing bacteria Citrobacter rodentium, we defined the mechanisms and contributions of diarrhea and intestinal barrier loss to host defense. Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. Permeability increases were limited to small molecules, as expected for the paracellular water and Na + channel formed by claudin-2. Relative to wild-type, claudin-2-deficient mice experienced severe disease, including increased mucosal colonization by C. rodentium, prolonged pathogen shedding, exaggerated cytokine responses, and greater tissue injury. Conversely, transgenic claudin-2 overexpression reduced disease severity. Chemically induced osmotic diarrhea reduced colitis severity and C. rodentium burden in claudin-2-deficient, but not transgenic, mice, demonstrating that claudin-2-mediated protection is the result of enhanced water efflux. Thus, IL-22-induced claudin-2 upregulation drives diarrhea and pathogen clearance. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.

    LENUS (Irish Health Repository)

    O'Connor, Terence M

    2012-02-03

    Substance P (SP) is a proinflammatory neuropeptide that is secreted by sensory nerves and inflammatory cells. Increased levels of SP are found in sarcoid bronchoalveolar lavage fluid. SP acts by binding to the neurokinin-1 receptor and increases secretion of tumor necrosis factor-alpha in many cell types. We sought to determine neurokinin-1 receptor expression in patients with sarcoidosis compared with normal controls. Neurokinin-1 receptor messenger RNA and protein expression were below the limits of detection by reverse transcriptase-polymerase chain reaction and immunohistochemistry in peripheral blood mononuclear cells of healthy volunteers (n = 9) or patients with stage 1 or 2 pulmonary sarcoidosis (n = 10), but were detected in 1\\/9 bronchoalveolar lavage cells of controls compared with 8\\/10 patients with sarcoidosis (p = 0.012) and 2\\/9 biopsies of controls compared with 9\\/10 patients with sarcoidosis (p = 0.013). Immunohistochemistry localized upregulated neurokinin-1 receptor expression to bronchial and alveolar epithelial cells, macrophages, lymphocytes, and sarcoid granulomas. The patient in whom neurokinin-1 receptor was not detected was taking corticosteroids. Incubation of the type II alveolar and bronchial epithelial cell lines A549 and SK-LU 1 with dexamethasone downregulated neurokinin-1 receptor expression. Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may potentiate substance P-induced proinflammatory cytokine production in patients with sarcoidosis.

  12. Upregulating Nonneuronal Cholinergic Activity Decreases TNF Release from Lipopolysaccharide-Stimulated RAW264.7 Cells

    Directory of Open Access Journals (Sweden)

    Yi Lv

    2014-01-01

    Full Text Available Nonneuronal cholinergic system plays a primary role in maintaining homeostasis. It has been proved that endogenous neuronal acetylcholine (ACh could play an anti-inflammatory role, and exogenous cholinergic agonists could weaken macrophages inflammatory response to lipopolysaccharide (LPS stimulation through activation of α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR. We assumed that nonneuronal cholinergic system existing in macrophages could modulate inflammation through autocrine ACh and expressed α7nAChR on the cells. Therefore, we explored whether LPS continuous stimulation could upregulate the nonneuronal cholinergic activity in macrophages and whether increasing autocrine ACh could decrease TNF release from the macrophages. The results showed that, in RAW264.7 cells incubated with LPS for 20 hours, the secretion of ACh was significantly decreased at 4 h and then gradually increased, accompanied with the enhancement of α7nAChR expression level. The release of TNF was greatly increased from RAW264.7 cells at 4 h and 8 h exposure to LPS; however, it was suppressed at 20 h. Upregulating choline acetyltransferase (ChAT expression through ChAT gene transfection could enhance ACh secretion and reduce TNF release from the infected RAW264. 7cells. The results indicated that LPS stimulation could modulate the activity of nonneuronal cholinergic system of RAW264.7 cells. Enhancing autocrine ACh production could attenuate TNF release from RAW264.7 cells.

  13. Molecular cloning and functional characterization of a mouse gene upregulated by lipopolysaccharide treatment reveals alternative splicing

    Energy Technology Data Exchange (ETDEWEB)

    Du, Kejun; Chen, Yaoming; Dai, Zongming; Bi, Yuan; Cai, Tongjian [Department of Occupational and Environmental Health, Fourth Military Medical University, Xi' an 710032, Shaanxi Province (China); Hou, Lichao [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032, Shaanxi Province (China); Chai, Yubo; Song, Qinghe; Chen, Sumin [Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi' an 710032, Shaanxi Province (China); Luo, Wenjing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health, Fourth Military Medical University, Xi' an 710032, Shaanxi Province (China); Chen, Jingyuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health, Fourth Military Medical University, Xi' an 710032, Shaanxi Province (China)

    2010-01-01

    Treatment of mouse cells with lipopolysaccharide (LPS) potently initiates an inflammatory response, but the underlying mechanisms are unclear. We therefore sought to characterize cDNA sequences of a new mouse LPS-responsive gene, and to evaluate the effects of MLrg. Full-length cDNAs were obtained from LPS-treated NIH3T3 cells. We report that the MLrg gene produces two alternative splice products (GenBank Accession Nos. (DQ316984) and (DQ320011)), respectively, encoding MLrgW and MLrgS polypeptides. Both proteins contain zinc finger and leucine zipper domains and are thus potential regulators of transcription. Expression of MLrgW and MLrgS were robustly upregulated following LPS treatment, and the proteins were localized predominantly in the nuclear membrane and cytoplasm. In stable transfectants over-expressing MLrgW the proportion of cells in G1 phase was significantly reduced, while in cells over-expressing MLrgS the proportion of cells in G2 was significantly increased; both proteins are thus potential regulators of cell cycle progression. Upregulation of MLrgW and MLrgS may be an important component of the LPS inflammatory pathway and of the host response to infection with GNB.

  14. Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis

    Directory of Open Access Journals (Sweden)

    Karin Zins

    2014-01-01

    Full Text Available The early growth response transcription factor Egr-1 controls cell specific responses to proliferation, differentiation and apoptosis. Expression of Egr-1 and downstream transcription is closely controlled and cell specific upregulation induced by processes such as hypoxia and ischemia has been previously linked to multiple aspects of cardiovascular injury. In this study, we showed constitutive expression of Egr-1 in cultured human ventricular cardiac fibroblasts, used adenoviral mediated gene transfer to study the effects of continuous Egr-1 overexpression and studied downstream transcription by Western blotting, immunohistochemistry and siRNA transfection. Apoptosis was assessed by fluorescence microscopy and flow cytometry in the presence of caspase inhibitors. Overexpression of Egr-1 directly induced apoptosis associated with caspase activation in human cardiac fibroblast cultures in vitro assessed by fluorescence microscopy and flow cytometry. Apoptotic induction was associated with a caspase activation associated loss of mitochondrial membrane potential and transient downstream transcriptional up-regulation of the pro-apoptotic gene product Siva-1. Suppression of Siva-1 induction by siRNA partially reversed Egr-1 mediated loss of cell viability. These findings suggest a previously unknown role for Egr-1 and transcriptional regulation of Siva-1 in the control of cardiac accessory cell death.

  15. Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats.

    Directory of Open Access Journals (Sweden)

    Gloria E Hoffman

    Full Text Available A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC, would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness.

  16. Hibiscus chlorotic ringspot virus coat protein upregulates sulfur metabolism genes for enhanced pathogen defense.

    Science.gov (United States)

    Gao, Ruimin; Ng, Florence Kai Lin; Liu, Peng; Wong, Sek-Man

    2012-12-01

    In both Hibiscus chlorotic ringspot virus (HCRSV)-infected and HCRSV coat protein (CP) agroinfiltrated plant leaves, we showed that sulfur metabolism pathway related genes-namely, sulfite oxidase (SO), sulfite reductase, and adenosine 5'-phosphosulfate kinase-were upregulated. It led us to examine a plausible relationship between sulfur-enhanced resistance (SED) and HCRSV infection. We broadened an established method to include different concentrations of sulfur (0S, 1S, 2S, and 3S) to correlate them to symptom development of HCRSV-infected plants. We treated plants with glutathione and its inhibitor to verify the SED effect. Disease resistance was induced through elevated glutathione contents during HCRSV infection. The upregulation of SO was related to suppression of symptom development induced by sulfur treatment. In this study, we established that HCRSV-CP interacts with SO which, in turn, triggers SED and leads to enhanced plant resistance. Thus, we have discovered a new function of SO in the SED pathway. This is the first report to demonstrate that the interaction of a viral protein and host protein trigger SED in plants. It will be interesting if such interaction applies generally to other host-pathogen interactions that will lead to enhanced pathogen defense.

  17. Honey constituents up-regulate detoxification and immunity genes in the western honey bee Apis mellifera.

    Science.gov (United States)

    Mao, Wenfu; Schuler, Mary A; Berenbaum, May R

    2013-05-28

    As a managed pollinator, the honey bee Apis mellifera is critical to the American agricultural enterprise. Recent colony losses have thus raised concerns; possible explanations for bee decline include nutritional deficiencies and exposures to pesticides and pathogens. We determined that constituents found in honey, including p-coumaric acid, pinocembrin, and pinobanksin 5-methyl ether, specifically induce detoxification genes. These inducers are primarily found not in nectar but in pollen in the case of p-coumaric acid (a monomer of sporopollenin, the principal constituent of pollen cell walls) and propolis, a resinous material gathered and processed by bees to line wax cells. RNA-seq analysis (massively parallel RNA sequencing) revealed that p-coumaric acid specifically up-regulates all classes of detoxification genes as well as select antimicrobial peptide genes. This up-regulation has functional significance in that that adding p-coumaric acid to a diet of sucrose increases midgut metabolism of coumaphos, a widely used in-hive acaricide, by ∼60%. As a major component of pollen grains, p-coumaric acid is ubiquitous in the natural diet of honey bees and may function as a nutraceutical regulating immune and detoxification processes. The widespread apicultural use of honey substitutes, including high-fructose corn syrup, may thus compromise the ability of honey bees to cope with pesticides and pathogens and contribute to colony losses.

  18. Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP

    Science.gov (United States)

    Zhao, Xiaoqi; Liu, Yuzhou; Zhong, Yucheng; Liu, Bo; Yu, Kunwu; Shi, Huairui; Zhu, Ruirui; Meng, Kai; Zhang, Wei; Wu, Bangwei

    2015-01-01

    Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE−/− mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells. PMID:26063978

  19. Upregulation of cytosolic NADP+-dependent isocitrate dehydrogenase by hyperglycemia protects renal cells against oxidative stress.

    Science.gov (United States)

    Lee, Soh-Hyun; Ha, Sun-Ok; Koh, Ho-Jin; Kim, KilSoo; Jeon, Seon-Min; Choi, Myung-Sook; Kwon, Oh-Shin; Huh, Tae-Lin

    2010-02-28

    Hyperglycemia-induced oxidative stress is widely recognized as a key mediator in the pathogenesis of diabetic nephropathy, a complication of diabetes. We found that both expression and enzymatic activity of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) were upregulated in the renal cortexes of diabetic rats and mice. Similarly, IDPc was induced in murine renal proximal tubular OK cells by high hyperglycemia, while it was abrogated by co-treatment with the antioxidant N-Acetyl-Cysteine (NAC). In OK cells, increased expression of IDPc by stable transfection prevented hyperglycemia-mediated reactive oxygen species (ROS) production, subsequent cellular oxidative stress and extracellular matrix accumulation, whereas these processes were all stimulated by decreased IDPc expression. In addition, production of NADPH and GSH in the cytosol was positively correlated with the expression level of IDPc in OK cells. These results together indicate that upregulation of IDPc in response to hyperglycemia might play an essential role in preventing the progression of diabetic nephropathy, which is accompanied by ROS-induced cellular damage and fibrosis, by providing NADPH, the reducing equivalent needed for recycling reduced glutathione and low molecular weight antioxidant thiol proteins.

  20. In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine treatment in baboon using SPECT

    International Nuclear Information System (INIS)

    Kassiou, Michael; Eberl, Stefan; Meikle, Steven R.; Birrell, Alex; Constable, Chris; Fulham, Michael J.; Wong, Dean F.; Musachio, John L.

    2001-01-01

    To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[ 123 I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[ 123 I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (V d ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal V d was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in V d or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment

  1. Thioredoxin reductase 1 upregulates MCP-1 release in human endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhen-Bo [Institute of Biophysics, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Beijing (China); Shen, Xun, E-mail: shenxun@sun5.ibp.ac.cn [Institute of Biophysics, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Beijing (China)

    2009-09-04

    To know if thioredoxin reductase 1 (TrxR1) plays a role in antioxidant defense mechanisms against atherosclerosis, effect of TrxR1 on expression/release of monocyte chemoattractant protein (MCP-1) was investigated in activated human endothelial-like EAhy926 cells. The MCP-1 release and expression, cellular generation of reactive oxygen species (ROS), nuclear translocation and DNA-binding activity of NF-{kappa}B subunit p65 were assayed in cells either overexpressing recombinant TrxR1 or having their endogenous TrxR1 knocked down. It was found that overexpression of TrxR1 enhanced, while knockdown of TrxR1 reduced MCP-1 release and expression. Upregulation of MCP-1 by TrxR1 was associated with increasing generation of intracellular ROS generation, enhanced nuclear translocation and DNA-binding activity of NF-{kappa}B. Assay using NF-{kappa}B reporter revealed that TrxR1 upregulated transcriptional activity of NF-{kappa}B. This study suggests that TrxR1 enhances ROS generation, NF-{kappa}B activity and subsequent MCP-1 expression in endothelial cells, and may promote rather than prevent vascular endothelium from forming atherosclerotic plaque.

  2. Genes up-regulated during red coloration in UV-B irradiated lettuce leaves.

    Science.gov (United States)

    Park, Jong-Sug; Choung, Myoung-Gun; Kim, Jung-Bong; Hahn, Bum-Soo; Kim, Jong-Bum; Bae, Shin-Chul; Roh, Kyung-Hee; Kim, Yong-Hwan; Cheon, Choong-Ill; Sung, Mi-Kyung; Cho, Kang-Jin

    2007-04-01

    Molecular analysis of gene expression differences between green and red lettuce leaves was performed using the SSH method. BlastX comparisons of subtractive expressed sequence tags (ESTs) indicated that 7.6% of clones encoded enzymes involved in secondary metabolism. Such clones had a particularly high abundance of flavonoid-metabolism proteins (6.5%). Following SSH, 566 clones were rescreened for differential gene expression using dot-blot hybridization. Of these, 53 were found to overexpressed during red coloration. The up-regulated expression of six genes was confirmed by Northern blot analyses. The expression of chalcone synthase (CHS), flavanone 3-hydroxylase (F3H), and dihydroflavonol 4-reductase (DFR) genes showed a positive correlation with anthocyanin accumulation in UV-B-irradiated lettuce leaves; flavonoid 3',5'-hydroxylase (F3',5'H) and anthocyanidin synthase (ANS) were expressed continuously in both samples. These results indicated that the genes CHS, F3H, and DFR coincided with increases in anthocyanin accumulation during the red coloration of lettuce leaves. This study show a relationship between red coloration and the expression of up-regulated genes in lettuce. The subtractive cDNA library and EST database described in this study represent a valuable resource for further research for secondary metabolism in the vegetable crops.

  3. Dux4 induces cell cycle arrest at G1 phase through upregulation of p21 expression

    International Nuclear Information System (INIS)

    Xu, Hongliang; Wang, Zhaoxia; Jin, Suqin; Hao, Hongjun; Zheng, Lemin; Zhou, Boda; Zhang, Wei; Lv, He; Yuan, Yun

    2014-01-01

    Highlights: • Dux4 induced TE671 cell proliferation defect and G1 phase arrest. • Dux4 upregulated p21 expression without activating p53. • Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. • Sp1 binding site was required for Dux4-induced p21 promoter activation. - Abstract: It has been implicated that Dux4 plays crucial roles in development of facioscapulohumeral dystrophy. But the underlying myopathic mechanisms and related down-stream events of this retrogene were far from clear. Here, we reported that overexpression of Dux4 in a cell model TE671 reduced cell proliferation rate, and increased G1 phase accumulation. We also determined the impact of Dux4 on p53/p21 signal pathway, which controls the checkpoint in cell cycle progression. Overexpression of Dux4 increased p21 mRNA and protein level, while expression of p53, phospho-p53 remained unchanged. Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. Furthermore, we demonstrated that enhanced Dux4 expression increased p21 promoter activity and elevated expression of Sp1 transcription factor. Mutation of Sp1 binding site decreased dux4 induced p21 promoter activation. Chromatin immunoprecipitation (ChIP) assays confirmed the Dux4-induced binding of Sp1 to p21 promoter in vivo. These results suggest that Dux4 might induce proliferation inhibition and G1 phase arrest through upregulation of p21

  4. Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription

    Directory of Open Access Journals (Sweden)

    Bin Hong

    2012-06-01

    Full Text Available Apolipoprotein A-I (Apo A-I is the principal protein component of high density lipoprotein (HDL, which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeutic approaches. To identify novel agents that can upregulate Apo A-I expression, we performed a cell-based reporter assay to screen 25,600 small molecules. Based on the dataset obtained from screening, a series of novel analogs of substituted benzamides containing azaspiro rings were assessed for their ability to induce the transcription of the Apo A-I gene, and the structure-activity relationship (SAR around these analogs was also proposed. The results indicated that the trifluoromethyl substituted benzamide containing an azaspiro ring is a promising backbone for designing Apo A-I transcriptional upregulator and could be viable leads for development of new drugs to prevent and treat atherosclerosis in the future.

  5. TRX is up-regulated by fibroblast growth factor-2 in lung carcinoma.

    Science.gov (United States)

    Deng, Zheng-Hao; Cao, Hui-Qiu; Hu, Yong-Bin; Wen, Ji-Fang; Zhou, Jian-Hua

    2011-01-01

    We have previously shown that exogenous fibroblast growth factor-2 (FGF-2) inhibits apoptosis of the small-cell lung cancer (SCLC) cell line NCI-H446, but the underlying mechanism remains unknown. In this study, the protein profiles of FGF-2-treated and untreated NCI-H446 cells were determined by 2-D gel electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and bioinformatics. Differential expression analysis of the protein profiles after FGF-2 treatment identified a total of 24 protein spots, of which nine were up-regulated and 15 were down-regulated. Four proteins were identified by MALDI-TOF-MS: thioredoxin (TRX), visfatin, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) and Cu/Zn superoxide dismutase (CuZn-SOD). Western blotting revealed that TRX was up-regulated in NCI-H446 and A549 cells treated with FGF-2. Furthermore, immunohistochemical staining confirmed that both FGF-2 and TRX were overexpressed in lung cancer tissues and could be correlated with both lymph node metastasis and clinical stage. These data indicate that TRX may be involved in the FGF-2 signaling pathway. © 2010 The Authors. APMIS © 2010 APMIS.

  6. A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Rasmussen, Rune N; Mo, Junying

    2016-01-01

    Ibuprofen is a widely used drug. It has been identified as an inhibitor of several transporters, but it is not clear if ibuprofen is a substrate of any transporter itself. In the present work, we have characterized a transporter of ibuprofen, which is upregulated by hyperosmotic culture conditions...... in Madin-Darby canine kidney I (MDCK I) renal cells. [(3)H]-Ibuprofen uptake rate was measured in MDCK I cell cultured under normal (300 mOsm) and hyperosmotic (500 mOsm) conditions. Hyperosmotic conditions were obtained by supplementing urea, NaCl, mannitol, or raffinose to culture medium. The effect...... of increased osmolarity was investigated for different incubation times. [(3)H]-Ibuprofen uptake in MDCK I cells was upregulated by hyperosmotic culture condition, and was saturable with a Km value of 0.37 ± 0.08 μM and a Vmax of 233.1 ± 17.2 pmol· cm(-2)· min(-1). Racemic [(3)H]-ibuprofen uptake could...

  7. Upregulation of cyclooxygenase-2 expression in porcine macula densa with chronic nitric oxide synthase inhibition.

    Science.gov (United States)

    Kommareddy, M; McAllister, R M; Ganjam, V K; Turk, J R; Laughlin, M Harold

    2011-11-01

    The objective of this study was to investigate the effects of chronic inhibition of nitric oxide synthase (NOS) on cyclooxygenase-2 (COX-2) expression in the macula densa (MD) of swine, as well as the effects on expression of related proteins. Adult female Yucatan swine were given either tap water (control, n = 6) or water with N (G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/liter, n = 5) for a minimum of 30 days. Duplicate samples of kidney were fixed or snap frozen. There was a significant (P = .0082) upregulation of COX-2 mRNA expression in the MD of L-NAME, as well as an apparent increase in COX-2 protein. Plasma renin activity also increased with L-NAME treatment (control, 0.34 ± 0.08 ng/ml; L-NAME, 1.26 ± 0.03 ng/ml; P = .00000003). There were no differences between groups in expression of either inducible NOS or renin protein or in serum electrolyte concentrations. In conclusion, with chronic inhibition of NOS, COX-2 in MD is upregulated, perhaps to compensate for loss of nitric oxide. Increases in COX-2 products may counteract renal arteriolar constriction and sustain renin release.

  8. Incomplete KLK7 Secretion and Upregulated LEKTI Expression Underlie Hyperkeratotic Stratum Corneum in Atopic Dermatitis.

    Science.gov (United States)

    Igawa, Satomi; Kishibe, Mari; Minami-Hori, Masako; Honma, Masaru; Tsujimura, Hisashi; Ishikawa, Junko; Fujimura, Tsutomu; Murakami, Masamoto; Ishida-Yamamoto, Akemi

    2017-02-01

    Atopic dermatitis (AD) is a common inflammatory skin disorder. Chronic AD lesions present hyperkeratosis, indicating a disturbed desquamation process. KLK7 is a serine protease involved in the proteolysis of extracellular corneodesmosome components, including desmocollin 1 and corneodesmosin, which leads to desquamation. KLK7 is secreted by lamellar granules and upregulated in AD lesional skin. However, despite increased KLK7 protein levels, immunostaining and electron microscopy indicated numerous corneodesmosomes remaining in the uppermost layer of the stratum corneum from AD lesions. We aimed to clarify the discrepancy between KLK7 overexpression and retention of corneodesmosomes on AD corneocytes. Western blot analysis indicated abnormal corneodesmosin degradation patterns in stratum corneum from AD lesions. The KLK activity of tape-stripped corneocytes from AD lesions was not significantly elevated in in situ zymography, which was our new attempt to detect the protease activity more precisely than conventional assays. This ineffective KLK activation was associated with impaired KLK7 secretion from lamellar granules and increased expression of LEKTI in AD. Such imbalances in protease-protease inhibitor interactions could lead to abnormal proteolysis of corneodesmosomes and compact hyperkeratosis. Upregulated expression of LEKTI might be a compensatory mechanism to prevent further barrier dysfunction in AD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Advanced glycation endproducts link inflammatory cues to upregulation of galectin-1 in diabetic retinopathy.

    Science.gov (United States)

    Kanda, Atsuhiro; Dong, Yoko; Noda, Kousuke; Saito, Wataru; Ishida, Susumu

    2017-11-23

    Diabetic retinopathy (DR) is an inflammatory and progressive vaso-occlusive disease resulting in angiogenesis. Galectin-1 is a hypoxia-induced angiogenic factor associated with cancer and proliferative DR. Here we reveal a significant upregulation of galectin-1 in eyes of DR patients along with progression of clinical stages beginning from the pre-ischemic, inflammatory stage with diabetic macular edema, but not in eyes with non-diabetic retinal vascular occlusions. As for its regulatory mechanism unrelated to hypoxia but selective to DR, in vitro galectin-1/LGALS1 expression was shown to increase after application to Müller glial cells with interleukin (IL)-1β, which was induced in monocyte-derived macrophages and microglial cells via toll-like receptor (TLR) 4 signaling stimulated by advanced glycation endproducts (AGE). In vivo inhibition of AGE generation with aminoguanidine, macrophage depletion with clodronate liposomes, and antibody-based blockade of Il-1β and Tlr4 attenuated diabetes-induced retinal Lgals1 expression in mice. Fibrovascular tissues from proliferative DR eyes were immunoreactive for AGE, TRL4 and IL-1β in macrophages, and IL-1β receptor-positive glial cells expressed galectin-1. Therefore, diabetes-induced retinal AGE accumulation was suggested to activate IL-1β-related inflammatory cues in macrophages followed by Müller cells, linking to galectin-1 upregulation in human DR with time. Our data highlight AGE-triggered inflammation as the DR-selective inducer of galectin-1.

  10. Artemisia Extract Improves Insulin Sensitivity in Women With Gestational Diabetes Mellitus by Up-Regulating Adiponectin.

    Science.gov (United States)

    Sun, Xia; Sun, Hong; Zhang, Jing; Ji, Xianghong

    2016-12-01

    Gestational diabetes mellitus (GDM) has affected a great number of pregnant women worldwide. Artemisia extracts have been found to exhibit a potent antidiabetic effect in the treatment of type 2 diabetes mellitus. We aimed to examine the effects of Artemisia extract on insulin resistance and lipid profiles in pregnant GDM patients. Patients in their second trimester were randomly assigned to the Artemisia extract group (AE) or to a placebo group (PO). They were instructed to consume either AE or PO daily for a period of 10 weeks. Glucose and insulin profiles and adiponectin level were assessed at baseline (week 0) and after the treatment (week 10). Compared to the PO group, fasting plasma glucose, serum insulin levels, homeostasis model of assessment of insulin resistance (HOMA-IR), and β-cell function (HOMA-B) were significantly reduced in the AE group participants. Moreover, levels of circulating adiponectin were also significantly up-regulated in the AE group, which also positively contributed to improved insulin sensitivity. Daily administration of Artemisia extract improves insulin sensitivity by up-regulating adiponectin in women with gestational diabetes mellitus. © 2016, The American College of Clinical Pharmacology.

  11. Activation of the HMGB1-RAGE axis upregulates TH expression in dopaminergic neurons via JNK phosphorylation.

    Science.gov (United States)

    Kim, Soo Jeong; Ryu, Min Jeong; Han, Jeongsu; Jang, Yunseon; Kim, Jungim; Lee, Min Joung; Ryu, Ilhwan; Ju, Xianshu; Oh, Eungseok; Chung, Woosuk; Kweon, Gi Ryang; Heo, Jun Young

    2017-11-04

    The derangement of tyrosine hydroxylase (TH) activity reduces dopamine synthesis and is implicated in the pathogenesis of Parkinson's disease. However, the extracellular modulator and intracellular regulatory mechanisms of TH have yet to be identified. Recently, high-mobility group box 1 (HMGB1) was reported to be actively secreted from glial cells and is regarded as a mediator of dopaminergic neuronal loss. However, the mechanism for how HMGB1 affects TH expression, particularly through the receptor for advanced glycation endproducts (RAGE), has not yet been investigated. We found that recombinant HMGB1 (rHMGB1) upregulates TH mRNA expression via simultaneous activation of JNK phosphorylation, and this induction of TH expression is blocked by inhibitors of RAGE and JNK. To investigate how TH expression levels change through the HMGB1-RAGE axis as a result of MPP + toxicity, we co-treated SN4741 dopaminergic cells with MPP + and rHMGB1. rHMGB1 blocked the reduction of TH mRNA following MPP + treatment without altering cell survival rates. Our results suggest that HMGB1 upregulates TH expression to maintain dopaminergic neuronal function via activating RAGE, which is dependent on JNK phosphorylation. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Armet, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death

    International Nuclear Information System (INIS)

    Apostolou, Andria; Shen Yuxian; Liang Yan; Luo Jun; Fang Shengyun

    2008-01-01

    The accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress that initiates the unfolded protein response (UPR). UPR activates both adaptive and apoptotic pathways, which contribute differently to disease pathogenesis. To further understand the functional mechanisms of UPR, we identified 12 commonly UPR-upregulated genes by expression microarray analysis. Here, we describe characterization of Armet/MANF, one of the 12 genes whose function was not clear. We demonstrated that the Armet/MANF protein was upregulated by various forms of ER stress in several cell lines as well as by cerebral ischemia of rat. Armet/MANF was localized in the ER and Golgi and was also a secreted protein. Silencing Armet/MANF by siRNA oligos in HeLa cells rendered cells more susceptible to ER stress-induced death, but surprisingly increased cell proliferation and reduced cell size. Overexpression of Armet/MANF inhibited cell proliferation and improved cell viability under glucose-free conditions and tunicamycin treatment. Based on its inhibitory properties for both proliferation and cell death we have demonstrated, Armet is, thus, a novel secreted mediator of the adaptive pathway of UPR

  13. Dux4 induces cell cycle arrest at G1 phase through upregulation of p21 expression

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Hongliang; Wang, Zhaoxia; Jin, Suqin; Hao, Hongjun [Department of Neurology, Peking University First Hospital, Beijing 100034 (China); Zheng, Lemin [The Institute of Cardiovascular Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing 100191 (China); Zhou, Boda [The Department of Cardiology, Peking University Third Hospital, Beijing 100191 (China); Zhang, Wei; Lv, He [Department of Neurology, Peking University First Hospital, Beijing 100034 (China); Yuan, Yun, E-mail: yuanyun2002@sohu.com [Department of Neurology, Peking University First Hospital, Beijing 100034 (China)

    2014-03-28

    Highlights: • Dux4 induced TE671 cell proliferation defect and G1 phase arrest. • Dux4 upregulated p21 expression without activating p53. • Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. • Sp1 binding site was required for Dux4-induced p21 promoter activation. - Abstract: It has been implicated that Dux4 plays crucial roles in development of facioscapulohumeral dystrophy. But the underlying myopathic mechanisms and related down-stream events of this retrogene were far from clear. Here, we reported that overexpression of Dux4 in a cell model TE671 reduced cell proliferation rate, and increased G1 phase accumulation. We also determined the impact of Dux4 on p53/p21 signal pathway, which controls the checkpoint in cell cycle progression. Overexpression of Dux4 increased p21 mRNA and protein level, while expression of p53, phospho-p53 remained unchanged. Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. Furthermore, we demonstrated that enhanced Dux4 expression increased p21 promoter activity and elevated expression of Sp1 transcription factor. Mutation of Sp1 binding site decreased dux4 induced p21 promoter activation. Chromatin immunoprecipitation (ChIP) assays confirmed the Dux4-induced binding of Sp1 to p21 promoter in vivo. These results suggest that Dux4 might induce proliferation inhibition and G1 phase arrest through upregulation of p21.

  14. Neural cell 3D microtissue formation is marked by cytokines' up-regulation.

    Directory of Open Access Journals (Sweden)

    Yinzhi Lai

    Full Text Available Cells cultured in three dimensional (3D scaffolds as opposed to traditional two-dimensional (2D substrates have been considered more physiologically relevant based on their superior ability to emulate the in vivo environment. Combined with stem cell technology, 3D cell cultures can provide a promising alternative for use in cell-based assays or biosensors in non-clinical drug discovery studies. To advance 3D culture technology, a case has been made for identifying and validating three-dimensionality biomarkers. With this goal in mind, we conducted a transcriptomic expression comparison among neural progenitor cells cultured on 2D substrates, 3D porous polystyrene scaffolds, and as 3D neurospheres (in vivo surrogate. Up-regulation of cytokines as a group in 3D and neurospheres was observed. A group of 13 cytokines were commonly up-regulated in cells cultured in polystyrene scaffolds and neurospheres, suggesting potential for any or a combination from this list to serve as three-dimensionality biomarkers. These results are supportive of further cytokine identification and validation studies with cells from non-neural tissue.

  15. Utrophin up-regulation by an artificial transcription factor in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Elisabetta Mattei

    2007-08-01

    Full Text Available Duchenne Muscular Dystrophy (DMD is a severe muscle degenerative disease, due to absence of dystrophin. There is currently no effective treatment for DMD. Our aim is to up-regulate the expression level of the dystrophin related gene utrophin in DMD, complementing in this way the lack of dystrophin functions. To this end we designed and engineered several synthetic zinc finger based transcription factors. In particular, we have previously shown that the artificial three zinc finger protein named Jazz, fused with the appropriate effector domain, is able to drive the transcription of a test gene from the utrophin promoter "A". Here we report on the characterization of Vp16-Jazz-transgenic mice that specifically over-express the utrophin gene at the muscular level. A Chromatin Immunoprecipitation assay (ChIP demonstrated the effective access/binding of the Jazz protein to active chromatin in mouse muscle and Vp16-Jazz was shown to be able to up-regulate endogenous utrophin gene expression by immunohistochemistry, western blot analyses and real-time PCR. To our knowledge, this is the first example of a transgenic mouse expressing an artificial gene coding for a zinc finger based transcription factor. The achievement of Vp16-Jazz transgenic mice validates the strategy of transcriptional targeting of endogenous genes and could represent an exclusive animal model for use in drug discovery and therapeutics.

  16. Upregulation of metastasis-associated gene 2 promotes cell proliferation and invasion in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Wu MH

    2016-03-01

    Full Text Available Minhua Wu,1,2,* Xiaoxia Ye,2,* Xubin Deng,3,* Yanxia Wu,4 Xiaofang Li,4 Lin Zhang11Department of Histology and Embryology, Southern Medical University, Guangzhou, 2Department of Histology and Embryology, Guangdong Medical University, Zhanjiang, 3Affiliated Cancer Hospital of Guangzhou Medical University, Cancer Center of Guangzhou Medical University, Guangzhou, 4Pathological Diagnosis and Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China*These authors contributed equally to this workAims: Metastasis-associated gene 2 (MTA2 is reported to play an important role in tumor progression, but little is known about the role of MTA2 in nasopharyngeal carcinoma (NPC. The aim of the study was to explore the expression and function of MTA2 in NPC.Methods: Expression of MTA2 in NPC tissues and cell lines was detected by immunohistochemistry and Western blotting. Relationship between MTA2 expression and clinicopathological features was analyzed. Stable MTA2-overexpressing and MTA2-siliencing NPC cells were established by transfection with plasmids encoding MTA2 cDNA and lentivirus-mediated short hairpin RNA, respectively. Cell viability was determined by Cell Counting Kit-8 and colony formation assay. Cell migration ability was evaluated by wound healing and transwell invasion assay. The impact of MTA2 knockdown on growth and metastasis of CNE2 cells in vivo was determined by nude mouse xenograft models. Expression of several Akt pathway proteins was detected by Western blotting.Results: MTA2 was upregulated in NPC tissues and three NPC cell lines detected (CNE1, CNE2, and HNE1. MTA2 expression was related to clinical stage and lymph node metastasis of patients with NPC. MTA2 upregulation promoted proliferation and invasion of CNE1 cells, while MTA2 depletion had opposite effects on CNE2 cells. Moreover, MTA2 depletion suppressed growth and metastasis of CNE2 cells in vivo. MTA2 overexpression

  17. BAG3 promotes chondrosarcoma progression by upregulating the expression of β-catenin

    Science.gov (United States)

    Shi, Huijuan; Chen, Wenfang; Dong, Yu; Lu, Xiaofang; Zhang, Wenhui; Wang, Liantang

    2018-01-01

    To investigate the roles of B-cell lymphoma-2 associated athanogene 3 (BAG3) in human chondrosarcoma and the potential mechanisms, the expression levels of BAG3 were detected in the present study, and the associations between BAG3 and clinical pathological parameters, clinical stage as well as the survival of patients were analyzed. The present study detected BAG3 mRNA and protein expression in the normal cartilage cell line HC-a and in SW1353 chondrosarcoma cells by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The BAG3 protein expression in 59 cases of chondrosarcoma, 30 patients with endogenous chondroma and 8 cases of normal cartilage was semi-quantitatively analyzed using the immunohistochemical method. In addition, the BAG3 protein expression level, the clinical pathological parameters, clinical stage and the survival time of patients with chondrosarcoma were analyzed. The plasmid transfection method was employed to upregulate the expression BAG3 and small RNA interference to downregulate the expression of BAG3 in SW1353 cells. The expression levels of BAG3 protein and mRNA were significantly increased in the chondrosarcoma cell line when compared with the normal cartilage cell line. The immunohistochemistry results indicated that BAG3 protein was overexpressed in the tissue of human chondrosarcoma. Statistical analysis showed that the expression level of BAG3 was significantly increased in the different Enneking staging of patients with chondrosarcoma and Tumor staging, and there were no statistical differences in age, gender, histological classification and tumor size. In the in vitro experiments, the data revealed that BAG3 significantly promoted chondrosarcoma cell proliferation, colony-formation, migration and invasion; however, it inhibited chondrosarcoma cell apoptosis. It was observed that BAG3 upregulated β-catenin expression at the mRNA and protein levels. In addition, BAG3 induced the expression of runt

  18. E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation

    International Nuclear Information System (INIS)

    Hao, Hongying; Dong, Yanbin; Bowling, Maria T; Gomez-Gutierrez, Jorge G; Zhou, H Sam; McMasters, Kelly M

    2007-01-01

    PUMA is a pro-apoptotic Bcl-2 family member that has been shown to be involved in apoptosis in many cell types. We sought to ascertain whether induction of PUMA plays a crucial role in E2F-1-induced apoptosis in melanoma cells. PUMA gene and protein expression levels were detected by real-time PCR and Western blot in SK-MEL-2 and HCT116 cell lines after Ad-E2F-1 infection. Activation of the PUMA promoter by E2F-1 overexpression was detected by dual luciferase reporter assay. E2F-1-induced Bax translocation was shown by immunocytochemistry. The induction of caspase-9 activity was measured by caspase-9 colorimetric assay kit. Up-regulation of the PUMA gene and protein by E2F-1 overexpression was detected by real-time PCR and Western blot analysis in the SK-MEL-2 melanoma cell line. In support of this finding, we found six putative E2F-1 binding sites within the PUMA promoter. Subsequent dual luciferase reporter assay showed that E2F-1 expression could increase the PUMA gene promoter activity 9.3 fold in SK-MEL-2 cells. The role of PUMA in E2F-1-induced apoptosis was further investigated in a PUMA knockout cell line. Cell viability assay showed that the HCT116 PUMA-/- cell line was more resistant to Ad-E2F-1-mediated cell death than the HCT116 PUMA+/+ cell line. Moreover, a 2.2-fold induction of the PUMA promoter was also noted in the HCT116 PUMA+/+ colon cancer cell line after Ad-E2F-1 infection. Overexpression of a truncated E2F-1 protein that lacks the transactivation domain failed to up-regulate PUMA promoter, suggesting that PUMA may be a transcriptional target of E2F-1. E2F-1-induced cancer cell apoptosis was accompanied by Bax translocation from the cytosol to mitochondria and the induction of caspase-9 activity, suggesting that E2F-1-induced apoptosis is mediated by PUMA through the cytochrome C/Apaf-1-dependent pathway. Our studies strongly demonstrated that E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation. The signaling

  19. Upregulation of a tonoplast-localized cytochrome P450 during petal senescence in Petunia inflata

    Directory of Open Access Journals (Sweden)

    Ishida Hiroyuki

    2006-04-01

    Full Text Available Abstract Background Gene expression in Petunia inflata petals undergoes major changes following compatible pollination. Severe flower wilting occurs reproducibly within 36 hours, providing an excellent model for investigation of petal senescence and programmed cell death. Expression of a number of genes and various enzyme activities involved in the degradation and remobilization of macromolecules have been found to be upregulated during the early stages of petal senescence. Results By performing differential display of cDNAs during Petunia inflata petal senescence, a highly upregulated gene encoding a cytochrome P450 was identified. Analysis of the complete cDNA sequence revealed that the predicted protein is a member of the CYP74C family (CYP74C9 and is highly similar to a tomato CYP74C allene oxide synthase (AOS that is known to be active on 9-hydroperoxides. Cloning of the petunia genomic DNA revealed an intronless gene with a promoter region that carries signals found in stress-responsive genes and potential binding sites for Myb transcription factors. Transcripts were present at detectable levels in root and stem, but were 40 times more abundant in flowers 36 hours after pollination. Ethylene and jasmonate treatment resulted in transitory increases in expression in detached flowers. A protein fusion of the CYP74C coding region to a C-terminal GFP was found to be located in the tonoplast. Conclusion Though oxylipins, particularly jasmonates, are known to be involved in stress responses, the role of other products of CYP74 enzymes is less well understood. The identification of a CYP74C family member as a highly upregulated gene during petal senescence suggests that additional products of fatty acid metabolism may play important roles during programmed cell death. In contrast to the chloroplast localization of AOS proteins in the CYP74A subfamily, GFP fusion data indicates that the petunia CYP74C9 enzyme is in the tonoplast. This result

  20. BAG3 promotes chondrosarcoma progression by upregulating the expression of β-catenin.

    Science.gov (United States)

    Shi, Huijuan; Chen, Wenfang; Dong, Yu; Lu, Xiaofang; Zhang, Wenhui; Wang, Liantang

    2018-04-01

    To investigate the roles of B‑cell lymphoma‑2 associated athanogene 3 (BAG3) in human chondrosarcoma and the potential mechanisms, the expression levels of BAG3 were detected in the present study, and the associations between BAG3 and clinical pathological parameters, clinical stage as well as the survival of patients were analyzed. The present study detected BAG3 mRNA and protein expression in the normal cartilage cell line HC‑a and in SW1353 chondrosarcoma cells by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The BAG3 protein expression in 59 cases of chondrosarcoma, 30 patients with endogenous chondroma and 8 cases of normal cartilage was semi-quantitatively analyzed using the immunohistochemical method. In addition, the BAG3 protein expression level, the clinical pathological parameters, clinical stage and the survival time of patients with chondrosarcoma were analyzed. The plasmid transfection method was employed to upregulate the expression BAG3 and small RNA interference to downregulate the expression of BAG3 in SW1353 cells. The expression levels of BAG3 protein and mRNA were significantly increased in the chondrosarcoma cell line when compared with the normal cartilage cell line. The immunohistochemistry results indicated that BAG3 protein was overexpressed in the tissue of human chondrosarcoma. Statistical analysis showed that the expression level of BAG3 was significantly increased in the different Enneking staging of patients with chondrosarcoma and Tumor staging, and there were no statistical differences in age, gender, histological classification and tumor size. In the in vitro experiments, the data revealed that BAG3 significantly promoted chondrosarcoma cell proliferation, colony‑formation, migration and invasion; however, it inhibited chondrosarcoma cell apoptosis. It was observed that BAG3 upregulated β‑catenin expression at the mRNA and protein levels. In addition, BAG3 induced the

  1. Upregulation of endothelial cell adhesion molecules characterizes veins close to granulomatous infiltrates in the renal cortex of cats with feline infectious peritonitis and is indirectly triggered by feline infectious peritonitis virus-infected monocytes in vitro.

    Science.gov (United States)

    Acar, Delphine D; Olyslaegers, Dominique A J; Dedeurwaerder, Annelike; Roukaerts, Inge D M; Baetens, Wendy; Van Bockstael, Sebastiaan; De Gryse, Gaëtan M A; Desmarets, Lowiese M B; Nauwynck, Hans J

    2016-10-01

    One of the most characteristic pathological changes in cats that have succumbed to feline infectious peritonitis (FIP) is a multifocal granulomatous phlebitis. Although it is now well established that leukocyte extravasation elicits the inflammation typically associated with FIP lesions, relatively few studies have aimed at elucidating this key pathogenic event. The upregulation of adhesion molecules on the endothelium is a prerequisite for stable leukocyte-endothelial cell (EC) adhesion that necessarily precedes leukocyte diapedesis. Therefore, the present work focused on the expression of the EC adhesion molecules and possible triggers of EC activation during the development of FIP. Immunofluorescence analysis revealed that the endothelial expression of P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was elevated in veins close to granulomatous infiltrates in the renal cortex of FIP patients compared to non-infiltrated regions and specimens from healthy cats. Next, we showed that feline venous ECs become activated when exposed to supernatant from feline infectious peritonitis virus (FIPV)-infected monocytes, as indicated by increased adhesion molecule expression. Active viral replication seemed to be required to induce the EC-stimulating activity in monocytes. Finally, adhesion assays revealed an increased adhesion of naive monocytes to ECs treated with supernatant from FIPV-infected monocytes. Taken together, our results strongly indicate that FIPV activates ECs to increase monocyte adhesion by an indirect route, in which proinflammatory factors released from virus-infected monocytes act as key intermediates.

  2. SET mediates TCE-induced liver cell apoptosis through dephosphorylation and upregulation of nucleolin.

    Science.gov (United States)

    Ren, Xiaohu; Huang, Xinfeng; Yang, Xifei; Liu, Yungang; Liu, Wei; Huang, Haiyan; Wu, Desheng; Zou, Fei; Liu, Jianjun

    2017-06-20

    Trichloroethylene (TCE) is an occupational and environmental chemical that can cause severe hepatotoxicity. While our previous studies showed that the phosphatase inhibitor SET is a key mediator of TCE-induced liver cell apoptosis, the molecular mechanisms remain elusive. Using quantitative phosphoproteomic analysis, we report here that nucleolin is a SET-regulated phosphoprotein in human liver HL-7702 cells. Functional analysis suggested that SET promoted dephosphorylation of nucleolin, decreased its binding to its transcriptional activator, c-myc, and upregulated nucleolin expression in TCE-treated cells. Importantly, TCE-induced hepatocyte apoptosis was significantly attenuated when nucleolin was downregulated with specific siRNAs. These findings indicate that TCE may induce hepatocyte apoptosis via SET-mediated dephosphorylation and overexpression of nucleolin.

  3. Upregulation of proinflammatory genes in skin lesions may be the cause of keloid formation (Review)

    Science.gov (United States)

    DONG, XIANGLIN; MAO, SHAOLIN; WEN, HAO

    2013-01-01

    It was previously demonstrated that the main cause behind keloid formation may be keloid fibroblast abnormalities, which are closely associated with the microenvironment of the keloid lesion. The post-traumatic and chronic inflammation of the keloid lesion area suggest that inflammatory mediators play an important role in the keloid microenvironment and are crucial for keloid fibroblast abnormalities. In this study, we hypothesized that the mechanism underlying keloid formation may involve the continuous upregulation of proinflammatory gene expression in keloid lesions. This hypothesis may explain the inflammatory response, invasive growth and recurrence following resection of keloids, as well as the selective localization of keloids in specific parts of a patient’s body and the differences in localization among different patients. PMID:24649037

  4. Lipopolysaccharide-induced Pulpitis Up-regulates TRPV1 in Trigeminal Ganglia

    Science.gov (United States)

    Chung, M.-K.; Lee, J.; Duraes, G.; Ro, J.Y.

    2011-01-01

    Tooth pain often accompanies pulpitis. Accumulation of lipopolysaccharides (LPS), a product of Gram-negative bacteria, is associated with painful clinical symptoms. However, the mechanisms underlying LPS-induced tooth pain are not clearly understood. TRPV1 is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and hyperalgesia under inflammation or injury. Although TRPV1 is expressed in pulpal afferents, it is not known whether the application of LPS to teeth modulates TRPV1 in trigeminal nociceptors. By assessing the levels of protein and transcript of TRPV1 in mouse trigeminal ganglia, we demonstrate that dentinal application of LPS increases the expression of TRPV1. Our results suggest that the up-regulation of TRPV1 in trigeminal nociceptors following bacterial infection could contribute to hyperalgesia under pulpitis conditions. PMID:21712529

  5. Up-regulation of β-adrenoreceptors by drugs which cause depression

    International Nuclear Information System (INIS)

    Brand, L.; Van Rooyen, J.M.; Offermeier, J.

    1988-01-01

    A number of drugs associated with depressive episodes in man were investigated for their effects on rat cortical β-adrenoceptors, in view of the down-regulation of β-adrenoceptors caused by chronic administration of anti-depressant drugs. Scatchard analyses of [ 3 H]dihydro-alprenolol binding data provided B max and K D values for the cortical β-adrenoceptors. Up-regulation of the receptors occurred after daily injections of phenobarbitone for seven days (by 55%), pentobarbitone (by 143%), reserpine (by 82%) and propranolol (by 64%). β-adrenoceptors were not affected by daily injections of clonidine, chlorpromazine and flupenthixol for seven days. This work confirms the up-regulatory effect on β-adrenoceptors of certain drugs which produce depressions in man

  6. Sevoflurane suppresses proliferation by upregulating microRNA-203 in breast cancer cells.

    Science.gov (United States)

    Liu, Jiaying; Yang, Longqiu; Guo, Xia; Jin, Guangli; Wang, Qimin; Lv, Dongdong; Liu, Junli; Chen, Qiu; Song, Qiong; Li, Baolin

    2018-05-03

    Rapid proliferation is one of the critical characteristics of breast cancer. However, the underlying regulatory mechanism of breast cancer cell proliferation is largely unclear. The present study indicated that sevoflurane, one of inhalational anesthetics, could significantly suppress breast cancer cell proliferation by arresting cell cycle at G1 phase. Notably, the rescue experiment indicated that miR-203 was upregulated by sevoflurane and mediated the function of sevoflurane on suppressing the breast cancer cell proliferation. The present study indicated the function of the sevoflurane/miR-203 signaling pathway on regulating breast cancer cell proliferation. These results provide mechanistic insight into how the sevoflurane/miR-203 signaling pathway supresses proliferation of breast cancer cells, suggesting the sevoflurane/miR-203 pathway may be a potential target in the treatment of breast cancer.

  7. Upregulation of endothelin ETB receptor-mediated vasoconstriction in rat coronary artery after organ culture

    DEFF Research Database (Denmark)

    Eskesen, Karen; Edvinsson, Lars

    2006-01-01

    The aim of this study was to examine if endothelin ET(B) receptor-mediated contraction occurred in isolated segments of rat coronary arteries during organ culture. Presence of contractile endothelin ET(B) receptors was studied by measuring the change in isometric tension in rings of left anterior......(+)-solution was not modified after 1 day in culture medium. The experiments indicate that organ culture of rat coronary arteries upregulate endothelin ET(B) receptor-mediated contraction by inducing synthesis of new protein....... descending coronary arteries isolated from hearts of rats as response to application of the selective endothelin ET(B) receptor agonist, Sarafotoxin 6c and endothelin-1. In segments cultured 1 day in serum free Dulbecco's Modified Eagle's Medium, Sarafotoxin 6c induced a concentration dependent contraction...

  8. Maggot debridement therapy promotes diabetic foot wound healing by up-regulating endothelial cell activity.

    Science.gov (United States)

    Sun, Xinjuan; Chen, Jin'an; Zhang, Jie; Wang, Wei; Sun, Jinshan; Wang, Aiping

    2016-03-01

    To determine the role of maggot debridement therapy (MDT) on diabetic foot wound healing, we compared growth related factors in wounds before and after treatment. Furthermore, we utilized human umbilical vein endothelial cells (HUVECs) to explore responses to maggot excretions/secretions on markers of angiogenesis and proliferation. The results showed that there was neo-granulation and angiogenesis in diabetic foot wounds after MDT. Moreover, significant elevation in CD34 and CD68 levels was also observed in treated wounds. In vitro, ES increased HUVEC proliferation, improved tube formation, and increased expression of vascular endothelial growth factor receptor 2 in a dose dependent manner. These results demonstrate that MDT and maggot ES can promote diabetic foot wound healing by up-regulating endothelial cell activity. Copyright © 2016. Published by Elsevier Inc.

  9. SET protein up-regulated testosterone production in the cultured preantral follicles

    Directory of Open Access Journals (Sweden)

    Xu Boqun

    2013-02-01

    Full Text Available Abstract Background We found previously that the expression of SET gene was up-regulated in polycystic ovaries. Evidences suggested that SET protein was essential for regulating both the promoter activity of CYP17A1 and the biological activity of P450c17. In this study, we explored whether SET regulated androgen production in preantral follicles. Methods The mouse preantral follicles were cultured in vitro. Testosterone secretion and expression of steroidogenic enzymes were observed in the preantral follicles treated in vitro by SET overexpression and knockdown. Results Testosterone levels in the media of the AdCMV-SET infected follicles significantly increased, and the CYP17A1 and HSD3B2 expression also significantly increased (P P  Conclusions SET played a positive role in regulating ovarian androgen biosynthesis by enhancing the transcription of steroidogenic enzymes CYP17A1 and HSD3B2, which maybe contribute to the hyperandrogenism in PCOS.

  10. Fascaplysin sensitizes cells to TRAIL-induced apoptosis through upregulating DR5 expression

    Science.gov (United States)

    Wang, Feng; Chen, Haimin; Yan, Xiaojun; Zheng, Yanling

    2013-05-01

    This study investigated the molecular mechanism of anti-tumor effect of fascaplysin, a nitrogenous red pigment firstly isolated from a marine sponge. Microarray analysis show that the TNF and TNF receptor superfamily in human umbilical vein endothelial cells (HUVEC) and human hepatocarcinoma cells (BEL-7402) were significantly regulated by fascaplysin. Western Blot results reveal that fascaplysin increased the expression of cleaved caspase-9, active caspase-3, and decreased the level of procaspase-8 and Bid. Flow cytometry and cytotoxicity tests indicate that fascaplysin sensitized cells to tumor necrosis-related apoptosisinducing ligand-(TRAIL) induced apoptosis, which was markedly blocked by TRAIL R2/Fc chimera, a dominant negative form of TRAIL receptor DR5. Therefore, our results demonstrate that fascaplysin promotes apoptosis through the activation of TRAIL signaling pathway by upregulating DR5 expression.

  11. SPARC is up-regulated during skeletal muscle regeneration and inhibits myoblast differentiation

    DEFF Research Database (Denmark)

    Petersson, Stine Juhl; Jørgensen, Louise Helskov; Andersen, Ditte C.

    2013-01-01

    Skeletal muscle repair is mediated primarily by the muscle stem cell, the satellite cell. Several factors, including extracellular matrix, are known to regulate satellite cell function and regeneration. One factor, the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) is highly up......-regulated during skeletal muscle disease, but its function remains elusive. In the present study, we demonstrate a prominent yet transient increase in SPARC mRNA and protein content during skeletal muscle regeneration that correlates with the expression profile of specific muscle factors like MyoD, Myf5, Myf6......, Myogenin, NCAM, CD34, and M-Cadherin, all known to be implicated in satellite cell activation/proliferation following muscle damage. This up regulation was detected in more cell types. Ectopic expression of SPARC in the muscle progenitor cell line C2C12 was performed to mimic the high levels of SPARC seen...

  12. γ-Tocotrienol upregulates aryl hydrocarbon receptor expression and enhances the anticancer effect of baicalein

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Shuya; Baba, Kiwako; Makio, Akiko; Kumazoe, Motofumi; Huang, Yuhui; Lin, I-Chian; Bae, Jaehoon; Murata, Motoki; Yamada, Shuhei; Tachibana, Hirofumi, E-mail: tatibana@agr.kyushu-u.ac.jp

    2016-05-13

    Previous studies have identified biomolecules that mediate the physiological actions of food factors, such as amino acids, vitamins, fatty acids, minerals, plant polyphenols, and lactobacilli, suggesting that our bodies are equipped with an innate system that senses which food factors are required to maintain our health. However, the effects of environmental factors on food factor sensing (FFS) remains largely unknown. Tocotorienols (T3s), which belongs to the vitamin E family, possess several physiological functions, including cholesterol lowering and neuroprotective effects. Here, we investigated the effects of naturally abundant γ-T3 on FFS-related gene expressions in melanoma using a DNA chip. Our results showed that γ-T3 increased the expression level of aryl hydrocarbon receptor (AhR), a sensing molecule to plant polyphenol baicalein. The co-treatment with γ-T3 and baicalein enhanced the anti-proliferative activity of baicalein, accompanied by the downstream events of AhR-activation induced by baicalein. These data suggest that γ-T3 upregulates AhR expression and enhances its sensitivity to baicalein. - Highlights: • γ-T3 upregulated the expression of AhR in mouse melanoma. • Promotion of the binding activity of Sp1 is associated with the increasing effect of γ-T3 on AhR expression. • γ-T3 enhanced the anti-proliferative activity of baicalein that has an AhR ligand activity. • γ-T3 enhanced the inducing activity of baicalein on the expression of AhR target genes.

  13. Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1.

    Science.gov (United States)

    Kwon, Sora; Jeon, Ji-Sook; Kim, Su Bin; Hong, Young-Kwon; Ahn, Curie; Sung, Jung-Suk; Choi, Inho

    2016-02-27

    Although the prolonged use of rapamycin may cause unwanted side effects such as hyperlipidemia, the underlying mechanism remains unknown. Prox1 is a transcription factor responsible for the development of several tissues including lymphatics and liver. There is growing evidences that Prox1 participates in metabolism in addition to embryogenesis. However, whether Prox1 is directly related to lipid metabolism is currently unknown. HepG2 human hepatoma cells were treated with rapamycin and total lipids were analyzed by thin layer chromatography. The effect of rapamycin on the expression of Prox1 was determined by western blotting. To investigate the role of Prox1 in triglycerides regulation, siRNA and overexpression system were employed. Rapamycin was injected into mice for 2 weeks and total lipids and proteins in liver were measured by thin layer chromatography and western blot analysis, respectively. Rapamycin up-regulated the amount of triglyceride and down-regulated the expression of Prox1 in HepG2 cells by reducing protein half-life but did not affect its transcript. The loss-of-function of Prox1 was coincident with the increase of triglycerides in HepG2 cells treated with rapamycin. The up-regulation of triglycerides by rapamycin in HepG2 cells reverted to normal levels by the compensation of Prox1 using the overexpression system. Rapamycin also down-regulated Prox1 expression but increased triglycerides in mouse liver. This study suggests that rapamycin can increase the amount of triglycerides by down-regulating Prox1 expression in hepatocytes, which means that the mammalian target of rapamycin (mTOR) signaling is important for the regulation of triglycerides by maintaining Prox1 expression.

  14. To investigate the necessity of STRA6 upregulation in T cells during T cell immune responses.

    Directory of Open Access Journals (Sweden)

    Rafik Terra

    Full Text Available Our earlier study revealed that STRA6 (stimulated by retinoic acid gene 6 was up-regulated within 3 h of TCR stimulation. STRA6 is the high-affinity receptor for plasma retinol-binding protein (RBP and mediates cellular vitamin A uptake. We generated STRA6 knockout (KO mice to assess whether such up-regulation was critical for T-cell activation, differentiation and function. STRA6 KO mice under vitamin A sufficient conditions were fertile without apparent anomalies upon visual inspection. The size, cellularity and lymphocyte subpopulations of STRA6 KO thymus and spleen were comparable to those of their wild type (WT controls. KO and WT T cells were similar in terms of TCR-stimulated proliferation in vitro and homeostatic expansion in vivo. Naive KO CD4 cells differentiated in vitro into Th1, Th2, Th17 as well as regulatory T cells in an analogous manner as their WT counterparts. In vivo experiments revealed that anti-viral immune responses to lymphocytic choriomeningitis virus in KO mice were comparable to those of WT controls. We also demonstrated that STRA6 KO and WT mice had similar glucose tolerance. Total vitamin A levels are dramatically lower in the eyes of KO mice as compared to those of WT mice, but the levels in other organs were not significantly affected after STRA6 deletion under vitamin A sufficient conditions, indicating that the eye is the mouse organ most sensitive to the loss of STRA6. Our results demonstrate that 1 in vitamin A sufficiency, the deletion of STRA6 in T cells does no affect the T-cell immune responses so-far tested, including those depend on STAT5 signaling; 2 STRA6-independent vitamin A uptake compensated the lack of STRA6 in lymphoid organs under vitamin A sufficient conditions in mice; 3 STRA6 is critical for vitamin A uptake in the eyes even in vitamin A sufficiency.

  15. Cardiorespiratory upregulation during seawater acclimation in rainbow trout: effects on gastrointestinal perfusion and postprandial responses.

    Science.gov (United States)

    Brijs, Jeroen; Gräns, Albin; Ekström, Andreas; Olsson, Catharina; Axelsson, Michael; Sandblom, Erik

    2016-05-01

    Increased gastrointestinal blood flow is essential for euryhaline fishes to maintain osmotic homeostasis during the initial phase of a transition from freshwater to seawater. However, the cardiorespiratory responses and hemodynamic changes required for a successful long-term transition to seawater remain largely unknown. In the present study, we simultaneously measured oxygen consumption rate (ṀO2), cardiac output (CO), heart rate (HR), and gastrointestinal blood flow (GBF) in rainbow trout (Oncorhynchus mykiss) acclimated to either freshwater or seawater for at least 6 wk. Seawater-acclimated trout displayed significantly elevated ṀO2 (day: 18%, night: 19%), CO (day: 22%, night: 48%), and GBF (day: 96%, night: 147%), demonstrating that an overall cardiorespiratory upregulation occurs during seawater acclimation. The elevated GBF was achieved via a combination of increased CO, mediated through elevated stroke volume (SV), and a redistribution of blood flow to the gastrointestinal tract. Interestingly, virtually all of the increase in CO of seawater-acclimated trout was directed to the gastrointestinal tract. Although unfed seawater-acclimated trout displayed substantially elevated cardiorespiratory activity, the ingestion of a meal resulted in a similar specific dynamic action (SDA) and postprandial GBF response as in freshwater-acclimated fish. This indicates that the capacity for the transportation of absorbed nutrients, gastrointestinal tissue oxygen delivery, and acid-base regulation is maintained during digestion in seawater. The novel findings presented in this study clearly demonstrate that euryhaline fish upregulate cardiovascular function when in seawater, while retaining sufficient capacity for the metabolic and cardiovascular changes associated with the postprandial response. Copyright © 2016 the American Physiological Society.

  16. Green tea diet decreases PCB 126-induced oxidative stress in mice by upregulating antioxidant enzymes

    Science.gov (United States)

    Newsome, Bradley J; Petriello, Michael C; Han, Sung Gu; Murphy, Margaret O; Eske, Katryn E; Sunkara, Manjula; Morris, Andrew J; Hennig, Bernhard

    2013-01-01

    Superfund chemicals such as polychlorinated biphenyls pose a serious human health risk due to their environmental persistence and link to multiple diseases. Selective bioactive food components such as flavonoids have been shown to ameliorate PCB toxicity, but primarily in an in vitro setting. Here, we show that mice fed a green tea-enriched diet and subsequently exposed to environmentally relevant doses of coplanar PCB exhibit decreased overall oxidative stress primarily due to the upregulation of a battery of antioxidant enzymes. C57BL/6 mice were fed a low fat diet supplemented with green tea extract (GTE) for 12 weeks and exposed to 5 μmol PCB 126/kg mouse weight (1.63 mg/kg-day) on weeks 10, 11 and 12 (total body burden: 4.9 mg/kg). F2-Isoprostane and its metabolites, established markers of in vivo oxidative stress, measured in plasma via HPLC-MS/MS exhibited five-fold decreased levels in mice supplemented with GTE and subsequently exposed to PCB compared to animals on a control diet exposed to PCB. Livers were collected and harvested for both mRNA and protein analyses, and it was determined that many genes transcriptionally controlled by AhR and Nrf2 proteins were upregulated in PCB-exposed mice fed the green tea supplemented diet. An increased induction of genes such as SOD1, GSR, NQO1 and GST, key antioxidant enzymes, in these mice (green tea plus PCB) may explain the observed decrease in overall oxidative stress. A diet supplemented with green tea allows for an efficient antioxidant response in the presence of PCB 126 which supports the emerging paradigm that healthful nutrition may be able to bolster and buffer a physiological system against the toxicities of environmental pollutants. PMID:24378064

  17. Upregulation of CPE promotes cell proliferation and tumorigenicity in colorectal cancer

    International Nuclear Information System (INIS)

    Liang, Xing-Hua; He, Wen-guang; Huang, Yan-Nian; Zeng, Xian-Cheng; Li, Ling-ling; Wu, Geng-Gang; Xie, Yi-Cheng; Zhang, Guang-Xian; Chen, Wei; Yang, Hai-Feng; Liu, Qi-Long; Li, Wen-Hong

    2013-01-01

    Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death. Although the mortality rate of CRC is decreasing, finding novel targets for its therapy remains urgent. Carboxypeptidase E (CPE), a member of the pro-protein convertases, which are involved in the maturation of protein precursors, has recently been reported as elevated in many types of cancer. However, its role and mechanisms in tumor progression are poorly understood. In the present study, we investigated expression of CPE in CRC cell lines and tumor tissues using Western blot and real-time qRT-PCR. Plasmids for overexpression and depletion of CPE were constructed and analyzed by Western blot, MTT and colony formation assays and bromodeoxyuridine incorporation assays. The relative expression of p21, p27, and cyclin D1 were analyzed by Real-time qRT-PCR in the indicated cells. Our study showed that CPE was significantly upregulated in CRC cell lines and tumor tissues. MTT and colony formation assays indicated that overexpression of CPE enhanced cell growth rates. BrdU incorporation and flow-cytometry assays showed that ectopic expression of CPE increased the S-phase fraction cells. Soft agar assay proved enhanced tumorigenicity activity in CPE over-expressing CRC cells. Further studies of the molecular mechanisms of CPE indicated that is promoted cell proliferation and tumorigenicity through downregulation of p21 and p27, and upregulation of cyclin D1. Taken together, these data suggest that CPE plays an important role in cell cycle regulation and tumorigenicity, and may serve as a potential target for CRC therapeutics

  18. Effects of hepatocyte CD14 upregulation during cholestasis on endotoxin sensitivity.

    Directory of Open Access Journals (Sweden)

    Ming-Huei Chou

    Full Text Available Cholestasis is frequently related to endotoxemia and inflammatory response. Our previous investigation revealed a significant increase in plasma endotoxin and CD14 levels during biliary atresia. We therefore propose that lipopolysacharides (LPS may stimulate CD14 production in liver cells and promote the removal of endotoxins. The aims of this study are to test the hypothesis that CD14 is upregulated by LPS and investigate the pathophysiological role of CD14 production during cholestasis. Using Western blotting, qRT-PCR, and promoter activity assay, we demonstrated that LPS was associated with a significant increase in CD14 and MD2 protein and mRNA expression and CD14 promoter activity in C9 rat hepatocytes but not in the HSC-T6 hepatic stellate cell line in vitro. To correlate CD14 expression and endotoxin sensitivity, in vivo biliary LPS administration was performed on rats two weeks after they were subjected to bile duct ligation (BDL or a sham operation. CD14 expression and endotoxin levels were found to significantly increase after LPS administration in BDL rats. These returned to basal levels after 24 h. In contrast, although endotoxin levels were increased in sham-operated rats given LPS, no increase in CD14 expression was observed. However, mortality within 24 h was more frequent in the BDL animals than in the sham-operated group. In conclusion, cholestasis and LPS stimulation were here found to upregulate hepatic CD14 expression, which may have led to increased endotoxin sensitivity and host proinflammatory reactions, causing organ failure and death in BDL rats.

  19. Intestinal upregulation of melanin-concentrating hormone in TNBS-induced enterocolitis in adult zebrafish.

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    Brenda M Geiger

    Full Text Available BACKGROUND: Melanin-concentrating hormone (MCH, an evolutionarily conserved appetite-regulating neuropeptide, has been recently implicated in the pathogenesis of inflammatory bowel disease (IBD. Expression of MCH is upregulated in inflamed intestinal mucosa in humans with colitis and MCH-deficient mice treated with trinitrobenzene-sulfonic acid (TNBS develop an attenuated form of colitis compared to wild type animals. Zebrafish have emerged as a new animal model of IBD, although the majority of the reported studies concern zebrafish larvae. Regulation MCH expression in the adult zebrafish intestine remains unknown. METHODS: In the present study we induced enterocolitis in adult zebrafish by intrarectal administration of TNBS. Follow-up included survival analysis, histological assessment of changes in intestinal architecture, and assessment of intestinal infiltration by myeloperoxidase positive cells and cytokine transcript levels. RESULTS: Treatment with TNBS dose-dependently reduced fish survival. This response required the presence of an intact microbiome, since fish pre-treated with vancomycin developed less severe enterocolitis. At 6 hours post-challenge, we detected a significant influx of myeloperoxidase positive cells in the intestine and upregulation of both proinflammatory and anti-inflammatory cytokines. Most importantly, and in analogy to human IBD and TNBS-induced mouse experimental colitis, we found increased intestinal expression of MCH and its receptor in TNBS-treated zebrafish. CONCLUSIONS: Taken together these findings not only establish a model of chemically-induced experimental enterocolitis in adult zebrafish, but point to effects of MCH in intestinal inflammation that are conserved across species.

  20. MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.

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    Tu'uhevaha J Kaitu'u-Lino

    Full Text Available Preeclampsia is a major pregnancy complication, characterized by severe endothelial dysfunction, hypertension and maternal end-organ damage. Soluble endoglin is an anti-angiogenic protein released from placenta and thought to play a central role in causing the endothelial dysfunction and maternal organ injury seen in severe preeclampsia. We recently reported MMP-14 was the protease producing placentally-derived soluble endoglin by cleaving full-length endoglin present on the syncytiotrophoblast surface. This find identifies a specific drug target for severe preeclampsia; interfering with MMP-14 mediated cleavage of endoglin could decrease soluble endoglin production, ameliorating clinical disease. However, experimental MMP-14 inhibition alone only partially repressed soluble endoglin production, implying other proteases might have a role in producing soluble endoglin. Here we investigated whether MMP-15--phylogenetically the closest MMP relative to MMP-14 with 66% sequence similarity--also cleaves endoglin to produce soluble endoglin. MMP-15 was localized to the syncytiotrophoblast layer of the placenta, the same site where endoglin was localized. Interestingly, it was significantly (p = 0.03 up-regulated in placentas from severe early-onset preeclamptic pregnancies (n = 8 compared to gestationally matched preterm controls (n = 8. However, siRNA knockdown of MMP-15 yielded no significant decrease of soluble endoglin production from either HUVECs or syncytialised BeWo cells in vitro. Importantly, concurrent siRNA knockdown of both MMP-14 and MMP-15 in HUVECS did not yield further decrease in soluble endoglin production compared to MMP-14 siRNA alone. We conclude MMP-15 is up-regulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.

  1. Upregulation of human heme oxygenase gene expression by Ets-family proteins.

    Science.gov (United States)

    Deramaudt, B M; Remy, P; Abraham, N G

    1999-03-01

    Overexpression of human heme oxygenase-1 has been shown to have the potential to promote EC proliferation and angiogenesis. Since Ets-family proteins have been shown to play an important role in angiogenesis, we investigated the presence of ETS binding sites (EBS), GGAA/T, and ETS protein contributing to human HO-1 gene expression. Several chloramphenicol acetyltransferase constructs were examined in order to analyze the effect of ETS family proteins on the transduction of HO-1 in Xenopus oocytes and in microvessel endothelial cells. Heme oxygenase promoter activity was up-regulated by FLI-1ERGETS-1 protein(s). Chloramphenicol acetyltransferase (CAT) assays demonstrated that the promoter region (-1500 to +19) contains positive and negative control elements and that all three members of the ETS protein family were responsible for the up-regulation of HHO-1. Electrophoretic mobility shift assays (EMSA), performed with nuclear extracts from endothelial cells overexpressing HHO-1 gene, and specific HHO-1 oligonucleotides probes containing putative EBS resulted in a specific and marked bandshift. Synergistic binding was observed in EMSA between AP-1 on the one hand, FLI-1, ERG, and ETS-1 protein on the other. Moreover, 5'-deletion analysis demonstrated the existence of a negative control element of HHO-1 expression located between positions -1500 and -120 on the HHO-1 promoter. The presence of regulatory sequences for transcription factors such as ETS-1, FLI-1, or ERG, whose activity is associated with cell proliferation, endothelial cell differentiation, and matrix metalloproteinase transduction, may be an indication of the important role that HO-1 may play in coronary collateral circulation, tumor growth, angiogenesis, and hemoglobin-induced endothelial cell injuries.

  2. Alteration in gene expression profile and oncogenicity of esophageal squamous cell carcinoma by RIZ1 upregulation.

    Science.gov (United States)

    Dong, Shang-Wen; Li, Dong; Xu, Cong; Sun, Pei; Wang, Yuan-Guo; Zhang, Peng

    2013-10-07

    To investigate the effect of retinoblastoma protein-interacting zinc finger gene 1 (RIZ1) upregulation in gene expression profile and oncogenicity of human esophageal squamous cell carcinoma (ESCC) cell line TE13. TE13 cells were transfected with pcDNA3.1(+)/RIZ1 and pcDNA3.1(+). Changes in gene expression profile were screened and the microarray results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR). Nude mice were inoculated with TE13 cells to establish ESCC xenografts. After two weeks, the inoculated mice were randomly divided into three groups. Tumors were injected with normal saline, transfection reagent pcDNA3.1(+) and transfection reagent pcDNA3.1(+)/RIZ1, respectively. Tumor development was quantified, and changes in gene expression of RIZ1 transfected tumors were detected by RT-PCR and Western blotting. DNA microarray data showed that RIZ1 transfection induced widespread changes in gene expression profile of cell line TE13, with 960 genes upregulated and 1163 downregulated. Treatment of tumor xenografts with RIZ1 recombinant plasmid significantly inhibited tumor growth, decreased tumor size, and increased expression of RIZ1 mRNA compared to control groups. The changes in gene expression profile were also observed in vivo after RIZ1 transfection. Most of the differentially expressed genes were associated with cell development, supervision of viral replication, lymphocyte costimulatory and immune system development in esophageal cells. RIZ1 gene may be involved in multiple cancer pathways, such as cytokine receptor interaction and transforming growth factor beta signaling. The development and progression of esophageal cancer are related to the inactivation of RIZ1. Virus infection may also be an important factor.

  3. Medicago truncatula SOC1 Genes Are Up-regulated by Environmental Cues That Promote Flowering

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    Jared B. Fudge

    2018-04-01

    Full Text Available Like Arabidopsis thaliana, the flowering of the legume Medicago truncatula is promoted by long day (LD photoperiod and vernalization. However, there are differences in the molecular mechanisms involved, with orthologs of two key Arabidopsis thaliana regulators, FLOWERING LOCUS C (FLC and CONSTANS (CO, being absent or not having a role in flowering time function in Medicago. In Arabidopsis, the MADS-box transcription factor gene, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (AtSOC1, plays a key role in integrating the photoperiodic and vernalization pathways. In this study, we set out to investigate whether the Medicago SOC1 genes play a role in regulating flowering time. Three Medicago SOC1 genes were identified and characterized (MtSOC1a–MtSOC1c. All three MtSOC1 genes, when heterologously expressed, were able to promote earlier flowering of the late-flowering Arabidopsis soc1-2 mutant. The three MtSOC1 genes have different patterns of expression. However, consistent with a potential role in flowering time regulation, all three MtSOC1 genes are expressed in the shoot apex and are up-regulated in the shoot apex of plants in response to LD photoperiods and vernalization. The up-regulation of MtSOC1 genes was reduced in Medicago fta1-1 mutants, indicating that they are downstream of MtFTa1. Insertion mutant alleles of Medicago soc1b do not flower late, suggestive of functional redundancy among Medicago SOC1 genes in promoting flowering.

  4. Dextromethorphan upregulates osteoblast and osteoclast activity but does not attenuate ovariectomy-induced osteoporosis.

    Science.gov (United States)

    Wu, Jia-Lin; Tsai, Wei-Yuan; Chen, Jian-Horng; Wong, Chih-Shung

    2017-03-15

    Study on the in vivo regulatory role of glutamate in osteoblast (OB) and osteoclast (OC) differentiation is less advanced. The present study investigated the effect of dextromethorphan (DXM), an N-methyl-d-aspartate receptors (NMDARs) antagonist, on osteoporosis development. In order to examine the role of glutamate in bone metabolism, ovariectomized (Ovx) female Wistar rats were injected three times per week for 8weeks with either saline, or 15μg/kg of β-estrodiol, or DXM (40mg/kg) intraperitoneally. Serum samples were collected every two weeks for measuring osteocalcin and C-terminal telopeptide of type I collagen (CTX-1) level. Rats were then sacrificed at week 8 and the femurs harvested for micro-CT scanning and mechanical strength. In saline-treated group, osteocalcin level significantly lower than that of sham-operated rats at 8weeks after operation, while CTX-1 levels were not affected. Estrogen treatment, as a positive control, partially inhibited the Ovx-induced reduction of osteocalcin serum level. DXM injection prevented the Ovx-induced reduction of osteocalcin expression and significantly upregulated CTX-1 expression. The micro-CT scan showed that the bone volume density decreased significantly in DXM treated rats compared to the sham-operated rats. In the mechanical strength assay, the maximum failure load for DXM treatment was significantly lower than the other groups. Treatment with DXM upregulated OB and OC markers in Ovx rats, however with a greater effect on the OC marker, and had no significant benefit on bone volume density or bone strength. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor metastasis

    International Nuclear Information System (INIS)

    Yu, Haitao; Jin, Sufeng; Zhang, Na; Xu, Qi

    2016-01-01

    GTP binding protein 4(GTPBP4), a member of GTP-binding protein family, was previously characterized as a tumor suppressor that regulates and requires merlin to suppress cell proliferation. However, the role of GTPBP4 in the metastasis of colorectal carcinoma (CRC) remains unelucidated. Here, we observed that GTPBP4 was detected at higher levels in CRC metastatic tissues than that in the primary tumor tissues. Notably, up-regulation of GTPBP4 was closely correlated with tumor metastasis in CRCs. Kaplan-Meier and multivariate Cox regression analysis indicated GTPBP4 as an independent prognostic factor for CRC patients (hazard ratio = 2.693, 95% confident interval: 1.193–6.083, p = 0.017). Functional studies established that knockdown of GTPBP4 impeded, whereas ectopic expression of GTPBP4 enhanced cell motility and tumor metastasis in CRC cells. Interestingly, mechanistic investigations suggested that GTPBP4 may disorganize actin cytoskeleton through repressing RhoA signaling. Taken together, our research uncovered that GTPBP4 promotes CRC metastasis by disrupting actin cytoskeleton, which is mediated by the reduced RhoA activity. Strategies targeting GTPBP4 will be promising for CRC patients with metastases. - Highlights: • Up-regulation of GTPBP4 is detected in CRC metastatic tissues and closely correlated with tumor metastasis. • Increase of GTPBP4 is closely associated with poor prognosis. • GTPBP4 promotes cell motility and tumor metastasis in CRC cells. • GTPBP4 induces filamentous actin rearrangement specifically by repressing the activity of RhoA. • GTPBP4 may be a novel therapeutic target for CRC patients with metastasis.

  6. PPAR-γ Silencing Inhibits the Apoptosis of A549 Cells by Upregulating Bcl-2

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    Jingyu YANG

    2013-03-01

    Full Text Available Background and objective Drug resistance is the one of primary causes of death in patients with lung cancer, PPAR-γ could induce the apoptosis and reverse drug resistance. The aim of this study is to investigate the expression of PPAR-γ on cisplatin sensitivity and apoptosis response of human lung cancer cell line A549. Methods Reconstruction of PPAR-γ silencing A549 cells (A549/PPAR-γ(- by siRNA. MTT assay was employed to determine the effect of cisplatin on the proliferation of A549/PPAR-γ(-, flow cytometry to determine the effect of cisplatin on the cell apoptosis, Western blot to determine the change of phosphorylation of Akt, caspase-3 and expression of bcl-2/bax. Finally, RT-PCR was employed to determine the transcriptional level of bcl-2. Results Two PPAR-γ silencing A549 cell clones were established successfully, and the expression of PPAR-γ was downregulated significantly as confirmed by RT-PCR and Western blot. After PPAR-γ silencing, the resistance of these two A549 clones to cisplatin was increased by 1.29-fold and 1.60-fold respectively. Flow cytometry showed that the apoptosis rate was decreased, and Western Blot showed that the phosphorylation of Akt and expression of bcl-2/bax were upregulated, caspase-3 was downregulated. Finally, RT-PCR showed that the transcriptional level of bcl-2 was upregulated as well. Conclusion Downregulation of PPAR-γ in A549 cells led to increase of cisplatin resistance. One of the mechanisms was upregulatin of phosphorylation of Akt and expression of bcl-2, which inhibited the apoptosis of cells. The downregulation of PPAR-γ is a possible mechanism that leads to the clinical drug resistance of cancer.

  7. Biotin deficiency up-regulates TNF-alpha production in murine macrophages.

    Science.gov (United States)

    Kuroishi, Toshinobu; Endo, Yasuo; Muramoto, Koji; Sugawara, Shunji

    2008-04-01

    Biotin, a water-soluble vitamin of the B complex, functions as a cofactor of carboxylases that catalyze an indispensable cellular metabolism. Although significant decreases in serum biotin levels have been reported in patients with chronic inflammatory diseases, the biological roles of biotin in inflammatory responses are unclear. In this study, we investigated the effects of biotin deficiency on TNF-alpha production. Mice were fed a basal diet or a biotin-deficient diet for 8 weeks. Serum biotin levels were significantly lower in biotin-deficient mice than biotin-sufficient mice. After i.v. administration of LPS, serum TNF-alpha levels were significantly higher in biotin-deficient mice than biotin-sufficient mice. A murine macrophage-like cell line, J774.1, was cultured in a biotin-sufficient or -deficient medium for 4 weeks. Cell proliferation and biotinylation of intracellular proteins were decreased significantly in biotin-deficient cells compared with biotin-sufficient cells. Significantly higher production and mRNA expression of TNF-alpha were detected in biotin-deficient J774.1 cells than biotin-sufficient cells in response to LPS and even without LPS stimulation. Intracellular TNF-alpha expression was inhibited by actinomycin D, indicating that biotin deficiency up-regulates TNF-alpha production at the transcriptional level. However, the expression levels of TNF receptors, CD14, and TLR4/myeloid differentiation protein 2 complex were similar between biotin-sufficient and -deficient cells. No differences were detected in the activities of the NF-kappaB family or AP-1. The TNF-alpha induction by biotin deficiency was down-regulated by biotin supplementation in vitro and in vivo. These results indicate that biotin deficiency may up-regulate TNF-alpha production or that biotin excess down-regulates TNF-alpha production, suggesting that biotin status may influence inflammatory diseases.

  8. Fasting enhances TRAIL-mediated liver natural killer cell activity via HSP70 upregulation.

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    Vu T A Dang

    Full Text Available Acute starvation, which is frequently observed in clinical practice, sometimes augments the cytolytic activity of natural killer cells against neoplastic cells. In this study, we investigated the molecular mechanisms underlying the enhancement of natural killer cell function by fasting in mice. The total number of liver resident natural killer cells in a unit weight of liver tissue obtained from C57BL/6J mice did not change after a 3-day fast, while the proportions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL+ and CD69+ natural killer cells were significantly elevated (n = 7, p <0.01, as determined by flow cytometric analysis. Furthermore, we found that TRAIL- natural killer cells that were adoptively transferred into Rag-2-/- γ chain-/- mice could convert into TRAIL+ natural killer cells in fasted mice at a higher proportion than in fed mice. Liver natural killer cells also showed high TRAIL-mediated antitumor function in response to 3-day fasting. Since these fasted mice highly expressed heat shock protein 70 (n = 7, p <0.05 in liver tissues, as determined by western blot, the role of this protein in natural killer cell activation was investigated. Treatment of liver lymphocytes with 50 µg/mL of recombinant heat shock protein 70 led to the upregulation of both TRAIL and CD69 in liver natural killer cells (n = 6, p <0.05. In addition, HSP70 neutralization by intraperitoneally injecting an anti- heat shock protein 70 monoclonal antibody into mice prior to fasting led to the downregulation of TRAIL expression (n = 6, p <0.05. These findings indicate that acute fasting enhances TRAIL-mediated liver natural killer cell activity against neoplastic cells through upregulation of heat shock protein 70.

  9. Radiation induces invasiveness of pancreatic cancer via up-regulation of heparanase

    International Nuclear Information System (INIS)

    Lerner, I.; Bensoussan, E.; Meirovitz, A.; Elkin, M.; Vlodavsky, I.

    2013-01-01

    The full text of the publication follows. Pancreatic cancer is one of the most aggressive neoplasms with an extremely low survival rate. Because most pancreatic carcinoma patients miss the opportunity for complete surgical resection at the time of diagnosis, radiotherapy remains a major component of treatment modalities. However, pancreatic cancer often shows resistance to radiation therapy. Ionizing radiation (IR)-induced aggressiveness is emerging as one of the important mechanisms responsible for the limited benefit of radiation therapy in pancreatic cancer, but the identity of downstream effectors responsible for this effect remains poorly investigated. Here we report that IR promotes pancreatic cancer aggressiveness through up-regulation of the heparanase. Heparanase is a predominant mammalian enzyme capable of degrading heparan sulfate (HS), the main polysaccharide component of the basement membrane and other types of extracellular matrix (ECM). Cleavage of HS by heparanase leads to disassembly of ECM, enables cell invasion, releases HS-bound angiogenic and growth factors from the ECM depots, and generates bioactive HS fragments. We found that clinically relevant doses of IR augment invasive ability of pancreatic cells in vitro and in vivo via induction of heparanase. Our results indicate that the effect of IR on heparanase expression is mediated by Egr1 transcription factor. Moreover, specific inhibitor of heparanase enzymatic activity abolished IR-induced invasiveness of pancreatic carcinoma cells in vitro, while combined treatment with IR and the heparanase inhibitor, but not IR alone, attenuated ortho-topic pancreatic tumor progression in vivo. The proposed up-regulation of heparanase by IR represents a new molecular pathway through which IR may promote pancreatic tumor aggressiveness, providing explanation for the limited benefit from radiation therapy in pancreatic cancer. Our research is expected to offer a new approach to improve the efficacy of

  10. Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3

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    Zhao Lei

    2012-12-01

    Full Text Available Abstract Background Epidermal growth factor receptor (EGFR is suggested to predict the radiosensitivity and/or prognosis of human esophageal squamous cell carcinoma (ESCC. The objective of this study was to investigate the efficacy of Nimotuzumab (an anti-EGFR monoclonal antibody on ESCC radiotherapy (RT and underlying mechanisms. Methods Nimotuzumab was administrated to 2 ESCC cell lines KYSE30 and TE-1 treated with RT. Cell growth, colony formation and apoptosis were used to measure anti-proliferation effects. The method of RNA interference was used to investigate the role of insulin-like growth factor binding protein-3 (IGFBP-3 in ESCC cells radiosensitivity treated with Nimotuzumab. In vivo effect of Nimotuzumab on ESCC radiotherapy was done using a mouse xenograft model. Results Nimotuzumab enhanced radiation response of KYSE30 cells (with high EGFR expression in vitro, as evidenced by increased radiation-inhibited cell growth and colony formation and radiation-mediated apoptosis. Mechanism study revealed that Nimotuzumab inhibited phosphorylated EGFR (p-EGFR induced by EGF in KYSE30 cells. In addition, knockdown of IGFBP-3 by short hairpin RNA significantly reduced KYSE30 cells radiosensitivity (PP>0.05. In KYSE30 cell xenografts, Nimotuzumab combined with radiation led to significant tumor growth delay, compared with that of radiation alone (P=0.029, and also with IGFBP-3 up-regulation in tumor tissue. Conclusions Nimotuzumab could enhance the RT effect of ESCC cells with a functional active EGFR pathway. In particular, the increased ESCC radiosensitivity by Nimotuzumab might be dependent on the up-regulation of IGFBP-3 through EGFR-dependent pathway.

  11. Pro-inflammatory cytokines upregulate sympathoexcitatory mechanisms in the subfornical organ of the rat

    Science.gov (United States)

    Wei, Shun-Guang; Yu, Yang; Zhang, Zhi-Hua; Felder, Robert B.

    2015-01-01

    Our previous work indicated that the subfornical organ (SFO) is an important brain sensor of blood-borne pro-inflammatory cytokines, mediating their central effects on autonomic and cardiovascular function. However, the mechanisms by which SFO mediates the central effects of circulating pro-inflammatory cytokines remain unclear. We hypothesized that pro-inflammatory cytokines act within the SFO to upregulate the expression of excitatory and inflammatory mediators that drive sympathetic nerve activity. In urethane-anesthetized Sprague-Dawley rats, direct microinjection of TNF-α (25 ng) or IL-1β (25 ng) into SFO increased mean blood pressure, heart rate and renal sympathetic nerve activity within 15–20 minutes, mimicking the response to systemically administered pro-inflammatory cytokines. Pretreatment of SFO with microinjections of the angiotensin II type 1 receptor (AT1R) blocker losartan (1 µg), angiotensin-converting enzyme (ACE) inhibitor captopril (1 µg) or cyclooxygenase (COX)-2 inhibitor NS-398 (2 µg) attenuated those responses. Four hours after the SFO microinjection of TNF-α (25 ng) or IL-1β (25 ng), mRNA for ACE, AT1R, TNF-α and the p55 TNF-α receptor TNFR1, IL-1β and the IL-1R receptor, and COX-2 had increased in SFO, and mRNA for ACE, AT1R and COX-2 had increased downstream in the hypothalamic paraventricular nucleus. Confocal immunofluorescent images revealed that immunoreactivity for TNFR1 and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, co-localized with ACE, AT1R-like, COX-2 and prostaglandin E2 EP3 receptor immunoreactivity in SFO neurons. These data suggest that pro-inflammatory cytokines act within the SFO to upregulate the expression of inflammatory and excitatory mediators that drive sympathetic excitation. PMID:25776070

  12. Licochalcone A Upregulates Nrf2 Antioxidant Pathway and Thereby Alleviates Acetaminophen-Induced Hepatotoxicity

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    Hongming Lv

    2018-03-01

    Full Text Available Acetaminophen (APAP overdose-induced fatal hepatotoxicity is majorly characterized by overwhelmingly increased oxidative stress while enhanced nuclear factor-erythroid 2-related factor 2 (Nrf2 is involved in prevention of hepatotoxicity. Although Licochalcone A (Lico A upregulates Nrf2 signaling pathway against oxidative stress-triggered cell injury, whether it could protect from APAP-induced hepatotoxicity by directly inducing Nrf2 activation is still poorly elucidated. This study aims to explore the protective effect of Lico A against APAP-induced hepatotoxicity and its underlying molecular mechanisms. Our findings indicated that Lico A effectively decreased tert-butyl hydroperoxide (t-BHP- and APAP-stimulated cell apoptosis, mitochondrial dysfunction and reactive oxygen species generation and increased various anti-oxidative enzymes expression, which is largely dependent on upregulating Nrf2 nuclear translocation, reducing the Keap1 protein expression, and strengthening the antioxidant response element promoter activity. Meanwhile, Lico A dramatically protected against APAP-induced acute liver failure by lessening the lethality; alleviating histopathological liver changes; decreasing the alanine transaminase and aspartate aminotransferase levels, malondialdehyde formation, myeloperoxidase level and superoxide dismutase depletion, and increasing the GSH-to-GSSG ratio. Furthermore, Lico A not only significantly modulated apoptosis-related protein by increasing Bcl-2 expression, and decreasing Bax and caspase-3 cleavage expression, but also efficiently alleviated mitochondrial dysfunction by reducing c-jun N-terminal kinase phosphorylation and translocation, inhibiting Bax mitochondrial translocation, apoptosis-inducing factor and cytochrome c release. However, Lico A-inhibited APAP-induced the lethality, histopathological changes, hepatic apoptosis, and mitochondrial dysfunction in WT mice were evidently abrogated in Nrf2-/- mice. These

  13. Upregulation of Mrps18a in breast cancer identified by selecting phage antibody libraries on breast tissue sections

    DEFF Research Database (Denmark)

    Sørensen, Karen Marie Juul; Meldgaard, Theresa; Melchjorsen, Connie Jenning

    2017-01-01

    BACKGROUND: One of the hallmarks of cancer is an altered energy metabolism, and here, mitochondria play a central role. Previous studies have indicated that some mitochondrial ribosomal proteins change their expression patterns upon transformation. METHOD: In this study, we have used the selection...... of recombinant antibody libraries displayed on the surface of filamentous bacteriophage as a proteomics discovery tool for the identification of breast cancer biomarkers. A small subpopulation of breast cells expressing both cytokeratin 19 and cytokeratin 14 was targeted using a novel selection procedure....... RESULTS: We identified the mitochondrial ribosomal protein s18a (Mrps18a) as a protein which is upregulated in breast cancer. However, Mrps18a was not homogeneously upregulated in all cancer cells, suggesting the existence of sub-populations within the tumor. The upregulation was not confined...

  14. Up-regulation of microRNA-1290 impairs cytokinesis and affects the reprogramming of colon cancer cells.

    Science.gov (United States)

    Wu, Jia; Ji, Xiaowei; Zhu, Linlin; Jiang, Qiaoli; Wen, Zhenzhen; Xu, Song; Shao, Wei; Cai, Jianting; Du, Qin; Zhu, Yongliang; Mao, Jianshan

    2013-02-28

    Abnormal cytokinesis increases the possibility of nuclear fusion in tumor cells. However, the role of microRNAs (miRNAs) in abnormal cytokinesis is unclear. Here, we found that miR-1290 was significantly up-regulated in clinical colon cancer tissues. Up-regulation of miR-1290 postponed cytokinesis and led to the formation of multinucleated cells. KIF13B was a target of miR-1290 that was involved in aberrant cytokinesis. Furthermore, enforced expression of miR-1290 activated the Wnt pathway and increased the reprogramming-related transcript factors c-Myc and Nanog. Our results suggest that up-regulation of miR-1290 in colon cancer cells impaired cytokinesis and affected reprogramming. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Effects of chronic fructose overload on renal dopaminergic system: alteration of urinary L-dopa/dopamine index correlates to hypertension and precedes kidney structural damage.

    Science.gov (United States)

    Rukavina Mikusic, Natalia L; Kouyoumdzian, Nicolás M; Del Mauro, Julieta S; Cao, Gabriel; Trida, Verónica; Gironacci, Mariela M; Puyó, Ana M; Toblli, Jorge E; Fernández, Belisario E; Choi, Marcelo R

    2018-01-01

    Insulin resistance induced by a high-fructose diet has been associated to hypertension and renal damage. The aim of this work was to assess alterations in the urinary L-dopa/dopamine ratio over three time periods in rats with insulin resistance induced by fructose overload and its correlation with blood pressure levels and the presence of microalbuminuria and reduced nephrin expression as markers of renal structural damage. Male Sprague-Dawley rats were randomly divided into six groups: control (C) (C4, C8 and C12) with tap water to drink and fructose-overloaded (FO) rats (FO4, FO8 and FO12) with a fructose solution (10% w/v) to drink for 4, 8 and 12 weeks. A significant increase of the urinary L-dopa/dopamine ratio was found in FO rats since week 4, which positively correlated to the development of hypertension and preceded in time the onset of microalbuminuria and reduced nephrin expression observed on week 12 of treatment. The alteration of this ratio was associated to an impairment of the renal dopaminergic system, evidenced by a reduction in renal dopamine transporters and dopamine D1 receptor expression, leading to an overexpression and overactivation of the enzyme Na + , K + -ATPase with sodium retention. In conclusion, urinary L-dopa/dopamine ratio alteration in rats with fructose overload positively correlated to the development of hypertension and preceded in time the onset of renal structural damage. This is the first study to propose the use of the urinary L-dopa/dopamine index as marker of renal dysfunction that temporarily precedes kidney structural damage induced by fructose overload. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Confocal laser Raman microspectroscopy of biomineralization foci in UMR 106 osteoblastic cultures reveals temporally synchronized protein changes preceding and accompanying mineral crystal deposition.

    Science.gov (United States)

    Wang, Chuanyi; Wang, Yong; Huffman, Nichole T; Cui, Chaoying; Yao, Xiaomei; Midura, Sharon; Midura, Ronald J; Gorski, Jeff P

    2009-03-13

    Mineralization in UMR 106-01 osteoblastic cultures occurs within extracellular biomineralization foci (BMF) within 12 h after addition of beta-glycerol phosphate to cells at 64 h after plating. BMF are identified by their enrichment with an 85-kDa glycoprotein reactive with Maackia amurensis lectin. Laser Raman microspectroscopic scans were made on individual BMF at times preceding (64-76 h) and following the appearance of mineral crystals (76-88 h). The range of variation between spectra for different BMF in the same culture was rather small. In contrast, significant differences were observed for spectral bands at 957-960, 1004, and 1660 cm(-1) when normalized BMF spectra at different times were compared. Protein-dependent spectral bands at 1004 and 1660 cm(-1) increased and then decreased preceding the detection of hydroxyapatite crystals via the phosphate stretching peak at 959-960 cm(-1). When sodium phosphate was substituted for beta-glycerol phosphate, mineralization occurred 3-6 h earlier. Irrespective of phosphate source, the Raman full peak width at half-maximum ratio for 88 h cultures was similar to that for 10-day-old marrow ablation primary bone. However, if mineralization was blocked with serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride, 64-88-h BMF spectra remained largely invariant. In summary, Raman spectral data demonstrate for the first time that formation of hydroxyapatite crystals within individual BMF is a multistep process. Second, changes in protein-derived signals at 1004 and 1660 cm(-1) reflect events within BMFs that precede or accompany mineral crystal production because they are blocked by mineralization inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride. Finally, the low extent of spectral variability detected among different BMF at the same time point indicates that mineralization of individual BMF within a culture is synchronized.

  17. Confocal Laser Raman Microspectroscopy of Biomineralization Foci in UMR 106 Osteoblastic Cultures Reveals Temporally Synchronized Protein Changes Preceding and Accompanying Mineral Crystal Deposition*

    Science.gov (United States)

    Wang, Chuanyi; Wang, Yong; Huffman, Nichole T.; Cui, Chaoying; Yao, Xiaomei; Midura, Sharon; Midura, Ronald J.; Gorski, Jeff P.

    2009-01-01

    Mineralization in UMR 106-01 osteoblastic cultures occurs within extracellular biomineralization foci (BMF) within 12 h after addition of β-glycerol phosphate to cells at 64 h after plating. BMF are identified by their enrichment with an 85-kDa glycoprotein reactive with Maackia amurensis lectin. Laser Raman microspectroscopic scans were made on individual BMF at times preceding (64–76 h) and following the appearance of mineral crystals (76–88 h). The range of variation between spectra for different BMF in the same culture was rather small. In contrast, significant differences were observed for spectral bands at 957–960, 1004, and 1660 cm-1 when normalized BMF spectra at different times were compared. Protein-dependent spectral bands at 1004 and 1660 cm-1 increased and then decreased preceding the detection of hydroxyapatite crystals via the phosphate stretching peak at 959–960 cm-1. When sodium phosphate was substituted for β-glycerol phosphate, mineralization occurred 3–6 h earlier. Irrespective of phosphate source, the Raman full peak width at half-maximum ratio for 88 h cultures was similar to that for 10-day-old marrow ablation primary bone. However, if mineralization was blocked with serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride, 64–88-h BMF spectra remained largely invariant. In summary, Raman spectral data demonstrate for the first time that formation of hydroxyapatite crystals within individual BMF is a multistep process. Second, changes in protein-derived signals at 1004 and 1660 cm-1 reflect events within BMFs that precede or accompany mineral crystal production because they are blocked by mineralization inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride. Finally, the low extent of spectral variability detected among different BMF at the same time point indicates that mineralization of individual BMF within a culture is synchronized. PMID:19116206

  18. Specific β-turns precede PPIIL structures binding to allele-specific HLA-DRβ1* PBRs in fully-protective malaria vaccine components

    Science.gov (United States)

    Bermudez, Adriana; Alba, Martha P.; Vanegas, Magnolia; Patarroyo, Manuel A.; Patarroyo, Manuel E.

    2018-04-01

    The 3D structural analysis of 62 peptides derived from highly pathogenic Plasmodium falciparum malaria parasite proteins involved in host cell invasion led to finding a striking association between particular β-turn types located in the N-terminal peripheral flanking residue region (preceding the polyproline II left-handed structures fitting into the HLA-DRβ* allele family) and modified immune protection-inducing protein structure induced long-lasting protective immunity. This is the first time association between two different secondary structures associated with a specific immunological function has been described: full, long-lasting protective immunity.

  19. A close connection between the PERK and IRE arms of the UPR and the transcriptional regulation of autophagy.

    Science.gov (United States)

    Deegan, Shane; Koryga, Izabela; Glynn, Sharon A; Gupta, Sanjeev; Gorman, Adrienne M; Samali, Afshin

    2015-01-02

    Endoplasmic reticulum (ER) stress is known to lead to activation of both the unfolded protein response (UPR) and autophagy. Although regulatory connections have been identified between the UPR and autophagy, it is still unclear to what extent the UPR regulates the genes involved at the different stages of the autophagy pathway. Here, we carried out a microarray analysis of HCT116 cells subjected to ER stress and observed the transcriptional upregulation of a large cohort of autophagy-related genes. Of particular interest, we identified the transcriptional upregulation of the autophagy receptor genes SQSTM1/p62, NBR1 and BNIP3L/NIX in response to ER stress and show that the inhibition of the UPR transmembrane receptors, PERK and IRE1, abrogates this upregulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Perinatal exposure to environmental tobacco smoke is associated with changes in DNA methylation that precede the adult onset of lung disease in a mouse model.

    Science.gov (United States)

    Cole, Elizabeth; Brown, Traci A; Pinkerton, Kent E; Postma, Britten; Malany, Keegan; Yang, Mihi; Kim, Yang Jee; Hamilton, Raymond F; Holian, Andrij; Cho, Yoon Hee

    2017-08-01

    Prenatal and early-life environmental tobacco smoke (ETS) exposure can induce epigenetic alterations associated with inflammation and respiratory disease. The objective of this study was to address the long-term epigenetic consequences of perinatal ETS exposure on latent respiratory disease risk, which are still largely unknown. C57BL/6 mice were exposed to prenatal and early-life ETS; offspring lung pathology, global DNA, and gene-specific methylation were measured at two adult ages. Significant alterations in global DNA methylation and promoter methylation of IFN-γ and Thy-1 were found in ETS-exposed offspring at 10-12 and 20 weeks of age. These sustained epigenetic alterations preceded the onset of significant pulmonary pathologies observed at 20 weeks of age. This study suggests that perinatal ETS exposure induces persistent epigenetic alterations in global DNA, as well as IFN-γ and Thy-1 promoter methylation that precede the adult onset of fibrotic lung pathology. These epigenetic findings could represent potential biomarkers of latent respiratory disease risk.

  1. Characteristics of invasive breast cancer and overall survival of patients eligible for mass breast cancer screening in Guadeloupe compared to those of the preceding age group.

    Science.gov (United States)

    Kadhel, Philippe; Borja De Mozota, Daphné; Gaumond, Stéphanie; Deloumeaux, Jacqueline

    2017-10-01

    Mass breast cancer screening is offered to French women between the ages of 50 and 74. In the French overseas department of Guadeloupe, where the population is of mostly African ancestry, a low age at diagnosis of breast cancer has been reported, as for African-Americans. This raises the question of whether breast cancer is more aggressive in the age group preceding that eligible for mass screening (40-49) in Guadeloupe. We compared the tumor-related prognostic factors, first line therapy and overall survival rates of breast cancer cases diagnosed between the 40-49 and 50-74 age groups, based on reports of the cancer registry of Guadeloupe for the period 2008-2013. The characteristics studied, risk of death after breast cancer (HR 0.84 [95% CI: 0.58-1.22] and overall survival, did not differ significantly between the two groups, except for higher tumor size (28.8 vs 24.0; p=0.004) in the younger group. These results do not show a pattern of more aggressive breast cancer in the age group preceding that eligible for mass screening in Guadeloupe. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Bauhinia championi (Benth.) Benth. polysaccharides upregulate Wnt/β-catenin signaling in chondrocytes.

    Science.gov (United States)

    Li, Huiting; Li, Xihai; Liu, Guozhong; Chen, Jiashou; Weng, Xiaping; Liu, Fayuan; Xu, Huifeng; Liu, Xianxiang; Ye, Hongzhi

    2013-12-01

    Bauhinia championi (Benth.) Benth. polysaccharides (BCBPs), extracted from Bauhinia championi (Benth.) Benth., which has been used in traditional Chinese medicine (TCM) for the treatment of osteoarthritis (OA), are the bioactive constituents of Bauhinia championi (Benth.) rattan. However, the molecular mechanisms responsible for their effects on OA are poorly understood. The Wnt/β-catenin signaling pathway plays an important role in the proliferation of chondrocytes. In the present study, the effects of BCBPs on Wnt/β-catenin signaling in chondrocytes were investigated. BCBPs were obtained by hot-water extraction and identified by the modified high performance liquid chromatography (HPLC) method. Chondrocytes were isolated from the knees of Sprague‑Dawley rats and identified by type II collagen immunohistochemistry. The chondrocytes were treated with or without BCBPs for 48 h. Cell viability was evaluated by MTT assay. The mRNA and protein levels of Wnt-4, β-catenin, Frizzled-2, glycogen synthase kinase (GSK)-3β, cyclin D1 and collagen II were detected by western blot analysis and reverse transcription PCR (RT-PCR), respectively. We found that the BCBPs contained at least seven monosaccharides, including D-mannose, rhamnose, D-(+) glucuronic acid, D-(+) galacturonic acid, D-glucose, galactose and arabinose. The cell viability of the chondrocytes treated with 50, 100 and 200 µg/ml BCBPs was significantly higher than that of the chondroctyes in the control group (treated with 0 µg/ml BCBPs). Furthermore, compared with the control group, the mRNA and protein expression of Wnt-4, β-catenin, Frizzled-2 and cyclin D1 in the BCBP-treated groups markedly increased, whereas the mRNA and protein expression of GSK-3β significantly decreased. Of note, the dose of 100 µg/ml BCBPs was more effective than the dose of 50 µg/ml BCBPs and 200 µg/ml BCBPs. In addition, we found that treatment with BCBPs upregulated the protein levels of collagen II in the

  3. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Alcendor Donald J

    2012-05-01

    Full Text Available Abstract Background Congenital human cytomegalovirus (HCMV infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV, microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC. However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha, interleukin-1 beta (IL-1beta, and interleukin-6 (IL-6. Pericytes exposed to SBCMV elicited

  4. Genistein up-regulates tumor suppressor microRNA-574-3p in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Takeshi Chiyomaru

    Full Text Available Genistein has been shown to inhibit cancers both in vitro and in vivo, by altering the expression of several microRNAs (miRNAs. In this study, we focused on tumor suppressor miRNAs regulated by genistein and investigated their function in prostate cancer (PCa and target pathways. Using miRNA microarray analysis and real-time RT-PCR we observed that miR-574-3p was significantly up-regulated in PCa cells treated with genistein compared with vehicle control. The expression of miR-574-3p was significantly lower in PCa cell lines and clinical PCa tissues compared with normal prostate cells (RWPE-1 and adjacent normal tissues. Low expression level of miR-574-3p was correlated with advanced tumor stage and higher Gleason score in PCa specimens. Re-expression of miR-574-3p in PCa cells significantly inhibited cell proliferation, migration and invasion in vitro and in vivo. miR-574-3p restoration induced apoptosis through reducing Bcl-xL and activating caspase-9 and caspase-3. Using GeneCodis software analysis, several pathways affected by miR-574-3p were identified, such as 'Pathways in cancer', 'Jak-STAT signaling pathway', and 'Wnt signaling pathway'. Luciferase reporter assays demonstrated that miR-574-3p directly binds to the 3' UTR of several target genes (such as RAC1, EGFR and EP300 that are components of 'Pathways in cancer'. Quantitative real-time PCR and Western analysis showed that the mRNA and protein expression levels of the three target genes in PCa cells were markedly down-regulated with miR-574-3p. Loss-of-function studies demonstrated that the three target genes significantly affect cell proliferation, migration and invasion in PCa cell lines. Our results show that genistein up-regulates tumor suppressor miR-574-3p expression targeting several cell signaling pathways. These findings enhance understanding of how genistein regulates with miRNA in PCa.

  5. Triethylene Glycol Up-Regulates Virulence-Associated Genes and Proteins in Streptococcus mutans.

    Science.gov (United States)

    Sadeghinejad, Lida; Cvitkovitch, Dennis G; Siqueira, Walter L; Santerre, J Paul; Finer, Yoav

    2016-01-01

    Triethylene glycol dimethacrylate (TEGDMA) is a diluent monomer used pervasively in dental composite resins. Through hydrolytic degradation of the composites in the oral cavity it yields a hydrophilic biodegradation product, triethylene glycol (TEG), which has been shown to promote the growth of Streptococcus mutans, a dominant cariogenic bacterium. Previously it was shown that TEG up-regulated gtfB, an important gene contributing to polysaccharide synthesis function in biofilms. However, molecular mechanisms related to TEG's effect on bacterial function remained poorly understood. In the present study, S. mutans UA159 was incubated with clinically relevant concentrations of TEG at pH 5.5 and 7.0. Quantitative real-time PCR, proteomics analysis, and glucosyltransferase enzyme (GTF) activity measurements were employed to identify the bacterial phenotypic response to TEG. A S. mutans vicK isogenic mutant (SMΔvicK1) and its associated complemented strain (SMΔvicK1C), an important regulatory gene for biofilm-associated genes, were used to determine if this signaling pathway was involved in modulation of the S. mutans virulence-associated genes. Extracted proteins from S. mutans biofilms grown in the presence and absence of TEG were subjected to mass spectrometry for protein identification, characterization and quantification. TEG up-regulated gtfB/C, gbpB, comC, comD and comE more significantly in biofilms at cariogenic pH (5.5) and defined concentrations. Differential response of the vicK knock-out (SMΔvicK1) and complemented strains (SMΔvicK1C) implicated this signalling pathway in TEG-modulated cellular responses. TEG resulted in increased GTF enzyme activity, responsible for synthesizing insoluble glucans involved in the formation of cariogenic biofilms. As well, TEG increased protein abundance related to biofilm formation, carbohydrate transport, acid tolerance, and stress-response. Proteomics data was consistent with gene expression findings for the selected

  6. NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells

    International Nuclear Information System (INIS)

    Pecorelli, Alessandra; Bocci, Velio; Acquaviva, Alessandra; Belmonte, Giuseppe; Gardi, Concetta; Virgili, Fabio; Ciccoli, Lucia; Valacchi, Giuseppe

    2013-01-01

    During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O 3 per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H 2 O 2 ) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozo