WorldWideScience

Sample records for early events involved

  1. Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells.

    Science.gov (United States)

    Monetti, Emanuela; Kadono, Takashi; Tran, Daniel; Azzarello, Elisa; Arbelet-Bonnin, Delphine; Biligui, Bernadette; Briand, Joël; Kawano, Tomonori; Mancuso, Stefano; Bouteau, François

    2014-03-01

    Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·(-)) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·(-) generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca(2+)]cyt increase and singlet oxygen production, do not seem to be involved in PCD.

  2. Root secreted metabolites and proteins are involved in the early events of plant-plant recognition prior to competition.

    Directory of Open Access Journals (Sweden)

    Dayakar V Badri

    Full Text Available The mechanism whereby organisms interact and differentiate between others has been at the forefront of scientific inquiry, particularly in humans and certain animals. It is widely accepted that plants also interact, but the degree of this interaction has been constricted to competition for space, nutrients, water and light. Here, we analyzed the root secreted metabolites and proteins involved in early plant neighbor recognition by using Arabidopsis thaliana Col-0 ecotype (Col as our focal plant co-cultured in vitro with different neighbors [A. thaliana Ler ecotype (Ler or Capsella rubella (Cap]. Principal component and cluster analyses revealed that both root secreted secondary metabolites and proteins clustered separately between the plants grown individually (Col-0, Ler and Cap grown alone and the plants co-cultured with two homozygous individuals (Col-Col, Ler-Ler and Cap-Cap or with different individuals (Col-Ler and Col-Cap. In particularly, we observed that a greater number of defense- and stress-related proteins were secreted when our control plant, Col, was grown alone as compared to when it was co-cultured with another homozygous individual (Col-Col or with a different individual (Col-Ler and Col-Cap. However, the total amount of defense proteins in the exudates of the co-cultures was higher than in the plant alone. The opposite pattern of expression was identified for stress-related proteins. These data suggest that plants can sense and respond to the presence of different plant neighbors and that the level of relatedness is perceived upon initial interaction. Furthermore, the role of secondary metabolites and defense- and stress-related proteins widely involved in plant-microbe associations and abiotic responses warrants reassessment for plant-plant interactions.

  3. Early events of overused supraspinatus tendons involve matrix metalloproteinases and EMMPRIN/CD147 in the absence of inflammation.

    Science.gov (United States)

    Attia, Mohamed; Huet, Eric; Gossard, Camille; Menashi, Suzanne; Tassoni, Marie-Claude; Martelly, Isabelle

    2013-04-01

    The principal feature of tendon degeneration is structural change of the extracellular matrix (ECM) including collagens. In painful tendons, alterations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been described; however, the initial molecular mechanism at the origin of these alterations is still poorly understood. A rat model of supraspinatus tendon overuse has been developed, which may be predictive of pathological tendon alterations. To determine which MMPs are involved in early ECM remodeling during overuse and their relationship with the inflammatory context. Controlled laboratory study. Analyses were performed on rat supraspinatus tendons at 2 and 4 weeks of overuse on a downhill treadmill. Transcript levels of MMPs and TIMPs were assessed by semiquantitative reverse transcription polymerase chain reaction. Western blotting and/or immunolabeling were used for MMP-2, MMP-3, MMP-13, and extracellular MMP inducer (EMMPRIN, also called cluster of differentiation [CD] 147) detection. In situ and/or sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) gelatin zymography was performed for MMP-2 and MMP-9. TIMP activity was revealed by reverse zymography. Inflammation was assessed by cytokine antibody array and/or immunolabeling. Compared with a control, overused supraspinatus tendons showed a significantly higher gelatinolytic activity at 2 weeks, which slightly decreased at 4 weeks. MMP-9 and MMP-13 were undetectable; MMP-3 was downregulated in overused tendons. Only MMP-2, particularly its active form, and the MMP-2 activator MMP-14 were upregulated at 2 weeks of overuse when an increase in TIMP-2 transcripts was observed. MMP-2 upregulation occurred in the absence of inflammation but was associated with an increase of EMMPRIN/CD147. EMMPRIN/CD147-regulated MMP-2 and MMP-14, associated with low MMP-3, appear as the main characteristics of ECM remodeling in early overused tendons. Whether alterations

  4. Early traumatic events in psychopaths.

    Science.gov (United States)

    Borja, Karina; Ostrosky, Feggy

    2013-07-01

    The relationship between diverse early traumatic events and psychopathy was studied in 194 male inmates. Criminal history transcripts were revised, and clinical interviews were conducted to determine the level of psychopathy using the Psychopathy Checklist-Revised (PCL-R) Form, and the Early Trauma Inventory was applied to assess the incidence of abuse before 18 years of age. Psychopathic inmates presented a higher victimization level and were more exposed to certain types of intended abuse than sociopathic inmates, while the sum of events and emotional abuse were associated with the PCL-R score. Our studies support the influence of early adverse events in the development of psychopathic offenders.

  5. Purchase decision involvement: Event management segments and related event behavior

    Science.gov (United States)

    Rodney B. Warnick; David C. Bojanic

    2012-01-01

    The goal of this research was to examine the relationships between different levels of event purchase decision involvement (PDI) segments and their respective event behaviors (e.g., expenditures, travel behavior, event consumption and satisfaction). The specific purpose was to answer two major research questions: 1) Can PDI identify different levels or segments of...

  6. Early events in axon/dendrite polarization.

    Science.gov (United States)

    Cheng, Pei-lin; Poo, Mu-ming

    2012-01-01

    Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure.

  7. Early events in the generation of autophagosomes are required for the formation of membrane structures involved in hepatitis C virus genome replication.

    Science.gov (United States)

    Mohl, Bjorn-Patrick; Bartlett, Christopher; Mankouri, Jamel; Harris, Mark

    2016-03-01

    Hepatitis C virus (HCV) infection has been shown to induce autophagy but the mechanisms underpinning this process remain to be elucidated. Induction of autophagy requires the class III phosphatidylinositol 3-kinase, Vps34, which produces phosphatidylinositol 3-phosphate (PI3P) within the endoplasmic reticulum (ER) membrane. This recruits proteins with PI3P binding domains such as the double-FYVE-containing protein 1 (DFCP1). DFCP1 generates cup-shaped protrusions from the ER membrane, termed omegasomes, which provide a platform for the production of autophagosomes. Here we present data demonstrating that both Vps34 and DFCP1 are required for HCV genome replication, in the context of both a subgenomic replicon and virus infection, but did not affect virus entry or initial translation. Using live cell fluorescence microscopy we demonstrated that early during HCV infection the nascent viral genome replication complexes (identified by using non-structural protein NS5A as a marker) transiently colocalize with DFCP1-positive punctae (omegasomes), before the two structures move apart from each other. This observation is reminiscent of the transient association of LC3 and DFCP1 during omegasome formation, and therefore we propose that omegasomes are utilized by HCV to generate the double-membrane vesicles which are the hallmark of HCV replication complexes.

  8. Turkish Early Childhood Educators on Parental Involvement

    Science.gov (United States)

    Hakyemez, Sevcan

    2015-01-01

    Research conducted over recent decades show that parental involvement plays a significant role in children's academic achievement as well as their cognitive, social and emotional development. For effective parental involvement, understanding the conceptualization of early childhood educators should be significant. This research investigated the…

  9. Involvement in Internet Aggression during Early Adolescence

    Science.gov (United States)

    Werner, Nicole E.; Bumpus, Matthew F.; Rock, Daquarii

    2010-01-01

    The current study examined concurrent and longitudinal predictors of early adolescents' involvement in Internet aggression. Cross-sectional results (N = 330; 57% female) showed that the likelihood of reporting Internet aggression was higher among youth who spent more time using Internet-based technologies to communicate with friends and who were…

  10. Pulmonary involvement in early rheumatoid arthritis patients.

    Science.gov (United States)

    Habib, Hisham M; Eisa, Ashraf A; Arafat, Waleed R; Marie, Mohamed A

    2011-02-01

    Pulmonary involvement in rheumatoid arthritis (RA) is common and can be due to the disease itself as well as to the therapies used to treat it. The purpose of this study was to disclose the pulmonary involvement in early RA patients not more than 2 years disease duration using the computed tomography (CT) as well as the pulmonary function tests as ways of pulmonary involvement assessment. Forty patients aged 37.6 ± 10.3 with early rheumatoid arthritis not more than 2 years of disease duration were recruited for the study. All patients were assessed clinically for their RA with DAS28, which was utilized for disease activity determination. Ten percent of our patients were found to be clinically involved by interstitial lung disease (ILD), where 27% have abnormal HRCT finding and 32.5% with abnormal PFT. Predilection for clinically manifest ILD was evident in active RA patients with high DAS28 score, seropositive RA patients, and in patients receiving steroids and anti-TNFα therapy. ILD occurs early in the course of RA, with more predilection for clinically active RA disease.

  11. Involvement in internet aggression during early adolescence.

    Science.gov (United States)

    Werner, Nicole E; Bumpus, Matthew F; Rock, Daquarii

    2010-06-01

    The current study examined concurrent and longitudinal predictors of early adolescents' involvement in Internet aggression. Cross-sectional results (N = 330; 57% female) showed that the likelihood of reporting Internet aggression was higher among youth who spent more time using Internet-based technologies to communicate with friends and who were themselves targets of Internet aggression. Offline relational aggression and beliefs supportive of relational and physical aggression also predicted concurrent involvement in Internet aggression. We used longitudinal data (N = 150; 51% female) to distinguish between youth who were aggressive in traditional contexts only (i.e., school) from those who were aggressive both online and offline. These results indicated that youth who were aggressive both online and offline were older at the initial assessment, were targets of Internet aggression, and held beliefs more supportive of relational aggression than youth who were aggressive offline only. Implications and directions for future research are discussed.

  12. Influence of Early Literacy Parental Involvement on Science ...

    African Journals Online (AJOL)

    Influence of early literacy on science achievement of Junior Secondary ... School II (JSSII) students(162 females and 198 males, mean age 13.47years, SD= ... science achievement was found and, parental involvement in children's early ...

  13. Quantitative proteomic assessment of very early cellular signaling events

    DEFF Research Database (Denmark)

    Dengjel, Joern; Akimov, Vyacheslav; Olsen, Jesper V

    2007-01-01

    Technical limitations have prevented proteomic analyses of events occurring less than 30 s after signal initiation. We developed an automated, continuous quench-flow system allowing quantitative proteomic assessment of very early cellular signaling events (qPACE) with a time resolution of 1 s...

  14. Scaled biotic disruption during early Eocene global warming events

    NARCIS (Netherlands)

    Gibbs, S.J.; Bown, P.R.; Murphy, B.H.; Sluijs, A.|info:eu-repo/dai/nl/311474748; Edgar, K.M.; Pälike, H.; Bolton, C.T.; Zachos, J.C.

    2012-01-01

    Late Paleocene and early Eocene hyperthermals are transient warming events associated with massive perturbations of the global carbon cycle, and are considered partial analogues for current anthropogenic climate change. Because the magnitude of carbon release varied between the events, they are

  15. Scaled biotic disruption during early Eocene global warming events

    NARCIS (Netherlands)

    Gibbs, S.J.; Bown, P.R.; Murphy, B.H.; Sluijs, A.; Edgar, K.M.; Pälike, H.; Bolton, C.T.; Zachos, J.C.

    2012-01-01

    Late Paleocene and early Eocene hyperthermals are transient warming events associated with massive perturbations of the global carbon cycle, and are considered partial analogues for current anthropogenic climate change. Because the magnitude of carbon release varied between the events, they are natu

  16. Parathyroid involvement in thyroid cancer: an unforeseen event

    Directory of Open Access Journals (Sweden)

    Chrisoulidou Alexandra

    2012-06-01

    Full Text Available Abstract Background Parathyroid metastatic disease from thyroid cancer has not been studied extensively, mainly due to the need for parathyroid preservation during thyroid surgery. Methods We reviewed files from 1,770 patients with thyroid cancer followed up in our department and 10 patients with parathyroid metastases (0.5% were identified. Patient and tumor characteristics were recorded. Results Six out of ten patients had metastases from papillary thyroid cancer, three from follicular thyroid cancer and one from anaplastic thyroid cancer. In nine patients parathyroid infiltration from thyroid cancer was found in direct contact with the thyroid cancer, and in one patient metastatic foci were observed not in continuity with the thyroid cancer. Conclusions Parathyroid involvement, although infrequent, may occur in thyroid cancer independently of patient age and tumor size. The clinical significance of such event is not clear. The influence on disease outcome remains to be elucidated.

  17. influence of early literacy parental involvement on science ...

    African Journals Online (AJOL)

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    Influence of early literacy on science achievement of Junior Secondary School students was examined in this ... were highly involved in their children's early literacy acquisition; parental involvement in literacy ... Curriculum Studies and Instructional Technology Department, Faculty of education. ..... Albany,. NY: Suny Press.

  18. Exploring Parental Involvement in Early Years Education in China: Development and Validation of the Chinese Early Parental Involvement Scale (CEPIS)

    Science.gov (United States)

    Lau, Eva Yi Hung; Li, Hui; Rao, Nirmala

    2012-01-01

    This study developed and validated an instrument, the Chinese Early Parental Involvement Scale (CEPIS), that can be widely used in both local and international contexts to assess Chinese parental involvement in early childhood education. The study was carried out in two stages: (1) focus group interviews were conducted with 41 teachers and 35…

  19. Scaled biotic disruption during early Eocene global warming events

    OpenAIRE

    Gibbs, S. J.; Bown, P. R.; Murphy, B. H.; Sluijs, A.; Edgar, K. M.; Pälike, H.; C. T. Bolton; Zachos, J. C.

    2012-01-01

    Late Paleocene and early Eocene hyperthermals are transient warming events associated with massive perturbations of the global carbon cycle, and are considered partial analogues for current anthropogenic climate change. Because the magnitude of carbon release varied between the events, they are natural experiments ideal for exploring the relationship between carbon cycle perturbations, climate change and biotic response. Here we quantify marine biotic variability through three million years o...

  20. Method for early detection of cooling-loss events

    Energy Technology Data Exchange (ETDEWEB)

    Bermudez, Sergio A.; Hamann, Hendrik F.; Marianno, Fernando J.

    2015-12-22

    A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

  1. Method for early detection of cooling-loss events

    Energy Technology Data Exchange (ETDEWEB)

    Bermudez, Sergio A.; Hamann, Hendrik; Marianno, Fernando J.

    2015-06-30

    A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

  2. Breaking barriers : Early events in chikungunya and dengue virus infections

    NARCIS (Netherlands)

    Hoornweg, Tabitha Elina

    2016-01-01

    Breaking Barriers – early events in chikungunya and dengue virus infections Chikungunya en dengue zijn twee door muggen overdraagbare virussen die voornamelijk voorkomen in (sub)tropische gebieden. Sinds 2006 verspreidt het chikungunyavirus zich in een razend tempo over de wereld. Miljoenen mensen r

  3. Breaking barriers : Early events in chikungunya and dengue virus infections

    NARCIS (Netherlands)

    Hoornweg, Tabitha Elina

    2016-01-01

    Breaking Barriers – early events in chikungunya and dengue virus infections Chikungunya en dengue zijn twee door muggen overdraagbare virussen die voornamelijk voorkomen in (sub)tropische gebieden. Sinds 2006 verspreidt het chikungunyavirus zich in een razend tempo over de wereld. Miljoenen mensen r

  4. Scaled biotic disruption during early Eocene global warming events

    Directory of Open Access Journals (Sweden)

    S. J. Gibbs

    2012-01-01

    Full Text Available Late Paleocene and early Eocene hyperthermals are transient global warming events associated with massive carbon injection or carbon redistribution in the ocean-atmosphere system, and are considered partial analogues for current anthropogenic climate change. Because the magnitude of carbon release varied between the events, they are natural experiments ideal for exploring the relationship between carbon cycle perturbations, climate change and biotic response. Here we quantify marine biotic variability through three million years of the early Eocene, including five hyperthermals, utilizing a method that allows us to integrate the records of different plankton groups through scenarios ranging from background to major extinction events. Our long-time-series calcareous nannoplankton record indicates a scaling of biotic disruption to climate change associated with the amount of carbon released during the various hyperthermals. Critically, only the three largest hyperthermals, the Paleocene Eocene Thermal Maximum (PETM, Eocene Thermal Maximum 2 (ETM2 and the I1 event, show above-background variance, suggesting that the magnitude of carbon input and associated climate change needs to surpass a threshold value to cause significant biotic disruption.

  5. Scaled biotic disruption during early Eocene global warming events

    Directory of Open Access Journals (Sweden)

    S. J. Gibbs

    2012-11-01

    Full Text Available Late Paleocene and early Eocene hyperthermals are transient warming events associated with massive perturbations of the global carbon cycle, and are considered partial analogues for current anthropogenic climate change. Because the magnitude of carbon release varied between the events, they are natural experiments ideal for exploring the relationship between carbon cycle perturbations, climate change and biotic response. Here we quantify marine biotic variability through three million years of the early Eocene that include five hyperthermals, utilizing a method that allows us to integrate the records of different plankton groups through scenarios ranging from background to major extinction events. Our long time-series calcareous nannoplankton record indicates a scaling of biotic disruption to climate change associated with the amount of carbon released during the various hyperthermals. Critically, only the three largest hyperthermals, the Paleocene–Eocene Thermal Maximum (PETM, Eocene Thermal Maximum 2 (ETM2 and the I1 event, show above-background variance, suggesting that the magnitude of carbon input and associated climate change needs to surpass a threshold value to cause significant biotic disruption.

  6. Impact Constraints on Major Events in Early Mars History

    Science.gov (United States)

    Frey, H. V.

    2004-01-01

    MOLA data have revealed a large population of "Quasi-Circular Depressions" (QCDs) with little or no visible expression in image data. These likely buried impact basins have important implications for the age of the lowland crust, how that compares with original highland crust, and when and how the crustal dichotomy may have formed. The buried lowlands are of Early Noachian age, likely slightly younger than the buried highlands but older than the exposed (visible) highland surface. A depopulation of large visible basins at diameters 800 to 1300 km suggests some global scale event early in martian history, maybe related to the formation of the lowlands and/or the development of Tharsis. A suggested early disappearance of the global magnetic field can be placed within a temporal sequence of formation of the very largest impact basins. The global field appears to have disappeared at about the time the lowlands formed. It seems likely the topographic crustal dichotomy was produced very early in martian history by processes which operated very quickly. Thus there appears to have been a northern lowland throughout nearly all of martian history, predating the last of the really large impacts (Hellas, Argyre and Isidis) and their likely very significant environmental consequences.

  7. EVENT PRESTIGE AS A MEDIATOR BETWEEN SPORT INVOLVEMENT AND INTENT TO CONTINUE PARTICIPATION.

    Science.gov (United States)

    Kim, Seungmo; Liu, Jing Dong; Love, Adam

    2015-10-01

    The current study examined perceived event prestige as a mediator between sport involvement and sport participation behavioral intent. A total of 455 participants (M age = 28.6 yr., SD = 9.1) were recruited at the 2013 Standard Chartered Hong Kong Marathon. The findings indicated that a model in which perceived event prestige partially mediated the relationship between sport involvement and intent to return to the event was most representative of the data. While individuals with higher sport involvement were more likely to indicate an interest in continued participation, this relationship was strongest among those who perceived the event to be particularly prestigious. Thus, those who market mass participation sporting events should use strategies designed to emphasize the prestigious stature of the event and should employ measures to increase sport involvement among participants.

  8. The very early events following photoexcitation of carotenoids.

    Science.gov (United States)

    Hashimoto, Hideki; Yanagi, Kazuhiro; Yoshizawa, Masayuki; Polli, Dario; Cerullo, Giulio; Lanzani, Guglielmo; De Silvestri, Sandro; Gardiner, Alastair T; Cogdell, Richard J

    2004-10-01

    The recent availability of laser pulses with 10-20 fs duration, tunable throughout the visible and near infrared wavelengths, has facilitated the investigation, with unprecedented temporal resolution, into the very early events of energy relaxation in carotenoids [Science 298 (2002) 2395; Synth. Metals 139 (2003) 893]. This has enabled us to clearly demonstrate the existence of an additional intermediate state, Sx, lying between the S2 (1(1)Bu+) and S1 (2(1)Ag-) states. In addition, by applying time-resolved stimulated Raman spectroscopy with femtosecond time resolution, it has also been shown that vibrational relaxation in electronic excited states plays an important role in these interconversions. In this mini-review, we describe briefly the current understanding of Sx and the other intermediate excited states that can be formed by relaxation from S2, mainly focusing attention on the above two topics. Emphasis is also placed on some of the major remaining unsolved issues in carotenoid photochemistry.

  9. Critical early events in hematopoietic cell seeding and engraftment.

    Directory of Open Access Journals (Sweden)

    Jerry Stein

    2005-12-01

    Full Text Available Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic cells with the bone marrow stroma evolves as the most important early event. Adhesion to the marrow, rather than the vascular endothelium, determines the efficiency of both homing and seeding, and is absolutely essential to maintain cell viability in the marrow. Seeding and engraftment may be improved either by bypassing homing or by localized transplant of a large number of cells in a relatively small marrow space. There is functional redundancy in the molecular pathways that mediate the cell-stroma interaction, such that blockage of a single pathway has only minor effect on homing and seeding. We hypothesize that successfully seeding-engrafting cells undergo extensive phenotypic changes as a consequence of interaction with the stroma, without engaging in rapid proliferation. Surprisingly, Fas-ligand appears to promote hematopoietic cell engraftment by immunomodulatory and trophic effects.

  10. Critical early events in hematopoietic cell seeding and engraftment.

    Science.gov (United States)

    Stein, Jerry; Yaniv, Isaac; Askenasy, Nadir

    2005-01-01

    Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic cells with the bone marrow stroma evolves as the most important early event. Adhesion to the marrow, rather than the vascular endothelium, determines the efficiency of both homing and seeding, and is absolutely essential to maintain cell viability in the marrow. Seeding and engraftment may be improved either by bypassing homing or by localized transplant of a large number of cells in a relatively small marrow space. There is functional redundancy in the molecular pathways that mediate the cell-stroma interaction, such that blockage of a single pathway has only minor effect on homing and seeding. We hypothesize that successfully seeding-engrafting cells undergo extensive phenotypic changes as a consequence of interaction with the stroma, without engaging in rapid proliferation. Surprisingly, Fas-ligand appears to promote hematopoietic cell engraftment by immunomodulatory and trophic effects.

  11. Specific posttranslational modification regulates early events in mammary carcinoma formation.

    Science.gov (United States)

    Guo, Hua-Bei; Johnson, Heather; Randolph, Matthew; Nagy, Tamas; Blalock, Ryan; Pierce, Michael

    2010-12-07

    The expression of an enzyme, GnT-V, that catalyzes a specific posttranslational modification of a family of glycoproteins, namely a branched N-glycan, is transcriptionally up-regulated during breast carcinoma oncogenesis. To determine the molecular basis of how early events in breast carcinoma formation are regulated by GnT-V, we studied both the early stages of mammary tumor formation by using 3D cell culture and a her-2 transgenic mouse mammary tumor model. Overexpression of GnT-V in MCF-10A mammary epithelial cells in 3D culture disrupted acinar morphogenesis with impaired hollow lumen formation, an early characteristic of mammary neoplastic transformation. The disrupted acinar morphogenesis of mammary tumor cells in 3D culture caused by her-2 expression was reversed in tumors that lacked GnT-V expression. Moreover, her-2-induced mammary tumor onset was significantly delayed in the GnT-V null tumors, evidence that the lack of the posttranslational modification catalyzed by GnT-V attenuated tumor formation. Inhibited activation of both PKB and ERK signaling pathways was observed in GnT-V null tumor cells. The proportion of tumor-initiating cells (TICs) in the mammary tumors from GnT-V null mice was significantly reduced compared with controls, and GnT-V null TICs displayed a reduced ability to form secondary tumors in NOD/SCID mice. These results demonstrate that GnT-V expression and its branched glycan products effectively modulate her-2-mediated signaling pathways that, in turn, regulate the relative proportion of tumor initiating cells and the latency of her-2-driven tumor onset.

  12. Serious adverse events in a hospital using early warning score - what went wrong?

    DEFF Research Database (Denmark)

    Petersen, John Asger; Mackel, Rebecca; Antonsen, Kristian

    2014-01-01

    AIM: To evaluate the performance of a new early warning score (EWS) system by reviewing all serious adverse events in our hospital over a 6-month time period. METHOD: All incidents of unexpected death (UD), cardiac arrest (CA) and unanticipated intensive care unit admission(UICU) of adult patients...... of EWS were recorded in 87, 94 and 75% of UICU, CA and UD. Patients were monitored according to the escalation protocol in 13, 31 and 13% of UICU, CA and UD. Nurses escalated care and contacted physicians in 64% and 60% of events of UICU and the corresponding proportions for CO were 58% and 55%. On call...... physicians provided adequate care in 49% of cases of UICU and 29% of cases of the CO. Senior staff was involved according to protocol in 53% and 36% of cases of UICU and CO, respectively. CONCLUSION: Poor compliance with the escalation protocol was commonly found when serious adverse events occurred...

  13. Carbonate platform evidence of ocean acidification at the onset of the early Toarcian oceanic anoxic event

    Science.gov (United States)

    Trecalli, Alberto; Spangenberg, Jorge; Adatte, Thierry; Föllmi, Karl B.; Parente, Mariano

    2012-12-01

    The early Toarcian oceanic anoxic event (Early Jurassic;˜183 Myr ago) is associated with one of the largest negative carbon isotope excursion (CIE) in the whole Phanerozoic (3-7‰). Estimates of the magnitude and rate of CO2 injection in the ocean-atmosphere system are compatible with a scenario of ocean acidification. Many carbonate platforms drowned in the Pliensbachian, well before the early Toarcian event. In this paper we test the hypothesis of surface water ocean acidification by presenting data from a resilient carbonate platform: the Apennine Carbonate Platform of southern Italy. The studied sections document a dramatic shift of the carbonate factory from massive biocalcification to chemical precipitation. Lithiotis bivalves and calcareous algae (Palaeodasycladus mediterraneus), which were the most prolific carbonate producers of Pliensbachian carbonate platforms, disappear during the first phase of the early Toarcian CIE, before the most depleted values are reached. We discuss the local versus supraregional significance of this shift and propose a scenario involving abrupt decline of carbonate saturation, forced by CO2 release at the beginning of the early Toarcian CIE, followed by a calcification overshoot, driven by the recovery of ocean alkalinity. Attribution of the demise of carbonate platform hypercalcifiers to ocean acidification is supported by palaeophysiology and reinforced by experimental data on the detrimental effects of ocean acidification on recent shellfishes and calcareous algae.

  14. Comparison of Auditory Event-Related Potential P300 in Sighted and Early Blind Individuals

    Directory of Open Access Journals (Sweden)

    Fatemeh Heidari

    2010-06-01

    Full Text Available Background and Aim: Following an early visual deprivation, the neural network involved in processing auditory spatial information undergoes a profound reorganization. In order to investigate this process, event-related potentials provide accurate information about time course neural activation as well as perception and cognitive processes. In this study, the latency and amplitude of auditory P300 were compared in sighted and early blind individuals in age range of 18-25 years old.Methods: In this cross-sectional study, auditory P300 potential was measured in conventional oddball paradigm by using two tone burst stimuli (1000 and 2000 Hz on 40 sighted subjects and 19 early blind subjects with mean age 20.94 years old.Results: The mean latency of P300 in early blind subjects was significantly smaller than sighted subjects (p=0.00.( There was no significant difference in amplitude between two groups (p>0.05.Conclusion: Reduced latency of P300 in early blind subjects in comparison to sighted subjects probably indicates the rate of automatic processing and information categorization is faster in early blind subjects because of sensory compensation. It seems that neural plasticity increases the rate of auditory processing and attention in early blind subjects.

  15. Does Sport Event Involvement Influence Brand Recognition of Official Sponsors and Ambush Marketers?

    Directory of Open Access Journals (Sweden)

    Piątkowska Monika

    2016-12-01

    Full Text Available The main aim of the study is to verify how event involvement in the UEFA Euro 2012 influenced the recognition of both sponsors’ and ambushers’ brands. Computer-Assisted Personal Interviews were conducted on a representative sample of the Polish society (N = 1,000. On the basis of five groups of consumers regarding involvement in the event, authors examined brand recognition, using Top of Mind Awareness (TOMA tests of official sponsors and ambushers.

  16. Early Warning and Early Action during the 2015-16 El Nino Event

    Science.gov (United States)

    Robertson, A. W.; Goddard, L. M.

    2016-12-01

    Strong El Niño events have a marked impact on regional climate worldwide through their influence on large-scale atmospheric circulation. As a result, seasonal climate forecasts show greater skill during El Niño events, which provide communities, governments and humanitarian agencies greater ability to plan and prepare. The scientific community has advanced considerably in the quality and content of information provided about El Niño and its impacts. As a result, society has become better aware of and engaged with this information. This talk will present some details on how we navigate the fine line between expectations and probabilistic forecasts, and how this information was used during the 2015-16 El Niño event. Examples are drawn from the health sector and food security community. Specific attention will be given to the importance of problem-focus and data availability in the appropriate tailoring of climate information for Early Warning/Early Action.

  17. Dissemination of a highly virulent pathogen: tracking the early events that define infection.

    Directory of Open Access Journals (Sweden)

    Rodrigo J Gonzalez

    2015-01-01

    Full Text Available The series of events that occurs immediately after pathogen entrance into the body is largely speculative. Key aspects of these events are pathogen dissemination and pathogen interactions with the immune response as the invader moves into deeper tissues. We sought to define major events that occur early during infection of a highly virulent pathogen. To this end, we tracked early dissemination of Yersinia pestis, a highly pathogenic bacterium that causes bubonic plague in mammals. Specifically, we addressed two fundamental questions: (1 do the bacteria encounter barriers in disseminating to draining lymph nodes (LN, and (2 what mechanism does this nonmotile bacterium use to reach the LN compartment, as the prevailing model predicts trafficking in association with host cells. Infection was followed through microscopy imaging in addition to assessing bacterial population dynamics during dissemination from the skin. We found and characterized an unexpected bottleneck that severely restricts bacterial dissemination to LNs. The bacteria that do not pass through this bottleneck are confined to the skin, where large numbers of neutrophils arrive and efficiently control bacterial proliferation. Notably, bottleneck formation is route dependent, as it is abrogated after subcutaneous inoculation. Using a combination of approaches, including microscopy imaging, we tested the prevailing model of bacterial dissemination from the skin into LNs and found no evidence of involvement of migrating phagocytes in dissemination. Thus, early stages of infection are defined by a bottleneck that restricts bacterial dissemination and by neutrophil-dependent control of bacterial proliferation in the skin. Furthermore, and as opposed to current models, our data indicate an intracellular stage is not required by Y. pestis to disseminate from the skin to draining LNs. Because our findings address events that occur during early encounters of pathogen with the immune response

  18. NIPPLE AREOLA COMPLEX INVOLVEMENT IN EARLY AND LATE CARCINOMA BREAST

    Directory of Open Access Journals (Sweden)

    Firoz

    2015-08-01

    Full Text Available BACKGROUND : The last several decades h ave witnessed significant advances in the surgical management of carcinoma breast. Many have embraced breast conservation as the procedure of choice in carefully selected patients. It provides excellent cosmetic results side by side being oncologically saf e. Recent evidences have shown that involvement of nipple areola complex in breast cancer have been over estimated in the past based on older concept of occult tumor in the region of nipple and areola. Preservation of nipple and areola improves the quality of life and reduces the feeling of mutilation and thus is a logical step in conservative management of breast carcinoma. AIMS: (a To investigate the actual involvement of nipple areola complex clinically and histopathologically. (b To determine the asso ciated risk factors like site, size, distance, grading and lymph node status. MATERIALS AND METHOD S: This was a prospective study over a period of 2008 - 2011 carried out at Department of General Surgery of a tertiary care centre. Total number of patients i ncluded in the study was 54. All patients included in the study had undergone mastectomy for carcinoma of breast (excluding those patients who had clinical involvement of nipple areola complex. RESULTS: Among the patients of the study group majority of br east cancer occurred in age group 41 - 60 years (42.6% while incidence of nipple areola involvement was highest in age group 20 - 40 years. Majority of the patients detected with breast cancer were in stage II (44.4% while incidence of nipple areola involvem ent was highest in stage IV in our study. Mean largest dimension of the tumor was between 2 - 5cms while nipple areola involvement was found to be highest when the tumor is >5cms in largest dimension. Among the cases mean nipple tumor margin distance was bet ween 0 - 4cms while nipple areola involvement was found to be highest when the nipple tumor margin distance was < 2cms. CONCLUSION: It can

  19. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas; Forestier, Erik; Frandsen, Thomas L; Harila-Saari, Arja; Heyman, Mats; Jonsson, Olafur G; Lähteenmäki, Päivi M; Lausen, Birgitte; Vaitkevičienė, Goda; Asberg, Ann; Schmiegelow, Kjeld

    2014-08-01

    Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744 patients on Nordic-Baltic trials. CNS status was classified as CNS1 (no CSF blasts), CNS2 ( 0.15). The 12-year event-free survival for patients with leukemic mass on neuroimaging did not differ from patients with negative or no scan (0.50 vs. 0.60; P = 0.7) or between patients with symptoms or signs suggestive of CNS leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia. © 2014 Wiley Periodicals, Inc.

  20. Heterologous microarray experiments allow the identification of the early events associated with potato tuber cold sweetening

    Directory of Open Access Journals (Sweden)

    Vitulli Federico

    2008-04-01

    Full Text Available Abstract Background Since its discovery more than 100 years ago, potato (Solanum tuberosum tuber cold-induced sweetening (CIS has been extensively investigated. Several carbohydrate-associated genes would seem to be involved in the process. However, many uncertainties still exist, as the relative contribution of each gene to the process is often unclear, possibly as the consequence of the heterogeneity of experimental systems. Some enzymes associated with CIS, such as β-amylases and invertases, have still to be identified at a sequence level. In addition, little is known about the early events that trigger CIS and on the involvement/association with CIS of genes different from carbohydrate-associated genes. Many of these uncertainties could be resolved by profiling experiments, but no GeneChip is available for the potato, and the production of the potato cDNA spotted array (TIGR has recently been discontinued. In order to obtain an overall picture of early transcriptional events associated with CIS, we investigated whether the commercially-available tomato Affymetrix GeneChip could be used to identify which potato cold-responsive gene family members should be further studied in detail by Real-Time (RT-PCR (qPCR. Results A tomato-potato Global Match File was generated for the interpretation of various aspects of the heterologous dataset, including the retrieval of best matching potato counterparts and annotation, and the establishment of a core set of highly homologous genes. Several cold-responsive genes were identified, and their expression pattern was studied in detail by qPCR over 26 days. We detected biphasic behaviour of mRNA accumulation for carbohydrate-associated genes and our combined GeneChip-qPCR data identified, at a sequence level, enzymatic activities such as β-amylases and invertases previously reported as being involved in CIS. The GeneChip data also unveiled important processes accompanying CIS, such as the induction of redox

  1. Issues in Informal Education: Event-Based Science Communication Involving Planetaria and the Internet

    Science.gov (United States)

    Adams, M.; Gallagher, D. L.; Whitt, A.; Six, N. Frank (Technical Monitor)

    2002-01-01

    For the past four years the Science Directorate at Marshall Space Flight Center has carried out a diverse program of science communication through the web resources on the Internet. The program includes extended stories about NAS.4 science, a curriculum resource for teachers tied to national education standards, on-line activities for students, and webcasts of real-time events. Events have involved meteor showers, solar eclipses, natural very low frequency radio emissions, and amateur balloon flights. In some cases broadcasts accommodate active feedback and questions from Internet participants. We give here, examples of events, problems, and lessons learned from these activities.

  2. EARLY READING ASSESSMENT INSTRUMENTS: ABILITIES AND PROCESSES INVOLVED

    Directory of Open Access Journals (Sweden)

    Ana Cláudia de Souza

    2017-04-01

    Full Text Available This study investigates the following early reading assessment instruments: “Bateria de Recepção e Produção da Linguagem Verbal” (SCLIAR-CABRAL, 2003a and “Teste de Competência de Leitura de Palavras e Pseudopalavras” (SEABRA; CAPOVILLA, 2010. The main research goal is to analyze in each one of these reading assessment instruments some of the multiple cognitive processes and basic low-level abilities involved in reading. In this sense, decoding, word recognition, lexical access, syntactic and textual processing, and comprehension are the cognitive processes taken into account. With regard to the basic reading abilities, accuracy and fluency (rhythm, prosody and speed are considered. The results indicate that each one of the analyzed reading assessment instruments assesses different aspects of the reading processes and abilities, mainly through off-line measures. ScliarCabral’s assessment battery allows the researcher or the teacher to evaluate the following processes: perception of the grapheme opposition in minimal pairs of words and in sentences, difficulties in sentence processing, skills in decoding the graphemic-phonemic relationship, and textual comprehension. In its turn, the reading assessment instrument proposed by Seabra e Capovilla allows one to evaluate student’s reading development level, by classifying the kind of processing as logographic, alphabetic or orthographic.

  3. Early and extensive spinal white matter involvement in neuromyelitis optica.

    Science.gov (United States)

    Hayashida, Shotaro; Masaki, Katsuhisa; Yonekawa, Tomomi; Suzuki, Satoshi O; Hiwatashi, Akio; Matsushita, Takuya; Watanabe, Mitsuru; Yamasaki, Ryo; Suenaga, Toshihiko; Iwaki, Toru; Murai, Hiroyuki; Kira, Jun-Ichi

    2017-05-01

    endfoot protein loss may emerge. Spinal white matter involvement may also appear in early NMO, similar to cerebral white matter lesions. © 2016 International Society of Neuropathology.

  4. Notch pathway regulates female germ cell meiosis progression and early oogenesis events in fetal mouse.

    Science.gov (United States)

    Feng, Yan-Min; Liang, Gui-Jin; Pan, Bo; Qin, Xun-Si; Zhang, Xi-Feng; Chen, Chun-Lei; Li, Lan; Cheng, Shun-Feng; De Felici, Massimo; Shen, Wei

    2014-01-01

    A critical process of early oogenesis is the entry of mitotic oogonia into meiosis, a cell cycle switch regulated by a complex gene regulatory network. Although Notch pathway is involved in numerous important aspects of oogenesis in invertebrate species, whether it plays roles in early oogenesis events in mammals is unknown. Therefore, the rationale of the present study was to investigate the roles of Notch signaling in crucial processes of early oogenesis, such as meiosis entry and early oocyte growth. Notch receptors and ligands were localized in mouse embryonic female gonads and 2 Notch inhibitors, namely DAPT and L-685,458, were used to attenuate its signaling in an in vitro culture system of ovarian tissues from 12.5 days post coitum (dpc) fetus. The results demonstrated that the expression of Stra8, a master gene for germ cell meiosis, and its stimulation by retinoic acid (RA) were reduced after suppression of Notch signaling, and the other meiotic genes, Dazl, Dmc1, and Rec8, were abolished or markedly decreased. Furthermore, RNAi of Notch1 also markedly inhibited the expression of Stra8 and SCP3 in cultured female germ cells. The increased methylation status of CpG islands within the Stra8 promoter of the oocytes was observed in the presence of DAPT, indicating that Notch signaling is probably necessary for maintaining the epigenetic state of this gene in a way suitable for RA stimulation. Furthermore, in the presence of Notch inhibitors, progression of oocytes through meiosis I was markedly delayed. At later culture periods, the rate of oocyte growth was decreased, which impaired subsequent primordial follicle assembly in cultured ovarian tissues. Taken together, these results suggested new roles of the Notch signaling pathway in female germ cell meiosis progression and early oogenesis events in mammals.

  5. An EAS event observed in the early stage of development

    Energy Technology Data Exchange (ETDEWEB)

    Barroso, S.L.C. [Centro Brasileiro de Pesquisas Fisicas, 22290-180 Rio de Janeiro, RJ (Brazil); Beggio, P.C. [Laboratorio de Ciencias Matematicas, UENF, Campos de Goytacazes, RJ (Brazil); Carvalho, A.O. de; Chinellato, J.A.; Mariano, A.; Oliveira, R. de; Shibuya, E.H. [Instituto de Fisica ' Gleb Wataghin' /UNICAMP, 13083-970 Campinas, SP (Brazil)

    2008-01-15

    Since 1969 the experiments of Brazil-Japan Collaboration showed the occurrence of a series of events, showing a region with a high concentration of electromagnetic particles, surrounded by isolated and/or groups of showers. These events were named 'halo events' or 'super-families'. Currently, we have more than a dozen of such events. The first of them, due to its aspect, was named 'Andromeda'. We present here the main characteristics of a similar halo event, named C21S087I075. It has a halo region with many high energy showers in its border. Other small energy showers spread over the central and surrounding blocks (S088, S100, S101, I074). These isolated showers, classified as of hadronic or electromagnetic origin, present a fractional energy distribution compatible with that of a Centauro candidate event (C16S087I037), reported at this symposium [S.L.C. Barroso, P.C. Beggio, J.A. Chinellato, A.O. Carvalho, A. Mariano, R. Oliveira, E.H. Shibuya, in this issue of XIV ISVHECRI]. Moreover, the lateral distribution in the halo region is similar to that observed in other 3 halo events.

  6. Early adverse events, HPA activity and rostral anterior cingulate volume in MDD.

    Directory of Open Access Journals (Sweden)

    Michael T Treadway

    Full Text Available BACKGROUND: Prior studies have independently reported associations between major depressive disorder (MDD, elevated cortisol concentrations, early adverse events and region-specific decreases in grey matter volume, but the relationships among these variables are unclear. In the present study, we sought to evaluate the relationships between grey matter volume, early adverse events and cortisol levels in MDD. METHODS/RESULTS: Grey matter volume was compared between 19 controls and 19 individuals with MDD using voxel-based morphometry. A history of early adverse events was assessed using the Childhood Trauma Questionnaire. Subjects also provided salivary cortisol samples. Depressed patients showed decreased grey matter volume in the rostral ACC as compared to controls. Rostral ACC volume was inversely correlated with both cortisol and early adverse events. CONCLUSIONS: These findings suggest a key relationship between ACC morphology, a history of early adverse events and circulating cortisol in the pathophysiology of MDD.

  7. Impaired Early Attentional Processes in Parkinson's Disease: A High-Resolution Event-Related Potentials Study.

    Directory of Open Access Journals (Sweden)

    Perrine Bocquillon

    Full Text Available The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. A previous study using the P3 component of the event-related potentials suggested that a reduced ability to resist interference could be responsible for attention disorders at early stages of Parkinson's disease (PD, with a possible role of the dorsolateral prefrontal cortex (DLPFC.Our objective was to better determine the origin of this impairment, by studying an earlier ERP component, the N2, and its subcomponents, as they reflect early inhibition processes and as they are known to have sources in the anterior cingulate cortex (ACC, which is involved together with the DLPFC in inhibition processes. Fifteen early-stage PD patients and 15 healthy controls (HCs performed a three-stimulus visual oddball paradigm, consisting in detecting target inputs amongst standard stimuli, while resisting interference from distracter ones. A 128-channel electroencephalogram was recorded during this task and the generators of the N2 subcomponents were identified using standardized weighted low-resolution electromagnetic tomography (swLORETA.PD patients displayed fewer N2 generators than HCs in both the DLPFC and the ACC, for all types of stimuli. In contrast to controls, PD patients did not show any differences between their generators for different N2 subcomponents.Our data suggest that impaired inhibition in PD results from dysfunction of the DLPFC and the ACC during the early stages of attentional processes.

  8. Life Event Stress and Binge Eating Among Adolescents: The Roles of Early Maladaptive Schemas and Impulsivity.

    Science.gov (United States)

    Zhu, Hong; Luo, Xingwei; Cai, Taisheng; He, Jinbo; Lu, Yao; Wu, Siyao

    2016-10-01

    This study examined the relationships between life event stress, early maladaptive schemas, impulsivity and binge eating among adolescents and investigated the effects of early maladaptive schemas and impulsivity on the relationship between life event stress and binge eating. Specifically, we examined a moderated mediation model in which early maladaptive schemas mediated this relationship and impulsivity moderated the mediation effect. Life event stress, early maladaptive schemas, impulsivity and binge eating were investigated in a sample of 2172 seventh-, eighth- and tenth-grade middle and high school students (mean age = 14.55 years, standard deviation = 1.29). The results indicated that adolescents with greater life event stress, more early maladaptive schemas and higher levels of impulsivity displayed more severe binge eating. In addition, early maladaptive schemas mediated the relationship between life event stress and binge eating, while impulsivity moderated this relationship. Furthermore, impulsivity also moderated the mediation effect of early maladaptive schemas; as impulsivity levels increased, the strength of the association between life event stress and early maladaptive schemas increased. This study illustrates the importance of understanding individual differences and their effects on the relationship between life event stress and binge eating. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meeren, A.; Tourdes, F.; Gremy, O.; Grillon, G.; Abram, M.C.; Poncy, J.L.; Griffiths, N. [CEA, DSV, DRR, SRCA, Centre DAM Ile de France, F-91297 Bruyeres Le Chatel, Arpajon (France)

    2008-07-01

    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO{sub 2} or different isotopic compositions (70% or 97% {sup 239}Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO{sub 2}-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% {sup 239}Pu than for 70% {sup 239}Pu. (authors)

  10. Pupil cycle time and early autonomic involvement in ocular leprosy.

    OpenAIRE

    Karaçorlu, M A; Sürel, Z; Cakiner, T; Hanyaloğlu, E; Saylan, T; MAT, C.

    1991-01-01

    Ocular complications of leprosy patients often develop insidiously and with few if any symptoms. This study involves measurement of the pupil cycle time (PCT) to evaluate the autonomic nerve system of the iris to determine the presence of subclinical intraocular involvement. The study included 19 lepromatous (LL), 19 borderline lepromatous (BL), and five borderline tuberculoid (BT) leprosy patients and involved 25 healthy volunteers, 10 patients with pulmonary tuberculosis and eight with Duhr...

  11. Catching jetted tidal disruption events early in millimetre

    CERN Document Server

    Yuan, Qiang; Lei, Wei-Hua; Gao, He; Zhang, Bing

    2016-01-01

    Relativistic jets can form from at least some tidal disruption events (TDEs) of (sub-)stellar objects around supermassive black holes. We detect the millimeter (MM) emission of IGR J12580+0134 --- the nearest TDE known in the galaxy NGC 4845 at the distance of only 17 Mpc, based on Planck all-sky survey data. The data show significant flux jumps after the event, followed by substantial declines, in all six high frequency Planck bands from 100 GHz to 857 GHz. We further show that the evolution of the MM flux densities are well consistent with our model prediction from an off-axis jet, as was initially suggested from radio and X-ray observations. This detection represents the second TDE with MM detections; the other is Sw J1644+57, an on-axis jetted TDE at redshift of 0.35. Using the on- and off-axis jet models developed for these two TDEs as templates, we estimate the detection potential of similar events with the Large Millimeter Telescope (LMT) and the Atacama Large Millimeter/submillimeter Array (ALMA). Ass...

  12. Analyzing Parental Involvement Dimensions in Early Childhood Education

    Science.gov (United States)

    Kurtulmus, Zeynep

    2016-01-01

    The importance of parental involvement in children's academic and social development has been widely accepted. For children's later school success, the first years are crucial. Majority of the research focuses on enhancing and supporting parental involvement in educational settings. The purpose of this study was to analyze dimensions of parental…

  13. Inhibiting Self-Pollen: Self-Incompatibility in Papaver Involves Integration of Several Signaling Events

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Cellular responses rely on signal perception and integration. A nice example of this is self incompatibility (SI), which is an important mechanism to prevent inbreeding. It prevents self-fertilization by using a highly discriminatory cellular recognition and rejection mechanism. Most S1 systems are genetically specified by the S-locus, which has a pollen and a pistil S-component. A receptor-ligand interaction is used by Papaver rhoeas to control SI. S proteins encoded by the pistil part of the S-locus interact with incompatible pollen to achieve rapid inhibition of tip growth. The incompatible SI interaction triggers a Ca2+ -dependent signaling cascade. A number of SI-specific events are triggered in incompatible pollen, including rapid depolymerization of the actin cytoskeleton; phosphorylation of soluble inorganic pyrophosphatases (SPPases), Prp26.1; activation of a mitogen activated protein kinase, p56; programmed cell death (PCD) involving a caspase-3-like activlty. These events contribute to prevent self-fertilization. We are attempting to establish the functional signiflcance of these events, and their possible involvement in integrating a coordinated signaling response. Here we describe the identification of these components shown to be involved in SI, together with recent progress in identifying links between some of them. These data constitute the first steps in elucidating how SI signaling is integrated.

  14. Critical early events in hematopoietic cell seeding and engraftment.

    OpenAIRE

    Jerry Stein; Isaac Yaniv; Nadir Askenasy

    2005-01-01

    Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic ce...

  15. Early involvement of dorsal and ventral pathways in visual word recognition: an ERP study.

    Science.gov (United States)

    Rosazza, Cristina; Cai, Qing; Minati, Ludovico; Paulignan, Yves; Nazir, Tatjana A

    2009-05-26

    Visual expertise underlying reading is attributed to processes involving the left ventral visual pathway. However, converging evidence suggests that the dorsal visual pathway is also involved in early levels of visual word processing, especially when words are presented in unfamiliar visual formats. In the present study, event-related potentials (ERPs) were used to investigate the time course of the early engagement of the ventral and dorsal pathways during processing of orthographic stimuli (high and low frequency words, pseudowords and consonant strings) by manipulating visual format (familiar horizontal vs. unfamiliar vertical format). While early ERP components (P1 and N1) already distinguished between formats, the effect of stimulus type emerged at the latency of the N2 component (225-275 ms). The N2 scalp topography and sLORETA source localisation for this differentiation showed an occipito-temporal negativity for the horizontal format and a negativity that extended towards the dorsal regions for the vertical format. In a later time window (350-425 ms) ERPs elicited by vertically displayed stimuli distinguished words from pseudowords in the ventral area, as confirmed by source localisation. The sustained contribution of occipito-temporal processes for vertical stimuli suggests that the ventral pathway is essential for lexical access. Parietal regions appear to be involved when a serial mechanism of visual attention is required to shift attention from one letter to another. The two pathways cooperate during visual word recognition and processing in these pathways should not be considered as alternative but as complementary elements of reading.

  16. Recognition events in AM symbiosis: analysis of fungal gene expression at the early appressorium stage.

    Science.gov (United States)

    Breuninger, Magadalene; Requena, Natalia

    2004-08-01

    Arbuscular mycorrhizal symbiosis is induced upon a series of recognition events involving the reorganization of both plant and fungal cellular programs culminating in the formation of appressoria on the epidermal root cells. In this work we monitored for the first time the genetic changes occurring in the fungal partner during early appressorium development. We established an in vitro system of Glomus mosseae and Petroselinum crispum for studying appressorium formation and found that after 120 h first appressoria developed in the root epidermis. We have constructed a fungal subtractive suppressive library enriched in genes up-regulated at this stage. Our aim was to identify early signaling events during plant recognition leading to appressoria formation. The library contains 375 clones with an average size of 500 bp. From these, 200 clones were sequenced and most of them represent gene fragments with no known homologues (63%) and therefore putative new genes specific to the mycorrhiza symbiosis. Reverse-Northern blot and RT-PCR analyses confirmed that ca. 30% of the genes present in the library were up-regulated upon plant induction after 120 h. Among the genes with homologues in other organisms we found several genes common to other plant-microbe interactions including some genes related to Ca2+-dependent signaling. The up-regulation of these genes opens the possibility that Ca2+ plays a role in the early stages of mycorrhiza formation as it has been found in other plant-microbe interactions such as the Rhizobium symbiosis or the Magnaporthe grisea/rice pathogenic interaction.

  17. Financial Strain, Major Family Life Events, and Parental Academic Involvement During Adolescence.

    Science.gov (United States)

    Camacho-Thompson, Daisy E; Gillen-O'Neel, Cari; Gonzales, Nancy A; Fuligni, Andrew J

    2016-06-01

    Parental academic involvement-whether through school participation and communication, or supervision and assistance at home-often has been cited as a way to enhance academic achievement. Yet, little is known about how the financial and life pressures faced by families can compromise parents' ability to become involved in their adolescents' education. In the current study, these dynamics were examined among Mexican-origin families, who often may face challenging financial and familial circumstances, and whose students may have more difficulty in secondary school. Parents of Mexican-origin ninth and tenth grade students from two high schools in Los Angeles (N = 428; 50 % female) completed quantitative interviews. The results revealed that financial strain predicted less involvement at school, and major family life events predicted less involvement at home, even after controlling for potentially confounding factors. Moreover, both of the associations between parental stress and parental academic involvement were mediated by lower levels of relationship quality between parents and adolescents, but not by conflict within the parent-adolescent dyad or parental depressive and somatic symptoms. The findings suggest that stress may limit parents' ability to become involved their adolescents' education, and highlight the importance of understanding family dynamics when examining parental academic involvement among Mexican-origin families.

  18. Pupil cycle time and early autonomic involvement in ocular leprosy.

    Science.gov (United States)

    Karaçorlu, M A; Sürel, Z; Cakiner, T; Hanyaloğlu, E; Saylan, T; Mat, C

    1991-01-01

    Ocular complications of leprosy patients often develop insidiously and with few if any symptoms. This study involves measurement of the pupil cycle time (PCT) to evaluate the autonomic nerve system of the iris to determine the presence of subclinical intraocular involvement. The study included 19 lepromatous (LL), 19 borderline lepromatous (BL), and five borderline tuberculoid (BT) leprosy patients and involved 25 healthy volunteers, 10 patients with pulmonary tuberculosis and eight with Duhring disease. The PCT was measured in these groups. In all leprosy groups included in the study the PCT was higher than in the control groups. Moreover, the PCT of the leprosy patients without any intraocular involvement was higher than in the controls. These results show that in the ophthalmic examination of leprosy patients without any symptoms the fact that autonomic nerve system of the eye is affected by the leprosy can often be determined by measuring the PCT.

  19. Early psychosocial interventions after disasters, terrorism, and other shocking events: Guideline development.

    NARCIS (Netherlands)

    Brake, H. te; Dückers, M.; Vries, M. de; Duin, D. van; Rooze, M.; Spreeuwenberg, C.

    2009-01-01

    Background: Internationally, several initiatives exist to describe standards for post-disaster psychosocial care. Objective: This study explored the level of consensus of experts within Europe on a set of recommendations on early psychosocial intervention after shocking events (Dutch guidelines),

  20. Iron Oxide Magnetic Nanoparticles Highlight Early Involvement of the Choroid Plexus in Central Nervous System Inflammation

    Directory of Open Access Journals (Sweden)

    Jason M. Millward

    2013-03-01

    Full Text Available Neuroinflammation during multiple sclerosis involves immune cell infiltration and disruption of the BBB (blood–brain barrier. Both processes can be visualized by MRI (magnetic resonance imaging, in multiple sclerosis patients and in the animal model EAE (experimental autoimmune encephalomyelitis. We previously showed that VSOPs (very small superparamagnetic iron oxide particles reveal CNS (central nervous system lesions in EAE which are not detectable by conventional contrast agents in MRI. We hypothesized that VSOP may help detect early, subtle inflammatory events that would otherwise remain imperceptible. To investigate the capacity of VSOP to reveal early events in CNS inflammation, we induced EAE in SJL mice using encephalitogenic T-cells, and administered VSOP prior to onset of clinical symptoms. In parallel, we administered VSOP to mice at peak disease, and to unmanipulated controls. We examined the distribution of VSOP in the CNS by MRI and histology. Prior to disease onset, in asymptomatic mice, VSOP accumulated in the choroid plexus and in spinal cord meninges in the absence of overt inflammation. However, VSOP was undetectable in the CNS of non-immunized control mice. At peak disease, VSOP was broadly distributed; we observed particles in perivascular inflammatory lesions with apparently preserved glia limitans. Moreover, at peak disease, VSOP was prominent in the choroid plexus and was seen in elongated endothelial structures, co-localized with phagocytes, and diffusely disseminated in the parenchyma, suggesting multiple entry mechanisms of VSOP into the CNS. Thus, using VSOP we were able to discriminate between inflammatory events occurring in established EAE and, importantly, we identified CNS alterations that appear to precede immune cell infiltration and clinical onset.

  1. Iron oxide magnetic nanoparticles highlight early involvement of the choroid plexus in central nervous system inflammation

    Directory of Open Access Journals (Sweden)

    Carmen Infante‑Duarte

    2013-03-01

    Full Text Available Neuroinflammation during multiple sclerosis involves immune cell infiltration and disruption of the BBB (blood–brain barrier. Both processes can be visualized by MRI (magnetic resonance imaging, in multiple sclerosis patients and in the animal model EAE (experimental autoimmune encephalomyelitis. We previously showed that VSOPs (very small superparamagnetic iron oxide particles reveal CNS (central nervous system lesions in EAE which are not detectable by conventional contrast agents in MRI. We hypothesized that VSOP may help detect early, subtle inflammatory events that would otherwise remain imperceptible. To investigate the capacity of VSOP to reveal early events in CNS inflammation, we induced EAE in SJL mice using encephalitogenic T-cells, and administered VSOP prior to onset of clinical symptoms. In parallel, we administered VSOP to mice at peak disease, and to unmanipulated controls. We examined the distribution of VSOP in the CNS by MRI and histology. Prior to disease onset, in asymptomatic mice, VSOP accumulated in the choroid plexus and in spinal cord meninges in the absence of overt inflammation. However, VSOP was undetectable in the CNS of non-immunized control mice. At peak disease, VSOP was broadly distributed; we observed particles in perivascular inflammatory lesions with apparently preserved glia limitans. Moreover, at peak disease, VSOP was prominent in the choroid plexus and was seen in elongated endothelial structures, co-localized with phagocytes, and diffusely disseminated in the parenchyma, suggesting multiple entry mechanisms of VSOP into the CNS. Thus, using VSOP we were able to discriminate between inflammatory events occurring in established EAE and, importantly, we identified CNS alterations that appear to precede immune cell infiltration and clinical onset.

  2. Iron oxide magnetic nanoparticles highlight early involvement of the choroid plexus in central nervous system inflammation.

    Science.gov (United States)

    Millward, Jason M; Schnorr, Jörg; Taupitz, Matthias; Wagner, Susanne; Wuerfel, Jens T; Infante-Duarte, Carmen

    2013-01-01

    Neuroinflammation during multiple sclerosis involves immune cell infiltration and disruption of the BBB (blood-brain barrier). Both processes can be visualized by MRI (magnetic resonance imaging), in multiple sclerosis patients and in the animal model EAE (experimental autoimmune encephalomyelitis). We previously showed that VSOPs (very small superparamagnetic iron oxide particles) reveal CNS (central nervous system) lesions in EAE which are not detectable by conventional contrast agents in MRI. We hypothesized that VSOP may help detect early, subtle inflammatory events that would otherwise remain imperceptible. To investigate the capacity of VSOP to reveal early events in CNS inflammation, we induced EAE in SJL mice using encephalitogenic T-cells, and administered VSOP prior to onset of clinical symptoms. In parallel, we administered VSOP to mice at peak disease, and to unmanipulated controls. We examined the distribution of VSOP in the CNS by MRI and histology. Prior to disease onset, in asymptomatic mice, VSOP accumulated in the choroid plexus and in spinal cord meninges in the absence of overt inflammation. However, VSOP was undetectable in the CNS of non-immunized control mice. At peak disease, VSOP was broadly distributed; we observed particles in perivascular inflammatory lesions with apparently preserved glia limitans. Moreover, at peak disease, VSOP was prominent in the choroid plexus and was seen in elongated endothelial structures, co-localized with phagocytes, and diffusely disseminated in the parenchyma, suggesting multiple entry mechanisms of VSOP into the CNS. Thus, using VSOP we were able to discriminate between inflammatory events occurring in established EAE and, importantly, we identified CNS alterations that appear to precede immune cell infiltration and clinical onset.

  3. Early immune events in the induction of allergic contact dermatitis.

    Science.gov (United States)

    Kaplan, Daniel H; Igyártó, Botond Z; Gaspari, Anthony A

    2012-01-13

    The skin is a barrier site that is exposed to a wide variety of potential pathogens. As in other organs, pathogens that invade the skin are recognized by pattern-recognition receptors (PRRs). Recently, it has been recognized that PRRs are also engaged by chemical contact allergens and, in susceptible individuals, this elicits an inappropriate immune response that results in allergic contact dermatitis. In this Review, we focus on how contact allergens promote inflammation by activating the innate immune system. We also examine how innate immune cells in the skin, including mast cells and dendritic cells, cooperate with each other and with T cells and keratinocytes to initiate and drive early responses to contact allergens.

  4. Early user involvement in designing intelligent products and environments

    NARCIS (Netherlands)

    Kuijt-Evers, L.; Steen, M.

    2008-01-01

    A literature review was conducted on user involvement in design. The focus of the review was on how researchers and designers attempt to cooperate with end-users, with the goal of making a better match with end-users’ needs and preferences. The main goal of the research was to get insight in which m

  5. Viral fitness does not correlate with three genotype displacement events involving infectious hematopoietic necrosis virus

    Science.gov (United States)

    Kell, Alison M.; Wargo, Andrew R.; Kurath, Gael

    2014-01-01

    Viral genotype displacement events are characterized by the replacement of a previously dominant virus genotype by a novel genotype of the same virus species in a given geographic region. We examine here the fitness of three pairs of infectious hematopoietic necrosis virus (IHNV) genotypes involved in three major genotype displacement events in Washington state over the last 30 years to determine whether increased virus fitness correlates with displacement. Fitness was assessed using in vivo assays to measure viral replication in single infection, simultaneous co-infection, and sequential superinfection in the natural host, steelhead trout. In addition, virion stability of each genotype was measured in freshwater and seawater environments at various temperatures. By these methods, we found no correlation between increased viral fitness and displacement in the field. These results suggest that other pressures likely exist in the field with important consequences for IHNV evolution.

  6. Relationship between early and late stages of information processing: an event-related potential study

    Directory of Open Access Journals (Sweden)

    Claudio Portella

    2012-11-01

    Full Text Available The brain is capable of elaborating and executing different stages of information processing. However, exactly how these stages are processed in the brain remains largely unknown. This study aimed to analyze the possible correlation between early and late stages of information processing by assessing the latency to, and amplitude of, early and late event-related potential (ERP components, including P200, N200, premotor potential (PMP and P300, in healthy participants in the context of a visual oddball paradigm. We found a moderate positive correlation among the latency of P200 (electrode O2, N200 (electrode O2, PMP (electrode C3, P300 (electrode PZ and the reaction time (RT. In addition, moderate negative correlation between the amplitude of P200 and the latencies of N200 (electrode O2, PMP (electrode C3, P300 (electrode PZ was found. Therefore, we propose that if the secondary processing of visual input (P200 latency occurs faster, the following will also happen sooner: discrimination and classification process of this input (N200 latency, motor response processing (PMP latency, reorganization of attention and working memory update (P300 latency, and RT. N200, PMP, and P300 latencies are also anticipated when higher activation level of occipital areas involved in the secondary processing of visual input rise (P200 amplitude.

  7. Relationship between early and late stages of information processing: an event-related potential study

    Science.gov (United States)

    Portella, Claudio; Machado, Sergio; Arias-Carrión, Oscar; Sack, Alexander T.; Silva, Julio Guilherme; Orsini, Marco; Leite, Marco Antonio Araujo; Silva, Adriana Cardoso; Nardi, Antonio E.; Cagy, Mauricio; Piedade, Roberto; Ribeiro, Pedro

    2012-01-01

    The brain is capable of elaborating and executing different stages of information processing. However, exactly how these stages are processed in the brain remains largely unknown. This study aimed to analyze the possible correlation between early and late stages of information processing by assessing the latency to, and amplitude of, early and late event-related potential (ERP) components, including P200, N200, premotor potential (PMP) and P300, in healthy participants in the context of a visual oddball paradigm. We found a moderate positive correlation among the latency of P200 (electrode O2), N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) and the reaction time (RT). In addition, moderate negative correlation between the amplitude of P200 and the latencies of N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) was found. Therefore, we propose that if the secondary processing of visual input (P200 latency) occurs faster, the following will also happen sooner: discrimination and classification process of this input (N200 latency), motor response processing (PMP latency), reorganization of attention and working memory update (P300 latency), and RT. N200, PMP, and P300 latencies are also anticipated when higher activation level of occipital areas involved in the secondary processing of visual input rise (P200 amplitude). PMID:23355929

  8. Early Events in the Nonadiabatic Relaxation Dynamics of 4-(N,N-Dimethylamino)benzonitrile.

    Science.gov (United States)

    Kochman, Michał A; Tajti, Attila; Morrison, Carole A; Miller, R J Dwayne

    2015-03-10

    4-(N,N-Dimethylamino)benzonitrile (DMABN) is the archetypal system for dual fluorescence. Several past studies, both experimental and theoretical, have examined the mechanism of its relaxation in the gas phase following photoexcitation to the S2 state, without converging to a single description. In this contribution, we report first-principles simulations of the early events involved in this process performed using the nonadiabatic trajectory surface hopping (TSH) approach in combination with the ADC(2) electronic structure method. ADC(2) is verified to reproduce the ground- and excited-state structures of DMABN in reasonably close agreement with previous theoretical benchmarks. The TSH simulations predict that internal conversion from the S2 state to the S1 takes place as early as 8.5 fs, on average, after the initial photoexcitation, and with no significant torsion of the dimethylamino group relative to the aromatic ring. As evidenced by supporting EOM-CCSD calculations, the population transfer from S2 to S1 can be attributed to the skeletal deformation modes of the aromatic ring and the stretching of the ring-dimethylamino nitrogen bond. The non- or slightly twisted locally excited structure is the predominant product of the internal conversion, and the twisted intramolecular charge transfer structure is formed through equilibration with the locally excited structure with no change of adiabatic state. These findings point toward a new interpretation of data from previous time-resolved experiments.

  9. TLEs and early VLF events: Simulating the important impact of transmitter-disturbance-receiver geometry

    Science.gov (United States)

    NaitAmor, S.; Ghalila, H.; Cohen, M. B.

    2017-01-01

    Early very low frequency (VLF) events are perturbations to subionospherically propagating VLF radio transmitters which sometimes occur when lightning activity is near the transmitter-receiver path. They are often correlated to Transient Luminous Events (TLEs). Recent analysis have focused on a new type of early events whose recovery time persists for many minutes, called LOng Recovery Events (LOREs). The underlying cause of these events is still unclear. Curiously, LOREs sometimes appear on only one path, while the same event observed on a different transmitter-receiver path does not indicate a LORE. In this paper we observe and simulate two cases of early signal perturbations: The first is a typical early VLF event, and the second is a LORE. Both were recorded by two AWESOME VLF receivers in North Africa on 12 December 2009, during the EuroSprite campaign. We combine observations with theoretical modeling to infer the electron density change that most closely reproduces the observed perturbation. Our results explain the cases where LOREs are detected on only one path as resulting from transmitter-receiver geometry significantly which impacts the modal content and therefore the observed VLF recovery time.

  10. Involvement of healthcare professionals in an adverse event: the role of management in supporting their work force

    OpenAIRE

    Van Gerven, Eva; Seys, Deborah; Panella, Massimiliano; Sermeus, Walter; Euwema, Martin; Federico, Frank; Kenney, Linda; Vanhaecht, Kris

    2014-01-01

    Introduction After an adverse event, not only do patients and family members become victims, but healthcare professionals involved in the event also suffer. More than 50% of all healthcare professionals suffer emotionally and professionally after being involved in an adverse event. Support is needed for these “second victims” to prevent a further negative impact on patient care. Objectives To evaluate the prevalence and content of organizational-level support systems for healthcare profe...

  11. Early events in alphavirus replication determine the outcome of infection.

    Science.gov (United States)

    Frolov, Ilya; Akhrymuk, Maryna; Akhrymuk, Ivan; Atasheva, Svetlana; Frolova, Elena I

    2012-05-01

    Alphaviruses are a group of important human and animal pathogens. They efficiently replicate to high titers in vivo and in many commonly used cell lines of vertebrate origin. They have also evolved effective means of interfering with development of the innate immune response. Nevertheless, most of the alphaviruses are known to induce a type I interferon (IFN) response in vivo. The results of this study demonstrate that the first hours postinfection play a critical role in infection spread and development of the antiviral response. During this window, a balance is struck between virus replication and spread in vertebrate cells and IFN response development. The most important findings are as follows: (i) within the first 2 to 4 h postinfection, alphavirus-infected cells become unable to respond to IFN-β, and this occurs before the virus-induced decrease in STAT1 phosphorylation in response to IFN treatment. (ii) Most importantly, very low, subprotective doses of IFN-β, which do not induce the antiviral response in uninfected cells, have a very strong stimulatory effect on the cells' ability to express type I IFN and activate interferon-stimulated genes during subsequent infection with Sindbis virus (SINV). (iii) Small changes in SINV nsP2 protein affect its ability to inhibit cellular transcription and IFN release. Thus, the balance between type I IFN induction and the ability of the virus to develop further rounds of infection is determined in the first few hours of virus replication, when only low numbers of cells and infectious virus are involved.

  12. Involvement of Notch signaling in early chick ovarian follicle development.

    Science.gov (United States)

    Li, Jun; Zhao, Dan; Guo, Changquan; Li, Jian; Mi, Yuling; Zhang, Caiqiao

    2016-01-01

    The formation of primordial follicles is a crucial process in the establishment of follicle pools required for the female's reproductive life span. For laying hens, ample follicles are a prerequisite for high laying performance. Notch signaling plays critical roles in germ cell cysts breakdown and in the formation of primordial follicles. Here, we investigated the role of Notch signaling in the ovarian development of post-hatch chicks. Results showed that around post-hatch day 4 (H4), the germ cell cysts broke apart, oocytes became surrounded by squamous pregranulosa cells, and the primordial follicles were then formed. Subsequently, we detected the expression of Notch signaling-related genes including Notch receptors (Notch1, 2), ligands (Jag1, 2 and Dll1, 4), and target genes (Hes1, Hey1). These genes all showed expression at H4 and some of these genes were up-regulated during primordial follicle formation. To evaluate the Notch signaling requirement for early follicular development, we adopted an in vitro ovary culture system. Suppression of Notch signaling by γ-secretase inhibitor induced a decrease of primordial follicles and an increase of germ cells in cysts. Attenuating Notch signaling also inhibited the phosphatidylinositol 3-kinase/protein kinase B pathways and suppressed cadherin expression. These results suggest that Notch signaling is endowed with an indispensable role in primordial follicle formation in post-hatch chicks.

  13. Regulation of signaling events involved in the pathophysiology of neovascular AMD.

    Science.gov (United States)

    Wang, Haibo; Hartnett, M Elizabeth

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is a complex disease in which an individual's genetic predisposition is affected by aging and environmental stresses, which trigger signaling pathways involving inflammation, oxidation, and/or angiogenesis in the RPE cells and choroidal endothelial cells (CECs), to lead to vision loss from choroidal neovascularization. Antiangiogenic therapies have greatly improved clinical outcomes in the last decade; however, vision improves in less than half of patients treated for neovascular AMD, and treatments remain inadequate for atrophic AMD. Many studies focus on genetic predisposition or the association of outcomes in trials of human neovascular AMD but are unable to evaluate the effects between different cell types involved in AMD and the signaling events that take place to cause pathologic biologic events. This manuscript complements other reviews in that it describes what is known generally in human AMD studies and clinical trials testing methods to inhibit vascular endothelial growth factor (VEGF inhibitors) and presents pathologic signaling events that develop in two important cell types, the RPE cells and the CECs, when stimulated by stresses or placed into conditions similar to what is currently understood to occur in neovascular AMD. This manuscript complements other reviews by discussing signaling events that are activated by cell-cell or cell-matrix interactions. These considerations are particularly important when considering growth factors, such as VEGF, which are important in physiologic and pathologic processes, or GTPases that are present but active only if GTP bound. In either case, it is essential to understand the role of signaling activation to distinguish what is pathologic from what is physiologic. Particularly important is the essential role of activated Rac1 in CEC transmigration of the RPE monolayer, an important step in blindness associated with neovascular AMD. Other concepts discussed include

  14. Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease.

    Science.gov (United States)

    Mota, Sandra I; Costa, Rui O; Ferreira, Ildete L; Santana, Isabel; Caldeira, Gladys L; Padovano, Carmela; Fonseca, Ana C; Baldeiras, Inês; Cunha, Catarina; Letra, Liliana; Oliveira, Catarina R; Pereira, Cláudia M F; Rego, Ana Cristina

    2015-07-01

    Oxidative stress and endoplasmic reticulum (ER) stress have been associated with Alzheimer's disease (AD) progression. In this study we analyzed whether oxidative stress involving changes in Nrf2 and ER stress may constitute early events in AD pathogenesis by using human peripheral blood cells and an AD transgenic mouse model at different disease stages. Increased oxidative stress and increased phosphorylated Nrf2 (p(Ser40)Nrf2) were observed in human peripheral blood mononuclear cells (PBMCs) isolated from individuals with mild cognitive impairment (MCI). Moreover, we observed impaired ER Ca2+ homeostasis and increased ER stress markers in PBMCs from MCI individuals and mild AD patients. Evidence of early oxidative stress defense mechanisms in AD was substantiated by increased p(Ser40)Nrf2 in 3month-old 3xTg-AD male mice PBMCs, and also with increased nuclear Nrf2 levels in brain cortex. However, SOD1 protein levels were decreased in human MCI PBMCs and in 3xTg-AD mice brain cortex; the latter further correlated with reduced SOD1 mRNA levels. Increased ER stress was also detected in the brain cortex of young female and old male 3xTg-AD mice. We demonstrate oxidative stress and early Nrf2 activation in AD human and mouse models, which fails to regulate some of its targets, leading to repressed expression of antioxidant defenses (e.g., SOD-1), and extending to ER stress. Results suggest markers of prodromal AD linked to oxidative stress associated with Nrf2 activation and ER stress that may be followed in human peripheral blood mononuclear cells.

  15. High ABCC2 and Low ABCG2 Gene Expression Are Early Events in the Colorectal Adenoma-Carcinoma Sequence

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Vogel, Lotte K.; Kopp, Tine Iskov

    2015-01-01

    Development of colorectal cancer (CRC) may result from a dysfunctional interplay between diet, gut microbes and the immune system. The ABC transport proteins ABCB1 (P-glycoprotein, Multidrug resistance protein 1, MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) are involved in transport of various compounds...... across the epithelial barrier. Low mRNA level of ABCB1 has previously been identified as an early event in colorectal carcinogenesis (Andersen et al., PLoS One. 2013 Aug 19; 8(8): e72119). ABCC2 and ABCG2 mRNA levels were assessed in intestinal tissue from 122 CRC cases, 106 adenoma cases (12 with severe...... in carcinogenesis suggesting that these ABC transporters are involved in the early steps of carcinogenesis as previously reported for ABCB1. These results suggest that dysfunctional transport across the epithelial barrier may contribute to colorectal carcinogenesis....

  16. The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome

    Directory of Open Access Journals (Sweden)

    Anthony M. Cadena

    2016-05-01

    Full Text Available Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease.

  17. The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome.

    Science.gov (United States)

    Cadena, Anthony M; Flynn, JoAnne L; Fortune, Sarah M

    2016-04-05

    Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease.

  18. Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

    Science.gov (United States)

    Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

    2015-01-01

    We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury.

  19. Parental involvement in early intervention. An analysis of conditions of successful cooperation between parents and early intervention professionals

    Directory of Open Access Journals (Sweden)

    Pia Rothlaender

    2014-11-01

    Full Text Available Parental involvement is an important part of current early intervention concepts aimed at children with developmental disabilities. The article at hand focuses on the preconditions necessary for successful parental involvement and surveys the current international state of research for empirically confirmed determinants in parental involvement. Factors identified within the literature review include parent characteristics (sociodemographic attributes, resources and beliefs towards disabilities and intervention programs as well as features inherent in early intervention programs and its personnel. The predictive power of these factors varies depending on the dimension of parental participation and the living situation of the family. Implications for research and practice in the field of early interventions programs are discussed.

  20. Can Parents' Involvement in Children's Education Offset the Effects of Early Insensitivity on Academic Functioning?

    Science.gov (United States)

    Monti, Jennifer D.; Pomerantz, Eva M.; Roisman, Glenn I.

    2014-01-01

    Data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,312) were analyzed to examine whether the adverse effects of early insensitive parenting on children's academic functioning can be offset by parents' later involvement in children's education. Observations of mothers' early…

  1. Anti-radical power gives insight into early lipid oxidation events during frying

    NARCIS (Netherlands)

    Loon, W.A.M.; Linssen, J.P.H.; Legger, A.; Voragen, A.G.J.

    2006-01-01

    The aim of this research was to use anti-radical power (ARP) to study early lipid oxidation events during frying. The 2,2-diphenyl-1-picrylhydrazyl radical (DPPH¿) test was used to determine the ARP. As oil does not dissolve completely in methanol, which is generally used for the DPPH¿ test, butanol

  2. Anti-radical power gives insight into early lipid oxidation events during frying

    NARCIS (Netherlands)

    Loon, W.A.M.; Linssen, J.P.H.; Legger, A.; Voragen, A.G.J.

    2006-01-01

    The aim of this research was to use anti-radical power (ARP) to study early lipid oxidation events during frying. The 2,2-diphenyl-1-picrylhydrazyl radical (DPPH¿) test was used to determine the ARP. As oil does not dissolve completely in methanol, which is generally used for the DPPH¿ test, butanol

  3. Neighborhood Disadvantage, Stressful Life Events, and Adjustment among Mexican American Early Adolescents

    Science.gov (United States)

    Roosa, Mark W.; Burrell, Ginger L.; Nair, Rajni L.; Coxe, Stefany; Tein, Jenn-Yun; Knight, George P.

    2010-01-01

    This study examined a stress process model in which stressful life events and association with delinquent peers mediated the relationship of neighborhood disadvantage to Mexican American early adolescents' mental health. The authors also proposed that child gender, child generation, and neighborhood informal social control would moderate the…

  4. Let's Party! How To Plan Special Events and Raise Money in Early Childhood Programs.

    Science.gov (United States)

    Rice, Judith Anne

    This guide for early childhood program administrators provides guidelines and makes suggestions for planning special events to facilitate opportunities for parents, children, teachers, and organizations to connect in ways that strengthen individuals and communities and raise money for the organization. Part 1, "Planning," focuses on…

  5. A 3-Year Study of a School-Based Parental Involvement Program in Early Literacy

    Science.gov (United States)

    Crosby, Susan Ann; Rasinski, Timothy; Padak, Nancy; Yildirim, Kasim

    2015-01-01

    Although parental involvement in children's literacy development has been recognized for its potential in helping children develop early literacy achievement, studies of the effectiveness and sustainability of school-based parent involvement programs are not numerous. This study examines the effectiveness and durability of a school-based…

  6. Early Childhood Spaces: Involving Young Children and Practitioners in the Design Process. Working Papers in Early Childhood Development, No. 45

    Science.gov (United States)

    Clark, Alison

    2007-01-01

    This working paper explores the methodology and initial issues raised in seeking to involve young children in the design process. It reports a study concerned with how young children can play an active role in the designing and developing of children's spaces. The focus is on children under 6 years old in early childhood provision. (Contains 2…

  7. Consumer Motivations to Participate in Marketing-Events: The Role of Predispositional Involvement

    OpenAIRE

    Wohlfeil, Markus; Whelan, Susan

    2006-01-01

    Confronted with the decreasing effectiveness of classic marketing communications, event-marketing has become an increasingly popular alternative for marketers in dealing with a changing marketing environment. Event-marketing is defined as the creation of 3-dimensional, interactive brand-related hyperrealities for consumers by staging marketing-events, which would result in an emotional attachment to the brand. However, as a pull strategy within marketing communications, successful event-marke...

  8. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

  9. The impact of emotional involvement on online service buying decisions: an event-related potentials perspective.

    Science.gov (United States)

    Zhao, Meina; Wang, Jing; Han, Weiwei

    2015-12-02

    When examining a buying process, changes in human brain signals and their event-related potential (ERP) components can be considered a reflection of the consumers' emotions. In this experiment, participants were shown 12 products and related services that were available for purchase. After recording ERP components, we used a questionnaire to measure the individuals' emotional involvement toward the services (i.e. the same services shown in the stimuli) of the 12 products to measure the emotional valence of the services. The emotional ERP components and the late positive potential (LPP) were elicited under the service conditions and distributed over the left frontal regions. We determined that the services may evoke an LPP and that services with a high emotional value may evoke a larger LPP, which suggests that positive emotion may be measured using the LPP amplitude in the left frontal regions. This result helps elucidate whether positive emotions are stimulated during the product-service system decision-making process and helps understand the emotional valences of different services. Our analysis of the emotional motivation of the consumer suggests that the LPP may be useful as an emotional indicator for measuring consumers' evaluation of services that provides a neural view of product-service system buying decisions.

  10. BRCA1 and its phosphorylation involved in caffeine-inhibitable event upstream of G2 checkpoint

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Caffeine,which specifically inhibits ATM/ATR kinases,efficiently abrogates the ionizing radiation(IR)-induced G2 arrest and increases the sensitivity of various tumor cells to IR.Mechanisms for the effect of caffeine remain to be elucidated.As a target of ATM/ATR kinases,BRCA1 becomes activated and phosphorylated in response to IR.Thus,in this work,we investigated the possible role of BRCA1 in the effect of caffeine on G2 checkpoint and observed how BRCA1 phosphorylation was regulated in this process.For these purposes,the BRCA1 protein level and the phosphorylation states were analyzed by Western blotting by using an antibody against BRCA1 and phospho-specific antibodies against Ser-1423 and Ser-1524 residues in cells exposed to a combination of IR and caffeine.The results showed that caffeine down-regulated IR-induced BRCA1 expression and specifically abolished BRCA1 phosphorylation of Ser-1524,which was followed by an override of G2 arrest by caffeine.In addition,the ability of BRCA1 to transactivate p21 may be required for MCF-7 but not necessary for Hela response to caffeine.These data suggest that BRCA1 may be a potential target of caffeine.BRCA1 and its phosphorylation are most likely to be involved in the caffeine-inhibitable event upstream of G2 arrest.

  11. The Longitudinal Process of Early Parent Involvement on Student Achievement: A Path Analysis.

    Science.gov (United States)

    Hayakawa, Momoko; Englund, Michelle M; Warner-Richter, Mallory N; Reynolds, Arthur J

    2013-01-01

    This longitudinal study investigated the process whereby early parent involvement in preschool effects student achievement from kindergarten through 6(th) grade. Participants were 1,539 low-income, mainly African American children and their mothers, in the Chicago Longitudinal Study. Program children (N = 989) received one or two years of the Child-Parent Center (CPC) program - a preschool intervention that strongly promoted parents' development of parent involvement skills within the school and at home. Children from similar backgrounds who did not attend the CPC, but participated in available local resources (e.g. day care), were obtained as a comparison group (N = 550). Path analysis revealed an interactive process between parent involvement, academic achievement, and children's motivation. Early parent involvement directly influenced kindergarten achievement, which in turn influenced first grade student motivation. Highly motivated children then encouraged parents to continue involvement. The cyclic nature of this process across elementary school was observed. The model accounted for 61% of the variance in 6(th) grade achievement. Findings suggest that early parent involvement promoted in the CPC program, sets the stage for subsequent parent involvement, student motivation, and academic achievement throughout early and middle childhood.

  12. Identifying early events of gene expression in breast cancer with systems biology phylogenetics.

    Science.gov (United States)

    Abu-Asab, M S; Abu-Asab, N; Loffredo, C A; Clarke, R; Amri, H

    2013-01-01

    Advanced omics technologies such as deep sequencing and spectral karyotyping are revealing more of cancer heterogeneity at the genetic, genomic, gene expression, epigenetic, proteomic, and metabolomic levels. With this increasing body of emerging data, the task of data analysis becomes critical for mining and modeling to better understand the relevant underlying biological processes. However, the multiple levels of heterogeneity evident within and among populations, healthy and diseased, complicate the mining and interpretation of biological data, especially when dealing with hundreds to tens of thousands of variables. Heterogeneity occurs in many diseases, such as cancers, autism, macular degeneration, and others. In cancer, heterogeneity has hampered the search for validated biomarkers for early detection, and it has complicated the task of finding clonal (driver) and nonclonal (nonexpanded or passenger) aberrations. We show that subtyping of cancer (classification of specimens) should be an a priori step to the identification of early events of cancers. Studying early events in oncogenesis can be done on histologically normal tissues from diseased individuals (HNTDI), since they most likely have been exposed to the same mutagenic insults that caused the cancer in their neighboring tissues. Polarity assessment of HNTDI data variables by using healthy specimens as outgroup(s), followed by the application of parsimony phylogenetic analysis, produces a hierarchical classification of specimens that reveals the early events of the disease ontogeny within its subtypes as shared derived changes (abnormal changes) or synapomorphies in phylogenetic terminology. Copyright © 2013 S. Karger AG, Basel.

  13. Constraints on early events in Martian history as derived from the cratering record

    Science.gov (United States)

    Barlow, Nadine G.

    1990-01-01

    Constrains on early events in Martian history are derived using the planet's cratering record. Variations in the shapes of the crater size-frequency distribution curves are interpreted as indicative of the size-frequency distribution of the production populations, thus providing information about the age of the unit relative to the end of the heavy bombardment period. Results from the analysis of craters superposed on heavily cratered units across the Martian surface provide constraints on the hemispheric dichotomy and the early erosional conditions on Mars.

  14. MAX inactivation is an early event in GIST development that regulates p16 and cell proliferation

    Science.gov (United States)

    Schaefer, Inga-Marie; Wang, Yuexiang; Liang, Cher-wei; Bahri, Nacef; Quattrone, Anna; Doyle, Leona; Mariño-Enríquez, Adrian; Lauria, Alexandra; Zhu, Meijun; Debiec-Rychter, Maria; Grunewald, Susanne; Hechtman, Jaclyn F.; Dufresne, Armelle; Antonescu, Cristina R.; Beadling, Carol; Sicinska, Ewa T.; van de Rijn, Matt; Demetri, George D.; Ladanyi, Marc; Corless, Christopher L.; Heinrich, Michael C.; Raut, Chandrajit P.; Bauer, Sebastian; Fletcher, Jonathan A.

    2017-01-01

    KIT, PDGFRA, NF1 and SDH mutations are alternate initiating events, fostering hyperplasia in gastrointestinal stromal tumours (GISTs), and additional genetic alterations are required for progression to malignancy. The most frequent secondary alteration, demonstrated in ∼70% of GISTs, is chromosome 14q deletion. Here we report hemizygous or homozygous inactivating mutations of the chromosome 14q MAX gene in 16 of 76 GISTs (21%). We find MAX mutations in 17% and 50% of sporadic and NF1-syndromic GISTs, respectively, and we find loss of MAX protein expression in 48% and 90% of sporadic and NF1-syndromic GISTs, respectively, and in three of eight micro-GISTs, which are early GISTs. MAX genomic inactivation is associated with p16 silencing in the absence of p16 coding sequence deletion and MAX induction restores p16 expression and inhibits GIST proliferation. Hence, MAX inactivation is a common event in GIST progression, fostering cell cycle activity in early GISTs. PMID:28270683

  15. Occurrence of early adverse events after vaccination against influenza at a brazilian reference center

    Directory of Open Access Journals (Sweden)

    Marta Heloísa Lopes

    2008-01-01

    Full Text Available INTRODUCTION: Since 1999, the Ministry of Health in Brazil has conducted campaigns of vaccination against influenza targeted towards the elderly, chronically-diseased people and health care workers. The vaccine against influenza is associated with adverse events of minor importance. OBJECTIVE: To investigate the early adverse events related to the vaccine against influenza. CASUISTICS AND METHODS: One hundred and ninety seven elderly individuals and health care workers vaccinated against influenza were included. An inquiry regarding adverse events related to the vaccine was applied seven days after the vaccination. RESULTS: Local adverse events were reported by 32.5% and systemic effects by 26.4% of the vaccinated subjects. Pain in the region of the injection, headache, myalgia, malaise, and coryza were more frequent in the workers than in the elderly (p<0.05. There was no statistically significant difference in the occurrence of fever. CONCLUSIONS: The belief of part of the population that credits frequent and uncomfortable adverse events to the vaccine was not confirmed. The subjective adverse events were more frequent in the health care workers, which can influence, in a negative way, the disclosure of the benefits of this vaccine due to their role as opinion makers.

  16. University Response to Crisis Events Involving International Populations: The Case of Seven Directors of International Offices

    Science.gov (United States)

    Andrews, James P.

    2012-01-01

    This qualitative research study focuses on crisis events affecting university international populations. It explores how seven directors of university international offices at seven different geographical locations in Texas respond to those events. The study findings shed light on the current state of crisis preparedness in higher education from…

  17. Abrupt uplift of Tibetan Plateau at the end of early Pleistocene and Australasian impact event

    Institute of Scientific and Technical Information of China (English)

    REN Shoumai; LIU Yongjiang; GE Xiaohong

    2009-01-01

    The latest sharp uplift of the Tibetan Plateau and adjacent mountains occurred at the end of the early Pleistocene. The uplift of the Plateau resulted from Late Mesozoic- -Cenozoic compressional structure due to the subduction of the Indian Plate beneath the Asian continent. This event definitively effected the formation of basin-mountain relief, Cenozoic basin deformation, large scale aridity and desertification of western China. The Australasian meteorites impact event happened ca. 0.8 Ma ago, located in the triangle area of the Indian Ocean ridge (20°S/67°E). The impact may have resulted in an acceleration of speeding of the Indian Ocean ridge pushing the Indian Plate to subduct rapidly northward. Thus, the impact event can give reasonable explanation for the dynamic background of the latest rapid uplift of the Tibetan Plateau and the continental deformation of western China and even of the Middle Asia.

  18. An Early Warning System for Loan Risk Assessment Based on Rare Event Simulation

    Science.gov (United States)

    Zhou, Hong; Qiu, Yue; Wu, Yueqin

    System simulation is one of important tool for risk assessment. In this paper, a new method is presented to deal with credit risk assessment problems for commercial banks based on rare event simulation. The failure probability of repaying loans of listed company is taken as the criterion to measure the level of credit risk. The rare-event concept is adopted to construct the model of credit risk identification in commercial banks, and cross-entropy scheme is designed to implement the rare event simulation, based on which the loss probability can be assessed. Numerical experiments have shown that the method has a strong capability to identify the credit risk for commercial banks and offers a good tool for early warning.

  19. The Longitudinal Process of Early Parent Involvement on Student Achievement: A Path Analysis

    OpenAIRE

    Hayakawa, Momoko; Englund, Michelle M.; Warner-Richter, Mallory N.; Reynolds, Arthur J.

    2013-01-01

    This longitudinal study investigated the process whereby early parent involvement in preschool effects student achievement from kindergarten through 6th grade. Participants were 1,539 low-income, mainly African American children and their mothers, in the Chicago Longitudinal Study. Program children (N = 989) received one or two years of the Child-Parent Center (CPC) program – a preschool intervention that strongly promoted parents' development of parent involvement skills within the school an...

  20. Involving patient in the early stages of health technology assessment (HTA): a study protocol

    OpenAIRE

    Gagnon, Marie-Pierre; Candas, Bernard; Desmartis, Marie; Gagnon, Johanne; Roche, Daniel La; Rhainds, Marc; Coulombe, Martin; Dipankui, Mylène Tantchou; Légaré, France

    2014-01-01

    Background Public and patient involvement in the different stages of the health technology assessment (HTA) process is increasingly encouraged. The selection of topics for assessment, which includes identifying and prioritizing HTA questions, is a constant challenge for HTA agencies because the number of technologies requiring an assessment exceeds the resources available. Public and patient involvement in these early stages of HTA could make assessments more relevant and acceptable to them. ...

  1. Neuroinflammation - an early event in both the history and pathogenesis of Alzheimer's disease.

    Science.gov (United States)

    Eikelenboom, Piet; van Exel, Erik; Hoozemans, Jeroen J M; Veerhuis, Rob; Rozemuller, Annemieke J M; van Gool, Willem A

    2010-01-01

    About hundred years ago, Oskar Fischer proposed that the senile plaques are the consequence of the deposition of a foreign substance that could induce an inflammatory response leading to an abnormal neuritic response of the surrounding neurons. To show that the interest in inflammation in Alzheimer's disease (AD) is not only an early event in the history of AD but that inflammation is also an early event in the pathogenesis of AD. Evaluation of the neuropathological, epidemiological and genetic evidence for a role of inflammation early in the pathogenesis of AD. Neuropathological studies show presence of activated microglia and inflammation-related mediators in the cerebral neocortex of autopsied patients with a low Braak stage for AD pathology. Prospective population-based cohort studies indicate that higher serum levels of acute phase proteins predict dementia. On a genetic level, it was found that the production capacity of proinflammatory cytokines after stimulation with lipopolysaccharide (a process that is under strong genetic control) is higher in offspring with a parental history of late-onset AD. Neuropathological studies show that a neuroinflammatory response in the cerebral neocortex parallels the early stages of AD pathology and precedes the late stage, tau-related pathology. Epidemiological and genetic studies indicate that systemic markers of the innate immunity are risk factors for late-onset AD. Copyright 2010 S. Karger AG, Basel.

  2. Early Decay of Peccei-Quinn Fermion and the IceCube Neutrino Events

    CERN Document Server

    Ema, Yohei

    2016-01-01

    IceCube observed high-energy neutrino flux in the energy region from TeV to PeV. The decay of a massive long-lived particle in the early universe can be the origin of the IceCube neutrino events, which we call an "early decay scenario." In this paper, we construct a particle physics model that contains such a massive long-lived particle based on the Peccei-Quinn model. We calculate the present neutrino flux, taking account of realistic initial energy distributions of particles produced by the decay of the massive long-lived particle. We show that the early decay scenario naturally fits into the Peccei-Quinn model, and that the neutrino flux observed by IceCube can be explained in such a framework. We also see that, based on that model, a consistent cosmological history that explains the abundance of the massive long-lived particle is realized.

  3. Evidence for cold events in the early Holocene from the Guliya ice core, Tibetan Plateau, China

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Evidence for the "8.2 ka cold event" has been provided mostly from the circum-North Atlantic area. However, whether this cold event occurred in other places is a key to understanding its cause. Here, we provide the evidence for the "8.2 ka cold event" from the Guliya ice core in the northwest Tibetan Plateau, and it was found that the peak cooling (~8.3-8.2 ka) in this ice core was about 7.8-10℃, which was larger than the cooling in the North Atlantic region. The primary causes for this episode were diminished solar activity and weakened thermohaline circulation. Moreover, another weak cold event, centered about 9.4 ka, was also recorded in the Guliya ice core record. These two cold events were concurrent with the ice-rafting episodes in the North Atlantic during the early Holocene, which implies that the millennial-scale climatic cyclicity might exist in the Tibetan Plateau as well as in the North Atlantic.

  4. The Long-Term Effects of Early Parent Involvement and Parent Expectation in the USA

    Science.gov (United States)

    Froiland, John Mark; Peterson, Aubrey; Davison, Mark L.

    2013-01-01

    Building on social-cognitive theory and the expectancy-value theory, this study indicated that early parent expectations for children’s post-secondary educational attainment have a stronger effect on 8th-grade achievement than home-based parental involvement. With a nationally representative sample of kindergarten students and their parents in the…

  5. The Long-Term Effects of Early Parent Involvement and Parent Expectation in the USA

    Science.gov (United States)

    Froiland, John Mark; Peterson, Aubrey; Davison, Mark L.

    2013-01-01

    Building on social-cognitive theory and the expectancy-value theory, this study indicated that early parent expectations for children’s post-secondary educational attainment have a stronger effect on 8th-grade achievement than home-based parental involvement. With a nationally representative sample of kindergarten students and their parents in the…

  6. Staff supported parental involvement in effective early interventions for at-risk children

    DEFF Research Database (Denmark)

    Larsen, Michael Søgaard; Holm, Anders; Jensen, Bente

    The article presents a review of international research on the effect of early interventions with parental involvement. Ten international and national databases were searched. Hits were supplemented with references from the review group. The search process found 1933 unique references, which were...

  7. Interobserver delineation uncertainty in involved-node radiation therapy (INRT) for early-stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Aznar, Marianne C; Girinsky, Theodore; Berthelsen, Anne Kiil

    2017-01-01

    BACKGROUND AND PURPOSE: In early-stage classical Hodgkin lymphoma (HL) the target volume nowadays consists of the volume of the originally involved nodes. Delineation of this volume on a post-chemotherapy CT-scan is challenging. We report on the interobserver variability in target volume definiti...

  8. Evaluation of Parent Involvement in Early Childhood Programs 1979-1980. Technical Summary, Report No. 8130.

    Science.gov (United States)

    McKinney, John

    Evaluation of parent involvement in the following ten early childhood programs in the Philadelphia school district is presented: (1) Child Care (CC); (2) Head Start (HS); (3) Parent Nursery (PN); (4) Get Set (GS); (5) Durham Child Development Center (DCD); (6) Preschool Child Development Project (PCD); (7) Original Follow Through (OFT); (8) Follow…

  9. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure.

    Science.gov (United States)

    Stypula-Cyrus, Yolanda; Damania, Dhwanil; Kunte, Dhananjay P; Cruz, Mart Dela; Subramanian, Hariharan; Roy, Hemant K; Backman, Vadim

    2013-01-01

    Normal cell function is dependent on the proper maintenance of chromatin structure. Regulation of chromatin structure is controlled by histone modifications that directly influence chromatin architecture and genome function. Specifically, the histone deacetylase (HDAC) family of proteins modulate chromatin compaction and are commonly dysregulated in many tumors, including colorectal cancer (CRC). However, the role of HDAC proteins in early colorectal carcinogenesis has not been previously reported. We found HDAC1, HDAC2, HDAC3, HDAC5, and HDAC7 all to be up-regulated in the field of human CRC. Furthermore, we observed that HDAC2 up-regulation is one of the earliest events in CRC carcinogenesis and observed this in human field carcinogenesis, the azoxymethane-treated rat model, and in more aggressive colon cancer cell lines. The universality of HDAC2 up-regulation suggests that HDAC2 up-regulation is a novel and important early event in CRC, which may serve as a biomarker. HDAC inhibitors (HDACIs) interfere with tumorigenic HDAC activity; however, the precise mechanisms involved in this process remain to be elucidated. We confirmed that HDAC inhibition by valproic acid (VPA) targeted the more aggressive cell line. Using nuclease digestion assays and transmission electron microscopy imaging, we observed that VPA treatment induced greater changes in chromatin structure in the more aggressive cell line. Furthermore, we used the novel imaging technique partial wave spectroscopy (PWS) to quantify nanoscale alterations in chromatin. We noted that the PWS results are consistent with the biological assays, indicating a greater effect of VPA treatment in the more aggressive cell type. Together, these results demonstrate the importance of HDAC activity in early carcinogenic events and the unique role of higher-order chromatin structure in determining cell tumorigenicity.

  10. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure.

    Directory of Open Access Journals (Sweden)

    Yolanda Stypula-Cyrus

    Full Text Available Normal cell function is dependent on the proper maintenance of chromatin structure. Regulation of chromatin structure is controlled by histone modifications that directly influence chromatin architecture and genome function. Specifically, the histone deacetylase (HDAC family of proteins modulate chromatin compaction and are commonly dysregulated in many tumors, including colorectal cancer (CRC. However, the role of HDAC proteins in early colorectal carcinogenesis has not been previously reported. We found HDAC1, HDAC2, HDAC3, HDAC5, and HDAC7 all to be up-regulated in the field of human CRC. Furthermore, we observed that HDAC2 up-regulation is one of the earliest events in CRC carcinogenesis and observed this in human field carcinogenesis, the azoxymethane-treated rat model, and in more aggressive colon cancer cell lines. The universality of HDAC2 up-regulation suggests that HDAC2 up-regulation is a novel and important early event in CRC, which may serve as a biomarker. HDAC inhibitors (HDACIs interfere with tumorigenic HDAC activity; however, the precise mechanisms involved in this process remain to be elucidated. We confirmed that HDAC inhibition by valproic acid (VPA targeted the more aggressive cell line. Using nuclease digestion assays and transmission electron microscopy imaging, we observed that VPA treatment induced greater changes in chromatin structure in the more aggressive cell line. Furthermore, we used the novel imaging technique partial wave spectroscopy (PWS to quantify nanoscale alterations in chromatin. We noted that the PWS results are consistent with the biological assays, indicating a greater effect of VPA treatment in the more aggressive cell type. Together, these results demonstrate the importance of HDAC activity in early carcinogenic events and the unique role of higher-order chromatin structure in determining cell tumorigenicity.

  11. Early changes in Huntington's disease patient brains involve alterations in cytoskeletal and synaptic elements.

    Science.gov (United States)

    DiProspero, Nicholas A; Chen, Er-Yun; Charles, Vinod; Plomann, Markus; Kordower, Jeffrey H; Tagle, Danilo A

    2004-09-01

    Huntington's disease (HD) is caused by a polyglutamine repeat expansion in the N-terminus of the huntingtin protein. Huntingtin is normally present in the cytoplasm where it may interact with structural and synaptic elements. The mechanism of HD pathogenesis remains unknown but studies indicate a toxic gain-of-function possibly through aberrant protein interactions. To investigate whether early degenerative changes in HD involve alterations of cytoskeletal and vesicular components, we examined early cellular changes in the frontal cortex of HD presymptomatic (PS), early pathological grade (grade 1) and late-stage (grade 3 and 4) patients as compared to age-matched controls. Morphologic analysis using silver impregnation revealed a progressive decrease in neuronal fiber density and organization in pyramidal cell layers beginning in presymptomatic HD cases. Immunocytochemical analyses for the cytoskeletal markers alpha -tubulin, microtubule-associated protein 2, and phosphorylated neurofilament demonstrated a concomitant loss of staining in early grade cases. Immunoblotting for synaptic proteins revealed a reduction in complexin 2, which was marked in some grade 1 HD cases and significantly reduced in all late stage cases. Interestingly, we demonstrate that two synaptic proteins, dynamin and PACSIN 1, which were unchanged by immunoblotting, showed a striking loss by immunocytochemistry beginning in early stage HD tissue suggesting abnormal distribution of these proteins. We propose that mutant huntingtin affects proteins involved in synaptic function and cytoskeletal integrity before symptoms develop which may influence early disease onset and/or progression.

  12. Early surgical managment of penetrating ocular injuries involving the posterior segment.

    Science.gov (United States)

    Michels, R G

    1976-09-01

    Pars plana vitrectomy technic can be used in the early management of certain penetrating ocular injuries involving the posterior segment, including selected intraocular foreign bodies. This study reports the results of ten consecutive cases of intraocular foreign bodies in the posterior segment treated by a combination of vitrectomy (including lensectomy when necessary) and foreign-body extraction with forceps. The foreign body was successfully removed in nine of ten eyes, and nine of ten eyes were salvaged. This favorable experience using early vitreous surgery suggests that the vitrectomy technic can be used in other penetrating injuries involving the posterior segment that are not associated with intraocular foreign bodies. Possible indications for early vitrectomy are presented, including cases with a poor prognosis when managed by conventional methods.

  13. The two-step development of a duplex retina involves distinct events of cone and rod neurogenesis and differentiation.

    Science.gov (United States)

    Valen, Ragnhild; Eilertsen, Mariann; Edvardsen, Rolf Brudvik; Furmanek, Tomasz; Rønnestad, Ivar; van der Meeren, Terje; Karlsen, Ørjan; Nilsen, Tom Ole; Helvik, Jon Vidar

    2016-08-15

    Unlike in mammals, persistent postembryonic retinal growth is a characteristic feature of fish, which includes major remodeling events that affect all cell types including photoreceptors. Consequently, visual capabilities change during development, where retinal sensitivity to different wavelengths of light (photopic vision), -and to limited photons (scotopic vision) are central capabilities for survival. Differently from well-established model fish, Atlantic cod has a prolonged larval stage where only cone photoreceptors are present. Rods do not appear until juvenile transition (metamorphosis), a hallmark of indirect developing species. Previously we showed that whole gene families of lws (red-sensitive) and sws1 (UV-sensitive) opsins have been lost in cod, while rh2a (green-sensitive) and sws2 (blue-sensitive) genes have tandem duplicated. Here, we provide a comprehensive characterization of a two-step developing duplex retina in Atlantic cod. The study focuses on cone subtype dynamics and delayed rod neurogenesis and differentiation in all cod life stages. Using transcriptomic and histological approaches we show that different opsins disappear in a topographic manner during development where central to peripheral retina is a key axis of expressional change. Early cone differentiation was initiated in dorso-temporal retina different from previously described in fish. Rods first appeared during initiation of metamorphosis and expression of the nuclear receptor transcription factor nr2e3-1, suggest involvement in rod specification. The indirect developmental strategy thus allows for separate studies of cones and rods development, which in nature correlates with visual changes linked to habitat shifts. The clustering of key retinal genes according to life stage, suggests that Atlantic cod with its sequenced genome may be an important resource for identification of underlying factors required for development and function of photopic and scotopic vision.

  14. Grandmother Involvement as a Protective Factor for Early Childhood Social Adjustment

    Science.gov (United States)

    Barnett, Melissa A.; Scaramella, Laura V.; Neppl, Tricia K.; Ontai, Lenna L.; Conger, Rand D.

    2010-01-01

    Despite high rates of grandmother involvement with young grandchildren, very little research has examined the associations between non-residential grandmother involvement and grandchild social adjustment. The present study draws 127 families enrolled in the Family Transitions Project to consider the degree to which mother-reported maternal grandmother involvement buffers 3- and 4-year old grandchildren from economic, parenting, and child temperamental risks for reduced social competence and elevated externalizing behaviors. Findings indicate that higher levels of mother-reported grandmother involvement reduced the negative association between observed grandchild negative emotional reactivity and social competence. Further, high levels of mother-reported grandmother involvement protected grandchildren from the positive association between observed harsh mother parenting and grandchild externalizing behaviors. These findings underscore the relevance of moving beyond the nuclear family to understand factors linked to social adjustment during early childhood. PMID:20954774

  15. Marine ecosystem resilience during extreme deoxygenation: the Early Jurassic oceanic anoxic event.

    Science.gov (United States)

    Caswell, Bryony A; Frid, Christopher L J

    2017-01-01

    Global warming during the Early Jurassic, and associated widespread ocean deoxygenation, was comparable in scale with the changes projected for the next century. This study quantifies the impact of severe global environmental change on the biological traits of marine communities that define the ecological roles and functions they deliver. We document centennial-millennial variability in the biological trait composition of Early Jurassic (Toarcian) seafloor communities and examine how this changed during the event using biological traits analysis. Environmental changes preceding the global oceanic anoxic event (OAE) produced an ecological shift leading to stressed benthic palaeocommunities with reduced resilience to the subsequent OAE. Changes in traits and ecological succession coincided with major environmental changes; and were of similar nature and magnitude to those in severely deoxygenated benthic communities today despite the very different timescales. Changes in community composition were linked to local redox conditions whereas changes in populations of opportunists were driven by primary productivity. Throughout most of the OAE substitutions by tolerant taxa conserved the trait composition and hence functioning, but periods of severe deoxygenation caused benthic defaunation that would have resulted in functional collapse. Following the OAE recovery was slow probably because the global nature of the event restricted opportunities for recruitment from outside the basin. Our findings suggest that future systems undergoing deoxygenation may initially show functional resilience, but severe global deoxygenation will impact traits and ecosystem functioning and, by limiting the species pool, will slow recovery rates.

  16. Parental Substance Abuse As an Early Traumatic Event. Preliminary Findings on Neuropsychological and Personality Functioning in Young Drug Addicts Exposed to Drugs Early

    Science.gov (United States)

    Parolin, Micol; Simonelli, Alessandra; Mapelli, Daniela; Sacco, Marianna; Cristofalo, Patrizia

    2016-01-01

    Parental substance use is a major risk factor for child development, heightening the risk of drug problems in adolescence and young adulthood, and exposing offspring to several types of traumatic events. First, prenatal drug exposure can be considered a form of trauma itself, with subtle but long-lasting sequelae at the neuro-behavioral level. Second, parents' addiction often entails a childrearing environment characterized by poor parenting skills, disadvantaged contexts and adverse childhood experiences (ACEs), leading to dysfunctional outcomes. Young adults born from/raised by parents with drug problems and diagnosed with a Substance Used Disorder (SUD) themselves might display a particularly severe condition in terms of cognitive deficits and impaired personality function. This preliminary study aims to investigate the role of early exposure to drugs as a traumatic event, capable of affecting the psychological status of young drug addicts. In particular, it intends to examine the neuropsychological functioning and personality profile of young adults with severe SUDs who were exposed to drugs early in their family context. The research involved three groups, each consisting of 15 young adults (aged 18–24): a group of inpatients diagnosed with SUDs and exposed to drugs early, a comparison group of non-exposed inpatients and a group of non-exposed youth without SUDs. A neuropsychological battery (Esame Neuropsicologico Breve-2), an assessment procedure for personality disorders (Shedler-Westen Assessment Procedure-200) and the Symptom CheckList-90-Revised were administered. According to present preliminary results, young drug addicts exposed to drugs during their developmental age were characterized by elevated rates of neuropsychological impairments, especially at the expense of attentive and executive functions (EF); personality disorders were also common but did not differentiate them from non-exposed youth with SUDs. Alternative multi-focused prevention and

  17. Parametrial involvement in women with low-risk, early-stage cervical cancer.

    Science.gov (United States)

    Vanichtantikul, A; Tantbirojn, P; Manchana, T

    2017-09-01

    This study identified the incidence of parametrial involvement in low risk, early-stage cervical cancer patients and evaluated the factors associated with parametrial involvement. All stage IA2-IB1 cervical cancer patients who underwent radical hysterectomy with pelvic lymphadenectomy were retrospectively reviewed. Patients with squamous cell carcinoma or adenocarcinoma grade 1-2, tumour size less than 2 cm, no lymphovascular space invasion (LVSI), negative pelvic nodes and depth of stromal invasion (DSI) less than 10 mm were identified as the low-risk group. A total of 243 patients were eligible. Squamous cell carcinomas were the most frequent histological cell type (65%). Most patients (81.5%) had tumour size less than 2 cm. Thirteen patients (5.3%) had parametrial involvement, 77 (31.7%) had DSI more than 10 mm, 121 (49.8%) had more than 50% invasion, 119 (49%) had LVSI and 19 (7.5%) had node metastasis. Ninety-five patients (39.1%) were defined as low risk. None of low-risk group had parametrial involvement. DSI more than 10 mm or more than 50% stromal invasion, presence of LVSI and pelvic node metastasis were significant factors associated with parametrial involvement. Parametrial involvement in low-risk, early-stage cervical cancer is extremely low. Less radical surgery may be an alternative treatment option. © 2016 John Wiley & Sons Ltd.

  18. Event-related brain potentials reveal the time-course of language change detection in early bilinguals.

    Science.gov (United States)

    Kuipers, Jan-Rouke; Thierry, Guillaume

    2010-05-01

    Using event-related brain potentials, we investigated the temporal course of language change detection in proficient bilinguals as compared to matched controls. Welsh-English bilingual participants and English controls were presented with a variant of the oddball paradigm involving picture-word pairs. The language of the spoken word was manipulated such that English was the frequent stimulus (75%) and Welsh the infrequent stimulus (25%). We also manipulated semantic relatedness between pictures and words, such that only half of the pictures were followed by a word that corresponded with the identity of the picture. The P2 wave was significantly modulated by language in the bilingual group only, suggesting that this group detected a language change as early as 200 ms after word onset. Monolinguals also reliably detected the language change, but at a later stage of semantic integration (N400 range), since Welsh words were perceived as meaningless. The early detection of a language change in bilinguals triggered stimulus re-evaluation mechanisms reflected by a significant P600 modulation by Welsh words. Furthermore, compared to English unrelated words, English words matching the picture identity elicited significantly greater P2 amplitudes in the bilingual group only, suggesting that proficient bilinguals validate an incoming word against their expectation based on the context. Overall, highly proficient bilinguals appear to detect language changes very early on during speech perception and to consciously monitor language changes when they occur.

  19. Multi-events earthquake early warning algorithm using a Bayesian approach

    Science.gov (United States)

    Wu, S.; Yamada, M.; Tamaribuchi, K.; Beck, J. L.

    2015-02-01

    Current earthquake early warning (EEW) systems lack the ability to appropriately handle multiple concurrent earthquakes, which led to many false alarms during the 2011 Tohoku earthquake sequence in Japan. This paper uses a Bayesian probabilistic approach to handle multiple concurrent events for EEW. We implement the theory using a two-step algorithm. First, an efficient approximate Bayesian model class selection scheme is used to estimate the number of concurrent events. Then, the Rao-Blackwellized Importance Sampling method with a sequential proposal probability density function is used to estimate the earthquake parameters, that is hypocentre location, origin time, magnitude and local seismic intensity. A real data example based on 2 months data (2011 March 9-April 30) around the time of the 2011 M9 Tohoku earthquake is studied to verify the proposed algorithm. Our algorithm results in over 90 per cent reduction in the number of incorrect warnings compared to the existing EEW system operating in Japan.

  20. Modeling Tool for Decision Support during Early Days of an Anthrax Event

    Science.gov (United States)

    Meltzer, Martin I.; Shadomy, Sean; Bower, William A.; Hupert, Nathaniel

    2017-01-01

    Health officials lack field-implementable tools for forecasting the effects that a large-scale release of Bacillus anthracis spores would have on public health and hospitals. We created a modeling tool (combining inhalational anthrax caseload projections based on initial case reports, effects of variable postexposure prophylaxis campaigns, and healthcare facility surge capacity requirements) to project hospitalizations and casualties from a newly detected inhalation anthrax event, and we examined the consequences of intervention choices. With only 3 days of case counts, the model can predict final attack sizes for simulated Sverdlovsk-like events (1979 USSR) with sufficient accuracy for decision making and confirms the value of early postexposure prophylaxis initiation. According to a baseline scenario, hospital treatment volume peaks 15 days after exposure, deaths peak earlier (day 5), and recovery peaks later (day 23). This tool gives public health, hospital, and emergency planners scenario-specific information for developing quantitative response plans for this threat. PMID:27983505

  1. Lanthanum Prevents Salt Stress-induced Programmed Cell Death in Rice Root Tip Cells by Controlling Early Induction Events

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In a previous study, a salt stress-induced programmed cell death (PCD) model was established in rice root tip cells. Here,by using Wuyunjing 8th rice seedlings, the effects of lanthanum on salt stress-induced PCD early events were studied. The peroxidase (APX). Imidazole (20 mmol/L), the inhibitor of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), could alleviate the occurrence of PCD obviously, and such alleviation could be enhanced by the addition of La3+,indicating the involvement of NADPH oxidase in the salt stress-induced PCD process. Taken together, lanthanum could prevent salt stress-induced PCD occurrence in the rice root tip cells by blocking the calcium influx under stress, which was followed by inhibiting calcium-dependent NADPH oxidase activity to prevent O2·-production and, enhancing the cytosolic antioxidative enzyme activities to scavenge the reactive oxygen species.

  2. Events

    Directory of Open Access Journals (Sweden)

    Igor V. Karyakin

    2016-02-01

    Full Text Available The 9th ARRCN Symposium 2015 was held during 21st–25th October 2015 at the Novotel Hotel, Chumphon, Thailand, one of the most favored travel destinations in Asia. The 10th ARRCN Symposium 2017 will be held during October 2017 in the Davao, Philippines. International Symposium on the Montagu's Harrier (Circus pygargus «The Montagu's Harrier in Europe. Status. Threats. Protection», organized by the environmental organization «Landesbund für Vogelschutz in Bayern e.V.» (LBV was held on November 20-22, 2015 in Germany. The location of this event was the city of Wurzburg in Bavaria.

  3. Patterns and predictors of paternal involvement in early adolescents' type 1 diabetes management over 3 years.

    Science.gov (United States)

    Hilliard, Marisa E; Rohan, Jennifer M; Rausch, Joseph R; Delamater, Alan; Pendley, Jennifer Shroff; Drotar, Dennis

    2014-01-01

    To document trajectories of paternal involvement in diabetes management and examine bidirectional associations with diabetes outcomes across early adolescence. 3-year prospective assessment of paternal involvement, diabetes self-management, and glycemic control among 136 youth (age 9-12 at baseline) and their mothers and fathers. Unconditional growth curves demonstrated decreasing amount (maternal report: F(1,128) = 14.79; paternal report: F(1,111) = 12.95, ps Controlling for covariates, lower youth self-management predicted an increasing slope in fathers' self-reported amount of involvement (b = -0.15 to -0.22, p management (b = -0.01, p management. Communication about ways to enhance fathers' involvement before this transition may help prevent or reduce declining diabetes management and control common in adolescence.

  4. Delinquency, parental involvement, early adult criminality, and sex: Evidence of moderated mediation.

    Science.gov (United States)

    Walters, Glenn D

    2013-08-01

    One purpose of this study was to determine whether parental involvement, measured in late adolescence, mediates the relationship between delinquency in mid-adolescence and crime in early adulthood. This study's second purpose was to ascertain whether this relationship is moderated by sex, such that late adolescent parental involvement mediates the delinquency-crime relationship in females but not in males. A secondary analysis of data provided by 579 (272 males, 307 females) members of the National Longitudinal Survey of Youth-Child (NLSYC) was conducted in an effort to evaluate the possibility of moderated mediation in the relationship between delinquency at age 16, parental involvement at age 18, and criminality at age 24. Moderated mediation analysis, path analysis, and causal mediation analysis revealed the presence of a conditional indirect relationship between delinquency, parental involvement, and adult crime moderated by sex. These results are consistent with views on cumulative disadvantage and gendered pathways to crime.

  5. Children with autism spectrum disorder: teaching conversation involving feelings about events.

    Science.gov (United States)

    Conallen, K; Reed, P

    2017-03-01

    Two procedures were developed to teach individuals with Autism Spectrum Disorders labels (tacts) for various private events (emotions): Study 1 attempted to distinguish them from pure tacts and mands (requests); and Study 2 attempted to train initiating a conversation with grammatically correct subject-verb-comment construction. A multiple treatment reversal design was used in both studies, followed by a probe to see if the tacts were used across novel settings. The children were prompted to initiate a series of language exchanges, which resulted in an increased ability to participate in conversations about private events. Together, the results of both studies suggest that, by providing an effective and reinforcing means of teaching both the function and the form of these tacts, conversations can be successfully initiated by children with ASD. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  6. Transcriptomic events involved in melon mature-fruit abscission comprise the sequential induction of cell-wall degrading genes coupled to a stimulation of endo and exocytosis.

    Directory of Open Access Journals (Sweden)

    Jorge Corbacho

    Full Text Available BACKGROUND: Mature-fruit abscission (MFA in fleshy-fruit is a genetically controlled process with mechanisms that, contrary to immature-fruit abscission, has not been fully characterized. Here, we use pyrosequencing to characterize the transcriptomes of melon abscission zone (AZ at three stages during AZ-cell separation in order to understand MFA control at an early stage of AZ-activation. PRINCIPAL FINDINGS: The results show that by early induction of MFA, the melon AZ exhibits major gene induction, while by late induction of MFA, melon AZ shows major gene repression. Although some genes displayed similar regulation in both early and late induction of abscission, such as EXT1-EXT4, EGase1, IAA2, ERF1, AP2D15, FLC, MADS2, ERAF17, SAP5 and SCL13 genes, the majority had different expression patterns. This implies that time-specific events occur during MFA, and emphasizes the value of characterizing multiple time-specific abscission transcriptomes. Analysis of gene-expression from these AZs reveal that a sequential induction of cell-wall-degrading genes is associated with the upregulation of genes involved in endo and exocytosis, and a shift in plant-hormone metabolism and signaling genes during MFA. This is accompanied by transcriptional activity of small-GTPases and synthaxins together with tubulins, dynamins, V-type ATPases and kinesin-like proteins potentially involved in MFA signaling. Early events are potentially controlled by down-regulation of MADS-box, AP2/ERF and Aux/IAA transcription-factors, and up-regulation of homeobox, zinc finger, bZIP, and WRKY transcription-factors, while late events may be controlled by up-regulation of MYB transcription-factors. SIGNIFICANCE: Overall, the data provide a comprehensive view on MFA in fleshy-fruit, identifying candidate genes and pathways associated with early induction of MFA. Our comprehensive gene-expression profile will be very useful for elucidating gene regulatory networks of the MFA in

  7. Early psychosocial interventions after disasters, terrorism and other shocking events: is there a gap between norms and practice in Europe?

    NARCIS (Netherlands)

    Brake, H. te; Dückers, M.

    2013-01-01

    Background: Internationally, several initiatives exist to describe standards for post-disaster psychosocial care. Objective: This study explored the level of consensus of experts within Europe on a set of recommendations on early psychosocial intervention after shocking events (Dutch guidelines),

  8. Early Morphological and Physiological Events Occurring During Germination of Maize Seeds

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The early morphological and physiological events occurring during maize (Zea mays cv. Nongda 108) seed imbibition and germination were studied. Water uptake of seeds exhibited a triphasic pattern with a marked increase during the initial phase of imbibition, and then a slow increase, followed by a second substantial increase. Imbibition time for 10 and 50% of seed germination was about 26 and 46 h at 30℃, respectively. The relative conductivity of maize seeds dramatically decreased during the initial phase of imbibition, followed by a substantial increase. Respiratory rate of seeds gradually increased with imbibition. Length of root cap cells decreased during the initial phase and then increased; those of meristematic zone cells increased during the initial phase and then decreased; and those of elongation zone cells and of the whole elongation zone of the radicle gradually increased during germination. The contents of soluble sugars and starch in embryos gradually decreased as the activities of α- and β-amylase strikingly increased with imbibition. In the meantime, protein contents of embryos gradually decreased and free amino acid content increased. The activities of aminopeptidase and endopeptidase increased until 12 h of imbibition and then decreased. It is concluded that germination of maize seeds is mainly completed by extension of cells in the elongation zone of the radicle, and that mobilization of stored reserves in the embryo during the initial phase of imbibition is also an early event during seed germination.

  9. The early Toarcian anoxic event: what the beginning and the end of the story are?

    Science.gov (United States)

    Mattioli, Emanuela; Plancq, Julien; Raucsik, Béla

    2010-05-01

    The early Toarcian anoxic event: what the beginning and the end of the story are? E. Mattioli (1), J. Plancq (1), and B. Rauksik (2) (1) UMR 5125 PEPS, CNRS, France; Université Lyon 1, Campus de la DOUA, Bâtiment Géode, 69622 Villeurbanne Cedex, France (emanuela.mattioli@univ-lyon1.fr) (2) Department of Earth and Environmental Sciences, University of Pannonia, Veszprém, Hungary The early Toarcian anoxic event (T-OAE) and the associated biotic crisis have received much attention in the last decade. However, the events forewarning the crisis as well as its aftermath are still poorly known. The T-OAE coincides with a prominent carbon isotope negative excursion (T-CIE) that is preceded by an excursion of similar intensity at the Pliensbachian-Toarcian boundary (Hesselbo et al., 2007). The onset of T-CIE occurred some 700 kyr later than the end of the Boundary-CIE (Suan et al., 2008a). This succession of events demonstrates that the T-OAE was a complex suite of environmental perturbations. In this work, we focused on calcareous nannofossil assemblages occurring in the Peniche section (Portugal) during the Boundary-CIE with the aim to understand if calcifying plankton reacted in a similar/different way to the two CIEs. Also, two sections and one borehole located along a W-E transect, along the NW-Tethyan shelf (in the Yorkshire coast, in the E Paris Basin, and in Mecsek Basin, respectively), were investigated to assess which way calcareous nannoplankton recovered after the crisis, and if the recovery was a synchronous event. The production by nannoplankton collapsed during the T-CIE, as demonstrated by the lowest absolute abundance of nannofossils measured in Peniche and other studied sites (Mattioli et al., 2008). Besides this nannofossil abundance decrease, also the size of the incertae sedis Schizosphaerella test was drastically reduced (Suan et al., 2008b). If a similar size decrease is also recorded during the Boundary-CIE, calcareous nannofossil abundances are

  10. Neural mirroring and social interaction: Motor system involvement during action observation relates to early peer cooperation.

    Science.gov (United States)

    Endedijk, H M; Meyer, M; Bekkering, H; Cillessen, A H N; Hunnius, S

    2017-04-01

    Whether we hand over objects to someone, play a team sport, or make music together, social interaction often involves interpersonal action coordination, both during instances of cooperation and entrainment. Neural mirroring is thought to play a crucial role in processing other's actions and is therefore considered important for social interaction. Still, to date, it is unknown whether interindividual differences in neural mirroring play a role in interpersonal coordination during different instances of social interaction. A relation between neural mirroring and interpersonal coordination has particularly relevant implications for early childhood, since successful early interaction with peers is predictive of a more favorable social development. We examined the relation between neural mirroring and children's interpersonal coordination during peer interaction using EEG and longitudinal behavioral data. Results showed that 4-year-old children with higher levels of motor system involvement during action observation (as indicated by lower beta-power) were more successful in early peer cooperation. This is the first evidence for a relation between motor system involvement during action observation and interpersonal coordination during other instances of social interaction. The findings suggest that interindividual differences in neural mirroring are related to interpersonal coordination and thus successful social interaction. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Genes of both parental origins are differentially involved in early embryogenesis of a tobacco interspecies hybrid.

    Directory of Open Access Journals (Sweden)

    Jun-E Zhang

    Full Text Available BACKGROUND: In animals, early embryonic development is largely dependent on maternal transcripts synthesized during gametogenesis. However, in higher plants, the extent of maternal control over zygote development and early embryogenesis is not fully understood yet. Nothing is known about the activity of the parental genomes during seed formation of interspecies hybrids. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that an interspecies hybridization system between SR1 (Nicotiana tabacum and Hamayan (N. rustica has been successfully established. Based on the system we selected 58 genes that have polymorphic sites between SR1 and Hamayan, and analyzed the allele-specific expression of 28 genes in their hybrid zygotes (Hamayan x SR1. Finally the allele-specific expressions of 8 genes in hybrid zygotes were repeatedly confirmed. Among them, 4 genes were of paternal origin, 1 gene was of maternal origin and 3 genes were of biparental origin. These results revealed obvious biparental involvement and differentially contribution of parental-origin genes to zygote development in the interspecies hybrid. We further detected the expression pattern of the genes at 8-celled embryo stage found that the involvement of the parental-origin genes may change at different stages of embryogenesis. CONCLUSIONS/SIGNIFICANCE: We reveal that genes of both parental origins are differentially involved in early embryogenesis of a tobacco interspecies hybrid and functions in a developmental stage-dependent manner. This finding may open a window to seek for the possible molecular mechanism of hybrid vigor.

  12. The nummulithoclast event within the Lower Eocene in the Southern Tethyan margin: Mechanisms involved, analogy with the filament event and climate implication (Kairouan, Central Tunisia)

    Science.gov (United States)

    Mardassi, Besma

    2017-10-01

    Early Eocene deposits in Tunisia are marked by clear variations in terms of facies and thickness. Each facies corresponds to an appropriate depositional environment. Shallow water deposits pass gradually offshore into deeper carbonates along a homoclinal ramp. In Central Tunisia, detailed investigation of carbonate facies under transmitted light shows a particular richness of the middle part of Early Eocene deposits in nummulithoclasts. These facies are often frequent within corrugated banks. They are overlaying Globigerina rich well-bedded limestones and overlain by nummulites and Discocyclina rich massively-bedded carbonates. Nummulithoclasts occurrence is recorded on field by an abrupt vertical change from autochthonous thinly-bedded limestones to massively-bedded fossiliferous carbonates. Change concerns structures, textures and limestones' composition. Nummulithoclasts are associated either to planktonic micro-organisms or to benthic fauna and phosphates grains. The middle and the upper parts of the Early Eocene deposits, particularly, fossilize hummocky cross-stratifications and megaripples. Their presence advocates the role of energetic currents in sweeping nummulites from lower circatidal to upper bathyal environments. The absence of a slope break helped the settling of reworked nummulites within deeper environments. The abrupt change, nummulithoclast associations and current structures arouse reflection and make them not reliable to characterize depositional environments. However, their preferential occurrence within the middle part of Early Eocene deposits and the tight linkage with storm activity lead them to be considered as event. The large scale hummocks recorded on field suggests that nummulite fragmentation was triggered by tropical cyclones rather than humble storms. The frequent occurrence of cyclones which correspond to low pressure atmospheric systems seems in relation with a global warming enhancing the sea surface temperature.

  13. Traumatic events involving elderly patients treated with anticoagulants for atrial fibrillation: the downside of stroke prevention

    Directory of Open Access Journals (Sweden)

    Alessandro Riccardi

    2016-08-01

    Full Text Available A group of oral anticoagulant-treated patients affected by permanent atrial fibrillation was evaluated after their access to the emergency room as a result of a traumatic accident. In these patients, the re-evaluation of their risk of thromboembolism and bleeding was performed together with the evaluation of their risk of falling and institutionalization. Results show that the emergency department identifies a cohort of very elderly frail patients, who should be carefully reconsidered for anticoagulant therapy after a traumatic event.

  14. Early Molecular Events in Murine Gastric Epithelial Cells Mediated by Helicobacter pylori CagA.

    Science.gov (United States)

    Banerjee, Aditi; Basu, Malini; Blanchard, Thomas G; Chintalacharuvu, Subba R; Guang, Wei; Lillehoj, Erik P; Czinn, Steven J

    2016-10-01

    Murine models of Helicobacter pylori infection are used to study host-pathogen interactions, but lack of severe gastritis in this model has limited its usefulness in studying pathogenesis. We compared the murine gastric epithelial cell line GSM06 to the human gastric epithelial AGS cell line to determine whether similar events occur when cultured with H. pylori. The lysates of cells infected with H. pylori isolates or an isogenic cagA-deficient mutant were assessed for translocation and phosphorylation of CagA and for activation of stress pathway kinases by immunoblot. Phosphorylated CagA was detected in both cell lines within 60 minutes. Phospho-ERK 1/2 was present within several minutes and distinctly present in GSM06 cells at 60 minutes. Similar results were obtained for phospho-JNK, although the 54 kDa phosphoprotein signal was dominant in AGS, whereas the lower molecular weight band was dominant in GSM06 cells. These results demonstrate that early events in H. pylori pathogenesis occur within mouse epithelial cells similar to human cells and therefore support the use of the mouse model for the study of acute CagA-associated host cell responses. These results also indicate that reduced disease in H. pylori-infected mice may be due to lack of the Cag PAI, or by differences in the mouse response downstream of the initial activation events. © 2016 John Wiley & Sons Ltd.

  15. Early Adverse Events and Attrition in SSRI Treatment: A Suicide Assessment Methodology Study (SAMS) Report

    Science.gov (United States)

    Warden, Diane; Trivedi, Madhukar H.; Wisniewski, Stephen R.; Kurian, Benji; Zisook, Sidney; Kornstein, Susan G.; Friedman, Edward S.; Miyahara, Sachiko; Leuchter, Andrew F.; Fava, Maurizio; Rush, John

    2011-01-01

    Adverse events during selective serotonin reuptake inhibitor (SSRI) treatment are frequent and may lead to premature treatment discontinuation. If attrition is associated with early worsening of side effects or the frequency, intensity, or burden of side effects, interventions to maximize retention could be focused on patients with these events. Outpatient participants (n=265) with nonpsychotic major depressive disorder entered an 8-week trial with an SSRI. At baseline and week 2, specific side effects were evaluated with the Systematic Assessment for Treatment Emergent Events – Systematic Inquiry, and at week 2 the Frequency, Intensity, and Burden of Side Effects Rating globally assessed side effects. Attrition was defined by those participants who left treatment after week 2 but before week 8. No specific week 2 side effect, either treatment emergent or with worsening intensity, was independently associated with attrition. Global ratings of side effect frequency, intensity, or burden at week 2 were also not associated with subsequent attrition. Neither global ratings nor specific side effects at week 2 were related to patient attrition during SSRI treatment. Other factors appear to contribute to patient decisions about continuing with treatment. PMID:20473060

  16. Early events of citrus greening (Huanglongbing) disease development at the ultrastructural level.

    Science.gov (United States)

    Folimonova, Svetlana Y; Achor, Diann S

    2010-09-01

    Citrus greening (Huanglongbing [HLB]) is one of the most destructive diseases of citrus worldwide. The causal agent of HLB in Florida is thought to be 'Candidatus Liberibacter asiaticus'. Understanding of the early events in HLB infection is critical for the development of effective measures to control the disease. In this work, we conducted cytopathological studies by following the development of the disease in citrus trees graft inoculated with 'Ca. L. asiaticus'-containing material under greenhouse conditions to examine the correlation between ultrastructural changes and symptom production, with the main objective of characterizing the early events of infection. Based on our observations, one of the first degenerative changes induced upon invasion of the pathogen appears to be swelling of middle lamella between cell walls surrounding sieve elements. This anatomical aberration was often observed in samples from newly growing flushes in inoculated sweet orange and grapefruit trees at the early "presymptomatic" stage of HLB infection. Development of symptoms and their progression correlated with an increasing degree of microscopic aberrations. Remarkably, the ability to observe the bacterium in the infected tissue also correlated with the degree of the disease progression. Large numbers of bacterial cells were found in phloem sieve tubes in tissue samples from presymptomatic young flushes. In contrast, we did not observe the bacteria in highly symptomatic leaf samples, suggesting a possibility that, at more advanced stages of the disease, a major proportion of 'Ca. L. asiaticus' is present in a nonviable state. We trust that observations reported here advance our understanding of how 'Ca. L. asiaticus' causes disease. Furthermore, they may be an important aid in answering a question: when and where within an infected tree the tissue serves as a better inoculum source for acquisition and transmission of the bacterium by its psyllid vector.

  17. YAP activation is an early event and a potential therapeutic target in liver cancer development.

    Science.gov (United States)

    Perra, Andrea; Kowalik, Marta Anna; Ghiso, Elena; Ledda-Columbano, Giovanna Maria; Di Tommaso, Luca; Angioni, Maria Maddalena; Raschioni, Carlotta; Testore, Elena; Roncalli, Massimo; Giordano, Silvia; Columbano, Amedeo

    2014-11-01

    Although the growth suppressing Hippo pathway has been implicated in hepatocellular carcinoma (HCC) pathogenesis, it is unknown at which stage of hepatocarcinogenesis its dysregulation occurs. We investigated in rat and human preneoplastic lesions whether overexpression of the transcriptional co-activator Yes-associated protein (YAP) is an early event. The experimental model used is the resistant-hepatocyte (R-H) rat model. Gene expression was determined by qRT-PCR or immunohistochemistry. Forward genetic experiments were performed in human HCC cells and in murine oval cells. All foci of preneoplastic hepatocytes, generated in rats 4weeks after diethylnitrosamine (DENA) treatment, displayed YAP accumulation. This was associated with down-regulation of the β-TRCP ligase, known to mediate YAP degradation, and of microRNA-375, targeting YAP. YAP accumulation was paralleled by the up-regulation of its target genes. Increased YAP expression was also observed in human early dysplastic nodules and adenomas. Animal treatment with verteporfin (VP), which disrupts the formation of the YAP-TEAD complex, significantly reduced preneoplastic foci and oval cell proliferation. In vitro experiments confirmed that VP-mediated YAP inhibition impaired cell growth in HCC and oval cells; notably, oval cell transduction with wild type or active YAP conferred tumorigenic properties in vitro and in vivo. These results suggest that (i) YAP overexpression is an early event in rat and human liver tumourigenesis; (ii) it is critical for the clonal expansion of carcinogen-initiated hepatocytes and oval cells, and (iii) VP-induced disruption of the YAP-TEAD interaction may provide an important approach for the treatment of YAP-overexpressing cancers. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  18. Discrete event simulation for petroleum transfers involving harbors, refineries and pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Marcella S.R.; Lueders, Ricardo; Delgado, Myriam R.B.S. [Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil)

    2009-07-01

    Nowadays a great effort has been spent by companies to improve their logistics in terms of programming of events that affect production and distribution of products. In this case, simulation can be a valuable tool for evaluating different behaviors. The objective of this work is to build a discrete event simulation model for scheduling of operational activities in complexes containing one harbor and two refineries interconnected by a pipeline infrastructure. The model was developed in Arena package, based on three sub-models that control pier allocation, loading of tanks, and transfers to refineries through pipelines. Preliminary results obtained for a given control policy, show that profit can be calculated by taking into account many parameters such as oil costs on ships, pier using, over-stay of ships and interface costs. Such problem has already been considered in the literature but using different strategies. All these factors should be considered in a real-world operation where decision making tools are necessary to obtain high returns. (author)

  19. The Longitudinal Relation Between Accumulation of Adverse Life Events and Body Mass Index From Early Adolescence to Young Adulthood

    NARCIS (Netherlands)

    Elsenburg, Leonie K.; Smidt, Nynke; Liefbroer, Aart C.

    2017-01-01

    Objective: Stressors, such as adverse life events, can cause weight changes through behavioral and biological mechanisms. Whether the accumulation of adverse life events is related to body mass index (BMI) across multiple time points from early adolescence to young adulthood has not been investigate

  20. Patterns in early diffusion-weighted MRI in children with haemolytic uraemic syndrome and CNS involvement

    Energy Technology Data Exchange (ETDEWEB)

    Donnerstag, Frank; Ding, Xiaoqi; Bueltmann, Eva; Zajaczek, Jan; Lanfermann, Heinrich [Hannover Medical School, Institute of Diagnostic and Therapeutic Neuroradiology, Hannover (Germany); Pape, Lars; Das, Anibh Martin; Ehrich, Jochen; Hartmann, Hans [Hannover Medical School, Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Hannover (Germany); Luecke, Thomas [Hannover Medical School, Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Hannover (Germany); University of Bochum, Department of Neuropediatrics, Pediatric Hospital, Bochum (Germany); Hoy, Ludwig [Hannover Medical School, Institute of Biometrics, Hannover (Germany)

    2012-03-15

    Diffusion-weighted imaging (DWI) in children with diarrhoea associated haemolytic uraemic syndrome (D+HUS) and cerebral involvement was evaluated retrospectively. DWI within 24 h of onset of neurological symptoms. The apparent diffusion coefficient (ADC) was measured in grey/white matter and correlated with clinical and laboratory findings. DWI was abnormal in all. Abnormal ADC was detected in the supratentorial white matter (6/12) and cortex (1/12), the basal ganglia (5/12), the thalami (4/12), and the cerebellum (1/12). ADC was reduced in 5/12, increased in 4/12, and both in 3/12. Mean serum sodium was lower in patients with DWI abnormalities affecting the white matter (6/12), than in those with basal ganglia/thalamic involvement (6/12). Neurological outcome was normal in 4/11 and abnormal in 7/11, and 1 patient died, outcome did not correlate to either localisation or type of DWI abnormality. In D+HUS with neurological symptoms, early DWI may reveal abnormal ADC not only in the basal ganglia/thalami, but also in the white matter/cortex. Besides thrombotic microangiopathy, toxic effects of shiga toxin, azotaemia and hyponatraemia / hypoosmolality may be involved in cerebral involvement in children with D+HUS. Findings on early MRI seem not to predict clinical course or outcome. (orig.)

  1. Effect of personal involvement in traumatic events on memory: the case of the Dolphinarium explosion.

    Science.gov (United States)

    Nachson, Israel; Slavutskay-Tsukerman, Irena

    2010-04-01

    The association between memories of the terrorist explosion at the Dolphinarium discotheque in Tel Aviv and the level of personal involvement in the explosion was investigated. Memories of injured victims, uninjured eyewitnesses, and uninvolved controls who learned about the explosion from the mass media were compared. It was expected that memory of the explosion would be most and least detailed and accurate among the victims and the controls, respectively. The participants responded to an open-ended question about the explosion, as well as to specific and multiple-choice questions. Data analyses showed that the victims and the eyewitnesses remembered more details than the controls, and that the victims remembered both central and peripheral details more accurately than the other participants. Degree of involvement in the same traumatic experience was thus shown to be differentially associated with memory accuracy.

  2. Conservatism in effective dose calculations for accident events involving fuel reprocessing waste tanks.

    Science.gov (United States)

    Bevelacqua, J J

    2011-07-01

    Conservatism in the calculation of the effective dose following an airborne release from an accident involving a fuel reprocessing waste tank is examined. Within the regulatory constraints at the Hanford Site, deterministic effective dose calculations are conservative by at least an order of magnitude. Deterministic calculations should be used with caution in reaching decisions associated with required safety systems and mitigation philosophy related to the accidental release of airborne radioactive material to the environment.

  3. Regulation of signaling events involved in the pathophysiology of neovascular AMD

    OpenAIRE

    Wang, Haibo; Hartnett, M. Elizabeth

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is a complex disease in which an individual’s genetic predisposition is affected by aging and environmental stresses, which trigger signaling pathways involving inflammation, oxidation, and/or angiogenesis in the RPE cells and choroidal endothelial cells (CECs), to lead to vision loss from choroidal neovascularization. Antiangiogenic therapies have greatly improved clinical outcomes in the last decade; however, vision improves in less than ha...

  4. Television viewing through ages 2-5 years and bullying involvement in early elementary school.

    Science.gov (United States)

    Verlinden, Marina; Tiemeier, Henning; Veenstra, René; Mieloo, Cathelijne L; Jansen, Wilma; Jaddoe, Vincent W V; Raat, Hein; Hofman, Albert; Verhulst, Frank C; Jansen, Pauline W

    2014-02-12

    High television exposure time at young age has been described as a potential risk factor for developing behavioral problems. However, less is known about the effects of preschool television on subsequent bullying involvement. We examined the association between television viewing time through ages 2-5 and bullying involvement in the first grades of elementary school. We hypothesized that high television exposure increases the risk of bullying involvement. TV viewing time was assessed repeatedly in early childhood using parental report. To combine these repeated assessments we used latent class analysis. Four exposure classes were identified and labeled "low", "mid-low", "mid-high" and "high". Bullying involvement was assessed by teacher questionnaire (n=3423, mean age 6.8 years). Additionally, peer/self-report of bullying involvement was obtained using a peer nomination procedure (n=1176, mean age 7.6 years). We examined child risk of being a bully, victim or a bully-victim (compared to being uninvolved in bullying). High television exposure class was associated with elevated risks of bullying and victimization. Also, in both teacher- and child-reported data, children in the high television exposure class were more likely to be a bully-victim (OR=2.11, 95% CI: 1.42-3.13 and OR=3.68, 95% CI: 1.75-7.74 respectively). However, all univariate effect estimates attenuated and were no longer statistically significant once adjusted for maternal and child covariates. The association between television viewing time through ages 2-5 and bullying involvement in early elementary school is confounded by maternal and child socio-demographic characteristics.

  5. Television viewing through ages 2-5 years and bullying involvement in early elementary school

    Science.gov (United States)

    2014-01-01

    Background High television exposure time at young age has been described as a potential risk factor for developing behavioral problems. However, less is known about the effects of preschool television on subsequent bullying involvement. We examined the association between television viewing time through ages 2-5 and bullying involvement in the first grades of elementary school. We hypothesized that high television exposure increases the risk of bullying involvement. Method TV viewing time was assessed repeatedly in early childhood using parental report. To combine these repeated assessments we used latent class analysis. Four exposure classes were identified and labeled “low”, “mid-low”, “mid-high” and “high”. Bullying involvement was assessed by teacher questionnaire (n = 3423, mean age 6.8 years). Additionally, peer/self-report of bullying involvement was obtained using a peer nomination procedure (n = 1176, mean age 7.6 years). We examined child risk of being a bully, victim or a bully-victim (compared to being uninvolved in bullying). Results High television exposure class was associated with elevated risks of bullying and victimization. Also, in both teacher- and child-reported data, children in the high television exposure class were more likely to be a bully-victim (OR = 2.11, 95% CI: 1.42-3.13 and OR = 3.68, 95% CI: 1.75-7.74 respectively). However, all univariate effect estimates attenuated and were no longer statistically significant once adjusted for maternal and child covariates. Conclusions The association between television viewing time through ages 2-5 and bullying involvement in early elementary school is confounded by maternal and child socio-demographic characteristics. PMID:24520886

  6. PERFORMANCE EVALUATION OF DISCRETE EVENT SYSTEMS INVOLVING HENSTOCK-KURZWEIL INTEGRAL

    Institute of Scientific and Technical Information of China (English)

    Calin CIUFUDEAN; Bianca SATCO

    2009-01-01

    This paper presents a study on the performance of flexible manufacturing systems (FMSs), by using discrete event system (DES) models, considering resource losses modelled by a parameter entitled coverage factor. We conclude that the resources cell loss distribution between the tasks of a FSM is a real function that cannot be integrated, in order to calculate its primitive, in the classical sense of Riemann or Lebesgue, but only in the sense of Henstock-Kurzweil integral. Our result allows one to study more general processes where highly oscillatory functions occur. The method used to deduce the function describing the resources cell loss distribution is compared with a classical method related in the literature, respectively rational interpolants. An example has been constructed to emphasize what we believe to be, new approaches.

  7. Resolving Early Signaling Events in T-Cell Activation Leading to IL-2 and FOXP3 Transcription

    Directory of Open Access Journals (Sweden)

    Jeffrey P. Perley

    2014-11-01

    Full Text Available Signal intensity and feedback regulation are known to be major factors in the signaling events stemming from the T-cell receptor (TCR and its various coreceptors, but the exact nature of these relationships remains in question. We present a mathematical model of the complex signaling network involved in T-cell activation with cross-talk between the Erk, calcium, PKC and mTOR signaling pathways. The model parameters are adjusted to fit new and published data on TCR trafficking, Zap70, calcium, Erk and Isignaling. The regulation of the early signaling events by phosphatases, CD45 and SHP1, and the TCR dynamics are critical to determining the behavior of the model. Additional model corroboration is provided through quantitative and qualitative agreement with experimental data collected under different stimulating and knockout conditions. The resulting model is analyzed to investigate how signal intensity and feedback regulation affect TCR- and coreceptor-mediated signal transduction and their downstream transcriptional profiles to predict the outcome for a variety of stimulatory and knockdown experiments. Analysis of the model shows that: (1 SHP1 negative feedback is necessary for preventing hyperactivity in TCR signaling; (2 CD45 is required for TCR signaling, but also partially suppresses it at high expression levels; and (3 elevated FOXP3 and reduced IL-2 signaling, an expression profile often associated with T regulatory cells (Tregs, is observed when the system is subjected to weak TCR and CD28 costimulation or a severe reduction in CD45 activity.

  8. Does Silent Reading Speed in Normal Adult Readers Depend on Early Visual Processes? Evidence from Event-Related Brain Potentials

    Science.gov (United States)

    Korinth, Sebastian Peter; Sommer, Werner; Breznitz, Zvia

    2012-01-01

    Little is known about the relationship of reading speed and early visual processes in normal readers. Here we examined the association of the early P1, N170 and late N1 component in visual event-related potentials (ERPs) with silent reading speed and a number of additional cognitive skills in a sample of 52 adult German readers utilizing a Lexical…

  9. A deployable in vivo EPR tooth dosimeter for triage after a radiation event involving large populations

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Benjamin B., E-mail: Benjamin.B.Williams@dartmouth.edu [Dartmouth Physically Based Biodosimetry Center for Medical Countermeasures Against Radiation (Dart-Dose CMCR), Dartmouth Medical School, Hanover, NH 03768 (United States); Section of Radiation Oncology, Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH (United States); Dong, Ruhong [Dartmouth Physically Based Biodosimetry Center for Medical Countermeasures Against Radiation (Dart-Dose CMCR), Dartmouth Medical School, Hanover, NH 03768 (United States); Flood, Ann Barry [Dartmouth Physically Based Biodosimetry Center for Medical Countermeasures Against Radiation (Dart-Dose CMCR), Dartmouth Medical School, Hanover, NH 03768 (United States); Clin-EPR, LLC, Lyme, NH (United States); Grinberg, Oleg [Clin-EPR, LLC, Lyme, NH (United States); Kmiec, Maciej; Lesniewski, Piotr N.; Matthews, Thomas P.; Nicolalde, Roberto J.; Raynolds, Tim [Dartmouth Physically Based Biodosimetry Center for Medical Countermeasures Against Radiation (Dart-Dose CMCR), Dartmouth Medical School, Hanover, NH 03768 (United States); Salikhov, Ildar K. [Clin-EPR, LLC, Lyme, NH (United States); Swartz, Harold M. [Dartmouth Physically Based Biodosimetry Center for Medical Countermeasures Against Radiation (Dart-Dose CMCR), Dartmouth Medical School, Hanover, NH 03768 (United States); Clin-EPR, LLC, Lyme, NH (United States)

    2011-09-15

    In order to meet the potential need for emergency large-scale retrospective radiation biodosimetry following an accident or attack, we have developed instrumentation and methodology for in vivo electron paramagnetic resonance spectroscopy to quantify concentrations of radiation-induced radicals within intact teeth. This technique has several very desirable characteristics for triage, including independence from confounding biologic factors, a non-invasive measurement procedure, the capability to make measurements at any time after the event, suitability for use by non-expert operators at the site of an event, and the ability to provide immediate estimates of individual doses. Throughout development there has been a particular focus on the need for a deployable system, including instrumental requirements for transport and field use, the need for high throughput, and use by minimally trained operators. Numerous measurements have been performed using this system in clinical and other non-laboratory settings, including in vivo measurements with unexposed populations as well as patients undergoing radiation therapies. The collection and analyses of sets of three serially-acquired spectra with independent placements of the resonator, in a data collection process lasting approximately 5 min, provides dose estimates with standard errors of prediction of approximately 1 Gy. As an example, measurements were performed on incisor teeth of subjects who had either received no irradiation or 2 Gy total body irradiation for prior bone marrow transplantation; this exercise provided a direct and challenging test of our capability to identify subjects who would be in need of acute medical care. -- Highlights: > Advances in radiation biodosimetry are needed for large-scale emergency response. > Radiation-induced radicals in tooth enamel can be measured using in vivo EPR. > A novel transportable spectrometer was applied in the laboratory and at remote sites. > The current instrument

  10. Factors involved in the inflammatory events of cervical ripening in humans

    Directory of Open Access Journals (Sweden)

    Wang Hong

    2004-10-01

    Full Text Available Abstract Background Cervical ripening is an inflammatory reaction. The glucocorticoid receptor (GR mediates glucocorticoid anti-inflammatory reactions, whereas nuclear factor (NFkappaB is a key pro-inflammatory transcription factor. Prostaglandins as well as platelet activating factor (PAF are inflammatory mediators. Inducible nitric oxide synthase (iNOS regulates the level of nitric oxide (NO in response to various inflammatory stimuli. We hypothesize that a changed biological response to glucocorticoids could be a mechanism regulating the inflammatory events resulting in cervical ripening. Methods We monitored GR and NFkappaB, prostaglandin synthases cyclooxygenase (COX-1 and -2, iNOS, as well as the PAF-receptor (PAF-R in the uterine cervix from term pregnant women (with unripe cervices before the onset of labor (TP, immediately after parturition (PP, as compared to non-pregnant (NP, using immunohistochemistry and RT-PCR. Results The GR protein was detected by immunohistochemistry in the nuclei of stroma and squamous epithelium (SQ. Stromal GR staining was increased in TP as compared to the NP group and decreased again after parturition. GR staining in SQ was decreased after parturition as compared to term. NFkappaB was present in SQ and glandular epithelium (GE, stroma and vascular endothelium. Increased nuclear NFkappaB staining was observed postpartum as compared to term pregnancy in stroma and GE. Stromal immunostaining for COX-1 as well as COX-2 was increased in the TP and PP groups as compared to the NP, and GE displayed an intensely increased COX-2 immunostaining at term and postpartum. Stromal PAF-R immunostaining was highest at term, while it was greatly increased in GE postpartum. No difference in the immunostaining for iNOS was found between the groups. RT-PCR showed a predominance of GRalpha to GRbeta mRNA in cervical tissue. The COX-2 mRNA level was increased in the PP group as compared to the TP group. Conclusions There is a

  11. How to Cope with the Rare Human Error Events Involved with organizational Factors in Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sa Kil; Luo, Meiling; Lee, Yong Hee [Korea Atomic Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    The current human error guidelines (e.g. US DOD handbooks, US NRC Guidelines) are representative tools to prevent human errors. These tools, however, have limits that they do not adapt all operating situations and circumstances such as design base events. In other words, these tools are only adapted foreseeable standardized operating situations and circumstances. In this study, our research team proposed an evidence-based approach such as UK's safety case to coping with the rare human error events such as TMI, Chernobyl, Fukushima accidents. These accidents are representative events involved with rare human errors. Our research team defined the 'rare human errors' as the follow three characterized events; Extremely low frequency Extremely high complicated structure Extremely serious damage of human life and property A safety case is a structured argument, supported by evidence, intended to justify that a system is acceptably safe. The definition by UK defense standard 00-56 issue 4 states that such an evidence-based approach can be contrast with a prescriptive approach to safety certification, which require safety to be justified using a prescribed process. Safety managements and safety regulatory activities based on safety case are effective to control organizational factors in terms of integrated safety management. Especially safety issues relevant with public acceptance are useful to provide practical evidences to the public reasonably. European Union including UK has developed the concept of engineered safety management system to deal with public acceptance using the safety case. In Korea nuclear industry, the Korean Atomic Research Institute has firstly performed a basic research to adapt the safety case in the field of radioactive waste according to the IAEA SSG-23(KAERI/TR-4497, 4531). Excepting the radioactive waste, there is no try to adapt the safety case yet. Most incidents and accidents involved human during operating NPPs have a tendency

  12. Early somatosensory event-related potentials reveal attentional bias for internal stimuli in social anxiety.

    Science.gov (United States)

    Kanai, Yoshihiro; Nittono, Hiroshi; Kubo, Kenta; Sasaki-Aoki, Shoko; Iwanaga, Makoto

    2012-03-01

    The present study used event-related brain potentials (ERPs) to investigate allocation of attentional resources to internal and external stimuli in individuals with social anxiety. High and low socially anxious individuals were presented with depictions of various facial expressions or household objects, followed by an internal (vibration presented to the finger) or external probe (the letter "E"). Participants were told that the vibration signals physiological changes and were asked to detect both probes. High socially anxious individuals showed larger front-central N140 amplitudes in response to vibratory internal probes as compared to non-anxious controls. ERPs elicited by picture stimuli and external probes and reaction times in response to both probe types did not differ between high and low social anxiety individuals. Early somatosensory ERPs reveal an attentional bias for internal stimuli that does not appear in overt behavior.

  13. Auditory event-related brain potentials for an early discrimination between normal and pathological brain aging

    Institute of Scientific and Technical Information of China (English)

    Juliana Dushanova; Mario Christov

    2013-01-01

    The brain as a system with gradually decreasing resources maximizes its chances by reorganizing neural networks to ensure efficient performance. Auditory event-related potentials were recorded in 28 healthy volunteers comprising 14 young and 14 elderly subjects in auditory discrimination motor task (low frequency tone – right hand movement and high frequency tone – left hand movement). The amplitudes of the sensory event-related potential components (N1, P2) were more pronounced with increasing age for either tone and this effect for P2 amplitude was more pronounced in the frontal region. The latency relationship of N1 between the groups was tone-dependent, while that of P2 was tone-independent with a prominent delay in the elderly group over all brain regions. The amplitudes of the cognitive components (N2, P3) diminished with increasing age and the hemispheric asymmetry of N2 (but not for P3) reduced with increasing age. Prolonged N2 latency with increasing age was widespread for either tone while between-group difference in P3 latency was tone-dependent. High frequency tone stimulation and movement requirements lead to P3 delay in the elderly group. The amplitude difference of the sensory components between the age groups could be due to a general greater alertness, less expressed habituation, or decline in the ability to retreat attentional resources from the stimuli in the elderly group. With aging, a neural circuit reorganization of the brain activity affects the cognitive processes. The approach used in this study is useful for an early discrimination between normal and pathological brain aging for early treatment of cognitive alterations and dementia.

  14. Multiple Evolutionary Events Involved in Maintaining Homologs of Resistance to Powdery Mildew 8 in Brassica napus

    Science.gov (United States)

    Li, Qin; Li, Jing; Sun, Jin-Long; Ma, Xian-Feng; Wang, Ting-Ting; Berkey, Robert; Yang, Hui; Niu, Ying-Ze; Fan, Jing; Li, Yan; Xiao, Shunyuan; Wang, Wen-Ming

    2016-01-01

    The Resistance to Powdery Mildew 8 (RPW8) locus confers broad-spectrum resistance to powdery mildew in Arabidopsis thaliana. There are four Homologous to RPW8s (BrHRs) in Brassica rapa and three in Brassica oleracea (BoHRs). Brassica napus (Bn) is derived from diploidization of a hybrid between B. rapa and B. oleracea, thus should have seven homologs of RPW8 (BnHRs). It is unclear whether these genes are still maintained or lost in B. napus after diploidization and how they might have been evolved. Here, we reported the identification and sequence polymorphisms of BnHRs from a set of B. napus accessions. Our data indicated that while the BoHR copy from B. oleracea is highly conserved, the BrHR copy from B. rapa is relatively variable in the B. napus genome owing to multiple evolutionary events, such as gene loss, point mutation, insertion, deletion, and intragenic recombination. Given the overall high sequence homology of BnHR genes, it is not surprising that both intragenic recombination between two orthologs and two paralogs were detected in B. napus, which may explain the loss of BoHR genes in some B. napus accessions. When ectopically expressed in Arabidopsis, a C-terminally truncated version of BnHRa and BnHRb, as well as the full length BnHRd fused with YFP at their C-termini could trigger cell death in the absence of pathogens and enhanced resistance to powdery mildew disease. Moreover, subcellular localization analysis showed that both BnHRa-YFP and BnHRb-YFP were mainly localized to the extra-haustorial membrane encasing the haustorium of powdery mildew. Taken together, our data suggest that the duplicated BnHR genes might have been subjected to differential selection and at least some may play a role in defense and could serve as resistance resource in engineering disease-resistant plants. PMID:27493652

  15. Multiple Evolutionary Events Involved in Maintaining Homologs of Resistance to Powdery Mildew 8 in Brassica napus.

    Science.gov (United States)

    Li, Qin; Li, Jing; Sun, Jin-Long; Ma, Xian-Feng; Wang, Ting-Ting; Berkey, Robert; Yang, Hui; Niu, Ying-Ze; Fan, Jing; Li, Yan; Xiao, Shunyuan; Wang, Wen-Ming

    2016-01-01

    The Resistance to Powdery Mildew 8 (RPW8) locus confers broad-spectrum resistance to powdery mildew in Arabidopsis thaliana. There are four Homologous to RPW8s (BrHRs) in Brassica rapa and three in Brassica oleracea (BoHRs). Brassica napus (Bn) is derived from diploidization of a hybrid between B. rapa and B. oleracea, thus should have seven homologs of RPW8 (BnHRs). It is unclear whether these genes are still maintained or lost in B. napus after diploidization and how they might have been evolved. Here, we reported the identification and sequence polymorphisms of BnHRs from a set of B. napus accessions. Our data indicated that while the BoHR copy from B. oleracea is highly conserved, the BrHR copy from B. rapa is relatively variable in the B. napus genome owing to multiple evolutionary events, such as gene loss, point mutation, insertion, deletion, and intragenic recombination. Given the overall high sequence homology of BnHR genes, it is not surprising that both intragenic recombination between two orthologs and two paralogs were detected in B. napus, which may explain the loss of BoHR genes in some B. napus accessions. When ectopically expressed in Arabidopsis, a C-terminally truncated version of BnHRa and BnHRb, as well as the full length BnHRd fused with YFP at their C-termini could trigger cell death in the absence of pathogens and enhanced resistance to powdery mildew disease. Moreover, subcellular localization analysis showed that both BnHRa-YFP and BnHRb-YFP were mainly localized to the extra-haustorial membrane encasing the haustorium of powdery mildew. Taken together, our data suggest that the duplicated BnHR genes might have been subjected to differential selection and at least some may play a role in defense and could serve as resistance resource in engineering disease-resistant plants.

  16. Multiple evolutionary events involved in maintaining homologs of Resistance to Powdery Mildew 8 in Brassica napus

    Directory of Open Access Journals (Sweden)

    Qin Li

    2016-07-01

    Full Text Available The Resistance to Powdery Mildew 8 (RPW8 locus confers broad-spectrum resistance to powdery mildew in Arabidopsis thaliana. There are four Homologous to RPW8s (BrHRs in Brassica rapa and three in B. oleracea (BoHRs. B. napus (Bn is derived from diploidization of a hybrid between B. rapa and B. oleracea, thus should have seven homologs of RPW8 (BnHRs. It is unclear whether these genes are still maintained or lost in B. napus after diploidization and how they might have been evolved. Here we reported the identification and sequence polymorphisms of BnHRs from a set of B. napus accessions. Our data indicated that while the BoHR copy from B. oleracea is highly conserved, the BrHR copy from B. rapa is relatively variable in the B. napus genome owing to multiple evolutionary events, such as gene loss, point mutation, insertion, deletion and intragenic recombination. Given the overall high sequence homology of BnHR genes, it is not surprising that both intragenic recombination between two orthologs and two paralogs were detected in B. napus, which may explain the loss of BoHR genes in some B. napus accessions. When ectopically expressed in Arabidopsis, a C-terminally truncated version of BnHRa and BnHRb, as well as the full length BnHRd fused with YFP at their C-termini could trigger cell death in the absence of pathogens and enhanced resistance to powdery mildew disease. Moreover, subcellular localization analysis showed that both BnHRa-YFP and BnHRb-YFP were mainly localized to the extra-haustorial membrane (EHM encasing the haustorium of powdery mildew. Taken together, our data suggest that the duplicated BnHR genes might have been subjected to differential selection and at least some may play a role in defense and could serve as resistance resource in engineering disease-resistant plants.

  17. A human xenograft model for testing early events of epithelial neoplastic invasion

    Science.gov (United States)

    McCANDLESS, JOHN R.; CRESS, ANNE E.; RABINOVITZ, ISAAC; PAYNE, CLAIRE M.; BOWDEN, G. TIM; KNOX, J. DAVID; NAGLE, RAY B.

    2017-01-01

    We report on a model of human prostate tumor cell invasion using the SCID (severe combined immunodeficient) mouse diaphragm. Tumor cells were injected into SCID mice intraperitoneally and the diaphragms harvested three to five weeks later. Electron microscopy showed tumor cell penetration of the mesothelial cell layer and adhesion to the underlying basement membrane on the inferior surface of the mouse diaphragm, where colonies developed. Immunohistochemistry showed invasion by tumor cells through the basement membrane into the muscle of the diaphragm, presence of human tumor cells among the muscle cells and the presence of selected proteins on the invasion front of the tumor cells. Digital image analysis enabled quantitative comparison of events in the metastatic cascade by variants of the tumor cell line and evaluation of the effectiveness of a putative tumor inhibitor. Results suggest that the SCID mouse diaphragm model is a convenient, effective, easily oriented and reproducible in vivo model of the early events associated with human prostate tumor cell invasion. PMID:21533373

  18. New Early Jurassic Tetrapod Assemblages Constrain Triassic-Jurassic Tetrapod Extinction Event

    Science.gov (United States)

    Olsen, P. E.; Shubin, N. H.; Anders, M. H.

    1987-08-01

    The discovery of the first definitively correlated earliest Jurassic (200 million years before present) tetrapod assemblage (Fundy basin, Newark Supergroup, Nova Scotia) allows reevaluation of the duration of the Triassic-Jurassic tetrapod extinction event. Present are tritheledont and mammal-like reptiles, prosauropod, theropod, and ornithischian dinosaurs, protosuchian and sphenosuchian crocodylomorphs, sphenodontids, and hybodont, semionotid, and palaeonisciform fishes. All of the families are known from Late Triassic and Jurassic strata from elsewhere; however, pollen and spore, radiometric, and geochemical correlation indicate an early Hettangian age for these assemblages. Because all ``typical Triassic'' forms are absent from these assemblages, most Triassic-Jurassic tetrapod extinctions occurred before this time and without the introduction of new families. As was previously suggested by studies of marine invertebrates, this pattern is consistent with a global extinction event at the Triassic-Jurassic boundary. The Manicouagan impact structure of Quebec provides dates broadly compatible with the Triassic-Jurassic boundary and, following the impact theory of mass extinctions, may be implicated in the cause.

  19. Accuracy of episodic autobiographical memory in children with early thyroid hormone deficiency using a staged event

    Directory of Open Access Journals (Sweden)

    Karen A. Willoughby

    2014-07-01

    Full Text Available Autobiographical memory (AM is a highly constructive cognitive process that often contains memory errors. No study has specifically examined AM accuracy in children with abnormal development of the hippocampus, a crucial brain region for AM retrieval. Thus, the present study investigated AM accuracy in 68 typically and atypically developing children using a staged autobiographical event, the Children's Autobiographical Interview, and structural magnetic resonance imaging. The atypically developing group consisted of 17 children (HYPO exposed during gestation to insufficient maternal thyroid hormone (TH, a critical substrate for hippocampal development, and 25 children with congenital hypothyroidism (CH, who were compared to 26 controls. Groups differed significantly in the number of accurate episodic details recalled and proportion accuracy scores, with controls having more accurate recollections of the staged event than both TH-deficient groups. Total hippocampal volumes and anterior hippocampal volumes were positively correlated with proportion accuracy scores, but not total accurate episodic details, in HYPO and CH. In addition, greater severity of TH deficiency predicted lower proportion accuracy scores in both HYPO and CH. Overall, these results indicate that children with early TH deficiency have deficits in AM accuracy and that the anterior hippocampus may play a particularly important role in accurate AM retrieval.

  20. Laboratory tests to identify patients at risk of early major adverse events: a prospective pilot study.

    Science.gov (United States)

    Kaufman, M; Bebee, B; Bailey, J; Robbins, R; Hart, G K; Bellomo, R

    2014-10-01

    To test whether commonly measured laboratory variables can identify surgical patients at risk of major adverse events (death, unplanned intensive care unit (ICU) admission or rapid response team (RRT) activation). We conducted a prospective observational study in a surgical ward of a university-affiliated hospital in a cohort of 834 surgical patients admitted for >24 h. We applied a previously validated multivariable model-derived risk assessment to each combined set of common laboratory tests to identify patients at risk. We compared the clinical course of such patients with that of control patients from the same ward who had blood tests but were identified as low risk. We studied 7955 batches and 73,428 individual tests in 834 patients (males 55%; average age 65.8 ± 17.6 years). Among these patients, 66 (7.9%) were identified as 'high risk'. High-risk patients were older (75.9 vs 61.8 years of age; P identify surgical ward patients at risk of early major adverse events. Further studies are needed to assess whether such identification system can be used to trigger interventions that help improve patient outcomes. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

  1. Background- versus event-level biotic variability: Hyperthermals of the late Paleocene and early Eocene

    Science.gov (United States)

    Gibbs, S.; Murphy, B. H.; Pälike, H.

    2009-12-01

    The Paleocene-Eocene Thermal Maximum (PETM) was an abrupt global warming event 55 million years ago (Ma) which has received much attention in recent years as an analogue for anthropogenic carbon emissions. We now know that the PETM was not unique, but was perhaps the most extreme of a number of abrupt carbon cycle perturbations throughout the late Paleocene and early Eocene. These inferred transient warming events, or ‘hyperthermals’, all have characteristic negative carbon isotope excursions (CIE). Unlike the PETM, it is currently unclear whether there was a significant biotic response to these additional CIEs, and if so, whether the amplitude of response varied systematically with excursion magnitude. Here, we present high-resolution nannofossil records from a two million year interval spanning the Paleocene-Eocene boundary at Ocean Drilling Program (ODP) Site 1209 in the paleo-subequatorial Pacific. This interval, from ~55 to 53 Ma, includes the PETM, a second hyperthermal named the Eocene Thermal Maximum 2 (ETM2 or ‘Elmo’), and a further number of smaller excursions. These data allow us to look for common biotic signatures and to document the level of assemblage variability relative to the inferred levels of environmental change associated with each CIE. We use this dataset as a case-study for investigating different statistical means of quantifying and comparing biotic responses to background and event-level perturbation. Preliminary analyses suggest that, as expected, the PETM exhibited the greatest level of assemblage variability, well above background levels, followed in order of CIE magnitude by the ETM2. Several of the smaller excursions have no significant assemblage variability above background levels, pointing to a critical threshold level of environmental perturbation.

  2. Early Maternal Deprivation Enhances Voluntary Alcohol Intake Induced by Exposure to Stressful Events Later in Life

    Directory of Open Access Journals (Sweden)

    Sara Peñasco

    2015-01-01

    Full Text Available In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9, on voluntary alcohol intake in adolescent male and female Wistar rats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake.

  3. Early maternal deprivation enhances voluntary alcohol intake induced by exposure to stressful events later in life.

    Science.gov (United States)

    Peñasco, Sara; Mela, Virginia; López-Moreno, Jose Antonio; Viveros, María-Paz; Marco, Eva M

    2015-01-01

    In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9), on voluntary alcohol intake in adolescent male and female Wistar rats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v) was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake.

  4. Cryptotanshinone inhibits TNF-α-induced early atherogenic events in vitro.

    Science.gov (United States)

    Ahmad, Zuraini; Ng, Chin Theng; Fong, Lai Yen; Bakar, Nurul Ain Abu; Hussain, Nor Hayuti Mohd; Ang, Kok Pian; Ee, Gwendoline Cheng Lian; Hakim, Muhammad Nazrul

    2016-05-01

    Endothelial dysfunction has been implicated in the pathogenesis of atherosclerosis. Salvia miltiorrhiza (danshen) is a traditional Chinese medicine that has been effectively used to treat cardiovascular disease. Cryptotanshinone (CTS), a major lipophilic compound isolated from S. miltiorrhiza, has been reported to possess cardioprotective effects. However, the anti-atherogenic effects of CTS, particularly on tumor necrosis factor-α (TNF-α)-induced endothelial cell activation, are still unclear. This study aimed to determine the effect of CTS on TNF-α-induced increased endothelial permeability, monocyte adhesion, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), monocyte chemoattractant protein 1 (MCP-1) and impaired nitric oxide production in human umbilical vein endothelial cells (HUVECs), all of which are early events occurring in atherogenesis. We showed that CTS significantly suppressed TNF-α-induced increased endothelial permeability, monocyte adhesion, sICAM-1, sVCAM-1 and MCP-1, and restored nitric oxide production. These observations suggest that CTS possesses anti-inflammatory properties and could be a promising treatment for the prevention of cytokine-induced early atherogenesis.

  5. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. © 2015 Authors; published by Portland Press Limited.

  6. Early spring, severe frost events, and drought induce rapid carbon loss in high elevation meadows.

    Directory of Open Access Journals (Sweden)

    Chelsea Arnold

    Full Text Available By the end of the 20th century, the onset of spring in the Sierra Nevada mountain range of California has been occurring on average three weeks earlier than historic records. Superimposed on this trend is an increase in the presence of highly anomalous "extreme" years, where spring arrives either significantly late or early. The timing of the onset of continuous snowpack coupled to the date at which the snowmelt season is initiated play an important role in the development and sustainability of mountain ecosystems. In this study, we assess the impact of extreme winter precipitation variation on aboveground net primary productivity and soil respiration over three years (2011 to 2013. We found that the duration of snow cover, particularly the timing of the onset of a continuous snowpack and presence of early spring frost events contributed to a dramatic change in ecosystem processes. We found an average 100% increase in soil respiration in 2012 and 2103, compared to 2011, and an average 39% decline in aboveground net primary productivity observed over the same time period. The overall growing season length increased by 57 days in 2012 and 61 days in 2013. These results demonstrate the dependency of these keystone ecosystems on a stable climate and indicate that even small changes in climate can potentially alter their resiliency.

  7. Enhanced tocopherol levels during early germination events in Chamaerops humilis var. humilis seeds.

    Science.gov (United States)

    Siles, Laura; Alegre, Leonor; Tijero, Verónica; Munné-Bosch, Sergi

    2015-10-01

    Most angiosperms accumulate vitamin E in the form of tocopherols in seeds, exerting a protective antioxidant role. However, several palm trees principally accumulate tocotrienols, rather than tocopherols, in seeds, as it occurs in other monocots. To unravel the protective role of either tocopherols or tocotrienols against lipid peroxidation during seed germination in Chamaerops humilis var. humilis; seed viability, natural and induced germination capacity, seed water content, malondialdehyde levels (as an indicator of the extent of lipid peroxidation) and vitamin E levels (including both tocopherols and tocotrienols) were examined at various germination phases in a simulated, natural seed bank. At the very early stages of germination (operculum removal), malondialdehyde levels increased 2.8-fold, to decrease later up to 74%, thus indicating a transient lipid peroxidation at early stages of germination. Tocopherol levels were absent in quiescent seeds and did not increase during operculum removal, but increased later presumably dampening malondialdehyde accumulation. Thereafter, tocopherols continued increasing, while lipid peroxidation levels decreased. By contrast, tocotrienols levels remained constant or even decreased as germination progressed, showing no correlation with lipid peroxidation levels. We hypothesize that despite their high tocotrienol content, seeds synthesize tocopherols during germination to protect lipids from peroxidation events.

  8. Children's early child care and their mothers' later involvement with schools.

    Science.gov (United States)

    Crosnoe, Robert; Augustine, Jennifer March; Huston, Aletha C

    2012-01-01

    Theory and policy highlight the role of child care in preparing children for the transition into school. Approaching this issue in a different way, this study investigated whether children's care experiences before this transition promoted their mothers' school involvement after it, with the hypothesized mechanism for this link being the cultivation of children's social and academic skills. Analyses of 1,352 children (1 month-6 years) and parents in the NICHD Study of Early Child Care and Youth Development revealed that mothers were more involved at their children's schools when children had prior histories of high-quality nonparental care. This pattern, which was fairly stable across levels of maternal education and employment, was mediated by children's academic skills and home environments.

  9. Modeling evidences for global warming, Arctic seawater freshening, and sluggish oceanic circulation during the Early Toarcian anoxic event

    National Research Council Canada - National Science Library

    Dera, Guillaume; Donnadieu, Yannick

    2012-01-01

    ...). We show that, in association with stronger high‐latitude precipitation rates and enhanced continental runoff, the demise of polar sea ice due to the global warming event involved a regional freshening...

  10. A catastrophic event in Lake Geneva region during the Early Bronze Age?

    Science.gov (United States)

    Kremer, Katrina; Yrro, Blé; Marillier, François; Hilbe, Michael; Corboud, Pierre; Rachoud-Schneider, Anne-Marie; Girardclos, Stéphanie

    2013-04-01

    Similarly to steep oceanic continental margins, lake slopes can collapse, producing large sublacustrine landslides and tsunamis. Lake sediments are excellent natural archives of such mass movements and their study allows the reconstructions of these prehistoric events, such as the 563 AD large tsunami over Lake Geneva (Kremer et al, 2012). In Lake Geneva, more than 100 km of high-resolution seismic reflection profiles reveal the late Holocene sedimentation history. The seismic record shows a succession of five large lens-shaped seismic units (A to I), characterized by transparent/chaotic seismic facies with irregular lower boundaries, and interpreted as mass-movement deposits. These units are interbedded with parallel, continuous and strong amplitude reflections, interpreted as the 'background' lake sediments. The oldest dated mass movement (Unit D) covers a surface of 22 km2 in the deep basin, near the city of Lausanne. This deposit has an estimated minimum volume of 0.18 km3 and thus was very likely tsunamigenic (Kremer et al, 2012). A 12-m-long sediment core confirms the seismic interpretation of the mass movement unit and shows that the uppermost 3 m of Unit D are characterized by deformed hemipelagic sediments topped by a 5 cm thick turbidite. This deposit can be classified as a slump whose scar can be interpreted in the seismic data and visualized by multibeam bathymetry. This slump of Lausanne was likely triggered by an earthquake but a spontaneous slope collapse cannot be excluded (Girardclos et al, 2007). Radiocarbon dating of plant macro-remains reveals that the unit D happened during Early Bronze Age. Three other mass wasting deposits occurred during the same time period and may have been triggered during the same event, either by a single earthquake or by a tsunami generated by the slump of Lausanne. Although the exact trigger mechanism of the all these mass-wasting deposits remains unknown, a tsunami likely generated by this event may have affected the

  11. A pilot study on factors involved with work participation in the early stages of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Karin Van der Hiele

    Full Text Available Up to 30% of recently diagnosed MS patients lose their jobs in the first four years after diagnosis. Taking into account the personal and socio-economic importance of sustaining employment, it is of the utmost importance to examine factors involved with work participation.To investigate differences in self-reported functioning in recently diagnosed MS patients with and without a paid job.Self-reports of physical and cognitive functioning, depression, anxiety and fatigue were gathered from 44 relapsing-remitting MS patients diagnosed within 3 years.Patients with a paid job (57% reported better physical functioning (p<0.001, better memory functioning (p = 0.01 and a lower physical impact of fatigue (p = 0.018 than patients without a paid job. Physical functioning was the main predictor of employment status in a logistic regression model. In those with a paid job better memory functioning (r = 0.54, p = 0.005 and a lower social impact of fatigue (r =  -0.46, p = 0.029 correlated with an increased number of working hours.Better physical functioning is the primary factor involved with increased work participation in early MS. Better self-reported memory functioning and less social fatigue were associated with increased working hours. These findings highlight the importance of battling these symptoms in the early stages of MS.

  12. Search for the genes involved in oocyte maturation and early embryo development in the hen

    Directory of Open Access Journals (Sweden)

    Blesbois Elisabeth

    2008-02-01

    Full Text Available Abstract Background The initial stages of development depend on mRNA and proteins accumulated in the oocyte, and during these stages, certain genes are essential for fertilization, first cleavage and embryonic genome activation. The aim of this study was first to search for avian oocyte-specific genes using an in silico and a microarray approaches, then to investigate the temporal and spatial dynamics of the expression of some of these genes during follicular maturation and early embryogenesis. Results The in silico approach allowed us to identify 18 chicken homologs of mouse potential oocyte genes found by digital differential display. Using the chicken Affymetrix microarray, we identified 461 genes overexpressed in granulosa cells (GCs and 250 genes overexpressed in the germinal disc (GD of the hen oocyte. Six genes were identified using both in silico and microarray approaches. Based on GO annotations, GC and GD genes were differentially involved in biological processes, reflecting different physiological destinations of these two cell layers. Finally we studied the spatial and temporal dynamics of the expression of 21 chicken genes. According to their expression patterns all these genes are involved in different stages of final follicular maturation and/or early embryogenesis in the chicken. Among them, 8 genes (btg4, chkmos, wee, zpA, dazL, cvh, zar1 and ktfn were preferentially expressed in the maturing occyte and cvh, zar1 and ktfn were also highly expressed in the early embryo. Conclusion We showed that in silico and Affymetrix microarray approaches were relevant and complementary in order to find new avian genes potentially involved in oocyte maturation and/or early embryo development, and allowed the discovery of new potential chicken mature oocyte and chicken granulosa cell markers for future studies. Moreover, detailed study of the expression of some of these genes revealed promising candidates for maternal effect genes in the

  13. Conflict monitoring and stimulus categorization processes involved in the prosocial attitude implicit association test: Evidence from event-related potentials.

    Science.gov (United States)

    Xiao, Fengqiu; Zheng, Zhiwei; Wang, Ya; Cui, Jifang; Chen, Yinghe

    2015-08-01

    The implicit association test (IAT) is a promising method used to assess individual implicit attitudes by indirectly measuring the strengths of associations between target and attribute categories. To date, the cognitive processes involved in the prosocial attitude IAT task have received little attention. The present study examined the temporal dynamics of the IAT that measures prosocial attitude using event-related potentials (ERPs). ERP results revealed enhanced N2 amplitudes for incongruent trials when compared with congruent trials and enhanced P300 amplitudes for congruent trials when compared with incongruent trials. In addition, the N2 amplitude differences were significantly correlated with individual prosocial behavior (the amount of donation). Our findings suggest that conflict monitoring and stimulus categorization processes are involved in the prosocial attitude IAT task and that the ERP indices of IATs that measure prosocial attitude may predict individual prosocial behavior.

  14. Effects of temporal trial-by-trial cuing on early and late stages of auditory processing: evidence from event-related potentials.

    Science.gov (United States)

    Lampar, Alexa; Lange, Kathrin

    2011-08-01

    Temporal-cuing studies show faster responding to stimuli at an attended versus unattended time point. Whether the mechanisms involved in this temporal orienting of attention are located early or late in the processing stream has not been answered unequivocally. To address this question, we measured event-related potentials in two versions of an auditory temporal cuing task: Stimuli at the uncued time point either required a response (Experiment 1) or did not (Experiment 2). In both tasks, attention was oriented to the cued time point, but attention could be selectively focused on the cued time point only in Experiment 2. In both experiments, temporal orienting was associated with a late positivity in the timerange of the P3. An early enhancement in the timerange of the auditory N1 was observed only in Experiment 2. Thus, temporal attention improves auditory processing at early sensory levels only when it can be focused selectively.

  15. Subsurface warming in the subpolar North Atlantic during rapid climate events in the Early and Mid-Pleistocene

    Science.gov (United States)

    Hernández-Almeida, Iván; Sierro, Francisco; Cacho, Isabel; Abel Flores, José

    2014-05-01

    A new high-resolution reconstruction of the temperature and salinity of the subsurface waters using paired Mg/Ca-δ18O measurements on the planktonic foraminifera Neogloboquadrina pachyderma sinistrorsa (sin.) was conducted on a deep-sea sediment core in the subpolar North Atlantic (Site U1314). This study aims to reconstruct millennial-scale subsurface hydrography variations during the Early and Mid-Pleistocene (MIS 31-19). These rapid climate events are characterized by abrupt shifts between warm/cold conditions, and ice-sheet oscillations, as evidenced by major ice rafting events recorded in the North Atlantic sediments (Hernández-Almeida et al., 2012), similar to those found during the Last Glacial period (Marcott et al, 2011). The Mg/Ca derived paleotemperature and salinity oscillations prior and during IRD discharges at Site U1314 are related to changes in intermediate circulation. The increases in Mg/Ca paleotemperatures and salinities during the IRD event are preceded by short episodes of cooling and freshening of subsurface waters. The response of the AMOC to this perturbation is an increased of warm and salty water coming from the south, transported to high latitudes in the North Atlantic beneath the thermocline. This process is accompanied by a southward shift in the convection cell from the Nordic Seas to the subpolar North Atlantic and better ventilation of the North Atlantic at mid-depths. Poleward transport of warm and salty subsurface subtropical waters causes intense basal melting and thinning of marine ice-shelves, that culminates in large-scale instability of the ice sheets, retreat of the grounding line and iceberg discharge. The mechanism proposed involves the coupling of the AMOC with ice-sheet dynamics, and would explain the presence of these fluctuations before the establishment of high-amplitude 100-kyr glacial cycles. Hernández-Almeida, I., Sierro, F.J., Cacho, I., Flores, J.A., 2012. Impact of suborbital climate changes in the North

  16. Involved-Site Image-Guided Intensity Modulated Versus 3D Conformal Radiation Therapy in Early Stage Supradiaphragmatic Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it [Department of Oncology, University of Torino, Torino (Italy); Ciammella, Patrizia [Radiation Therapy Unit, Department of Oncology and Advanced Technology, ASMN Hospital IRCCS, Reggio Emilia (Italy); Piva, Cristina; Ragona, Riccardo [Department of Oncology, University of Torino, Torino (Italy); Botto, Barbara [Hematology, Città della Salute e della Scienza, Torino (Italy); Gavarotti, Paolo [Hematology, University of Torino and Città della Salute e della Scienza, Torino (Italy); Merli, Francesco [Hematology Unit, ASMN Hospital IRCCS, Reggio Emilia (Italy); Vitolo, Umberto [Hematology, Città della Salute e della Scienza, Torino (Italy); Iotti, Cinzia [Radiation Therapy Unit, Department of Oncology and Advanced Technology, ASMN Hospital IRCCS, Reggio Emilia (Italy); Ricardi, Umberto [Department of Oncology, University of Torino, Torino (Italy)

    2014-06-01

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows for margin reduction and highly conformal dose distribution, with consistent advantages in sparing of normal tissues. The purpose of this retrospective study was to compare involved-site IG-IMRT with involved-site 3D conformal RT (3D-CRT) in the treatment of early stage Hodgkin lymphoma (HL) involving the mediastinum, with efficacy and toxicity as primary clinical endpoints. Methods and Materials: We analyzed 90 stage IIA HL patients treated with either involved-site 3D-CRT or IG-IMRT between 2005 and 2012 in 2 different institutions. Inclusion criteria were favorable or unfavorable disease (according to European Organization for Research and Treatment of Cancer criteria), complete response after 3 to 4 cycles of an adriamycin- bleomycin-vinblastine-dacarbazine (ABVD) regimen plus 30 Gy as total radiation dose. Exclusion criteria were chemotherapy other than ABVD, partial response after ABVD, total radiation dose other than 30 Gy. Clinical endpoints were relapse-free survival (RFS) and acute toxicity. Results: Forty-nine patients were treated with 3D-CRT (54.4%) and 41 with IG-IMRT (45.6%). Median follow-up time was 54.2 months for 3D-CRT and 24.1 months for IG-IMRT. No differences in RFS were observed between the 2 groups, with 1 relapse each. Three-year RFS was 98.7% for 3D-CRT and 100% for IG-IMRT. Grade 2 toxicity events, mainly mucositis, were recorded in 32.7% of 3D-CRT patients (16 of 49) and in 9.8% of IG-IMRT patients (4 of 41). IG-IMRT was significantly associated with a lower incidence of grade 2 acute toxicity (P=.043). Conclusions: RFS rates at 3 years were extremely high in both groups, albeit the median follow-up time is different. Acute tolerance profiles were better for IG-IMRT than for 3D-CRT. Our preliminary results support the clinical safety and efficacy of advanced RT planning and delivery techniques in patients affected with early stage HL, achieving complete

  17. When Business Gets Involved: A Case Study of Business Community Involvement in Minnesota's Early Childhood Education Policy

    Science.gov (United States)

    Kovach, Melissa

    2009-01-01

    The report details Minnesota's early childhood education (ECE) activities from 2003 to the present, with a particular focus on the role of the business community. Although the report illustrates how fact-based information, partnered with dedicated and well-connected people and organized task forces, creates change, there remain components of…

  18. When Business Gets Involved: A Case Study of Business Community Involvement In Illinois' Early Childhood Education Policy

    Science.gov (United States)

    Kovach, Melissa

    2009-01-01

    As the first state to offer universal preschool to three-year-olds, Illinois' experience with early childhood education (ECE) policy reform efforts offers lessons about how such change takes shape. This report details Illinois' ECE activities from 1992 to the present, with a particular focus on the business role in ECE policy. Lessons learned…

  19. Relation between change in blood pressure in acute stroke and risk of early adverse events and poor outcome

    DEFF Research Database (Denmark)

    Sandset, Else C; Murray, Gordon D; Bath, Philip M W;

    2012-01-01

    The Scandinavian Candesartan Acute Stroke Trial (SCAST) found no benefits of candesartan in acute stroke. In the present analysis we aim to investigate the effect of change in blood pressure during the first 2 days of stroke on the risk of early adverse events and poor outcome.......The Scandinavian Candesartan Acute Stroke Trial (SCAST) found no benefits of candesartan in acute stroke. In the present analysis we aim to investigate the effect of change in blood pressure during the first 2 days of stroke on the risk of early adverse events and poor outcome....

  20. Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events.

    Science.gov (United States)

    Noble, Linda J; Donovan, Frances; Igarashi, Takuji; Goussev, Staci; Werb, Zena

    2002-09-01

    Inflammation in general and proteinases generated as a result are likely mediators of early secondary pathogenesis after spinal cord injury. We report that matrix metalloproteinase-9 (MMP-9) plays an important role in blood-spinal cord barrier dysfunction, inflammation, and locomotor recovery. MMP-9 was present in the meninges and neurons of the uninjured cord. MMP-9 increased rapidly after a moderate contusion spinal cord injury, reaching a maximum at 24 hr, becoming markedly reduced by 72 hr, and not detectable at 7 d after injury. It was seen in glia, macrophages, neutrophils, and vascular elements in the injured spinal cord at 24 hr after injury. The natural tissue inhibitors of MMPs were unchanged over this time course. MMP-9-null mice exhibited significantly less disruption of the blood-spinal cord barrier, attenuation of neutrophil infiltration, and significant locomotor recovery compared with wild-type mice. Similar findings were observed in mice treated with a hydroxamic acid MMP inhibitor from 3 hr to 3 d after injury, compared with the vehicle controls. Moreover, the area of residual white matter at the lesion epicenter was significantly greater in the inhibitor-treated group. This study provides evidence that MMP-9 plays a key role in abnormal vascular permeability and inflammation within the first 3 d after spinal cord injury, and that blockade of MMPs during this critical period attenuates these vascular events and leads to improved locomotor recovery. Our findings suggest that early inhibition of MMPs may be an efficacious strategy for the spinal cord-injured patient.

  1. A Candida albicans early stage biofilm detachment event in rich medium

    Directory of Open Access Journals (Sweden)

    Nantel Andre

    2009-02-01

    Full Text Available Abstract Background Dispersal from Candida albicans biofilms that colonize catheters is implicated as a primary factor in the link between contaminated catheters and life threatening blood stream infections (BSI. Appropriate in vitro C. albicans biofilm models are needed to probe factors that induce detachment events. Results Using a flow through system to culture C. albicans biofilms we characterized a detachment process which culminates in dissociation of an entire early stage biofilm from a silicone elastomer surface. We analyzed the transcriptome response at time points that bracketed an abrupt transition in which a strong adhesive association with the surface is weakened in the initial stages of the process, and also compared batch and biofilm cultures at relevant time points. K means analysis of the time course array data revealed categories of genes with similar patterns of expression that were associated with adhesion, biofilm formation and glycoprotein biosynthesis. Compared to batch cultures the biofilm showed a pattern of expression of metabolic genes that was similar to the C. albicans response to hypoxia. However, the loss of strong adhesion was not obviously influenced by either the availability of oxygen in the medium or at the silicone elastomer surface. The detachment phenotype of mutant strains in which selected genes were either deleted or overexpressed was characterized. The microarray data indicated that changes associated with the detachment process were complex and, consistent with this assessment, we were unable to demonstrate that transcriptional regulation of any single gene was essential for loss of the strong adhesive association. Conclusion The massive dispersal of the early stage biofilm from a biomaterial surface that we observed is not orchestrated at the level of transcriptional regulation in an obvious manner, or is only regulated at this level by a small subpopulation of cells that mediate adhesion to the

  2. Early events of fertilization in sea urchin eggs are sensitive to actin-binding organic molecules.

    Science.gov (United States)

    Chun, Jong T; Limatola, Nunzia; Vasilev, Filip; Santella, Luigia

    2014-08-01

    We previously demonstrated that many aspects of the intracellular Ca(2+) increase in fertilized eggs of starfish are significantly influenced by the state of the actin cytoskeleton. In addition, the actin cytoskeleton appeared to play comprehensive roles in modulating cortical granules exocytosis and sperm entry during the early phase of fertilization. In the present communication, we have extended our work to sea urchin which is believed to have bifurcated from the common ancestor in the phylogenetic tree some 500 million years ago. To corroborate our earlier findings in starfish, we have tested how the early events of fertilization in sea urchin eggs are influenced by four different actin-binding drugs that promote either depolymerization or stabilization of actin filaments. We found that all the actin drugs commonly blocked sperm entry in high doses and significantly reduced the speed of the Ca(2+) wave. At low doses, however, cytochalasin B and phalloidin increased the rate of polyspermy. Overall, certain aspects of Ca(2+) signaling in these eggs were in line with the morphological changes induced by the actin drugs. That is, the time interval between the cortical flash and the first Ca(2+) spot at the sperm interaction site (the latent period) was significantly prolonged in the eggs pretreated with cytochalasin B or latrunculin A, whereas the Ca(2+) decay kinetics after the peak was specifically attenuated in the eggs pretreated with jasplakinolide or phalloidin. In addition, the sperm interacting with the eggs pretreated with actin drugs often generated multiple Ca(2+) waves, but tended to fail to enter the egg. Thus, our results indicated that generation of massive Ca(2+) waves is neither indicative of sperm entry nor sufficient for cortical granules exocytosis in the inseminated sea urchin eggs, whereas the structure and functionality of the actin cytoskeleton are the major determining factors in the two processes.

  3. ATP Depletion Via Mitochondrial F1F0 Complex by Lethal Factor is an Early Event in B. Anthracis-Induced Sudden Cell Death

    Directory of Open Access Journals (Sweden)

    Mitchell W. Woodberry

    2009-08-01

    Full Text Available Bacillus anthracis’ primary virulence factor is a tripartite anthrax toxin consisting of edema factor (EF, lethal factor (LF and protective antigen (PA. In complex with PA, EF and LF are internalized via receptor-mediated endocytosis. EF is a calmodulin- dependent adenylate cyclase that induces tissue edema. LF is a zinc-metalloprotease that cleaves members of mitogen-activated protein kinase kinases. Lethal toxin (LT: PA plus LF-induced death of macrophages is primarily attributed to expression of the sensitive Nalp1b allele, inflammasome formation and activation of caspase-1, but early events that initiate these processes are unknown. Here we provide evidence that an early essential event in pyroptosis of alveolar macrophages is LF-mediated depletion of cellular ATP. The underlying mechanism involves interaction of LF with F1F0-complex gamma and beta subunits leading to increased ATPase activity in mitochondria. In support, mitochondrial DNA-depleted MH-S cells have decreased F1F0 ATPase activity due to the lack of F06 and F08 polypeptides and show increased resistance to LT. We conclude that ATP depletion is an important early event in LT-induced sudden cell death and its prevention increases survival of toxin-sensitive cells.

  4. A late Eocene-early Oligocene transgressive event in the Golfo San Jorge basin: palynological results and stratigraphic implications

    OpenAIRE

    Paredes, José M.; Foix, Nicolas; Guerstein, Gladys Raquel; Guler, Maria Veronica; Irigoyen, Martin; Moscoso, Pablo; Giordano, Sergio

    2016-01-01

    A new Cenozoic dataset in the subsurface of the South Flank of the Golfo San Jorge Basin (Santa Cruz province) allowed to identify a non-previously recognized transgressive event of late Eocene to early Oligocene age. Below of a marine succession containing a dinoflagellate cyst assemblage that characterizes the C/G palynological zone of the Chenque Formation (early Miocene), a 80–110 m thick marine succession contains a palynological assemblage integrated by Gelatia inflata, Diphyes colliger...

  5. Early events associated with infection of Epstein-Barr virus infection of primary B-cells.

    Directory of Open Access Journals (Sweden)

    Sabyasachi Halder

    Full Text Available Epstein Barr virus (EBV is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology was used to introduce an expression cassette of green fluorescent protein (GFP by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6-7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6-12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection.

  6. Early life events carry over to influence pre-migratory condition in a free-living songbird.

    Directory of Open Access Journals (Sweden)

    Greg W Mitchell

    Full Text Available Conditions experienced during development can have long-term consequences for individual success. In migratory songbirds, the proximate mechanisms linking early life events and survival are not well understood because tracking individuals across stages of the annual cycle can be extremely challenging. In this paper, we first use a 13 year dataset to demonstrate a positive relationship between 1(st year survival and nestling mass in migratory Savannah sparrows (Passerculus sandwichensis. We also use a brood manipulation experiment to show that nestlings from smaller broods have higher mass in the nest relative to individuals from larger broods. Having established these relationships, we then use three years of field data involving multiple captures of individuals throughout the pre-migratory period and a multi-level path model to examine the hypothesis that conditions during development limit survival during migration by affecting an individual's ability to accumulate sufficient lean tissue and fat mass prior to migration. We found a positive relationship between fat mass during the pre-migratory period (Sept-Oct and nestling mass and a negative indirect relationship between pre-migratory fat mass and fledging date. Our results provide the first evidence that conditions during development limit survival during migration through their effect on fat stores. These results are particularly important given recent evidence showing that body condition of songbirds at fledging is affected by climate change and anthropogenic changes to landscape structure.

  7. Early events in hepatitis B virus infection: From the cell surface to the nucleus.

    Science.gov (United States)

    Hayes, C Nelson; Zhang, Yizhou; Makokha, Grace Naswa; Hasan, Md Zobaer; Omokoko, Magot D; Chayama, Kazuaki

    2016-02-01

    While most adults are able to clear acute hepatitis B virus (HBV) infection, chronic HBV infection is recalcitrant to current therapy because of the persistence of covalently closed circular DNA in the nucleus. Complete clearance of the virus in these patients is rare, and long-term therapy with interferon and/or nucleoside analogues may be required in an attempt to suppress viral replication and prevent progressive liver damage. The difficulty of establishing HBV infection in cell culture and experimental organisms has hindered efforts to elucidate details of the HBV life cycle, but it has also revealed the importance of the cellular microenvironment required for HBV binding and entry. Recent studies have demonstrated an essential role of sodium-taurocholate cotransporting polypeptide as a functional receptor in HBV infection, which has facilitated the development of novel infection systems and opened the way for more detailed understanding of the early steps of HBV infection as well as a potential new therapeutic target. However, many gaps remain in understanding of how HBV recognizes and attaches to hepatocytes prior to binding to sodium-taurocholate cotransporting polypeptide, as well as events that are triggered after binding, including entry into the cell, intracellular transport, and passage through the nuclear pore complex. This review summarizes current knowledge of the initial stages of HBV infection leading to the establishment of covalently closed circular DNA in the nucleus. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  8. The level of claudin-7 is reduced as an early event in colorectal carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tveit Kjell M

    2011-02-01

    Full Text Available Abstract Background Compromised epithelial barriers are found in dysplastic tissue of the gastrointestinal tract. Claudins are transmembrane proteins important for tight junctions. Claudins regulate the paracellular transport and are crucial for maintaining a functional epithelial barrier. Down-regulation of the oncogenic serine protease, matriptase, induces leakiness in epithelial barriers both in vivo and in vitro. We found in an in-silico search tight co-regulation between matriptase and claudin-7 expression. We have previously shown that the matriptase expression level decreases during colorectal carcinogenesis. In the present study we investigated whether claudin-7 expression is likewise decreased during colorectal carcinogenesis, thereby causing or contributing to the compromised epithelial leakiness of dysplastic tissue. Methods The mRNA level of claudin-7 (CLDN7 was determined in samples from 18 healthy individuals, 100 individuals with dysplasia and 121 colorectal cancer patients using quantitative real time RT-PCR. In addition, immunohistochemical stainings were performed on colorectal adenomas and carcinomas, to confirm the mRNA findings. Results A 2.7-fold reduction in the claudin-7 mRNA level was found when comparing the biopsies from healthy individuals with the biopsies of carcinomas (p claudin-7 mRNA levels were also detected in mild/moderate dysplasia (p Conclusions Our results show that the claudin-7 mRNA level is decreased already as an early event in colorectal carcinogenesis, probably contributing to the compromised epithelial barrier in adenomas.

  9. Early life events influence whole-of-life metabolic health via gut microflora and gut permeability.

    Science.gov (United States)

    Kerr, Caroline A; Grice, Desma M; Tran, Cuong D; Bauer, Denis C; Li, Dongmei; Hendry, Phil; Hannan, Garry N

    2015-01-01

    The capacity of our gut microbial communities to maintain a stable and balanced state, termed 'resilience', in spite of perturbations is vital to our achieving and maintaining optimal health. A loss of microbial resilience is observed in a number of diseases including obesity, diabetes and metabolic syndrome. There are large gaps in our understanding of why an individual's co-evolved microflora consortium fail to develop resilience thereby establishing a trajectory towards poor metabolic health. This review examines the connections between the developing gut microbiota and intestinal barrier function in the neonate, infant and during the first years of life. We propose that the effects of early life events on the gut microflora and permeability, whilst it is in a dynamic and vulnerable state, are fundamental in shaping the microbial consortia's resilience and that it is the maintenance of resilience that is pivotal for metabolic health throughout life. We review the literature supporting this concept suggesting new potential research directions aimed at developing a greater understanding of the longitudinal effects of the gut microflora on metabolic health and potential interventions to recalibrate the 'at risk' infant gut microflora in the direction of enhanced metabolic health.

  10. Fractal analysis of GPS time series for early detection of disastrous seismic events

    Science.gov (United States)

    Filatov, Denis M.; Lyubushin, Alexey A.

    2017-03-01

    A new method of fractal analysis of time series for estimating the chaoticity of behaviour of open stochastic dynamical systems is developed. The method is a modification of the conventional detrended fluctuation analysis (DFA) technique. We start from analysing both methods from the physical point of view and demonstrate the difference between them which results in a higher accuracy of the new method compared to the conventional DFA. Then, applying the developed method to estimate the measure of chaoticity of a real dynamical system - the Earth's crust, we reveal that the latter exhibits two distinct mechanisms of transition to a critical state: while the first mechanism has already been known due to numerous studies of other dynamical systems, the second one is new and has not previously been described. Using GPS time series, we demonstrate efficiency of the developed method in identification of critical states of the Earth's crust. Finally we employ the method to solve a practically important task: we show how the developed measure of chaoticity can be used for early detection of disastrous seismic events and provide a detailed discussion of the numerical results, which are shown to be consistent with outcomes of other researches on the topic.

  11. Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.

    Directory of Open Access Journals (Sweden)

    Aditi Narendra Borkar

    Full Text Available Protein denaturation plays a crucial role in cellular processes. In this study, denaturation of HIV-1 Protease (PR was investigated by all-atom MD simulations in explicit solvent. The PR dimer and monomer were simulated separately in 9 M acetic acid (9 M AcOH solution and water to study the denaturation process of PR in acetic acid environment. Direct visualization of the denaturation dynamics that is readily available from such simulations has been presented. Our simulations in 9 M AcOH reveal that the PR denaturation begins by separation of dimer into intact monomers and it is only after this separation that the monomer units start denaturing. The denaturation of the monomers is flagged off by the loss of crucial interactions between the α-helix at C-terminal and surrounding β-strands. This causes the structure to transit from the equilibrium dynamics to random non-equilibrating dynamics. Residence time calculations indicate that denaturation occurs via direct interaction of the acetic acid molecules with certain regions of the protein in 9 M AcOH. All these observations have helped to decipher a picture of the early events in acetic acid denaturation of PR and have illustrated that the α-helix and the β-sheet at the C-terminus of a native and functional PR dimer should maintain both the stability and the function of the enzyme and thus present newer targets for blocking PR function.

  12. Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension

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    Joseph P. Grande

    2013-09-01

    Full Text Available Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethhylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3+ T cells and F4/80+ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy.

  13. Modulation of early and late event-related potentials by emotion

    Directory of Open Access Journals (Sweden)

    Sarah J. Hart

    2012-11-01

    Full Text Available Although emotionally salient stimuli influence higher order information processing, the relative vulnerability of specific stages of cognitive processing to modulation by emotional input remains elusive. To test the temporal dynamics of emotional interference during executive function, we recorded event-related potentials while participants performed an effortful anticipation task with aversive emotional and neutral distracters. Participants were presented with a modified delayed Stroop task that dissociated the anticipation of an easier or more difficult task (instructional cues to attend to word versus color from the response to the Stroop stimulus, while aversive and neutral pictures were displayed during the delay period. Our results indicated a relative decrease in the amplitude of the contingent negative variation (CNV during aversive trials that was greater during the early anticipatory phase than during the later response preparation phase, and greater during (the more difficult color than word trials. During the initial stage of cue processing, there was also significant interaction between emotion and anticipatory difficulty on N1 amplitude, where emotional stimuli led to significantly enhanced negativity during color cues relative to word cues. These results suggest that earlier processes of orientation and effortful anticipation may reflect executive engagement that is influenced by emotional interference while later phases of response preparation may be modulated by emotional interference regardless of anticipatory difficulty.

  14. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus.

    Science.gov (United States)

    Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D; Saeed, Fahad; Michael Payne, D; Chen, Shu-Hui; Fenton, Robert A; Pisitkun, Trairak

    2015-12-17

    Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.

  15. Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c

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    David S. Kliger

    2009-04-01

    Full Text Available Kinetic studies of the early events in cytochrome c folding are reviewed with a focus on the evidence for folding intermediates on the submillisecond timescale. Evidence from time-resolved absorption, circular dichroism, magnetic circular dichroism, fluorescence energy and electron transfer, small-angle X-ray scattering and amide hydrogen exchange studies on the t £ 1 ms timescale reveals a picture of cytochrome c folding that starts with the ~ 1-ms conformational diffusion dynamics of the unfolded chains. A fractional population of the unfolded chains collapses on the 1 – 100 ms timescale to a compact intermediate IC containing some native-like secondary structure. Although the existence and nature of IC as a discrete folding intermediate remains controversial, there is extensive high time-resolution kinetic evidence for the rapid formation of IC as a true intermediate, i.e., a metastable state separated from the unfolded state by a discrete free energy barrier. Final folding to the native state takes place on millisecond and longer timescales, depending on the presence of kinetic traps such as heme misligation and proline mis-isomerization. The high folding rates observed in equilibrium molten globule models suggest that IC may be a productive folding intermediate. Whether it is an obligatory step on the pathway to the high free energy barrier associated with millisecond timescale folding to the native state, however, remains to be determined.

  16. New type IV pili-related genes involved in early stages of Ralstonia solanacearum potato infection.

    Science.gov (United States)

    Siri, María Inés; Sanabria, Analía; Boucher, Christian; Pianzzola, María Julia

    2014-07-01

    This study provides insights into the pathogenesis of Ralstonia solanacearum, in particular with regards to strains belonging to phylotype IIB, sequevar 1 (IIB-1) and their interaction with potato, its natural host. We performed a comparative genomic analysis among IIB-1 R. solanacearum strains with different levels of virulence in order to identify candidate virulence genes. With this approach, we identified a 33.7-kb deletion in a strain showing reduced virulence on potato. This region contains a cluster of six genes putatively involved in type IV pili (Tfp) biogenesis. Functional analysis suggests that these proteins contribute to several Tfp-related functions such as twitching motility and biofilm formation. In addition, this genetic cluster was found to contribute to early bacterial wilt pathogenesis and colonization fitness of potato roots.

  17. Gene Expression Analysis for the Identification of Genes Involved in Early Tumour Development

    Science.gov (United States)

    Forte, Stefano; Scarpulla, Salvatore; Lagana, Alessandro; Memeo, Lorenzo; Gulisano, Massimo

    Prostatic tissues can undergo to cancer insurgence and prostate cancer is one of the most common types of malignancies affecting adult men in the United States. Primary adenocarcinoma of the seminal vesi-cles (SVCA) is a very rare neoplasm with only 48 histologically confirmed cases reported in the European and United States literature. Prostatic tissues, seminal vesicles and epididymis belongs all to the same microenvironment, shows a very close morphology and share the same embryological origin. Despite these common features the rate of cancer occurrence is very different. The understanding of molecular differences between non neoplastic prostatic tissues and non neoplastic epididymis or seminal vesicles may suggest potential mechanisms of resistance to tumour occurrence. The comparison of expression patterns of non neoplastic prostatic and seminal vesicles tissues to identify differentially expressed genes can help researchers in the identification of biological actors involved in the early stages of the tumour development.

  18. An SK3 channel/nWASP/Abi-1 complex is involved in early neurogenesis.

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    Stefan Liebau

    Full Text Available BACKGROUND: The stabilization or regulated reorganization of the actin cytoskeleton is essential for cellular structure and function. Recently, we could show that the activation of the SK3-channel that represents the predominant SK-channel in neural stem cells, leads to a rapid local outgrowth of long filopodial processes. This observation indicates that the rearrangement of the actin based cytoskeleton via membrane bound SK3-channels might selectively be controlled in defined micro compartments of the cell. PRINCIPAL FINDINGS: We found two important proteins for cytoskeletal rearrangement, the Abelson interacting protein 1, Abi-1 and the neural Wiskott Aldrich Syndrome Protein, nWASP, to be in complex with SK3- channels in neural stem cells (NSCs. Moreover, this interaction is also found in spines and postsynaptic compartments of developing primary hippocampal neurons and regulates neurite outgrowth during early phases of differentiation. Overexpression of the proteins or pharmacological activation of SK3 channels induces obvious structural changes in NSCs and hippocampal neurons. In both neuronal cell systems SK3 channels and nWASP act synergistic by strongly inducing filopodial outgrowth while Abi-1 behaves antagonistic to its interaction partners. CONCLUSIONS: Our results give good evidence for a functional interplay of a trimeric complex that transforms incoming signals via SK3-channel activation into the local rearrangement of the cytoskeleton in early steps of neuronal differentiation involving nWASP and Abi-1 actin binding proteins.

  19. Early Discrimination Of Microorganisms Involved In Ventilator Associated Pneumonia Using Qualitative Volatile Fingerprints

    Science.gov (United States)

    Planas, Neus; Kendall, Catherine; Barr, Hugh; Magan, Naresh

    2009-05-01

    This study has examined the use of an electronic nose for the detection of volatile organic compounds produced by different microorganisms responsible for ventilator-associated pneumonia (VAP), an important disease among patients who require mechanical ventilation. Based on the analysis of the volatile organic compounds, electronic nose technology is being evaluated for the early detection and identification of many diseases. It has been shown that effective discrimination of two bacteria (Enterobacter cloacae and Klebsiella pneumoniae) and yeast (Candida albicans), could be obtained after 24 h and filamentous fungus (Aspergillus fumigatus) after 72 h. Discrimination between blank samples and those with as initial concentration of 102 CFU ml-1 was shown with 24 h incubation for bacteria and 48 h for fungi. Effective discrimination between all the species was achieved 72 h after incubation. Initial studies with mixtures of microorganisms involved in VAP suggest that complex interactions between species occur which influences the ability to differentiate dominant species using volatile production patterns. A nutrient agar base medium was found to be optimum for early discrimination between two microorganisms (Klebsiella pneumoniae and Candida albicans).

  20. A Colletotrichum graminicola mutant deficient in the establishment of biotrophy reveals early transcriptional events in the maize anthracnose disease interaction.

    Science.gov (United States)

    Torres, Maria F; Ghaffari, Noushin; Buiate, Ester A S; Moore, Neil; Schwartz, Scott; Johnson, Charles D; Vaillancourt, Lisa J

    2016-03-08

    Colletotrichum graminicola is a hemibiotrophic fungal pathogen that causes maize anthracnose disease. It progresses through three recognizable phases of pathogenic development in planta: melanized appressoria on the host surface prior to penetration; biotrophy, characterized by intracellular colonization of living host cells; and necrotrophy, characterized by host cell death and symptom development. A "Mixed Effects" Generalized Linear Model (GLM) was developed and applied to an existing Illumina transcriptome dataset, substantially increasing the statistical power of the analysis of C. graminicola gene expression during infection and colonization. Additionally, the in planta transcriptome of the wild-type was compared with that of a mutant strain impaired in the establishment of biotrophy, allowing detailed dissection of events occurring specifically during penetration, and during early versus late biotrophy. More than 2000 fungal genes were differentially transcribed during appressorial maturation, penetration, and colonization. Secreted proteins, secondary metabolism genes, and membrane receptors were over-represented among the differentially expressed genes, suggesting that the fungus engages in an intimate and dynamic conversation with the host, beginning prior to penetration. This communication process probably involves reception of plant signals triggering subsequent developmental progress in the fungus, as well as production of signals that induce responses in the host. Later phases of biotrophy were more similar to necrotrophy, with increased production of secreted proteases, inducers of plant cell death, hydrolases, and membrane bound transporters for the uptake and egress of potential toxins, signals, and nutrients. This approach revealed, in unprecedented detail, fungal genes specifically expressed during critical phases of host penetration and biotrophic establishment. Many encoded secreted proteins, secondary metabolism enzymes, and receptors that may

  1. A 2-component system is involved in the early stages of the Pisolithus tinctorius-Pinus greggii symbiosis

    Science.gov (United States)

    Herrera-Martínez, Aseneth; Ruiz-Medrano, Roberto; Galván-Gordillo, Santiago Valentín; Toscano-Morales, Roberto; Gómez-Silva, Lidia; Valdés, María; Hinojosa-Moya, Jesús; Xoconostle-Cázares, Beatriz

    2014-01-01

    Ectomycorrhizal symbiosis results in profound morphological and physiological modifications in both plant and fungus. This in turn is the product of differential gene expression in both co-symbionts, giving rise to specialized cell types capable of performing novel functions. During the precolonization stage, chemical signals from root exudates are sensed by the ectomycorrhizal fungus, and vice versa, which are in principle responsible for the observed change in the symbionts developmental program. Little is known about the molecular mechanisms involved in the signaling and recognition between ectomycorrhizal fungi and their host plants. In the present work, we characterized a novel lactone, termed pinelactone, and identified a gene encoding for a histidine kinase in Pisolithus tictorius, the function of which is proposed to be the perception of the aforementioned metabolites. In this study, the use of closantel, a specific inhibitor of histidine kinase phosphorylation, affected the capacity for fungal colonization in the symbiosis between Pisolithus tinctorius and Pinus greggii, indicating that a 2-component system (TCS) may operate in the early events of plant-fungus interaction. Indeed, the metabolites induced the accumulation of Pisolithus tinctorius mRNA for a putative histidine kinase (termed Pthik1). Of note, Pthik1 was able to partially complement a S. cerevisiae histidine kinase mutant, demonstrating its role in the response to the presence of these metabolites. Our results indicate a role of a TCS pathway in the early stages of ectomycorrhizal symbiosis before colonization. Furthermore, a novel lactone from Pinus greggii root exudates may activate a signal transduction pathway that contributes to the establishment of the ectomycorrhizal symbiosis. PMID:24704731

  2. EFFECT OF ARSENICALS ON THE EXPRESSION OF CELL CYCLE PROTEINS AND EARLY SIGNALING EVENTS IN PRIMARY HUMAN KERATINOCYTES.

    Science.gov (United States)

    Effect of Arsenicals on the Expression of Cell Cycle Proteins and Early Signaling Events in Primary Human Keratinocytes.Mudipalli, A, Owen R. D. and R. J. Preston, Environmental Carcinogenesis Division, USEPA, RTP, NC 27711.Environmental exposure to arsenic is a m...

  3. Parental Involvement and General Cognitive Ability as Predictors of Domain-Specific Academic Achievement in Early Adolescence

    Science.gov (United States)

    Karbach, Julia; Gottschling, Juliana; Spengler, Marion; Hegewald, Katrin; Spinath, Frank M.

    2013-01-01

    Numerous studies showed that general cognitive ability (GCA) is a reliable predictor of academic achievement. In addition, parental involvement in their children's academic development is of major importance in early adolescence. This study investigated the incremental validity of parental involvement over GCA in the prediction of academic…

  4. Familias Latinas: Participando en la educacion de sus hijos (Latino Families: Getting Involved in Your Children's Education). Early Childhood Digest.

    Science.gov (United States)

    Levine, Eliot

    Noting that many Latino parents have questions about parent participation in their children's education and how to go about getting involved, this Spanish-language early childhood digest answers some of those questions by providing suggestions for ways parents can involve themselves in a child's education both at school and at home. Following a…

  5. Modeling the Early Events of Severe Acute Respiratory Syndrome Coronavirus Infection In Vitro

    Science.gov (United States)

    Yen, Yu-Ting; Liao, Fang; Hsiao, Cheng-Hsiang; Kao, Chuan-Liang; Chen, Yee-Chun; Wu-Hsieh, Betty A.

    2006-01-01

    The clinical picture of severe acute respiratory syndrome (SARS) is characterized by pulmonary inflammation and respiratory failure, resembling that of acute respiratory distress syndrome. However, the events that lead to the recruitment of leukocytes are poorly understood. To study the cellular response in the acute phase of SARS coronavirus (SARS-CoV)-host cell interaction, we investigated the induction of chemokines, adhesion molecules, and DC-SIGN (dendritic cell-specific ICAM-3-grabbing nonintegrin) by SARS-CoV. Immunohistochemistry revealed neutrophil, macrophage, and CD8 T-cell infiltration in the lung autopsy of a SARS patient who died during the acute phase of illness. Additionally, pneumocytes and macrophages in the patient's lung expressed P-selectin and DC-SIGN. In in vitro study, we showed that the A549 and THP-1 cell lines were susceptible to SARS-CoV. A549 cells produced CCL2/monocyte chemoattractant protein 1 (MCP-1) and CXCL8/interleukin-8 (IL-8) after interaction with SARS-CoV and expressed P-selectin and VCAM-1. Moreover, SARS-CoV induced THP-1 cells to express CCL2/MCP-1, CXCL8/IL-8, CCL3/MIP-1α, CXCL10/IP-10, CCL4/MIP-1β, and CCL5/RANTES, which attracted neutrophils, monocytes, and activated T cells in a chemotaxis assay. We also demonstrated that DC-SIGN was inducible in THP-1 as well as A549 cells after SARS-CoV infection. Our in vitro experiments modeling infection in humans together with the study of a lung biopsy of a patient who died during the early phase of infection demonstrated that SARS-CoV, through a dynamic interaction with lung epithelial cells and monocytic cells, creates an environment conducive for immune cell migration and accumulation that eventually leads to lung injury. PMID:16501078

  6. Shorter exposures to harder X-rays trigger early apoptotic events in Xenopus laevis embryos.

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    JiaJia Dong

    Full Text Available BACKGROUND: A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems. METHODOLOGY/PRINCIPAL FINDINGS: We explored how the energy of individual X-ray photons and exposure time, both factors that determine the total dose, influence the occurrence of cell death in early Xenopus embryo. Three different experimental scenarios were analyzed and morphological and biochemical hallmarks of apoptosis were evaluated. Initially, we examined cell death events in embryos exposed to increasing incident energies when the exposure time was preset. Then, we evaluated the embryo's response when the exposure time was augmented while the energy value remained constant. Lastly, we studied the incidence of apoptosis in embryos exposed to an equal total dose of radiation that resulted from increasing the incoming energy while lowering the exposure time. CONCLUSIONS/SIGNIFICANCE: Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system. In particular, for embryos exposed under identical conditions and delivered the same absorbed dose of radiation, the response is significantly increased when shorter bursts of more energetic photons are used. These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and

  7. Evaluation of an early warning system for glacial lake outburst flood (GLOF) events in Huaraz, Peru

    Science.gov (United States)

    McKinney, D. C.; Somos-Valenzuela, M. A.

    2014-12-01

    People in Cordillera Blanca range in Peru have a long history dealing with natural disasters associated to high mountains; particularly Glacier Lakes Outburst Flood (GLOF). Examples in the Cordillera Blanca vary from a GLOF that occurred in 1941 that killed more than 5000 people in the city of Huaraz to recent events from Lake Artison Baja in 2012 and Lake 513 on 2010, which were not devastating thanks to safety systems previously installed in those lakes. However, glaciers continue melting leaving new lakes or changing the characteristics of lakes that were previously controlled making safety systems obsolete that worked successfully in the past protecting communities downstream. Lake Palcacocha has evolved from being safe after the installation of a safety system in 1970 to an imminent source of GLOF risk due to the expansion that has occurred during the last 40 years increasing from a volume of 500,000 to 17 million m3. In response to this risk the community in Huaraz is planning an Early Warning System (EWS) that will allow the population to mobilize to a safe area in case a GLOF occurs. In this work we present an adaptation of the LifeSIM model to calculate the benefits from such an EWS using 2007 census data and a FLO-2D flood simulation model. The outputs are the number of people in Huaraz that could lose their life due to a GLOF. Our results indicate that without an EWS around 19,773 people could lose their life; whereas, if an EWS is installed the number of victims reduces to 7344. Finally, if mobilization of the affected population is improved the value reduces to 2865. The results show the importance of the EWS as well as informing and training the population to how to react if a GLOF occurs.

  8. Inhibition of early upstream events in prodromal Alzheimer's disease by use of targeted antioxidants.

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    Prasad, Kedar N; Bondy, Stephen C

    2014-01-01

    A link between Alzheimer's disease (AD) and an excess presence of oxidant free radicals in the brain has frequently been reported. It is generally assumed that such oxidative stress and related cellular damage is caused by inflammatory changes in the brain and is consequent to amyloid deposition. This review makes the argument that elevated oxidative stress in AD is an early causal event in the initiation and advancement of this disease. Oxidative stress can be decreased by enhancing antioxidant enzymes through activation of the cytoplasmic transcriptional factor (Nrf2)/ARE (antioxidant response element) pathway, and by dietary and endogenous antioxidant chemicals. Reduction in the binding ability of Nrf2 to ARE lowers antioxidant enzyme levels. Decreased levels of Nrf2 and augmentation of oxidative stress in AD suggest that the ROS-dependent mechanism of activating the Nrf2/ARE pathway has become unresponsive. A combination of agents that can either activate the Nrf2-ARE pathway by ROS-independent mechanisms, or by acting directly as antioxidant chemicals, may be necessary to reduce oxidative stress in AD. Earlier shortcomings of using individual antioxidants may be due to consideration of antioxidants as pharmacological agents, ignoring the fact that individual antioxidants can be transmuted in the highly oxidant milieu that is present in AD. Interactions between various cellular compartments may require simultaneous examination of more than one agent. The clinical utility of such a more integrative method can reveal interactive effects such as those found in nutritional research and this can compensate for any mechanistic shortcomings of simultaneous testing of more than a single agent.

  9. Phase noise reveals early category-specific modulation of the event-related potentials.

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    Németh, Kornél; Kovács, Petra; Vakli, Pál; Kovács, Gyula; Zimmer, Márta

    2014-01-01

    Previous studies have found that the amplitude of the early event-related potential (ERP) components evoked by faces, such as N170 and P2, changes systematically as a function of noise added to the stimuli. This change has been linked to an increased perceptual processing demand and to enhanced difficulty in perceptual decision making about faces. However, to date it has not yet been tested whether noise manipulation affects the neural correlates of decisions about face and non-face stimuli similarly. To this end, we measured the ERPs for faces and cars at three different phase noise levels. Subjects performed the same two-alternative age-discrimination task on stimuli chosen from young-old morphing continua that were created from faces as well as cars and were calibrated to lead to similar performances at each noise-level. Adding phase noise to the stimuli reduced performance and enhanced response latency for the two categories to the same extent. Parallel to that, phase noise reduced the amplitude and prolonged the latency of the face-specific N170 component. The amplitude of the P1 showed category-specific noise dependence: it was enhanced over the right hemisphere for cars and over the left hemisphere for faces as a result of adding phase noise to the stimuli, but remained stable across noise levels for cars over the left and for faces over the right hemisphere. Moreover, noise modulation altered the category-selectivity of the N170, while the P2 ERP component, typically associated with task decision difficulty, was larger for the more noisy stimuli regardless of stimulus category. Our results suggest that the category-specificity of noise-induced modulations of ERP responses starts at around 100 ms post-stimulus.

  10. Functional characterization of chitinase-3 reveals involvement of chitinases in early embryo immunity in zebrafish.

    Science.gov (United States)

    Teng, Zinan; Sun, Chen; Liu, Shousheng; Wang, Hongmiao; Zhang, Shicui

    2014-10-01

    The function and mechanism of chitinases in early embryonic development remain largely unknown. We show here that recombinant chitinase-3 (rChi3) is able to hydrolyze the artificial chitin substrate, 4-methylumbelliferyl-β-D-N,N',N″-triacetylchitotrioside, and to bind to and inhibit the growth of the fungus Candida albicans, implicating that Chi3 plays a dual function in innate immunity and chitin-bearing food digestion in zebrafish. This is further corroborated by the expression profile of Chi3 in the liver and gut, which are both immune- and digestion-relevant organs. Compared with rChi3, rChi3-CD lacking CBD still retains partial capacity to bind to C. albicans, but its enzymatic and antifungal activities are significantly reduced. By contrast, rChi3-E140N with the putative catalytic residue E140 mutated shows little affinity to chitin, and its enzymatic and antifungal activities are nearly completely lost. These suggest that both enzymatic and antifungal activities of Chi3 are dependent on the presence of CBD and E140. We also clearly demonstrate that in zebrafish, both the embryo extract and the developing embryo display antifungal activity against C. albicans, and all the findings point to chitinase-3 (Chi3) being a newly-identified factor involved in the antifungal activity. Taken together, a dual function in both innate immunity and food digestion in embryo is proposed for zebrafish Chi3. It also provides a new angle to understand the immune role of chitinases in early embryonic development of animals.

  11. Different frontal involvement in ALS and PLS revealed by Stroop event-related potentials and reaction times

    Directory of Open Access Journals (Sweden)

    Ninfa eAmato

    2013-12-01

    Full Text Available BACKGROUND: A growing body of evidence suggests a link between cognitive and pathological changes in amyotrophic lateral sclerosis (ALS and in frontotemporal lobar dementia (FTLD. Cognitive deficits have been investigated much less extensively in primary lateral sclerosis (PLS than in ALS. OBJECTIVE: to investigate bioelectrical activity to Stroop test, assessing frontal function, in ALS, PLS and control groups. METHODS: 32 non-demented ALS patients, 10 non-demented PLS patients and 27 healthy subjects were included. Twenty-nine electroencephalography (EEG channels with binaural reference were recorded during covert Stroop task performance, involving mental discrimination of the stimuli and not vocal or motor response. Group effects on event related potentials (ERPs latency were analyzed using statistical multivariate analysis. Topographic analysis was performed using low resolution brain electromagnetic tomography (LORETA. RESULTS: ALS patients committed more errors in the execution of the task but they were not slower, whereas PLS patients did not show reduced accuracy, despite a slowing of reaction times (RTs. The main ERP components were delayed in ALS, but not in PLS, compared with controls. Moreover, RTs speed but not ERP latency correlated with clinical scores. ALS had decreased frontotemporal activity in the P2, P3 and N4 time windows compared to controls. CONCLUSION: These findings suggest a different pattern of psychophysiological involvement in ALS compared with PLS. The former is increasingly recognized to be a multisystems disorder, with a spectrum of executive and behavioural impairments reflecting frontotemporal dysfunction. The latter seems to mainly involve the motor system, with largely spared cognitive functions. Moreover, our results suggest that the covert version of the Stroop task used in the present study, may be useful to assess cognitive state in the very advanced stage of the disease, when other cognitive tasks are not

  12. Estimation of loci involved in non-shattering of seeds in early rice domestication.

    Science.gov (United States)

    Ishikawa, Ryo; Nishimura, Akinori; Htun, Than Myint; Nishioka, Ryo; Oka, Yumi; Tsujimura, Yuki; Inoue, Chizuru; Ishii, Takashige

    2017-04-01

    Rice (Oryza sativa L.) is widely cultivated around the world and is known to be domesticated from its wild form, O. rufipogon. A loss of seed shattering is one of the most obvious phenotypic changes selected for during rice domestication. Previously, three seed-shattering loci, qSH1, sh4, and qSH3 were reported to be involved in non-shattering of seeds of Japonica-type cultivated rice, O. sativa cv. Nipponbare. In this study, we focused on non-shattering characteristics of O. sativa Indica cv. IR36 having functional allele at qSH1. We produced backcross recombinant inbred lines having chromosomal segments from IR36 in the genetic background of wild rice, O. rufipogon W630. Histological and quantitative trait loci analyses of abscission layer formation were conducted. In the analysis of quantitative trait loci, a strong peak was observed close to sh4. We, nevertheless, found that some lines showed complete abscission layer formation despite carrying the IR36 allele at sh4, implying that non-shattering of seeds of IR36 could be regulated by the combination of mutations at sh4 and other seed-shattering loci. We also genotyped qSH3, a recently identified seed-shattering locus. Lines that have the IR36 alleles at sh4 and qSH3 showed inhibition of abscission layer formation but the degree of seed shattering was different from that of IR36. On the basis of these results, we estimated that non-shattering of seeds in early rice domestication involved mutations in at least three loci, and these genetic materials produced in this study may help to identify novel seed-shattering loci.

  13. Involvement of lysosomal dysfunction in autophagosome accumulation and early pathologies in adipose tissue of obese mice.

    Science.gov (United States)

    Mizunoe, Yuhei; Sudo, Yuka; Okita, Naoyuki; Hiraoka, Hidenori; Mikami, Kentaro; Narahara, Tomohiro; Negishi, Arisa; Yoshida, Miki; Higashibata, Rikako; Watanabe, Shukoh; Kaneko, Hiroki; Natori, Daiki; Furuichi, Takuma; Yasukawa, Hiromine; Kobayashi, Masaki; Higami, Yoshikazu

    2017-04-03

    Whether obesity accelerates or suppresses autophagy in adipose tissue is still debatable. To clarify dysregulation of autophagy and its role in pathologies of obese adipose tissue, we focused on lysosomal function, protease maturation and activity, both in vivo and in vitro. First, we showed that autophagosome formation was accelerated, but autophagic clearance was impaired in obese adipose tissue. We also found protein and activity levels of CTSL (cathepsin L) were suppressed in obese adipose tissue, while the activity of CTSB (cathepsin B) was significantly enhanced. Moreover, cellular senescence and inflammasomes were activated in obese adipose tissue. In 3T3L1 adipocytes, downregulation of CTSL deteriorated autophagic clearance, upregulated expression of CTSB, promoted cellular senescence and activated inflammasomes. Upregulation of CTSB promoted additional activation of inflammasomes. Therefore, we suggest lysosomal dysfunction observed in obese adipose tissue leads to lower autophagic clearance, resulting in autophagosome accumulation. Simultaneously, lysosomal abnormalities, including deteriorated CTSL function and compensatory activation of CTSB, caused cellular senescence and inflammasome activation. Our findings strongly suggest lysosomal dysfunction is involved in early pathologies of obese adipose tissue.

  14. Early pulmonary involvement in ankylosing spondylitis: Assessment with thin-section CT

    Energy Technology Data Exchange (ETDEWEB)

    Turetschek, Karl; Ebner, Wolfgang; Fleischmann, Dominik; Wunderbaldinger, Patrick; Erlacker, Ludwig; Zontsich, Thomas; Bankier, Alexander A

    2000-08-01

    AIM: To determine the frequency and the distribution of early pulmonary lesions in patients with ankylosing spondylitis (AS) and a normal chest X-ray on thin-section CT and to correlate the CT findings with the results of pulmonary function tests and clinical data. MATERIALS AND METHODS: Twenty-five patients with clinically proven AS and no history of smoking underwent clinical examinations, pulmonary function tests (PFT), chest radiography, and thin-section CT. Four of 25 patients (16%), who had obvious signs on plain films suggestive of pre-existing disorders unrelated to AS were excluded. RESULTS: Fifteen of 21 patients (71%) had abnormalities on thin-section CT. The most frequent abnormalities were thickening of the interlobular septa in seven of 21 patients (33%), mild bronchial wall thickening in (6/21, 29%), pleural thickening and pleuropulmonary irregularities (both 29%) and linear septal thickening (6/21, 29%). In six patients there were no signs of pleuropulmonary involvement. Eight of 15 patients (53%) with abnormal and four of six patients (67%) with normal CT findings revealed mild restrictive lung function impairment. CONCLUSION: Patients with AS but a normal chest radiograph frequently have abnormalities on thin-section CT. As these abnormalities are usually subtle and their extent does not correlate with functional and clinical data, the overall routine impact of thin-section CT in the diagnosis of AS is limited. Turetschek, K., (2000)

  15. Episodic retrieval involves early and sustained effects of reactivating information from encoding.

    Science.gov (United States)

    Johnson, Jeffrey D; Price, Mason H; Leiker, Emily K

    2015-02-01

    Several fMRI studies have shown a correspondence between the brain regions activated during encoding and retrieval, consistent with the view that memory retrieval involves hippocampally-mediated reinstatement of cortical activity. With the limited temporal resolution of fMRI, the precise timing of such reactivation is unclear, calling into question the functional significance of these effects. Whereas reactivation influencing retrieval should emerge with neural correlates of retrieval success, that signifying post-retrieval monitoring would trail retrieval. The present study employed EEG to provide a temporal landmark of retrieval success from which we could investigate the sub-trial time course of reactivation. Pattern-classification analyses revealed that early-onsetting reactivation differentiated the outcome of recognition-memory judgments and was associated with individual differences in behavioral accuracy, while reactivation was also evident in a sustained form later in the trial. The EEG findings suggest that, whereas prior fMRI findings could be interpreted as reflecting the contribution of reinstatement to retrieval success, they could also indicate the maintenance of episodic information in service of post-retrieval evaluation.

  16. ADAM10 Is Involved in Cell Junction Assembly in Early Porcine Embryo Development.

    Directory of Open Access Journals (Sweden)

    Jeongwoo Kwon

    Full Text Available ADAM10 (A Disintegrin and Metalloprotease domain-containing protein 10 is a cell surface protein with a unique structure possessing both potential adhesion and protease domains. However, the role of ADAM10 in preimplantation stage embryos is not clear. In this study, we examined the expression patterns and functional roles of ADAM10 in porcine parthenotes during preimplantation development. The transcription level of ADAM10 dramatically increased from the morula stage onward. Immunostaining revealed that ADAM10 was present in both the nucleus and cytoplasm in early cleavage stage embryos, and localized to the apical region of the outer cells in morula and blastocyst embryos. Knockdown (KD of ADAM10 using double strand RNA did not alter preimplantation embryo development until morula stage, but resulted in significantly reduced development to blastocyst stage. Moreover, the KD blastocyst showed a decrease in gene expression of adherens and tight junction (AJ/TJ, and an increase in trophectoderm TJ permeability by disrupting TJ assembly. Treatment with an ADAM10 specific chemical inhibitor, GI254023X, at the morula stage also inhibited blastocyst development and led to disruption of TJ assembly. An in situ proximity ligation assay demonstrated direct interaction of ADAM10 with coxsackie virus and adenovirus receptor (CXADR, supporting the involvement of ADAM10 in TJ assembly. In conclusion, our findings strongly suggest that ADADM10 is important for blastocyst formation rather than compaction, particularly for TJ assembly and stabilization in preimplantation porcine parthenogenetic development.

  17. Organic Geochemistry of the Early Jurassic Oil Shale from the Shuanghu Area in Northern Tibet and the Early Toarcian Oceanic Anoxic Event

    Institute of Scientific and Technical Information of China (English)

    CHEN Lan; YI Haisheng; HU Ruizhong; ZHONG Hong; ZOU Yanrong

    2005-01-01

    This paper presents new geological and geochemical data from the Shuanghu area in northern Tibet, which recorded the Early Toarcian Oceanic Anoxic Event. The stratigraphic succession in the Shuanghu area consists mostly of grey to dark-colored alternating oil shales, marls and mudstones. Ammonite beds are found at the top of the Shuanghu oil shale section, which are principally of early Toarcian age, roughly within the Harplocearasfalciferrum Zone. Therefore,the oil shale strata at Shuanghu can be correlated with early Toarcian black shales distributing extensively in the European epicontinental seas that contain the records of an Oceanic Anoxic Event. Sedimentary organic matter of laminated shale anomalously rich in organic carbon across the Shuanghu area is characterized by high organic carbon contents, ranging from 1.8 % to 26.1%. The carbon isotope curve displays the δ13C values of the kerogen (δ 13Ckerogen) fluctuating from -26.22to -23.53‰ PDB with a positive excursion close to 2.17‰, which, albeit significantly smaller, may also have been associated with other Early Toarcian Oceanic Anoxic Events (OAEs) in Europe. The organic atomic C/N ratios range between 6 and 43, and the curve of C/N ratios is consistent with that of the δ13Ckerogen values. The biological assemblage,characterized by scarcity of benthic organisms and bloom of calcareous nannofossils (coccoliths), reveals high biological productivity in the surface water and an unfavorable environment for the benthic fauna in the bottom water during the Oceanic Anoxic Event. On the basis of organic geochemistry and characteristics of the biological assemblage, this study suggests that the carbon-isotope excursion is caused by the changes of sea level and productivity, and that the black shale deposition, especially oil shales, is related to the bloom and high productivity of coccoliths.

  18. High acceptance of an early dyslexia screening test involving genetic analyses in Germany

    National Research Council Canada - National Science Library

    Wilcke, Arndt; Müller, Bent; Schaadt, Gesa; Kirsten, Holger; Boltze, Johannes

    2016-01-01

    ... the end of the 2nd grade, resulting in the loss of several years for early therapy. Currently, research is focusing on the development of early tests for dyslexia, which may be based on EEG and genetics...

  19. Low ABCB1 gene expression is an early event in colorectal carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Vibeke Andersen

    Full Text Available The ABCB1/MDR1 gene product ABCB1/P-glycoprotein is implicated in the development of colorectal cancer (CRC. NFKB1 encodes transcription factors regulating expression of a number of genes including ABCB1. We have previously found association between the ABCB1 C-rs3789243-T polymorphism and CRC risk and interactions between the ABCB1 C-rs3789243-T and C3435T polymorphisms and meat intake in relation to CRC risk (Andersen, BMC Cancer, 2009, 9, 407. ABCB1 and NFKB1 mRNA levels were assessed in intestinal tissue from 122 CRC cases, 101 adenoma cases (12 with severe dysplasia, 89 with mild-moderate dysplasia and from 18 healthy individuals, together with gene polymorphisms in ABCB1 and NFKB1. ABCB1 mRNA levels were highest in the healthy individuals and significantly lower in mild/moderate and severe dysplasia tissue (P<0.05 for both, morphologically normal tissues close to the tumour (P<0.05, morphologically normal tissue at a distance from the tumour (P<0.05 and CRC tissue (P<0.001. Furthermore, ABCB1 mRNA levels were lower in adenomas and carcinomas compared to morphologically normal tissue from the same individuals (P<0.01. The ABCB1 C-rs3789243-T and NFKB1 -94ins/del homozygous variant genotypes were associated with low ABCB1 mRNA levels in morphologically normal sigmoid tissue from adenoma cases (P<0.05 for both. NFKB1 mRNA levels were lower in both tumour and normal tissue from cancer patients (P<0.001 as compared to healthy individuals but we were unable to show association between NFKB1 -94ins/del genotype and NFKB1 mRNA levels. This study suggests that low ABCB1 mRNA levels are an early event in CRC development and that the two polymorphisms affect ABCB1 mRNA levels whereas low NFKB1 mRNA levels occur later in carcinogenesis. Low ABCB1 protein levels may promote colorectal carcinogenesis through increasing intracellular exposure to carcinogenic ABCB1 substrates.

  20. Organic geochemistry of the early Toarcian oceanic anoxic event in Hawsker Bottoms, Yorkshire, England

    Science.gov (United States)

    French, K. L.; Sepúlveda, J.; Trabucho-Alexandre, J.; Gröcke, D. R.; Summons, R. E.

    2014-03-01

    A comprehensive organic geochemical investigation of the Hawsker Bottoms outcrop section in Yorkshire, England has provided new insights about environmental conditions leading into and during the Toarcian oceanic anoxic event (T-OAE; ∼183 Ma). Rock-Eval and molecular analyses demonstrate that the section is uniformly within the early oil window. Hydrogen index (HI), organic petrography, polycyclic aromatic hydrocarbon (PAH) distributions, and tricyclic terpane ratios mark a shift to a lower relative abundance of terrigenous organic matter supplied to the sampling locality during the onset of the T-OAE and across a lithological transition. Unlike other ancient intervals of anoxia and extinction, biomarker indices of planktonic community structure do not display major changes or anomalous values. Depositional environment and redox indicators support a shift towards more reducing conditions in the sediment porewaters and the development of a seasonally stratified water column during the T-OAE. In addition to carotenoid biomarkers for green sulfur bacteria (GSB), we report the first occurrence of okenane, a marker of purple sulfur bacteria (PSB), in marine samples younger than ∼1.64 Ga. Based on modern observations, a planktonic source of okenane's precursor, okenone, would require extremely shallow photic zone euxinia (PZE) and a highly restricted depositional environment. However, due to coastal vertical mixing, the lack of planktonic okenone production in modern marine sulfidic environments, and building evidence of okenone production in mat-dwelling Chromatiaceae, we propose a sedimentary source of okenone as an alternative. Lastly, we report the first parallel compound-specific δC13 record in marine- and terrestrial-derived biomarkers across the T-OAE. The δC13 records of short-chain n-alkanes, acyclic isoprenoids, and long-chain n-alkanes all encode negative carbon isotope excursions (CIEs), and together, they support an injection of isotopically light

  1. The Cenozoic Diversity of Agglutinated Foraminifera - Evidence for a late Oligocene to early Miocene diversification event

    Science.gov (United States)

    Kaminski, Michael; Setoyama, Eiichi; Kender, Sev; Cetean, Claudia

    2014-05-01

    The agglutinated foraminifera are among the most abundant micro-organisms in the deep marine environment and have a diversity record extending back to the late Precambrian. We present an updated diversity curve for agglutinated foraminiferal genera based on the stratigraphic ranges of all the agglutinated genera recognized as valid in the classification of Kaminski (2014). The data set for this analysis is based on the stratigraphic ranges of agglutinated genera published in Foraminiferal Genera and their Classification, which has been subsequently updated based on published studies and our new observations. The mean standing diversity of agglutinated foraminiferal genera was compiled by counting the number of boundary crossers rather than the number of genera in each stage. In this study, we report the stratigraphic and geographical occurrence of a benthic foraminiferal diversification event that has previously received little attention. In the latest Oligocene to earliest Miocene a number of trochospiral agglutinated genera with alveolar or canaliculate walls first appeared in the fossil record. Our studies of late Oligocene of the Congo fan, offshore Angola (Kender et al., 2008; Cetean and Kaminski, 2011) have revealed a diverse assemblage that includes new taxa of deep-water agglutinated foraminifera. In a biostratigraphic study of the Miocene foraminiferal assemblages Kender et al. (2008) noted steadily increasing diversity and proportions of infaunal agglutinated foraminiferal morphotypes over the lower Miocene interval. The proportion of infaunal agglutinated foraminifera assigned to the order Textularida increased dramatically in the lower mid-Miocene, suggesting expansion of the oxygen minimum zone into deeper waters. In addition to the trochospiral alveolar genera, several species of Reticulophragmium and Cyclammina display rapid diversification into numerous separate lineages that are at present not reflected in our generic diversity record owing to

  2. Early Verb Learning: How Do Children Learn How to Compare Events?

    Science.gov (United States)

    Childers, Jane B.; Parrish, Rebecca; Olson, Christina V.; Burch, Clare; Fung, Gavin; McIntyre, Kevin P.

    2016-01-01

    An important problem verb learners must solve is how to extend verbs. Children could use cross-situational information to guide their extensions; however, comparing events is difficult. In 2 studies, researchers tested whether children benefit from initially seeing a pair of similar events ("progressive alignment") while learning new…

  3. Early thromboembolic events ≤1week after fast-track total hip and knee arthroplasty

    DEFF Research Database (Denmark)

    Jørgensen, Christoffer C; Kehlet, Henrik; Laursen, Mogens Berg

    2016-01-01

    IntroductionThromboembolic events (TEE) are serious complications after total hip (THA) and knee arthroplasty (TKA), with reported in-hospital incidences of about 0.5?1% for venous thromboembolic events (VTE) and 0.2% for myocardial infarctions (MI) and stroke. However, little data exist on in...

  4. Stressful Events and Temperament Change during Early and Middle Adolescence : The TRAILS Study

    NARCIS (Netherlands)

    Laceulle, O. M.; Nederhof, E.; Karreman, A.; Ormel, J.; Van Aken, M. A. G.

    2012-01-01

    This project investigates how stressful events are related to deviations from normative temperament development during adolescence. Temperament traits were assessed at ages 11 and 16?years. Life-event data was captured using an interview (total n?=?1197). Normative changes were found in all traits.

  5. Excessive milk production during breast-feeding prior to breast cancer diagnosis is associated with increased risk for early events

    OpenAIRE

    Gustbée, Emma; Anesten, Charlotte; Markkula, Andrea; Simonsson, Maria; Rose, Carsten; Ingvar, Christian; Jernström, Helena

    2013-01-01

    Breast-feeding is a known protective factor against breast cancer. Breast-feeding duration is influenced by hormone levels, milk production, and lifestyle factors. The aims were to investigate how breast-feeding duration and milk production affected tumor characteristics and risk for early breast cancer events in primary breast cancer patients. Between 2002 and 2008, 634 breast cancer patients in Lund, Sweden, took part in an ongoing prospective cohort study. Data were extracted from question...

  6. Early detection of atrial high rate episodes predicts atrial fibrillation and thromboembolic events in patients with cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Witt, Christoffer Tobias; Kronborg, Mads Brix; Nohr, Ellen Aagaard

    2015-01-01

    BACKGROUND: In patients without any history of atrial fibrillation (AF), detection of subclinical atrial high rate episodes (AHRE) by implanted devices has been associated with an increased thromboembolic risk. The predictive value of AHRE in patients with cardiac resynchronization therapy (CRT...... of AF, detection of early AHRE after CRT implantation is associated with a significantly increased risk of clinical AF and thromboembolic events, particularly AHRE longer than 24 hours....

  7. Involvement of FGF and BMP family proteins and VEGF in early human kidney development.

    Science.gov (United States)

    Carev, Dominko; Saraga, Marijan; Saraga-Babic, Mirna

    2008-07-01

    The spatial and temporal pattern of the appearance of the fibroblast growth factor proteins (FGF-8 and FGF-10), the bone morphogenetic proteins (BMP-2/4 subfamily and BMP-7) and the vascular endothelial growth factor protein (VEGF) was investigated in the human mesonephros and metanephros of the 5-9 week-old conceptuses. In the mesonephros, both FGF's and BMP's were found in all structures and their expression slightly decreased in the early fetal period. VEGF positivity appeared in all mesonephric structures, and increased in the fetal period coincidently with formation of the mesonephric blood vessel network. In the metanephros, FGF-8 first appeared only in the metanephric mesenchyme, but from the 7th week on, its reactivity increased and spread to other metanephric structures. FGF-10 positive cells appeared in all metanephric structures already in the 5th week, and slightly intensified with progression of development. Cell survival and nephrogenesis in the permanent kidney might be associated with the appearance of both growth factors. Both BMP-2/4 and BMP-7 displayed a similar pattern of reactivity in all metanephric structures, and their reactivity intensified with advancing development. Alterations in their pattern of appearance might lead to the formation of small and dysplastic kidneys. Already in the earliest developmental stages, VEGF protein appeared in all metanephric structures. At later stages, VEGF showed more intense reaction in the collecting system than in the differentiating nephrons and interstitium. Due to VEGF involvement in vasculogenesis and angiogenesis, abnormal VEGF appearance might lead to impaired formation of the blood vessel network in the human permanent kidney.

  8. Involvement of metabolites in early defense mechanism of oil palm (Elaeis guineensis Jacq.) against Ganoderma disease.

    Science.gov (United States)

    Nusaibah, S A; Siti Nor Akmar, A; Idris, A S; Sariah, M; Mohamad Pauzi, Z

    2016-12-01

    Understanding the mechanism of interaction between the oil palm and its key pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen leads to a major loss of revenue in leading palm oil producing countries in Southeast Asia. Here in this study, we assess the morphological and biochemical changes in Ganoderma disease infected oil palm seedling roots in both resistant and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were applied as a source of inoculum to artificially infect the roots of resistant and susceptible oil palm progenies. Gas chromatography-mass spectrometry was used to measure an array of plant metabolites in 100 resistant and susceptible oil palm seedling roots treated with pathogenic Ganoderma boninense fungus. Statistical effects, univariate and multivariate analyses were used to identify key-Ganoderma disease associated metabolic agitations in both resistant and susceptible oil palm root tissues. Ganoderma disease related defense shifts were characterized based on (i) increased antifungal activity in crude extracts, (ii) increased lipid levels, beta- and gamma-sitosterol particularly in the resistant progeny, (iii) detection of heterocyclic aromatic organic compounds, benzo [h] quinoline, pyridine, pyrimidine (iv) elevation in antioxidants, alpha- and beta-tocopherol (iv) degraded cortical cell wall layers, possibly resulting from fungal hydrolytic enzyme activity needed for initial penetration. The present study suggested that plant metabolites mainly lipids and heterocyclic aromatic organic metabolites could be potentially involved in early oil palm defense mechanism against G. boninense infection, which may also highlight biomarkers for disease detection, treatment, development of resistant variety and monitoring. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Consumption of hydrogen-rich water protects against ferric nitrilotriacetate-induced nephrotoxicity and early tumor promotional events in rats.

    Science.gov (United States)

    Li, Fang-Yin; Zhu, Shao-Xing; Wang, Zong-Ping; Wang, Hua; Zhao, Yang; Chen, Gui-Ping

    2013-11-01

    The aim of this work was to test whether consumption with hydrogen-rich water (HW) alleviated renal injury and inhibited early tumor promotional events in Ferric nitrilotriacetate (Fe-NTA)-treated rats. Rats were injected with Fe-NTA solution (7.5mg Fe/kg body weight) intraperitoneally to induce renal injury and simultaneously treated with HW (1.3 ± 0.2mg/l). We found that consumption with HW ameliorated Fe-NTA-induced renal injuries including suppressing elevation of serum creatinine and blood urea nitrogen and inhibited early tumor promotional events including decreasing ornithine decarboxylase activity and incorporation of [3H]thymidine into renal DNA. Consumption with HW suppressed Fe-NTA-induced oxidative stress through decreasing formation of lipid peroxidation and peroxynitrite and activities of NADPH oxidase and xanthine oxidase, increasing activity of catalase, and restoring mitochondrial function in kidneys. Consumption with HW suppressed Fe-NTA-induced inflammation marked by reduced NF-κB, IL-6, and MCP-1 expression and macrophage accumulating in kidneys. In addition, consumption with HW suppressed VEGF expression, STAT3 phosphorylation and PCNA expression in kidneys of Fe-NTA-treated rats. Consumption with HW decreased the incidence of renal cell carcinoma and suppressed tumor growth in Fe-NTA-treated in rats. In conclusion, drinking with HW attenuated Fe-NTA-induced renal injury and inhibited early tumor promotional events in rats.

  10. Early Paleozoic (Pan African) thermal event of the Larsemann Hills and its neighbours, Prydz Bay, East Antarctica

    Institute of Scientific and Technical Information of China (English)

    赵越; 宋彪; 张宗清; 富云莲; 陈廷愚; 王彦斌; 任留东; 姚玉鹏; 李继亮; 刘小汉

    1995-01-01

    The early Paleozoic (Pan African) thermal event of the Larsemann Hills and its adjacent areas, East Antarctica is discussed based upon the isotope ages we obtained. An Sm-Nd internal isochron for a representative mafic granulite yields an age of 540 Ma±75 Ma. Another Sm-Nd internal isochron, which is made up of the assemblage of the peak metamorphism and its whole rock as well, gives an age of 497 Ma ± 7 Ma The isotopic chronological data of single zircon stepwise evaporation dating and 40Ar-39Ar analysis provide further evidence for the early Paleozoic event of high-grade metamorphism in the region. The data from the field geological investigation in the Larsemann Hills also show that there is not only strong regional partial melting but also low-pressure granulite-facies metamorphism accompanied by it in the region. The early Paleozoic (Pan African) thermal event of the region may be related to the final formation of the East Antarctica craton, even of Gondwanaland.

  11. Larger N2 and smaller early contingent negative variation during the processing of uncertainty about future emotional events.

    Science.gov (United States)

    Lin, Huiyan; Gao, Hongwei; You, Jin; Liang, Jiafeng; Ma, Junpeng; Yang, Nan; Xu, Huan; Jin, Hua

    2014-12-01

    Uncertainty increases individuals' anxiety and fear. Identifying its neural processing may contribute to understanding the detrimental effects of uncertainty on well-being and psychological symptoms. Using high temporal resolution event-related potentials (ERPs), employing the classical paradigm in which neutral signs were used as certain and uncertain cues and anticipating arousal-balanced positive and negative pictures, the present study aimed to further investigate the temporal dynamics of brain activation by uncertainty about future emotional events. ERPs were recorded while participants observed uncertain cues and certain cues about future positive and negative pictures. Results showed that the uncertain cues produced larger N2 than did the certain cues about both future positive and negative pictures, and uncertain cues produced smaller early contingent negative variation (CNV) than did the certain cues about future negative pictures. The results provide evidence that the specific processing of uncertainty about future emotional events occurs at different cognitive stages.

  12. Modeling Temporal Processes in Early Spacecraft Design: Application of Discrete-Event Simulations for Darpa's F6 Program

    Science.gov (United States)

    Dubos, Gregory F.; Cornford, Steven

    2012-01-01

    While the ability to model the state of a space system over time is essential during spacecraft operations, the use of time-based simulations remains rare in preliminary design. The absence of the time dimension in most traditional early design tools can however become a hurdle when designing complex systems whose development and operations can be disrupted by various events, such as delays or failures. As the value delivered by a space system is highly affected by such events, exploring the trade space for designs that yield the maximum value calls for the explicit modeling of time.This paper discusses the use of discrete-event models to simulate spacecraft development schedule as well as operational scenarios and on-orbit resources in the presence of uncertainty. It illustrates how such simulations can be utilized to support trade studies, through the example of a tool developed for DARPA's F6 program to assist the design of "fractionated spacecraft".

  13. Interrelationships between yeast ribosomal protein assembly events and transient ribosome biogenesis factors interactions in early pre-ribosomes.

    Directory of Open Access Journals (Sweden)

    Steffen Jakob

    Full Text Available Early steps of eukaryotic ribosome biogenesis require a large set of ribosome biogenesis factors which transiently interact with nascent rRNA precursors (pre-rRNA. Most likely, concomitant with that initial contacts between ribosomal proteins (r-proteins and ribosome precursors (pre-ribosomes are established which are converted into robust interactions between pre-rRNA and r-proteins during the course of ribosome maturation. Here we analysed the interrelationship between r-protein assembly events and the transient interactions of ribosome biogenesis factors with early pre-ribosomal intermediates termed 90S pre-ribosomes or small ribosomal subunit (SSU processome in yeast cells. We observed that components of the SSU processome UTP-A and UTP-B sub-modules were recruited to early pre-ribosomes independently of all tested r-proteins. On the other hand, groups of SSU processome components were identified whose association with early pre-ribosomes was affected by specific r-protein assembly events in the head-platform interface of the SSU. One of these components, Noc4p, appeared to be itself required for robust incorporation of r-proteins into the SSU head domain. Altogether, the data reveal an emerging network of specific interrelationships between local r-protein assembly events and the functional interactions of SSU processome components with early pre-ribosomes. They point towards some of these components being transient primary pre-rRNA in vivo binders and towards a role for others in coordinating the assembly of major SSU domains.

  14. Reduced early visual emotion discrimination as an index of diminished emotion processing in Parkinson's disease? - Evidence from event-related brain potentials.

    Science.gov (United States)

    Wieser, Matthias J; Klupp, Elisabeth; Weyers, Peter; Pauli, Paul; Weise, David; Zeller, Daniel; Classen, Joseph; Mühlberger, Andreas

    2012-10-01

    Although Parkinson's disease (PD) is defined by its motor symptoms, it is now well recognized that cognitive and affective domains, such as recognition of emotion from facial expressions, may also be impaired. To examine brain mechanisms involved in processing of emotion recognition from facial expressions, we obtained affective ratings and visual event-related potentials (ERPs) in response to facial expressions from 18 PD patients under dopamine-replacement therapy, and 17 healthy age- and sex-matched controls. In control subjects, the early posterior negativity (EPN) of the ERP, which is thought to reflect early perceptual emotion discrimination, was larger in response to emotional compared to neutral facial expressions. In contrast, this emotional modulation of the EPN was absent in PD patients indicating impaired early emotion discrimination. Behaviorally, PD patients showed no impairments in emotion recognition as measured by affective ratings. These findings suggest that facial emotion processing may be disrupted at an early stage of visual neural processing in PD. Absence of behavioral impairment may point to compensatory strategies of emotion recognition in medicated PD patients. Further research should clarify these dissociations between behavioral and neurophysiological levels of emotion processing in PD. Copyright © 2011 Elsevier Srl. All rights reserved.

  15. Early involvement of lysosome dysfunction in the degeneration of cerebral cortical neurons caused by the lipid peroxidation product 4-hydroxynonenal.

    Science.gov (United States)

    Zhang, Shi; Eitan, Erez; Mattson, Mark P

    2017-03-01

    Free radical-mediated oxidative damage to proteins, lipids, and DNA occurs in neurons during acute brain injuries and in neurodegenerative disorders. Membrane lipid peroxidation contributes to neuronal dysfunction and death, in part by disrupting neuronal ion homeostasis and cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced during lipid peroxidation, impairs the function of various proteins involved in neuronal homeostasis. Here we tested the hypothesis that HNE impairs the cellular system that removes damaged proteins and organelles, the autophagy-lysosome pathway in rat primary cortical neurons. We found that HNE, at a concentration that causes apoptosis over a 48-72 h period, increases protein levels of LC3 II and p62 and within 1 and 4 h of exposure, respectively; LC3 II and p62 immunoreactive puncta were observed in the cytoplasm of HNE-treated neurons at 6 h. The extent of up-regulation of p62 and LC3 II in response to HNE was not affected by co-treatment with the lysosome inhibitor bafilomycin A1, suggesting that the effects of HNE on autophagy were secondary to lysosome inhibition. Indeed, we found that neurons exposed to HNE exhibit elevated pH levels, and decreased protein substrate hydrolysis and cathepsin B activity. Neurons exposed to HNE also exhibited the accumulation of K63-linked polyubiquitinated proteins, which are substrates targeted for lysosomal degradation. Moreover, we found that the levels of LAMP2a and constitutively active heat-shock protein 70, and numbers of LAMP2a-positive lysosomes, are decreased in neurons exposed to HNE. Our findings demonstrate that the lipid peroxidation product HNE causes early impairment of lysosomes which may contribute to the accumulation of damaged and dysfunctional proteins and organelles and consequent neuronal death. Because impaired lysosome function is increasingly recognized as an early event in the neuronal death that occurs in neurodegenerative

  16. Massive Expansion of Marine Archaea During The Early Albian Oceanic Anoxic Event 1B

    Science.gov (United States)

    Kuypers, M. M.; Kuypers, M. M.; Blokker, P.; Erbacher, J.; Kinkel, H.; Pancost, R. D.; Pancost, R. D.; Schouten, S.; Sinninghe Damsté, J. S.

    2001-12-01

    Oceanic anoxic events (OAEs), periods of globally enhanced burial of organic matter (OM) in the marine realm, played an important role in the mid-Cretaceous `greenhouse climate' by effectively reducing atmospheric carbon dioxide concentrations. It is generally believed that these OAEs were caused either by decreased remineralisation or increased production of phytoplanktonic OM. Here we show that enhanced organic carbon (OC) burial during the early Albian OAE1b (~112 My) was caused by a different process. Combined biogeochemical and stable carbon isotopic analyses indicate that black shales from this period contain up to 80% of OC derived from archaea. Archaea-derived isoprenoidal tetraether membrane lipids and free and macromolecularly bound isoprenoid alkanes are abundantly present in these black shales. More specifically the presence of certain ether lipids (cyclic biphytane tetraethers) indicates representatives of the pelagic archaea. To the best of our knowledge this is the earliest fossil evidence for marine planktonic archaea, extending their geological record by more than 60 million years. The diversity of archaeal lipids recovered from the OAE1b black shales suggests that they derive from a multitude of archaeal species. However, the specific 13C enrichment of all such lipids indicates a common `heavy' (13C-rich) carbon source for the archaea and/or a common pathway of carbon-fixation with a reduced 13C fractionation effect compared to the Calvin cycle used by algae, cyanobacteria and higher plants. The large differences (up to 12%) in 13C/12C ratios between the algal biomarkers and the much more abundant archaeal molecular fossils suggest that the latter were not living heterotrophically on photoautotrophic biomass. It seems likely that the archaea present during OAE1b used a chemical energy source (possibly ammonium) for carbon fixation since photoautotrophy within the domain of the Archaea is restricted to only a few species from hypersaline

  17. Is epigenetics an important link between early life events and adult disease?

    Science.gov (United States)

    Epigenetic mechanisms provide one potential explanation for how environmental influences in early life cause long-term changes in chronic disease susceptibility. Whereas epigenetic dysregulation is increasingly implicated in various rare developmental syndromes and cancer, the role of epigenetics in...

  18. An abrupt cooling event early in the last interglacial in the northern South China Sea

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The high-resolution quantitative analysis of the planktonic foraminifera and the δ18O records of the section between 96.49-137.6 mcd at ODP Site 1144 on the continental slope ot northern South China Sea reveals an abrupt cooling event of sea surface temperature (SST) dur ing the last interglacial (MIS 5.5, i.e. 5e). The dropping range of the winter SST may come to 7.5℃corresponding to 1.2‰ of the δ18O value of sea surface water. This event is comparable with those discovered in the west Europe and the northern Atlantic Ocean, but expressed in a more intensive way. It is inferred that this event may have been induced by middle- to Iow-latitude processes rather than by polar ice sheet change. Since the Kuroshio-index species Pulleniatina obliquilocu lata displayed the most distinct change at the event, it may also be related to the paleocean ographic change of the Iow-latitude area in the western Pacific Ocean. This event can be consid ered as one of "Younger Dryas-style coolings" and is indicative of climate variability of the last in terglacial stage.

  19. Seismology-based early identification of dam-formation landquake events

    Science.gov (United States)

    Wu, Y. M.; Chao, W. A.

    2015-12-01

    Flooding resulting from the bursting of dams formed by landquake events such as rock avalanches, landslides and debris flows can lead to serious bank erosion and inundation of populated areas near rivers. Seismic waves can be generated by landquake events which can be described as time-dependent forces (unloading/reloading cycles) acting on the Earth. In this study, we conduct inversions of long-period (LP, period ≥ 20 sec) waveforms for different source mechanisms. Results show that single-force (SF) mechanism better explains the observed seismograms generated by landquake events. We then perform inversions for the landquake force histories (LFHs) of ten events, which provide quantitative characterization of the initiation, propagation and termination stages of the slope failures. When the results obtained from LP waveforms are analyzed together with high-frequency (HF, 1-3 Hz) seismic signals, we find a relatively strong late-arriving seismic phase (dubbed Dam-forming phase or D-phase) recorded clearly in the HF waveforms at the closest stations, which potentially marks the time when the collapsed masses sliding into river and perhaps even impacting the topographic barrier on the opposite bank. Consequently, our approach to analyzing the LP and HF waveforms developed in this study has a high potential for identifying five dam-forming landquake events (DFLEs) in near real-time using broadband seismic records, which can provide timely warnings of the impending floods to downstream residents.

  20. Early Elementary School Adjustment of Maltreated Children in Foster Care: The Roles of Inhibitory Control and Caregiver Involvement

    Science.gov (United States)

    Pears, Katherine C.; Fisher, Philip A.; Bruce, Jacqueline; Kim, Hyoun K.; Yoerger, Karen

    2010-01-01

    In this study, 85 maltreated foster children and 56 nonmaltreated community children (M age = 3-6 years) were assessed across kindergarten and first grade to examine the hypothesis that inhibitory control and caregiver involvement mediate associations between a history of maltreatment and foster placement and early school adjustment. Specifically,…

  1. La Participacion de los Padres en los Programas Preescolares. (Hispanic Parent Involvement in Early Childhood Programs.) ERIC Digest.

    Science.gov (United States)

    Espinosa, Linda M.

    To determine effective strategies for involving Hispanic parents in their children's early childhood programs, educators need to develop a greater understanding of the features of the Hispanic culture that influence parents' childrearing practices and orientation toward formal education. Educators should be aware of Hispanics' diversity in terms…

  2. Factors involved in early polarization of the anterior-posterior axis in the milkweed bug Oncopeltus fasciatus.

    Science.gov (United States)

    Ginzburg, Neta; Cohen, Mira; Chipman, Ariel D

    2017-05-01

    The axes of insect embryos are defined early in the blastoderm stage. Genes involved in this polarization are well known in Drosophila, but less so in other insects, such as the milkweed bug Oncopeltus fasciatus. Using quantitative PCR, we looked at differential expression of several candidate genes for early anterior-posterior patterning and found that none of them are expressed asymmetrically in the early blastoderm. We then used an RNA-Seq approach to identify novel candidate genes that might be involved in early polarization in Oncopeltus. We focused on transcription factors (TFs) as these are likely to be central players in developmental processes. Using both homology and domain based identification approaches, we were unable to find any TF encoding transcripts that are expressed asymmetrically along the anterior-posterior axis at early stages. Using a GO-term analysis of all asymmetrically expressed mRNAs, we found an enrichment of genes relating to mitochondrial function in the posterior at the earliest studied time-point. We also found a gradual enrichment of transcription related activities, giving us a putative time frame for the maternal to zygotic transition. Our dataset provides us with a list of new candidate genes in early development, which can be followed up experimentally. © 2017 Wiley Periodicals, Inc.

  3. Predicting addiction potential on the basis of early traumatic events, dissociative experiences, and suicide ideation.

    Science.gov (United States)

    Sajadi, Seyedeh Fatemeh; Hajjari, Zahra; Zargar, Yadollah; Mehrabizade Honarmand, Mahnaz; Arshadi, Nasrin

    2014-12-01

    There is a great deal of medical literature suggesting that substance use disorder is a serious clinical concern, affecting general population and associated with considerable economic, societal, and personal costs. This study sought to clarify the relationship between early trauma, dissociative experience, and suicide ideation as predictive factors of active and passive addiction potential (A/PAP) in high-school students. Three hundred students with the mean age of 15.72 y were selected via multistage random sampling. All participants were asked to complete Iranian addiction potential scale, early trauma inventory, dissociative experiences scale, and Beck's suicide ideation scale. Analyzing data was done using canonical correlation. Structural coefficients showed that the pattern of high scores in A/PAP correlates with the pattern of high scores in early trauma, dissociative experience and suicide ideation. The findings of the study showed that the combination of low A/PAP can probably decrease the likelihood of early trauma, dissociative experience and suicide ideation. Early trauma, dissociative experience, and suicide ideation can predict A/PAP and explain the considerable variance of survival index.

  4. Seismology-based early identification of dam-formation landquake events

    Science.gov (United States)

    Chao, Wei-An; Zhao, Li; Chen, Su-Chin; Wu, Yih-Min; Chen, Chi-Hsuan; Huang, Hsin-Hua

    2016-01-01

    Flooding resulting from the bursting of dams formed by landquake events such as rock avalanches, landslides and debris flows can lead to serious bank erosion and inundation of populated areas near rivers. Seismic waves can be generated by landquake events which can be described as time-dependent forces (unloading/reloading cycles) acting on the Earth. In this study, we conduct inversions of long-period (LP, period ≥20 s) waveforms for the landquake force histories (LFHs) of ten events, which provide quantitative characterization of the initiation, propagation and termination stages of the slope failures. When the results obtained from LP waveforms are analyzed together with high-frequency (HF, 1–3 Hz) seismic signals, we find a relatively strong late-arriving seismic phase (dubbed Dam-forming phase or D-phase) recorded clearly in the HF waveforms at the closest stations, which potentially marks the time when the collapsed masses sliding into river and perhaps even impacting the topographic barrier on the opposite bank. Consequently, our approach to analyzing the LP and HF waveforms developed in this study has a high potential for identifying five dam-forming landquake events (DFLEs) in near real-time using broadband seismic records, which can provide timely warnings of the impending floods to downstream residents. PMID:26753931

  5. Early referential context effects in sentence processing: Evidence from event-related brain potentials

    NARCIS (Netherlands)

    Berkum, J.J.A. van; Brown, C.M.; Hagoort, P.

    1999-01-01

    An event-related brain potentials experiment was carried out to examine the interplay of referential and structural factors during sentence processing in discourse. Subjects read (Dutch) sentences beginning like “David told the girl that … ” in short story contexts that had introduced either one or

  6. It's the Little Things: Exploring the Importance of Commonplace Events for Early-Career Teachers' Motivation

    Science.gov (United States)

    Kitching, Karl; Morgan, Mark; O'Leary, Michael

    2009-01-01

    This paper seeks to provide a rationale for further researching the everyday events that keep teachers motivated or that discourage them. We put forward the idea that routine Affect Triggering Incidents (ATIs) are an important area for researchers to investigate in terms of how they impact teacher motivation and resilience. Two groups of…

  7. Astronomical pacing of late Palaeocene to early Eocene global warming events

    NARCIS (Netherlands)

    Lourens, L.J.; Sluijs, A.; Kroon, D.; Zachos, J.C.; Thomas, E.; Röhl, U.; Bowles, J.; Raffi, I.

    2005-01-01

    At the boundary between the Palaeocene and Eocene epochs, about 55 million years ago, the Earth experienced a strong global warming event, the Palaeocene–Eocene thermal maximum. The leading hypothesis to explain the extreme greenhouse conditions prevalent during this period is the dissociation of 1,

  8. Skin carcinomas in organ-transplant recipients : from early oncogenic events to therapy

    NARCIS (Netherlands)

    Graaf, Ymke Grete Leontien de

    2008-01-01

    Skin carcinomas develop at a high rate in organ-transplant recipients who are kept on immune suppressive drugs to prevent graft rejection. The present study dealt with a broad range of aspects of this elevated carcinoma risk, starting from the earliest oncogenic events to the ultimate therapy.

  9. Early Perception of Written Syllables in French: An Event-Related Potential Study

    Science.gov (United States)

    Doignon-Camus, Nadege; Bonnefond, Anne; Touzalin-Chretien, Pascale; Dufour, Andre

    2009-01-01

    The present study examined whether written syllable units are perceived in first steps of letter string processing. An illusory conjunction experiment was conducted while event-related potentials were recorded. Colored pseudowords were presented such that there was a match or mismatch between the syllable boundaries and the color boundaries. The…

  10. Skin carcinomas in organ-transplant recipients : from early oncogenic events to therapy

    NARCIS (Netherlands)

    Graaf, Ymke Grete Leontien de

    2008-01-01

    Skin carcinomas develop at a high rate in organ-transplant recipients who are kept on immune suppressive drugs to prevent graft rejection. The present study dealt with a broad range of aspects of this elevated carcinoma risk, starting from the earliest oncogenic events to the ultimate therapy. Advan

  11. Origins of Early Adolescents' Hope: Personality, Parental Attachment, and Stressful Life Events

    Science.gov (United States)

    Otis, Kristin L.; Huebner, E. Scott; Hills, Kimberly J.

    2016-01-01

    Psychology has recently increased attention to identifying psychological qualities in individuals that indicate positive mental health, such as hope. In an effort to understand further the origins of hope, we examined the relations among parental attachment, stressful life events, personality variables, and hope in a sample of 647 middle school…

  12. Integrating Sentence-Structural and Event Information in Early Verb Learning

    Science.gov (United States)

    Yuan, Sylvia Hsin Wei

    2009-01-01

    Children use syntax as well as observations of events to learn verb meanings. This is known as syntactic bootstrapping. This dissertation investigated the origins and mechanisms of syntactic bootstrapping. Prior evidence suggested that two-year-olds, but not younger children, could use aspects of sentence structure to assign different…

  13. Risk Factors for Preschool Depression: The Mediating Role of Early Stressful Life Events

    Science.gov (United States)

    Luby, Joan L.; Belden, Andy C.; Spitznagel, Edward

    2006-01-01

    Background: Family history of mood disorders and stressful life events are both established risk factors for childhood depression. However, the role of mediators in risk trajectories, which are potential targets for intervention, remains understudied. To date, there have been no investigations of mediating relationships between risk factors and…

  14. Seismology-based early identification of dam-formation landquake events

    Science.gov (United States)

    Chao, Wei-An; Zhao, Li; Chen, Su-Chin; Wu, Yih-Min; Chen, Chi-Hsuan; Huang, Hsin-Hua

    2016-01-01

    Flooding resulting from the bursting of dams formed by landquake events such as rock avalanches, landslides and debris flows can lead to serious bank erosion and inundation of populated areas near rivers. Seismic waves can be generated by landquake events which can be described as time-dependent forces (unloading/reloading cycles) acting on the Earth. In this study, we conduct inversions of long-period (LP, period ≥20 s) waveforms for the landquake force histories (LFHs) of ten events, which provide quantitative characterization of the initiation, propagation and termination stages of the slope failures. When the results obtained from LP waveforms are analyzed together with high-frequency (HF, 1-3 Hz) seismic signals, we find a relatively strong late-arriving seismic phase (dubbed Dam-forming phase or D-phase) recorded clearly in the HF waveforms at the closest stations, which potentially marks the time when the collapsed masses sliding into river and perhaps even impacting the topographic barrier on the opposite bank. Consequently, our approach to analyzing the LP and HF waveforms developed in this study has a high potential for identifying five dam-forming landquake events (DFLEs) in near real-time using broadband seismic records, which can provide timely warnings of the impending floods to downstream residents.

  15. Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

    Science.gov (United States)

    Berghella, Libera; Ferraro, Elisabetta

    2012-01-01

    Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

  16. Early Healing Events around Titanium Implant Devices with Different Surface Microtopography: A Pilot Study in an In Vivo Rabbit Model

    Directory of Open Access Journals (Sweden)

    Ester Orsini

    2012-01-01

    Full Text Available In the present pilot study, the authors morphologically investigated sandblasted, acid-etched surfaces (SLA at very early experimental times. The tested devices were titanium plate-like implants with flattened wide lateral sides and jagged narrow sides. Because of these implant shape and placement site, the device gained a firm mechanical stability but the largest portion of the implant surface lacked direct contact with host bone and faced a wide peri-implant space rich in marrow tissue, intentionally created in order to study the interfacial interaction between metal surface and biological microenvironment. The insertion of titanium devices into the proximal tibia elicited a sequence of healing events. Newly formed bone proceeded through an early distance osteogenesis, common to both surfaces, and a delayed contact osteogenesis which seemed to follow different patterns at the two surfaces. In fact, SLA devices showed a more osteoconductive behavior retaining a less dense blood clot, which might be earlier and more easily replaced, and leading to a surface-conditioning layer which promotes osteogenic cell differentiation and appositional new bone deposition at the titanium surface. This model system is expected to provide a starting point for further investigations which clarify the early cellular and biomolecular events occurring at the metal surface.

  17. TP53 mutations are early events in chronic lymphocytic leukemia disease progression and precede evolution to complex karyotypes.

    Science.gov (United States)

    Lazarian, Gregory; Tausch, Eugen; Eclache, Virginie; Sebaa, Amel; Bianchi, Vincent; Letestu, Remi; Collon, Jean-Francois; Lefebvre, Valerie; Gardano, Laura; Varin-Blank, Nadine; Soussi, Thierry; Stilgenbauer, Stephen; Cymbalista, Florence; Baran-Marszak, Fanny

    2016-10-15

    TP53 abnormalities lead to resistance to purine analogues and are found in over 40% of patients with refractory chronic lymphocytic leukemia (CLL). At diagnosis, no more than 5% of patients carry the 17p deletion, most cases harbour mutations within the other TP53 allele. The incidence of a TP53 mutation as the only alteration is approximately 5%, but this depends on the sensitivity of the technique. Recently, having a complex karyotype has been considered a strong adverse prognostic factor. However, there are no longitudinal studies simultaneously examining the presence of the 17p deletion, TP53 mutations and karyotype abnormalities. We conducted a retrospective longitudinal study of 31 relapsed/refractory CLL patients. Two to six blood samples per patient were analyzed, with a median follow-up of 8 years. In this report, we assessed the sequence of events of TP53 clonal evolution and correlated the presence of TP53 abnormalities to genetic instability during progression and treatment. Next-generation sequencing allowed the early detection of TP53 mutated clones and was able to be performed on a routine basis, demonstrating an excellent correlation between the Illumina and Ion Torrent technologies. We concluded that TP53 mutations are early events and precede clonal evolution to complex karyotypes. We strongly recommend the early and iterated detection of TP53 mutations in progressive cases.

  18. Remembering or Concealing Mythical and Historical Events in the Cityscape of Early Roman Ephesus

    DEFF Research Database (Denmark)

    2015-01-01

    The cityscape of early Roman Ephesus incorporated and referenced narratives from the city’s past. But there are some gaps in the stories being told. Do these gaps in the narratives demonstrate an intentional concealment of segments of the city’s history? This article discusses the meanings of the...

  19. Astrochronology of extreme global warming events during the early Eocene greenhouse climate

    NARCIS (Netherlands)

    Lauretano, V.

    2016-01-01

    The early Eocene represents an ideal case study to analyse the impact of enhanced global warming on the ocean-atmosphere system and the relationship between carbon cycling and climate. During this time interval, the Earth’s surface experienced a long-term warming trend that culminated in a period of

  20. Coping with a life event in bipolar disorder : ambulatory measurement, signalling and early treatment

    NARCIS (Netherlands)

    Knapen, Stefan E; Riemersma-van der Lek, Rixt F; Haarman, Bartholomeus C M; Schoevers, Robert A

    2016-01-01

    Disruption of the biological rhythm in patients with bipolar disorder is a known risk factor for a switch in mood. This case study describes how modern techniques using ambulatory assessment of sleep parameters can help in signalling a mood switch and start early treatment. We studied a 40-year-old

  1. Spiders do not evoke greater early posterior negativity in the event-related potential as snakes.

    Science.gov (United States)

    He, Hongshen; Kubo, Kenta; Kawai, Nobuyuki

    2014-09-10

    It has been long believed that both snakes and spiders are archetypal fear stimuli for humans. Furthermore, snakes have been assumed as stronger threat cues for nonhuman primates. However, it is still unclear whether spiders hold a special status in human perception. The current study explored to what extent spider pictures draw early visual attention [as assessed with early posterior negativity (EPN)] when compared with insects similar to spiders. To measure the EPN, participants watched a random rapid serial presentation of pictures, which consisted of two conditions: spider condition (spider, wasp, bumblebee, beetle) and snake condition (snake, bird). EPN amplitudes revealed no significant difference between spider, wasp, bumblebee, and beetle pictures, whereas EPN amplitudes were significantly larger for snake pictures relative to bird pictures. In addition, EPN amplitudes were significantly larger for snake pictures relative to spider pictures. These results suggest that the early visual attentional capture of animate objects is stronger for snakes, whereas spiders do not appear to hold special early attentional value.

  2. Early Top-Down Influences on Bistable Perception Revealed by Event-Related Potentials

    Science.gov (United States)

    Pitts, Michael A.; Gavin, William J.; Nerger, Janice L.

    2008-01-01

    A longstanding debate exists in the literature concerning bottom-up vs. top-down influences on bistable perception. Recently, a technique has been developed to measure early changes in brain activity (via ERPs) related to perceptual reversals (Kornmeier & Bach, 2004). An ERP component, the reversal negativity (RN) has been identified, and is…

  3. Mortality in Acute Pancreatitis: Is It an Early or a Late Event?

    Directory of Open Access Journals (Sweden)

    Antonio Carnovale

    2005-09-01

    Full Text Available Context Many prior studies have suggested that the majority of deaths in severe acute pancreatitis occur late in the course of the disease as a result of pancreatic sepsis or pancreatic septic-like syndrome. Other have observed that at least half of the deaths occur early as a result of multisystem organ failure. Objective The aim of the present study was to determine the timing of mortality of severe acute pancreatitis and to analyze the course of the disease in a large series of patients. Patients All consecutive patients with a diagnosis of acute pancreatitis admitted to our Centre from October 1984 to December 2000 were retrospectively studied. One thousand one hundred and fifty episodes of acute pancreatitis occurred in 1,135 patients. Main outcome measures Total mortality and frequency of early deaths (less than or equal to 14 days after admission. The clinical features of patients who died were also compared in the early and late mortality groups. Results The overall mortality rate of acute pancreatitis was 4.8% (55 deaths out of 1,135 cases and when considering the severe forms only, it was13.5% (55 deaths out of 408 cases; 28 deaths (50.9% occurred within the first two weeks of hospitalization (median day 8, range 2-14 whereas 27 cases (49.1% occurred after two weeks (median day 28, range 15-56. Early deaths resulted primarily from multisystem organ failure; late deaths occurred mainly from complications in patients having infected necrosis. Conclusion Early deaths in severe acute pancreatitis occur in the half of patients within the first 14 days owing to multi-organ system failure. The remainder of deaths occur later from complications secondary to the infection of pancreatic necrosis; in this subgroup of patients, the association of infected necrosis with organ failure is found frequently.

  4. The Sky in Early Modern English Literature A Study of Allusions to Celestial Events in Elizabethan and Jacobean Writing, 1572-1620

    CERN Document Server

    Levy, David H

    2011-01-01

    When a dissertation gets completed, the normal rule is that it is never read. By anyone.  David H. Levy’s dissertation - The Sky in Early Modern English Literature:  A Study of Allusions to Celestial Events in Elizabethan and Jacobean Writing, 1572-1620 - is different.  It opens a whole new interdisciplinary field, which involves the beautiful relationship between the night sky and the works of the early modern period of English Literature.  Although the sky enters into much of literature through the ages, the period involving William Shakespeare and his colleagues is particularly rich.               When Shakespeare was about 8 years old, his father probably took him outside his Stratford home into their northward-facing back yard.  There, father and son gazed upon the first great new star visible in the past 500 years, shining forth as brightly as Venus, and even visible in daylight.  This new star, which we now know as a supernova, completely unhinged old ideas about the cosmos.  Com...

  5. AN EVENT DRIVEN SIMULATION FOR ADAPTIVE GENTLE RANDOM EARLY DETECTION (AGRED ALGORITHM

    Directory of Open Access Journals (Sweden)

    Omid Seifaddini

    2014-01-01

    Full Text Available Simulations are used to find optimum answers for problems in wide areas. Active queue management algorithms such as RED, GRED, typically use simulators like ns2 which is an open source simulator or OPNET, OMNET which are commercial simulators. However, beside the benefits of using simulators like having defined modules, parameters. There are problems such as complexity, large integrated components and licensing cost. To have an ideal balance in mentioned benefits and problems and to further complement the repository of simulators, this study presents the description of a general-purpose programming language based discrete event simulation for active queue management. This research has focused at developing a discrete event simulator to implement one of active queue management algorithms which is called AGRED. The results showed that the developed simulator has successfully produced the same results with an average deviation of 1.5% as previous simulator in AGRED.

  6. Predicting early post-chemotherapy adverse events in patients with hematological malignancies: a retrospective study.

    Science.gov (United States)

    Fei, Xiaoming; Lei, Fang; Zhang, Haifeng; Lu, Hua; Zhu, Yan; Tang, Yu

    2016-06-01

    The purpose of this study was to develop a mathematical model that predicts the definite adverse events following chemotherapy in patients with hematological malignancies (HMs). This is a retrospective cohort study including 1157 cases with HMs. Firstly, we screened and verified the independent risk factors associated with post-chemotherapy adverse events by both univariate and multivariate logistic regression analysis using 70 % of randomly selected cases (training set). Secondly, we proposed a mathematical model based on those selected factors. The calibration and discrimination of the model were assessed by Hosmer-Lemeshow (H-L) test and area under the receiver operating characteristic (ROC) curve, respectively. Lastly, the predicative power of this model was further tested in the remaining 30 % of cases (validation set). Our statistical analysis indicated that liver dysfunction (OR = 2.164), active infection (OR = 3.619), coagulation abnormalities (OR = 4.614), intensity of chemotherapy (OR = 10.001), acute leukemia (OR = 2.185), and obesity (OR = 1.604) were independent risk factors for post-chemotherapy adverse events in HM patients (all P point, the sensitivity and specificity of this predictive model in validation sets was 72.7 and 87.4 %, respectively. Furthermore, this proposed model's positive predictive value, negative predictive value, and consistency rate were 87.3, 73.0 and 80.0 %, respectively. Our study indicated that this six risk factor-based mathematical model is accurate and sufficient enough to predict definite post-chemotherapy adverse events in a HM patient and it may aid clinicians to optimize treatment for a HM patient.

  7. Early-Onset Alzheimer Disease and Candidate Risk Genes Involved in Endolysosomal Transport.

    Science.gov (United States)

    Kunkle, Brian W; Vardarajan, Badri N; Naj, Adam C; Whitehead, Patrice L; Rolati, Sophie; Slifer, Susan; Carney, Regina M; Cuccaro, Michael L; Vance, Jeffery M; Gilbert, John R; Wang, Li-San; Farrer, Lindsay A; Reitz, Christiane; Haines, Jonathan L; Beecham, Gary W; Martin, Eden R; Schellenberg, Gerard D; Mayeux, Richard P; Pericak-Vance, Margaret A

    2017-09-01

    Mutations in APP, PSEN1, and PSEN2 lead to early-onset Alzheimer disease (EOAD) but account for only approximately 11% of EOAD overall, leaving most of the genetic risk for the most severe form of Alzheimer disease unexplained. This extreme phenotype likely harbors highly penetrant risk variants, making it primed for discovery of novel risk genes and pathways for AD. To search for rare variants contributing to the risk for EOAD. In this case-control study, whole-exome sequencing (WES) was performed in 51 non-Hispanic white (NHW) patients with EOAD (age at onset 65 years) from the Alzheimer's Disease Genetics Consortium. The study was conducted from January 21, 2013, to October 13, 2016. Alzheimer disease diagnosed according to standard National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer Disease and Related Disorders Association criteria. Association between Alzheimer disease and genetic variants and genes was measured using logistic regression and sequence kernel association test-optimal gene tests, respectively. Of the 1524 NHW patients with EOAD, 765 (50.2%) were women and mean (SD) age was 60.0 (4.9) years; of the 7046 NHW patients with LOAD, 4171 (59.2%) were women and mean (SD) age was 77.4 (8.6) years; and of the 7001 NHW controls, 4215 (60.2%) were women and mean (SD) age was 77.4 (8.6) years. The gene PSD2, for which multiple unrelated NHW cases had rare missense variants, was significantly associated with EOAD (P = 2.05 × 10-6; Bonferroni-corrected P value [BP] = 1.3 × 10-3) and LOAD (P = 6.22 × 10-6; BP = 4.1 × 10-3). A missense variant in TCIRG1, present in a NHW patient and segregating in 3 cases of a Hispanic family, was more frequent in EOAD cases (odds ratio [OR], 2.13; 95% CI, 0.99-4.55; P = .06; BP = 0.413), and significantly associated with LOAD (OR, 2.23; 95% CI, 1.37-3.62; P = 7.2 × 10-4; BP = 5.0 × 10-3). A missense variant in the LOAD risk

  8. Transcriptomic profiling of bovine IVF embryos revealed candidate genes and pathways involved in early embryonic development

    Directory of Open Access Journals (Sweden)

    Yandell Brian S

    2010-01-01

    Full Text Available Abstract Background Early embryonic loss is a large contributor to infertility in cattle. Although genetic factors are known to affect early embryonic development, the discovery of such factors has been a serious challenge. The objective of this study was to identify genes differentially expressed between blastocysts and degenerative embryos at early stages of development. Results Using microarrays, genome-wide RNA expression was profiled and compared for in vitro fertilization (IVF - derived blastocysts and embryos undergoing degenerative development up to the same time point. Surprisingly similar transcriptomic profiles were found in degenerative embryos and blastocysts. Nonetheless, we identified 67 transcripts that significantly differed between these two groups of embryos at a 15% false discovery rate, including 33 transcripts showing at least a two-fold difference. Several signaling and metabolic pathways were found to be associated with the developmental status of embryos, among which were previously known important steroid biosynthesis and cell communication pathways in early embryonic development. Conclusions This study presents the first direct and comprehensive comparison of transcriptomes between IVF blastocysts and degenerative embryos, providing important information for potential genes and pathways associated with early embryonic development.

  9. Indirect Effects of Attributional Style for Positive Events on Depressive Symptoms Through Self-Esteem During Early Adolescence.

    Science.gov (United States)

    Rueger, Sandra Yu; George, Rachel

    2017-04-01

    Research on adolescent depression has overwhelmingly focused on risk factors, such as stressful negative events and cognitive vulnerabilities, but much important information can be gained by focusing on protective factors. Thus, the current study aimed to broaden understanding on adolescent depression by considering the role of two positive elements as protective factors, attributional style for positive events and self-esteem, in a model of depression. The sample included 491 middle school students (52 % female; n = 249) with an age range from 12 to 15 years (M = 13.2, SD = .70). The sample was ethnically/racially diverse, with 55 % White, 22 % Hispanic, 10 % Asian American, 3 % African American, and 10 % Biracial/Other. Correlational analyses indicated significant cross-sectional and longitudinal associations between an enhancing attributional style (internal, stable, global attributions for positive events), self-esteem and depressive symptoms. Further, prospective analyses using bootstrapping methodology demonstrated significant indirect effects of an enhancing attributional style on decreases in depressive symptoms through its effects on self-esteem. These findings highlight the importance of considering attributional style for positive events as a protective factor in the developmental course of depressive symptoms during early adolescence.

  10. The Emerging Roles of Early Protein Folding Events in the Secretory Pathway in the Development of Neurodegenerative Maladies

    Science.gov (United States)

    Dubnikov, Tatyana; Cohen, Ehud

    2017-01-01

    Although, protein aggregation and deposition are unifying features of various neurodegenerative disorders, recent studies indicate that different mechanisms can lead to the development of the same malady. Among these, failure in early protein folding and maturation emerge as key mechanistic events that lead to the manifestation of a myriad of illnesses including Alzheimer's disease and prion disorders. Here we delineate the cascade of maturation steps that nascent polypeptides undergo in the secretory pathway to become functional proteins, and the chaperones that supervise and assist this process, focusing on the subgroup of proline cis/trans isomerases. We also describe the chaperones whose failure was found to be an underlying event that initiates the run-up toward neurodegeneration as well as chaperones whose activity impairs protein homeostasis (proteostasis) and thus, promotes the manifestation of these maladies. Finally, we discuss the roles of aggregate deposition sites in the cellular attempt to maintain proteostasis and point at potential targets for therapeutic interventions. PMID:28223916

  11. Involving Parents in Indicated Early Intervention for Childhood PTSD Following Accidental Injury

    Science.gov (United States)

    Cobham, Vanessa E.; March, Sonja; De Young, Alexandra; Leeson, Fiona; Nixon, Reginald; McDermott, Brett; Kenardy, Justin

    2012-01-01

    Accidental injuries represent the most common type of traumatic event to which a youth is likely to be exposed. While the majority of youth who experience an accidental injury will recover spontaneously, a significant proportion will go on to develop Post-Traumatic Stress Disorder (PTSD). And yet, there is little published treatment outcome…

  12. Radiation and chemotherapy bystander effects induce early genomic instability events: Telomere shortening and bridge formation coupled with mitochondrial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Gorman, Sheeona; Tosetto, Miriam [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland); Lyng, Fiona; Howe, Orla [Radiation and Environmental Science Centre, Dublin Institute of Technology and St. Luke' s Hospital, Dublin (Ireland); Sheahan, Kieran; O' Donoghue, Diarmuid; Hyland, John; Mulcahy, Hugh [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland); O' Sullivan, Jacintha, E-mail: jacintha.osullivan@ucd.ie [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland)

    2009-10-02

    The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if radiation and chemotherapy bystander effects induce early genomic instability events such as telomere shortening and bridge formation using a human colon cancer explant model. We assessed telomere lengths, bridge formations, mitochondrial membrane potential and levels of reactive oxygen species in bystander cells exposed to medium from irradiated and chemotherapy-treated explant tissues. Bystander cells exposed to media from 2 Gy, 5 Gy, FOLFOX treated tumor and matching normal tissue showed a significant reduction in telomere lengths (all p values <0.018) and an increase in bridge formations (all p values <0.017) compared to bystander cells treated with media from unirradiated tissue (0 Gy) at 24 h. There was no significant difference between 2 Gy and 5 Gy treatments, or between effects elicited by tumor versus matched normal tissue. Bystander cells exposed to media from 2 Gy irradiated tumor tissue showed significant depolarisation of the mitochondrial membrane potential (p = 0.012) and an increase in reactive oxygen species levels. We also used bystander cells overexpressing a mitochondrial antioxidant manganese superoxide dismutase (MnSOD) to examine if this antioxidant could rescue the mitochondrial changes and subsequently influence nuclear instability events. In MnSOD cells, ROS levels were reduced (p = 0.02) and mitochondrial membrane potential increased (p = 0.04). These events were coupled with a decrease in percentage of cells with anaphase bridges and a decrease in the number of cells undergoing telomere length shortening (p values 0.01 and 0.028 respectively). We demonstrate that radiation and chemotherapy bystander responses induce early genomic instability coupled with defects in mitochondrial function. Restoring

  13. Radiation and chemotherapy bystander effects induce early genomic instability events: telomere shortening and bridge formation coupled with mitochondrial dysfunction.

    LENUS (Irish Health Repository)

    Gorman, Sheeona

    2012-02-01

    The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if radiation and chemotherapy bystander effects induce early genomic instability events such as telomere shortening and bridge formation using a human colon cancer explant model. We assessed telomere lengths, bridge formations, mitochondrial membrane potential and levels of reactive oxygen species in bystander cells exposed to medium from irradiated and chemotherapy-treated explant tissues. Bystander cells exposed to media from 2Gy, 5Gy, FOLFOX treated tumor and matching normal tissue showed a significant reduction in telomere lengths (all p values <0.018) and an increase in bridge formations (all p values <0.017) compared to bystander cells treated with media from unirradiated tissue (0Gy) at 24h. There was no significant difference between 2Gy and 5Gy treatments, or between effects elicited by tumor versus matched normal tissue. Bystander cells exposed to media from 2Gy irradiated tumor tissue showed significant depolarisation of the mitochondrial membrane potential (p=0.012) and an increase in reactive oxygen species levels. We also used bystander cells overexpressing a mitochondrial antioxidant manganese superoxide dismutase (MnSOD) to examine if this antioxidant could rescue the mitochondrial changes and subsequently influence nuclear instability events. In MnSOD cells, ROS levels were reduced (p=0.02) and mitochondrial membrane potential increased (p=0.04). These events were coupled with a decrease in percentage of cells with anaphase bridges and a decrease in the number of cells undergoing telomere length shortening (p values 0.01 and 0.028 respectively). We demonstrate that radiation and chemotherapy bystander responses induce early genomic instability coupled with defects in mitochondrial function. Restoring mitochondrial

  14. Early psychosocial interventions after disasters, terrorism and other shocking events: is there a gap between norms and practice in Europe?

    Science.gov (United States)

    Te Brake, Hans; Dückers, Michel

    2013-01-01

    Internationally, several initiatives exist to describe standards for post-disaster psychosocial care. This study explored the level of consensus of experts within Europe on a set of recommendations on early psychosocial intervention after shocking events (Dutch guidelines), and to what degree these standards are implemented into mental health care practice. Two hundred and six (mental) health care professionals filled out a questionnaire to assess the extent to which they consider the guidelines' scope and recommendations relevant and part of the regular practice in their own country. Forty-five European experts from 24 EU countries discussed the guidelines at an international seminar. The data suggest overall agreement on the standards although many of the recommendations appear not (yet) to be embedded in everyday practice. Although large consensus exists on standards for early psychosocial care, a chasm between norms and practice appears to exist throughout the EU, stressing the general need for investments in guideline development and implementation.

  15. Early events in speciation: polymorphism for hybrid male sterility in Drosophila.

    Science.gov (United States)

    Reed, Laura K; Markow, Therese A

    2004-06-15

    Capturing the process of speciation early enough to determine the initial genetic causes of reproductive isolation remains a major challenge in evolutionary biology. We have found, to our knowledge, the first example of substantial intraspecific polymorphism for genetic factors contributing to hybrid male sterility. Specifically, we show that the occurrence of hybrid male sterility in crosses between Drosophila mojavensis and its sister species, Drosophila arizonae, is controlled by factors present at different frequencies in different populations of D. mojavensis. In addition, we show that hybrid male sterility is a complex phenotype; some hybrid males with motile sperm still cannot sire offspring. Because male sterility factors in hybrids between these species are not yet fixed within D. mojavensis, this system provides an invaluable opportunity to characterize the genetics of reproductive isolation at an early stage.

  16. Early events in Populus hybrid and Fagus sylvatica leaves exposed to ozone.

    Science.gov (United States)

    Desotgiu, R; Bussotti, F; Faoro, F; Iriti, M; Agati, G; Marzuoli, R; Gerosa, G; Tani, C

    2010-04-01

    This paper aims to investigate early responses to ozone in leaves of Fagus sylvatica (beech) and Populus maximowiczii x Populus berolinensis (poplar). The experimental setup consisted of four open-air (OA) plots, four charcoal-filtered (CF) open-top chambers (OTCs), and four nonfiltered (NF) OTCs. Qualitative and quantitative analyses were carried out on nonsymptomatic (CF) and symptomatic (NF and OA) leaves of both species. Qualitative analyses were performed applying microscopic techniques: Evans blue staining for detection of cell viability, CeCl3 staining of transmission electron microscope (TEM) samples to detect the accumulation of H2O2, and multispectral fluorescence microimaging and microspectrofluorometry to investigate the accumulation of fluorescent phenolic compounds in the walls of the damaged cells. Quantitative analyses consisted of the analysis of the chlorophyll a fluorescence transients (fast kinetics). The early responses to ozone were demonstrated by the Evans blue and CeCl3 staining techniques that provided evidence of plant responses in both species 1 month before foliar symptoms became visible. The fluorescence transients analysis, too, demonstrated the breakdown of the oxygen evolving system and the inactivation of the end receptors of electrons at a very early stage, both in poplar and in beech. The accumulation of phenolic compounds in the cell walls, on the other hand, was a species-specific response detected in poplar, but not in beech. Evans blue and CeCl3 staining, as well as the multispectral fluorescence microimaging and microspectrofluorometry, can be used to support the field diagnosis of ozone injury, whereas the fast kinetics of chlorophyll fluorescence provides evidence of early physiological responses.

  17. Early Events in Populus Hybrid and Fagus sylvatica Leaves Exposed to Ozone

    Directory of Open Access Journals (Sweden)

    R. Desotgiu

    2010-01-01

    Full Text Available This paper aims to investigate early responses to ozone in leaves of Fagus sylvatica (beech and Populus maximowiczii x Populus berolinensis (poplar. The experimental setup consisted of four open-air (OA plots, four charcoal-filtered (CF open-top chambers (OTCs, and four nonfiltered (NF OTCs. Qualitative and quantitative analyses were carried out on nonsymptomatic (CF and symptomatic (NF and OA leaves of both species. Qualitative analyses were performed applying microscopic techniques: Evans blue staining for detection of cell viability, CeCl3 staining of transmission electron microscope (TEM samples to detect the accumulation of H2O2, and multispectral fluorescence microimaging and microspectrofluorometry to investigate the accumulation of fluorescent phenolic compounds in the walls of the damaged cells. Quantitative analyses consisted of the analysis of the chlorophyll a fluorescence transients (fast kinetics. The early responses to ozone were demonstrated by the Evans blue and CeCl3 staining techniques that provided evidence of plant responses in both species 1 month before foliar symptoms became visible. The fluorescence transients analysis, too, demonstrated the breakdown of the oxygen evolving system and the inactivation of the end receptors of electrons at a very early stage, both in poplar and in beech. The accumulation of phenolic compounds in the cell walls, on the other hand, was a species-specific response detected in poplar, but not in beech. Evans blue and CeCl3 staining, as well as the multispectral fluorescence microimaging and microspectrofluorometry, can be used to support the field diagnosis of ozone injury, whereas the fast kinetics of chlorophyll fluorescence provides evidence of early physiological responses.

  18. IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy

    Science.gov (United States)

    Millar, Neal L.; Akbar, Moeed; Campbell, Abigail L.; Reilly, James H.; Kerr, Shauna C.; McLean, Michael; Frleta-Gilchrist, Marina; Fazzi, Umberto G.; Leach, William J.; Rooney, Brian P.; Crowe, Lindsay A. N.; Murrell, George A. C.; McInnes, Iain B.

    2016-01-01

    Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in ‘early tendinopathy’ compared to both matched samples and non-matched control samples (p tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders. PMID:27263531

  19. High acceptance of an early dyslexia screening test involving genetic analyses in Germany.

    Science.gov (United States)

    Wilcke, Arndt; Müller, Bent; Schaadt, Gesa; Kirsten, Holger; Boltze, Johannes

    2016-02-01

    Dyslexia is a developmental disorder characterized by severe problems in the acquisition of reading and writing skills. It has a strong neurobiological basis. Genetic influence is estimated at 50-70%. One of the central problems with dyslexia is its late diagnosis, normally not before the end of the 2nd grade, resulting in the loss of several years for early therapy. Currently, research is focusing on the development of early tests for dyslexia, which may be based on EEG and genetics. Our aim was to determine the acceptance of such a future test among parents. We conducted a representative survey in Germany with 1000 parents of children aged 3-7 years, with and without experience of dyslexia. 88.7% of the parents supported the introduction of an early test for dyslexia based on EEG and genetics; 82.8% would have their own children tested, and 57.9% were willing to pay for the test if health insurance did not cover the costs. Test acceptance was significantly higher if parents had prior experience with dyslexia. The perceived benefits of such a test were early recognition and remediation and, preventing deficits. Concerns regarded the precision of the test, its potentially stigmatizing effect and its costs. The high overall support for the test leads to the conclusion that parents would accept a test for dyslexia based on EEG and genetics.

  20. High acceptance of an early dyslexia screening test involving genetic analyses in Germany

    Science.gov (United States)

    Wilcke, Arndt; Müller, Bent; Schaadt, Gesa; Kirsten, Holger; Boltze, Johannes; Angela, h c; Friederici, D; Emmrich, Frank; Brauer, Jens; Wilcke, Arndt; Neef, Nicole; Boltze, Johannes; Skeide, Michael; Kirsten, Holger; Schaadt, Gesa; Müller, Bent; Kraft, Indra; Czepezauer, Ivonne; Bobovnikov, Nadin

    2016-01-01

    Dyslexia is a developmental disorder characterized by severe problems in the acquisition of reading and writing skills. It has a strong neurobiological basis. Genetic influence is estimated at 50–70%. One of the central problems with dyslexia is its late diagnosis, normally not before the end of the 2nd grade, resulting in the loss of several years for early therapy. Currently, research is focusing on the development of early tests for dyslexia, which may be based on EEG and genetics. Our aim was to determine the acceptance of such a future test among parents. We conducted a representative survey in Germany with 1000 parents of children aged 3–7 years, with and without experience of dyslexia. 88.7% of the parents supported the introduction of an early test for dyslexia based on EEG and genetics; 82.8% would have their own children tested, and 57.9% were willing to pay for the test if health insurance did not cover the costs. Test acceptance was significantly higher if parents had prior experience with dyslexia. The perceived benefits of such a test were early recognition and remediation and, preventing deficits. Concerns regarded the precision of the test, its potentially stigmatizing effect and its costs. The high overall support for the test leads to the conclusion that parents would accept a test for dyslexia based on EEG and genetics. PMID:26036858

  1. Early onset of cannabis use: Does personality modify the relation with changes in perceived parental involvement?

    NARCIS (Netherlands)

    Creemers, Hanneke E.; Buil, J. Marieke; van Lier, Pot A. C.; Keijsers, Loes; Meeus, W.H.J.; Koot, Hans M.; Huizink, Anja C.

    2015-01-01

    Background The present study examined (1) the association between changes in perceived parental control and support from age 13 to 15 and early onset of cannabis use (before age 16), and (2) whether personality modifies the association between a decline in perceived parental control and support and

  2. Brain Network Involved in the Recognition of Facial Expressions of Emotion in the Early Blind

    Directory of Open Access Journals (Sweden)

    Ryo Kitada

    2011-10-01

    Full Text Available Previous studies suggest that the brain network responsible for the recognition of facial expressions of emotion (FEEs begins to emerge early in life. However, it has been unclear whether visual experience of faces is necessary for the development of this network. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI experiments to test the hypothesis that the brain network underlying the recognition of FEEs is not dependent on visual experience of faces. Early-blind, late-blind and sighted subjects participated in the psychophysical experiment. Regardless of group, subjects haptically identified basic FEEs at above-chance levels, without any feedback training. In the subsequent fMRI experiment, the early-blind and sighted subjects haptically identified facemasks portraying three different FEEs and casts of three different shoe types. The sighted subjects also completed a visual task that compared the same stimuli. Within the brain regions activated by the visually-identified FEEs (relative to shoes, haptic identification of FEEs (relative to shoes by the early-blind and sighted individuals activated the posterior middle temporal gyrus adjacent to the superior temporal sulcus, the inferior frontal gyrus, and the fusiform gyrus. Collectively, these results suggest that the brain network responsible for FEE recognition can develop without any visual experience of faces.

  3. Forming the face of green products: Mood boards and early consumer involvement in ship interior design

    NARCIS (Netherlands)

    Murto, P.; Ahola, M.; Person, F.E.O.K.

    2013-01-01

    In this paper, we study mood boards and the process by which they can be used to understand consumer inferences about environmental sustainability in the early stages of green product development. As a component of a research project on sustainable ship design, we created mood boards showcasing thre

  4. The Need for More Effective Father Involvement in Early Autism Intervention: A Systematic Review and Recommendations

    Science.gov (United States)

    Flippin, Michelle; Crais, Elizabeth R.

    2011-01-01

    Fathers of children with autism spectrum disorders (ASD) are underrepresented in both early intervention and research. However, fathers have unique interaction styles that make important contributions to the language and symbolic play development of typically developing children. Fathers may make similar contributions to the development of their…

  5. Obesity Prevention Interventions in Early Childhood Education and Care Settings with Parental Involvement: A Systematic Review

    Science.gov (United States)

    Morris, Heather; Skouteris, Helen; Edwards, Susan; Rutherford, Leonie

    2015-01-01

    Partnering early childhood education and care (ECEC) and the home together may be more effective in combating obesogenic risk factors in preschool children. Thus, an evaluation of ECEC obesity prevention interventions with a parental component was conducted, exploring parental engagement and its effect on obesity and healthy lifestyle outcomes. A…

  6. Forming the face of green products: Mood boards and early consumer involvement in ship interior design

    NARCIS (Netherlands)

    Murto, P.; Ahola, M.; Person, F.E.O.K.

    2013-01-01

    In this paper, we study mood boards and the process by which they can be used to understand consumer inferences about environmental sustainability in the early stages of green product development. As a component of a research project on sustainable ship design, we created mood boards showcasing thre

  7. Oncological and Functional Outcome after Surgical Treatment of Early Glottic Carcinoma without Anterior Commissure Involvement

    Directory of Open Access Journals (Sweden)

    Jovica Milovanovic

    2014-01-01

    Full Text Available Introduction. Glottic carcinoma can be successfully diagnosed in its early stages and treated with high percentage of success. Organ preservation and optimal functional outcomes could be achieved with wide array of surgical techniques for early glottic cancer, including endoscopic approaches or open laryngeal preserving procedures, making surgery the preferred method of treatment of early glottic carcinoma in the last few years. Material and Methods. Prospective study was done on 59 patients treated for Tis and T1a glottic carcinoma over a one-year time period in a tertiary medical center. Patients were treated with endoscopic laser cordectomy (types II–IV cordectomies according to European Laryngological Society classification of endoscopic cordectomies and open cordectomy through laryngofissure. Follow-up period was 60 months. Clinical and oncological results were followed postoperatively. Voice quality after the treatment was assessed using multidimensional voice analysis 12 months after the treatment. Results. There were no significant differences between oncological and functional results among two groups of patients, though complications were more frequent in patients treated with open cordectomy. Conclusion. Endoscopic laser surgery should be the first treatment of choice in treatment of early glottic carcinomas, though open approach through laryngofissure should be available for selected cases where anatomical factors present limiting adequate tumor removal.

  8. RECYCLING PATHWAYS OF GLUCOSYLCERAMIDE IN BHK CELLS - DISTINCT INVOLVEMENT OF EARLY AND LATE ENDOSOMES

    NARCIS (Netherlands)

    KOK, JW; HOEKSTRA, K; ESKELINEN, S; HOEKSTRA, D

    1992-01-01

    Recycling pathways of the sphingolipid glucosylceramide were studied by employing a fluorescent analog of glucosylceramide, 6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]hexanoylglucosylsphingosine (C6-NBD-glucosylceramide). Direct recycling of the glycolipid from early endosomes to the plasma membra

  9. Obesity Prevention Interventions in Early Childhood Education and Care Settings with Parental Involvement: A Systematic Review

    Science.gov (United States)

    Morris, Heather; Skouteris, Helen; Edwards, Susan; Rutherford, Leonie

    2015-01-01

    Partnering early childhood education and care (ECEC) and the home together may be more effective in combating obesogenic risk factors in preschool children. Thus, an evaluation of ECEC obesity prevention interventions with a parental component was conducted, exploring parental engagement and its effect on obesity and healthy lifestyle outcomes. A…

  10. Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines.

    NARCIS (Netherlands)

    Girinsky, T.; Maazen, R.W.M. van der; Specht, L.; Aleman, B.; Poortmans, P.; Lievens, Y.; Meijnders, P.; Ghalibafian, M.; Meerwaldt, J.H.; Noordijk, E.M.

    2006-01-01

    BACKGROUND AND PURPOSE: To describe new concepts for radiation fields in patients with early stage Hodgkin lymphoma treated with a combined modality. PATIENTS AND MATERIALS: Patients receiving combined modality therapy with at least 2 or 3 cycles of chemotherapy prior to radiotherapy. Pre- and postc

  11. Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines

    DEFF Research Database (Denmark)

    Girinsky, Theodore; van der Maazen, Richard; Specht, Lena

    2006-01-01

    BACKGROUND AND PURPOSE: To describe new concepts for radiation fields in patients with early stage Hodgkin lymphoma treated with a combined modality. PATIENTS AND MATERIALS: Patients receiving combined modality therapy with at least 2 or 3 cycles of chemotherapy prior to radiotherapy. Pre- and po...

  12. Forming the face of green products: Mood boards and early consumer involvement in ship interior design

    NARCIS (Netherlands)

    Murto, P.; Ahola, M.; Person, F.E.O.K.

    2013-01-01

    In this paper, we study mood boards and the process by which they can be used to understand consumer inferences about environmental sustainability in the early stages of green product development. As a component of a research project on sustainable ship design, we created mood boards showcasing

  13. Extreme climate events, migration for cultivation and policies: A case study in the early Qing Dynasty of China

    Institute of Scientific and Technical Information of China (English)

    FANG XiuQi; YE Yu; ZENG ZaoZao

    2007-01-01

    Based on the historical records of the annual increase in the workforce(men older than 16 years of age),the annual new taxed cropland in the Shengjing area (Northeast China),the extreme climate events in North China,and related management policies in Northeast China during 1661-1680,a case study has been conducted to investigate the relationship between the extreme climate events in North China and the migration to Northeast China for cultivation.This study has found that the migration to Northeast China for cultivation from 1661 to 1680 was a response to the drought events that occurred in North China.The upsurge of migration,which occurred in 1665-1680,was a response to the drought period during 1664-1680 in North China while the fewer disasters period in Northeast China.There were three migratory peaks during the upsurge of migration,which corresponded to the three drought events.The peaks of migration,however,often lagged behind the drought events about 1-2 years.The encouraging-migration policy,which was adopted to encourage cultivation in Northeast China,did not produce much migration into the region in the early Qing Dynasty.It did,however,provide a policy background,which ensured more than 10000 migrants per year to Northeast China when North China suffered from drought/flood disasters.As a response to the highest peak of migration induced by the severe droughts in North China during 1664-1667,a prohibiting-migration policy restricted further migration to Northeast China was carried out in 1668.Although the prohibiting-migration policy could not entirely stop the migrants fleeing from famine in North China to Northeast China,the migrants and cultivation were significantly reduced under the policy.The frequent changes of the policy on the years when taxation started after the land was cultivated were also related to climate events.The extreme climate events in North China,migration to Northeast China for cultivation,and the related management policies showed

  14. Extreme climate events,migration for cultivation and policies:A case study in the early Qing Dynasty of China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Based on the historical records of the annual increase in the workforce (men older than 16 years of age), the annual new taxed cropland in the Shengjing area (Northeast China), the extreme climate events in North China, and related management policies in Northeast China during 1661―1680, a case study has been conducted to investigate the relationship between the extreme climate events in North China and the migration to Northeast China for cultivation. This study has found that the migration to Northeast China for cultivation from 1661 to 1680 was a response to the drought events that occurred in North China. The upsurge of migration, which occurred in 1665―1680, was a response to the drought period during 1664―1680 in North China while the fewer disasters period in Northeast China. There were three migratory peaks during the upsurge of migration, which corresponded to the three drought events. The peaks of migration, however, often lagged behind the drought events about 1―2 years. The encourag-ing-migration policy, which was adopted to encourage cultivation in Northeast China, did not produce much migration into the region in the early Qing Dynasty. It did, however, provide a policy background, which ensured more than 10000 migrants per year to Northeast China when North China suffered from drought/flood disasters. As a response to the highest peak of migration induced by the severe droughts in North China during 1664―1667, a prohibiting-migration policy restricted further migration to Northeast China was carried out in 1668. Although the prohibiting-migration policy could not entirely stop the migrants fleeing from famine in North China to Northeast China, the migrants and cultivation were significantly reduced under the policy. The frequent changes of the policy on the years when taxation started after the land was cultivated were also related to climate events. The extreme climate events in North China, migration to Northeast China for cultivation

  15. 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

    that the drop in cerebral blood flow (CBF) and wall tension experienced by cerebral arteries in acute SAH is a key triggering event. We here investigate the importance of the duration of this acute CBF drop in a rat SAH model in which a fixed amount of blood is injected into the prechiasmatic cistern either......Upregulation of vasoconstrictor receptors in cerebral arteries, including endothelin B (ETB) and 5-hydroxytryptamine 1B (5-HT(1B)) receptors, has been suggested to contribute to delayed cerebral ischemia, a feared complication after subarachnoid hemorrhage (SAH). This receptor upregulation has been...

  16. The structural involvement of the cingulate cortex in premanifest and early Huntington's disease.

    Science.gov (United States)

    Hobbs, Nicola Z; Pedrick, Amy V; Say, Miranda J; Frost, Chris; Dar Santos, Rachelle; Coleman, Allison; Sturrock, Aaron; Craufurd, David; Stout, Julie C; Leavitt, Blair R; Barnes, Josephine; Tabrizi, Sarah J; Scahill, Rachael I

    2011-08-01

    The impact of Huntington's disease neuropathology on the structure of the cingulate is uncertain, with evidence of both cortical enlargement and atrophy in this structure in early clinical disease. We sought to determine differences in cingulate volume between premanifest Huntington's disease and early Huntington's disease groups compared with controls using detailed manual measurements. Thirty controls, 30 subjects with premanifest Huntington's disease, and 30 subjects with early Huntington's disease were selected from the Vancouver site of the TRACK-HD study. Subjects underwent 3 Tesla magnetic resonance imaging and motor, cognitive, and neuropsychiatric assessment. The cingulate was manually delineated and subdivided into rostral, caudal, and posterior segments. Group differences in volume and associations with performance on 4 tasks thought to utilize cingulate function were examined, with adjustment for appropriate covariates. Cingulate volumes were, on average, 1.7 mL smaller in early Huntington's disease (P=.001) and 0.9 mL smaller in premanifest Huntington's disease (P=.1) compared with controls. Smaller volumes in subsections of the cingulate were associated with impaired recognition of negative emotions (P=.04), heightened depression (P=.009), and worse visual working memory performance (P=.01). There was no evidence of associations between volume and ability on a performance-monitoring task. This study disputes previous findings of enlargement of the cingulate cortex in Huntington's disease and instead suggests that the cingulate undergoes structural degeneration during early Huntington's disease with directionally consistent, nonsignificant differences seen in premanifest Huntington's disease. Cingulate atrophy may contribute to deficits in mood, emotional processing, and visual working memory in Huntington's disease.

  17. ABA inhibits embryo cell expansion and early cell division events during coffee (Coffea arabica 'Rubi') seed germination.

    Science.gov (United States)

    Da Silva, E A Amaral; Toorop, Peter E; Van Lammeren, André A M; Hilhorst, Henk W M

    2008-09-01

    Coffee seed germination represents an interplay between the embryo and the surrounding endosperm. A sequence of events in both parts of the seed determines whether germination will be successful or not. Following previous studies, the aim here was to further characterize the morphology of endosperm degradation and embryo growth with respect to morphology and cell cycle, and the influence of abscisic acid on these processes. Growth of cells in a fixed region of the axis was quantified from light micrographs. Cell cycle events were measured by flow cytometry and by immunocytochemistry, using antibodies against beta-tubulin. Aspects of the endosperm were visualized by light and scanning electron microscopy. The embryonic axis cells grew initially by isodiametric expansion. This event coincided with reorientation and increase in abundance of microtubules and with accumulation of beta-tubulin. Radicle protrusion was characterized by a shift from isodiametric expansion to elongation of radicle cells and further accumulation of beta-tubulin. Early cell division events started prior to radicle protrusion. Abscisic acid decreased the abundance of microtubules and inhibited the growth of the embryo cells, the reorganization of the microtubules, DNA replication in the embryonic axis, the formation of a protuberance and the completion of germination. The endosperm cap cells had smaller and thinner cell walls than the rest of the endosperm. Cells in the endosperm cap displayed compression followed by loss of cell integrity and the appearance of a protuberance prior to radicle protrusion. Coffee seed germination is the result of isodiametric growth of the embryo followed by elongation, at the expense of integrity of endosperm cap cells. The cell cycle, including cell division, is initiated prior to radicle protrusion. ABA inhibits expansion of the embryo, and hence subsequent events, including germination.

  18. The Impact of Early Dermatologic Events in the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib.

    Science.gov (United States)

    Branco, Fernanda; Alencar, Regiane S M; Volt, Fernanda; Sartori, Giovana; Dode, Andressa; Kikuchi, Luciana; Tani, Claudia M; Chagas, Aline L; Pfiffer, Tulio; Hoff, Paulo; Carrilho, Flair J; Mattos, Angelo A

    2017-01-01

    The presence of dermatologic reaction as an adverse event to sorafenib treatment in patients with unresectable hepatocellular carcinoma has been indicated as a prognostic factor for survival in a recent prospective analysis. To date, this is the only clinical predictor of treatment response, which can be evaluated earlier in the treatment and, therefore, contribute to a better and more individualized patient management. This retrospective study included 127 patients treated with sorafenib under real-life practice conditions in two hepatology reference centers in Brazil. Demographic data, disease/medical history and time of sorafenib administration as well as adverse events related to the medication were recorded in a database. Cirrhosis was present in 94% of patients, 85.6% were Child-Pugh A, 80.3%BCLC-C, 81% had vascular invasion and/or extrahepatic spread and 95% had a performance status 0 to 1.The median duration of treatment was 10.1 months (range: 0.1-47 months).The most common adverse event within the first 60 days of treatment were diarrhea (62.2%) and dermatological reaction (42%).The median overall survival for the cohort was 20 months, and it was higher for patients who developed dermatological reactions within the first 60 days compared to those who did not present this adverse event. This retrospective analysis showed the use of sorafenib in patients selected according to BCLC staging, and it is the first external validation of early dermatologic adverse events as a predictor of overall survival in patients with advanced hepatocellular carcinoma.

  19. Event Management

    OpenAIRE

    Havlenová, Tereza

    2016-01-01

    Event is an experience that is perceived by all the senses. Event management is a process involving the various activities that are assigned to staffers. Organizing special events became an individual field. If the manager understand the events as a communication platform gets into the hands of a modern, multifunctional and very impressive tool. The procedure to implement a successful event in a particular area is part of this work. The first part explains the issues of event management on th...

  20. Hypomethylation of Long Interspersed Nuclear Element-1 is Involved in the Early Tumorigenesis of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Wenhua Piao

    2014-08-01

    high FAL group. No associations between the level of hypomethylation of LINE-1 and HBV infection, age, sex, and cirrhosis were found. Conclusions: These results are strongly suggested that the hypomethylation of LINE-1 plays a role in the hepatocarcinogenesis; moreover, the hypomethylation of LINE-1 occurs not only in the progression of HCC, but also in the early stage of HCC tumorigenesis. [J Interdiscipl Histopathol 2014; 2(4.000: 191-196

  1. Early events following radiolytic and photogeneration of radical cations in hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Werst, D.W.; Trifunac, A.D.

    1992-11-01

    Real-time studies in hydrocarbons have revealed a richness of chemistry involving the initial ionic species produced in radiolysis and photoionization. A modified radical cation mechanism patterned after the core mechanism for alkane radiolysis-formation of radical cations and their disappearance via ion-molecule reactions - is capable of explaining a wide range of observations in high-energy photochemistry, and thus unifies two high-energy regimes. Fundamental studies of radical cations suggest strategies for mitigating radiation effects in materials.

  2. Early events following radiolytic and photogeneration of radical cations in hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Werst, D.W.; Trifunac, A.D.

    1992-01-01

    Real-time studies in hydrocarbons have revealed a richness of chemistry involving the initial ionic species produced in radiolysis and photoionization. A modified radical cation mechanism patterned after the core mechanism for alkane radiolysis-formation of radical cations and their disappearance via ion-molecule reactions - is capable of explaining a wide range of observations in high-energy photochemistry, and thus unifies two high-energy regimes. Fundamental studies of radical cations suggest strategies for mitigating radiation effects in materials.

  3. African American adolescent mothers' early caregiving involvement and childrens' behavior and academic performance at age 7.

    Science.gov (United States)

    Oberlander, Sarah E; Black, Maureen M

    2011-01-01

    The United States continues to have the highest incidence of adolescent births among industrialized nations. This study used transactional and life span theories of development to examine whether caregiving patterns assessed over the first 24 months postpartum predicted children's behavior and academic achievement at 7 years. Participants included 120 primiparous, urban, low-income, African American adolescent mothers who participated in a randomized controlled trial of home intervention. Group-based trajectories were used to examine the pattern of caregiving involvement over time. Two distinct, consistent trajectories of caregiving involvement were found: maternal and shared. Maternal caregiving involvement over the first 24 months postpartum predicted positive child behavior and academic achievement at 7 years. In keeping with both transactional and life span theories, findings suggest that adoption of the parent role may lead to positive long-term outcomes for children of adolescent mothers.

  4. Insights into the early dissolution events of amlodipine using UV imaging and Raman spectroscopy

    DEFF Research Database (Denmark)

    Boetker, Johan P; Savolainen, Marja; Koradia, Vishal

    2011-01-01

    Traditional dissolution testing determines drug release to the bulk, but does not enable an understanding of the events happening close to the surface of a solid or a tablet. UV imaging is a new imaging approach that can be used to study the dissolution behavior of chemical compounds. The UV...... imaging instrumentation offers recording of absorbance maps with a high spatial and temporal resolution which facilitates the abundant collection of information regarding the evolving solution concentrations. In this study, UV imaging was used to visualize the dissolution behavior of amlodipine besylate...... (amorphous and dihydrate forms) and amlodipine free base. The dissolution of amlodipine besylate was faster from the amorphous form than from the crystalline forms. The UV imaging investigations suggested that a solvent mediated phase transformation occurred for the amorphous amlodipine besylate...

  5. Staff supported parental involvement in effective early interventions for at-risk children

    DEFF Research Database (Denmark)

    Larsen, Michael Søgaard; Holm, Anders; Jensen, Bente

    review system. Thirteen interventions with evidence-based positive effects on the cognitive, emotional, and social development of the children were identified. The interventions were then described in terms of curriculum, theoretical framework, empirical basis, and methods of parental involvement....... The study shows that parents are involved through a variety of activities, which include: (1) educators visit the homes and provide guidance for parents and their children there; (2) parents conduct specific activities with the children at home and or in the institution; (3) parents participate...

  6. Early Oligocene geomagnetic field behavior from ODP Site 1128: Complex records of short-period polarity events

    Science.gov (United States)

    Molina-Garza, R. S.; Fuller, M. D.

    2001-12-01

    At Site 1128, in the Great Australian Bight, Leg 182 of the Ocean Drilling Program recovered a thick (~350 m) section of Upper Eocene and Lower Oligocene marine calcareous clays. Shipboard measurements established a magnetostratigraphy that can unambiguously be correlated to chrons C13n to C10n of the global polarity time scale (GPTS), and a less complete record of chrons C17n to C15r (due to poor core recovery). Correlation to the GPTS is further supported by available biostratigraphic data. For the Lower Oligocene sequence, average sedimentation rate is estimated at ~4 cm/kyr. The sediments recovered thus allow to test for the completeness and reliability of the geomagnetic field polarity during the Early Oligocene. The original shipboard long-core measurements suggested the presence of additional short polarity events or geomagnetic field excursions during chrons C13n, C12r, C11r, and C11n. In order to examine the reliability of the record and the nature of possible short-polarity events, we obtained discrete samples from the entire sequence at ~1 m intervals, with a closer sample spacing in critical intervals (~10 cm). The natural remanence of these sediments is normally simple. After removing a small soft overprint, the magnetization decays towards the origin with distributed coercivities and distributed unblocking temperatures. Demagnetization behavior and other rock magnetic data indicate that the remanence resides primarily in a cubic phase such as magnetite or maghemite, with a small contribution from hematite. Discrete samples from chron C12r did not reproduce the long-core record for two of the supposed events, single samples suggest the presence of short events or cryptochrons near the base of both C13n and C12r, and multiple samples suggest the existence of short-period normal polarity events during C11r and near the top of C12r. The records of these events are, however, complex. Demagnetization results indicate that the magnetization consists of an

  7. Identification of early zygotic genes in the yellow fever mosquito Aedes aegypti and discovery of a motif involved in early zygotic genome activation.

    Directory of Open Access Journals (Sweden)

    James K Biedler

    Full Text Available During early embryogenesis the zygotic genome is transcriptionally silent and all mRNAs present are of maternal origin. The maternal-zygotic transition marks the time over which embryogenesis changes its dependence from maternal RNAs to zygotically transcribed RNAs. Here we present the first systematic investigation of early zygotic genes (EZGs in a mosquito species and focus on genes involved in the onset of transcription during 2-4 hr. We used transcriptome sequencing to identify the "pure" (without maternal expression EZGs by analyzing transcripts from four embryonic time ranges of 0-2, 2-4, 4-8, and 8-12 hr, which includes the time of cellular blastoderm formation and up to the start of gastrulation. Blast of 16,789 annotated transcripts vs. the transcriptome reads revealed evidence for 63 (P<0.001 and 143 (P<0.05 nonmaternally derived transcripts having a significant increase in expression at 2-4 hr. One third of the 63 EZG transcripts do not have predicted introns compared to 10% of all Ae. aegypti genes. We have confirmed by RT-PCR that zygotic transcription starts as early as 2-3 hours. A degenerate motif VBRGGTA was found to be overrepresented in the upstream sequences of the identified EZGs using a motif identification software called SCOPE. We find evidence for homology between this motif and the TAGteam motif found in Drosophila that has been implicated in EZG activation. A 38 bp sequence in the proximal upstream sequence of a kinesin light chain EZG (KLC2.1 contains two copies of the mosquito motif. This sequence was shown to support EZG transcription by luciferase reporter assays performed on injected early embryos, and confers early zygotic activity to a heterologous promoter from a divergent mosquito species. The results of these studies are consistent with the model of early zygotic genome activation via transcriptional activators, similar to what has been found recently in Drosophila.

  8. Safety evaluation of laninamivir octanoate hydrate through analysis of adverse events reported during early post-marketing phase vigilance.

    Science.gov (United States)

    Nakano, Takashi; Okumura, Akihisa; Tanabe, Takuya; Niwa, Shimpei; Fukushima, Masato; Yonemochi, Rie; Eda, Hisano; Tsutsumi, Hiroyuki

    2013-06-01

    Abnormal behavior and delirium are common in children with influenza. While abnormal behavior and delirium are considered to be associated with influenza encephalopathy, an increased risk of such neuropsychiatric symptoms in patients receiving neuraminidase inhibitor treatment is suspected. Laninamivir octanoate hydrate, recently approved in Japan, is a long-acting neuraminidase inhibitor. It is important to establish a safety profile for laninamivir early, based on post-marketing experiences. Spontaneous safety reports collected in the early post-marketing phase vigilance were analyzed. Adverse events of interest such as abnormal behavior/delirium, dizziness/vertigo, respiratory disorders, shock/syncope, and any other serious events were intensively reviewed by the Safety Evaluation Committee. Abnormal behavior/delirium was a frequently reported event. Almost all the reported cases were considered to be due to influenza and not laninamivir. There were 32 cases of abnormal behavior/delirium that could lead to dangerous accidents, and these were observed more frequently in males and teenagers. Syncope probably related to the act of inhalation per se of laninamivir was reported during this survey. This safety review revealed that the safety profile of laninamivir for abnormal behavior/delirium and syncope was similar to that of other neuraminidase inhibitors. As stated in the labeling, teenage patients inhaling laninamivir should remain under constant parental supervision for at least 2 days and should be closely monitored for behavioral changes to prevent serious accidents associated with abnormal behavior/delirium. Furthermore, to avoid syncope because of inhalation, patients should be instructed to inhale in a relaxed sitting position.

  9. Television viewing through ages 2-5 years and bullying involvement in early elementary school

    NARCIS (Netherlands)

    V.J.A. Verlinden (Vincent); H.W. Tiemeier (Henning); R. Veenstra (René); C.L. Mieloo (Cathelijne); W. Jansen (Wilma); V.W.V. Jaddoe (Vincent); H. Raat (Hein); A. Hofman (Albert); F.C. Verhulst (Frank); P.W. Jansen (Pauline)

    2014-01-01

    textabstractBackground: High television exposure time at young age has been described as a potential risk factor for developing behavioral problems. However, less is known about the effects of preschool television on subsequent bullying involvement. We examined the association between television

  10. Television viewing through ages 2-5 years and bullying involvement in early elementary school

    NARCIS (Netherlands)

    Verlinden, Marina; Tiemeier, Henning; Veenstra, René; Mieloo, Cathelijne; Jansen, Wilma; Jaddoe, Vincent W. V.; Raat, Hein; Hofman, Albert; Verhulst, Frank C.; Jansen, Pauline W.

    2014-01-01

    Background: High television exposure time at young age has been described as a potential risk factor for developing behavioral problems. However, less is known about the effects of preschool television on subsequent bullying involvement. We examined the association between television viewing time

  11. Could early septal involvement in the remodeling process be related to the advance hypertensive heart disease?

    Directory of Open Access Journals (Sweden)

    Fatih Yalçin

    2015-06-01

    Conclusions: LV diastolic dysfunction becomes more severe in septal wall than lateral wall in hypertensive LVH. Septal myocardial performance is more dominantly affected by hypertension possibly due to earlier septal involvement in disease course. Septal MPI is correlated moderately with septal wall thickness.

  12. Doses to head and neck normal tissues for early stage Hodgkin lymphoma after involved node radiotherapy

    DEFF Research Database (Denmark)

    Maraldo, M. V.; Brodin, N. P.; Aznar, M. C.;

    2014-01-01

    To evaluate dose plans for head and neck organs at risk (OARs) for classical Hodgkin lymphoma (HL) patients using involved node radiotherapy (INRT) delivered as 3D conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), and intensity modulated proton therapy (PT), in comparison t...... to the past mantle field (MF)....

  13. Parent Involvement in Early Childhood Special Education: Selected Activities for Preschool Teachers.

    Science.gov (United States)

    Carlson, Betty Clark

    The manual is designed to provide special education preschool teachers with a guide for parent involvement activities. The guide presents 32 activities divided into three topical areas: (1) communicating with parents (orientation packet, newsletter, school-home notebook, bulletin board for parents); (2) resource activities (field trips, home…

  14. Television viewing through ages 2-5 years and bullying involvement in early elementary school

    NARCIS (Netherlands)

    Verlinden, Marina; Tiemeier, Henning; Veenstra, René; Mieloo, Cathelijne; Jansen, Wilma; Jaddoe, Vincent W. V.; Raat, Hein; Hofman, Albert; Verhulst, Frank C.; Jansen, Pauline W.

    2014-01-01

    Background: High television exposure time at young age has been described as a potential risk factor for developing behavioral problems. However, less is known about the effects of preschool television on subsequent bullying involvement. We examined the association between television viewing time th

  15. Television viewing through ages 2-5 years and bullying involvement in early elementary school

    NARCIS (Netherlands)

    Verlinden, Marina; Tiemeier, Henning; Veenstra, René; Mieloo, Cathelijne; Jansen, Wilma; Jaddoe, Vincent W. V.; Raat, Hein; Hofman, Albert; Verhulst, Frank C.; Jansen, Pauline W.

    2014-01-01

    Background: High television exposure time at young age has been described as a potential risk factor for developing behavioral problems. However, less is known about the effects of preschool television on subsequent bullying involvement. We examined the association between television viewing time th

  16. Risk of Cerebrovascular Events in Elderly Patients After Radiation Therapy Versus Surgery for Early-Stage Glottic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Julian C.; Kruser, Tim J. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Gondi, Vinai [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Central Dupage Hospital Cancer Center, Warrenville, Illinois (United States); Mohindra, Pranshu; Cannon, Donald M.; Harari, Paul M. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Bentzen, Søren M., E-mail: bentzen@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States)

    2013-10-01

    Purpose: Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for early-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: We identified patients ≥66 years of age with early-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular events, and SEER data for stroke as the cause of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. Results: A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). Conclusions: Elderly patients with early-stage laryngeal cancer have a high burden of cerebrovascular events after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients.

  17. Long-term impact of early life events on physiology and behaviour.

    Science.gov (United States)

    Boersma, G J; Bale, T L; Casanello, P; Lara, H E; Lucion, A B; Suchecki, D; Tamashiro, K L

    2014-09-01

    This review discusses the effects of stress and nutrition throughout development and summarises studies investigating how exposure to stress or alterations in nutrition during the pre-conception, prenatal and early postnatal periods can affect the long-term health of an individual. In general, the data presented here suggest that that anything signalling potential adverse conditions later in life, such as high levels of stress or low levels of food availability, will lead to alterations in the offspring, possibly of an epigenetic nature, preparing the offspring for these conditions later in life. However, when similar environmental conditions are not met in adulthood, these alterations may have maladaptive consequences, resulting in obesity and heightened stress sensitivity. The data also suggest that the mechanism underlying these adult phenotypes might be dependent on the type and the timing of exposure.

  18. Early visual experience and the recognition of basic facial expressions: involvement of the middle temporal and inferior frontal gyri during haptic identification by the early blind.

    Science.gov (United States)

    Kitada, Ryo; Okamoto, Yuko; Sasaki, Akihiro T; Kochiyama, Takanori; Miyahara, Motohide; Lederman, Susan J; Sadato, Norihiro

    2013-01-01

    Face perception is critical for social communication. Given its fundamental importance in the course of evolution, the innate neural mechanisms can anticipate the computations necessary for representing faces. However, the effect of visual deprivation on the formation of neural mechanisms that underlie face perception is largely unknown. We previously showed that sighted individuals can recognize basic facial expressions by haptics surprisingly well. Moreover, the inferior frontal gyrus (IFG) and posterior superior temporal sulcus (pSTS) in the sighted subjects are involved in haptic and visual recognition of facial expressions. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI) experiments to determine the nature of the neural representation that subserves the recognition of basic facial expressions in early blind individuals. In a psychophysical experiment, both early blind and sighted subjects haptically identified basic facial expressions at levels well above chance. In the subsequent fMRI experiment, both groups haptically identified facial expressions and shoe types (control). The sighted subjects then completed the same task visually. Within brain regions activated by the visual and haptic identification of facial expressions (relative to that of shoes) in the sighted group, corresponding haptic identification in the early blind activated regions in the inferior frontal and middle temporal gyri. These results suggest that the neural system that underlies the recognition of basic facial expressions develops supramodally even in the absence of early visual experience.

  19. Early visual experience and the recognition of basic facial expressions: Involvement of the middle temporal and inferior frontal gyri during haptic identification by the early blind

    Directory of Open Access Journals (Sweden)

    Ryo eKitada

    2013-01-01

    Full Text Available Face perception is critical for social communication. Given its fundamental importance in the course of evolution, the innate neural mechanisms can anticipate the computations necessary for representing faces. However, the effect of visual deprivation on the formation of neural mechanisms that underlie face perception is largely unknown. We previously showed that sighted individuals can recognize basic facial expressions by haptics surprisingly well. Moreover, the inferior frontal gyrus and posterior superior temporal sulcus in the sighted subjects are involved in haptic and visual recognition of facial expressions. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI experiments to determine the nature of the neural representation that subserves the recognition of basic facial expressions in early-blind individuals. In a psychophysical experiment, both early-blind and sighted subjects haptically identified basic facial expressions at levels well above chance. In the subsequent fMRI experiment, both groups haptically identified facial expressions and shoe types (control. The sighted subjects then completed the same task visually. Within brain regions activated by the visual and haptic identification of facial expressions (relative to that of shoes in the sighted group, corresponding haptic identification in the early blind activated regions in the inferior frontal and middle temporal gyri. These results suggest that the neural system that underlies the recognition of basic facial expressions develops supramodally even in the absence of early visual experience.

  20. Early canine plaque biofilms: characterization of key bacterial interactions involved in initial colonization of enamel.

    Directory of Open Access Journals (Sweden)

    Lucy J Holcombe

    Full Text Available Periodontal disease (PD is a significant problem in dogs affecting between 44% and 63.6% of the population. The main etiological agent for PD is plaque, a microbial biofilm that colonizes teeth and causes inflammation of the gingiva. Understanding how this biofilm initiates on the tooth surface is of central importance in developing interventions against PD. Although the stages of plaque development on human teeth have been well characterized little is known about how canine plaque develops. Recent studies of the canine oral microbiome have revealed distinct differences between the canine and human oral environments and the bacterial communities they support, particularly with respect to healthy plaque. These differences mean knowledge about the nature of plaque formation in humans may not be directly translatable to dogs. The aim of this study was to identify the bacterial species important in the early stages of canine plaque formation in vivo and then use isolates of these species in a laboratory biofilm model to develop an understanding of the sequential processes which take place during the initial colonization of enamel. Supra-gingival plaque samples were collected from 12 dogs at 24 and 48 hour time points following a full mouth descale and polish. Pyrosequencing of the 16S rDNA identified 134 operational taxonomic units after statistical analysis. The species with the highest relative abundance were Bergeyella zoohelcum, Neisseria shayeganii and a Moraxella species. Streptococcal species, which tend to dominate early human plaque biofilms, had very low relative abundance. In vitro testing of biofilm formation identified five primary colonizer species, three of which belonged to the genus Neisseria. Using these pioneer bacteria as a starting point, viable two and three species communities were developed. Combining in vivo and in vitro data has led us to construct novel models of how the early canine plaque biofilm develops.

  1. Dramatic decrease of pelagic carbonate production by nannoplankton across the Early Toarcian anoxic event (T-OAE)

    Science.gov (United States)

    Mattioli, Emanuela; Pittet, Bernard; Petitpierre, Laurent; Mailliot, Samuel

    2009-02-01

    In this account we present estimates of nannofossil fluxes in four sections and one borehole all belonging to the Early Jurassic western Tethys. This study aims to map the distribution of pelagic carbonate production across the Early Toarcian anoxic event (T-OAE), and to understand which environmental parameters did control such production. Our results indicate important changes in carbonate production by nannoplankton occurring within the western Tethys and its variations through time. Nannofossil fluxes (specimens per m 2 per year) are extremely low during the T-OAE in all the studied settings. Higher fluxes are encountered in the westernmost part of the Tethys Ocean before the T-OAE, whilst pelagic carbonate production shifted towards the northern margin of the Tethys after the recovery from anoxic conditions. The dramatic decrease in nannoplankton production during the T-OAE has been interpreted in previous works as a biocalcification crisis related to high pCO 2 in the atmosphere/hydrosphere system. Although a high pCO 2 may have lowered the carbonate saturation state of Early Jurassic oceans and finally hampered biocalcification, we speculate that the most important effects of CO 2 increase were indirect, and affected pelagic producers via changes on climate and sea-level. Namely, it seems that precipitation/evaporation budgets and continental runoff that controlled nutrient levels and salinity in surface oceanic waters were important factors for pelagic biocalcifiers.

  2. Xenopus FRS2 is involved in early embryogenesis in cooperation with the Src family kinase Laloo

    OpenAIRE

    Kusakabe, Morioh; Masuyama, Norihisa; Hanafusa, Hiroshi; Nishida, Eisuke

    2001-01-01

    FRS2 has been identified in mammalian cells as a protein that is tyrosine phosphorylated and binds to Grb2 and Shp2 in response to fibroblast growth factor (FGF) or nerve growth factor (NGF) stimulation. But neither its existence in other vertebrate classes or invertebrates nor its function during embryonic development has been defined. Here we have identified and characterized a Xenopus homolog of FRS2 (xFRS2). xFRS2 is tyrosine phosphorylated in early embryos, and overexpression of an unpho...

  3. Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events.

    Science.gov (United States)

    Buckner, Lyndsey R; Amedee, Angela M; Albritton, Hannah L; Kozlowski, Pamela A; Lacour, Nedra; McGowin, Chris L; Schust, Danny J; Quayle, Alison J

    2016-01-01

    Chlamydia trachomatis causes a predominantly asymptomatic, but generally inflammatory, genital infection that is associated with an increased risk for HIV acquisition. Endocervical epithelial cells provide the major niche for this obligate intracellular bacterium in women, and the endocervix is also a tissue in which HIV transmission can occur. The mechanism by which CT infection enhances HIV susceptibility at this site, however, is not well understood. Utilizing the A2EN immortalized endocervical epithelial cell line grown on cell culture inserts, we evaluated the direct role that CT-infected epithelial cells play in facilitating HIV transmission events. We determined that CT infection significantly enhanced the apical-to-basolateral migration of cell-associated, but not cell-free, HIVBaL, a CCR5-tropic strain of virus, across the endocervical epithelial barrier. We also established that basolateral supernatants from CT-infected A2EN cells significantly enhanced HIV replication in peripheral mononuclear cells and a CCR5+ T cell line. These results suggest that CT infection of endocervical epithelial cells could facilitate both HIV crossing the mucosal barrier and subsequent infection or replication in underlying target cells. Our studies provide a mechanism by which this common STI could potentially promote the establishment of founder virus populations and the maintenance of local HIV reservoirs in the endocervix. Development of an HIV/STI co-infection model also provides a tool to further explore the role of other sexually transmitted infections in enhancing HIV acquisition.

  4. A Threshold-Based Earthquake Early-Warning System for Offshore Events in Southern Iberia

    Science.gov (United States)

    Picozzi, M.; Colombelli, S.; Zollo, A.; Carranza, M.; Buforn, E.

    2015-09-01

    The south of the Iberian Peninsula is situated at the convergence of the Eurasian and African plates. This region experiences large earthquakes with long separation in time, the best known of which was the great 1755 Lisbon Earthquake, which occurred SW of San Vicente Cape (SW Iberian Peninsula). The high risk of damaging earthquakes has recently led Carranza et al. (Geophys. Res. Lett. 40, 2013) to investigate the feasibility of an EEWS in this region. Analysis of the geometry for the Iberian seismic networks and the San Vicente Cape area led the authors to conclude that a threshold-based approach, which would not require real-time location of the earthquake, might be the best option for an EEWS in SW Iberia. In this work we investigate this hypothesis and propose a new EEW approach that extends standard P-wave threshold-based single-station analysis to the whole network. The proposed method enables real-time estimation of the potential damage at stations that are triggered by P-waves and those which are not triggered, with the advantage of greater lead-times for release of alerts. Results of tests made with synthetic data mimicking the scenario of the great 1755 Lisbon Earthquake, and those conducted by applying the new approach to available recordings, indicate that an EEW estimation of the potential damage associated with an event in the San Vicente Cape area can be obtained for a very large part of the Iberian Peninsula.

  5. Prior chronic clopidogrel therapy is associated with increased adverse events and early stent thrombosis.

    Science.gov (United States)

    Asher, Elad; Fefer, Paul; Sabbag, Avi; Herscovici, Romana; Regev, Ehud; Mazin, Israel; Shlomo, Nir; Zahger, Doron; Atar, Shaul; Hammerman, Haim; Polak, Arthur; Beigel, Roy; Matetzky, Shlomi

    2016-01-01

    Despite the growing use of clopidogrel, limited data exist regarding the prognostic significance of chronic clopidogrel therapy in patients sustaining acute coronary syndrome (ACS). Our aim was to determine whether patients sustaining ACS while on chronic clopidogrel therapy have a worse prognosis than clopidogrel-naïve patients. A total of 5,386 consecutive ACS patients were prospectively characterised and followed-up for 30 days. Of them, 680 (13%) were treated with clopidogrel prior to the index ACS. Major adverse cardiovascular events (MACE) were defined as death, recurrent ACS, stroke and/or stent thrombosis. Compared with clopidogrel-naïve, chronic clopidogrel-treated patients were older (66 ± 12 vs 63 ± 13, respectively; pclopidogrel therapy was associated with a two-fold increase in in-hospital (1.6% vs 0.6%, respectively; p =0.006) as well as 30-day stent thrombosis (2.2% vs 1.0%, respectively; p=0.007). MACE at 30 days was also higher among chronic clopidogrel-treated compared with clopidogrel-naïve patients [12.3% vs 9.4%, respectively; pclopidogrel treatment was an independent predictor of stent thrombosis [OR=2.6 (95%CI 1.2-5.6), p=0.001]. Patients sustaining ACS while on chronic clopidogrel treatment are at higher risk for in-hospital and 30-day adverse outcomes, including stent thrombosis.

  6. Salt stress sensing and early signalling events in plant roots: Current knowledge and hypothesis.

    Science.gov (United States)

    Shabala, Sergey; Wu, Honghong; Bose, Jayakumar

    2015-12-01

    Soil salinity is a major environmental constraint to crop production. While the molecular identity and functional expression of Na(+) transport systems mediating Na(+) exclusion from the cytosol has been studied in detail, far less is known about the mechanisms by which plants sense high Na(+) levels in the soil and the rapid signalling events that optimise plant performance under saline conditions. This review aims to fill this gap. We first discuss the nature of putative salt stress sensors, candidates which include Na(+) transport systems, mechanosensory proteins, proteins with regulatory Na(+) binding sites, sensing mediated by cyclic nucleotide-gated channels, purine receptors, annexin and voltage gating. We suggest that several transport proteins may be clustered together to form a microdomain in a lipid raft, allowing rapid changes in the activity of an individual protein to be translated into stress-induced Ca(2+) and H2O2 signatures. The pathways of stress signalling to downstream targets are discussed, and the kinetics and specificity of salt stress signalling between glycophytes and halophytes is compared. We argue that these sensing mechanisms operate in parallel, providing plants with a robust system for decoding information about the specific nature and severity of the imposed salt stress.

  7. Iron oxide magnetic nanoparticles highlight early involvement of the choroid plexus in central nervous system inflammation

    OpenAIRE

    Millward, Jason M.; Jörg Schnorr; Matthias Taupitz; Susanne Wagner; Jens T. Wuerfel; Carmen Infante-Duarte

    2013-01-01

    Neuroinflammation during multiple sclerosis involves immune cell infiltration and disruption of the BBB (blood–brain barrier). Both processes can be visualized by MRI (magnetic resonance imaging), in multiple sclerosis patients and in the animal model EAE (experimental autoimmune encephalomyelitis). We previously showed that VSOPs (very small superparamagnetic iron oxide particles) reveal CNS (central nervous system) lesions in EAE which are not detectable by conventional contrast agents in M...

  8. Astronomy in the ancient world early and modern views on celestial events

    CERN Document Server

    McLeod, Alexus

    2016-01-01

    Alexus McLeod explores every aspect of the lesser-known history of astronomy in the Americas (Mesoamerica and North America), China and India, each through the frame of a particular astronomical phenomena. Part One considers the development of astronomy in the Americas as a response, in part, to the Supernova of 1054, which may have led to a cultural renaissance in astronomy. He then goes on to explore the contemporary understanding of supernovae, contrasting it with that of the ancient Americas.  Part Two is framed through the appearances of great comets, which had major divinatory significance in early China. The author discusses the advancement of observational astronomy in China, its influence on politics and its role in the survival or failure of empires.  Furthermore, the contemporary understanding of comets is also discussed for comparison.  Part Three, on India, considers the magnificent observatories of the Rajput king Jai Singh II, and the question of their purpose. The origins of Indian ast...

  9. An abrupt cooling event early in the last interglacial in the northern South China Sea

    Institute of Scientific and Technical Information of China (English)

    TU; Xia

    2001-01-01

    [1]Grootes, P. M., Stulver, M., Johnson, J. W. C. et al., Comparison of oxygen isotope records from GISP2 and GRIP Greenland ice cores, Nature, 1993, 366:552-554.[2]Maslin, M., Sarnthein, M., Knaack, J. J. et al., Intra-interglacial cold events: An Eemian-Holocene comparison, The Geo logical Society of London, Special Publications, 1998, 131:91-99.[3]Wang, P., Prell, W., Blum, P. et al., Proceedings of the Ocean Drilling Program, Initial Reports, 2000, 184.[4]Thompson, P. R., Bé, A. W. H., Disappearrence of pink-pigmented Globigerinoides ruber at 120,000yr BP in the Indian and Pacific Oceans, Nature, 1976, 280:554-558.[5]Martinson, D. G., Piasias, N. G., Hays, J. D. et al., Age dating and the orbital theory of the ice ages: Development of a high-resolution 0 to 300000-year chronostratigraphy, Quaternary Research, 1987, 27: 1-29.[6]Thompson, P. R., Planktonic foraminifera in the West North Pacific during the past 150,000 years: Comparison of modern and fossil assemblages, Palaeogeogr. Palaeoclimatol. Palaeoecol., 1981, 35:241-279.[7]Tu, X., Zheng, F., Chen, M. et al., Planktonic foraminifera in continental slope of southern South China Sea and their im plications to paleotemperature of surface sea water, Tropic Oceanology (in Chinese with English abstract), 2000, 19(3): 40-49.[8]Wang, L., Sarnthein, M., Erlenkeuser, H. et al., East Asian monsoon climate during the late Pleistocene: High-resolution sediment records from the South China Sea, Marine Geology, 1999, 156: 245-284.[9]Eglintin, G., Bradshaw, S. A., Rosell, A. et al., Molecular record of secular sea surface temperature changes on 100-year timescales for glacial terminations I, Ⅱ, and IV, Nature, 1992, 356: 423-426.[10]Maslin, M., Sarnthein, M., Knaack, J.-J., Subtropical Eastern Atlantic climate during the Eamian, Naturwissenschaften,1996, 83:122-126.[11]Sarnthein, M., Tiedemann, R., Younger Dryas-style cooling events at glacial terminations I-VI at ODP Site 658

  10. Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra.

    Science.gov (United States)

    Shen, Joel; Overland, Maya; Sinclair, Adriane; Cao, Mei; Yue, Xuan; Cunha, Gerald; Baskin, Laurence

    We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube. Copyright © 2016 International Society

  11. Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra

    Science.gov (United States)

    Sinclair, Adriane; Cao, Mei; Yue, Xuan; Cunha, Gerald; Baskin, Laurence

    2016-01-01

    We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization (“opening zipper”) opens the solid urethral plate into a groove, and fusion (“closing zipper”) closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal “cords”. Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube. PMID:27397682

  12. Early events of secretory granule formation in the rat parotid acinar cell under the influence of isoproterenol. An ultrastructural and lectin cytochemical study

    Directory of Open Access Journals (Sweden)

    F D’Amico

    2009-12-01

    Full Text Available The events involved in the maturation process of acinar secretory granules of rat parotid gland were investigated ultrastructurally and cytochemically by using a battery of four lectins [Triticum vulgaris agglutinin (WGA, Ulex europaeus agglutinin I (UEA-I, Glycine max agglutinin (SBA, Arachys hypogaea agglutinin (PNA]. In order to facilitate the study, parotid glands were chronically stimulated with isoproterenol to induce secretion. Specimens were embedded in the Lowicryl K4M resin. The trans-Golgi network (TGN derived secretory granules, which we refer to as immature secretory granules, were found to be intermediate structures in the biogenesis process of the secretory granules in the rat parotid acinar cell. These early structures do not seem to be the immediate precursor of the mature secretory granules: in fact, a subsequent interaction process between these early immature granule forms and TGN elements seems to occur, leading, finally, to the mature granules. These findings could explain the origin of the polymorphic subpopulations of the secretory granules in the normal acinar cells of the rat parotid gland. The lectin staining patterns were characteristic of each lectin. Immature and mature secretory gran- ules were labelled with WGA, SBA, PNA, and lightly with UEA-I. Cis and intermediate cisternae of the Golgi apparatus were labelled with WGA, and trans cisternae with WGA and SBA.

  13. The PRESSCA operational early warning system for landslide forecasting: the 11-12 November 2013 rainfall event in Central Italy.

    Science.gov (United States)

    Ciabatta, Luca; Brocca, Luca; Ponziani, Francesco; Berni, Nicola; Stelluti, Marco; Moramarco, Tommaso

    2014-05-01

    The Umbria Region, located in Central Italy, is one of the most landslide risk prone area in Italy, almost yearly affected by landslides events at different spatial scales. For early warning procedures aimed at the assessment of the hydrogeological risk, the rainfall thresholds represent the main tool for the Italian Civil Protection System. As shown in previous studies, soil moisture plays a key-role in landslides triggering. In fact, acting on the pore water pressure, soil moisture influences the rainfall amount needed for activating a landslide. In this work, an operational physically-based early warning system, named PRESSCA, that takes into account soil moisture for the definition of rainfall thresholds is presented. Specifically, the soil moisture conditions are evaluated in PRESSCA by using a distributed soil water balance model that is recently coupled with near real-time satellite soil moisture product obtained from ASCAT (Advanced SCATterometer) and from in-situ monitoring data. The integration of three different sources of soil moisture information allows to estimate the most accurate possible soil moisture condition. Then, both observed and forecasted rainfall data are compared with the soil moisture-based thresholds in order to obtain risk indicators over a grid of ~ 5 km. These indicators are then used for the daily hydrogeological risk evaluation and management by the Civil Protection regional service, through the sharing/delivering of near real-time landslide risk scenarios (also through an open source web platform: www.cfumbria.it). On the 11th-12th November, 2013, Umbria Region was hit by an exceptional rainfall event with up to 430mm/72hours that resulted in significant economic damages, but fortunately no casualties among the population. In this study, the results during the rainfall event of PRESSCA system are described, by underlining the model capability to reproduce, two days in advance, landslide risk scenarios in good spatial and temporal

  14. The importance of early involvement of paediatric palliative care for patients with severe congenital heart disease.

    Science.gov (United States)

    Bertaud, Sophie; Lloyd, David F A; Laddie, Joanna; Razavi, Reza

    2016-10-01

    Growing numbers of patients with severe congenital heart disease (CHD) are surviving into late childhood and beyond. This increasingly complex patient group may experience multiple formidable and precarious interventions, lifelong morbidity and the very real risk of premature death on many occasions throughout their childhood. In this paper, we discuss the advantages of a fully integrated palliative care ethos in patients with CHD, offering the potential for improved symptom control, more informed decision-making and enhanced support for patients and their families throughout their disease trajectory. These core principles may be delivered alongside expert cardiac care via non-specialists within pre-existing networks or via specialists in paediatric palliative care when appropriate. By broaching these complex issues early-even from the point of diagnosis-an individualised set of values can be established around not just end-of-life but also quality-of-life decisions, with clear benefits for patients and their families regardless of outcome.

  15. Involvement of insulin in early development of mouse one-cell stage embryos

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Recent studies have suggested that growth factors and hormones play important roles in cell prolif-eration and differentiation during early embryonic development. In the present study, we examined the expression and localization of insulin in the mouse oocytes and one-cell stage embryos by quantitative ELISA, RT-PCR, Western blot and immunofluorescence. In the mouse oocytes and one-cell stage em-bryos, expression of insulin was uniformly distributed in the cytoplasm. We also examined the expres-sion, activity and localization of mTOR (mammalian target of rapamycin) and p70S6K. The expression of mTOR and p70S6K was not significantly different at the cell cycle of mouse one-cell stage embryos. mTOR and S6K were distributed evenly in the cytoplasm at G1, G2 and M phase phase, but at S phase, the distribution of mTOR and S6K was around the pronucleus. At different phases, the activity of mTOR fluctuated. We also used the PI3K specific inhibitor-Wortmannin to investigate the cleavage rate of eggs. The result showed that the rate obviously decreased. When the mTOR specific inhibitor Rapa-mycin was used, the first mitotic division of the mouse one-cell stage embryo was delayed. These re-sults suggested that insulin was expressed both in mouse oocytes and one-cell stage embryos, and may play functional roles in regulation of mouse early embryogenesis by activating the signal pathway of PI3K/PKB/mTOR/S6K.

  16. Involvement of insulin in early development of mouse one-cell stase embryos

    Institute of Scientific and Technical Information of China (English)

    YU BingZhi; YU DaHai; ZHANG Zhe; DENG Xin; XU XiaoYan; FENG Chen; LI YanXiao; CUI Cheng; SU WenHui; ZHAO HongMei

    2008-01-01

    Recent studies have suggested that growth factors and hormones play important roles in cell prolif-eration and differentiation during early embryonic development. In the present study, we examined the expression and localization of insulin in the mouse oocytes and one-cell stage embryos by quantitative ELISA, RT-PCR, Western blot and immunofluorescence. In the mouse oocytes and one-cell stage em-bryos, expression of insulin was uniformly distributed in the cytoplasm. We also examined the expres-sion, activity and localization of mTOR (mammalian target of rapamycin) and p70S6K. The expression of mTOR and p70S6K was not significantly different at the cell cycle of mouse one-cell stage embryos. mTOR and S6K were distributed evenly in the cytoplasm at G1, G2 and M phase phase, but at S phase, the distribution of mTOR and S6K was around the pronucleus. At different phases, the activity of mTOR fluctuated. We also used the PI3K specific inhibitor-Wortmannin to investigate the cleavage rate of eggs. The result showed that the rate obviously decreased. When the mTOR specific inhibitor Rapa-mycin was used, the first mitotic division of the mouse one-cell stage embryo was delayed. These re-suits suggested that insulin was expressed both in mouse oocytes and one-cell stage embryos, and may play functional roles in regulation of mouse early embryogenesis by activating the signal pathway of PI3K/PKB/mTOR/S6K.

  17. Complement inhibition decreases early fibrogenic events in the lung of septic baboons

    Science.gov (United States)

    Silasi-Mansat, Robert; Zhu, Hua; Georgescu, Constantin; Popescu, Narcis; Keshari, Ravi S; Peer, Glenn; Lupu, Cristina; Taylor, Fletcher B; Pereira, Heloise Anne; Kinasewitz, Gary; Lambris, John D; Lupu, Florea

    2015-01-01

    Acute respiratory distress syndrome (ARDS) induced by severe sepsis can trigger persistent inflammation and fibrosis. We have shown that experimental sepsis in baboons recapitulates ARDS progression in humans, including chronic inflammation and long-lasting fibrosis in the lung. Complement activation products may contribute to the fibroproliferative response, suggesting that complement inhibitors are potential therapeutic agents. We have been suggested that treatment of septic baboons with compstatin, a C3 convertase inhibitor protects against ARDS-induced fibroproliferation. Baboons challenged with 109 cfu/kg (LD50) live E. coli by intravenous infusion were treated or not with compstatin at the time of challenge or 5 hrs thereafter. Changes in the fibroproliferative response at 24 hrs post-challenge were analysed at both transcript and protein levels. Gene expression analysis showed that sepsis induced fibrotic responses in the lung as early as 24 hrs post-bacterial challenge. Immunochemical and biochemical analysis revealed enhanced collagen synthesis, induction of profibrotic factors and increased cell recruitment and proliferation. Specific inhibition of complement with compstatin down-regulated sepsis-induced fibrosis genes, including transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), tissue inhibitor of metalloproteinase 1 (TIMP1), various collagens and chemokines responsible for fibrocyte recruitment (e.g. chemokine (C-C motif) ligand 2 (CCL2) and 12 (CCL12)). Compstatin decreased the accumulation of myofibroblasts and proliferating cells, reduced the production of fibrosis mediators (TGF-β, phospho-Smad-2 and CTGF) and inhibited collagen deposition. Our data demonstrate that complement inhibition effectively attenuates collagen deposition and fibrotic responses in the lung after severe sepsis. Inhibiting complement could prove an attractive strategy for preventing sepsis-induced fibrosis of the lung. PMID:26337158

  18. Loss of disabled-2 expression is an early event in esophageal squamous tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Kumar Anupam; Chatopadhyay Tusharkant; Siddhartha Datta Gupta; Ralhan Ranju

    2006-01-01

    AIM: Disabled-2 (D4B2) is a candidate tumor-suppressor gene identified in ovarian cancer that negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In a recent study, we observed down-regulation of DAB2 transcripts in ESCCs using cDNA microarrays. In the present study, we aimed to determine the clinical significance of loss of DAB2protein in esophageal tumorigenesis, hypothesizing that DAB2 promoter hypermethylation-mediated gene silencing may account for loss of the protein.METHODS: DAB2 expression was analyzed by immunohistochemistry in 50 primary esophageal squamous cell carcinomas (ESCCs), 30 distinct hyperplasia, 15 dysplasia and 10 non-malignant esophageal tissues. To determine whether promoter hypermethylation contributes to loss of DAB2 expression in ESCCs, methylation status of DAB2 promoter was analyzed in DAB2 immuno-negative tumors using methylation-specific PCR.RESULTS: Loss of DAB2 protein was observed in 5/30 (17%) hyperplasia, 10/15 (67%) dysplasia and 34/50 (68%) ESCCs. Significant loss of DAB2 protein was observed from esophageal normal mucosa to hyperplasia, dysplasia and invasive cancer (Ptrend < 0.001).Promoter hypermethylation of DAB2 was observed in 2of 10 (20%) DAB2 immuno-negative ESCCs.CONCLUSION: Loss of DAB2 protein expression occurs in early pre-neoplastic stages of development of esophageal cancer and is sustained down the tumorigenic pathway. Infrequent DAB2 promoter methylation in ESCCs suggests that epigenetic gene silencing is only one of the mechanisms causing loss of DAB2 expression in ESCCs.

  19. Early events following experimental infection with Peste-Des-Petits ruminants virus suggest immune cell targeting.

    Directory of Open Access Journals (Sweden)

    Robert A Pope

    Full Text Available Peste-des-petits ruminants virus (PPRV is a viral pathogen that causes a devastating plague of small ruminants. PPRV is an economically significant disease that continues to be a major obstacle to the development of sustainable agriculture across the developing world. The current understanding of PPRV pathogenesis has been heavily assumed from the closely related rinderpest virus (RPV and other morbillivirus infections alongside data derived from field outbreaks. There have been few studies reported that have focused on the pathogenesis of PPRV and very little is known about the processes underlying the early stages of infection. In the present study, 15 goats were challenged by the intranasal route with a virulent PPRV isolate, Côte d'Ivoire '89 (CI/89 and sacrificed at strategically defined time-points post infection to enable pre- and post-mortem sampling. This approach enabled precise monitoring of the progress and distribution of virus throughout the infection from the time of challenge, through peak viraemia and into a period of convalescence. Observations were then related to findings of previous field studies and experimental models of PPRV to develop a clinical scoring system for PPRV. Importantly, histopathological investigations demonstrated that the initial site for virus replication is not within the epithelial cells of the respiratory mucosa, as has been previously reported, but is within the tonsillar tissue and lymph nodes draining the site of inoculation. We propose that virus is taken up by immune cells within the respiratory mucosa which then transport virus to lymphoid tissues where primary virus replication occurs, and from where virus enters circulation. Based on these findings we propose a novel clinical scoring methodology for PPRV pathogenesis and suggest a fundamental shift away from the conventional model of PPRV pathogenesis.

  20. Early events following experimental infection with Peste-Des-Petits ruminants virus suggest immune cell targeting.

    Science.gov (United States)

    Pope, Robert A; Parida, Satya; Bailey, Dalan; Brownlie, Joe; Barrett, Thomas; Banyard, Ashley C

    2013-01-01

    Peste-des-petits ruminants virus (PPRV) is a viral pathogen that causes a devastating plague of small ruminants. PPRV is an economically significant disease that continues to be a major obstacle to the development of sustainable agriculture across the developing world. The current understanding of PPRV pathogenesis has been heavily assumed from the closely related rinderpest virus (RPV) and other morbillivirus infections alongside data derived from field outbreaks. There have been few studies reported that have focused on the pathogenesis of PPRV and very little is known about the processes underlying the early stages of infection. In the present study, 15 goats were challenged by the intranasal route with a virulent PPRV isolate, Côte d'Ivoire '89 (CI/89) and sacrificed at strategically defined time-points post infection to enable pre- and post-mortem sampling. This approach enabled precise monitoring of the progress and distribution of virus throughout the infection from the time of challenge, through peak viraemia and into a period of convalescence. Observations were then related to findings of previous field studies and experimental models of PPRV to develop a clinical scoring system for PPRV. Importantly, histopathological investigations demonstrated that the initial site for virus replication is not within the epithelial cells of the respiratory mucosa, as has been previously reported, but is within the tonsillar tissue and lymph nodes draining the site of inoculation. We propose that virus is taken up by immune cells within the respiratory mucosa which then transport virus to lymphoid tissues where primary virus replication occurs, and from where virus enters circulation. Based on these findings we propose a novel clinical scoring methodology for PPRV pathogenesis and suggest a fundamental shift away from the conventional model of PPRV pathogenesis.

  1. Early Events following Experimental Infection with Peste-Des-Petits Ruminants Virus Suggest Immune Cell Targeting

    Science.gov (United States)

    Pope, Robert A.; Parida, Satya; Bailey, Dalan; Brownlie, Joe; Barrett, Thomas; Banyard, Ashley C.

    2013-01-01

    Peste-des-petits ruminants virus (PPRV) is a viral pathogen that causes a devastating plague of small ruminants. PPRV is an economically significant disease that continues to be a major obstacle to the development of sustainable agriculture across the developing world. The current understanding of PPRV pathogenesis has been heavily assumed from the closely related rinderpest virus (RPV) and other morbillivirus infections alongside data derived from field outbreaks. There have been few studies reported that have focused on the pathogenesis of PPRV and very little is known about the processes underlying the early stages of infection. In the present study, 15 goats were challenged by the intranasal route with a virulent PPRV isolate, Côte d’Ivoire ’89 (CI/89) and sacrificed at strategically defined time-points post infection to enable pre- and post-mortem sampling. This approach enabled precise monitoring of the progress and distribution of virus throughout the infection from the time of challenge, through peak viraemia and into a period of convalescence. Observations were then related to findings of previous field studies and experimental models of PPRV to develop a clinical scoring system for PPRV. Importantly, histopathological investigations demonstrated that the initial site for virus replication is not within the epithelial cells of the respiratory mucosa, as has been previously reported, but is within the tonsillar tissue and lymph nodes draining the site of inoculation. We propose that virus is taken up by immune cells within the respiratory mucosa which then transport virus to lymphoid tissues where primary virus replication occurs, and from where virus enters circulation. Based on these findings we propose a novel clinical scoring methodology for PPRV pathogenesis and suggest a fundamental shift away from the conventional model of PPRV pathogenesis. PMID:23418464

  2. High-content analysis of sequential events during the early phase of influenza A virus infection.

    Science.gov (United States)

    Banerjee, Indranil; Yamauchi, Yohei; Helenius, Ari; Horvath, Peter

    2013-01-01

    Influenza A virus (IAV) represents a worldwide threat to public health by causing severe morbidity and mortality every year. Due to high mutation rate, new strains of IAV emerge frequently. These IAVs are often drug-resistant and require vaccine reformulation. A promising approach to circumvent this problem is to target host cell determinants crucial for IAV infection, but dispensable for the cell. Several RNAi-based screens have identified about one thousand cellular factors that promote IAV infection. However, systematic analyses to determine their specific functions are lacking. To address this issue, we developed quantitative, imaging-based assays to dissect seven consecutive steps in the early phases of IAV infection in tissue culture cells. The entry steps for which we developed the assays were: virus binding to the cell membrane, endocytosis, exposure to low pH in endocytic vacuoles, acid-activated fusion of viral envelope with the vacuolar membrane, nucleocapsid uncoating in the cytosol, nuclear import of viral ribonucleoproteins, and expression of the viral nucleoprotein. We adapted the assays to automated microscopy and optimized them for high-content screening. To quantify the image data, we performed both single and multi-parametric analyses, in combination with machine learning. By time-course experiments, we determined the optimal time points for each assay. Our quality control experiments showed that the assays were sufficiently robust for high-content analysis. The methods we describe in this study provide a powerful high-throughput platform to understand the host cell processes, which can eventually lead to the discovery of novel anti-pathogen strategies.

  3. Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses.

    Science.gov (United States)

    DeJoy, David M; Smith, Todd D; Woldu, Henok; Dyal, Mari-Amanda; Steege, Andrea L; Boiano, James M

    2017-07-01

    Antineoplastic drugs pose risks to the healthcare workers who handle them. This fact notwithstanding, adherence to safe handling guidelines remains inconsistent and often poor. This study examined the effects of pertinent organizational safety practices and perceived safety climate on the use of personal protective equipment, engineering controls, and adverse events (spill/leak or skin contact) involving liquid antineoplastic drugs. Data for this study came from the 2011 National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers which included a sample of approximately 1,800 nurses who had administered liquid antineoplastic drugs during the past seven days. Regression modeling was used to examine predictors of personal protective equipment use, engineering controls, and adverse events involving antineoplastic drugs. Approximately 14% of nurses reported experiencing an adverse event while administering antineoplastic drugs during the previous week. Usage of recommended engineering controls and personal protective equipment was quite variable. Usage of both was better in non-profit and government settings, when workers were more familiar with safe handling guidelines, and when perceived management commitment to safety was higher. Usage was poorer in the absence of specific safety handling procedures. The odds of adverse events increased with number of antineoplastic drugs treatments and when antineoplastic drugs were administered more days of the week. The odds of such events were significantly lower when the use of engineering controls and personal protective equipment was greater and when more precautionary measures were in place. Greater levels of management commitment to safety and perceived risk were also related to lower odds of adverse events. These results point to the value of implementing a comprehensive health and safety program that utilizes available hazard controls and effectively communicates

  4. Brain MRI and SPECT in the diagnosis of early neurological involvement in Wilson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Piga, Mario; Satta, Loredana; Serra, Alessandra; Loi, Gianluigi [Policlinico Universitario, University of Cagliari, Nuclear Medicine, Department of Medical Science, Monserrato, Cagliari (Italy); Murru, Alessandra; Demelia, Luigi [Policlinico Universitario, University of Cagliari, Gastroenterology, Department of Medical Science, Monserrato, Cagliari (Italy); Sias, Alessandro [Policlinico Universitario, University of Cagliari, Radiology, Department of Medical Science, Monserrato, Cagliari (Italy); Marrosu, Francesco [Policlinico Universitario, University of Cagliari, Neurology, Department of Medical Science, Monserrato, Cagliari (Italy)

    2008-04-15

    To evaluate the impact of brain MRI and single-photon emission computed tomography (SPECT) in early detection of central nervous system abnormalities in patients affected by Wilson's disease (WD) with or without neurological involvement. Out of 25 consecutive WD patients, 13 showed hepatic involvement, ten hepatic and neurological manifestations, and twp hepatic, neurological, and psychiatric symptoms, including mainly movement disorders, major depression, and psychosis. Twenty-four healthy, age-gender matched subjects served as controls. All patients underwent brain MRI and {sup 99m}Tc-ethyl-cysteinate dimer (ECD) SPECT before starting specific therapy. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare differences in {sup 99m}Tc-ECD brain uptake between the two groups. Brain MRI showed T2-weighted hyperintensities in seven patients (28%), six of whom were affected by hepatic and neurological forms. Brain perfusion SPECT showed pathological data in 19 patients (76%), revealing diffuse or focal hypoperfusion in superior frontal (Brodmann area (BA) 6), prefrontal (BA 9), parietal (BA 40), and occipital (BA 18, BA 39) cortices in temporal gyri (BA 37, BA 21) and in caudatus and putamen. Moreover, hepatic involvement was detected in nine subjects; eight presented both hepatic and neurological signs, while two exhibited WD-correlated hepatic, neurological, and psychiatric alterations. All but one patient with abnormal MRI matched with abnormal ECD SPECT. Pathologic MRI findings were obtained in six out of ten patients with hepatic and neurological involvement while abnormal ECD SPECT was revealed in eight patients. Both patients with hepatic, neurological, and psychiatric involvement displayed abnormal ECD SPECT and one displayed an altered MRI. These findings suggest that ECD SPECT might be useful in detecting early brain damage in WD, not only in the perspective of assessing and treating motor impairment but also in evaluating

  5. Counterfactual Reasoning for Regretted Situations Involving Controllable Versus Uncontrollable Events: The Modulating Role of Contingent Self-Esteem

    OpenAIRE

    2015-01-01

    We report a study that examined the modulating impact of contingent self-esteem on regret\\ud intensity for regretted outcomes associated with controllable versus uncontrollable events.\\ud The Contingent Self-Esteem Scale (e.g., Kernis & Goldman, 2006) was used to assess the extent\\ud to which a person’s sense of self-worth is based on self and others’ expectations. We found\\ud that there was an influence of self-esteem contingency for controllable but not for uncontrollable\\ud regret types. F...

  6. Involvement of skeletal muscle protein, glycogen, and fat metabolism in the adaptation on early lactation of dairy cows.

    Science.gov (United States)

    Kuhla, Björn; Nürnberg, Gerd; Albrecht, Dirk; Görs, Solvig; Hammon, Harald M; Metges, Cornelia C

    2011-09-02

    During early lactation, high-yielding dairy cows cannot consume enough feed to meet nutrient requirements. As a consequence, animals drop into negative energy balance and mobilize body reserves including muscle protein and glycogen for milk production, direct oxidation, and hepatic gluconeogenesis. To examine which muscle metabolic processes contribute to the adaptation during early lactation, six German Holstein cows were blood sampled and muscle biopsied throughout the periparturient period. From pregnancy to lactation, the free plasma amino acid pattern imbalanced and plasma glucose decreased. Several muscle amino acids, as well as total muscle protein, fat, and glycogen, and the expression of glucose transporter-4 were reduced within the first 4 weeks of lactation. The 2-DE and MALDI-TOF-MS analysis identified 43 differentially expressed muscle protein spots throughout the periparturient period. In early lactation, expression of cytoskeletal proteins and enzymes involved in glycogen synthesis and in the TCA cycle was decreased, whereas proteins related to glycolysis, fatty acid degradation, lactate, and ATP production were increased. On the basis of these results, we propose a model in which the muscle breakdown in early lactation provides substrates for milk production by a decoupled Cori cycle favoring hepatic gluconeogenesis and by interfering with feed intake signaling.

  7. Early Holocene High Magnitude Debris Flow Events and Environmental Change as Illustrated by the Moxi Platform, Hengduan Mountains, SW China

    Institute of Scientific and Technical Information of China (English)

    ZHANG Junyan; CHENG Genwei; LI Yongfei

    2006-01-01

    Thick debris flow deposits in the Hengduan Mountains of southwestern China record landscape instability at the close of the last glaciation and in the early Holocene. The deposits, ranging in thickness from 100 to 200 m, are common and in high magnitude in the valleys of this region. They are products of large debris flows induced by glacier and enabled by the presence of large amount of glacial debris on the landscape. The carbon 14 dating from Moxi Platform indicates that a period of catastrophic debris flows occurred at c. 7 kyr B.P., and was concurrent with other glacial-fluvial fans and terraces which tied to regional climatic oscillations elsewhere in the Himalaya. The comparable events suggest a strong climatic control on earth surface processes for the dynamics, magnitude, and frequency in this region.

  8. Aneuploidy involving chromosome 1 may be an early predictive marker of intestinal type gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Williams, L. [Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant CF72 8XR (United Kingdom); Somasekar, A. [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom); Neath Port Talbot Hospital, Abertawe Bro Morgannwg University NHS Trust, Baglan Way, Port Talbot SA12 7BX (United Kingdom); Davies, D.J.; Cronin, J.; Doak, S.H. [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom); Alcolado, R. [Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant CF72 8XR (United Kingdom); Williams, J.G. [Neath Port Talbot Hospital, Abertawe Bro Morgannwg University NHS Trust, Baglan Way, Port Talbot SA12 7BX (United Kingdom); Griffiths, A.P. [Department of Histopathology, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Morriston, SA66NL (United Kingdom); Baxter, J.N. [Department of Surgery, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Morriston, SA66NL (United Kingdom); Jenkins, G.J.S., E-mail: g.j.jenkins@swansea.ac.uk [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom)

    2009-10-02

    Intestinal type gastric cancer is a significant cause of mortality, therefore a better understanding of its molecular basis is required. We assessed if either aneuploidy or activity of the oncogenic transcription factor nuclear factor kappa B (NF-{kappa}B), increased incrementally during pre-malignant gastric histological progression and also if they correlated with each other in patient samples, as they are both induced by oxygen free radicals. In a prospective study of 54 (aneuploidy) and 59 (NF-{kappa}B) consecutive patients, aneuploidy was assessed by interphase fluorescent in situ hybridisation (FISH) for chromosome 1. NF-{kappa}B was assessed by expression of interleukin-8 (IL-8), and in a subset, by immunohistochemistry (IHC) for active p65. Aneuploidy levels increased incrementally across the histological series. 2.76% of cells with normal histology (95% CI, 2.14-3.38%) showed background levels of aneuploidy, this increased to averages of 3.78% (95% CI, 3.21-4.35%), 5.89% (95% CI, 3.72-8.06%) and 7.29% (95% CI, 4.73-9.85%) of cells from patients with gastritis, Helicobacter pylori positive gastritis and atrophy/intestinal metaplasia (IM) respectively. IL-8 expression was only increased in patients with current H. pylori infection. NF-{kappa}B analysis showed some increased p65 activity in inflamed tissues. IL-8 expression and aneuploidy level were not linked in individual patients. Aneuploidy levels increased incrementally during histological progression; were significantly elevated at very early stages of neoplastic progression and could well be linked to cancer development and used to assess cancer risk. Reactive oxygen species (ROS) induced in early gastric cancer are presumably responsible for the stepwise accumulation of this particular mutation, i.e. aneuploidy. Hence, aneuploidy measured by fluorescent in situ hybridisation (FISH) coupled to brush cytology, would be worthy of consideration as a predictive marker in gastric cancer and could be

  9. The temporal dynamics of early visual cortex involvement in behavioral priming.

    Directory of Open Access Journals (Sweden)

    Christianne Jacobs

    Full Text Available Transcranial magnetic stimulation (TMS allows for non-invasive interference with ongoing neural processing. Applied in a chronometric design over early visual cortex (EVC, TMS has proved valuable in indicating at which particular time point EVC must remain unperturbed for (conscious vision to be established. In the current study, we set out to examine the effect of EVC TMS across a broad range of time points, both before (pre-stimulus and after (post-stimulus the onset of symbolic visual stimuli. Behavioral priming studies have shown that the behavioral impact of a visual stimulus can be independent from its conscious perception, suggesting two independent neural signatures. To assess whether TMS-induced suppression of visual awareness can be dissociated from behavioral priming in the temporal domain, we thus implemented three different measures of visual processing, namely performance on a standard visual discrimination task, a subjective rating of stimulus visibility, and a visual priming task. To control for non-neural TMS effects, we performed electrooculographical recordings, placebo TMS (sham, and control site TMS (vertex. Our results suggest that, when considering the appropriate control data, the temporal pattern of EVC TMS disruption on visual discrimination, subjective awareness and behavioral priming are not dissociable. Instead, TMS to EVC disrupts visual perception holistically, both when applied before and after the onset of a visual stimulus. The current findings are discussed in light of their implications on models of visual awareness and (subliminal priming.

  10. The temporal dynamics of early visual cortex involvement in behavioral priming.

    Science.gov (United States)

    Jacobs, Christianne; de Graaf, Tom A; Goebel, Rainer; Sack, Alexander T

    2012-01-01

    Transcranial magnetic stimulation (TMS) allows for non-invasive interference with ongoing neural processing. Applied in a chronometric design over early visual cortex (EVC), TMS has proved valuable in indicating at which particular time point EVC must remain unperturbed for (conscious) vision to be established. In the current study, we set out to examine the effect of EVC TMS across a broad range of time points, both before (pre-stimulus) and after (post-stimulus) the onset of symbolic visual stimuli. Behavioral priming studies have shown that the behavioral impact of a visual stimulus can be independent from its conscious perception, suggesting two independent neural signatures. To assess whether TMS-induced suppression of visual awareness can be dissociated from behavioral priming in the temporal domain, we thus implemented three different measures of visual processing, namely performance on a standard visual discrimination task, a subjective rating of stimulus visibility, and a visual priming task. To control for non-neural TMS effects, we performed electrooculographical recordings, placebo TMS (sham), and control site TMS (vertex). Our results suggest that, when considering the appropriate control data, the temporal pattern of EVC TMS disruption on visual discrimination, subjective awareness and behavioral priming are not dissociable. Instead, TMS to EVC disrupts visual perception holistically, both when applied before and after the onset of a visual stimulus. The current findings are discussed in light of their implications on models of visual awareness and (subliminal) priming.

  11. Myocardial involvement during the early course of type 2 diabetes mellitus: usefulness of Myocardial Performance Index

    Directory of Open Access Journals (Sweden)

    Goldoni Matteo

    2008-06-01

    Full Text Available Abstract To evaluate whether myocardial performance index detects a subclinical impairment of left ventricular systolic and diastolic function in patients with early stage of type 2 diabetes, without coronary artery disease, with or without hypertension. Furthermore, to evaluate whether some echocardiographic parameters relate to the metabolic control. Fourty-five consecutive male patients (mean age 52.5 years with type 2 diabetes mellitus of recent onset (23 hypertensives and 22 normotensives and 22 age matched healthy controls males were analysed. All participants had normal exercise ECG. All subjects underwent standard and Doppler echocardiography for the assessment of the isovolumic Doppler time interval and Doppler-derived myocardial performance index. In all diabetic patients a glycated haemoglobin test was also performed. No differences were observed in blood pressure, heart rate, and conventional echocardiographic parameters comparing the 2 subgroups of diabetic patients and the controls. Myocardial performance index was significantly higher in diabetic patients independently of the hypertension occurrence, compared to the controls (0.49 and 0.49 diabetic normotensives and hypertensives respectively vs. 0.39, p

  12. Localization of Magic-F1 Transgene, Involved in Muscular Hypertrophy, during Early Myogenesis

    Science.gov (United States)

    Ronzoni, Flavio; Bongio, Matilde; Conte, Silvio; Vercesi, Luigi; Cassano, Marco; Tribioli, Carla; Galli, Daniela; Bellazzi, Riccardo; Magenes, Giovanni; Cusella De Angelis, Maria Gabriella; Sampaolesi, Maurilio

    2011-01-01

    We recently showed that Magic-F1 (Met-activating genetically improved chimeric factor 1), a human recombinant protein derived from hepatocyte growth factor/scatter factor (HGF/SF) induces muscle cell hypertrophy but not progenitor cell proliferation, both in vitro and in vivo. Here, we examined the temporal and spatial expression pattern of Magic-F1 in comparison with Pax3 (paired box gene 3) transcription factor during embryogenesis. Ranging from 9.5 to 17.5 dpc (days post coitum) mouse embryos were analyzed by in situ hybridization using whole mounts during early stages of development (9.5–10.5–11.5 dpc) and cryostat sections for later stages (11.5–13.5–15.5–17.5 dpc). We found that Magic-F1 is expressed in developing organs and tissues of mesenchymal origin, where Pax3 signal appears to be downregulated respect to the wt embryos. These data suggest that Magic-F1 could be responsible of muscular hypertrophy, cooperating with Pax3 signal pathway in skeletal muscle precursor cells. PMID:22187527

  13. Hypoxanthine deregulates genes involved in early neuronal development. Implications in Lesch-Nyhan disease pathogenesis.

    Science.gov (United States)

    Torres, R J; Puig, J G

    2015-11-01

    Neurological manifestations in Lesch-Nyhan disease (LND) are attributed to the effect of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency on the nervous system development. HPRT deficiency causes the excretion of increased amounts of hypoxanthine into the extracellular medium and we hypothesized that HPRT deficiency related to hypoxanthine excess may then lead, directly or indirectly, to transcriptional aberrations in a variety of genes essential for the function and development of striatal progenitor cells. We have examined the effect of hypoxanthine excess on the differentiation of neurons in the well-established human NTERA-2 cl.D1 (NT2/D1) embryonic carcinoma neurogenesis model. NT2/D1 cells differentiate along neuroectodermal lineages after exposure to retinoic acid (RA). Hypoxanthine effects on RA-differentiation were examined by the changes on the expression of various transcription factor genes essential to neuronal differentiation and by the changes in tyrosine hydroxylase (TH), dopamine, adenosine and serotonin receptors (DRD, ADORA, HTR). We report that hypoxanthine excess deregulate WNT4, from Wnt/β-catenin pathway, and engrailed homeobox 1 gene and increased TH and dopamine DRD1, adenosine ADORA2A and serotonin HTR7 receptors, whose over expression characterize early neuro-developmental processes.

  14. Paracrine mechanisms involved in the control of early stages of mammalian spermatogenesis

    Directory of Open Access Journals (Sweden)

    Pellegrino eRossi

    2013-11-01

    Full Text Available Within the testis, Sertoli cell is the primary target of pituitary FSH. Several growth factors have been described to be produced specifically by Sertoli cells and modulate male germ cell development through paracrine mechanisms. Some have been shown to act directly on spermatogonia such as GDNF, which acts on self-renewal of spermatogonial stem cells (SSCs while inhibiting their differentiation; BMP4, which has both a proliferative and differentiative effect on these cells, and KL, which stimulates the KIT tyrosine-kinase receptor expressed by differentiating spermatogonia (but not by SSCs. KL not only controls the proliferative cycles of KIT positive spermatogonia, but it also stimulates the expression of genes that are specific of the early phases of meiosis, whereas the expression of typical spermatogonial markers is down-regulated. On the contrary, FGF9 acts as a meiotic inhibiting substance both in fetal gonocytes and in post-natal spermatogonia through the induction of the RNA-binding protein NANOS2. Vitamin A, which is metabolized to Retinoic Acid in Sertoli cells, controls both SSCs differentiation through KIT induction and NANOS2 inhibition, and meiotic entry of differentiating spermatogonia through STRA8 upregulation.

  15. Bacillus subtilis Early Colonization of Arabidopsis thaliana Roots Involves Multiple Chemotaxis Receptors.

    Science.gov (United States)

    Allard-Massicotte, Rosalie; Tessier, Laurence; Lécuyer, Frédéric; Lakshmanan, Venkatachalam; Lucier, Jean-François; Garneau, Daniel; Caudwell, Larissa; Vlamakis, Hera; Bais, Harsh P; Beauregard, Pascale B

    2016-11-29

    Colonization of plant roots by Bacillus subtilis is mutually beneficial to plants and bacteria. Plants can secrete up to 30% of their fixed carbon via root exudates, thereby feeding the bacteria, and in return the associated B. subtilis bacteria provide the plant with many growth-promoting traits. Formation of a biofilm on the root by matrix-producing B. subtilis is a well-established requirement for long-term colonization. However, we observed that cells start forming a biofilm only several hours after motile cells first settle on the plant. We also found that intact chemotaxis machinery is required for early root colonization by B. subtilis and for plant protection. Arabidopsis thaliana root exudates attract B. subtilis in vitro, an activity mediated by the two characterized chemoreceptors, McpB and McpC, as well as by the orphan receptor TlpC. Nonetheless, bacteria lacking these chemoreceptors are still able to colonize the root, suggesting that other chemoreceptors might also play a role in this process. These observations suggest that A. thaliana actively recruits B. subtilis through root-secreted molecules, and our results stress the important roles of B. subtilis chemoreceptors for efficient colonization of plants in natural environments. These results demonstrate a remarkable strategy adapted by beneficial rhizobacteria to utilize carbon-rich root exudates, which may facilitate rhizobacterial colonization and a mutualistic association with the host.

  16. Bacillus subtilis Early Colonization of Arabidopsis thaliana Roots Involves Multiple Chemotaxis Receptors

    Directory of Open Access Journals (Sweden)

    Rosalie Allard-Massicotte

    2016-11-01

    Full Text Available Colonization of plant roots by Bacillus subtilis is mutually beneficial to plants and bacteria. Plants can secrete up to 30% of their fixed carbon via root exudates, thereby feeding the bacteria, and in return the associated B. subtilis bacteria provide the plant with many growth-promoting traits. Formation of a biofilm on the root by matrix-producing B. subtilis is a well-established requirement for long-term colonization. However, we observed that cells start forming a biofilm only several hours after motile cells first settle on the plant. We also found that intact chemotaxis machinery is required for early root colonization by B. subtilis and for plant protection. Arabidopsis thaliana root exudates attract B. subtilis in vitro, an activity mediated by the two characterized chemoreceptors, McpB and McpC, as well as by the orphan receptor TlpC. Nonetheless, bacteria lacking these chemoreceptors are still able to colonize the root, suggesting that other chemoreceptors might also play a role in this process. These observations suggest that A. thaliana actively recruits B. subtilis through root-secreted molecules, and our results stress the important roles of B. subtilis chemoreceptors for efficient colonization of plants in natural environments. These results demonstrate a remarkable strategy adapted by beneficial rhizobacteria to utilize carbon-rich root exudates, which may facilitate rhizobacterial colonization and a mutualistic association with the host.

  17. The Intense Arctic Cyclone of Early August 2012: A Dynamically Driven Cyclogenesis Event

    Science.gov (United States)

    Bosart, L. F.; Turchioe, A.; Adamchcik, E.

    2013-12-01

    A series of surface cyclones formed along an anomalously strong northeast-southwest oriented baroclinic zone over north-central Russia on 1-3 August 2012. These cyclones moved northeastward, intensified slowly, and crossed the coast of Russia by 4 August. The last cyclone in the series strengthened rapidly as it moved poleward over the Arctic Ocean on 5-6 August, achieved a minimum sea level pressure of impact the Arctic Ocean in the modern data record going back to the International Geophysical Year in 1957-1958. The purpose of this presentation is to illustrate the structure and life cycle of this Arctic Ocean cyclone from a multiscale perspective. Anticyclonic wave breaking in the upper troposphere across Russia in late July and very early August 2012 created an anomalously strong baroclinic zone across northern Asia between 60-80°N. During 1-5 August, negative 850 hPa temperature anomalies between -2° and -4°C were found poleward of 70-75°N between 90°E and the Dateline over the Arctic Ocean while positive 850 hPa temperature anomalies of 8-9°C were found over eastern Russia near 60°N. The associated anomalously strong 850 hPa meridional temperature gradient of ~10°C (2000 km)-1 helped to sustain an anomalously strong (20-30 m s-1) 250 hPa jet along the coast of northeastern Russia. A local wind speed maximum (~50 m s-1 ) embedded in this 250 hPa jet corridor contributed to the extreme intensity of the trailing (last) surface cyclone in the series. Although the dominant surface cyclone in the series of surface cyclones intensified most rapidly over the relatively ice free Arctic Ocean, the impact of surface heat and moisture fluxes appeared to be secondary to jet-driven dynamical processes in the deepening process. Anomalously high observed 1000-500 hPa thickness values between 564-570 dam, precipitable water values between 30-40 mm, and CAPE values between 500-1000 J kg-1 in the warm sector of the developing cyclone over north-central Russia were

  18. Early pulmonary involvement of anti-CADM-140 autoantibody-positive rapidly progressive interstitial lung disease preceding typical cutaneous symptoms.

    Science.gov (United States)

    Tamai, Koji; Tachikawa, Ryo; Otsuka, Kyoko; Ueda, Hiroyuki; Hosono, Yuji; Tomii, Keisuke

    2014-01-01

    We herein report a patient with clinically amyopathic dermatomyositis (CADM) who developed anti-CADM-140 autoantibody in association with rapidly progressive interstitial lung disease (RP-ILD). Chest high-resolution computed tomography (HRCT) revealed early pulmonary involvement preceding typical cutaneous lesions. Primary lesions of patchy peribronchial opacity developed ground-glass opacity and consolidation with architectural distortion and traction bronchiectasis. The possibility of anti-CADM-140 autoantibody-associated RP-ILD should be considered when patchy peribronchial opacity of an unknown cause is visible on chest HRCT.

  19. Perillyl Alcohol Protects against Fe-NTA-Induced Nephrotoxicity and Early Tumor Promotional Events in Rat Experimental Model

    Directory of Open Access Journals (Sweden)

    Tamanna Jahangir

    2007-01-01

    Full Text Available Plants have been widely used as protective agents against a wide variety of processes and compounds that damage tissues via free radical mechanisms. Perillyl alcohol (PA is a naturally occurring monoterpene found in the essential oils of numerous species of plants including mints, cherries and celery seeds. This monocyclic monoterpene has shown antioxidant and therapeutic activity in various studies against various xenobiotics. In this study, we have analyzed the effects of PA against single intraperitoneal dose of ferric nitrilotriacetate (Fe-NTA (9 mg iron per kg body weight-induced nephrotoxicity and early tumor promotional events. The pretreatment of Fe-NTA-treated rats with 0.5% per kg body weight dose and 1% per kg body weight dose of PA for seven consecutive days significantly reversed the Fe-NTA-induced malondialdehyde formation, xanthine oxidase activity (P < 0.001, ornithine decarboxylase activity (P < 0.001 and 3[H]thymidine incorporation in renal DNA (P < 0.001 with simultaneous significant depletion in serum toxicity markers blood urea nitrogen and creatinine (P < 0.001. Significant restoration at both the doses was recorded in depleted renal glutathione content, and its dependent enzymes with prophylactic treatment of PA. Present results suggest that PA potentially attenuates against Fe-NTA-induced oxidative damage and tumor promotional events that preclude its development as a future drug to avert the free radical-induced toxicity.

  20. Involvement of ethylene biosynthesis and signalling in fruit set and early fruit development in zucchini squash (Cucurbita pepo L.).

    Science.gov (United States)

    Martínez, Cecilia; Manzano, Susana; Megías, Zoraida; Garrido, Dolores; Picó, Belén; Jamilena, Manuel

    2013-09-22

    We have identified a kind of parthenocarpy in zucchini squash which is associated with an incomplete andromonoecy, i.e. a partial conversion of female into bisexual flowers. Given that andromonoecy in this and other cucurbit species is caused by a reduction of ethylene production in the female flower, the associated parthenocarpic development of the fruit suggested the involvement of ethylene in fruit set and early fruit development. We have compared the production of ethylene as well as the expression of 13 ethylene biosynthesis and signalling genes in pollinated and unpollinated ovaries/fruits of two cultivars, one of which is parthenocarpic (Cavili), while the other is non-parthenocarpic (Tosca). In the latter, unpollinated ovaries show an induction of ethylene biosynthesis and ethylene signal transduction pathway genes three days after anthesis, which is concomitant with the initiation of fruit abortion and senescence. Fruit set and early fruit development in pollinated flowers of both cultivars and unpollinated flowers of Cavili is coupled with low ethylene biosynthesis and signalling, which would also explain the partial andromonoecy in the parthenocarpic genotype. The reduction of ethylene production in the ovary cosegregates with parthenocarpy and partial andromonoecy in the selfing progeny of Cavili. Moreover, the induction of ethylene in anthesis (by ethephon treatments) reduced the percentage of bisexual parthenocarpic flowers in Cavili, while the inhibition of ethylene biosynthesis or response (by AVG and STS treatments) induces not only andromonoecy but also the parthenocarpic development of the fruit in both cultivars. Results demonstrate that a reduction of ethylene production or signalling in the zucchini flower is able to induce fruit set and early fruit development, and therefore that ethylene is actively involved in fruit set and early fruit development. Auxin and TIBA treatments, inducing fruit set and early fruit development in this species

  1. Early start of combination therapy with hemodialysis and peritoneal dialysis prolongs survival and reduces cardiovascular events in male patients.

    Science.gov (United States)

    Suzuki, Hiromichi; Hoshi, Hitosi; Inoue, Tsutomu; Kikuta, Tomohiro; Tsuda, Masahiro; Takenaka, Tsuneo

    2012-01-01

    Although peritoneal dialysis (PD) has been recommended for initial dialysis therapy, a larger proportion of patients with end-stage renal disease choose hemodialysis (HD) instead. Several previous studies comparing the outcomes of these two therapies, including survival rates and cardiovascular events, have not clearly demonstrated the superiority of one over the other. Our recent study indicated that, compared with HD or PD alone, renal replacement therapy with HD and PD in combination prolongs survival and reduces cardiovascular events. However, the use of combination dialysis therapy is not widely accepted. We set out to analyze the efficacy of combination dialysis therapy with PD and HD in patients who started with PD as initial dialysis therapy. Our single-center retrospective cohort study included 401 patients (165 women, 236 men; 61 +/- 12 and 62 +/- 9 years of age respectively) who started PD during 1995-2005. Chart and electronic databases were used to obtain information on the course of dialysis therapy, including mortality and cardiovascular events. Treatment with HD and PD in combination was used in 103 patients. During 5 years of follow-up after the start of PD, 80 patients died. We observed no differences in cumulative mortality between the men (49, 200%) and women (31, 18%) and no difference in the cumulative incidence of catheter removal for various reasons (35% vs. 31%). There was a significant difference (p dialysis patient population, women on PD experience mortality similar to that in men. The reasons for those findings have not been fully explained. The present analysis suggests that an early start to HD therapy will prolong the survival of patients on PD, especially men.

  2. Counterfactual reasoning for regretted situations involving controllable versus uncontrollable events: the modulating role of contingent self-esteem.

    Science.gov (United States)

    Wilkinson, Meredith R; Ball, Linden J; Alford, David

    2015-01-01

    We report a study that examined the modulating impact of contingent self-esteem on regret intensity for regretted outcomes associated with controllable versus uncontrollable events. The Contingent Self-Esteem Scale (e.g., Kernis & Goldman, 2006) was used to assess the extent to which a person's sense of self-worth is based on self and others' expectations. We found that there was an influence of self-esteem contingency for controllable but not for uncontrollable regret types. For controllable regret types individuals with a high contingent (i.e., unstable) self-esteem reported greater regret intensity than those with a low contingent (i.e., stable) self-esteem. We interpret this finding as reflecting a functional and adaptive role of high contingent self-esteem in terms of mobilizing the application of counterfactual reasoning and planning mechanisms that can enable personal expectations to be achieved in the future.

  3. Counterfactual Reasoning for Regretted Situations Involving Controllable Versus Uncontrollable Events: The Modulating Role of Contingent Self-Esteem

    Science.gov (United States)

    Wilkinson, Meredith R.; Ball, Linden J.; Alford, David

    2015-01-01

    We report a study that examined the modulating impact of contingent self-esteem on regret intensity for regretted outcomes associated with controllable versus uncontrollable events. The Contingent Self-Esteem Scale (e.g., Kernis & Goldman, 2006) was used to assess the extent to which a person’s sense of self-worth is based on self and others’ expectations. We found that there was an influence of self-esteem contingency for controllable but not for uncontrollable regret types. For controllable regret types individuals with a high contingent (i.e., unstable) self-esteem reported greater regret intensity than those with a low contingent (i.e., stable) self-esteem. We interpret this finding as reflecting a functional and adaptive role of high contingent self-esteem in terms of mobilizing the application of counterfactual reasoning and planning mechanisms that can enable personal expectations to be achieved in the future. PMID:25883697

  4. Implicit processing of heroin and emotional cues in abstinent heroin users: early and late event-related potential effects.

    Science.gov (United States)

    Yang, Ling; Zhang, Jianxun; Zhao, Xin

    2015-05-01

    The abnormal cognitive processing of drug cues is a core characteristic of drug dependence. Previous research has suggested that the late positive potential (LPP) of heroin users is increased by heroin-related stimuli because of the attention-grabbing nature of such stimuli. The present research used a modified emotional Stroop (eStroop) task to examine whether there was an early posterior negativity (EPN) modulation to heroin cues compared with emotional or neutral stimuli in heroin dependent subjects. Fifteen former heroin users and 15 matched controls performed the eStroop task, which was composed of positive, negative, heroin-related, and neutral pictures with superimposed color squares. Participants responded to the color of the square and not to the picture while behavioral data and event-related potentials were recorded. There were no significant differences of EPN amplitudes to emotional and neutral stimuli between heroin users and controls. However, heroin users displayed increased EPN modulation for heroin cues, whereas this modulation was absent in controls. Drug-related cues acquire motivational salience and automatically capture the attention of heroin users at early processing stages, even when engaged in a non-drug-related task. The EPN to heroin cues could represent a novel electrophysiological index with clinical implications for selecting abstinent drug users who are at increased risk of relapse or to evaluate treatment interventions.

  5. Loss of inositol polyphosphate 5-phosphatase is an early event in development of cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Sekulic, Aleksandar; Kim, Su Y; Hostetter, Galen; Savage, Stephanie; Einspahr, Janine G; Prasad, Anil; Sagerman, Paul; Curiel-Lewandrowski, Clara; Krouse, Robert; Bowden, G Timothy; Warneke, James; Alberts, David S; Pittelkow, Mark R; DiCaudo, David; Nickoloff, Brian J; Trent, Jeffrey M; Bittner, Michael

    2010-10-01

    Cutaneous squamous cell carcinoma (SCC) occurs commonly and can metastasize. Identification of specific molecular aberrations and mechanisms underlying the development and progression of cutaneous SCC may lead to better prognostic and therapeutic approaches and more effective chemoprevention strategies. To identify genetic changes associated with early stages of cutaneous SCC development, we analyzed a series of 40 archived skin tissues ranging from normal skin to invasive SCC. Using high-resolution array-based comparative genomic hybridization, we identified deletions of a region on chromosome 10q harboring the INPP5A gene in 24% of examined SCC tumors. Subsequent validation by immunohistochemistry on an independent sample set of 71 SCC tissues showed reduced INPP5A protein levels in 72% of primary SCC tumors. Decrease in INPP5A protein levels seems to be an early event in SCC development, as it also is observed in 9 of 26 (35%) examined actinic keratoses, the earliest stage in SCC development. Importantly, further reduction of INPP5A levels is seen in a subset of SCC patients as the tumor progresses from primary to metastatic stage. The observed frequency and pattern of loss indicate that INPP5A, a negative regulator of inositol signaling, may play a role in development and progression of cutaneous SCC tumors.

  6. Response bias-related impairment of early subjective face discrimination in social anxiety disorders: An event-related potential study.

    Science.gov (United States)

    Qi, Yanyan; Gu, Ruolei; Cao, Jianqin; Bi, Xuejing; Wu, Haiyan; Liu, Xun

    2017-02-05

    Considerable research has shown that social anxiety disorder (SAD) is accompanied by various negative cognitive biases, such as social feedback expectancy bias, memory bias, and interpretation bias. However, whether the memory bias in individuals with SAD is actually a manifestation of response bias, and whether such response bias is associated with deficits in face discrimination, remains unclear. In the present study, we investigated response bias (i.e., a tendency to recognize more negative evaluations) to faces with positive (social acceptance) or negative (social rejection) social evaluations in individuals with SAD and healthy controls (HCs) using event-related potentials (ERPs). Behavioral results revealed significant group differences in response bias in the forced-choice recall task, but no difference in overall memory accuracy. ERP results demonstrated that HCs showed a larger N170 to faces that had rejected them as compared to those that had accepted them, but this effect was not evident in the SAD group. Further analysis showed that response bias was correlated with the ΔN170 (rejected - accepted) amplitude. We concluded that the response bias in individuals with SAD is resulted from impairments in early discrimination of social faces, as reflected by the absent early N170 differentiation effect, which was associated with their combined negative biases.

  7. Early event-related potentials indicate context-specific target processing for eye and hand motor systems.

    Science.gov (United States)

    Wehrspaun, Claudia C; Pfabigan, Daniela M; Sailer, Uta

    2013-01-01

    Concurrent eye and hand movements toward a common visual target require different motor programs based on identical visual input. We used event-related brain potentials (ERP) to determine if and when the processing of the visual target differs for the two motor systems. The N2, an index for target evaluation, was more negative for the target of a hand than of an eye movement in two experiments. A possible interpretation for this finding is different visual target processing. Targets for hand movements require a different weighting of visual information, for example concerning features such as surface structure which are important for hand but not for eye movements. In experiment 2, the early C1-component, which had an average maximum at 67 ms following target onset, was significantly more negative when subjects pointed at the stimuli. Traditionally, the C1 has been regarded as a sensory component, but recent studies have linked it to higher order processing, such as attention and expectations. Thus, the present data indicate that target processing for eye or hand movements is already context-specific during early visual information processing. We suggest that differences in a target's relevance for upcoming movements modify target processing as well as sensory expectations.

  8. Femtosecond transient absorption spectroscopy study of the early events of norfloxacin in aqueous solutions with varying pH values.

    Science.gov (United States)

    Su, Tao; Li, Ming-De; Ma, Jiani; Wong, Naikei; Phillips, David Lee

    2014-11-26

    The photophysics and photochemistry of norfloxacin (NF) have been investigated in aqueous solutions of different pH using femtosecond transient absorption spectroscopy (fs-TA). Resonance Raman spectroscopic experiments on NF have also been conducted in aqueous solutions of different pH to characterize the vibrational and structural information on the initial forms of NF. The experimental results in combination with density functional theory calculations of the key intermediates help us to elucidate the early events for NF after photoexcitation in aqueous solutions with varying pH values. The fs-TA results indicate that NF mainly underwent photophysical processes on the early delay time scale (before 3 ns), and no photochemical reactions occurred on this time scale. Specifically, after the irradiation of NF, the molecule reaches a higher excited singlet Sn and then decays to the lowest-lying excited singlet state S1 followed by intersystem crossing to transform into the lowest-lying triplet state T1 with a high efficiency, with an exception that there is a lower efficiency observed in basic aqueous solution due to the generation of an intramolecular electron transfer as an additional pathway to waste energy.

  9. The neurogenic effects of exogenous neuropeptide Y: early molecular events and long-lasting effects in the hippocampus of trimethyltin-treated rats.

    Directory of Open Access Journals (Sweden)

    Valentina Corvino

    Full Text Available Modulation of endogenous neurogenesis is regarded as a promising challenge in neuroprotection. In the rat model of hippocampal neurodegeneration obtained by Trimethyltin (TMT administration (8 mg/kg, characterised by selective pyramidal cell loss, enhanced neurogenesis, seizures and cognitive impairment, we previously demonstrated a proliferative role of exogenous neuropeptide Y (NPY, on dentate progenitors in the early phases of neurodegeneration. To investigate the functional integration of newly-born neurons, here we studied in adult rats the long-term effects of intracerebroventricular administration of NPY (2 µg/2 µl, 4 days after TMT-treatment, which plays an adjuvant role in neurodegeneration and epilepsy. Our results indicate that 30 days after NPY administration the number of new neurons was still higher in TMT+NPY-treated rats than in control+saline group. As a functional correlate of the integration of new neurons into the hippocampal network, long-term potentiation recorded in Dentate Gyrus (DG in the absence of GABAA receptor blockade was higher in the TMT+NPY-treated group than in all other groups. Furthermore, qPCR analysis of Kruppel-like factor 9, a transcription factor essential for late-phase maturation of neurons in the DG, and of the cyclin-dependent kinase 5, critically involved in the maturation and dendrite extension of newly-born neurons, revealed a significant up-regulation of both genes in TMT+NPY-treated rats compared with all other groups. To explore the early molecular events activated by NPY administration, the Sonic Hedgehog (Shh signalling pathway, which participates in the maintenance of the neurogenic hippocampal niche, was evaluated by qPCR 1, 3 and 5 days after NPY-treatment. An early significant up-regulation of Shh expression was detected in TMT+NPY-treated rats compared with all other groups, associated with a modulation of downstream genes. Our data indicate that the neurogenic effect of NPY

  10. A novel gene——samfR involved in early stage of Streptomyces ansochromogenes differentiation

    Institute of Scientific and Technical Information of China (English)

    田宇清; 刘钢; 聂丽平; 贾君永; 谭华荣; K.F.Chater

    1999-01-01

    A 4.6 kb DNA fragment was cloned from the DNA library of Streptomyces ansochromogenes using a partial DNA fragment located in the downstream of promoter-PTH4 as probe. The experiments revealed that this DNA fragment consists of saw D gene and a 1.4 kb Pvu Ⅱ fragment which can accelerate mycelium formation of S. ansochromogerms. The nucleofide sequence of 1.4 kb DNA fragment was determined and analysed; the result indicated that the fragment contains one complete open reading frame (ORF) which encodes a protein with 213 amino acids, and this gene was desiguated as samfR. The deduced protein has 36% amino acid identities and 52% amino acid similarities in comparison with that encoded by hppR gene, which is involved in the regulation of catabolism for 3-(3-hydroxyphenyl) propionate (3HPP) in Rhodococcus globerulus. The function of samfR gene was studied using strategy of gene disruption, and the resulting samfR mutant failed to form aerial hyphae and spores, its development and differentiation stopped

  11. Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Rocio Martin

    Full Text Available Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to

  12. Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells.

    Directory of Open Access Journals (Sweden)

    Roman J Krawetz

    Full Text Available BACKGROUND: The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK play pivotal roles in cell migration, apoptosis (membrane blebbing, cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined. METHODOLOGY/PRINCIPAL FINDINGS: P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a 'ground' state after the inhibition had been removed. CONCLUSIONS/SIGNIFICANCE: Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of

  13. Amyloid burden and metabolic function in early-onset Alzheimer's disease: parietal lobe involvement.

    Science.gov (United States)

    Ossenkoppele, Rik; Zwan, Marissa D; Tolboom, Nelleke; van Assema, Danielle M E; Adriaanse, Sofie F; Kloet, Reina W; Boellaard, Ronald; Windhorst, Albert D; Barkhof, Frederik; Lammertsma, Adriaan A; Scheltens, Philip; van der Flier, Wiesje M; van Berckel, Bart N M

    2012-07-01

    Alzheimer's disease with early onset often presents with a distinct cognitive profile, potentially reflecting a different distribution of underlying neuropathology. The purpose of this study was to examine the relationships between age and both in vivo fibrillary amyloid deposition and glucose metabolism in patients with Alzheimer's disease. Dynamic [(11)C]Pittsburgh compound-B (90 min) and static [(18)F]fluorodeoxyglucose (15 min) scans were obtained in 100 patients with Alzheimer's disease and 20 healthy controls. Parametric non-displaceable binding potential images of [(11)C]Pittsburgh compound-B and standardized uptake value ratio images of [(18)F]fluorodeoxyglucose were generated using cerebellar grey matter as reference tissue. Nine [(11)C]Pittsburgh compound-B-negative patients were excluded. The remaining patients were categorized into younger (n=45, age: 56 ± 4 years) and older (n=46, age: 69 ± 5 years) groups, based on the median age (62 years) at time of diagnosis. Younger patients showed more severe impairment on visuo-spatial function, attention and executive function composite scores (Pparietal and occipital and posterior cingulate cortices) as within subjects factor and [(11)C]Pittsburgh compound-B binding/[(18)F]fluorodeoxyglucose uptake as dependent variables. There was no main effect of age for [(11)C]Pittsburgh compound-B or [(18)F]fluorodeoxyglucose, suggesting that overall, the extent of amyloid deposition or glucose hypometabolism did not differ between groups. Regional distributions of [(11)C]Pittsburgh compound-B binding and [(18)F]fluorodeoxyglucose uptake (both P for interaction parietal cortex of younger patients (both Pparietal [(11)C]Pittsburgh compound-B binding for younger patients (standardized β: -0.37) and between visuo-spatial functioning and occipital binding for older patients (standardized β: -0.39). For [(18)F]fluorodeoxyglucose, associations were found between parietal uptake with visuo-spatial (standardized β: 0

  14. Early impact event and fluid activity on H chondrite parent body registered in the Pułtusk meteorite

    Science.gov (United States)

    Krzesinska, Agata

    2015-04-01

    Impact is one of the most important processes affecting asteroids, but it is neglected as a source for heat of these bodies. Recent modeling work show, however, that impact into warm planetesimals is able to cause global-scale temperature increase to the point of melting of silicates [1]. An obvious consequence of this fact is that the impact activity in early evolution of asteroids may promote formation of melt and its differentiation. H chondrites provide some lines of evidence for an early, 4.4 Ga impact event on their parent body. The event resulted in formation of heavily shocked and melted H chondrites with old gas retention ages [2, 3], including Portales Valley, an unique metal-rich breccia [e.g. 4]. The impact led also, very likely, to unmixing of silicate and metal-sulfide melts and to formation of silicate-iron non-magmatic IIE meteorites [5]. Additional evidence for this event, and for melting it caused, may come from highly equilibrated and recrystallized fragments of the Pułtusk meteorite containing vein-like metal accumulations [6]. In the Pułtusk, vein-like metal accumulations are kamacite-rich, and basically depleted in sulfides. They form many tendrils into the equilibrated, well recrystallized chondritic rock. Marked feature of the chondritic rock at the contact with accumulations is presence of unusually large phosphate and feldspar grains. The minerals bear record of crystallization from melt. Both vein-like metal accumulations and chondritic rock record, however, slow cooling rate. Phopshates are in the meteorite represented by merrillite and apatite, predominantly intergrown with each other. Merrillite poikilitically encloses silicate grains. It is probably of magmatic origin, since it contains detectable amount of potassium and high content of sodium. Apatite contains varying concentrations of chlorine, fluorine and missing structural component. Content of Cl and F are negatively correlated and both elements are heterogeneously distributed

  15. Analysis of Task Types and Error Types of the Human Actions Involved in the Human-related Unplanned Reactor Trip Events

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Whan; Park, Jin Kyun; Jung, Won Dea

    2008-02-15

    This report provides the task types and error types involved in the unplanned reactor trip events that have occurred during 1986 - 2006. The events that were caused by the secondary system of the nuclear power plants amount to 67 %, and the remaining 33 % was by the primary system. The contribution of the activities of the plant personnel was identified as the following order: corrective maintenance (25.7 %), planned maintenance (22.8 %), planned operation (19.8 %), periodic preventive maintenance (14.9 %), response to a transient (9.9 %), and design/manufacturing/installation (9.9%). According to the analysis of error modes, the error modes such as control failure (22.2 %), wrong object (18.5 %), omission (14.8 %), wrong action (11.1 %), and inadequate (8.3 %) take up about 75 % of all the unplanned trip events. The analysis of the cognitive functions involved showed that the planning function makes the highest contribution to the human actions leading to unplanned reactor trips, and it is followed by the observation function (23.4%), the execution function (17.8 %), and the interpretation function (10.3 %). The results of this report are to be used as important bases for development of the error reduction measures or development of the error mode prediction system for the test and maintenance tasks in nuclear power plants.

  16. Decoupling of carbon isotope records between organic matter and carbonate prior to the Toarcian Oceanic Anoxic Event (Early Jurassic)

    Science.gov (United States)

    Bodin, Stephane; Kothe, Tim; Krencker, Francois-Nicolas; Suan, Guillaume; Heimhofer, Ulrich; Immenhauser, Adrian

    2014-05-01

    Across the Pliensbachian-Toarcian boundary (P-To, Early Jurassic), ca. 1 Myr before the Toarcian Oceanic Anoxic Event (T-OAE), an initial negative carbon isotope excursion has been documented in western Tethys sedimentary rocks. In carbonate, its amplitude (2-3 permil) is similar to the subsequent excursion recorded at the onset of the T-OAE. Being also associated with a rapid warming event, the significance of this first carbon isotope shift, in terms of paleoenvironmental interpretation and triggering mechanism, remains however elusive. Taking advantage of expanded and rather continuous sections in the High Atlas of Morocco, several high-resolution, paired organic-inorganic carbon isotope records have been obtained across the Upper Pliensbachian - Lower Toarcian interval. At the onset of the T-OAE, an abrupt 1-2 permil negative shift is recorded in both organic and inorganic phases, succeeded by a relatively longer term 1-2 permil negative trend and a final slow return to pre-excursion conditions. In accordance with previous interpretations, this pattern indicates a perturbation of the entire exogenic carbon isotope reservoir at the onset of the T-OAE by the sudden release of isotopically light carbon into the atmosphere. By contrast, there is no negative shift in carbon isotopes for the P-To event recorded in bulk organic matter of Morocco. Given the strong dominance of terrestrial particles in the bulk organic matter fraction, this absence indicates that massive input of 12C-rich carbon into the atmosphere is not likely to have happened during the P-To event. A pronounced (2 permil) and abrupt negative shift in carbon isotope is however recorded in the bulk carbonate phase. We suggest that this decoupling between organic and inorganic phase is due to changes in the nature of the bulk carbonate phase. Indeed, the negative shift occurs at the lithological transition between Pliensbachian-lowermost Toarcian limestone-marl alternations and the Lower Toarcian marl

  17. Rapid changes in the redox conditions of the western Tethys Ocean during the early Aptian oceanic anoxic event

    Science.gov (United States)

    Westermann, Stéphane; Stein, Melody; Matera, Virginie; Fiet, Nicolas; Fleitmann, Dominik; Adatte, Thierry; Föllmi, Karl B.

    2013-11-01

    The early Aptian (125 to 121 Ma) records an episode of severe environmental change including a major perturbation of the carbon cycle, an oceanic anoxic event (OAE 1a, 122.5 Ma), a platform drowning episode and a biocalcification crisis. We propose to trace changes in the oxygenation state of the ocean during the early Aptian anoxic event using the redox-sensitive trace-element (RSTE) distribution, phosphorus accumulation rates (PARs) and organic-matter characterization in three different basins of the western Tethys. The following sections have been investigated: Gorgo a Cerbara (central Italy) in the Umbria Marche basin, Glaise (SE France) in the Vocontian basin and Cassis/La Bédoule (SE France) located in the Provencal basin. In the Gorgo a Cerbara section, RSTE distributions show a low background level along the main part of the section, contrasted by different maxima in concentrations within the Selli level. In the Glaise section, the Goguel level displays a weak increase in RSTE contents coeval with moderate TOC values. At Cassis/La Bédoule, no significant RSTE enrichments have been observed in sediments equivalent to the Selli level. These differences in the records of the geochemical proxies of the Selli level or its equivalent indicate the deposition under different redox conditions, probably related to the paleogeography. Our data indicate the development of anoxic-euxinic conditions in the deeper part of the Tethys during OAE 1a, whereas in the shallower environments, conditions were less reducing. Moreover, at Gorgo a Cerbara, the Selli level is characterized by rapid changes in the intensity of reducing conditions in the water column. Ocean eutrophication seems to be a major factor in the development and the persistence of anoxia as suggested by the PAR evolution. Higher PAR values at the onset of OAE 1a suggest an increase in nutrient input, whereas the return to lower values through the first part of the OAE 1a interval may be related to the

  18. Postweaning Exposure to Dietary Zearalenone, a Mycotoxin, Promotes Premature Onset of Puberty and Disrupts Early Pregnancy Events in Female Mice

    Science.gov (United States)

    Ye, Xiaoqin

    2013-01-01

    Zearalenone (ZEA) is a mycotoxin commonly found in contaminated livestock feed and human food with levels in the range of ppb and low ppm. It was hypothesized that ZEA, an endocrine disruptor, could affect puberty and early pregnancy. To test this hypothesis, newly weaned (3 weeks old) C57BL/6J female mice were exposed to 0, 0.002, 4, 10, and 40 ppm ZEA and 0.05 ppm diethylstilbestrol (positive control) in phytoestrogen-free AIN-93G diet. Females exposed to 10 and 40 ppm ZEA diets showed earlier onset of vaginal opening. Those treated with 40 ppm ZEA diet also had earlier first copulation plug and irregular estrous cyclicity. At 8 weeks old, all females were mated with untreated stud males on AIN-93G diet during mating. Treatment resumed upon identification of a vaginal plug on gestation day 0.5 (D0.5). Embryo implantation was assessed on D4.5. Exposure to 40 ppm ZEA diet resulted in reduced percentage of plugged mice with implantation sites, distended uterine appearance, and retained expression of progesterone receptor in D4.5 uterine epithelium. To determine the exposure timing and mechanisms of disrupted embryo implantation, four groups of females were fed with 0 or 40 ppm ZEA diets during premating (weaning to mating) and postmating (D0.5–D4.5), respectively. Premating exposure to 40 ppm ZEA diet reduced fertilization rate, whereas postmating exposure to 40 ppm ZEA diet delayed embryo transport and preimplantation embryo development, which subsequently affected embryo implantation. These data demonstrate that postweaning exposure to dietary ZEA can promote premature onset of puberty and disrupt early pregnancy events. PMID:23291560

  19. Early Jurassic schizosphaerellid crisis in Cantabria, Spain: Implications for calcification rates and phytoplankton evolution across the Toarcian oceanic anoxic event

    Science.gov (United States)

    Tremolada, Fabrizio; van de Schootbrugge, Bas; Erba, Elisabetta

    2005-06-01

    The Toarcian oceanic anoxic event (˜183 Myr ago) represents a global perturbation marked by increasing organic carbon burial and a general decrease in calcium carbonate production likely triggered by elevated carbon dioxide levels in the atmosphere. Here we present quantitative analyses of calcareous nannofossil diversity and abundance from the Castillo de Pedroso section in Cantabria, northern Spain. We compare these data with geochemical data (C and O isotopes) obtained from biogenic and bulk carbonate records in order to highlight the response of calcareous phytoplankton to major climatic and paleoceanographic changes. The Pliensbachian/Toarcian boundary is characterized by an abrupt decrease in abundance of Schizosphaerella punctulata, the most important lithogenic contributor to (hemi) pelagic carbonates in the Early Jurassic. The early Toarcian nannofloral assemblages show an increase in abundance of Mitrolithus jansae and small-sized r-selected taxa and a progressive decrease in S. punctulata percentages. The deep dwellers M. jansae and S. punctulata experienced a major crisis slightly prior to the deposition of the Toarcian black shales that are characterized by high abundances of eutrophic taxa such as Lotharingius spp. and Biscutum spp. The return of S. punctulata associated with lower percentages of eutrophic taxa was observed just above the Toarcian black shales. The Toarcian episode reveals that high CO2 levels and increasing primary productivity probably triggered a shift in abundance from highly calcified nannoliths such as S. punctulata and M. jansae to small-sized r-selected coccoliths that overall record a biocalcification crisis at the onset and during the Toarcian episode.

  20. HIV Aspartic Peptidase Inhibitors Modulate Surface Molecules and Enzyme Activities Involved with Physiopathological Events in Fonsecaea pedrosoi

    Directory of Open Access Journals (Sweden)

    Vanila F. Palmeira

    2017-05-01

    Full Text Available Fonsecaea pedrosoi is the main etiological agent of chromoblastomycosis, a recalcitrant disease that is extremely difficult to treat. Therefore, new chemotherapeutics to combat this fungal infection are urgently needed. Although aspartic peptidase inhibitors (PIs currently used in the treatment of human immunodeficiency virus (HIV have shown anti-F. pedrosoi activity their exact mechanisms of action have not been elucidated. In the present study, we have investigated the effects of four HIV-PIs on crucial virulence attributes expressed by F. pedrosoi conidial cells, including surface molecules and secreted enzymes, both of which are directly involved in the disease development. In all the experiments, conidia were treated with indinavir, nelfinavir, ritonavir and saquinavir (100 μM for 24 h, and then fungal cells were used to evaluate the effects of HIV-PIs on different virulence attributes expressed by F. pedrosoi. In comparison to untreated controls, exposure of F. pedrosoi cells to HIV-PIs caused (i reduction on the conidial granularity; (ii irreversible surface ultrastructural alterations, such as shedding of electron dense and amorphous material from the cell wall, undulations/invaginations of the plasma membrane with and withdrawal of this membrane from the cell wall; (iii a decrease in both mannose-rich glycoconjugates and melanin molecules and an increase in glucosylceramides on the conidial surface; (iv inhibition of ergosterol and lanosterol production; (v reduction in the secretion of aspartic peptidase, esterase and phospholipase; (vi significant reduction in the viability of non-pigmented conidia compared to pigmented ones. In summary, HIV-PIs are efficient drugs with an ability to block crucial biological processes of F. pedrosoi and can be seriously considered as potential compounds for the development of new chromoblastomycosis chemotherapeutics.

  1. Early transcriptional events linked to induction of diapause revealed by RNAseq in larvae of drosophilid fly, Chymomyza costata.

    Science.gov (United States)

    Poupardin, Rodolphe; Schöttner, Konrad; Korbelová, Jaroslava; Provazník, Jan; Doležel, David; Pavlinic, Dinko; Beneš, Vladimír; Koštál, Vladimír

    2015-09-21

    Diapause is a developmental alternative to direct ontogeny in many invertebrates. Its primary adaptive meaning is to secure survival over unfavourable seasons in a state of developmental arrest usually accompanied by metabolic suppression and enhanced tolerance to environmental stressors. During photoperiodically triggered diapause of insects, the ontogeny is centrally turned off under hormonal control, the molecular details of this transition being poorly understood. Using RNAseq technology, we characterized transcription profiles associated with photoperiodic diapause induction in the larvae of the drosophilid fly Chymomyza costata with the goal of identifying candidate genes and processes linked to upstream regulatory events that eventually lead to a complex phenotypic change. Short day photoperiod triggering diapause was associated to inhibition of 20-hydroxy ecdysone (20-HE) signalling during the photoperiod-sensitive stage of C. costata larval development. The mRNA levels of several key genes involved in 20-HE biosynthesis, perception, and signalling were significantly downregulated under short days. Hormonal change was translated into downregulation of a series of other transcripts with broad influence on gene expression, protein translation, alternative histone marking by methylation and alternative splicing. These changes probably resulted in blockade of direct development and deep restructuring of metabolic pathways indicated by differential expression of genes involved in cell cycle regulation, metabolism, detoxification, redox balance, protection against oxidative stress, cuticle formation and synthesis of larval storage proteins. This highly complex alteration of gene transcription was expressed already during first extended night, within the first four hours after the change of the photoperiodic signal from long days to short days. We validated our RNAseq differential gene expression results in an independent qRT-PCR experiment involving wild

  2. Crosstalk between intestinal microbiota, adipose tissue and skeletal muscle as an early event in systemic low-grade inflammation and the development of obesity and diabetes.

    Science.gov (United States)

    Bleau, Christian; Karelis, Antony D; St-Pierre, David H; Lamontagne, Lucie

    2015-09-01

    Obesity is associated with a systemic chronic low-grade inflammation that contributes to the development of metabolic disorders such as cardiovascular diseases and type 2 diabetes. However, the etiology of this obesity-related pro-inflammatory process remains unclear. Most studies have focused on adipose tissue dysfunctions and/or insulin resistance in skeletal muscle cells as well as changes in adipokine profile and macrophage recruitment as potential sources of inflammation. However, low-grade systemic inflammation probably involves a complex network of signals interconnecting several organs. Recent evidences have suggested that disturbances in the composition of the gut microbial flora and alterations in levels of gut peptides following the ingestion of a high-fat diet may be a cause of low-grade systemic inflammation that may even precede and predispose to obesity, metabolic disorders or type 2 diabetes. This hypothesis is appealing because the gastrointestinal system is first exposed to nutrients and may thereby represent the first link in the chain of events leading to the development of obesity-associated systemic inflammation. Therefore, the present review will summarize the latest advances interconnecting intestinal mucosal bacteria-mediated inflammation, adipose tissue and skeletal muscle in a coordinated circuitry favouring the onset of a high-fat diet-related systemic low-grade inflammation preceding obesity and predisposing to metabolic disorders and/or type 2 diabetes. A particular emphasis will be given to high-fat diet-induced alterations of gut homeostasis as an early initiator event of mucosal inflammation and adverse consequences contributing to the promotion of extended systemic inflammation, especially in adipose and muscular tissues.

  3. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa [Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba 292-0818 (Japan); Adam, Klaus-Peter; Alexander, Danny C.; Lawton, Kay A.; Milburn, Michael V.; Ryals, John A.; Wulff, Jacob E. [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States); Guo, Lining, E-mail: lguo@metabolon.com [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States)

    2013-04-01

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

  4. Influence of the gut microbiota on transcriptional regulation of genes involved in early life development of the intestinal mucus layer

    DEFF Research Database (Denmark)

    Bergström, Anders; Kristensen, Matilde Bylov; Metzdorff, Stine Broeng

    2010-01-01

    the mucosal surfaces of all epithelial linings by physical hindrance or specific binding of pathogenic agents including virus and bacteria. It has been shown that the presence and composition of the microbiota is directly involved in the regulation of gene transcription in the intestinal epithelium...... expression of all mucin genes are dependent on the presence of microorganisms and whether specific bacteria are capable of regulating mucus production in early life remains, however, to be established. The very first period after birth is believed to be vulnerable for establishment of the gut microbiota...... animal groups and the two different days tested, which will be presented at the meeting. This is the first study to examine effects of different colonizing bacteria on mucus related gene expression levels in new born mice. These results may thus improve our understanding of the complex interplay between...

  5. Influence of the gut microbiota on transcriptional regulation of genes involved in early life development of the intestinal mucus layer

    DEFF Research Database (Denmark)

    Bergström, Anders; Kristensen, Matilde Bylov; Metzdorff, Stine Broeng

    the mucosal surfaces of all epithelial linings by physical hindrance or specific binding of pathogenic agents including virus and bacteria. It has been shown that the presence and composition of the microbiota is directly involved in the regulation of gene transcription in the intestinal epithelium...... expression of all mucin genes are dependent on the presence of microorganisms and whether specific bacteria are capable of regulating mucus production in early life remains, however, to be established. The very first period after birth is believed to be vulnerable for establishment of the gut microbiota...... animal groups and the two different days tested, which will be presented at the meeting. This is the first study to examine effects of different colonizing bacteria on mucus related gene expression levels in new born mice. These results may thus improve our understanding of the complex interplay between...

  6. Involvement of two microRNAs in the early immune response to DNA vaccination against a fish rhabdovirus

    DEFF Research Database (Denmark)

    Bela-ong, Dennis Berbulla; Schyth, Brian Dall; Zou, Jun

    2015-01-01

    Mechanisms that account for the high protective efficacy in teleost fish of a DNA vaccine expressing the glycoprotein (G) of Viral hemorrhagic septicemia virus (VHSV) are thought to involve early innate immune responses mediated by interferons (IFNs). Microribonucleic acids (miRNAs) are a diverse...... trout infected with VHSV. In this study, we analyzed the expression of these miRNAs in fish following administration of the DNA vaccine and their potential functions. Quantitative RT-PCR analysis revealed the increased levels of miR-462, and miR-731 in the skeletal muscle tissue at the site of vaccine...... administration and in the liver of vaccinated fish relative to empty plasmid backbone-injected controls. The increased expression of these miRNAs in the skeletal muscle correlated with the increased levels of the type I interferon (IFN)-inducible gene Mx, type I IFN and IFN-γ genes at the vaccination site...

  7. Attention, cognitive control and motivation in ADHD: Linking event-related brain potentials and DNA methylation patterns in boys at early school age.

    Science.gov (United States)

    Heinrich, Hartmut; Grunitz, Juliane; Stonawski, Valeska; Frey, Stefan; Wahl, Simone; Albrecht, Björn; Goecke, Tamme W; Beckmann, Matthias W; Kornhuber, Johannes; Fasching, Peter A; Moll, Gunther H; Eichler, Anna

    2017-06-19

    In order to better understand the underpinnings of attention-deficit/hyperactivity disorder (ADHD), we targeted the relationship of attentional, cognitive control and motivational processes with DNA methylation patterns of 60 candidate genes in boys at early school age. Participants (6 to 8 years; N = 82) were selected from a German longitudinal cohort (FRANCES). ADHD-related behaviour was assessed via maternal ratings. Performance and event-related potential measures (inter alia Cue-P3 and Nogo-P3), which were recorded in a motivational go/nogo task, indicated diminished attentional orienting, reduced inhibitory response control and a larger motivational effect on performance in ADHD already at this relatively young age. Methylation patterns were analysed in buccal cell DNA with the Illumina HumanMethylation 450K array. For CpG sites at genes of the dopaminergic (COMT, ANKK1) and the neurotrophic (BDNF, NGFR) system, associations with the Nogo-P3 as well as ADHD symptom severity were found suggesting that these systems are involved in response control deficits in ADHD. Methylation effects related to both functional aspects and ADHD behaviour were also observed for DPP10 and TPH2. Epigenetic mechanisms may play a role in ADHD-associated deficits but findings need to be replicated in larger samples and are limited by the fact that only peripheral methylation could be considered.

  8. Subsurface North Atlantic warming as a trigger of rapid cooling events: evidences from the Early Pleistocene (MIS 31–19

    Directory of Open Access Journals (Sweden)

    I. Hernández-Almeida

    2014-10-01

    Full Text Available Subsurface water column dynamics in the subpolar North Atlantic were reconstructed in order to improve the understanding of the cause of abrupt IRD events during cold periods of the Early Pleistocene. We used Mg / Ca-based temperatures of deep-dwelling (Neogloboquadrina pachyderma sinistral planktonic foraminifera and paired Mg / Ca-δ18O measurements to estimate the subsurface temperatures and δ18O of seawater at Site U1314. Carbon isotopes on benthic and planktonic foraminifera from the same site provide information about the ventilation and water column nutrient gradient. Mg / Ca-based temperatures and δ18O of seawater suggest increased temperatures and salinities during ice-rafting, likely due to enhanced northward subsurface transport of subtropical waters during periods of AMOC reduction. Planktonic carbon isotopes support this suggestion, showing coincident increased subsurface ventilation during deposition of ice-rafted detritus (IRD. Warm waters accumulated at subsurface would result in basal warming and break-up of ice-shelves, leading to massive iceberg discharges in the North Atlantic. Release of heat and salt stored at subsurface would help to restart the AMOC. This mechanism is in agreement with modelling and proxy studies that observe a subsurface warming in the North Atlantic in response to AMOC slowdown during the MIS3.

  9. Sedimentary-volcanic tuffs formed during the early Middle Triassic volcanic event in Guizhou Province and their stratigraphic significance

    Institute of Scientific and Technical Information of China (English)

    XIAO Jiafei; HU Ruizhong

    2005-01-01

    The sedimentary-volcanic tuff (locally called "green-bean rock") formed during the early Middle Triassic volcanic event in Guizhou Province is characterized as being thin, stable, widespread, short in forming time and predominantly green in color. The green-bean rock is a perfect indicator for stratigraphic division. Its petrographic and geochemical features are unique, and it is composed mainly of glassy fragments and subordinately of crystal fragments and volcanic ash balls. Analysis of the major and trace elements and rare-earth elements (REE), as well as the related diagrams, permits us to believe that the green-bean rock is acidic volcanic material of the calc-alkaline series formed in the Indosinian orogenic belt on the Sino-Vietnam border, which was atmospherically transported to the tectonically stable areas and then deposited as sedimentary-volcanic rocks there. According to the age of green-bean rock, it is deduced that the boundary age of the Middle-Lower Triassic overlain by the sedimentary-volcanic tuff is about 247 Ma.

  10. Metoprolol in acute myocardial infarction reduces ventricular arrhythmias both in the early stage and after the acute event.

    Science.gov (United States)

    Rehnqvist, N; Olsson, G; Erhardt, L; Ekman, A M

    1987-06-01

    Fifty three of the 5778 patients included in the MIAMI (Metoprolol in Acute Myocardial Infarction) trial were investigated with long-term ECG recordings in order to evaluate the effect of acute beta-blockade on premature ventricular complexes in and after acute myocardial infarction. Twenty five patients were given placebo and 28 metoprolol in a double-blind randomized fashion for 15 days. After this period the patients were put on open beta-blockade without breaking individual study codes. The mean number of premature ventricular complexes during the inclusion day (day 0) was the same in the two groups. The median numbers were also similar in the two groups: 190 and 154 in the placebo and metoprolol groups, respectively. Metoprolol significantly reduced the median number of premature ventricular complexes in the randomized period. The median numbers on days 1, 2 and 15 were 146, 101, 84 in the placebo group and 73, 59 and 10 in the metoprolol group, respectively (P less than 0.05). Also during the further follow-up, when investigated 1, 3 and 6 months after the infarction, the median number of premature ventricular complexes was lower in the metoprolol group (74, 257, 142 in the placebo group and 7, 5 and 11 in the metoprolol group, P less than 0.05). This indicates that metoprolol treatment in the acute phase of myocardial infarction reduces ventricular arrhythmias both in the early stage and also after the acute event.

  11. Microgravity Effects on the Early Events of Biological Nitrogen Fixation in Medicago Truncatula: Results from the SyNRGE Experiment

    Science.gov (United States)

    Stutte, Gary W.; Roberts, Michael S.

    2013-02-01

    SyNRGE (Symbiotic Nodulation in a Reduced Gravity Environment) was a sortie mission on STS-135 in the Biological Research in Canisters (BRIC) hardware to study the effect of μg on a plant-microbe symbiosis resulting in biological nitrogen fixation. Medicago truncatula, a model species for the legume family, was inoculated with its bacterial symbiont, Sinorhizobium meliloti, to observe early biomolecular events associated with infection and nodulation in Petri Dish Fixation Units (PDFU’s). Two sets of experiments were conducted in orbit and in 24-hour delayed ground controls. Experiments were designed to determine if S. meliloti would infect M. truncatula and initiate biomolecular changes associated with nodule formation and if the μg environment altered the host plant and/or bacteria to induce nodule formation upon return to 1g. Initial analysis results demonstrate that the legumes and bacteria cultivated in μg have potential to develop a symbiotic interaction, but suggest that μg alters their ability to form nodules upon return to 1g. (Research supported by NASA ESMD/ Advance Capabilities Division grant NNX10AR09A)

  12. Indirect comparisons of adverse events and dropout rates in early Parkinson's disease trials of pramipexole, ropinirole, and rasagiline.

    Science.gov (United States)

    Zagmutt, Francisco J; Tarrants, Marcy L

    2012-07-01

    The comparative safety profiles of monotherapeutic treatments for Parkinson's disease (PD) can provide valuable therapeutic information. The objective of this study was to perform an indirect comparison of Adverse Events (AEs) and Dropout Rates (DRs) among clinical trials of pramipexole, ropinirole, and rasagiline. Outcomes analyzed included DRs, total AEs, and AE categories: Cognitive (CG), Gastrointestinal (GI), and Sleep/Fatigue (SF). The odds-ratio (OR) and Credible Interval (CrI) of outcomes between products using placebo as common comparator was calculated using indirect meta-analytical methods. AEs incidences for subjects receiving rasagiline were not significantly different from placebo, whereas DRs were significantly lower than for placebo (OR = 0.55; 95% CrI = 0.34-0.88). Patients receiving pramipexole or ropinirole had higher incidence of all AEs and DRs than patients taking rasagiline, except for the nonsignificant incidence of CG for ropinirole vs. rasagiline (1.76; 0.69-4.70). The incidence of GI (2.11; 1.13-4.06) and SF (2.75; 1.42-5.47) was significantly higher for ropinirole than for pramipexole, whereas the incidence of CG was significantly lower for ropinirole than for pramipexole (0.22; 0.07-0.69). Findings suggest that subjects with early PD treated with rasagiline have fewer AEs and DRs than those treated with pramipexole or ropinirole. GI and SF AEs were highest for subjects treated with ropinirole, while individuals treated with pramipexole exhibited the highest incidence of cognitive AEs.

  13. 5'-heterogeneity of glucocorticoid receptor messenger RNA is tissue specific: differential regulation of variant transcripts by early-life events.

    Science.gov (United States)

    McCormick, J A; Lyons, V; Jacobson, M D; Noble, J; Diorio, J; Nyirenda, M; Weaver, S; Ester, W; Yau, J L; Meaney, M J; Seckl, J R; Chapman, K E

    2000-04-01

    Glucocorticoid receptor (GR) gene expression is regulated in a complex tissue-specific manner, notably by early-life environmental events that program tissue GR levels. We have identified and characterized several new rat GR mRNAs. All encode a common protein, but differ in their 5'-leader sequences as a consequence of alternate splicing of, potentially, 11 different exon 1 sequences. Most are located in a 3-kb CpG island, upstream of exon 2, that exhibits substantial promoter activity in transfected cells. Ribonuclease (RNase) protection analysis demonstrated significant levels of six alternate exons 1 in vivo in rat, with differences between liver, hippocampus, and thymus reflecting tissue-specific differences in promoter activity. Two of the alternate exons 1 (exons 1(6) and 1(10)) were expressed in all tissues examined, together present in 77-87% of total GR mRNA. The remaining GR transcripts contained tissue-specific alternate first exons. Importantly, tissue-specific first exon usage was altered by perinatal environmental manipulations. Postnatal handling, which permanently increases GR in the hippocampus, causing attenuation of stress responses, selectively elevated GR mRNA containing the hippocampus-specific exon 1(7). Prenatal glucocorticoid exposure, which increases hepatic GR expression and produces adult hyperglycemia, decreased the proportion of hepatic GR mRNA containing the predominant exon 1(10), suggesting an increase in a minor exon 1 variant. Such tissue specificity of promoter usage allows differential GR regulation and programming.

  14. Inflammatory Reaction as Determinant of Foreign Body Reaction Is an Early and Susceptible Event after Mesh Implantation

    Directory of Open Access Journals (Sweden)

    Holger Gerullis

    2014-01-01

    Full Text Available Purpose. To investigate and relate the ultrashort-term and long-term courses of determinants for foreign body reaction as biocompatibility predictors for meshes in an animal model. Materials and Methods. Three different meshes (TVT, UltraPro, and PVDF were implanted in sheep. Native and plasma coated meshes were placed bilaterally: (a interaperitoneally, (b as fascia onlay, and (c as muscle onlay (fascia sublay. At 5 min, 20 min, 60 min, and 120 min meshes were explanted and histochemically investigated for inflammatory infiltrate, macrophage infiltration, vessel formation, myofibroblast invasion, and connective tissue accumulation. The results were related to long-term values over 24 months. Results. Macrophage invasion reached highest extents with up to 60% in short-term and decreased within 24 months to about 30%. Inflammatory infiltrate increased within the first 2 hours, the reached levels and the different extents and ranking among the investigated meshes remained stable during long-term follow up. For myofibroblasts, connective tissue, and CD31+ cells, no activity was detected during the first 120 min. Conclusion. The local inflammatory reaction is an early and susceptible event after mesh implantation. It cannot be influenced by prior plasma coating and does not depend on the localisation of implantation.

  15. Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass

    Directory of Open Access Journals (Sweden)

    Vivas Yurena

    2011-12-01

    Full Text Available Abstract Background The progression towards type 2 diabetes depends on the allostatic response of pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse failed to expand its beta cell mass. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Thus, comparison of these models islets particularly at early ages could provide some new insights on early PPARγ dependent transcriptional responses involved in the process of beta cell mass expansion Results Here we have investigated PPARγ dependent transcriptional responses occurring during the early stages of beta cell adaptation to insulin resistance in wild type, ob/ob, PPARγ2 KO and POKO mice. We have identified genes known to regulate both the rate of proliferation and the survival signals of beta cells. Moreover we have also identified new pathways induced in ob/ob islets that remained unchanged in POKO islets, suggesting an important role for PPARγ in maintenance/activation of mechanisms essential for the continued function of the beta cell. Conclusions Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with the activation of an immune response that fails to occur in POKO islets. We have also indentified other PPARγ dependent differentially regulated pathways including cholesterol biosynthesis, apoptosis through TGF-β signaling and decreased oxidative phosphorylation.

  16. Early detection of cardiac involvement in Miyoshi myopathy: 2D strain echocardiography and late gadolinium enhancement cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Kim Byoung

    2010-05-01

    Full Text Available Abstract Background Miyoshi myopathy (MM is an autosomal recessive distal myopathy characterized by early adult onset. Cardiomyopathy is a major clinical manifestation in other muscular dystrophies and an important prognostic factor. Although dysferlin is highly expressed in cardiac muscle, the effect of dysferlin deficiency in cardiac muscle has not been studied. We hypothesized that early myocardial dysfunction could be detected by 2D strain echocardiography and late gadolinium enhancement (LGE cardiovascular magnetic resonance (CMR. Method Five consecutive MM patients (3 male in whom we detected the DYSF gene mutation and age-matched healthy control subjects were included. None of the patients had history of cardiac disease or signs and symptoms of overt heart failure. Patients were studied using 2D strain echocardiography and CMR, with 2D strain being obtained using the Automated Function Imaging technique. Results All patients had preserved left ventricular systolic function. However, segmental Peak Systolic Longitudinal Strain (PSLS was decreased in 3 patients. Global PSLS was significantly lower in patients with MM than in control subjects (p = 0.005. Basal anterior septum, basal inferior septum, mid anterior, and mid inferior septum PSLS were significantly lower in patients with MM than in control subjects (P Conclusions Patients with MM showed subclinical involvement of the heart. 2D strain and LGE are sensitive methods for detecting myocardial dysfunction prior to the development of cardiovascular symptoms. The prognostic significance of these findings warrants further longitudinal follow-up.

  17. Parametrial Involvement on Magnetic Resonance Imaging Has No Effect on the Survival of Early-Stage Cervical Cancer Patients.

    Science.gov (United States)

    Yang, Kyungmi; Park, Won; Huh, Seung Jae; Park, Byung Kwan; Kim, Chan Kyo; Kim, Byoung-Gie; Bae, Duk-Soo; Lee, Jeong-Won

    2017-03-01

    Parametrial involvement (PMI) in patients with cervical cancer is known to be an unfavourable prognostic factor. The purpose of this study was to investigate the prognostic significance of PMI on magnetic resonance imaging (MRI) in patients with early-stage cervical cancer. Three hundred three patients with stage IB or IIA cervical cancer treated by adjuvant radiotherapy or concurrent chemoradiotherapy following primary surgery from 2001 to 2011 were enrolled in this study. We reviewed preoperative MRI and pathologic findings and compared recurrence and survival of group defined according to PMI status. There were 73 patients (24.1%) with PMI based on MRI and 52 patients (17.2%) with PMI based on surgical pathology. The accuracy of MRI for detecting PMI was 77.2% (sensitivity, 53.8%; specificity, 82.1%). In all patients, pathology-based evidence of PMI had a negative effect on both 5-year disease-free survival (73.2% vs 85.3%, P = 0.048) and 5-year overall survival (76.6% vs 91.4%, P = 0.009), but PMI on MRI did not have a significant effect on survival. In subgroups defined according to PMI status on MRI and surgical pathology, subgroups with pathology-based evidence of PMI showed a trend of a lower survival rate, regardless of PMI on MRI, but without statistical significance. Unlike pathologic results, PMI on MRI was not associated with recurrence or survival in patients with early-stage cervical cancer.

  18. BiodosEPR-2006 Meeting: Acute dosimetry consensus committee recommendations on biodosimetry applications in events involving uses of radiation by terrorists and radiation accidents

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, George A. [U.S. Department of Health and Human Services, Office of Preparedness and Emergency Operations, 200 Independence Avenue, SW, Room 403B-1, Washington, DC 20201 (United States); Swartz, Harold M. [Dept. of Radiology and Physiology Dept., Dartmouth Medical School, HB 7785, Vail 702, Rubin 601, Hanover, NH 03755 (United States); Amundson, Sally A. [Center for Radiological Research, Columbia University Medical Center, 630 W. 168th Street, VC11-215, New York, NY 10032 (United States); Blakely, William F. [Armed Forces Radiobiology Research Inst., 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: blakely@afrri.usuhs.mil; Buddemeier, Brooke [Science and Technology, U.S. Department of Homeland Security, Washington, DC 20528 (United States); Gallez, Bernard [Biomedical Magnetic Resonance Unit and Lab. of Medicinal Chemistry and Radiopharmacy, Univ. Catholique de Louvain, Brussels (Belgium); Dainiak, Nicholas [Dept. of Medicine, Bridgeport Hospital, 267 Grant Street, Bridgeport, CT 06610 (United States); Goans, Ronald E. [MJW Corporation, 1422 Eagle Bend Drive, Clinton, TN 37716-4029 (United States); Hayes, Robert B. [Remote Sensing Lab., MS RSL-47, P.O. Box 98421, Las Vegas, NV 89193 (United States); Lowry, Patrick C. [Radiation Emergency Assistance Center/Training Site (REAC/TS), Oak Ridge Associated Universities, P.O. Box 117, Oak Ridge, TN 37831-0117 (United States); Noska, Michael A. [Food and Drug Administration, FDA/CDRH, 1350 Piccard Drive, HFZ-240, Rockville, MD 20850 (United States); Okunieff, Paul [Dept. of Radiation Oncology (Box 647), Univ. of Rochester, 601 Elmwood Avenue, Rochester, NY 14642 (United States); Salner, Andrew L. [Helen and Harry Gray Cancer Center, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102 (United States); Schauer, David A. [National Council on Radiation Protection and Measurements, 7910 Woodmont Avenue, Suite 400, Bethesda, MD 20814-3095 (United States)] (and others)

    2007-07-15

    In the aftermath of a radiological terrorism incident or mass-casualty radiation accident, first responders and receivers require prior guidance and pre-positioned resources for assessment, triage and medical management of affected individuals [NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA]. Several recent articles [Dainiak, N., Waselenko, J.K., Armitage, J.O., MacVittie, T.J., Farese, A.M., 2003. The hematologist and radiation casualties. Hematology (Am. Soc. Hematol. Educ. Program) 473-496; Waselenko, J.K., MacVittie, T.J., Blakely, W.F., Pesik, N., Wiley, A.L., Dickerson, W.E., Tsu, H., Confer, D.L., Coleman, C.N., Seed, T., Lowry, P., Armitage, J.O., Dainiak, N., Strategic National Stockpile Radiation Working Group, 2004. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann. Intern. Med. 140(12), 1037-1051; Blakely, W.F., Salter, C.A., Prasanna, P.G., 2005. Early-response biological dosimetry-recommended countermeasure enhancements for mass-casualty radiological incidents and terrorism. Health Phys. 89(5), 494-504; Goans, R.E., Waselenko, J.K., 2005. Medical management of radiation casualties. Health Phys. 89(5), 505-512; Swartz, H.M., Iwasaki, A., Walczak, T., Demidenko, E., Salikhov, I., Lesniewski, P., Starewicz, P., Schauer, D., Romanyukha, A., 2005. Measurements of clinically significant doses of ionizing radiation using non-invasive in vivo EPR spectroscopy of teeth in situ. Appl. Radiat. Isot. 62, 293-299; . Acute radiation injury: contingency planning for triage, supportive care, and transplantation. Biol. Blood Marrow Transplant. 12(6), 672-682], national [. Management of persons accidentally contaminated with radionuclides. NCRP Report No. 65, Bethesda, Maryland, USA; . Management of terrorist events involving radioactive material. NCRP Report No. 138, Bethesda, Maryland

  19. Genomic rearrangements at the FRA2H common fragile site frequently involve non-homologous recombination events across LTR and L1(LINE) repeats.

    Science.gov (United States)

    Brueckner, Lena M; Sagulenko, Evgeny; Hess, Elisa M; Zheglo, Diana; Blumrich, Anne; Schwab, Manfred; Savelyeva, Larissa

    2012-08-01

    Common fragile sites (cFSs) are non-random chromosomal regions that are prone to breakage under conditions of replication stress. DNA damage and chromosomal alterations at cFSs appear to be critical events in the development of various human diseases, especially carcinogenesis. Despite the growing interest in understanding the nature of cFS instability, only a few cFSs have been molecularly characterised. In this study, we fine-mapped the location of FRA2H using six-colour fluorescence in situ hybridisation and showed that it is one of the most active cFSs in the human genome. FRA2H encompasses approximately 530 kb of a gene-poor region containing a novel large intergenic non-coding RNA gene (AC097500.2). Using custom-designed array comparative genomic hybridisation, we detected gross and submicroscopic chromosomal rearrangements involving FRA2H in a panel of 54 neuroblastoma, colon and breast cancer cell lines. The genomic alterations frequently involved different classes of long terminal repeats and long interspersed nuclear elements. An analysis of breakpoint junction sequence motifs predominantly revealed signatures of microhomology-mediated non-homologous recombination events. Our data provide insight into the molecular structure of cFSs and sequence motifs affected by their activation in cancer. Identifying cFS sequences will accelerate the search for DNA biomarkers and targets for individualised therapies.

  20. Selective depletion of non-specific T cells as an early event in T cell response to bacterial and viral infections

    Institute of Scientific and Technical Information of China (English)

    JIANG Jiu

    2005-01-01

    @@ Early T cell depletion occurs prior to the development of an effective immune response to infections.Both antigen-specific and non-specific T cells are induced to express early activation markers soon after microbial infections.This is followed by massive depletion of non-specific T cells and extensive proliferation of antigen-specific T cells.Proliferating antigen-specific cells exhibit a broad spectrum of late activation markers while non-specific cells exhibit no sign of further activation before succumbing to apoptosis.These results have crucial implications for the understanding of early events in the development of a robust T cell response.

  1. DOES FATHER INVOLVEMENT INFLUENCE THE AFFECT, LANGUAGE ACQUISITION, SOCIAL ENGAGEMENT AND BEHAVIOR IN YOUNG AUTISTIC CHILDREN? AN EARLY INTERVENTION STUDY

    Directory of Open Access Journals (Sweden)

    Preeti Tabitha LOUIS

    2015-11-01

    Full Text Available The present study adopts a randomized experimental design to evaluate the impact of a father-mediated therapy to improve the play skills, affect, language, social skills and behavior among 30 clinically diagnosed autistic children at the age of 3-5 years. Standardized inventories such as, The Play Based Observation (PBO, The Griffiths Mental Developmental Scales (GMDS, The Vineland Social Maturity Scale (VSMS and the Rendel Shorts Questionnaire were administered pre and post intervention. A special program that involved fathers in the caregiving and nurturing processes of these children was designed and implemented for 6 months after which the children were reassessed. Prior to the intervention, deficits in play skills and developmental delays across expressive and receptive language were observed Scores on the Vineland Social Maturity Scale and the Rendel Shorts revealed behavioral markers. Post intervention, we noticed significant differences in the play, language acquisition, social engagement and behavior in the treatment group in comparison to the control group. The results suggested that father-mediated therapeutic involvement significantly has proven to positively foster development in young autistic children and this is an important implication for practitioners in developing early intervention programs.

  2. FKBP5 and specific microRNAs via glucocorticoid receptor in the basolateral amygdala involved in the susceptibility to depressive disorder in early adolescent stressed rats.

    Science.gov (United States)

    Xu, Jingjing; Wang, Rui; Liu, Yuan; Liu, Dexiang; Jiang, Hong; Pan, Fang

    2017-08-14

    Exposure to stressful events induces depressive-like symptoms and increases susceptibility to depression. However, the molecular mechanisms are not fully understood. Studies reported that FK506 binding protein51 (FKBP5), the co-chaperone protein of glucocorticoid receptors (GR), plays a crucial role. Further, miR-124a and miR-18a are involved in the regulation of FKBP5/GR function. However, few studies have referred to effects of early life stress on depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a in the basolateral amygdala (BLA) from adolescence to adulthood. This study aimed to examine the dynamic alternations of depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a expressions in the BLA of chronic unpredictable mild stress (CUMS) rats and dexamethasone administration rats during the adolescent period. Meanwhile, the GR antagonist, RU486, was used as a means of intervention. We found that CUMS and dexamethasone administration in the adolescent period induced permanent depressive-like behaviours and memory impairment, decreased GR expression, and increased FKBP5 and miR-124a expression in the BLA of both adolescent and adult rats. However, increased miR-18a expression in the BLA was found only in adolescent rats. Depressive-like behaviours were positively correlated with the level of miR-124a, whereas GR levels were negatively correlated with those in both adolescent and adult rats. Our results suggested FKBP5/GR and miR-124a in the BLA were associated with susceptibility to depressive disorder in the presence of stressful experiences in early life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Evaluation of early healing events around mesenchymal stem cell-seeded collagen-glycosaminoglycan scaffold. An experimental study in Wistar rats.

    LENUS (Irish Health Repository)

    Alhag, Mohamed

    2011-03-01

    Tissue engineering using cell-seeded biodegradable scaffolds offers a new bone regenerative approach that might circumvent many of the limitations of current therapeutic modalities. The aim of this experiment was to study the early healing events around mesenchymal stem cell-seeded collagen-glycosaminoglycan scaffolds.

  4. Size-resolved aerosol chemical analysis of extreme haze pollution events during early 2013 in urban Beijing, China

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Shili; Pan, Yuepeng, E-mail: panyuepeng@mail.iap.ac.cn; Liu, Zirui; Wen, Tianxue; Wang, Yuesi, E-mail: wys@mail.iap.ac.cn

    2014-08-30

    Highlights: • Anthropogenic species substantially accumulated in both fine and coarse particles. • Secondary organic carbon in PM{sub 1.1} decreased from clear to haze days. • The mass peak shifted to larger particles from clear to haze days. • The NO{sub 3}{sup −}/SO{sub 4}{sup 2−} ratio decreased with enhanced haze pollution. • Both mobile local and stationary regional sources were vital for haze formation. - Abstract: Using size-resolved filter sampling and chemical characterization, high concentrations of water-soluble ions, carbonaceous species and heavy metals were found in both fine (PM{sub 2.1}) and coarse (PM{sub 2.1–9}) particles in Beijing during haze events in early 2013. Even on clear days, average mass concentration of submicron particles (PM{sub 1.1}) was several times higher than that previously measured in most of abroad urban areas. A high concentration of particulate matter on haze days weakens the incident solar radiation, which reduces the generation rate of secondary organic carbon in PM{sub 1.1}. We show that the peak mass concentration of particles shifted from 0.43–0.65 μm on clear days to 0.65–1.1 μm on lightly polluted days and to 1.1–2.1 μm on heavily polluted days. The peak shifts were also found for the following species: organic carbon, elemental carbon, NH{sub 4}{sup +}, SO{sub 4}{sup 2−}, NO{sub 3}{sup −}, K, Cu, Zn, Cd and Pb. Our findings demonstrate that secondary inorganic aerosols (36%) and organic matter (26%) dominated the fine particle mass on heavily polluted days, while their contribution reduced to 29% and 18%, respectively, on clear days. Besides fine particles, anthropogenic chemical species also substantially accumulated in the coarse mode, which suggests that particles with aerodynamic diameter larger than 2.1 μm cannot be neglected during severe haze events.

  5. Combined oxygen- and carbon-isotope records through the Early Jurassic: multiple global events and two modes of carbon-cycle/temperature coupling

    DEFF Research Database (Denmark)

    Hesselbo, Stephen P.; Korte, Christoph

    2010-01-01

    The Jurassic comprises some 55 million years of Earth history. However, within the Jurassic, only one major environmental change (hyperthermal) event is really well known - the Early Toarcian Oceanic Anoxic Event (OAE) at ~183 Ma - and until very recently the extent to which the accompanying...... environmental changes were global has been strongly debated. Nevertheless, partly as a result of the international effort to define Global Stratotype Sections and Points (GSSPs), much more is now being discovered about environmental changes taking place at and around the other Jurassic Age (Stage) boundaries......, to the extent that meaningful comparisons between these events can begin to be made. Here we present new carbon and oxygen isotope data from mollusks (bivalves and belemnites) and brachiopods collected through the marine Early Jurassic succession of NE England, including the Sinemurian-Plienbachian boundary...

  6. Reduction of the treated volume to involved node radiation therapy as part of combined modality treatment for early stage aggressive non-Hodgkin's lymphoma.

    NARCIS (Netherlands)

    Verhappen, M.H.; Poortmans, P.M.; Raaijmakers, E.; Raemaekers, J.M.M.

    2013-01-01

    BACKGROUND AND PURPOSE: This retrospective study investigated whether focused involved node radiation therapy (INRT) can safely replace involved field RT (IFRT) in patients with early stage aggressive NHL. PATIENTS AND METHODS: We included 258 patients with stage I/II aggressive NHL who received com

  7. Depletion of Key Meiotic Genes and Transcriptome-Wide Abiotic Stress Reprogramming Mark Early Preparatory Events Ahead of Apomeiotic Transition

    Science.gov (United States)

    Shah, Jubin N.; Kirioukhova, Olga; Pawar, Pallavi; Tayyab, Muhammad; Mateo, Juan L.; Johnston, Amal J.

    2016-01-01

    Molecular dissection of apomixis – an asexual reproductive mode – is anticipated to solve the enigma of loss of meiotic sex, and to help fixing elite agronomic traits. The Brassicaceae genus Boechera comprises of both sexual and apomictic species, permitting comparative analyses of meiotic circumvention (apomeiosis) and parthenogenesis. Whereas previous studies reported local transcriptome changes during these events, it remained unclear whether global changes associated with hybridization, polyploidy and environmental adaptation that arose during evolution of Boechera might serve as (epi)genetic regulators of early development prior apomictic initiation. To identify these signatures during vegetative stages, we compared seedling RNA-seq transcriptomes of an obligate triploid apomict and a diploid sexual, both isolated from a drought-prone habitat. Uncovered were several genes differentially expressed between sexual and apomictic seedlings, including homologs of meiotic genes ASYNAPTIC 1 (ASY1) and MULTIPOLAR SPINDLE 1 (MPS1) that were down-regulated in apomicts. An intriguing class of apomict-specific deregulated genes included several NAC transcription factors, homologs of which are known to be transcriptionally reprogrammed during abiotic stress in other plants. Deregulation of both meiotic and stress-response genes during seedling stages might possibly be important in preparation for meiotic circumvention, as similar transcriptional alteration was discernible in apomeiotic floral buds too. Furthermore, we noted that the apomict showed better tolerance to osmotic stress in vitro than the sexual, in conjunction with significant upregulation of a subset of NAC genes. In support of the current model that DNA methylation epigenetically regulates stress, ploidy, hybridization and apomixis, we noted that ASY1, MPS1 and NAC019 homologs were deregulated in Boechera seedlings upon DNA demethylation, and ASY1 in particular seems to be repressed by global DNA

  8. Defective mitochondrial dynamics is an early event in skeletal muscle of an amyotrophic lateral sclerosis mouse model.

    Directory of Open Access Journals (Sweden)

    Guo Luo

    Full Text Available Mitochondria are dynamic organelles that constantly undergo fusion and fission to maintain their normal functionality. Impairment of mitochondrial dynamics is implicated in various neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS is an adult-onset neuromuscular degenerative disorder characterized by motor neuron death and muscle atrophy. ALS onset and progression clearly involve motor neuron degeneration but accumulating evidence suggests primary muscle pathology may also be involved. Here, we examined mitochondrial dynamics in live skeletal muscle of an ALS mouse model (G93A harboring a superoxide dismutase mutation (SOD1(G93A. Using confocal microscopy combined with overexpression of mitochondria-targeted photoactivatable fluorescent proteins, we discovered abnormal mitochondrial dynamics in skeletal muscle of young G93A mice before disease onset. We further demonstrated that similar abnormalities in mitochondrial dynamics were induced by overexpression of mutant SOD1(G93A in skeletal muscle of normal mice, indicating the SOD1 mutation drives ALS-like muscle pathology in the absence of motor neuron degeneration. Mutant SOD1(G93A forms aggregates inside muscle mitochondria and leads to fragmentation of the mitochondrial network as well as mitochondrial depolarization. Partial depolarization of mitochondrial membrane potential in normal muscle by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP caused abnormalities in mitochondrial dynamics similar to that in the SOD1(G93A model muscle. A specific mitochondrial fission inhibitor (Mdivi-1 reversed the SOD1(G93A action on mitochondrial dynamics, indicating SOD1(G93A likely promotes mitochondrial fission process. Our results suggest that accumulation of mutant SOD1(G93A inside mitochondria, depolarization of mitochondrial membrane potential and abnormal mitochondrial dynamics are causally linked and cause intrinsic muscle pathology, which occurs early in the course of ALS and

  9. Prenatal and early life exposure to stressful life events and risk of autism spectrum disorders: population-based studies in Sweden and England.

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    Dheeraj Rai

    Full Text Available Exposure to stressful life events during pregnancy has been suggested as a potential risk factor for offspring Autism Spectrum Disorders (ASD, but the literature is limited and inconsistent. We tested the hypothesis that maternal exposure to stressful life events would be associated with increased risks of offspring ASD, and that these risks would be highest for exposures during the prenatal period.We used prospectively collected data from two large population based studies in Sweden and England. In the Swedish study of 4429 ASD cases and 43277 controls, our exposure comprised the occurrence of any severe life event before and during pregnancy and the child's early life. In the English study (maximum n = 11554, ASD n = 72, we studied the risk of offspring ASD in relation to a combined maternal exposure to multiple (up to 42 common and rare life events, as well as their perceived impact upon the mother during pregnancy and early life. In crude and adjusted regression analyses in both studies, we found no evidence of an association between prenatal life events, or their number and perceived impact and the risk of offspring ASD. Sub-group analysis of ASD with and without intellectual disability in the Swedish study yielded similar results.We found no evidence to support the hypotheses that exposure to stressful life events during the prenatal period is associated with an increased risk of offspring ASD.

  10. Apoptosis is an early event during phthalocyanine photodynamic therapy-induced ablation of chemically induced squamous papillomas in mouse skin.

    Science.gov (United States)

    Agarwal, R; Korman, N J; Mohan, R R; Feyes, D K; Jawed, S; Zaim, M T; Mukhtar, H

    1996-04-01

    Photodynamic therapy (PDT) is a promising new modality to treat malignant neoplasms including superficial skin cancers. In our search for an ideal photosensitizer for PDT, Pc 4, a silicon phthalocyanine, has shown promising results both in in vitro assays and in implanted tumors. In this study we assessed the efficacy of Pc 4 PDT in the ablation of murine skin tumors; and the evidence for apoptosis during tumor ablation was also obtained. The Pc 4 was administered through tail vein injection to SENCAR mice bearing chemically induced squamous papillomas, and 24 h later the lesions were illuminated with an argon ion-pumped dye laser tuned at 675 nm for a total light dose of 135 J/cm2. Within 72-96 h, almost complete tumor shrinkage occurred; no tumor regrowth was observed up to 90 days post-PDT. As evident by nucleosome-size DNA fragmentation, appearance of apoptotic bodies in hematoxylin and eosin staining and direct immunoperoxidase detection of digoxigenin-labeled genomic DNA in sections, apoptosis was clearly evident 6 h post-PDT at which time tumor shrinkage was less than 30%. The apoptotic bodies, as evident by the condensation of chromatin material around the periphery of the nucleus and increased vacuolization of the cytoplasm, were also observed in electron microscopic studies of the tumor tissues following Pc 4 PDT. The extent of apoptosis was greater at 15 h than at 6 and 10 h post-PDT. Taken together, our results clearly show that Pc 4 may be an effective photosensitizer for PDT of nonmelanoma skin cancer, and that apoptosis is an early event during this process.

  11. CCR4 Controls the Suppressive Effects of Regulatory T Cells on Early and Late Events during Severe Sepsis.

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    Raphael Molinaro

    Full Text Available Sepsis is a deadly disease characterized by an overwhelming release of inflammatory mediators and the activation of different types of cells. This altered state of cell activation, termed leukocyte reprogramming, contributes to patient outcome. However, the understanding of the process underlying sepsis and the role of regulatory T cells (Tregs in sepsis remains to be elucidated. In this study, we investigated the role of CCR4, the CCL17/CCL22 chemokine receptor, in the innate and acquired immune responses during severe sepsis and the role of Tregs in effecting the outcome. In contrast with wild-type (WT mice subjected to cecal ligation and puncture (CLP sepsis, CCR4-deficient (CCR4-/- septic mice presented an increased survival rate, significant neutrophil migration toward the infection site, a low bacterial count in the peritoneum, and reduced lung inflammation and serum cytokine levels. Thus, a better early host response may favor an adequate long-term response. Consequently, the CCR4-/- septic mice were not susceptible to secondary fungal infection, in contrast with the WT septic mice. Furthermore, Tregs cells from the CCR4-/- septic mice showed reduced suppressive effects on neutrophil migration (both in vivo and in vitro, lymphocyte proliferation and ROS production from activated neutrophils, in contrast with what was observed for Tregs from the WT septic mice. These data show that CCR4 is involved in immunosuppression after severe sepsis and suggest that CCR4+ Tregs negatively modulate the short and long-term immune responses.

  12. CCR4 Controls the Suppressive Effects of Regulatory T Cells on Early and Late Events during Severe Sepsis.

    Science.gov (United States)

    Molinaro, Raphael; Pecli, Cyntia; Guilherme, Rafael F; Alves-Filho, José Carlos; Cunha, Fernando Q; Canetti, Claudio; Kunkel, Steven L; Bozza, Marcelo T; Benjamim, Claudia F

    2015-01-01

    Sepsis is a deadly disease characterized by an overwhelming release of inflammatory mediators and the activation of different types of cells. This altered state of cell activation, termed leukocyte reprogramming, contributes to patient outcome. However, the understanding of the process underlying sepsis and the role of regulatory T cells (Tregs) in sepsis remains to be elucidated. In this study, we investigated the role of CCR4, the CCL17/CCL22 chemokine receptor, in the innate and acquired immune responses during severe sepsis and the role of Tregs in effecting the outcome. In contrast with wild-type (WT) mice subjected to cecal ligation and puncture (CLP) sepsis, CCR4-deficient (CCR4-/-) septic mice presented an increased survival rate, significant neutrophil migration toward the infection site, a low bacterial count in the peritoneum, and reduced lung inflammation and serum cytokine levels. Thus, a better early host response may favor an adequate long-term response. Consequently, the CCR4-/- septic mice were not susceptible to secondary fungal infection, in contrast with the WT septic mice. Furthermore, Tregs cells from the CCR4-/- septic mice showed reduced suppressive effects on neutrophil migration (both in vivo and in vitro), lymphocyte proliferation and ROS production from activated neutrophils, in contrast with what was observed for Tregs from the WT septic mice. These data show that CCR4 is involved in immunosuppression after severe sepsis and suggest that CCR4+ Tregs negatively modulate the short and long-term immune responses.

  13. Putative alternative polyadenylation (APA) events in the early interaction of Salmonella enterica Typhimurium and human host cells.

    Science.gov (United States)

    Afonso-Grunz, Fabian

    2015-12-01

    The immune response of epithelial cells upon infection is mediated by changing activity levels of a variety of proteins along with changes in mRNA, and also ncRNA abundance. Alternative polyadenylation (APA) represents a mechanism that diversifies gene expression similar to alternative splicing. T-cell activation, neuronal activity, development and several human diseases including viral infections involve APA, but at present it remains unclear if this mechanism is also implicated in the response to bacterial infections. Our recently published study of interacting Salmonella enterica Typhimurium and human host cells includes genome-wide expression profiles of human epithelial cells prior and subsequent to infection with the invasive pathogen. The generated dataset (GEO accession number: GSE61730) covers several points of time post infection, and one of these interaction stages was additionally profiled with MACE-based dual 3'Seq, which allows for identification of polyadenylation (PA) sites. The present study features the polyadenylation landscape in early interacting cells based on this data, and provides a comparison of the identified PA sites with those of a corresponding 3P-Seq dataset of non-interacting cells. Differential PA site usage of FTL, PRDX1 and VAPA results in transcription of mRNA isoforms with distinct sets of miRNA and protein binding sites that influence processing, localization, stability, and translation of the respective mRNA. APA of these candidate genes consequently harbors the potential to modulate the host cell response to bacterial infection.

  14. Putative alternative polyadenylation (APA events in the early interaction of Salmonella enterica Typhimurium and human host cells

    Directory of Open Access Journals (Sweden)

    Fabian Afonso-Grunz

    2015-12-01

    Full Text Available The immune response of epithelial cells upon infection is mediated by changing activity levels of a variety of proteins along with changes in mRNA, and also ncRNA abundance. Alternative polyadenylation (APA represents a mechanism that diversifies gene expression similar to alternative splicing. T-cell activation, neuronal activity, development and several human diseases including viral infections involve APA, but at present it remains unclear if this mechanism is also implicated in the response to bacterial infections. Our recently published study of interacting Salmonella enterica Typhimurium and human host cells includes genome-wide expression profiles of human epithelial cells prior and subsequent to infection with the invasive pathogen. The generated dataset (GEO accession number: GSE61730 covers several points of time post infection, and one of these interaction stages was additionally profiled with MACE-based dual 3'Seq, which allows for identification of polyadenylation (PA sites. The present study features the polyadenylation landscape in early interacting cells based on this data, and provides a comparison of the identified PA sites with those of a corresponding 3P-Seq dataset of non-interacting cells. Differential PA site usage of FTL, PRDX1 and VAPA results in transcription of mRNA isoforms with distinct sets of miRNA and protein binding sites that influence processing, localization, stability, and translation of the respective mRNA. APA of these candidate genes consequently harbors the potential to modulate the host cell response to bacterial infection.

  15. Early postprandial low-grade inflammation after high-fat meal in healthy rats: possible involvement of visceral adipose tissue.

    Science.gov (United States)

    Magné, Joëlle; Mariotti, François; Fischer, Romy; Mathé, Véronique; Tomé, Daniel; Huneau, Jean François

    2010-06-01

    In the postprandial period, low-grade inflammation may contribute to vascular endothelial dysfunction, a hallmark of atherogenesis. Little is known about the involvement of the adipose tissue in the initiation of the postprandial inflammatory response such as obtained after a high-saturated fat meal (HFM). In the present study, we first studied the time course of appearance of systemic inflammation after a HFM in healthy rats, and then we investigated whether a HFM activates the inflammatory signaling in the visceral adipose tissue, with a focus on the key component, nuclear factor-kappaB (NF-kappaB). Two hours after the HFM, plasma IL-6 and PAI-1, but not plasma C-reactive protein and soluble intracellular adhesion molecule-1, showed a marked, transient increase. These changes were specific to the postprandial state as not observed after a control water load. Neutrophils count and activation markers CD11B and CD62L, assessed by flow cytometry, also rose significantly 2 h after the HFM, while remaining steady after the control. At the same time, the HFM decreased significantly B-cell count and expression of the activation marker CD62L. Interestingly, at the same early time after the HFM, in the visceral adipose tissue, there was a 2.2-fold increase in the activation of NF-kappaB (p65) in nuclear extract and an increase in IL-6 mRNA. As far as we know, this is the first study evidencing an acute, postprandial activation of inflammation in visceral adipose tissue. This early activation of NF-kappaB pathway after a HFM may play a triggering role in the initiation of the complex postprandial proatherogenic phenotype. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  16. An early ethylene up-regulated gene encoding a calmodulin-binding protein involved in plant senescence and death

    Science.gov (United States)

    Yang, T.; Poovaiah, B. W.

    2000-01-01

    35S-Labeled calmodulin (CaM) was used to screen a tobacco anther cDNA library. A positive clone (NtER1) with high homology to an early ethylene-up-regulated gene (ER66) in tomato, and an Arabidopsis homolog was isolated and characterized. Based on the helical wheel projection, a 25-mer peptide corresponding to the predicted CaM-binding region of NtER1 (amino acids 796-820) was synthesized. The gel-mobility shift assay showed that the peptide formed a stable complex with CaM only in the presence of Ca(2+). CaM binds to NtER1 with high affinity (K(d) approximately 12 nm) in a calcium-dependent manner. Tobacco flowers at different stages of development were treated with ethylene or with 1-methylcyclopropene for 2 h before treating with ethylene. Northern analysis showed that the NtER1 was rapidly induced after 15 min of exposure to ethylene. However, the 2-h 1-methylcyclopropene treatment totally blocked NtER1 expression in flowers at all stages of development, suggesting that NtER1 is an early ethylene-up-regulated gene. The senescing leaves and petals had significantly increased NtER1 induction as compared with young leaves and petals, implying that NtER1 is developmentally regulated and acts as a trigger for senescence and death. This is the first documented evidence for the involvement of Ca(2+)/CaM-mediated signaling in ethylene action.

  17. An early ethylene up-regulated gene encoding a calmodulin-binding protein involved in plant senescence and death

    Science.gov (United States)

    Yang, T.; Poovaiah, B. W.

    2000-01-01

    35S-Labeled calmodulin (CaM) was used to screen a tobacco anther cDNA library. A positive clone (NtER1) with high homology to an early ethylene-up-regulated gene (ER66) in tomato, and an Arabidopsis homolog was isolated and characterized. Based on the helical wheel projection, a 25-mer peptide corresponding to the predicted CaM-binding region of NtER1 (amino acids 796-820) was synthesized. The gel-mobility shift assay showed that the peptide formed a stable complex with CaM only in the presence of Ca(2+). CaM binds to NtER1 with high affinity (K(d) approximately 12 nm) in a calcium-dependent manner. Tobacco flowers at different stages of development were treated with ethylene or with 1-methylcyclopropene for 2 h before treating with ethylene. Northern analysis showed that the NtER1 was rapidly induced after 15 min of exposure to ethylene. However, the 2-h 1-methylcyclopropene treatment totally blocked NtER1 expression in flowers at all stages of development, suggesting that NtER1 is an early ethylene-up-regulated gene. The senescing leaves and petals had significantly increased NtER1 induction as compared with young leaves and petals, implying that NtER1 is developmentally regulated and acts as a trigger for senescence and death. This is the first documented evidence for the involvement of Ca(2+)/CaM-mediated signaling in ethylene action.

  18. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  19. Selection of Top-Like Events in the Lepton+Jets Channels in Early 7 TeV LHC-Data with CMS

    CERN Document Server

    Chwalek, Thorsten

    2010-01-01

    The top quark is the heaviest known fermion in the standard model. Due to its large production cross section, pairs of top and antitop quarks will be copiously produced at the Large Hadron Collider (LHC). The event selection deemed for the selection of $t\\bar{t}$ events is applied to an early data set of proton-proton collisions at a center-of-mass energy of $7\\,\\mathrm{TeV}$ corresponding to an integrated luminosity of $0.84\\pm 0.09\\,\\mathrm{pb}^{-1}$. Since this data set is obviously too small to make a statement on the top quark cross section at the LHC, the focus is on the comparison of the predicted background yields and the overall yield of events collected. In addition data-driven techniques to estimate the background contribution from QCD multijet events are evaluated in sideband regions.

  20. Analysis of different device-based intrathoracic impedance vectors for detection of heart failure events (from the Detect Fluid Early from Intrathoracic Impedance Monitoring study).

    Science.gov (United States)

    Heist, E Kevin; Herre, John M; Binkley, Philip F; Van Bakel, Adrian B; Porterfield, James G; Porterfield, Linda M; Qu, Fujian; Turkel, Melanie; Pavri, Behzad B

    2014-10-15

    Detect Fluid Early from Intrathoracic Impedance Monitoring (DEFEAT-PE) is a prospective, multicenter study of multiple intrathoracic impedance vectors to detect pulmonary congestion (PC) events. Changes in intrathoracic impedance between the right ventricular (RV) coil and device can (RVcoil→Can) of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy ICDs (CRT-Ds) are used clinically for the detection of PC events, but other impedance vectors and algorithms have not been studied prospectively. An initial 75-patient study was used to derive optimal impedance vectors to detect PC events, with 2 vector combinations selected for prospective analysis in DEFEAT-PE (ICD vectors: RVring→Can + RVcoil→Can, detection threshold 13 days; CRT-D vectors: left ventricular ring→Can + RVcoil→Can, detection threshold 14 days). Impedance changes were considered true positive if detected heart failure events. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Early involvement in friendships predicts later plasma concentrations of oxytocin and vasopressin in juvenile rhesus macaques (Macaca mulatta

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    Tamara Aliza Rachel Weinstein

    2014-08-01

    Full Text Available The neuropeptides oxytocin (OT and vasopressin (AVP are involved in social bonding in attachment relationships, but their role in friendship is poorly understood. We investigated whether rhesus macaques’ (Macaca mulatta friendships at age one predicted plasma OT and AVP at two later time points. Subjects were 54 rhesus macaques at the California National Primate Research Center. Blood was drawn during a brief capture-and-release in the home cage, and plasma assayed for OT and AVP using an enzyme immunoassay. Separate linear mixed models for each sex tested the effects of dominance rank, age, sampling time point, housing condition, parturition status, two blood draw timing measures, and five friendship types: proximity friendships, play friendships, reciprocal friendships (a preference for a peer that also preferred the subject, multiplex friendships (friendships displayed in more than one behavioral domain, and total number of friendships. Females’ number of reciprocal and play friendships at age one significantly predicted later OT; additionally, these two friendship types interacted with rank, such that high-ranking females with the fewest friendships had the highest OT concentrations. Friendship did not predict later OT levels in males, however proximity, play, reciprocal, and total number of friendships predicted males’ plasma AVP. Play and total number of friendships also tended to predict AVP in females. Our results show that peripheral measures of neuroendocrine functioning in juvenile rhesus monkeys are influenced by early involvement in friendships. Friendships have an especially strong impact on an individual’s psychosocial development, and our data suggest OT and AVP as potential underlying mechanisms. Moreover, sex differences in the functioning of the OT and AVP systems, and their relation to friendship, may have important clinical implications for the use of OT as a therapeutic, as well as informing the social context in

  2. Endosomes and lysosomes are involved in early steps of Tl(III)-mediated apoptosis in rat pheochromocytoma (PC12) cells.

    Science.gov (United States)

    Hanzel, Cecilia E; Almeira Gubiani, María F; Verstraeten, Sandra V

    2012-11-01

    The mechanisms that mediate thallium (Tl) toxicity are still not completely understood. The exposure of rat pheochromocytoma (PC12) cells to Tl(I) or Tl(III) activates both mitochondrial (Tl(I) and Tl(III)) and extrinsic (Tl(III)) pathways of apoptosis. In this work we evaluated the hypothesis that the effects of Tl(III) may be mediated by the damage to lysosomes, where it might be incorporated following the route of iron uptake. PC12 cells exposed for 3 h to 100 μM Tl(III) presented marked endosomal acidification, effect that was absent when cells were incubated in a serum-free medium and that was fully recovered when the latter was supplemented with transferrin. After 6 h of incubation the colocalization of cathepsins D and B with the lysosomal marker Lamp-1 was decreased together with an increase in the total activity of the enzymes. A permanent damage to lysosomes after 18 h of exposure was evidenced from the impairment of acridine orange uptake. Cathepsin D caused the cleavage of pro-apoptotic protein BID that is involved in the activation of the intrinsic pathway of apoptosis. Supporting that, BID cleavage and the activation of caspase 3 by Tl(III) were fully prevented when cells were preincubated with cathepsin D inhibitor (pepstatin A) and only partially prevented when cathepsin B inhibitor (E64d) was used. None of these inhibitors affected BID cleavage or caspase 3 activation in Tl(I)-treated cells. Together, experimental results support the role of Tl(III) uptake by the acidic cell compartments and their involvement in the early steps of Tl(III)-mediated PC12 cells apoptosis.

  3. Effects of detector dead-time on quantitative analyses involving boron and multi-hit detection events in atom probe tomography.

    Science.gov (United States)

    Meisenkothen, Frederick; Steel, Eric B; Prosa, Ty J; Henry, Karen T; Prakash Kolli, R

    2015-12-01

    In atom probe tomography (APT), some elements tend to field evaporate preferentially in multi-hit detection events. Boron (B) is one such element. It is thought that a large fraction of the B signal may be lost during data acquisition and is not reported in the mass spectrum or in the 3-D APT reconstruction. Understanding the relationship between the field evaporation behavior of B and the limitations for detecting multi-hit events can provide insight into the signal loss mechanism for B and may suggest ways to improve B detection accuracy. The present work reports data for nominally pure B and for B-implanted silicon (Si) (NIST-SRM2137) at dose levels two-orders of magnitude lower than previously studied by Da Costa, et al. in 2012. Boron concentration profiles collected from SRM2137 specimens qualitatively confirmed a signal loss mechanism is at work in laser pulsed atom probe measurements of B in Si. Ion correlation analysis was used to graphically demonstrate that the detector dead-time results in few same isotope, same charge-state (SISCS) ion pairs being properly recorded in the multi-hit data, explaining why B is consistently under-represented in quantitative analyses. Given the important role of detector dead-time as a signal loss mechanism, the results from three different methods of estimating the detector dead-time are presented. The findings of this study apply to all quantitative analyses that involve multi-hit data, but the dead-time will have the greatest effect on the elements that have a significant quantity of ions detected in multi-hit events. Published by Elsevier B.V.

  4. What is the association of hypothyroidism with risks of cardiovascular events and mortality? A meta-analysis of 55 cohort studies involving 1,898,314 participants.

    Science.gov (United States)

    Ning, Yu; Cheng, Yun J; Liu, Li J; Sara, Jaskanwal D S; Cao, Zhi Y; Zheng, Wei P; Zhang, Tian S; Han, Hui J; Yang, Zhen Y; Zhang, Yi; Wang, Fei L; Pan, Rui Y; Huang, Jie L; Wu, Ling L; Zhang, Ming; Wei, Yong X

    2017-02-02

    Whether hypothyroidism is an independent risk factor for cardiovascular events is still disputed. We aimed to assess the association between hypothyroidism and risks of cardiovascular events and mortality. We searched PubMed and Embase from inception to 29 February 2016. Cohort studies were included with no restriction of hypothyroid states. Priori main outcomes were ischemic heart disease (IHD), cardiac mortality, cardiovascular mortality, and all-cause mortality. Fifty-five cohort studies involving 1,898,314 participants were identified. Patients with hypothyroidism, compared with euthyroidism, experienced higher risks of IHD (relative risk (RR): 1.13; 95% confidence interval (CI): 1.01-1.26), myocardial infarction (MI) (RR: 1.15; 95% CI: 1.05-1.25), cardiac mortality (RR: 1.96; 95% CI: 1.38-2.80), and all-cause mortality (RR: 1.25; 95% CI: 1.13-1.39); subclinical hypothyroidism (SCH; especially with thyrotropin level ≥10 mIU/L) was also associated with higher risks of IHD and cardiac mortality. Moreover, cardiac patients with hypothyroidism, compared with those with euthyroidism, experienced higher risks of cardiac mortality (RR: 2.22; 95% CI: 1.28-3.83) and all-cause mortality (RR: 1.51; 95% CI: 1.26-1.81). Hypothyroidism is a risk factor for IHD and cardiac mortality. Hypothyroidism is associated with higher risks of cardiac mortality and all-cause mortality compared with euthyroidism in the general public or in patients with cardiac disease.

  5. Identification of Rapeseed MicroRNAs Involved in Early Stage Seed Germination under Salt and Drought Stresses.

    Science.gov (United States)

    Jian, Hongju; Wang, Jia; Wang, Tengyue; Wei, Lijuan; Li, Jiana; Liu, Liezhao

    2016-01-01

    Drought and salinity are severe and wide-ranging abiotic stresses that substantially affect crop germination, development and productivity, and seed germination is the first critical step in plant growth and development. To comprehensively investigate small-RNA targets and improve our understanding of miRNA-mediated post-transcriptional regulation networks during Brassica napus seed imbibition under drought and salt stresses, we constructed three small-RNA libraries from B. napus variety ZS11 embryos exposed to salt (200 mM NaCl, denoted "S"), drought (200 g L(-1) PEG-6000, denoted "D"), and distilled water (denoted "CK") during imbibition and sequenced them using an Illumina Genome Analyzer. A total of 11,528,557, 12,080,081, and 12,315,608 raw reads were obtained from the CK, D, and S libraries, respectively. Further analysis identified 85 known miRNAs belonging to 31 miRNA families and 882 novel miRNAs among the three libraries. Comparison of the D and CK libraries revealed significant down-regulation of six miRNA families, miR156, miR169, miR860, miR399, miR171, and miR395, whereas only miR172 was significantly up-regulated. In contrast, comparison of the S library with the CK library showed significant down-regulation of only two miRNA families: miRNA393 and miRNA399. Putative targets for 336, 376, and 340 novel miRNAs were successfully predicted in the CK, D, and S libraries, respectively, and 271 miRNA families and 20 target gene families [including disease resistance protein (DIRP), drought-responsive family protein (DRRP), early responsive to dehydration stress protein (ERD), stress-responsive alpha-beta barrel domain protein (SRAP), and salt tolerance homolog2 (STH2)] were confirmed as being core miRNAs and genes involved in the seed imbibition response to salt and drought stresses. The sequencing results were partially validated by quantitative RT-PCR for both conserved and novel miRNAs as well as the predicted target genes. Our data suggest that diverse

  6. Subcellular distribution and early signalling events of P2X7 receptors from mouse cerebellar granule neurons.

    Science.gov (United States)

    Sánchez-Nogueiro, Jesús; Marín-García, Patricia; Bustillo, Diego; Olivos-Oré, Luis Alcides; Miras-Portugal, María Teresa; Artalejo, Antonio R

    2014-12-05

    The subcellular distribution and early signalling events of P2X7 receptors were studied in mouse cerebellar granule neurons. Whole-cell patch-clamp recordings evidenced inwardly directed non-desensitizing currents following adenosine 5'-triphosphate (ATP; 600 µM) or 2'-3'-o-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP; 100 µM) administration to cells bathed in a medium with no-added divalent cations (Ca(2+) and Mg(2+)). Nucleotide-activated currents were inhibited by superfusion of 2.5 mM Ca(2+), 1.2 mM Mg(2+) or 100 nM Brilliant Blue G (BBG), hence indicating the expression of ionotropic P2X7 receptors. Fura-2 calcium imaging showed [Ca(2+)]i elevations in response to ATP or BzATP at the somas and at a small number of axodendritic regions of granule neurons. Differential sensitivity of these [Ca(2+)]i increases to three different P2X7 receptor antagonists (100 nM BBG, 10 μM 4-[(2S)-2-[(5-isoquinolinylsulfonyl)methylamino]-3-oxo-3-(4-phenyl-1-piperazinyl)propyl] phenyl isoquinolinesulfonic acid ester, KN-62, and 1 μM 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methyl pyridine hydrochloride hydrate, A-438079) revealed that P2X7 receptors are co-expressed with different P2Y receptors along the plasmalemma of granule neurons. Finally, experiments with the fluorescent dye YO-PRO-1 indicated that prolonged stimulation of P2X7 receptors does not lead to the opening of a membrane pore permeable to large cations. Altogether, our results emphasise the expression of functional P2X7 receptors at both the axodendritic and somatic levels in mouse cerebellar granule neurons, and favour the notion that P2X7 receptors might function in a subcellular localisation-specific manner: presynaptically, by controlling glutamate release, and on the cell somas, by supporting granule neuron survival against glutamate excytotoxicity.

  7. Evolution of GHF5 endoglucanase gene structure in plant-parasitic nematodes: no evidence for an early domain shuffling event

    Directory of Open Access Journals (Sweden)

    Gheysen Godelieve

    2008-11-01

    PPN GHF5 endoglucanase gene most probably consisted of the whole gene cassette, i.e. the GHF5 catalytic domain and the CBM2, rather than that it evolved by domain shuffling. Our evolutionary model for the gene structure in PPN GHF5 endoglucanases implies the occurrence of an early duplication event, and more recent gene duplications at genus or species level.

  8. The influence of the thermal environment and other early life events on growth rate of piglets during lactation.

    Science.gov (United States)

    Pedersen, L J; Schild, S-L Aa; Malmkvist, J

    2015-09-01

    The effects of early life events on average daily weight gain from birth to day 21 (ADG) of suckling pigs kept at different room temperatures (15°C, 20°C and 25°C) from birth to weaning were investigated. Data were collected from litters born by 61 sows in a loose housing system. The ADG for piglets with low birth weight (estimated for birth weights below the 10% percentile) was estimated to be 20 to 30 g higher per day at room temperature 20°C to 25°C compared with 15°C. In contrast, the ADG during the lactation period decreased for larger piglets (estimated for birth weights above the 10% percentile) by 28 g/day at room temperature 25°C compared with 15°C. Thus, high ambient temperatures (20°C to 25°C) are favourable for the growth in smaller piglets during lactation. Neither latency to first suckle nor birth-induced hypoxia, measured as concentration of umbilical cord lactate, affected the growth rate of the piglets. Lowest rectal temperature during the first 24 h after birth had a long-term negative effect on ADG (Ptemperature of 32.8°C (10% percentile) had an ADG which was on average 19 g lower per day than piglets with a rectal temperature of 37.3°C (90% percentile). Our results showed that hypothermia at birth, low birth weight and high number of suckling piglets lead to reduced ADG during the suckling period. The results suggest that keeping the room temperature at 20°C during lactation to some extent could compensate for the otherwise negative effects of low birth weight on ADG in piglets without decreasing the ADG of high birth weight piglets. However, to avoid hypothermia in the smallest piglets it may be beneficial to increase the room temperature above 20°C during the farrowing period of loose housed sows.

  9. The Saccharomyces cerevisiae PRM1 homolog in Neurospora crassa is involved in vegetative and sexual cell fusion events but also has postfertilization functions.

    Science.gov (United States)

    Fleissner, André; Diamond, Spencer; Glass, N Louise

    2009-02-01

    Cell-cell fusion is essential for a variety of developmental steps in many eukaryotic organisms, during both fertilization and vegetative cell growth. Although the molecular mechanisms associated with intracellular membrane fusion are well characterized, the molecular mechanisms of plasma membrane merger between cells are poorly understood. In the filamentous fungus Neurospora crassa, cell fusion events occur during both vegetative and sexual stages of its life cycle, thus making it an attractive model for studying the molecular basis of cell fusion during vegetative growth vs. sexual reproduction. In the unicellular yeast Saccharomyces cerevisiae, one of the few proteins implicated in plasma membrane merger during mating is Prm1p; prm1Delta mutants show an approximately 50% reduction in mating cell fusion. Here we report on the role of the PRM1 homolog in N. crassa. N. crassa strains with deletions of a Prm1-like gene (Prm1) showed an approximately 50% reduction in both vegetative and sexual cell fusion events, suggesting that PRM1 is part of the general cell fusion machinery. However, unlike S. cerevisiae, N. crassa strains carrying a Prm1 deletion exhibited complete sterility as either a male or female mating partner, a phenotype that was not complemented in a heterokaryon with wild type (WT). Crosses with DeltaPrm1 strains were blocked early in sexual development, well before development of ascogenous hyphae. The DeltaPrm1 sexual defect in N. crassa was not suppressed by mutations in Sad-1, which is required for meiotic silencing of unpaired DNA (MSUD). However, mutations in Sad-1 increased the number of progeny obtained in crosses with a DeltaPrm1 (Prm1-gfp) complemented strain. These data indicate multiple roles for PRM1 during sexual development.

  10. An early-life hypoxia event has a long-term impact on protein digestion and growth in European sea bass juvenile.

    Science.gov (United States)

    Zambonino-Infante, José L; Mazurais, David; Servili, A; Cahu, C; Vanderplancke, G; Le Bayon, N; Huelvan, C; Claireaux, Guy

    2017-03-16

    Ocean warming, eutrophication and consequent decrease in oxygen lead to smaller average fish size. Although such responses are well-known in an evolutionary context, involving multiple generations, it appears to be incompatible with current rapid environmental change. Rather, phenotypic plasticity could provide a means for marine fish to cope with rapid environmental changes. However, little is known about the mechanisms underlying plastic responses to environmental conditions that favour small phenotypes.Our aim was to investigate how and why European sea bass that had experienced a short episode of moderate hypoxia during their larval stage subsequently exhibited a growth depression at the juvenile stage compared to the control group.We examined whether energy was used to cover higher costs for maintenance, digestion or activity metabolisms, as a result of differing metabolic rate. The lower growth was not a consequence of lower feed intake.We measured several respirometry parameters and we only found a higher SDA (Specific Dynamic Action) duration and lower SDA amplitude in a fish phenotype with lower growth; this phenotype was also associated with a lower protein digestive capacity in the intestine.Our results contribute to the understanding of the observed decrease in growth in response to climate change. They demonstrate that the reduced growth of juvenile fishes as a consequence of an early-life hypoxia event was not due to a change of fish aerobic scope, but to a specific change in the efficiency of protein digestive functions. The question remains of whether this effect is epigenetic and could be reversible in the offspring.

  11. Effect of an inpatient nursing risk early warning and control system in Shanghai: A retrospective study of adverse events

    Directory of Open Access Journals (Sweden)

    Qian Wu

    2015-06-01

    Conclusion: The establishment of an inpatient early warning and control system could effectively avoid nursing risk, improve risk prevention abilities, improve patient safety, and improve nursing quality.

  12. Environmental events and catastrophes from the end of early pleistocene to the early stage of middle pleistocene%早更新世末中更新世早期的环境事件与灾变

    Institute of Scientific and Technical Information of China (English)

    周厚云

    2000-01-01

    In this paper,the author describes several kinds of environmental events(including abnormal changes of climate,tectonic activation,erosion and deposition events,astronomical events,migrations of creature and some other events such as the reversal of paleo-magnetic polar)from the end of Early Pleistocene to the early stage of Middle Pleistocene,approximately 1.1-0.7MaB.P..Abnormal changes of climate and tectonic activation are the essential for some other environmental events,such as erosion,deposition events and migrations of creature,and control these events.There are two clusters of impact events which are supposed to happen at about 1.1MaB.P. and 0.7MaB.P. respectively and the paleo-magnetic polar reverse three times during the time of 1.1~0.7MaB.P.. Based on the characteristics of abnormal changes of climate and tectonic activation,the author combines these events together and regards the whole period from 1.1 to 0.7MaB.P. as a continuous procession full of abnormal environmental events.Some environmental events are the causes of catastrophes,and some are the results.There are close relationships between environmental events and natural catastrophes.%综述了发生在早更新世末到中更新世早期,即大致从1.1~0.7MaBP的各种环境事件,包括气候异常变化、构造活化、侵蚀沉积事件、天文事件、生物迁徙以及古地磁的异常等.其中气候异常和构造活化是基本的环境事件,对其它事件有控制作用.根据气候异常和构造活化的特征,可以认为,从1.1MaBP到0.7MaBP是一个连续的环境异常过程,这一时期各类环境事件集中发生,环境事件或为灾变的原因,或为灾变的结果,与自然界的灾变之间存在密切的关系.

  13. Reanalyses of Anomalous Gravitational Microlensing Events in the OGLE-III Early Warning System Database with Combined Data

    CERN Document Server

    Jeong, J; Han, C; Gould, A; Udalski, A; Szymański, M K; Pietrzyński, G; Soszyński, I; Poleski, R; Ulaczyk, K; Wyrzykowski, Ł; Abe, F; Bennett, D P; Bond, I A; Botzler, C S; Freeman, M; Fukui, A; Fukunaga, D; Itow, Y; Koshimoto, N; Masuda, K; Matsubara, Y; Muraki, Y; Namba, S; Ohnishi, K; Rattenbury, N J; Saito, To; Sullivan, D J; Sweatman, W L; Sumi, T; Suzuki, D; Tristram, P J; Tsurumi, N; Wada, K; Yamai, N; Yock, P C M; Yonehara, A; Albrow, M D; Batista, V; Beaulieu, J -P; Caldwell, J A R; Cassan, A; Cole, A; Coutures, C; Dieters, S; Dominik, M; Prester, D Dominis; Donatowicz, J; Fouqué, P; Greenhill, J; Hoffman, M; Huber, M; Jørgensen, U G; Kane, S R; Kubas, D; Martin, R; Marquette, J -B; Menzies, J; Pitrou, C; Pollard, K; Sahu, K C; Vinter, C; Wambsganss, J; Williams, A; Allen, W; Bolt, G; Choi, J -Y; Christie, G W; DePoy, D L; Drummond, J; Gaudi, B S; Hwang, K -H; Jung, Y K; Lee, C -U; Mallia, F; Maoz, D; Maury, A; McCormick, J; Monard, L A G; Moorhouse, D; Natusch, T; Ofek, E O; Park, B -G; Pogge, R W; Santallo, R; Shin, I -G; Thornley, G; Yee, J C; Bramich, D M; Horne, K; Hundertmark, M; Kains, N; Snodgrass, C; Steele, I; Street, R; Tsapras, Y

    2015-01-01

    We reanalyze microlensing events in the published list of anomalous events that were observed from the OGLE lensing survey conducted during 2004-2008 period. In order to check the existence of possible degenerate solutions and extract extra information, we conduct analyses based on combined data from other survey and follow-up observation and consider higher-order effects. Among the analyzed events, we present analyses of 8 events for which either new solutions are identified or additional information is obtained. We find that the previous binary-source interpretations of 5 events are better interpreted by binary-lens models. These events include OGLE-2006-BLG-238, OGLE-2007-BLG-159, OGLE-2007-BLG-491, OGLE-2008-BLG-143, and OGLE-2008-BLG-210. With additional data covering caustic crossings, we detect finite-source effects for 6 events including OGLE-2006-BLG-215, OGLE-2006-BLG-238, OGLE-2006-BLG-450, OGLE-2008-BLG-143, OGLE-2008-BLG-210, and OGLE-2008-BLG-513. Among them, we are able to measure the Einstein ...

  14. REANALYSES OF ANOMALOUS GRAVITATIONAL MICROLENSING EVENTS IN THE OGLE-III EARLY WARNING SYSTEM DATABASE WITH COMBINED DATA

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, J.; Park, H.; Han, C. [Department of Physics, Institute for Astrophysics, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Gould, A.; Poleski, R. [Department of Astronomy, Ohio State University, 140 W. 18th Ave., Columbus, OH 43210 (United States); Udalski, A.; Szymański, M. K.; Pietrzyński, G.; Soszyński, I.; Ulaczyk, K.; Wyrzykowski, Ł. [Warsaw University Observatory, Al. Ujazdowskie 4, 00-478 Warszawa (Poland); Abe, F.; Fukunaga, D.; Itow, Y. [Solar-Terrestrial Environment Laboratory, Nagoya University, Nagoya, 464-8601 (Japan); Bennett, D. P. [Department of Physics, University of Notre Dame, 225 Nieuwland Science Hall, Notre Dame, IN 46556-5670 (United States); Bond, I. A. [Institute of Information and Mathematical Sciences, Massey University, Private Bag 102-904, North Shore Mail Centre, Auckland (New Zealand); Botzler, C. S.; Freeman, M. [Department of Physics, University of Auckland, Private Bag 92-019, Auckland 1001 (New Zealand); Fukui, A. [Okayama Astrophysical Observatory, National Astronomical Observatory of Japan, Asakuchi, Okayama 719-0232 (Japan); Koshimoto, N. [Department of Earth and Space Science, Osaka University, Osaka 560-0043 (Japan); Collaboration: (The OGLE Collaboration); (The MOA Collaboration); (The PLANET Collaboration); (The μFUN Collaboration); (The RoboNet Collaboration); and others

    2015-05-01

    We reanalyze microlensing events in the published list of anomalous events that were observed from the Optical Gravitational Lensing Experiment (OGLE) lensing survey conducted during the 2004–2008 period. In order to check the existence of possible degenerate solutions and extract extra information, we conduct analyses based on combined data from other survey and follow-up observation and consider higher-order effects. Among the analyzed events, we present analyses of eight events for which either new solutions are identified or additional information is obtained. We find that the previous binary-source interpretations of five events are better interpreted by binary-lens models. These events include OGLE-2006-BLG-238, OGLE-2007-BLG-159, OGLE-2007-BLG-491, OGLE-2008-BLG-143, and OGLE-2008-BLG-210. With additional data covering caustic crossings, we detect finite-source effects for six events including OGLE-2006-BLG-215, OGLE-2006-BLG-238, OGLE-2006-BLG-450, OGLE-2008-BLG-143, OGLE-2008-BLG-210, and OGLE-2008-BLG-513. Among them, we are able to measure the Einstein radii of three events for which multi-band data are available. These events are OGLE-2006-BLG-238, OGLE-2008-BLG-210, and OGLE-2008-BLG-513. For OGLE-2008-BLG-143, we detect higher-order effects induced by the changes of the observer’s position caused by the orbital motion of the Earth around the Sun. In addition, we present degenerate solutions resulting from the known close/wide or ecliptic degeneracy. Finally, we note that the masses of the binary companions of the lenses of OGLE-2006-BLG-450 and OGLE-2008-BLG-210 are in the brown-dwarf regime.

  15. Genome-Wide Analyses Suggest Mechanisms Involving Early B-Cell Development in Canine IgA Deficiency

    Science.gov (United States)

    Frankowiack, Marcel; Kierczak, Marcin; Bergvall, Kerstin; Axelsson, Erik; Tintle, Linda; Marti, Eliane; Roosje, Petra; Leeb, Tosso; Hedhammar, Åke; Hammarström, Lennart; Lindblad-Toh, Kerstin

    2015-01-01

    Immunoglobulin A deficiency (IgAD) is the most common primary immune deficiency disorder in both humans and dogs, characterized by recurrent mucosal tract infections and a predisposition for allergic and other immune mediated diseases. In several dog breeds, low IgA levels have been observed at a high frequency and with a clinical resemblance to human IgAD. In this study, we used genome-wide association studies (GWAS) to identify genomic regions associated with low IgA levels in dogs as a comparative model for human IgAD. We used a novel percentile groups-approach to establish breed-specific cut-offs and to perform analyses in a close to continuous manner. GWAS performed in four breeds prone to low IgA levels (German shepherd, Golden retriever, Labrador retriever and Shar-Pei) identified 35 genomic loci suggestively associated (p IgA levels. In German shepherd, three genomic regions (candidate genes include KIRREL3 and SERPINA9) were genome-wide significantly associated (p IgA levels. A ~20kb long haplotype on CFA28, significantly associated (p = 0.0005) to IgA levels in Shar-Pei, was positioned within the first intron of the gene SLIT1. Both KIRREL3 and SLIT1 are highly expressed in the central nervous system and in bone marrow and are potentially important during B-cell development. SERPINA9 expression is restricted to B-cells and peaks at the time-point when B-cells proliferate into antibody-producing plasma cells. The suggestively associated regions were enriched for genes in Gene Ontology gene sets involving inflammation and early immune cell development. PMID:26225558

  16. The PI3K/Akt pathway is involved in early infection of some exogenous avian leukosis viruses.

    Science.gov (United States)

    Feng, Shao-zhen; Cao, Wei-sheng; Liao, Ming

    2011-07-01

    Avian leukosis virus (ALV) is an enveloped and oncogenic retrovirus. Avian leukosis caused by the members of ALV subgroups A, B and J has become one of the major problems challenging the poultry industry in China. However, the cellular factors such as signal transduction pathways involved in ALV infection are not well defined. In this study, our data demonstrated that ALV-J strain NX0101 infection in primary chicken embryo fibroblasts or DF-1 cells was correlated with the activity and phosphorylation of Akt. Akt activation was initiated at a very early stage of infection independently of NX0101 replication. The specific phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 or wortmannin could suppress Akt phosphorylation, indicating that NX0101-induced Akt phosphorylation is PI3K-dependent. ALV-A strain GD08 or ALV-B strain CD08 infection also demonstrated a similar profile of PI3K/Akt activation. Treatment of DF-1 cells with the drug 5-(N, N-hexamethylene) amiloride that inhibits the activity of chicken Na(+)/H(+) exchanger type 1 significantly reduced Akt activation induced by NX0101, but not by GD08 and CD08. Akt activation triggered by GD08 or CD08 was abolished by clathrin-mediated endocytosis inhibitor chlorpromazine. Receptor-mediated endocytosis inhibitor dansylcadaverine had a negligible effect on all ALV-induced Akt phosphorylation. Moreover, viral replication of ALV was suppressed by LY294002 in a dose-dependent manner, which was due to the inhibition of virus infection by LY294002. These data suggest that the activation of the PI3K/Akt signalling pathway by exogenous ALV infection plays an important role in viral entry, yet the precise mechanism remains under further investigation.

  17. Impact of sirolimus-eluting stent fractures without early cardiac events on long-term clinical outcomes: A multislice computed tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Tsuyoshi [Toyohashi Heart Center, Oyama-cho, Toyohashi (Japan); Nagoya City University Graduate School of Medical Sciences, Department of Cardio-Renal Medicine and Hypertension, Nagoya (Japan); Kimura, Masashi; Ehara, Mariko; Terashima, Mitsuyasu; Nasu, Kenya; Kinoshita, Yoshihisa; Habara, Maoto; Tsuchikane, Etsuo; Suzuki, Takahiko [Toyohashi Heart Center, Oyama-cho, Toyohashi (Japan)

    2014-05-15

    This study sought to evaluate the impact of sirolimus-eluting stent (SES) fractures on long-term clinical outcomes using multislice computed tomography (MSCT). In this study, 528 patients undergoing 6- to 18-month follow-up 64-slice MSCT after SES implantation without early clinical events were followed clinically (the median follow-up interval was 4.6 years). A CT-detected stent fracture was defined as a complete gap with Hounsfield units (HU) <300 at the site of separation. The major adverse cardiac events (MACEs), including cardiac death, stent thrombosis, and target lesion revascularisation, were compared according to the presence of stent fracture. Stent fractures were observed in 39 patients (7.4 %). MACEs were more common in patients with CT-detected stent fractures than in those without (46 % vs. 7 %, p < 0.01). Univariate Cox regression analysis indicated a significant relationship between MACE and stent fracture [hazard ratio (HR) 7.65; p < 0.01], age (HR 1.03; p = 0.04), stent length (HR 1.03; p < 0.01), diabetes mellitus (HR 1.77; p = 0.04), and chronic total occlusion (HR 2.54; p = 0.01). In the multivariate model, stent fracture (HR 5.36; p < 0.01) and age (HR 1.03; p = 0.04) remained significant predictors of MACE. An SES fracture detected by MSCT without early clinical events was associated with long-term clinical adverse events. (orig.)

  18. Environmental perturbations at the early Eocene ETM2, H2, and I1 events as inferred by Tethyan calcareous plankton (Terche section, northeastern Italy)

    Science.gov (United States)

    D'Onofrio, Roberta; Luciani, Valeria; Fornaciari, Eliana; Giusberti, Luca; Boscolo Galazzo, Flavia; Dallanave, Edoardo; Westerhold, Thomas; Sprovieri, Mario; Telch, Sonia

    2016-09-01

    Several early Eocene hyperthermals have been recently investigated and characterized in terms of temperature anomalies and oceanographic changes. The effects of these climatic perturbations on biotic communities are much less constrained. Here we present new records from the Terche section (northeastern Italy) that, for the first time, integrates data on planktic foraminifera and calcareous nannofossils across three post-Paleocene-Eocene Thermal Maximum negative carbon isotope excursions (CIEs). The biomagnetostratigraphic framework generated at Terche allows us to confidently relate such CIEs to the Eocene Thermal Maximum 2 (ETM2), H2, and I1 events. Each of these events coincides with lithological anomalies characterized by significantly lower calcium carbonate content (marly units, MUs). We interpret these MUs as mainly linked to an effect of increased terrigenous dilution, as dissolution proxies do not display significant variations. Calcareous plankton assemblages change significantly across these events and radiolarians increase. Observed changes suggest that transient warming and environmental perturbations, though more intense during ETM2, occurred during each of the three investigated perturbations. Variations among calcareous plankton suggest increase in surface-water eutrophication with respect to the pre-event conditions, coupled with a weakening of the upper water-column thermal stratification. Higher nutrient discharge was related to intensification of the hydrological cycle as a consequence of the warmer climate. These conditions persisted during the early CIE recovery, implying slower recovery rates for the environment and biota than for the carbon cycle.

  19. The spectral absorption coefficient at 254 nm as a real-time early warning proxy for detecting faecal pollution events at alpine karst water resources.

    Science.gov (United States)

    Stadler, H; Klock, E; Skritek, P; Mach, R L; Zerobin, W; Farnleitner, A H

    2010-01-01

    Because spring water quality from alpine karst aquifers can change very rapidly during event situations, water abstraction management has to be performed in near real-time. Four summer events (2005-2008) at alpine karst springs were investigated in detail in order to evaluate the spectral absorption coefficient at 254 nm (SAC254) as a real-time early warning proxy for faecal pollution. For the investigation Low-Earth-Orbit (LEO) Satellite-based data communication between portable hydrometeorological measuring stations and an automated microbiological sampling device was used. The method for event triggered microbial sampling and analyzing was already established and described in a previous paper. Data analysis including on-line event characterisation (i.e. precipitation, discharge, turbidity, SAC254) and comprehensive E. coli determination (n>800) indicated that SAC254 is a useful early warning proxy. Irrespective of the studied event situations SAC254 always increased 3 to 6 hours earlier than the onset of faecal pollution, featuring different correlation phases. Furthermore, it seems also possible to use SAC254 as a real-time proxy parameter for estimating the extent of faecal pollution after establishing specific spring and event-type calibrations that take into consideration the variability of the occurrence and the transferability of faecal material It should be highlighted that diffuse faecal pollution from wildlife and live stock sources was responsible for spring water contamination at the investigated catchments. In this respect, the SAC254 can also provide useful information to support microbial source tracking efforts where different situations of infiltration have to be investigated.

  20. The spectral absorption coefficient at 254nm as a real-time early warning proxy for detecting faecal pollution events at alpine karst water resources

    Science.gov (United States)

    Stadler, H.; Klock, E.; Skritek, P.; Mach, R.L.; Zerobin, W.; Farnleitner, A.H.

    2011-01-01

    Because spring water quality from alpine karst aquifers can change very rapidly during event situations, water abstraction management has to be performed in near real-time. Four summer events (2005-2008) at alpine karst springs were investigated in detail in order to evaluate the spectral absorption coefficient at 254nm (SAC254) as a real-time early warning proxy for faecal pollution. For the investigation Low-Earth-Orbit (LEO) Satellite-based data communication between portable hydrometeorological measuring stations and an automated microbiological sampling device was used. The method for event triggered microbial sampling and analyzing was already established and described in a previous paper (Stadler et al., Wat. Sci. Technol. 58(4): 899-909, 2008). Data analysis including on-line event characterisation (i.e. precipitation, discharge, turbidity, SAC254) and comprehensive E. coli determination (n > 800) indicated that SAC254 is a useful early warning proxy. Irrespective of the studied event situations SAC254 always increased 3 to 6 hours earlier than the onset of faecal pollution, featuring different correlation phases. Furthermore, it seems also possible to use SAC254 as a real-time proxy parameter for estimating the extent of faecal pollution after establishing specific spring and event-type calibrations that take into consideration the variability of the occurrence and the transferability of faecal material It should be highlighted that diffuse faecal pollution from wildlife and live stock sources was responsible for spring water contamination at the investigated catchments. In this respect, the SAC254 can also provide useful information to support microbial source tracking efforts where different situations of infiltration have to be investigated. PMID:20962406

  1. The effects of parental reading socialization and early school involvement on children's academic performance: A panel study of primary school pupils in the Netherlands

    NARCIS (Netherlands)

    Kloosterman, J.G.; Notten, N.J.W.R.; Tolsma, J.; Kraaykamp, G.L.M.

    2011-01-01

    This study examines the extent to which parental reading socialization and early school involvement account for performance differences between low-status and high-status children in successive primary school grades. It investigates not only the direct effects of these parental practices on children

  2. The effects of parental reading socialization and early school involvement on children's academic performance: a panel study of primary school pupils in the Netherlands

    NARCIS (Netherlands)

    Kloostermann, R.; Notten, N.; Tolsma, J.; Kraaykamp, G.

    2011-01-01

    This study examines the extent to which parental reading socialization and early school involvement account for performance differences between low-status and high-status children in successive primary school grades. It investigates not only the direct effects of these parental practices on children

  3. The effects of parental reading socialization and early school involvement on children's academicperformance : a panelstudy of primary school pupils in the Netherlands.

    NARCIS (Netherlands)

    Notten, N.; Tolsma, J.; Kraaykamp, G.; Kloosterman, R.

    2010-01-01

    This study examines the extent to which parental reading socialization and early school involvement account for performance differences between low-status and high-status children in successive primary school grades. It investigates not only the direct effects of these parental practices on children

  4. The effects of parental reading socialization and early school involvement on children's academicperformance : a panelstudy of primary school pupils in the Netherlands.

    NARCIS (Netherlands)

    Notten, N.; Tolsma, J.; Kraaykamp, G.; Kloosterman, R.

    2010-01-01

    This study examines the extent to which parental reading socialization and early school involvement account for performance differences between low-status and high-status children in successive primary school grades. It investigates not only the direct effects of these parental practices on

  5. The effects of parental reading socialization and early school involvement on children's academic performance: a panel study of primary school pupils in the Netherlands

    NARCIS (Netherlands)

    Kloostermann, R.; Notten, N.; Tolsma, J.; Kraaykamp, G.

    2011-01-01

    This study examines the extent to which parental reading socialization and early school involvement account for performance differences between low-status and high-status children in successive primary school grades. It investigates not only the direct effects of these parental practices on

  6. The effects of parental reading socialization and early school involvement on children's academic performance: A panel study of primary school pupils in the Netherlands

    NARCIS (Netherlands)

    Kloosterman, J.G.; Notten, N.J.W.R.; Tolsma, J.; Kraaykamp, G.L.M.

    2011-01-01

    This study examines the extent to which parental reading socialization and early school involvement account for performance differences between low-status and high-status children in successive primary school grades. It investigates not only the direct effects of these parental practices on

  7. An investigation of concepts and words used by Turkish children and teenagers to define their perceptions regarding events involving emotional situations.

    Science.gov (United States)

    Ozabaci, Nilüfer

    2011-06-01

    The present study aimed to determine the concepts and words children and teenagers use to define their perceptions of events that involve emotions. It attempted to identify words that children and teenagers use to express emotions and the differences between children and teenagers in this regard. The study focused on 214 children and adolescents, including 124 students from four primary schools in Eskisehir, Turkey (59 girls and 65 boys) and 90 students from one secondary school and two high schools (39 girls and 51 boys). The students were given a questionnaire that asked 10 questions focusing on three emotional categories (happiness, sadness and fear), two types of self-descriptive adjectives (positive and negative) and two neutral categories (semantically related and semantically unrelated). The questionnaire was developed from a form used by Doost et al. (1999). We concluded that the positive and negative expressions used by both children and teenagers were examined regardless of frequency of use, and the constituents, which were basically detected, were gathered under definite titles.

  8. 酿酒酵母减数分裂的事件和特异性基因%Meiosis Events and Specific Genes Involved in Saccharomyces cerevisiae

    Institute of Scientific and Technical Information of China (English)

    李丽

    2006-01-01

    Meiosis is the most important reproduce and favoured by organisms. The key events of meiosis identified are pairing, synapsis, genetic recombination, segregation. In this article, the specific genes of meiosis and pathways are described in these events in Saccharomyces cerevisiae. Two pathways have been identified in homolog pairing and Dmc1,Hop2, Rad51 and Mnd1 have function in pairing. In synapsis Red1, Hop1 and Zip1 are the components of synaptonemal complex. Hop2 is required for synapsis. Genetic recombination is the most important event of meiosis and provides genetic diversity for organisms to adapt the environment change. The meiosis specific genes involved in gene recombination are Spo11, Rad52 epistasis group, Dmc1, Mnd1, Msh4, Msh5, Mek1, Red1, and Hop1. Rec8,Spo13 and Sgo1 are involved in segregation.%减数分裂是生物体重要的有性生殖方式,它提供来自母本和父本的基因信息,产生具有生物多样性的子代,使其能够适应环境的变化而不断进化.本文简述了现已阐明的酿酒酵母减数分裂的重要事件如同源染色体配对、联会、基因重组、染色体分裂和特异性基因.在同源染色体配对的过程中现已发现了2条途径,一条由Rad51独立完成,另一条有Dmc1、Hop2、Rad51和Mnd1参与,同时Rad51也可能参与.Red1、Hop1和Zip1是联会复合体的组成成分,而联会也要求其他减数分裂的特异性基因如Hop2的参与.基因重组是减数分裂中最重要的事件,它为子代提供了新的遗传信息,是生物多样性的基础之一.Spo11、Rad52组、Dmc1、Mnd1、Msh4、Msh5、Mek1、Red1和Hop1参与了基因重组.Spo11是发现和研究得最早的启动基因重组的基因之一;Rec8、Spo13和Sgo1参与了染色体分裂的过程.

  9. High-resolution carbon isotope records of the Toarcian Oceanic Anoxic Event (Early Jurassic) from North America and implications for the global drivers of the Toarcian carbon cycle

    Science.gov (United States)

    Them, T. R.; Gill, B. C.; Caruthers, A. H.; Gröcke, D. R.; Tulsky, E. T.; Martindale, R. C.; Poulton, T. P.; Smith, P. L.

    2017-02-01

    The Mesozoic Era experienced several instances of abrupt environmental change that are associated with instabilities in the climate, reorganizations of the global carbon cycle, and elevated extinction rates. Often during these perturbations, oxygen-deficient conditions developed in the oceans resulting in the widespread deposition of organic-rich sediments - these events are referred to as Oceanic Anoxic Events or OAEs. Such events have been linked to massive injections of greenhouse gases into the ocean-atmosphere system by transient episodes of voluminous volcanism and the destabilization of methane clathrates within marine environments. Nevertheless, uncertainty surrounds the specific environmental drivers and feedbacks that occurred during the OAEs that caused perturbations in the carbon cycle; this is particularly true of the Early Jurassic Toarcian OAE (∼183.1 Ma). Here, we present biostratigraphically constrained carbon isotope data from western North America (Alberta and British Columbia, Canada) to better assess the global extent of the carbon cycle perturbations. We identify the large negative carbon isotope excursion associated with the OAE along with high-frequency oscillations and steps within the onset of this excursion. We propose that these high-frequency carbon isotope excursions reflect changes to the global carbon cycle and also that they are related to the production and release of greenhouse gases from terrestrial environments on astronomical timescales. Furthermore, increased terrestrial methanogenesis should be considered an important climatic feedback during Ocean Anoxic Events and other similar events in Earth history after the proliferation of land plants.

  10. Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort

    DEFF Research Database (Denmark)

    Urowitz, M B; Gladman, D D; Anderson, N M

    2016-01-01

    15 months of SLE diagnosis. MIs were reported and attributed on a specialised vascular event form. MIs were confirmed by one or more of the following: abnormal ECG, typical or atypical symptoms with ECG abnormalities and elevated enzymes (≥2 times upper limit of normal), or abnormal stress test...

  11. Orbital control on carbon cycle alterations and hyperthermal events in a cooling world: the late Early to Mid Eocene record at Possagno (southern Alps, Italy)

    Science.gov (United States)

    Galeotti, Simone; Sprovieri, Mario; Moretti, Matteo; Rio, Domenico; Fornaciari, Eliana; Giusberti, Luca; Agnini, Claudia; Backman, Jan; Lanci, Luca; Luciani, Valeria

    2013-04-01

    The late Early Eocene to Middle Eocene ~50-45 Million years ago (Ma) time interval in the middle bathyal, pelagic/hemipelagic succession of the Western Tethys Possagno section (southern Alps, Veneto), contains several episodes of negative carbon isotope excursions (CIEs) and concomitant dissolution of carbonates. These episodes are superimposed on a long term global climate cooling that started at about 51 Ma following the Early Eocene Climatic Optimum (EECO). Spectral analysis indicates that CIEs and dissolution events are paced by orbital forcing, confirming the global significance of previous finding on the same interval from Western and Southern Atlantic and Equatorial Pacific sites. The frequency and magnitude of CIEs through time is controlled by long-term modulations of orbital parameters, including long eccentricity (400 kyr) and a 1.2 million year modulation. Highest frequency of events - at the orbital scale - is observed across the EECO, which provides an observational basis to validate theoretical models predicting a threshold effect resulting from orbital forcing superimposed on gradually changing mean global boundary conditions. The observation of the 1.2 million year beat (long-term modulation of obliquity) together with previously published observation of enhanced obliquity (41 kyr) forcing across major CIEs and dissolution intervals indicates that high latitude feedbacks to orbital forcing played a fundamental role in the emplacement of the hyperthermals. The observed orbital forcing signature closely match that of early Eocene hyperthermals, suggesting similar driving processes.

  12. Effects of adverse early-life events on aggression and anti-social behaviours in animals and humans.

    Science.gov (United States)

    Haller, J; Harold, G; Sandi, C; Neumann, I D

    2014-10-01

    We review the impact of early adversities on the development of violence and antisocial behaviour in humans, and present three aetiological animal models of escalated rodent aggression, each disentangling the consequences of one particular adverse early-life factor. A review of the human data, as well as those obtained with the animal models of repeated maternal separation, post-weaning social isolation and peripubertal stress, clearly shows that adverse developmental conditions strongly affect aggressive behaviour displayed in adulthood, the emotional responses to social challenges and the neuronal mechanisms activated by conflict. Although similarities between models are evident, important differences were also noted, demonstrating that the behavioural, emotional and neuronal consequences of early adversities are to a large extent dependent on aetiological factors. These findings support recent theories on human aggression, which suggest that particular developmental trajectories lead to specific forms of aggressive behaviour and brain dysfunctions. However, dissecting the roles of particular aetiological factors in humans is difficult because these occur in various combinations; in addition, the neuroscientific tools employed in humans still lack the depth of analysis of those used in animal research. We suggest that the analytical approach of the rodent models presented here may be successfully used to complement human findings and to develop integrative models of the complex relationship between early adversity, brain development and aggressive behaviour.

  13. Early-Life events, including mode of delivery and type of feeding, siblings and gender, shape the developing gut microbiota

    NARCIS (Netherlands)

    Martin, Rocio; Makino, Hiroshi; Yavuz, Aysun Cetinyurek; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

    2016-01-01

    Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with

  14. Early-Life events, including mode of delivery and type of feeding, siblings and gender, shape the developing gut microbiota

    NARCIS (Netherlands)

    Martin, Rocio; Makino, Hiroshi; Yavuz, Aysun Cetinyurek; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

    2016-01-01

    Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with

  15. Math Achievement in Early Adolescence: The Role of Parental Involvement, Teachers' Behavior, and Students' Motivational Beliefs about Math

    Science.gov (United States)

    Levpuscek, Melita Puklek; Zupancic, Maja

    2009-01-01

    Contributions of parental involvement in educational pursuits as well as math teachers' classroom behavior to students' motivation and performance in math were investigated. By the end of the first school term, 365 Slovene eighth graders reported on their parents' academic involvement (pressure, support, and help) and their math teachers' behavior…

  16. Prevalence and predictors of early cardiovascular events after kidney transplantation: evaluation of pre-transplant cardiovascular work-up.

    Directory of Open Access Journals (Sweden)

    Marianne Delville

    Full Text Available Cardiovascular disease is the leading cause of mortality after renal transplantation. The purpose of this study was to analyze cardiovascular risk factors at transplantation, occurrence of cardiovascular events in the first year after transplantation and evaluate pre-transplant work-up.In total, 244 renal transplant recipients older than 50 years were included. The results of pre-transplant work-up, including clinical evaluation, electrocardiogram, echocardiography, myocardial perfusion testing and coronary angiography were analyzed.Patients had multiple risk factors at inclusion on renal transplantation waiting list as high blood pressure (94.7%, dyslipidemia (81.1%, smoking (45.3%, diabetes (23.6%, past history of cardiovascular disease (21.3% and obesity (12.7%. Following transplantation, 15.5% (n = 38 of patients experienced a cardiovascular event, including 2.8% (n = 7 acute coronary syndrome, 5.8% (n = 14 isolated increase in troponin level and 5.3% (n = 13 new onset atrial fibrillation. The pre-transplant parameters associated with a cardiovascular event were a past medical history of cardiovascular disease (HR = 2.06 [1.06-4.03], p = 0.03, echocardiographic left ventricular hypertrophy (HR = 2.04 [1.04-3.98], p = 0.037 and abnormal myocardial perfusion testing (HR = 2.25 [1.09 -5.96], p = 0.03. Pre-transplantation evaluation allowed the diagnosis of unknown coronary artery lesions in 8.9% of patients.

  17. Reflections on meta-analyses involving trials stopped early for benefit: is there a problem and if so, what is it?

    Science.gov (United States)

    Bassler, Dirk; Montori, Victor M; Briel, Matthias; Glasziou, Paul; Walter, Stephen D; Ramsay, Tim; Guyatt, Gordon

    2013-04-01

    We review controversies associated with randomized controlled trials (RCTs) stopped early for apparent benefit (truncated RCTs or tRCTs) and present our groups' perspective. Long-established theory, simulations and recent empirical evidence demonstrate that tRCTs will on average overestimate treatment effects, and this overestimation may be large, particularly when tRCTs have small number of events. Theoretical considerations and simulations demonstrate that on average, meta-analyses of RCTs with appropriate stopping rules will lead to only trivial overestimation of treatment effects. However, tRCTs will disproportionally contribute to meta-analytic estimates when tRCTs occur early in the sequence of trials with few subsequent studies, publication of nontruncated RCTs is delayed, there is publication bias, or tRCTs result in a 'freezing' effect in which 'correcting' trials are never undertaken. To avoid applying overestimates of effect to clinical decision-making, clinicians should view the results of individual tRCTs with small sample sizes and small number of events with skepticism. Pooled effects from meta-analyses including tRCTs are likely to overestimate effect when there is a substantial difference in effect estimates between the tRCTs and the nontruncated RCTs, and in which the tRCTs have a substantial weight in the meta-analysis despite themselves having a relatively small number of events. Such circumstances call for sensitivity analyses omitting tRCTs.

  18. Combined oxygen- and carbon-isotope records through the Early Jurassic: multiple global events and two modes of carbon-cycle/temperature coupling

    DEFF Research Database (Denmark)

    Hesselbo, Stephen P.; Korte, Christoph

    2010-01-01

    -isotope signature), but also some significant contrasts (oxygen-isotope based paleotemperatures which provide no evidence for warming). Significant contrast in oxygen- and carbon-isotope co-variation also occurs on a long timescale. There appear to be two modes in the co-variation of carbon and oxygen isotopes...... environmental changes were global has been strongly debated. Nevertheless, partly as a result of the international effort to define Global Stratotype Sections and Points (GSSPs), much more is now being discovered about environmental changes taking place at and around the other Jurassic Age (Stage) boundaries...... that both long-term and short-term carbon-isotope shifts from the UK Early Jurassic represent global changes in carbon cycle balances. The Sinemurian-Pliensbachian boundary event is an event of global significance and shows several similarities to the Toarcian OAE (relative sea-level change, carbon...

  19. Gonosomal mosaicism in myotonic dystrophy patients: Involvement of mitotic events in (CTG)[sub n] repeat variation and selection against extreme expansion in sperm

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, G.; Coerwinkel, M.; Wieringa, B.; Nillesen, W.; Smeets, H.; Brunner, H.; Wieringa, B. (Univ. of Nijmegen (Netherlands)); Willems, P.; Vits, L. (Univ. of Antwerp (Belgium)); Hoeweler, C. (Univ. of Maastricht (Netherlands))

    1994-04-01

    Myotonic dystrophy (DM) is caused by abnormal expansion of a polymorphic (CTG)[sub n] repeat, located in the DM protein kinase gene. The authors determined the (CTG)[sub n] repeat lengths in a broad range of tissue DNAs from patients with mild, classical, or congenital manifestation of DM. Differences in the repeat length were seen in somatic tissues from single DM individuals and twins. Repeats appeared to expand to a similar extent in tissues originating from the same embryonal origin. In most male patients carrying intermediate- or small-sized expansions in blood, the repeat lengths covered a markedly wider range in sperm. In contrast, male patients with large allele expansions in blood (>700 CTGs) had similar or smaller repeats in sperm, when detectable. Sperm alleles with >1,000 CTGs were not seen. The authors conclude that DM patients can be considered gonosomal mosaics, i.e., combined somatic and germ-line tissue mosaics. Most remarkably, they observed multiple cases where the length distributions of intermediate- or small-sized alleles in fathers' sperm were significantly different from that in their offspring's blood. The combined findings indicate that intergenerational length changes in the unstable CTG repeat are most likely to occur during early embryonic mitotic divisions in both somatic and germ-line tissue formation. Both the initial CTG length, the overall number of cell divisions involved in tissue formation, and perhaps a specific selection process in spermatogenesis may influence the dynamics of this process. A model explaining mitotic instability and sex-dependent segregation phenomena in DM manifestation is discussed. 59 refs., 5 figs.

  20. Residue-specific Fluorescent Probes of α-Synuclein: Detection of Early Events at the N- and C-termini during Fibril Assembly†

    Science.gov (United States)

    Yap, Thai Leong; Pfefferkorn, Candace M.; Lee, Jennifer C.

    2011-01-01

    In the Parkinson’s disease-associated state, α-synuclein (α-syn) undergoes large conformational changes forming ordered, β-sheet containing fibrils. To unravel the role of specific residues during the fibril assembly process, we prepared single-Cys mutants in the disordered (G7C and Y136C) and proximal (V26C and L100C) fibril core sites and derivatized them with environment sensitive dansyl (Dns) fluorophores. Dns fluorescence exhibits residue-specificity in spectroscopic properties as well as kinetic behavior; early kinetic events were revealed by probes located at positions 7 and 136 compared to those positioned at 26 and 100. PMID:21338068

  1. Most significant genome regions involved in the control of earliness traits in bread wheat, as revealed by QTL meta-analysis.

    Science.gov (United States)

    Hanocq, E; Laperche, A; Jaminon, O; Lainé, A-L; Le Gouis, J

    2007-02-01

    Earliness is one of the most important adaptation traits in plant breeding. Our purpose was to identify the genome regions of bread wheat involved in the control of earliness and its three components: photoperiod sensitivity (PS), vernalization requirement (VR) and intrinsic earliness (IE). A QTL meta-analysis was carried out to examine the replicability of QTL across 13 independent studies and to propose meta-QTL (MQTL). Initial QTL were projected on a recent consensus map (2004). Quality criteria were proposed to assess the reliability of this projection. These criteria were based on the distances between markers in the QTL regions. Chromosomes of groups 2 and 5 had a greater incidence on earliness control as they carry the known, major genes Ppd and Vrn. Other chromosome regions played an intermediate role in earliness control: 4A [heading date (HD) Meta-QTL], 4B (HD MQTL), 2B (VR MQTL) and 5B (IE MQTL). Markers at this four MQTL should prove helpful in marker-assisted selection, to better control earliness.

  2. Early Solar System Alkali Fractionation Events Recorded by K-Ca Isotopes in the Yamato-74442 LL-Chondritic Breccia

    Science.gov (United States)

    Tatsunori, T.; Misawa, K.; Okano, O.; Shih, C.-Y.; Nyquist, L. E.; Simon, J. I.; Tappa, M. J.; Yoneda, S.

    2015-01-01

    Radiogenic ingrowth of Ca-40 due to decay of K-40 occurred early in the solar system history causing the Ca-40 abundance to vary within different early-former reservoirs. Marshall and DePaolo ] demonstrated that the K-40/Ca-40 decay system could be a useful radiogenic tracer for studies of terrestrial rocks. Shih et al. [3,4] determined 40K/40Ca ages of lunar granitic rock fragments and discussed the chemical characteristics of their source materials. Recently, Yokoyama et al. [5] showed the application of the K-40/Ca-40 chronometer for high K/Ca materials in ordinary chondrites (OCs). High-precision calcium isotopic data are needed to constrain mixing processes among early solar system materials and the time of planetesimal formation. To better constrain the solar system calcium isotopic compositions among astromaterials, we have determined the calcium isotopic compositions of OCs and an angrite. We further estimated a source K/Ca ratio for alkali-rich fragments in a chondritic breccia using the estimated solar system initial Ca-40/Ca-44.

  3. The effect of rheumatoid arthritis-associated autoantibodies on the incidence of cardiovascular events in a large inception cohort of early inflammatory arthritis.

    Science.gov (United States)

    Barra, Lillian J; Pope, Janet E; Hitchon, Carol; Boire, Gilles; Schieir, Orit; Lin, Daming; Thorne, Carter J; Tin, Diane; Keystone, Edward C; Haraoui, Boulos; Jamal, Shahin; Bykerk, Vivian P

    2017-05-01

    . RA is associated with an increased risk of cardiovascular events (CVEs). The objective was to estimate independent effects of RA autoantibodies on the incident CVEs in patients with early RA. Patients were enrolled in the Canadian Early Inflammatory Arthritis Cohort, a prospective multicentre inception cohort. Incident CVEs, including acute coronary syndromes and cerebrovascular events, were self-reported by the patient and partially validated by medical chart review. Seropositive status was defined as either RF or ACPA positive. Multivariable Cox proportional hazards survival analysis was used to estimate the effects of seropositive status on incident CVEs, controlling for RA clinical variables and traditional cardiovascular risk factors. . A total of 2626 patients were included: the mean symptom duration at diagnosis was 6.3 months ( s . d . 4.6), the mean age was 53 years ( s . d . 15), 72% were female and 86% met classification criteria for RA. Forty-six incident CVEs occurred over 6483 person-years [incidence rate 7.1/1000 person-years (95% confidence interval 5.3, 9.4)]. The CVE rate did not differ in seropositive vs seronegative subjects and seropositivity was not associated with incident CVEs in multivariable Cox regression models. Baseline covariates independently associated with incident CVEs were older age, a history of hypertension and a longer duration of RA symptoms prior to diagnosis. The rate of CVEs early in the course of inflammatory arthritis was low; however, delays in the diagnosis of arthritis increased the rate of CVEs. Hypertension was the strongest independent risk factor for CVEs. Results support early aggressive management of RA disease activity and co-morbidities to prevent severe complications.

  4. Inflammatory cytokines imbalance in the very early phase of acute coronary syndrome: correlations with angiographic findings and in-hospital events.

    Science.gov (United States)

    Brunetti, Natale Daniele; Munno, Irene; Pellegrino, Pier Luigi; Ruggero, Vincenzo; Correale, Michele; De Gennaro, Luisa; Cuculo, Andrea; Campanale, Erasmo Giulio; Di Biase, Matteo

    2011-02-01

    The aim of this study is to investigate the release of some inflammatory cytokines (Cks) during the very early phase (first 24 h) of acute coronary syndrome (ACS). Twenty-six consecutive subjects admitted to coronary care unit with ACS underwent serial blood sampling in order to evaluate concentrations of interleukin (IL)-2, IL-10, IL-18, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Blood samples were taken within 6 h after onset of chest pain (T₀), at 12 h (T₁), and at 24 h (T₂). Patients were thus divided into four groups comparing pro-inflammatory Ck release (IL-2, TNF-α, and IFN-γ) and anti-inflammatory activity (IL-10). Clinical features, risk factors, incidence of adverse events, and coronary angiography findings were compared with Ck activation. Ck levels were significantly increased if compared with baseline. Subjects with marked inflammatory response showed a higher incidence of left anterior descending coronary disease (IL-2, p < 0.001; TNF-α and IFN-γ, p < 0.05) and more often incurred early complications (IL-2, p < 0.05; IFN-γ, p < 0.001). A correlation was detectable between IL-18 levels and myocardial enzyme release (creatine kinase, r = 0.47; lactate dehydrogenase, r = 0.54; troponin I, r = 0.58; p < 0.05). TNF-α levels were associated with a worse prognosis at follow-up (Log rank, p < 0.05). A Ck activation characterizes the early phase of ACS. Early inflammatory reaction seems to correlate with coronary disease and adverse events.

  5. Early events in xenograft development from the human embryonic stem cell line HS181--resemblance with an initial multiple epiblast formation.

    Science.gov (United States)

    Gertow, Karin; Cedervall, Jessica; Jamil, Seema; Ali, Rouknuddin; Imreh, Marta P; Gulyas, Miklos; Sandstedt, Bengt; Ahrlund-Richter, Lars

    2011-01-01

    Xenografting is widely used for assessing in vivo pluripotency of human stem cell populations. Here, we report on early to late events in the development of mature experimental teratoma from a well-characterized human embryonic stem cell (HESC) line, HS181. The results show an embryonic process, increasingly chaotic. Active proliferation of the stem cell derived cellular progeny was detected already at day 5, and characterized by the appearance of multiple sites of engraftment, with structures of single or pseudostratified columnar epithelium surrounding small cavities. The striking histological resemblance to developing embryonic ectoderm, and the formation of epiblast-like structures was supported by the expression of the markers OCT4, NANOG, SSEA-4 and KLF4, but a lack of REX1. The early neural marker NESTIN was uniformly expressed, while markers linked to gastrulation, such as BMP-4, NODAL or BRACHYURY were not detected. Thus, observations on day 5 indicated differentiation comparable to the most early transient cell populations in human post implantation development. Confirming and expanding on previous findings from HS181 xenografts, these early events were followed by an increasingly chaotic development, incorporated in the formation of a benign teratoma with complex embryonic components. In the mature HS181 teratomas not all types of organs/tissues were detected, indicating a restricted differentiation, and a lack of adequate spatial developmental cues during the further teratoma formation. Uniquely, a kinetic alignment of rare complex structures was made to human embryos at diagnosed gestation stages, showing minor kinetic deviations between HS181 teratoma and the human counterpart.

  6. A Randomised Controlled Trial to Determine the Effectiveness of an Early Psychological Intervention with Children Involved in Road Traffic Accidents

    Science.gov (United States)

    Stallard, Paul; Velleman, Richard; Salter, Emma; Howse, Imogen; Yule, William; Taylor, Gordon

    2006-01-01

    Objective: To determine whether an early intervention using a psychological debriefing format is effective in preventing psychological distress in child road traffic accident survivors. Design: Randomised controlled trial. Setting: Accident and Emergency Department, Royal United Hospital, Bath. Subjects: 158 children aged 7-18. Follow-up…

  7. Parents' Reports of Their Involvement in an Iranian Parent-Based Early Intervention Programme for Children with ASD

    Science.gov (United States)

    Samadi, Sayyed Ali; Mahmoodizadeh, Ameneh

    2013-01-01

    Based on the findings of several preliminary studies on support and services for children with autism spectrum disorder (ASD) and their parents in Iran, an early intervention programme called Omid was established. This programme is based on the social model of disability. To promote the Omid resource kit, which is a component of the "Omid…

  8. Can Service Learning Reinforce Social and Cultural Bias? Exploring a Popular Model of Family Involvement for Early Childhood Teacher Candidates

    Science.gov (United States)

    Dunn-Kenney, Maylan

    2010-01-01

    Service learning is often used in teacher education as a way to challenge social bias and provide teacher candidates with skills needed to work in partnership with diverse families. Although some literature suggests that service learning could reinforce cultural bias, there is little documentation. In a study of 21 early childhood teacher…

  9. HIV-1 infection of in vitro cultured human monocytes: early events and influence of anti HIV-1 antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Olofsson, S; Nielsen, Jens Ole;

    1994-01-01

    on this infection. Depending on the period of in vitro cultivation and the virus isolate used different patterns of susceptibility were detected. One week old monocyte/M phi s were highly susceptible to HIV-1 infection, in contrast to monocyte/M phi s cultured 4 weeks. The infection by virus isolated immediately...... to CD4 and that post binding events may be common to the infection of lymphocytes. Anti HIV-1 sera showed neutralizing activity against heterologous and even autologous escape virus. This finding, together with the observation that monocytes and M phi s are infected in vivo, suggests that protection...

  10. Knockin’ on pollen’s door: live cell imaging of early polarization events in germinating Arabidopsis pollen

    Directory of Open Access Journals (Sweden)

    Frank eVogler

    2015-04-01

    Full Text Available Pollen tubes are an excellent system for studying the cellular dynamics and complex signaling pathways that coordinate polarized tip growth. Although several signaling mechanisms acting in the tip-growing pollen tube have been described, our knowledge on the subcellular and molecular events during pollen germination and growth site selection at the pollen plasma membrane is rather scarce. To simultaneously track germinating pollen from up to 12 genetically different plants we developed an inexpensive and easy mounting technique, suitable for every standard microscope setup. We performed high magnification live-cell imaging during Arabidopsis pollen activation, germination, and the establishment of pollen tube tip growth by using fluorescent marker lines labeling either the pollen cytoplasm, vesicles, the actin cytoskeleton or the sperm cell nuclei and membranes. Our studies revealed distinctive vesicle and F-actin polarization during pollen activation and characteristic growth kinetics during pollen germination and pollen tube formation. Initially, the germinating Arabidopsis pollen tube grows slowly and forms a uniform roundish bulge, followed by a transition phase with vesicles heavily accumulating at the growth site before switching to rapid tip growth. Furthermore, we found the two sperm cells to be transported into the pollen tube after the phase of rapid tip growth has been initiated. The method presented here is suitable to quantitatively study subcellular events during Arabidopsis pollen germination and growth, and for the detailed analysis of pollen mutants with respect to pollen polarization, bulging, or growth site selection at the pollen plasma membrane.

  11. The Y. D. and climate abrupt events in the early and middle Holocene: Stalagmite oxygen isotope record from Maolan, Guizhou, China

    Institute of Scientific and Technical Information of China (English)

    QIN Jiaming; YUAN Daoxian; CHENG Hai; LIN Yushi; ZHANG Meiliang; WANG Fuxing; R. L. Edwards; WANG Hua; RAN Jingcheng

    2005-01-01

    The isotope records which range from 3.9 kaBP to 15.7 kaBP with an average resolution of 90 a have been obtained from 45 cm to 193.6 cm of the upper part of D4 stalagmite from Dongguo Cave in Libo, Guizhou, by using system TIMS U-series dating and carbon and oxygen stable isotope analyses.The study indicates that the last cold event, the YD (Younger Dryas) event, of the last glacial period was apparently shown in D4 record, which started from 12.80 kaBP and ended in 11.58 kaBP, with a great range of drop in temperature. The end of the last glacial period was consistent with the termination I in oceanic isotope records and was with time limit of 11.3 kaBP. The three most distinct cold events in the early and middle Holocene occurred respectively in 10.91 kaBP, 8.27 kaBP and 4.75 kaBP, with a range of drop in temperature reaching 2-5℃. The climate abrupt events in thousand and hundred years scale recorded in stalagmite δ18O can be compared to those in GISP2 ice cores from Greenland in their happening time and the range of their lasting time. The cold events in 8.27 kaBP and 4.75 kaBP can also be compared to CC3 stalagmite records in Ireland, which indicate that climate changes of short range in China monsoon areas, western Europe and polar regions, have the same driving factor. This has a global significance. In addition, the trend of record curves in some time- stages is apparently different, which reflects probably the difference between environment in monsoon climate areas and in polar regions.

  12. Ancient DNA from South-East Europe Reveals Different Events during Early and Middle Neolithic Influencing the European Genetic Heritage.

    Directory of Open Access Journals (Sweden)

    Montserrat Hervella

    Full Text Available The importance of the process of Neolithization for the genetic make-up of European populations has been hotly debated, with shifting hypotheses from a demic diffusion (DD to a cultural diffusion (CD model. In this regard, ancient DNA data from the Balkan Peninsula, which is an important source of information to assess the process of Neolithization in Europe, is however missing. In the present study we show genetic information on ancient populations of the South-East of Europe. We assessed mtDNA from ten sites from the current territory of Romania, spanning a time-period from the Early Neolithic to the Late Bronze Age. mtDNA data from Early Neolithic farmers of the Starčevo Criş culture in Romania (Cârcea, Gura Baciului and Negrileşti sites, confirm their genetic relationship with those of the LBK culture (Linienbandkeramik Kultur in Central Europe, and they show little genetic continuity with modern European populations. On the other hand, populations of the Middle-Late Neolithic (Boian, Zau and Gumelniţa cultures, supposedly a second wave of Neolithic migration from Anatolia, had a much stronger effect on the genetic heritage of the European populations. In contrast, we find a smaller contribution of Late Bronze Age migrations to the genetic composition of Europeans. Based on these findings, we propose that permeation of mtDNA lineages from a second wave of Middle-Late Neolithic migration from North-West Anatolia into the Balkan Peninsula and Central Europe represent an important contribution to the genetic shift between Early and Late Neolithic populations in Europe, and consequently to the genetic make-up of modern European populations.

  13. Commissioning with low-intensity beams helps prepare CMS for this year’s physics run. This event is one of the first low-intensity collisions recorded in the CMS detector, during the early hours of 23 April 2016

    CERN Multimedia

    AUTHOR|(CDS)2068005

    2016-01-01

    Commissioning with low-intensity beams helps prepare CMS for this year’s physics run. This event is one of the first low-intensity collisions recorded in the CMS detector, during the early hours of 23 April 2016

  14. Bridging the Faraoni and Selli oceanic anoxic events: late Hauterivian to early Aptian dysaerobic to anaerobic phases in the Tethys

    Directory of Open Access Journals (Sweden)

    K. B. Föllmi

    2012-01-01

    Full Text Available A detailed geochemical analysis was performed on the upper part of the Maiolica Formation in the Breggia (southern Switzerland and Capriolo sections (northern Italy. The analysed sediments consist of well-bedded, partly siliceous, pelagic carbonate, which lodges numerous thin, dark and organic-rich layers. Stable-isotope, phosphorus, organic-carbon and a suite of redox-sensitive trace-element contents (RSTE: Mo, U, Co, V and As were measured. The RSTE pattern and Corg:Ptot ratios indicate that most organic-rich layers were deposited under dysaerobic rather than anaerobic conditions and that latter conditions were likely restricted to short intervals in the latest Hauterivian, the early Barremian and the pre-Selli early Aptian.

    Correlations are both possible with organic-rich intervals in central Italy (the Gorgo a Cerbara section and the Boreal Lower Saxony Basin, as well as with the facies and drowning pattern in the Helvetic segment of the northern Tethyan carbonate platform. Our data and correlations suggest that the latest Hauterivian witnessed the progressive installation of dysaerobic conditions in the Tethys, which went along with the onset in sediment condensation, phosphogenesis and platform drowning on the northern Tethyan margin, and which culminated in the Faraoni anoxic episode. This episode is followed by further episodes of dysaerobic conditions in the Tethys and the Lower Saxony Basin, which became more frequent and progressively stronger in the late early Barremian. Platform drowning persisted and did not halt before the latest early Barremian. The late Barremian witnessed diminishing frequencies and intensities in dysaerobic conditions, which went along with the progressive installation of the Urgonian carbonate platform. Near the Barremian-Aptian boundary, the increasing density in dysaerobic episodes in the Tethyan and Lower Saxony Basins is paralleled by a change towards heterozoan carbonate

  15. Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors

    OpenAIRE

    Ivy, Autumn S.; Rex, Christopher S.; Chen, Yuncai; Dubé, Céline; Maras, Pamela M.; Grigoriadis, Dimitri E.; Christine M Gall; Lynch, Gary; Baram, Tallie Z.

    2010-01-01

    Chronic stress impairs learning and memory in humans and rodents and disrupts long-term potentiation (LTP) in animal models. These effects are associated with structural changes in hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible effects of chronic stress on adult rat hippocampus, we have previously found that the effects of early-life stress endure and worsen during adulthood, yet the mechanisms for these clinically important sequelae are poorly ...

  16. Involvement of reactive oxygen species during early stages of ectomycorrhiza establishment between Castanea sativa and Pisolithus tinctorius

    OpenAIRE

    Baptista, Paula; Martins, Anabela; Pais, M.S.; Tavares, Rui Manuel; Lino-Neto, Teresa

    2007-01-01

    Evidence for the participation of reactive oxygen species (ROS) and antioxidant systems in ectomycorrhizal(ECM) establishment is lacking. In this paper, we evaluated ROS production and the activities of superoxide dismutase (SOD) and catalase (CAT) during the early contact of the ECM fungus Pisolithus tinctorius with the roots of Castanea sativa (chestnut tree). Roots were placed in contact with P. tinctorius mycelia, and ROS production was evaluated by determining the level...

  17. Astaxanthin Alleviates Early Brain Injury Following Subarachnoid Hemorrhage in Rats: Possible Involvement of Akt/Bad Signaling

    Directory of Open Access Journals (Sweden)

    Xiang-Sheng Zhang

    2014-07-01

    Full Text Available Apoptosis has been proven to play a crucial role in early brain injury pathogenesis and to represent a target for the treatment of subarachnoid hemorrhage (SAH. Previously, we demonstrated that astaxanthin (ATX administration markedly reduced neuronal apoptosis in the early period after SAH. However, the underlying molecular mechanisms remain obscure. In the present study, we tried to investigate whether ATX administration is associated with the phosphatidylinositol 3-kinase-Akt (PI3K/Akt pathway, which can play an important role in the signaling of apoptosis. Our results showed that post-SAH treatment with ATX could cause a significant increase of phosphorylated Akt and Bad levels, along with a significant decrease of cleaved caspase-3 levels in the cortex after SAH. In addition to the reduced neuronal apoptosis, treatment with ATX could also significantly reduce secondary brain injury characterized by neurological dysfunction, cerebral edema and blood-brain barrier disruption. In contrast, the PI3K/Akt inhibitor, LY294002, could partially reverse the neuroprotection of ATX in the early period after SAH by downregulating ATX-induced activation of Akt/Bad and upregulating cleaved caspase-3 levels. These results provided the evidence that ATX could attenuate apoptosis in a rat SAH model, potentially, in part, through modulating the Akt/Bad pathway.

  18. Assessing the risk of pelvic and para-aortic nodal involvement in apparent early-stage ovarian cancer: A predictors- and nomogram-based analyses.

    Science.gov (United States)

    Bogani, Giorgio; Tagliabue, Elena; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Casarin, Jvan; Chiappa, Valentina; Dondi, Giulia; Leone Roberti Maggiore, Umberto; Scaffa, Cono; Borghi, Chiara; Montanelli, Luca; Lorusso, Domenica; Raspagliesi, Francesco

    2017-08-02

    To estimate the prevalence of lymph node involvement in early-stage epithelial ovarian cancer in order to assess the prognostic value of lymph node dissection. Data of consecutive patients undergoing staging for early-stage epithelial ovarian cancer were retrospectively evaluated. Logistic regression and a nomogram-based analysis were used to assess the risk of lymph node involvement. Overall, 290 patients were included. All patients had lymph node dissection including pelvic and para-aortic lymphadenectomy. Forty-two (14.5%) patients were upstaged due to lymph node metastatic disease. Pelvic and para-aortic nodal metastases were observed in 22 (7.6%) and 42 (14.5%) patients. Lymph node involvement was observed in 18/95 (18.9%), 1/37 (2.7%), 4/29 (13.8%), 11/63 (17.4%), 3/41 (7.3%) and 5/24 (20.8%) patients with high-grade serous, low-grade-serous, endometrioid G1, endometrioid G2&3, clear cell and undifferentiated, histology, respectively (p=0.12, Chi-square test). We observed that high-grade serous histology was associated with an increased risk of pelvic node involvement; while, histology rather than low-grade serous and bilateral tumors were independently associated with para-aortic lymph node involvement (pinvolvement in the pelvic and para-aortic areas were built. High-grade serous histology and bilateral tumors are the main characteristics suggesting lymph node positivity. Our data suggested that high-grade serous and bilateral early-stage epithelial ovarian cancer are at high risk of having disease harboring in the lymphatic tissues of both pelvic and para-aortic area. After receiving external validation, our data will help to identify patients deserving comprehensive retroperitoneal staging. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. How numbers, nature and immune status of Foxp3+ regulatory T cells shape the early immunological events in tumor development.

    Directory of Open Access Journals (Sweden)

    Guillaume eDarrasse-Jeze

    2013-09-01

    Full Text Available The influence of CD4+CD25+Foxp3+ regulatory T cells (Tregs on cancer progression has been demonstrated in a large number of preclinical models and confirmed in several types of malignancies. Neoplastic processes trigger an increase of Treg numbers in draining lymph nodes, spleen, blood, and tumors, leading to the suppression of anti-tumor responses. Treg depletion before or early in tumor development may lead to complete tumor eradication and extends survival of mice and humans. However this strategy is ineffective in established tumors, highlighting the critical role of the early Treg-tumor encounters. In this review, after discussing old and new concepts of immunological tumor tolerance, we focus on the nature (thymus-derived vs. peripherally-derived and status (naïve or activated / memory of the regulatory T cells at tumor emergence. The recent discoveries in this field suggest that the activation status of Tregs and effector T cells (Teffs at the first encounter with the tumor are essential to shape the fate and speed of the immune response across a variety of tumor models. The relative timing of activation/recruitment of antitumor cells versus tolerogenic cells at tumor emergence appears to be crucial in the identification of tumor cells as friend or foe, which has broad implications for the design of cancer immunotherapies.

  20. On Early Warning Mechanism of Group Events on Petitions to Governmental Agencies%论群体上访政府机关事件预警机制

    Institute of Scientific and Technical Information of China (English)

    欧雅捷

    2012-01-01

    The group events on petitions to governmental ening the security of government agencies. There have been government should strengthen the establishment of the early tions to the governmental agencies including the mechanisms and so on. agencies have become the key factor in threat- new trends in the group petition events. The warning mechanisms of group events on peti- of monitoring, forecast and in advance control%群体上访政府机关事件已成为威胁政府机关安全的重要因素。群体上访政府机关事件呈现一些新动向,政府相关部门应加强对群体上访政府机关事件的预警机制建设,即加强监测机制、预测预报机制、预控机制等建设。

  1. Wedelolactone mitigates UVB induced oxidative stress, inflammation and early tumor promotion events in murine skin: plausible role of NFkB pathway.

    Science.gov (United States)

    Ali, Farrah; Khan, Bilal Azhar; Sultana, Sarwat

    2016-09-05

    UVB (Ultra-violet B) radiation is one of the major etiological factors in various dermal pathology viz. dermatitis, actinic folliculitis, solar urticaria, psoriasis and cancer among many others. UVB causes toxic manifestation in tissues by inciting inflammatory and tumor promoting events. We have designed this study to assess the anti-inflammatory and anti-tumor promotion effect of Wedelolactone (WDL) a specific IKK inhibitor. Results indicate significant restoration of anti-oxidative enzymes due to WDL treatments. We also found that WDL was effective in mitigating inflammatory markers consisting of MPO (myeloperoxidase), Mast cells trafficking, Langerhans cells suppression and COX 2 expression up regulation due to UVB exposure. We also deduce that WDL presented a promising intervention in attenuating early tumor promotion events caused by UVB exposure as indicated by the results of ODC (Ornithine Decarboxylase), Thymidine assay, Vimentin and VEGF (Vascular-endothelial growth factor) expression. This study was able to provide substantial cues for the therapeutic ability of Wedelolactone against inflammatory and tumor promoting events in murine skin depicting plausible role of NFkB pathway.

  2. The Influence of Sensation-Seeking and Parental and Peer Influences in Early Adolescence on Risk Involvement through Middle Adolescence

    Science.gov (United States)

    Wang, Bo; Deveaux, Lynette; Lunn, Sonja; Dinaj-Koci, Veronica; Li, Xiaoming; Stanton, Bonita

    2016-01-01

    This study examined the relationships between youth and parental sensation-seeking, peer influence, parental monitoring and youth risk involvement in adolescence using structural equation modeling. Beginning in Grade 6, longitudinal data were collected from 543 students over 3 years. Youth sensation-seeking in Grade 6 contributed to risk…

  3. The Influence of Sensation-Seeking and Parental and Peer Influences in Early Adolescence on Risk Involvement through Middle Adolescence

    Science.gov (United States)

    Wang, Bo; Deveaux, Lynette; Lunn, Sonja; Dinaj-Koci, Veronica; Li, Xiaoming; Stanton, Bonita

    2016-01-01

    This study examined the relationships between youth and parental sensation-seeking, peer influence, parental monitoring and youth risk involvement in adolescence using structural equation modeling. Beginning in Grade 6, longitudinal data were collected from 543 students over 3 years. Youth sensation-seeking in Grade 6 contributed to risk…

  4. Developmental changes in enzymes involved in the conversion of hexose phosphate and its subsequent metabolites during early tuberization of potato

    NARCIS (Netherlands)

    Appeldoorn, N.J.G.; Bruijn, de S.M.; Koot-Gronsveld, E.A.M.; Visser, R.G.F.; Vreugdenhil, D.; Plas, van der L.H.W.

    1999-01-01

    A highly synchronized in vitro tuberization system, based on single-node cuttings containing an axillary bud, was used to investigate the activity patterns of enzymes involved in the conversion of hexose phosphates and related products during stolon-to-tuber transition of potato (Solanum tuberosum L

  5. Longitudinal Associations of Alcohol Involvement with Subjective Well-Being in Adolescence and Prediction to Alcohol Problems in Early Adulthood

    Science.gov (United States)

    Mason, W. Alex; Spoth, Richard L.

    2011-01-01

    Adolescent alcohol involvement is associated with numerous negative outcomes, but also appears to have positive correlates, including subjective well-being. Additional research is needed to understand these paradoxical findings. The current study examines alcohol use, adverse alcohol-related (and other substance-related) consequences, and…

  6. Observations of an early Agulhas current retroflection event in 2001: A temporary cessation of inter-ocean exchange south of Africa?

    Science.gov (United States)

    van Aken, H. M.; Lutjeharms, J. R. E.; Rouault, M.; Whittle, C.; de Ruijter, W. P. M.

    2013-02-01

    The exchange of heat and salt between the South Indian Ocean and South Atlantic Ocean, at the southern terminus of the Agulhas current, forms a crucial link in the global ocean circulation. It has been surmised that upstream retroflections in this current could produce temporary interruptions to the exchange, but that their impact would depend on the vertical extent of such retroflections and on their duration. The fortuitous presence at sea of a research vessel has now enabled us to investigate such an episode at subsurface levels in combination with remote sensing of the sea surface. We present here the first in situ evidence that an upstream or early retroflection can extend to a depth of well over 750 m and last for 5 months. This event was likely triggered upstream by the happenstance of two Natal Pulses, large cyclonic eddies inshore of the Agulhas current. These eddies short-circuited the Agulhas with its Return current, leading to the shedding of three large Agulhas rings in quick succession. The arrival of a third cyclonic eddy when the Retroflection was still quite retracted did not lead to another ring shedding event. The resulting early retroflection may have had the effect of stalling the shedding of Agulhas rings and their motion towards the Cape Basin. However, these early retroflections are too scarce to allow generic statements on their generation or consequences, and the relation with large-scale environmental factors. It is likely that the observed withdrawal of the retroflection into the Transkei Basin is a fortuitous result of a series of contingent interactions.

  7. Absence of major vegetation and palaeoatmospheric pCO 2 changes associated with oceanic anoxic event 1a (Early Aptian, SE France)

    Science.gov (United States)

    Heimhofer, Ulrich; Hochuli, Peter A.; Herrle, Jens O.; Andersen, Nils; Weissert, Helmut

    2004-07-01

    The deposition of organic-rich sediments during the late Early Aptian Oceanic Anoxic Event (OAE) 1a has been interpreted to result in a major decrease of palaeoatmospheric CO 2 concentrations, accompanied by significant changes in the terrestrial flora. In order to test this hypothesis, the OAE 1a interval in the Vocontian Basin (SE France) has been studied with a combined approach including stable carbon isotopes, organic geochemistry and palynology. To estimate changes in palaeoatmospheric CO 2 levels across the OAE 1a, the δ13C composition of presumed algal biomarkers (low molecular weight n-alkanes, steranes) and of bulk carbonate carbon are used. Our results yield estimated Early Aptian carbon dioxide partial pressure ( pCO 2) values three to four times the preindustrial level and only a moderate drop across the black shale event. This moderate drop in pCO 2 is supported by palynological results. The frequency patterns of climate-sensitive sporomorphs (incl. pteridophyte spores, bisaccate pollen and Classopollis spp.) display only minor fluctuations throughout the studied section and indicate relatively stable patterns of terrestrial vegetation during and after formation of the OAE 1a black shale. The occurrence of a characteristic Early Aptian carbon isotope pattern across the OAE 1a interval permits accurate chemostratigraphic correlation with the well-studied Livello Selli interval of the Cismon record (N Italy). The contemporaneous formation of individual black shale layers at both sites indicates that transient episodes of dysoxic-anoxic bottom waters prevailed over large areas in the W Tethys Ocean independent of depositional setting. Comparison of the palynological data from the two locations displays significant differences in the frequency patterns of bisaccate pollen. The contrasting pollen spectra are interpreted to reflect prominent changes in the palaeoceanographic current patterns and/or selective sorting due to sea-level rise rather than

  8. Analysis of early events in the interaction between Fusarium graminearum and the susceptible barley (Hordeum vulgare) cultivar Scarlett

    DEFF Research Database (Denmark)

    Yang, Fen; Jensen, J.D.; Svensson, Birte;

    2010-01-01

    after inoculation. This coincided with the appearance of discrete F. graminearum-induced proteolytic fragments of beta-amylase. Based on these results, analysis of grain proteome changes prior to extensive proteolysis enabled identification of barley proteins responding early to infection by the fungus...... function was identified. Quantitative real-time RT-PCR analysis of selected genes showed a correlation between high gene expression and detection of the corresponding proteins. Fungal genes encoding alkaline protease and endothiapepsin were expressed during 1-3 days after inoculation, making them...... candidates for generation of the observed beta-amylase fragments. These fragments have potential to be developed as proteome-level markers for fungal infection that are also informative about grain protein quality....

  9. Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis.

    Science.gov (United States)

    Herrera, Cristina; Macêdo, Jéssica Kele A; Feoli, Andrés; Escalante, Teresa; Rucavado, Alexandra; Gutiérrez, José María; Fox, Jay W

    2016-04-01

    The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed