Prognosis in contre-coup intracranial haematomas - a clinical and radiological study of 63 patients

International Nuclear Information System (INIS)

Jayakumar, P.N.; Sastry Kolluri, V.R.; Basavakumar, D.G.; Subbakrishna, D.K.; Arya, B.Y.T.; Das, B.S.; Narayana Reddy, G.N.

1991-01-01

The clinical and radiological profiles of 63 patients with contre-coup haematomas were studied. The overall mortality was 53 %. The mortality in patients with contre-coup haematomas alone was only half of that found in patients with associated coup injury (80 %). (Authors)

Synergism between a half-site and an imperfect estrogen-responsive element, and cooperation with COUP-TFI are required for estrogen receptor (ER) to achieve a maximal estrogen-stimulation of rainbow trout ER gene.

Science.gov (United States)

Petit, F G; Métivier, R; Valotaire, Y; Pakdel, F

1999-01-01

In all oviparous, liver represents one of the main E2-target tissues where estrogen receptor (ER) constitutes the key mediator of estrogen action. The rainbow trout estrogen receptor (rtER) gene expression is markedly up-regulated by estrogens and the sequences responsible for this autoregulation have been located in a 0.2 kb upstream transcription start site within - 40/- 248 enhancer region. Absence of interference with steroid hormone receptors and tissue-specific factors and a conserved basal transcriptional machinery between yeast and higher eukaryotes, make yeast a simple assay system that will enable determination of important cis-acting regulatory sequences within rtER gene promoter and identification of transcription factors implicated in the regulation of this gene. Deletion analysis allowed to show a synergistic effect between an imperfect estrogen-responsive element (ERE) and a consensus half-ERE to achieve a high hormone-dependent transcriptional activation of the rtER gene promoter in the presence of stably expressed rtER. As in mammalian cells, here we observed a positive regulation of the rtER gene promoter by the chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) through enhancing autoregulation. Using a point mutation COUP-TFI mutant unable to bind DNA demonstrates that enhancement of rtER gene autoregulation requires the interaction of COUP-TFI to the DNA. Moreover, this enhancement of transcriptional activation by COUP-TFI requires specifically the AF-1 transactivation function of ER and can be observed in the presence of E2 or 4-hydroxytamoxifen but not ICI 164384. Thus, this paper describes the reconstitution of a hormone-responsive transcription unit in yeast in which the regulation of rtER gene promoter could be enhanced by the participation of cis-elements and/or trans-acting factors, such as ER itself or COUP-TF.

FANCD2 functions as a critical factor downstream of MiTF to maintain the proliferation and survival of melanoma cells

OpenAIRE

Julie Bourseguin; Caroline Bonet; Emilie Renaud; Charlotte Pandiani; Marina Boncompagni; Sandy Giuliano; Patrycja Pawlikowska; Houda Karmous-Benailly; Robert Ballotti; Filippo Rosselli; Corine Bertolotto

2016-01-01

Proteins involved in genetic stability maintenance and safeguarding DNA replication act not only against cancer initiation but could also play a major role in sustaining cancer progression. Here, we report that the FANC pathway is highly expressed in metastatic melanoma harboring the oncogenic microphthalmia-associated transcription factor (MiTF). We show that MiTF downregulation in melanoma cells lowers the expression of several FANC genes and proteins. Moreover, we observe that, similarly t...

Brain cavernomas associated with en coup de sabre linear scleroderma: Two case reports

Directory of Open Access Journals (Sweden)

Laxer Ronald M

2011-07-01

Full Text Available Abstract Linear scleroderma is a form of localized scleroderma that primarily affects the pediatric population. When it occurs on the scalp or forehead, it is termed "en coup de sabre". In the en coup de sabre subtype, many extracutaneous associations, mostly neurological, have been described. A patient with linear scleroderma en coup de sabre was noted to have ipsilateral brain cavernomas by magnetic resonance imaging. Using a worldwide pediatric rheumatology electronic list-serve, another patient with the same 2 conditions was identified. These two patients are reported in this study. Consideration of neuroimaging studies to disclose abnormal findings in patients with linear scleroderma en coup de sabre is important for potentially preventing and treating neurological manifestations associated with this condition.

Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI

Science.gov (United States)

Tomassy, Giulio Srubek; De Leonibus, Elvira; Jabaudon, Denis; Lodato, Simona; Alfano, Christian; Mele, Andrea; Macklis, Jeffrey D.; Studer, Michèle

2010-01-01

Transcription factors with gradients of expression in neocortical progenitors give rise to distinct motor and sensory cortical areas by controlling the area-specific differentiation of distinct neuronal subtypes. However, the molecular mechanisms underlying this area-restricted control are still unclear. Here, we show that COUP-TFI controls the timing of birth and specification of corticospinal motor neurons (CSMN) in somatosensory cortex via repression of a CSMN differentiation program. Loss of COUP-TFI function causes an area-specific premature generation of neurons with cardinal features of CSMN, which project to subcerebral structures, including the spinal cord. Concurrently, genuine CSMN differentiate imprecisely and do not project beyond the pons, together resulting in impaired skilled motor function in adult mice with cortical COUP-TFI loss-of-function. Our findings indicate that COUP-TFI exerts critical areal and temporal control over the precise differentiation of CSMN during corticogenesis, thereby enabling the area-specific functional features of motor and sensory areas to arise. PMID:20133588

Molecular and Electrophysiological Characterization of GABAergic Interneurons Expressing the Transcription Factor COUP-TFII in the Adult Human Temporal Cortex

Science.gov (United States)

Varga, Csaba; Tamas, Gabor; Barzo, Pal; Olah, Szabolcs; Somogyi, Peter

2015-01-01

Transcription factors contribute to the differentiation of cortical neurons, orchestrate specific interneuronal circuits, and define synaptic relationships. We have investigated neurons expressing chicken ovalbumin upstream promoter transcription factor II (COUP-TFII), which plays a role in the migration of GABAergic neurons. Whole-cell, patch-clamp recording in vitro combined with colocalization of molecular cell markers in the adult cortex differentiates distinct interneurons. The majority of strongly COUP-TFII-expressing neurons were in layers I–III. Most calretinin (CR) and/or cholecystokinin- (CCK) and/or reelin-positive interneurons were also COUP-TFII-positive. CR-, CCK-, or reelin-positive neurons formed 80%, 20%, or 17% of COUP-TFII-positive interneurons, respectively. About half of COUP-TFII-/CCK-positive interneurons were CR-positive, a quarter of them reelin-positive, but none expressed both. Interneurons positive for COUP-TFII fired irregular, accommodating and adapting trains of action potentials (APs) and innervated mostly small dendritic shafts and rarely spines or somata. Paired recording showed that a calretinin-/COUP-TFII-positive interneuron elicited inhibitory postsynaptic potentials (IPSPs) in a reciprocally connected pyramidal cell. Calbindin, somatostatin, or parvalbumin-immunoreactive interneurons and most pyramidal cells express no immunohistochemically detectable COUP-TFII. In layers V and VI, some pyramidal cells expressed a low level of COUP-TFII in the nucleus. In conclusion, COUP-TFII is expressed in a diverse subset of GABAergic interneurons predominantly innervating small dendritic shafts originating from both interneurons and pyramidal cells. PMID:25787832

Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

Science.gov (United States)

Peng, Yujun; van Wersch, Rowan; Zhang, Yuelin

2018-04-01

Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

COUP-TFII controls mouse pancreatic β-cell mass through GLP-1-β-catenin signaling pathways.

Directory of Open Access Journals (Sweden)

Marie Boutant

Full Text Available The control of the functional pancreatic β-cell mass serves the key homeostatic function of releasing the right amount of insulin to keep blood sugar in the normal range. It is not fully understood though how β-cell mass is determined.Conditional chicken ovalbumin upstream promoter transcription factor II (COUP-TFII-deficient mice were generated and crossed with mice expressing Cre under the control of pancreatic duodenal homeobox 1 (pdx1 gene promoter. Ablation of COUP-TFII in pancreas resulted in glucose intolerance. Beta-cell number was reduced at 1 day and 3 weeks postnatal. Together with a reduced number of insulin-containing cells in the ductal epithelium and normal β-cell proliferation and apoptosis, this suggests decreased β-cell differentiation in the neonatal period. By testing islets isolated from these mice and cultured β-cells with loss and gain of COUP-TFII function, we found that COUP-TFII induces the expression of the β-catenin gene and its target genes such as cyclin D1 and axin 2. Moreover, induction of these genes by glucagon-like peptide 1 (GLP-1 via β-catenin was impaired in absence of COUP-TFII. The expression of two other target genes of GLP-1 signaling, GLP-1R and PDX-1 was significantly lower in mutant islets compared to control islets, possibly contributing to reduced β-cell mass. Finally, we demonstrated that COUP-TFII expression was activated by the Wnt signaling-associated transcription factor TCF7L2 (T-cell factor 7-like 2 in human islets and rat β-cells providing a feedback loop.Our findings show that COUP-TFII is a novel component of the GLP-1 signaling cascade that increases β-cell number during the neonatal period. COUP-TFII is required for GLP-1 activation of the β-catenin-dependent pathway and its expression is under the control of TCF7L2.

Brassinosteriod Insensitive 2 (BIN2) acts as a downstream effector of the Target of Rapamycin (TOR) signaling pathway to regulate photoautotrophic growth in Arabidopsis.

Science.gov (United States)

Xiong, Fangjie; Zhang, Rui; Meng, Zhigang; Deng, Kexuan; Que, Yumei; Zhuo, Fengping; Feng, Li; Guo, Sundui; Datla, Raju; Ren, Maozhi

2017-01-01

The components of the target of rapamycin (TOR) signaling pathway have been well characterized in heterotrophic organisms from yeast to humans. However, because of rapamycin insensitivity, embryonic lethality in tor null mutants and a lack of reliable ways of detecting TOR protein kinase in higher plants, the key players upstream and downstream of TOR remain largely unknown in plants. Using engineered rapamycin-sensitive Binding Protein 12-2 (BP12-2) plants, the present study showed that combined treatment with rapamycin and active-site TOR inhibitors (asTORis) results in synergistic inhibition of TOR activity and plant growth in Arabidopsis. Based on this system, we revealed that TOR signaling plays a crucial role in modulating the transition from heterotrophic to photoautotrophic growth in Arabidopsis. Ribosomal protein S6 kinase 2 (S6K2) was identified as a direct downstream target of TOR, and the growth of TOR-suppressed plants could be rescued by up-regulating S6K2. Systems, genetic, and biochemical analyses revealed that Brassinosteriod Insensitive 2 (BIN2) acts as a novel downstream effector of S6K2, and the phosphorylation of BIN2 depends on TOR-S6K2 signaling in Arabidopsis. By combining pharmacological with genetic and biochemical approaches, we determined that the TOR-S6K2-BIN2 signaling pathway plays important roles in regulating the photoautotrophic growth of Arabidopsis. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

COUP-TFI mitotically regulates production and migration of dentate granule cells and modulates hippocampal Cxcr4 expression.

Science.gov (United States)

Parisot, Joséphine; Flore, Gemma; Bertacchi, Michele; Studer, Michèle

2017-06-01

Development of the dentate gyrus (DG), the primary gateway for hippocampal inputs, spans embryonic and postnatal stages, and involves complex morphogenetic events. We have previously identified the nuclear receptor COUP-TFI as a novel transcriptional regulator in the postnatal organization and function of the hippocampus. Here, we dissect its role in DG morphogenesis by inactivating it in either granule cell progenitors or granule neurons. Loss of COUP-TFI function in progenitors leads to decreased granule cell proliferative activity, precocious differentiation and increased apoptosis, resulting in a severe DG growth defect in adult mice. COUP-TFI-deficient cells express high levels of the chemokine receptor Cxcr4 and migrate abnormally, forming heterotopic clusters of differentiated granule cells along their paths. Conversely, high COUP-TFI expression levels downregulate Cxcr4 expression, whereas increased Cxcr4 expression in wild-type hippocampal cells affects cell migration. Finally, loss of COUP-TFI in postmitotic cells leads to only minor and transient abnormalities, and to normal Cxcr4 expression. Together, our results indicate that COUP-TFI is required predominantly in DG progenitors for modulating expression of the Cxcr4 receptor during granule cell neurogenesis and migration. © 2017. Published by The Company of Biologists Ltd.

Choose your destiny: Make a cell fate decision with COUP-TFII.

Science.gov (United States)

Wu, San-Pin; Yu, Cheng-Tai; Tsai, Sophia Y; Tsai, Ming-Jer

2016-03-01

Cell fate specification is a critical process to generate cells with a wide range of characteristics from stem and progenitor cells. Emerging evidence demonstrates that the orphan nuclear receptor COUP-TFII serves as a key regulator in determining the cell identity during embryonic development. The present review summarizes our current knowledge on molecular mechanisms by which COUP-TFII employs to define the cell fates, with special emphasis on cardiovascular and renal systems. These novel insights pave the road for future studies of regenerative medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Opposite Smad and chicken ovalbumin upstream promoter transcription factor inputs in the regulation of the collagen VII gene promoter by transforming growth factor-beta.

Science.gov (United States)

Calonge, María Julia; Seoane, Joan; Massagué, Joan

2004-05-28

A critical component of the epidermal basement membrane, collagen type VII, is produced by keratinocytes and fibroblasts, and its production is stimulated by the cytokine transforming growth factor-beta (TGF-beta). The gene, COL7A1, is activated by TGF-beta via Smad transcription factors in cooperation with AP1. Here we report a previously unsuspected level of complexity in this regulatory process. We provide evidence that TGF-beta may activate the COL7A1 promoter by two distinct inputs operating through a common region of the promoter. One input is provided by TGF-beta-induced Smad complexes via two Smad binding elements that function redundantly depending on the cell type. The second input is provided by relieving the COL7A1 promoter from chicken ovalbumin upstream promoter transcription factor (COUP-TF)-mediated transcriptional repression. We identified COUP-TFI and -TFII as factors that bind to the TGF-beta-responsive region of the COL7A1 promoter in an expression library screening. COUP-TFs bind to a site between the two Smad binding elements independently of Smad or AP1 and repress the basal and TGF-beta-stimulated activities of this promoter. We provide evidence that endogenous COUP-TF activity represses the COL7A1 promoter. Furthermore, we show that TGF-beta addition causes a rapid and profound down-regulation of COUP-TF expression in keratinocytes and fibroblasts. The results suggest that TGF-beta signaling may exert tight control over COL7A1 by offsetting the balance between opposing Smad and COUP-TFs.

The 2006 Coup in Thailand: Lessons for Emerging Democracies

National Research Council Canada - National Science Library

Hearn, Stephen W

2008-01-01

.... This latest coup was fifteen years after the last one and a big step backward from the accomplishments made with the adoption of the 1997 constitution that first established constitutional supremacy...

The Ongoing Rediscovery of Après-Coup as a Central Freudian Concept.

Science.gov (United States)

House, Jonathan

2017-10-01

Après-coup, Freud's Nachträglichkeit, is an essential psychoanalytic concept structuring each of four concepts, four mental processes that lie at the foundation of Freud's thinking: psychic trauma, repression, the creation of the unconscious, and the creation of infantile sexuality. It is argued here that infantile sexual drives, in contrast to the self-preservative instincts, arise from a two-step process of translation and repression in which the residues of failed translation become source-objects of the drives. These residues of failed translation have an associative resonance with adult sexuality, and the child is driven to ongoing attempts to translate them, to make them meaningful après coup. Thus, après-coup is at the heart of the human subject as a sexual creature who requires, desires, and creates meaning.

Coupled Physics Environment (CouPE) library - Design, Implementation, and Release

Energy Technology Data Exchange (ETDEWEB)

Mahadevan, Vijay S. [Argonne National Lab. (ANL), Argonne, IL (United States)

2014-09-30

Over several years, high fidelity, validated mono-­physics solvers with proven scalability on peta-­scale architectures have been developed independently. Based on a unified component-­based architecture, these existing codes can be coupled with a unified mesh-­data backplane and a flexible coupling-­strategy-­based driver suite to produce a viable tool for analysts. In this report, we present details on the design decisions and developments on CouPE, an acronym that stands for Coupled Physics Environment that orchestrates a coupled physics solver through the interfaces exposed by MOAB array-­based unstructured mesh, both of which are part of SIGMA (Scalable Interfaces for Geometry and Mesh-­Based Applications) toolkit. The SIGMA toolkit contains libraries that enable scalable geometry and unstructured mesh creation and handling in a memory and computationally efficient implementation. The CouPE version being prepared for a full open-­source release along with updated documentation will contain several useful examples that will enable users to start developing their applications natively using the native MOAB mesh and couple their models to existing physics applications to analyze and solve real world problems of interest. An integrated multi-­physics simulation capability for the design and analysis of current and future nuclear reactor models is also being investigated as part of the NEAMS RPL, to tightly couple neutron transport, thermal-­hydraulics and structural mechanics physics under the SHARP framework. This report summarizes the efforts that have been invested in CouPE to bring together several existing physics applications namely PROTEUS (neutron transport code), Nek5000 (computational fluid-dynamics code) and Diablo (structural mechanics code). The goal of the SHARP framework is to perform fully resolved coupled physics analysis of a reactor on heterogeneous geometry, in order to reduce the overall numerical uncertainty while leveraging

Détermination de la vitesse de coupe en usinage à l'aide des réseaux de neurones

Science.gov (United States)

Amor, Noureddine; Noureddine, Ali; Kherfane, Riad Lakhdar

2018-02-01

En usinage par enlèvement de copeaux, il est nécessaire de connaître des éléments tels que la géométrie à obtenir, la matière à usiner, le type d'opération, la machine-outil, l'outil de coupe, la profondeur de passe, l'avance, la vitesse de coupe. Ces trois derniers éléments quantifiables sont déterminés à l'aide de tables, abaques, logiciel informatique dédié, ou système CFAO, offrant une large gamme de choix mais manquant de transparence et de flexibilité. La contribution de cet article est d'appliquer les techniques d'intelligence artificielle basées sur les réseaux de neurones artificiels (RNA) au développement d'un système de décision pour le choix des paramètres de coupe. Pour modéliser la vitesse de coupe, nous utilisons un RNA avec un algorithme de rétro-propagation. Des valeurs expérimentales provenant d'un abaque source serviront à construire et établir le RNA pour estimer la valeur de la vitesse de coupe, utilisant comme données un certain nombre de paramètres d'influence. La validité des résultats obtenus montre que cette méthode peut être appliquée avec succès et que son utilisation dans le domaine de l'usinage peut contribuer à optimiser les conditions de coupe par un choix plus précis et plus rapide de la vitesse de coupe.

ETUDE COMPARATIVE DU COMPORTEMENT A L’USURE DE CERTAINES NUANCES DE CERAMIQUE DE COUPE EN TOURNAGE

Directory of Open Access Journals (Sweden)

M A YALLESE

2002-06-01

Full Text Available Des essais de coupe ont été effectués par quatre outils en céramique, face à l’acier  AF37. Les résultats de ces essais nous ont permis d’étudier l’influence  des paramètres de coupe sur le comportement à l’usure des différentes céramiques étudiées. Pour ces différentes céramiques la relation entre la tenue et les paramètres de coupe a été exprimée suivant le modèle mathématique de Taylor.

Nouvelle procédure pour l'augmentation du temps d'usinage simulé en coupe orthogonale

OpenAIRE

Guediche , Mayssa; Mabrouki , Tarek; Donnet , Christophe; Bergheau , Jean-Michel; Hamdi , Hedi

2015-01-01

International audience; Cette étude présente une nouvelle méthodologie visant à augmenter le temps d'usinage simulé en coupe orthogonale .Le but est d'étudier ultérieurement l'évolution de l'usure des outils de coupe dans le cas de l'usinage de l'acier 42CD4. Un modèle lagrangien est donc développé sous le code de calcul ABAQUS simulant la formation du copeau. Une approche baptisée de « modélisation verticale » est développée dans le but d'augmenter le temps de coupe simulé tout en gardant un...

Endoglin inhibition leads to intussusceptive angiogenesis via activation of factors related to COUP-TFII signaling pathway.

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Ruslan Hlushchuk

Full Text Available Angiogenesis is a highly coordinated, extremely complex process orchestrated by multiple signaling molecules and blood flow conditions. While sprouting mode of angiogenesis is very well investigated, the molecular mechanisms underlying intussusception, the second mode of angiogenesis, remain largely unclear. In the current study two molecules involved in vascular growth and differentiation, namely endoglin (ENG/CD105 and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII were examined to unravel their specific roles in angiogenesis. Down- respectively up-regulation of both molecules tightly correlates with intussusceptive microvascular growth. Upon ENG inhibition in chicken embryo model, formation of irregular capillary meshwork accompanied by increased expression of COUP-TFII could be observed. This dynamic expression pattern of ENG and COUP-TFII during vascular development and remodeling correlated with formation of pillars and progression of intussusceptive angiogenesis. Similar findings could be observed in mammalian model of acute rat Thy1.1 glomerulonephritis, which was induced by intravenous injection of anti-Thy1 antibody and has shown upregulation of COUP-TFII in initial phase of intussusception, while ENG expression was not disturbed compared to the controls but decreased over the time of pillar formation. In this study, we have shown that ENG inhibition and at the same time up-regulation of COUP-TFII expression promotes intussusceptive angiogenesis.

Subtypes of coups d’état: recent transformations of a 17th century concept

Directory of Open Access Journals (Sweden)

Rafael Martínez

2014-12-01

Full Text Available Ostensibly, the coup d’état as a practice has been virtually eradicated, or confined, at least, to failed African states. Nevertheless, in recent years various changes of government in Latin America (and even Europe have provoked serious doubts to be raised as to their legality and legitimacy, and they have come to be regarded as coups d’état. In light of this reality, this study attempts to go deeper into the concept of the coup d’état, right through from its creation in the 17th century to our times, in order to determine the evolutionary changes that the concept has undergone and to extract the lowest common denominator that has remained unchanged. With these premises established, the presumed evolutionary course of the concept in the 21st century is plotted and the typologies it might generate are proposed.

Repression of COUP-TFI Improves Bone Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells

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Tao Zhang

2017-09-01

Full Text Available Identifying molecular mechanisms that regulate insulin expression in bone marrow-derived mesenchymal stem cells (bmMSCs can provide clues on how to stimulate the differentiation of bmMSCs into insulin-producing cells (IPCs, which can be used as a therapeutic approach against type 1 diabetes (T1D. As repression factors may inhibit differentiation, the efficiency of this process is insufficient for cell transplantation. In this study, we used the mouse insulin 2 (Ins2 promoter sequence and performed a DNA affinity precipitation assay combined with liquid chromatography-mass spectrometry to identify the transcription factor, chicken ovalbumin upstream promoter transcriptional factor I (COUP-TFI. Functionally, bmMSCs were reprogrammed into IPCs via COUP-TFI suppression and MafA overexpression. The differentiated cells expressed higher levels of genes specific for islet endocrine cells, and they released C-peptide and insulin in response to glucose stimulation. Transplantation of IPCs into streptozotocin-induced diabetic mice caused a reduction in hyperglycemia. Mechanistically, COUP-TFI bound to the DR1 (direct repeats with 1 spacer element in the Ins2 promoter, thereby negatively regulating promoter activity. Taken together, the data provide a novel mechanism by which COUP-TFI acts as a negative regulator in the Ins2 promoter. The differentiation of bmMSCs into IPCs could be improved by knockdown of COUP-TFI, which may provide a novel stem cell-based therapy for T1D. Keywords: siRNAs, differentiation, stem cell transplantation, diabetes, mesenchymal stem cells

Temporal effects of Notch signaling and potential cooperation with multiple downstream effectors on adenohypophysis cell specification in zebrafish.

Science.gov (United States)

Nakahara, Yoshinari; Muto, Akihiko; Hirabayashi, Ryo; Sakuma, Tetsushi; Yamamoto, Takashi; Kume, Shoen; Kikuchi, Yutaka

2016-05-01

The adenohypophysis (AH) consists of six distinct types of hormone-secreting cells. In zebrafish, although proper differentiation of all AH cell types has been shown to require Notch signaling within a period of 14-16 h postfertilization (hpf), the mechanisms underlying this process remain to be elucidated. Herein, we observed using the Notch inhibitor dibenzazepine (DBZ) that Notch signaling also contributed to AH cell specification beyond 16 hpf. Specification of distinct cell types was perturbed by DBZ treatment for different time frames, suggesting that AH cells are specified by Notch-dependent and cell-type-specific mechanisms. We also found that two hes-family genes, her4.1 and hey1, were expressed in the developing AH under the influence of Notch signaling. her4.1 knockdown reduced expression of proopiomelanocortin a (pomca), growth hormone (gh), and prolactin, whereas hey1 was responsible only for gh expression. Simultaneous loss of both Her4.1 and Hey1 produced milder phenotypes than that of DBZ-treated embryos. Moreover, DBZ treatment from 18 hpf led to a significant down-regulation of both gh and pomca genes only when combined with injection of a subthreshold level of her4.1-morpholino. These observations suggest that multiple downstream effectors, including Her4.1 and Hey1, mediate Notch signaling during AH cell specification. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

GOLPE CIVIL-MILITAR DE 1964: ORIGENS E NOTAS CARACTERIZADORAS / CIVIL-MILITARY COUP OF 1964: ORIGINS AND CHARACTERISTICS

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Ana Maria D’Ávila Lopes

2015-12-01

Full Text Available This article discusses about the origins and characteristics of the Coup of 64. In order to do so, we use the interdisciplinary bibliographic research. On the first topic the origins of the coup of 64 are analyzed, highlighting the role played by political, economic and social factors that were its tangential. Then, our research comments the characteristics of the coup of 64, especially the bureaucratic authoritarian character; consensual legitimacy of civil society; the extension of the central military power; State terrorism implemented through the institutionalization of enforcement agencies to commit serious human rights violations and the authoritarian legality. By the end, it is concluded that the coup of 64 is headquartered in factual and symbolic legacy of Vargas, represented in the imaginary of elites, mainly by the figure of the former president João Goulart, coupled to polarization between capitalism and communism at the global level and at economic struggles on opening markets, remittance of foreign exchange dealing abroad and increased investment from the state to the private sector. In the same way, it verifies that Brazil singled out for its bureaucratic authoritarianism, by legitimacy - of origin - consented by the sophistication of its state terrorism, as well as, the exacerbation of its authoritarian legality. Furthermore, it stresses the nature of the coup of 64, and not “revolution” and its hybridity, due to the support of civil seizure to the achievement of power by the military segments.

The Effect of Military Coup and Interventions on the Economic Performance: The Case of Turkey

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Arif ÖZSAĞIR

2013-12-01

Full Text Available Some factors that affect the economic life indirectly but substantially at the same time are assumed exogenous or fixed by the traditional economics. However, these factors are considered fixed are the factors that affect the economy deeply. Political stability, verdicts devoid of justice, military coups and interventions, oligarchical bureaucratic structure, and terrorism are important factors assumed to be fixed. Although these factors may seem irrelevant at first glance, they have crucial impacts on economies. Important determinants of Turkey’s economic performance have been political decisions, the verdicts devoid of justice, in other words biased verdicts, military coups and interventions, oligarchical bureaucratic structure, and terrorism rather than economic policies. In this study, it is discussed that the effects of military coups and interventions on the performance of the economy in the context of Turkey example; and the hypothesis is validated within the framework of an econometric model.

Atypical Neuroimaging Manifestations of Linear Scleroderma “en coup de sabre”

Science.gov (United States)

M. ALLMENDINGER, Andrew; A. RICCI, Joseph; S. DESAI, Naman; VISWANADHAN, Narayan; RODRIGUEZ, Diana

2015-01-01

Linear scleroderma “en coup de sabre” is a subset of localized scleroderma with band-like sclerotic lesions typically involving the fronto-parietal regions of the scalp. Patients often present with neurologic symptoms. On imaging, patients may have lesions in the cerebrum ipsilateral to the scalp abnormality. Infratentorial lesions and other lesions not closely associated with the overlying scalp abnormality, such as those found in the cerebellum, have been reported, but are extremely uncommon. We present a case of an 8-year-old boy with a left fronto-parietal “en coup de sabre” scalp lesion and describe the neuroimaging findings of a progressively enlarging left cerebellar lesion discovered incidentally on routine magnetic resonance imaging. Interestingly, the patient had no neurologic symptoms given the size of the mass identified. PMID:26401155

Turkish putsch through the eyes of Turkish people: image of the failed coup estimated by Turkish media in July 2016

Directory of Open Access Journals (Sweden)

Mamedov Zaur Imalverdi oglu

2017-07-01

Full Text Available This article analyses Turkish media on the subject of the coup in 2016. The reviewed materials were published in the first two weeks after the coup attempt, and these most clearly convey the atmosphere of those days. The purpose of this study is to examine the formation of public opinion in connection with the coup in Turkey. The uniqueness of the work lies in the fact that almost all types of mass media were involved in the analysis: television, press, popular sites.

A Re-Run in Turkey: A Coup in the Near Future?

National Research Council Canada - National Science Library

Foust, Shawn J

2007-01-01

... of coup activity in the near future, as has been seen in Turkey's history. Turkey has a proven status of importance to the United States by virtue of its strategic location, democratic pursuits, cultural status, and economic potential...

Complement Factor B is the Downstream Effector of Toll-Like Receptors and Plays an Important Role in a Mouse Model of Severe Sepsis¶

Science.gov (United States)

Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M.; Wu, Xiaobo; Atkinson, John P.; Chao, Wei

2013-01-01

Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of Toll-like receptors (TLRs) mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. Here, we show that activation of TLR2, TLR3 and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture (CLP) in a mouse model, augmented cfB levels in the serum, peritoneal cavity and major organs including the kidney and heart. CLP also led to the alternative pathway (AP) activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum AP via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 up-regulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function, and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

Two-finger (TF) SPUDT cells.

Science.gov (United States)

Martin, Guenter; Biryukov, Sergey V; Schmidt, Hagen; Steiner, Bernd; Wall, Bert

2011-03-01

SPUDT cells including two fingers are only known thus far for so-called NSPUDT directions. In that case, usual solid-finger cells are used. The purpose of the present paper is to find SPUDT cell types consisting of two fingers only for pure mode directions. Two-finger (TF) cells for pure mode directions on substrates like 128°YX LiNbO(3) and YZ LiNbO(3) were found by means of an optimization procedure. The forward direction of a TF-cell SPUDT on 128°YX LiNbO(3) was determined experimentally. The properties of the new cells are compared with those of conventional SPUDT cells. The reflectivity of TF cells on 128°YX LiNbO(3) turns out to be two to three times larger than that of distributed acoustic reflection transducer (DART) and Hanma-Hunsinger cells at the same metal layer thickness.

TfR Binding Peptide Screened by Phage Display Technology ...

African Journals Online (AJOL)

Purpose: To screen an hTfR affinity peptide and investigate its activity in vitro. Methods: hTfR ... Keywords: Peptide, hTfR, Transferrin receptor, Phage display technology, Enhanced green ..... mediated uptake of peptides that bind the human.

FunCoup 4: new species, data, and visualization

OpenAIRE

Ogris, Christoph; Guala, Dimitri; Kaduk, Mateusz; Sonnhammer, Erik L L

2017-01-01

Abstract This release of the FunCoup database (http://funcoup.sbc.su.se) is the fourth generation of one of the most comprehensive databases for genome-wide functional association networks. These functional associations are inferred via integrating various data types using a naive Bayesian algorithm and orthology based information transfer across different species. This approach provides high coverage of the included genomes as well as high quality of inferred interactions. In this update of ...

Thermo hydraulic and quench propagation characteristics of SST-1 TF coil

Energy Technology Data Exchange (ETDEWEB)

Sharma, A.N., E-mail: ansharma@ipr.res.in [Institute for Plasma Research, Gandhinagar (India); Pradhan, S. [Institute for Plasma Research, Gandhinagar (India); Duchateau, J.L. [CEA Cadarache, 13108 St Paul lez Durance Cedex (France); Khristi, Y.; Prasad, U.; Doshi, K.; Varmora, P.; Patel, D.; Tanna, V.L. [Institute for Plasma Research, Gandhinagar (India)

2014-02-15

Highlights: • Details of SST-1 TF coils, CICC. • Details of SST-1 TF coil cold test. • Quench analysis of TF magnet. • Flow changes following quench. • Predictive analysis of assembled magnet system. - Abstract: SST-1 toroidal field (TF) magnet system is comprising of sixteen superconducting modified ‘D’ shaped TF coils. During single coil test campaigns spanning from June 10, 2010 till January 24, 2011; the electromagnetic, thermal hydraulic and mechanical performances of each TF magnet have been qualified at its respective nominal operating current of 10,000 A in either two-phase or supercritical helium cooling conditions. During the current charging experiments, few quenches have initiated either as a consequence of irrecoverable normal zones or being induced in some of the TF magnets. Quench evolution in the TF coils have been analyzed in detail in order to understand the thermal hydraulic and quench propagation characteristics of the SST-1 TF magnets. The same were also simulated using 1D code Gandalf. This paper elaborates the details of the analyses and the quench simulation results. A predictive quench propagation analysis of 16 assembled TF magnets system has also been reported in this paper.

FunCoup 4: new species, data, and visualization.

Science.gov (United States)

Ogris, Christoph; Guala, Dimitri; Sonnhammer, Erik L L

2018-01-04

This release of the FunCoup database (http://funcoup.sbc.su.se) is the fourth generation of one of the most comprehensive databases for genome-wide functional association networks. These functional associations are inferred via integrating various data types using a naive Bayesian algorithm and orthology based information transfer across different species. This approach provides high coverage of the included genomes as well as high quality of inferred interactions. In this update of FunCoup we introduce four new eukaryotic species: Schizosaccharomyces pombe, Plasmodium falciparum, Bos taurus, Oryza sativa and open the database to the prokaryotic domain by including networks for Escherichia coli and Bacillus subtilis. The latter allows us to also introduce a new class of functional association between genes - co-occurrence in the same operon. We also supplemented the existing classes of functional association: metabolic, signaling, complex and physical protein interaction with up-to-date information. In this release we switched to InParanoid v8 as the source of orthology and base for calculation of phylogenetic profiles. While populating all other evidence types with new data we introduce a new evidence type based on quantitative mass spectrometry data. Finally, the new JavaScript based network viewer provides the user an intuitive and responsive platform to further evaluate the results. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Radioresistance of chordoma cells is associated with the ATM/ATR pathway, in which RAD51 serves as an important downstream effector.

Science.gov (United States)

Zhang, Chao; Wang, Bing; Li, Lei; Li, Yawei; Li, Pengzhi; Lv, Guohua

2017-09-01

Surgery followed by radiotherapy is the standard treatment for chordomas, which are a rare but low-grade type of bone cancer arising from remnants of the embryonic notochord. However, disease recurrence following radiotherapy is common, most likely due to endogenous DNA repair mechanisms that promote cell survival upon radiation strikes. The ataxia telangiectasia mutated/ataxia telangiectasia mutated and Rad3 related (ATM/ATR)-mediated pathway has a critical role in DNA repair mechanisms; however, it has rarely been investigated in chordomas. In the present study, the expression of signal molecules related to the ATM/ATR pathway in chordoma tissues and adjacent normal tissues were initially examined using immunohistochemistry and western blot analysis. Chordoma U-CH1 and U-CH2 cells were subsequently used to investigate cell responses to ionizing radiation and the potential protective actions mediated by the ATM/ATR pathway. Phosphorylated (p)-ATM, p-ATR, γ-H2A histone family, member X (H2AX) and RAD51 were significantly upregulated in chordoma tissues relative to adjacent normal tissues (PATM, γ-H2AX and RAD51 expression in U-CH1 cells (PATM, p-ATR and RAD51 levels in U-CH2 cells (PATM/ATR pathway, in which RAD51 serves as an important downstream effector. Thus, RAD51 presents a promising therapeutic target for improving the outcome of radiotherapy treatment in chordomas.

Operation of SST-1 TF power supply during SST-1 campaigns

International Nuclear Information System (INIS)

Sharma, Dinesh Kumar; Vora, Murtuza M.; Ojha, Amit; Singh, Akhilesh Kumar; Bhavsar, Chirag

2015-01-01

Highlights: • SST-1 TF power supply is 12 pulse SCR converter circuit. • TF power supply protection, measurement and control scheme are explained. • Quench, emergency and normal shot process is explained and results of SST-1 campaigns are shown. • Dynamic control of TF current. • The paper shows the results of last ten SST-1 campaigns. - Abstract: SST-1 TF power supply provides the direct current for the required magnetic field of TF coil. TF power supply includes transformer, 12-pulse converter, bus bar, water-cooled cable, protection and measuring equipments, and isolator, VME DAC system and GUI software. TF power supply is operated through GUI software built in TCL/Tk. VME DAC system monitors the parameters, provides On/Off commands, voltage and current references and initiates predefined reference to emergency shutdown. The emergency shutdown is hardwired to TF power supply from central control. During quench power supply converter opens DCCB and dump resistor is connected in the circuit and VME DAC system acquires bus bar voltage, dump voltage and dump current. Operation of TF power supply also requires monitoring of SCR and transformer temperature and water flow rate of water-cooled cable during high current long pulse shot. Before start up of TF power supply a quench simulation is performed to check the readiness of protection. This paper describes pre startup operation, normal shot operation, emergency and quench process, dynamic control and complete shutdown operation of TF power supply.

Operation of SST-1 TF power supply during SST-1 campaigns

Energy Technology Data Exchange (ETDEWEB)

Sharma, Dinesh Kumar, E-mail: dinesh@ipr.res.in; Vora, Murtuza M.; Ojha, Amit; Singh, Akhilesh Kumar; Bhavsar, Chirag

2015-10-15

Highlights: • SST-1 TF power supply is 12 pulse SCR converter circuit. • TF power supply protection, measurement and control scheme are explained. • Quench, emergency and normal shot process is explained and results of SST-1 campaigns are shown. • Dynamic control of TF current. • The paper shows the results of last ten SST-1 campaigns. - Abstract: SST-1 TF power supply provides the direct current for the required magnetic field of TF coil. TF power supply includes transformer, 12-pulse converter, bus bar, water-cooled cable, protection and measuring equipments, and isolator, VME DAC system and GUI software. TF power supply is operated through GUI software built in TCL/Tk. VME DAC system monitors the parameters, provides On/Off commands, voltage and current references and initiates predefined reference to emergency shutdown. The emergency shutdown is hardwired to TF power supply from central control. During quench power supply converter opens DCCB and dump resistor is connected in the circuit and VME DAC system acquires bus bar voltage, dump voltage and dump current. Operation of TF power supply also requires monitoring of SCR and transformer temperature and water flow rate of water-cooled cable during high current long pulse shot. Before start up of TF power supply a quench simulation is performed to check the readiness of protection. This paper describes pre startup operation, normal shot operation, emergency and quench process, dynamic control and complete shutdown operation of TF power supply.

Combined targeting of BRAF and CRAF or BRAF and PI3K effector pathways is required for efficacy in NRAS mutant tumors.

Directory of Open Access Journals (Sweden)

Bijay S Jaiswal

Full Text Available BACKGROUND: Oncogenic RAS is a highly validated cancer target. Attempts at targeting RAS directly have so far not succeeded in the clinic. Understanding downstream RAS-effectors that mediate oncogenesis in a RAS mutant setting will help tailor treatments that use RAS-effector inhibitors either alone or in combination to target RAS-driven tumors. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have investigated the sufficiency of targeting RAS-effectors, RAF, MEK and PI3-Kinase either alone or in combination in RAS mutant lines, using an inducible shRNA in vivo mouse model system. We find that in colon cancer cells harboring a KRAS(G13D mutant allele, knocking down KRAS alone or the RAFs in combination or the RAF effectors, MEK1 and MEK2, together is effective in delaying tumor growth in vivo. In melanoma cells harboring an NRAS(Q61L or NRAS(Q61K mutant allele, we find that targeting NRAS alone or both BRAF and CRAF in combination or both BRAF and PIK3CA together showed efficacy. CONCLUSION/SIGNIFICANCE: Our data indicates that targeting oncogenic NRAS-driven melanomas require decrease in both pERK and pAKT downstream of RAS-effectors for efficacy. This can be achieved by either targeting both BRAF and CRAF or BRAF and PIK3CA simultaneously in NRAS mutant tumor cells.

Mass Surveillance and the Militarization of Cyberspace in Post-Coup Thailand

Directory of Open Access Journals (Sweden)

Pinkaew Laungaramsri

2016-12-01

Full Text Available Post-coup Thailand has witnessed a troubling shift toward censorship, surveillance, and suppression in cyberspace. With cyber security ranking prominently on the military’s agenda and the expansion of the military’s cyber intervention, the country’s online infrastructure has undergone politicization, securitization, and militarization. This paper argues that the militarization of cyberspace in Thailand represents the process in which cyber warfare capabilities have been integrated with other military forces and with support from the masses. This process has been effective through at least three significant mechanisms, including mass surveillance, surveillance by the masses, and normalization of surveillance. Social media have been turned into an absolute digital panopticon. Cyber dystopia, created by the 2014 coup and supported by the masses, has served to sustain a ‘state of exception’ not only within the territorial borders of the state, but also more importantly, within the virtual space of civil society. Cyber surveillance by the military and the masses has continued to jeopardize the already vulnerable Thai democracy.

GTP- and GDP-Dependent Rab27a Effectors in Pancreatic Beta-Cells.

Science.gov (United States)

Yamaoka, Mami; Ishizaki, Toshimasa; Kimura, Toshihide

2015-01-01

Small guanosine triphosphatases (GTPases) participate in a wide variety of cellular functions including proliferation, differentiation, adhesion, and intracellular transport. Conventionally, only the guanosine 5'-triphosphate (GTP)-bound small GTPase interacts with effector proteins, and the resulting downstream signals control specific cellular functions. Therefore, the GTP-bound form is regarded as active, and the focus has been on searching for proteins that bind the GTP form to look for their effectors. The Rab family small GTPase Rab27a is highly expressed in some secretory cells and is involved in the control of membrane traffic. The present study reviews recent progress in our understanding of the roles of Rab27a and its effectors in pancreatic beta-cells. In the basal state, GTP-bound Rab27a controls insulin secretion at pre-exocytic stages via its GTP-dependent effectors. We previously identified novel guanosine 5'-diphosphate (GDP)-bound Rab27-interacting proteins. Interestingly, GDP-bound Rab27a controls endocytosis of the secretory membrane via its interaction with these proteins. We also demonstrated that the insulin secretagogue glucose converts Rab27a from its GTP- to GDP-bound forms. Thus, GTP- and GDP-bound Rab27a regulate pre-exocytic and endocytic stages in membrane traffic, respectively. Since the physiological importance of GDP-bound GTPases has been largely overlooked, we consider that the investigation of GDP-dependent effectors for other GTPases is necessary for further understanding of cellular function.

Extending TF1: Argument parsing, function composition, and vectorization

CERN Document Server

Tsang Mang Kin, Arthur Leonard

2017-01-01

In this project, we extend the functionality of the TF1 function class in root. We add argument parsing, making it possible to freely pass variables and parameters into pre-defined and user-defined functions. We also introduce a syntax to use certain compositions of functions, namely normalized sums and convolutions, directly in TF1. Finally, we introduce some simple vectorization functionality to TF1 and demonstrate the potential to speed up parallelizable computations.

Clustering of malaria treatment failure (TF) in Daraweesh: hints for host genetic susceptibility to TF with emphasis on immune-modulating SNPs

DEFF Research Database (Denmark)

Giha, Hayder A; ElGhazali, Gehad; Nasr, Amre

2010-01-01

In malaria, drug resistance and treatment failure (TF) are not synonymous, although are escalating together. Over 9 years of surveillances for malaria morbidity and TF in Daraweesh village in eastern Sudan (1991-2004), 136 donors (15-78 years) from 43 households, treated for 278 malaria episodes ...

Quench characterization and thermo hydraulic analysis of SST-1 TF magnet busbar

Energy Technology Data Exchange (ETDEWEB)

Sharma, A.N., E-mail: ansharma@ipr.res.in [Institute for Plasma Research, Gandhinagar (India); Pradhan, S. [Institute for Plasma Research, Gandhinagar (India); Duchateau, J.L. [CEA Cadarache, 13108 St Paul lez Durance Cedex (France); Khristi, Y.; Prasad, U.; Doshi, K.; Varmora, P.; Tanna, V.L.; Patel, D.; Panchal, A. [Institute for Plasma Research, Gandhinagar (India)

2015-01-15

Highlights: • Details of SST-1 TF busbar quench detection. • Simulation of slow propagating normal zone. • Thermo hydraulic analyses of TF busbar in current feeder system. - Abstract: Toroidal field (TF) magnet system of steady-state superconducting tokamak-1 (SST-1) has 16 superconducting coils. TF coils are cooled with forced flow supercritical helium at 0.4 MPa, at 4.5 K and operate at nominal current of 10,000 A. Prior to TF magnet system assembly in SST-1 tokamak, each TF coil was tested individually in a test cryostat. During these tests, TF coil was connected to a pair of conventional helium vapor cooled current leads. The connecting busbar was made from the same base cable-in-conduit-conductor (CICC) of SST-1 superconducting magnet system. Quenches experimentally observed in the busbar sections of the single coil test setups have been analyzed in this paper. A steady state thermo hydraulic analysis of TF magnet busbar in actual SST-1 tokamak assembly has been done. The experimental observations of quench and results of relevant thermo hydraulic analyses have been used to predict the safe operation regime of TF magnet system busbar during actual SST-1 tokamak operational scenarios.

miR-342-5p Regulates Neural Stem Cell Proliferation and Differentiation Downstream to Notch Signaling in Mice

Directory of Open Access Journals (Sweden)

Fang Gao

2017-04-01

Full Text Available Summary: Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout (Rbp-j cKO and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl, was negatively regulated by Notch signaling, probably through HES5. Transfection of miR-342-5p promoted the differentiation of neural stem cells (NSCs into intermediate neural progenitors (INPs in vitro and reduced the stemness of NSCs in vivo. Furthermore, miR-342-5p inhibited the differentiation of neural stem/intermediate progenitor cells into astrocytes, likely mediated by targeting GFAP directly. Our results indicated that miR-342-5p could function as a downstream effector of Notch signaling to regulate the differentiation of NSCs into INPs and astrocytes commitment. : In this article, Han and colleagues show that miR-342-5p acts as a downstream effector of Notch signaling in the mouse CNS. Notch signal inhibits miR-342-5p expression by regulating its host gene Evl. And with attenuated Notch signal in NSCs, miR-342-5p is upregulated to promote NSCs transition into INPs, and to inhibit astrocyte commitment by targeting GFAP. Keywords: neural stem cells, intermediate neural progenitors, Notch, RBP-J, neuron, glia, miR-342-5p

Status of GENIUS-TF-II and TF-III-The long-term stability of naked detectors in liquid nitrogen

Energy Technology Data Exchange (ETDEWEB)

Klapdor-Kleingrothaus, H.V. [Max-Planck-Institut fuer Kernphysik, P.O. Box 10 39 80, D-69029 Heidelberg (Germany)]. E-mail: H.Klapdor@mpi-hd.mpg.de; Krivosheina, I.V. [Max-Planck-Institut fuer Kernphysik, P.O. Box 10 39 80, D-69029 Heidelberg (Germany)

2006-10-15

GENIUS-TF-II is a setup of six naked high purity Ge detectors (15kg) in liquid nitrogen in Gran Sasso. It has been installed in October, 2004-after the first four naked Ge detectors had been installed on May 5, 2003 (GENIUS-TF-I). The GENIUS-Test-Facility (GENIUS-TF) is the first and up to now only setup ever testing the novel technique aiming at extreme background reduction in search for rare decays in particular underground. The goal of GENIUS-TF was to test some key operational parameters of the full GENIUS project proposal in 1997 [H.V. Klapdor-Kleingrothaus, Int. J. Mod. Phys. A 13 (1998) 3953; H.V. Klapdor-Kleingrothaus, J. Hellmig, M. Hirsch, GENIUS-Proposal, 20 November 1997; J. Hellmig and H.V. Klapdor-Kleingrothaus, Z. Phys. A 359 ( 1997) 351 and nucl-ex/9801004; H.V. Klapdor-Kleingrothaus, M. Hirsch, Z. Phys. A 359 (1997) 361; H.V. Klapdor-Kleingrothaus, J. Hellmig, M. Hirsch, J. Phys. G 24 (1998) 483; H.V. Klapdor-Kleingrothaus, CERN Courier, November 1997, pp. 16-18]. Simultaneous physical goal is to search for the annual modulation of the Dark Matter signal [H.V. Klapdor-Kleingrothaus, et al., Nucl. Instr. and Meth. A 481 (2002) 149; C. Tomei, A. Dietz, I. Krivosheina, H.V. Klapdor-Kleingrothaus, Nucl. Instr. and Meth. 508 (2003) 343]. After operation of GENIUS-TF over three years with finally six naked Ge detectors (15kg) in liquid nitrogen in Gran Sasso we realize serious problems for realization of a full-size GENIUS-like experiment: (1) Background from Rn222 diffusing into the setup, on a level far beyond the expectation. (2) Limited long-term stability of naked detectors in liquid nitrogen as result of increasing leakage current. None of the six detectors is running after three years with the nominal leakage current. Three of the six detectors do not work any more at all. The results of our three years of investigation of the long-term stability may cast doubt on the possibility to perform full GENIUS-like projects.

Status of GENIUS-TF-II and TF-III-The long-term stability of naked detectors in liquid nitrogen

International Nuclear Information System (INIS)

Klapdor-Kleingrothaus, H.V.; Krivosheina, I.V.

2006-01-01

GENIUS-TF-II is a setup of six naked high purity Ge detectors (15kg) in liquid nitrogen in Gran Sasso. It has been installed in October, 2004-after the first four naked Ge detectors had been installed on May 5, 2003 (GENIUS-TF-I). The GENIUS-Test-Facility (GENIUS-TF) is the first and up to now only setup ever testing the novel technique aiming at extreme background reduction in search for rare decays in particular underground. The goal of GENIUS-TF was to test some key operational parameters of the full GENIUS project proposal in 1997 [H.V. Klapdor-Kleingrothaus, Int. J. Mod. Phys. A 13 (1998) 3953; H.V. Klapdor-Kleingrothaus, J. Hellmig, M. Hirsch, GENIUS-Proposal, 20 November 1997; J. Hellmig and H.V. Klapdor-Kleingrothaus, Z. Phys. A 359 ( 1997) 351 and nucl-ex/9801004; H.V. Klapdor-Kleingrothaus, M. Hirsch, Z. Phys. A 359 (1997) 361; H.V. Klapdor-Kleingrothaus, J. Hellmig, M. Hirsch, J. Phys. G 24 (1998) 483; H.V. Klapdor-Kleingrothaus, CERN Courier, November 1997, pp. 16-18]. Simultaneous physical goal is to search for the annual modulation of the Dark Matter signal [H.V. Klapdor-Kleingrothaus, et al., Nucl. Instr. and Meth. A 481 (2002) 149; C. Tomei, A. Dietz, I. Krivosheina, H.V. Klapdor-Kleingrothaus, Nucl. Instr. and Meth. 508 (2003) 343]. After operation of GENIUS-TF over three years with finally six naked Ge detectors (15kg) in liquid nitrogen in Gran Sasso we realize serious problems for realization of a full-size GENIUS-like experiment: (1) Background from Rn222 diffusing into the setup, on a level far beyond the expectation. (2) Limited long-term stability of naked detectors in liquid nitrogen as result of increasing leakage current. None of the six detectors is running after three years with the nominal leakage current. Three of the six detectors do not work any more at all. The results of our three years of investigation of the long-term stability may cast doubt on the possibility to perform full GENIUS-like projects

“These called left intellectuals”: the IPM of PCB and the communist phenomenon in cultural production in post-coup

Directory of Open Access Journals (Sweden)

Rodrigo Czajka

2015-08-01

Full Text Available Among the many investigative actions taken by the military with the intention of collecting information about the "communist subversion" in the post-coup in 1964, one of the forms that really stood out was the Police-Military Investigation (IPM. This research instrument was designed to collect proof and evidence which subsequently formed the basis for criminal proceedings based on the National Security Law (LSN. Among the IPMs that gained greater impact was the Brazilian Communist Party (PCB, mainly because it was the starting point for other surveys that have unfolded in specific investigations. One of them, which is discussed in this article concerns the organization of a left intellectuality that if before the coup ground a debate on the political and social thought in Brazil, after the coup will gain even greater projection for his performance in resistance to the regime military. In the IPM of PCB the "intellectual left" or "communist intellectual" are defined by the military reports as having elements of a sophisticated speech of Soviet propaganda, then, should be thoroughly investigated by intelligence services.

HPV18 Persistence Impairs Basal and DNA Ligand-Mediated IFN-β and IFN-λ1 Production through Transcriptional Repression of Multiple Downstream Effectors of Pattern Recognition Receptor Signaling.

Science.gov (United States)

Albertini, Silvia; Lo Cigno, Irene; Calati, Federica; De Andrea, Marco; Borgogna, Cinzia; Dell'Oste, Valentina; Landolfo, Santo; Gariglio, Marisa

2018-03-15

Although it is clear that high-risk human papillomaviruses (HPVs) can selectively infect keratinocytes and persist in the host, it still remains to be unequivocally determined whether they can escape antiviral innate immunity by interfering with pattern recognition receptor (PRR) signaling. In this study, we have assessed the innate immune response in monolayer and organotypic raft cultures of NIKS cells harboring multiple copies of episomal HPV18 (NIKSmcHPV18), which fully recapitulates the persistent state of infection. We show for the first time, to our knowledge, that NIKSmcHPV18, as well as HeLa cells (a cervical carcinoma-derived cell line harboring integrated HPV18 DNA), display marked downregulation of several PRRs, as well as other PRR downstream effectors, such as the adaptor protein stimulator of IFN genes and the transcription factors IRF1 and 7. Importantly, we provide evidence that downregulation of stimulator of IFN genes, cyclic GMP-AMP synthase, and retinoic acid-inducible gene I mRNA levels occurs at the transcriptional level through a novel epigenetic silencing mechanism, as documented by the accumulation of repressive heterochromatin markers seen at the promoter region of these genes. Furthermore, stimulation of NIKSmcHPV18 cells with salmon sperm DNA or poly(deoxyadenylic-deoxythymidylic) acid, two potent inducers of PRR signaling, only partially restored PRR protein expression. Accordingly, the production of IFN-β and IFN-λ 1 was significantly reduced in comparison with the parental NIKS cells, indicating that HPV18 exerts its immunosuppressive activity through downregulation of PRR signaling. Altogether, our findings indicate that high-risk human papillomaviruses have evolved broad-spectrum mechanisms that allow simultaneous depletion of multiple effectors of the innate immunity network, thereby creating an unreactive cellular milieu suitable for viral persistence. Copyright © 2018 by The American Association of Immunologists, Inc.

Structural analysis of TFTR TF coils and support structure for 6 Tesla operation

International Nuclear Information System (INIS)

Zatz, I.J.; Cargulia, G.; Lontai, L.

1995-01-01

The Tokamak Fusion Test Reactor (TFTR), which has been on line since December 1982, has successfully operated at its design Toroidal Field (TF) of 5.2 Tesla. Analysis of test data has indicated that the measured peak D-D neutron power in supershots may be scaled to the fourth power of TF field. Increasing the TF field to 6 Tesla provides the opportunity to explore the possibility of improving the D-T fusion yield, with the use of tritium. This increase in TF field from 5.2 to 6.0 Tesla increases the centering force by 33% and the out-of-plane force by 15% over previous peak operating levels. To examine the impact of the increase in loads on the TF coil, case and supporting structure, finite element analyses (FEA) were performed with and without the presence of loose bolts in the TF case. Note that the loose bolts comprise a fraction of the total number of bolts fastening the TF case sidewalls to the inner and outer rings of the case. Extensive analysis was performed using the FEA results in conjunction with supplementary calculations. Results are presented for the TF case, bolts, copper conductors, insulation, and supporting structure which indicate that the TF coils can successfully operate at 6 Tesla for a reasonable number of pulses

Effects of mutant human Ki-rasG12C gene dosage on murine lung tumorigenesis and signaling to its downstream effectors

International Nuclear Information System (INIS)

Dance-Barnes, Stephanie T.; Kock, Nancy D.; Floyd, Heather S.; Moore, Joseph E.; Mosley, Libyadda J.; D'Agostino, Ralph B.; Pettenati, Mark J.; Miller, Mark Steven

2008-01-01

Studies in cell culture have suggested that the level of RAS expression can influence the transformation of cells and the signaling pathways stimulated by mutant RAS expression. However, the levels of RAS expression in vivo appear to be subject to feedback regulation, limiting the total amount of RAS protein that can be expressed. We utilized a bitransgenic mouse lung tumor model that expressed the human Ki-ras G12C allele in a tetracycline-inducible, lung-specific manner. Treatment for 12 months with 500 μg/ml of doxycycline (DOX) allowed for maximal expression of the human Ki-ras G12C allele in the lung, and resulted in the development of focal hyperplasia and adenomas. We determined if different levels of mutant RAS expression would influence the phenotype of the lung lesions. Treatment with 25, 100 and 500 μg/ml of DOX resulted in dose-dependent increases in transgene expression and tumor multiplicity. Microscopic analysis of the lungs of mice treated with the 25 μg/ml dose of DOX revealed infrequent foci of hyperplasia, whereas mice treated with the 100 and 500 μg/ml doses exhibited numerous hyperplastic foci and also adenomas. Immunohistochemical and RNA analysis of the downstream effector pathways demonstrated that different levels of mutant RAS transgene expression resulted in differences in the expression and/or phosphorylation of specific signaling molecules. Our results suggest that the molecular alterations driving tumorigenesis may differ at different levels of mutant Ki-ras G12C expression, and this should be taken into consideration when inducible transgene systems are utilized to promote tumorigenesis in mouse models

The 1965 coup and reformasi 1998: two critical moments in Indonesia-Malaysia relations during and after the Cold War.

Science.gov (United States)

Maksum, Ali; Bustami, Reevany

2014-01-01

This article discusses the significant impact of the two crucial moments in Indonesia namely, the 1965 coup and reformasi (reformation) in May 1998 and the impact towards the Indonesia-Malaysia relationship. History had demonstrated that both events were followed by some changes in the bilateral relationship. The 1965 coup for instance resulted the fall of Sukarno and the collapse of PKI, while reformasi brought the fall of Suharto and the collapse of New Order. However, it was undeniable that the demands of international situation especially during and after the Cold War were significant factor in driving of those events.

A COUP-TFII Human Embryonic Stem Cell Reporter Line to Identify and Select Atrial Cardiomyocytes

NARCIS (Netherlands)

Schwach, Verena; Verkerk, Arie O.; Mol, Mervyn; Monshouwer-Kloots, Jantine J.; Devalla, Harsha D.; Orlova, Valeria V.; Anastassiadis, Konstantinos; Mummery, Christine L.; Davis, Richard P.; Passier, Robert

2017-01-01

Reporter cell lines have already proven valuable in identifying, tracking, and purifying cardiac subtypes and progenitors during differentiation of human pluripotent stem cells (hPSCs). We previously showed that chick ovalbumin upstream promoter transcription factor II (COUP-TFII) is highly enriched

A-10/TF34 Turbine Engine Monitoring System (TEMS)

Science.gov (United States)

Christopher, R. G.

1981-01-01

The hardware and software development of the A-10/TF34 turbine engine monitoring system (TEMS) is described. The operation and interfaces of the A-10/TF34 TEMS hardware are discussed with particular emphasis on function, capabilities, and limitations. The TEMS data types are defined and the various data acquisition modes are explained. Potential data products are also discussed.

Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis.

Science.gov (United States)

Flore, Gemma; Di Ruberto, Giuseppina; Parisot, Joséphine; Sannino, Sara; Russo, Fabio; Illingworth, Elizabeth A; Studer, Michèle; De Leonibus, Elvira

2017-02-01

The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored. Here, we challenge the in vivo function of the nuclear receptor COUP-TFI (chicken ovalbumin upstream promoter transcription factor 1) in controlling the hippocampal, anatomical, and functional properties along its longitudinal axis. Loss of cortical COUP-TFI function results in a dysmorphic HP with altered shape, volume, and connectivity, particularly in its dorsal and intermediate regions. Notably, topographic inputs from the entorhinal cortex are strongly impaired in the dorsal portion of COUP-TFI mutants. These severe morphological changes are associated with selective spatial learning and memory impairment. These findings identify a novel transcriptional regulator required in the functional organization along the hippocampal septo-temporal axis supporting a genetic basis of the hippocampal volumetric growth with its final shape, circuit, and type of memory function. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Ethnic Politics of Coup Avoidance: Evidence from Zambia and Uganda Ethnopolitik und die Vermeidung von Militärputschen: Sambia und Uganda im Vergleich

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Stefan Lindemann

2011-01-01

Full Text Available Though military interventions seem endemic in sub-Saharan Africa, more than a third of all countries have been able to avoid military coups. To solve this puzzle, this article relates the likelihood of military coups to the degree of ethnic congruence between civilian and military leaders, arguing that coup avoidance is most likely when government and army either exhibit the same ethnic bias or are both ethnically balanced. This argument is illustrated by a comparison of the diverging experiences of Zambia and Uganda. While Zambia is among Africa’s coup-free countries, Uganda’s vulnerability to military intervention has varied over time – with four coups under Obote and the Uganda National Liberation Front (UNLF but no coups under Amin and Museveni. Drawing on original longitudinal data on the ethnic distribution of political and military posts, the article shows that the absence of military coups in Zambia goes back to the balanced composition of government and army. In Uganda, coup avoidance under Amin and Museveni can be linked to the fact that government and army exhibited the same ethnic bias, whereas the coups against the Obote and UNLF regimes reflected either ethnic incongruence between civilian and military leaders or the destabilising combination of a similarly polarised government and army.Politische Interventionen von Militärs scheinen im subsaharischen Afrika allgegenwärtig zu sein. In mehr als einem Drittel der afrikanischen Staaten kam es jedoch bislang nicht zu einem Militärputsch. Der Autor dieses Beitrags vermutet eine Verbindung zwischen dem Grad ethnischer Kongruenz in der zivilen und der militärischen Führung eines Staates und der Wahrscheinlichkeit von Militärinterventionen; er argumentiert, dass ein Putsch immer dann vermieden werden kann, wenn Regierung und militärische Führung entweder von der gleichen ethnischen Gruppe dominiert werden oder wenn beide ethnisch ausgewogen zusammengesetzt sind. Dieser Erkl

Understanding the Roots of West African Conflicts Through the Lens of Coup D’etats

Science.gov (United States)

2016-06-10

Lastly, the study assumes that the US will continue to remain involved in Liberia . This is based off the recent intervention during the Ebola ...external interest, ethnic/religious frictions, and military influences. 15. SUBJECT TERMS West Africa, Coup D’États, Liberia , Ivory Coast, Guinea...11 Liberia

Palmitoylation of Sindbis Virus TF Protein Regulates Its Plasma Membrane Localization and Subsequent Incorporation into Virions.

Science.gov (United States)

Ramsey, Jolene; Renzi, Emily C; Arnold, Randy J; Trinidad, Jonathan C; Mukhopadhyay, Suchetana

2017-02-01

Palmitoylation is a reversible, posttranslational modification that helps target proteins to cellular membranes. The alphavirus small membrane proteins 6K and TF have been reported to be palmitoylated and to positively regulate budding. 6K and TF are isoforms that are identical in their N termini but unique in their C termini due to a -1 ribosomal frameshift during translation. In this study, we used cysteine (Cys) mutants to test differential palmitoylation of the Sindbis virus 6K and TF proteins. We modularly mutated the five Cys residues in the identical N termini of 6K and TF, the four additional Cys residues in TF's unique C terminus, or all nine Cys residues in TF. Using these mutants, we determined that TF palmitoylation occurs primarily in the N terminus. In contrast, 6K is not palmitoylated, even on these shared residues. In the C-terminal Cys mutant, TF protein levels increase both in the cell and in the released virion compared to the wild type. In viruses with the N-terminal Cys residues mutated, TF is much less efficiently localized to the plasma membrane, and it is not incorporated into the virion. The three Cys mutants have minor defects in cell culture growth but a high incidence of abnormal particle morphologies compared to the wild-type virus as determined by transmission electron microscopy. We propose a model where the C terminus of TF modulates the palmitoylation of TF at the N terminus, and palmitoylated TF is preferentially trafficked to the plasma membrane for virus budding. Alphaviruses are a reemerging viral cause of arthritogenic disease. Recently, the small 6K and TF proteins of alphaviruses were shown to contribute to virulence in vivo Nevertheless, a clear understanding of the molecular mechanisms by which either protein acts to promote virus infection is missing. The TF protein is a component of budded virions, and optimal levels of TF correlate positively with wild-type-like particle morphology. In this study, we show that the

Special remote tooling developed and utilized to tighten TFTR TF coil casing bolts

International Nuclear Information System (INIS)

Burgess, T.W.; Walton, G.R.; Meighan, T.G.; Paul, B.L.

1993-01-01

Special tooling has been developed and used to tighten toroidal field (TF) coil casing bolts that have loosened from years of Tokamak Fusion Test Reactor (TFTR) operation. Due to their location, many of the TF casing bolts cannot be directly accessed or viewed; their condition was first discovered during unrelated inspections in 1988. Engineering solutions were, sought until 1992, when a remotely operated wrench concept was successfully demonstrated on a TF coil mockup. The concept was developed into several working tools that have successfully been applied to tighten several thousand TF casing bolts during recent scheduled outages. This effort has improved the integrity and reliability of the TF coil system in preparing for the final experimental phase of the TFTR. This paper discusses the design and application of this tooling

PRESSION PULSEE OU COUP DE BÉLIER HYDRAULIQUE. LE MIRACLE DE SAINT JANVIER : HYPOTHÈSE SUR L'ORIGINE DE L'HÉMORRAGIE CÉRÉBRALE DU SUJET HYPERTENDU.

OpenAIRE

Venet , Richard; Pavie , Alain; Léger , Philippe

2007-01-01

Un poète de l'entre deux guerres a décrit les circonstances de son accident vasculaire cérébral, nous évoquant « un coup de bélier hydraulique ». Pour Ahlqvist l'hémorragie cérébrale est secondaire à l'embolisation (occlusion instantanée) d'une artère cérébrale engendrant ainsi un coup de bélier responsable de la fissuration d'un micro-anévrisme de Charcot. Nous nous proposons dans cet article d'exposer le plus compendieusement possible la théorie du coup de bélier hydraulique. Appliquant cet...

The solar kettle-thermos flask (SK-TF) and solar vacuum tube oven

Energy Technology Data Exchange (ETDEWEB)

Yak, Alex Kee Koo [AkayConsult Enterprise, Johor Bahru (Malaysia)

2008-07-01

The Solar Kettle-Thermos Flask (SK-TF) and Solar Vacuum Tube Oven (SaVeTao): A Cost Effective, Sustainable and Renewable Water Pasteurization and Food Processing System For The Developing World. Based on the perfect solar thermal energy harvesting paradigm of maximum solar radiation absorption and minimum loss of stored converted solar thermal energy, Solar Vacuum Glass Tubes (SVGT) indefinitely delivers solar pasteurized safe drinking water, powered solely by free solar energy. The SVGT is the heart of the SK-TF. Being vacuum insulated, the SK-TF doubles up as a vacuum flask, delivering stored solar heated water in the morning before the Sun is up. With a high stagnation temperature of more than 200 C, the SK-TF can also be used for other heating purposes e.g. an oven or autoclave. Powered solely by free solar energy, the SK-TF and SaVeTaO could very well be the answer in providing safe solar pasteurized drinking water and cooking to the global poor and needy in a sustainable and renewable way. (orig.)

The emerging role of neutrophils in thrombosis – The journey of TF through NETs

Directory of Open Access Journals (Sweden)

Konstantinos eKambas

2012-12-01

Full Text Available The production of TF by neutrophils and their contribution in thrombosis was until recently a matter of scientific debate. Experimental data suggested the de novo TF production by neutrophils under inflammatory stimuli, while others proposed that these cells acquired microparticle-derived TF. Recent experimental evidence revealed the critical role of neutrophils in thrombotic events. Neutrophil derived TF has been implicated in this process in several human and animal models. Additionally, neutrophil extracellular trap (NET release has emerged as a major contributor in neutrophil-driven thrombogenicity in disease models including sepsis, deep venous thrombosis and malignancy. It is suggested that NETs provide the scaffold for fibrin deposition and platelet entrapment and subsequent activation. The recently reported autophagy-dependent extracellular delivery of TF in NETs further supports the involvement of neutrophils in thrombosis. Herein, we seek to review novel data regarding the role of neutrophils in thrombosis, emphasizing the implication of TF and NETs.

Expression of antigen tf and galectin-3 in fibroadenoma.

Science.gov (United States)

Gallegos, Itandehui Belem; Pérez-Campos, Eduardo; Martinez, Margarito; Mayoral, Miguel Ángel; Pérez, Laura; Aguilar, Sergio; Zenteno, Edgar; Pina, Maria del Socorro; Hernández, Pedro

2012-12-24

Fibroadenomas are benign human breast tumors, characterized by proliferation of epithelial and stromal components of the terminal ductal unit. They may grow, regress or remain unchanged, as the hormonal environment of the patient changes. Expression of antigen TF in mucin or mucin-type glycoproteins and of galectin-3 seems to contribute to proliferation and transformations events; their expression has been reported in ductal breast cancer and in aggressive tumors. Lectin histochemistry, immunohistochemistry, and immunofluorescence were used to examine the expression and distribution of antigen TF and galectin-3. We used lectins from Arachis hypogaea, Artocarpus integrifolia, and Amaranthus lecuocarpus to evaluate TF expression and a monoclonal antibody to evaluate galectin-3 expression. We used paraffin-embedded blocks from 10 breast tissues diagnosed with fibroadenoma and as control 10 healthy tissue samples. Histochemical and immunofluorescence analysis showed positive expression of galectin-3 in fibroadenoma tissue, mainly in stroma, weak interaction in ducts was observed; whereas, in healthy tissue samples the staining was also weak in ducts. Lectins from A. leucocarpus and A. integrifolia specificaly recognized ducts in healthy breast samples, whereas the lectin from A. hypogaea recognized ducts and stroma. In fibroadenoma tissue, the lectins from A. integrifolia, A. Hypogaea, and A. leucocarpus recognized mainly ducts. Our results suggest that expression of antigen TF and galectin-3 seems to participate in fibroadenoma development.

Expression of antigen tf and galectin-3 in fibroadenoma

Directory of Open Access Journals (Sweden)

Gallegos Itandehui Belem

2012-12-01

Full Text Available Abstract Background Fibroadenomas are benign human breast tumors, characterized by proliferation of epithelial and stromal components of the terminal ductal unit. They may grow, regress or remain unchanged, as the hormonal environment of the patient changes. Expression of antigen TF in mucin or mucin-type glycoproteins and of galectin-3 seems to contribute to proliferation and transformations events; their expression has been reported in ductal breast cancer and in aggressive tumors. Findings Lectin histochemistry, immunohistochemistry, and immunofluorescence were used to examine the expression and distribution of antigen TF and galectin-3. We used lectins from Arachis hypogaea, Artocarpus integrifolia, and Amaranthus lecuocarpus to evaluate TF expression and a monoclonal antibody to evaluate galectin-3 expression. We used paraffin-embedded blocks from 10 breast tissues diagnosed with fibroadenoma and as control 10 healthy tissue samples. Histochemical and immunofluorescence analysis showed positive expression of galectin-3 in fibroadenoma tissue, mainly in stroma, weak interaction in ducts was observed; whereas, in healthy tissue samples the staining was also weak in ducts. Lectins from A. leucocarpus and A. integrifolia specificaly recognized ducts in healthy breast samples, whereas the lectin from A. hypogaea recognized ducts and stroma. In fibroadenoma tissue, the lectins from A. integrifolia, A. Hypogaea, and A. leucocarpus recognized mainly ducts. Conclusions Our results suggest that expression of antigen TF and galectin-3 seems to participate in fibroadenoma development.

Oomycetes, effectors, and all that jazz.

Science.gov (United States)

Bozkurt, Tolga O; Schornack, Sebastian; Banfield, Mark J; Kamoun, Sophien

2012-08-01

Plant pathogenic oomycetes secrete a diverse repertoire of effector proteins that modulate host innate immunity and enable parasitic infection. Understanding how effectors evolve, translocate and traffic inside host cells, and perturb host processes are major themes in the study of oomycete-plant interactions. The last year has seen important progress in the study of oomycete effectors with, notably, the elucidation of the 3D structures of five RXLR effectors, and novel insights into how cytoplasmic effectors subvert host cells. In this review, we discuss these and other recent advances and highlight the most important open questions in oomycete effector biology. Copyright © 2012 Elsevier Ltd. All rights reserved.

Functionally redundant RXLR effectors from Phytophthora infestans act at different steps to suppress early flg22-triggered immunity.

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Xiangzi Zheng

2014-04-01

Full Text Available Genome sequences of several economically important phytopathogenic oomycetes have revealed the presence of large families of so-called RXLR effectors. Functional screens have identified RXLR effector repertoires that either compromise or induce plant defense responses. However, limited information is available about the molecular mechanisms underlying the modes of action of these effectors in planta. The perception of highly conserved pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs, such as flg22, triggers converging signaling pathways recruiting MAP kinase cascades and inducing transcriptional re-programming, yielding a generic anti-microbial response. We used a highly synchronizable, pathogen-free protoplast-based assay to identify a set of RXLR effectors from Phytophthora infestans (PiRXLRs, the causal agent of potato and tomato light blight that manipulate early stages of flg22-triggered signaling. Of thirty-three tested PiRXLR effector candidates, eight, called Suppressor of early Flg22-induced Immune response (SFI, significantly suppressed flg22-dependent activation of a reporter gene under control of a typical MAMP-inducible promoter (pFRK1-Luc in tomato protoplasts. We extended our analysis to Arabidopsis thaliana, a non-host plant species of P. infestans. From the aforementioned eight SFI effectors, three appeared to share similar functions in both Arabidopsis and tomato by suppressing transcriptional activation of flg22-induced marker genes downstream of post-translational MAP kinase activation. A further three effectors interfere with MAMP signaling at, or upstream of, the MAP kinase cascade in tomato, but not in Arabidopsis. Transient expression of the SFI effectors in Nicotiana benthamiana enhances susceptibility to P. infestans and, for the most potent effector, SFI1, nuclear localization is required for both suppression of MAMP signaling and virulence function. The present study provides a framework to decipher the

Reading paths, eye drawings, and word islands: Movement in Un coup de dés.

Science.gov (United States)

Loos, Ruth

2012-01-01

In the framework of an artistic-scientific project on eye-movements during reading, my collaborators from the psychology department at the KU Leuven and I had a close look at the poem "Un coup de dés jamais n'abolira le hasard" ("A throw of the dice will never abolish chance") by Stéphane Mallarmé. The poem is an intriguing example of nonlinear writing, of a typographic game with white and space, and of an interweaving of different reading lines. These specific features evoke multiple reading methods. The animation, Movement in Un coup de dés, created during the still-ongoing collaboration interweaves a horizontal and a vertical reading method, two spontaneous ways of reading that point at the poem's intriguing ambiguity. Not only are we interested in different methods of reading; the scientific representations of eye movements themselves are a rich source of images with much artistic potential. We explore eye movements as "eye drawings" in new images characterized both by a scientific and by an artistic perspective.

Reading Paths, Eye Drawings, and Word Islands: Movement in Un coup de dés

Directory of Open Access Journals (Sweden)

Ruth Loos

2012-01-01

Full Text Available In the framework of an artistic–scientific project on eye-movements during reading, my collaborators from the psychology department at the KU Leuven and I had a close look at the poem “Un coup de dés jamais n'abolira le hasard” (“A throw of the dice will never abolish chance” by Stéphane Mallarmé. The poem is an intriguing example of nonlinear writing, of a typographic game with white and space, and of an interweaving of different reading lines. These specific features evoke multiple reading methods. The animation, Movement in Un coup de dés, created during the still-ongoing collaboration interweaves a horizontal and a vertical reading method, two spontaneous ways of reading that point at the poem's intriguing ambiguity. Not only are we interested in different methods of reading; the scientific representations of eye movements themselves are a rich source of images with much artistic potential. We explore eye movements as “eye drawings” in new images characterized both by a scientific and by an artistic perspective.

Late onset ‘en coup de sabre’ following trauma: Rare presentation of a rare disease

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Tasleem Arif

2015-01-01

Full Text Available En coup de sabre (linear scleroderma of face is a rare type of morphea (localized scleroderma involving frontoparietal area of the forehead and scalp. Many triggering factors have been implicated in the development of morphea like trauma, immobilization, bacille Calmette–Guérin (BCG vaccination, injections of vitamin K, mechanical compression from clothing, etc. Linear scleroderma primarily affects the pediatric population, with 67% of patients diagnosed before 18 years of age. In this article, we describe a case of 26 year old female who presented with a three months history of brownish indurated plaque of skin on the frontal and forehead regions of the head. The patient gave a history of trauma at the same site six years back. The diagnosis of morphea was made clinically supported by histopathological features of the skin biopsy. Her neurological examination was normal. ANA was negative. Brain MRI didn’t reveal any abnormality. She was treated with topical tacrolimus 0.1% ointment. The late onset en coup de sabre is a rare presentation and hence reported.

The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to lysosomes.

Science.gov (United States)

Marwaha, Rituraj; Arya, Subhash B; Jagga, Divya; Kaur, Harmeet; Tuli, Amit; Sharma, Mahak

2017-04-03

Endocytic, autophagic, and phagocytic vesicles move on microtubule tracks to fuse with lysosomes. Small GTPases, such as Rab7 and Arl8b, recruit their downstream effectors to mediate this transport and fusion. However, the potential cross talk between these two GTPases is unclear. Here, we show that the Rab7 effector PLEKHM1 simultaneously binds Rab7 and Arl8b, bringing about clustering and fusion of late endosomes and lysosomes. We show that the N-terminal RUN domain of PLEKHM1 is necessary and sufficient for interaction with Arl8b and its subsequent localization to lysosomes. Notably, we also demonstrate that Arl8b mediates recruitment of HOPS complex to PLEKHM1-positive vesicle contact sites. Consequently, Arl8b binding to PLEKHM1 is required for its function in delivery and, therefore, degradation of endocytic and autophagic cargo in lysosomes. Finally, we also show that PLEKHM1 competes with SKIP for Arl8b binding, which dictates lysosome positioning. These findings suggest that Arl8b, along with its effectors, orchestrates lysosomal transport and fusion. © 2017 Marwaha et al.

The Organization of African Unity and Peacekeeping: The Pan-African Defense Force

Science.gov (United States)

1981-06-05

Diary " (hereafter cited TF 203 WD), p. 5. o i~i171bid. 18 The Commander of the Nigerian troops in Chad was different for TF 203 Commander. 19 FAT was...independence to help in training and organizing the armed forces. For example, the British officers working in K", aya argued against any expansion of...Happened in Chad?" West Africa, 21 April 1975, p. 442. "Matchet’s Diary ." West Africa, 21 April 1975, p. 445. "Chad. Desert Coup." Time, 26 February

Target of rapamycin complex 2 signals to downstream effector yeast protein kinase 2 (Ypk2) through adheres-voraciously-to-target-of-rapamycin-2 protein 1 (Avo1) in Saccharomyces cerevisiae.

Science.gov (United States)

Liao, Hsien-Ching; Chen, Mei-Yu

2012-02-24

The conserved Ser/Thr kinase target of rapamycin (TOR) serves as a central regulator in controlling cell growth-related functions. There exist two distinct TOR complexes, TORC1 and TORC2, each coupling to specific downstream effectors and signaling pathways. In Saccharomyces cerevisiae, TORC2 is involved in regulating actin organization and maintaining cell wall integrity. Ypk2 (yeast protein kinase 2), a member of the cAMP-dependent, cGMP-dependent, and PKC (AGC) kinase family, is a TORC2 substrate known to participate in actin and cell wall regulation. Employing avo3(ts) mutants with defects in TORC2 functions that are suppressible by active Ypk2, we investigated the molecular interactions involved in mediating TORC2 signaling to Ypk2. GST pulldown assays in yeast lysates demonstrated physical interactions between Ypk2 and components of TORC2. In vitro binding assays revealed that Avo1 directly binds to Ypk2. In avo3(ts) mutants, the TORC2-Ypk2 interaction was reduced and could be restored by AVO1 overexpression, highlighting the important role of Avo1 in coupling TORC2 to Ypk2. The interaction was mapped to an internal region (amino acids 600-840) of Avo1 and a C-terminal region of Ypk2. Ypk2(334-677), a truncated form of Ypk2 containing the Avo1-interacting region, was able to interfere with Avo1-Ypk2 interaction in vitro. Overexpressing Ypk2(334-677) in yeast cells resulted in a perturbation of TORC2 functions, causing defective cell wall integrity, aberrant actin organization, and diminished TORC2-dependent Ypk2 phosphorylation evidenced by the loss of an electrophoretic mobility shift. Together, our data support the conclusion that the direct Avo1-Ypk2 interaction is crucial for TORC2 signaling to the downstream Ypk2 pathway.

A new sample treatment for asialo-Tf determination with capillary electrophoresis: an added value to the analysis of CDT.

Science.gov (United States)

Porpiglia, Nadia Maria; De Palo, Elio Franco; Savchuk, Sergey Alexandrovich; Appolonova, Svetlana Alexandrovna; Bortolotti, Federica; Tagliaro, Franco

2018-05-10

The non-glycosylated glycoform of transferrin (Tf), known as asialo-Tf, was not selected (in favor of disialo-Tf) as the measurand for the standardization of carbohydrate deficient transferrin (CDT) determination because of a lower diagnostic sensitivity provided with the currently available analytical procedures for sera. However, asialo-Tf could provide an additional value to disialo-Tf in the CDT analysis employed in forensic toxicology contexts. The present work aimed at developing an easy sample preparation based on PEG precipitation in order to improve the detectability of asialo-Tf in capillary electrophoresis (CE). Equal volumes (35 μL) of serum and of 30% PEG-8000 were mixed and briefly vortexed. After centrifugation, the supernatant was iron saturated with a ferric solution (1:1, v/v). The mixture was analyzed in CE for asialo-Tf and disialo-Tf determination. PEG-8000 precipitation allowed the improvement of the baseline in the electropherograms in terms of interferences reduction particularly in the asialo-Tf migration region. The detection of asialo-Tf was possible in 89% of samples with disialo-Tf above the cut-off limit, whereas only 16% of them showed asialo-Tf by employing the traditional sample preteatment. Asialo-Tf represents an additional value to disialo-Tf as a biomarker of alcohol abuse in forensic toxicology. Copyright © 2018. Published by Elsevier B.V.

TF insert experiment log book. 2nd Experiment of CS model coil

International Nuclear Information System (INIS)

Sugimoto, Makoto; Isono, Takaaki; Matsui, Kunihiro

2001-12-01

The cool down of CS model coil and TF insert was started on August 20, 2001. It took almost one month and immediately started coil charge since September 17, 2001. The charge test of TF insert and CS model coil was completed on October 19, 2001. In this campaign, total shot numbers were 88 and the size of the data file in the DAS (Data Acquisition System) was about 4 GB. This report is a database that consists of the log list and the log sheets of every shot. This is an experiment logbook for 2nd experiment of CS model coil and TF insert for charge test. (author)

Simulating ectomycorrhiza in boreal forests: implementing ectomycorrhizal fungi model MYCOFON in CoupModel (v5)

Science.gov (United States)

He, Hongxing; Meyer, Astrid; Jansson, Per-Erik; Svensson, Magnus; Rütting, Tobias; Klemedtsson, Leif

2018-02-01

The symbiosis between plants and Ectomycorrhizal fungi (ECM) is shown to considerably influence the carbon (C) and nitrogen (N) fluxes between the soil, rhizosphere, and plants in boreal forest ecosystems. However, ECM are either neglected or presented as an implicit, undynamic term in most ecosystem models, which can potentially reduce the predictive power of models.In order to investigate the necessity of an explicit consideration of ECM in ecosystem models, we implement the previously developed MYCOFON model into a detailed process-based, soil-plant-atmosphere model, Coup-MYCOFON, which explicitly describes the C and N fluxes between ECM and roots. This new Coup-MYCOFON model approach (ECM explicit) is compared with two simpler model approaches: one containing ECM implicitly as a dynamic uptake of organic N considering the plant roots to represent the ECM (ECM implicit), and the other a static N approach in which plant growth is limited to a fixed N level (nonlim). Parameter uncertainties are quantified using Bayesian calibration in which the model outputs are constrained to current forest growth and soil C / N ratio for four forest sites along a climate and N deposition gradient in Sweden and simulated over a 100-year period.The nonlim approach could not describe the soil C / N ratio due to large overestimation of soil N sequestration but simulate the forest growth reasonably well. The ECM implicit and explicit approaches both describe the soil C / N ratio well but slightly underestimate the forest growth. The implicit approach simulated lower litter production and soil respiration than the explicit approach. The ECM explicit Coup-MYCOFON model provides a more detailed description of internal ecosystem fluxes and feedbacks of C and N between plants, soil, and ECM. Our modeling highlights the need to incorporate ECM and organic N uptake into ecosystem models, and the nonlim approach is not recommended for future long-term soil C and N predictions. We also

A Phytophthora sojae effector PsCRN63 forms homo-/hetero-dimers to suppress plant immunity via an inverted association manner.

Science.gov (United States)

Li, Qi; Zhang, Meixiang; Shen, Danyu; Liu, Tingli; Chen, Yanyu; Zhou, Jian-Min; Dou, Daolong

2016-05-31

Oomycete pathogens produce a large number of effectors to promote infection. Their mode of action are largely unknown. Here we show that a Phytophthora sojae effector, PsCRN63, suppresses flg22-induced expression of FRK1 gene, a molecular marker in pathogen-associated molecular patterns (PAMP)-triggered immunity (PTI). However, PsCRN63 does not suppress upstream signaling events including flg22-induced MAPK activation and BIK1 phosphorylation, indicating that it acts downstream of MAPK cascades. The PsCRN63-transgenic Arabidopsis plants showed increased susceptibility to bacterial pathogen Pseudomonas syringae pathovar tomato (Pst) DC3000 and oomycete pathogen Phytophthora capsici. The callose deposition were suppressed in PsCRN63-transgenic plants compared with the wild-type control plants. Genes involved in PTI were also down-regulated in PsCRN63-transgenic plants. Interestingly, we found that PsCRN63 forms an dimer that is mediated by inter-molecular interactions between N-terminal and C-terminal domains in an inverted association manner. Furthermore, the N-terminal and C-terminal domains required for the dimerization are widely conserved among CRN effectors, suggesting that homo-/hetero-dimerization of Phytophthora CRN effectors is required to exert biological functions. Indeed, the dimerization was required for PTI suppression and cell death-induction activities of PsCRN63.

FVIIa-sTF and Thrombin Inhibitory Activities of Compounds Isolated from Microcystis aeruginosa K-139

Directory of Open Access Journals (Sweden)

Andrea Roxanne J. Anas

2017-08-01

Full Text Available The rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake Kasumigaura, Ibaraki, Japan, as a promising cyanobacterium for isolation of fVIIa-sTF inhibitors. M. aeruginosa K-139 underwent reversed-phase solid-phase extraction (ODS-SPE from 20% MeOH to MeOH elution with 40%-MeOH increments, which afforded aeruginosin K-139 in the 60% MeOH fraction; micropeptin K-139 and microviridin B in the MeOH fraction. Aeruginosin K-139 displayed an fVIIa-sTF inhibitory activity of ~166 µM, within a 95% confidence interval. Micropeptin K-139 inhibited fVIIa-sTF with EC50 10.62 µM, which was more efficient than thrombin inhibition of EC50 26.94 µM. The thrombin/fVIIa-sTF ratio of 2.54 in micropeptin K-139 is higher than those in 4-amidinophenylmethane sulfonyl fluoride (APMSF and leupeptin, when used as positive controls. This study proves that M. aeruginosa K-139 is a new source of fVIIa-sTF inhibitors. It also opens a new avenue for micropeptin K-139 and related depsipeptides as fVIIa-sTF inhibitors.

A restructuring of TF package for MIDAS computer code

International Nuclear Information System (INIS)

Park, S. H.; Song, Y. M.; Kim, D. H.

2002-01-01

TF package which defines some interpolation and extrapolation condition through user defined table has been restructured in MIDAS computer code. To do this, data transferring methods of current MELCOR code are modified and adopted into TF package. The data structure of the current MELCOR code using FORTRAN77 causes a difficult grasping of the meaning of the variables as well as waste of memory. New features of FORTRAN90 make it possible to allocate the storage dynamically and to use the user-defined data type, which lead to an efficient memory treatment and an easy understanding of the code. Restructuring of TF package addressed in this paper does module development and subroutine modification, and treats MELGEN which is making restart file as well as MELCOR which is processing calculation. The validation has been done by comparing the results of the modified code with those from the existing code, and it is confirmed that the results are the same. It hints that the similar approach could be extended to the entire code package. It is expected that code restructuring will accelerate the code domestication thanks to direct understanding of each variable and easy implementation of modified or newly developed models

Repeat-containing protein effectors of plant-associated organisms

Directory of Open Access Journals (Sweden)

Carl H. Mesarich

2015-10-01

Full Text Available Many plant-associated organisms, including microbes, nematodes, and insects, deliver effector proteins into the apoplast, vascular tissue, or cell cytoplasm of their prospective hosts. These effectors function to promote colonization, typically by altering host physiology or by modulating host immune responses. The same effectors however, can also trigger host immunity in the presence of cognate host immune receptor proteins, and thus prevent colonization. To circumvent effector-triggered immunity, or to further enhance host colonization, plant-associated organisms often rely on adaptive effector evolution. In recent years, it has become increasingly apparent that several effectors of plant-associated organisms are repeat-containing proteins (RCPs that carry tandem or non-tandem arrays of an amino acid sequence or structural motif. In this review, we highlight the diverse roles that these repeat domains play in RCP effector function. We also draw attention to the potential role of these repeat domains in adaptive evolution with regards to RCP effector function and the evasion of effector-triggered immunity. The aim of this review is to increase the profile of RCP effectors from plant-associated organisms.

Senses of “revolução” and “revolución” in the coup written press of Brazil (1964 and Argentina (1966

Directory of Open Access Journals (Sweden)

María Alejandra Vitale

2013-06-01

Full Text Available In this article we cross the theoretical connections that can be established between Bakhtin Circle dialogism and some aspects of the discourse theory of Michel Pêcheux, considering the reading of both made by Jacqueline Authier-Revuz in the frame of her proposal about enunciative heterogeneities. We also try to describe the senses of the word "revolução" in O Globo and Folha de S. Paulo related to the Brazilian coup d’état of March 31st, 1964 and compare it to what happened in the Argentinean press with the word "revolución" facing the military coup of June 28th, 1966.

A Follow-Up Study from a Multisite, Randomized Controlled Trial for Traumatized Children Receiving TF-CBT.

Science.gov (United States)

Jensen, Tine K; Holt, Tonje; Ormhaug, Silje M

2017-11-01

Trauma-focused cognitive behavioral therapy (TF-CBT) is the treatment of choice for traumatized youth, however, follow-up studies are scarce, and treatment effects for co-occurring depression show mixed findings. The aims of this study were to examine whether treatment effects of TF-CBT are maintained at 18 month follow-up and whether degree of co-occurring depression influences treatment effects. As rapid improvement in psychological functioning is warranted for youth, we also investigated whether the symptom trajectory was different for TF-CBT compared to therapy as usual (TAU). The sample consisted of 156 youth (M age = 15.05, 79.50% girls) randomly assigned to TF-CBT or TAU. The youth were assessed for posttraumatic stress symptoms (PTSS), depression, anxiety and general mental health symptoms. Mixed effects analyses followed the symptom courses over 5 time points. Youth receiving TF-CBT maintained their symptom improvement at 18 months follow-up with scores below clinical cut-of on all symptom measures. The most depressed youth had also a significant decline in symptoms that were maintained at follow-up. Symptom trajectories differed as the TF-CBT group reported a more rapid symptom reduction compared to the TAU condition. In the TAU condition, participants received 1.5 times the number of treatment sessions compared to the TF-CBT participants. After 18 months the groups were significantly different on general mental health symptoms only. In conclusion, youth receiving TF-CBT experienced more efficient improvement in trauma related symptoms than youth receiving TAU and these improvements were maintained after 18 months. Also youth experiencing serious co-occurring depression benefitted from TF-CBT.

Neurologic Involvement in Scleroderma en Coup de Sabre

Science.gov (United States)

Amaral, Tiago Nardi; Marques Neto, João Francisco; Lapa, Aline Tamires; Peres, Fernando Augusto; Guirau, Caio Rodrigues; Appenzeller, Simone

2012-01-01

Localized scleroderma is a rare disease, characterized by sclerotic lesions. A variety of presentations have been described, with different clinical characteristics and specific prognosis. In scleroderma en coup de sabre (LScs) the atrophic lesion in frontoparietal area is the disease hallmark. Skin and subcutaneous are the mainly affected tissues, but case reports of muscle, cartilage, and bone involvement are frequent. These cases pose a difficult differential diagnosis with Parry-Romberg syndrome. Once considered an exclusive cutaneous disorder, the neurologic involvement present in LScs has been described in several case reports. Seizures are most frequently observed, but focal neurologic deficits, movement disorders, trigeminal neuralgia, and mimics of hemiplegic migraines have been reported. Computed tomography and magnetic resonance imaging have aided the characterization of central nervous system lesions, and cerebral angiograms have pointed to vasculitis as a part of disease pathogenesis. In this paper we describe the clinical and radiologic aspects of neurologic involvement in LScs. PMID:22319646

Late onset ‘en coup de sabre’ following trauma: Rare presentation of a rare disease

OpenAIRE

Tasleem Arif; Imran Majid; Mir Laieq Ishtiyaq Haji

2015-01-01

En coup de sabre (linear scleroderma of face) is a rare type of morphea (localized scleroderma) involving frontoparietal area of the forehead and scalp. Many triggering factors have been implicated in the development of morphea like trauma, immobilization, bacille Calmette–Guérin (BCG) vaccination, injections of vitamin K, mechanical compression from clothing, etc. Linear scleroderma primarily affects the pediatric population, with 67% of patients diagnosed before 18 years of age....

From data repositories to submission portals: rethinking the role of domain-specific databases in CollecTF.

Science.gov (United States)

Kılıç, Sefa; Sagitova, Dinara M; Wolfish, Shoshannah; Bely, Benoit; Courtot, Mélanie; Ciufo, Stacy; Tatusova, Tatiana; O'Donovan, Claire; Chibucos, Marcus C; Martin, Maria J; Erill, Ivan

2016-01-01

Domain-specific databases are essential resources for the biomedical community, leveraging expert knowledge to curate published literature and provide access to referenced data and knowledge. The limited scope of these databases, however, poses important challenges on their infrastructure, visibility, funding and usefulness to the broader scientific community. CollecTF is a community-oriented database documenting experimentally validated transcription factor (TF)-binding sites in the Bacteria domain. In its quest to become a community resource for the annotation of transcriptional regulatory elements in bacterial genomes, CollecTF aims to move away from the conventional data-repository paradigm of domain-specific databases. Through the adoption of well-established ontologies, identifiers and collaborations, CollecTF has progressively become also a portal for the annotation and submission of information on transcriptional regulatory elements to major biological sequence resources (RefSeq, UniProtKB and the Gene Ontology Consortium). This fundamental change in database conception capitalizes on the domain-specific knowledge of contributing communities to provide high-quality annotations, while leveraging the availability of stable information hubs to promote long-term access and provide high-visibility to the data. As a submission portal, CollecTF generates TF-binding site information through direct annotation of RefSeq genome records, definition of TF-based regulatory networks in UniProtKB entries and submission of functional annotations to the Gene Ontology. As a database, CollecTF provides enhanced search and browsing, targeted data exports, binding motif analysis tools and integration with motif discovery and search platforms. This innovative approach will allow CollecTF to focus its limited resources on the generation of high-quality information and the provision of specialized access to the data.Database URL: http://www.collectf.org/. © The Author(s) 2016

TF.Learn: TensorFlow's High-level Module for Distributed Machine Learning

OpenAIRE

Tang, Yuan

2016-01-01

TF.Learn is a high-level Python module for distributed machine learning inside TensorFlow. It provides an easy-to-use Scikit-learn style interface to simplify the process of creating, configuring, training, evaluating, and experimenting a machine learning model. TF.Learn integrates a wide range of state-of-art machine learning algorithms built on top of TensorFlow's low level APIs for small to large-scale supervised and unsupervised problems. This module focuses on bringing machine learning t...

Mutation in Torenia fournieri Lind. UFO homolog confers loss of TfLFY interaction and results in a petal to sepal transformation.

Science.gov (United States)

Sasaki, Katsutomo; Yamaguchi, Hiroyasu; Aida, Ryutaro; Shikata, Masahito; Abe, Tomoko; Ohtsubo, Norihiro

2012-09-01

We identified a Torenia fournieri Lind. mutant (no. 252) that exhibited a sepaloid phenotype in which the second whorls were changed to sepal-like organs. This mutant had no stamens, and the floral organs consisted of sepals and carpels. Although the expression of a torenia class B MADS-box gene, GLOBOSA (TfGLO), was abolished in the 252 mutant, no mutation of TfGLO was found. Among torenia homologs such as APETALA1 (AP1), LEAFY (LFY), and UNUSUAL FLORAL ORGANS (UFO), which regulate expression of class B genes in Arabidopsis, only accumulation of the TfUFO transcript was diminished in the 252 mutant. Furthermore, a missense mutation was found in the coding region of the mutant TfUFO. Intact TfUFO complemented the mutant phenotype whereas mutated TfUFO did not; in addition, the transgenic phenotype of TfUFO-knockdown torenias coincided with the mutant phenotype. Yeast two-hybrid analysis revealed that the mutated TfUFO lost its ability to interact with TfLFY protein. In situ hybridization analysis indicated that the transcripts of TfUFO and TfLFY were partially accumulated in the same region. These results clearly demonstrate that the defect in TfUFO caused the sepaloid phenotype in the 252 mutant due to the loss of interaction with TfLFY. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

The Art and Skill of Delivering Culturally Responsive TF-CBT in Tanzania and Kenya

Science.gov (United States)

Kava, Christine M.; Akiba, Christopher F.; Lucid, Leah; Dorsey, Shannon

2016-01-01

Objective This study explored the facilitators, barriers, and strategies used to deliver a child mental health evidence-based treatment (EBT), trauma-focused cognitive behavioral therapy (TF-CBT), in a culturally responsive manner. In low- and middle-income countries most individuals with mental health problems do not receive treatment due to a shortage of mental health professionals. One approach to addressing this problem is task-sharing, in which lay counselors are trained to deliver mental health treatment. Combining this approach with a focus on EBT provides a strategy for bridging the mental health treatment gap. However, little is known how about western-developed EBTs are delivered in a culturally responsive manner. Method Semistructured qualitative interviews were conducted with 12 TF-CBT lay counselors involved in a large randomized controlled trial of TF-CBT in Kenya and Tanzania. An inductive approach was used to analyze the data. Results Lay counselors described the importance of being responsive to TF-CBT participants’ customs, beliefs, and socioeconomic conditions and highlighted the value of TF-CBT for their community. They also discussed the importance of partnering with other organizations to address unmet socioeconomic needs. Conclusion The findings from this study provide support for the acceptability and appropriateness of TF-CBT as a treatment approach for improving child mental health. Having a better understanding of the strategies used by lay counselors to ensure that treatment is relevant to the cultural and socioeconomic context of participants can help to inform the implementation of future EBTs. PMID:27414470

Progressive Hemifacial Atrophy and Linear Scleroderma En Coup de Sabre: A Spectrum of the Same Disease?

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Irina Khamaganova

2018-01-01

Full Text Available Similar clinical and histhopathological features in progressive hemifacial atrophy and linear scleroderma en coup de sabre are well known. Trauma may predispose to the development of both diseases. The lack of association with anti-Borrelia antibodies was shown in both cases as well. The otolaryngological and endocrine disorders may be associated findings in both diseases. However, there are certain differences in neurological and ophthalmological changes in the diseases.

Fabrication of new joints for SST-1 TF coil winding packs

International Nuclear Information System (INIS)

Prasad, Upendra; Sharma, A.N.; Patel, Dipak; Doshi, Kalpesh; Khristi, Yohan; Varmora, Pankaj; Chauhan, Pradeep; Jadeja, S.J.; Gupta, Pratibha; Pradhan, S.

2013-01-01

Highlights: • We have carried out work related with sub-nanoohm joints for superconducting Tokamak winding packs. • We have established fine tune QA/QC procedures for sub-nanoohm joints fabrication. • We have optimised welding parameters for cable in conduit conductors for fusion relevant magnets. • We have established precised measurement data acquisition system for low resistance measurements at cryogenic temperature. -- Abstract: The Toroidal Field (TF) magnet system of SST-1 has sixteen NbTi/Cu based coils with about one hundred Inter-Pancake (IP) and Inter-Coil (IC) joints. New box type helium leak tight, low DC resistance joints have been designed, fabricated and tested at 5 K temperature and 10 kA DC transport current. The prototype of this joint has been validated in laboratory as well as on spare TF coil winding pack. Moreover, the performance of these joints has been realised and validated on actual sixteen TF winding packs, the joint resistance of ∼0.5 nΩ repeatedly measured on hundreds of IP joints. The quality of terminations and joints was ensured at various stages of fabrication. The quality of joint box material was ensured by visual inspection, chemical analysis, radiography test, ultrasonic test, eddy current test, etc. This paper describes joint design drivers, joint design detail, prototype joint fabrication processes, quality assurance (QA)/quality control (QC) adopted during prototype and actual joint fabrication process, joint resistance measurement on actual TF coils and analysis of measured joint resistance in detail

Tight aspect ratio tokamak power reactor with superconducting TF coils

International Nuclear Information System (INIS)

Nishio, S.; Tobita, K.; Konishi, S.; Ando, T.; Hiroki, S.; Kuroda, T.; Yamauchi, M.; Azumi, M.; Nagata, M.

2003-01-01

Tight aspect ratio tokamak power reactor with super-conducting toroidal field (TF) coils has been proposed. A center solenoid coil system and an inboard blanket were discarded. The key point was how to find the engineering design solution of the TF coil system with the high field and high current density. The coil system with the center post radius of less than 1 m can generate the maximum field of ∼ 20 T. This coil system causes a compact reactor concept, where the plasma major and minor radii of 3.75 m and 1.9 m, respectively and the fusion power of 1.8 GW. (author)

Taking Stock (with discomfort of the Military Dictatorship Fifty Years after the 1964 Coup: a Bibliographical Essay

Directory of Open Access Journals (Sweden)

Maria Celina D’Araujo

2015-12-01

Full Text Available This essay reviews the main analyses produced for publication in 2014 alluding to the 50th anniversary of the 1964 coup and the dictatorship that followed (1964-85. It is noteworthy that most of these analyses, authored by historians and journalists, relativize several Manichaean concepts and versions; chiefly, they enhance society's responsibility for this authoritarian experiment. The coup, they claim, was not an atypical event in the country's political history; it simply expanded conservative and authoritarian values. In daring fashion, they point out the precarious or absent democratic vocation of the forces of the Left, as well as the advances in terms of the country's economic and social modernization under the military governments. The duration of the dictatorship is also questioned. In the eyes of some, it lasted only from 1964 to 1979, and arguments to this end are exhaustively presented. The fact that the report of the National Truth Commission (NTC was released also in 2014 raised an intense debate in the press and in academia about repression and the crimes of the dictatorship, especially against urban guerrilla organizations, which are also examined in instigating fashion in this bibliography.

Monitoring gaseous CO2 and ethanol above champagne glasses: flute versus coupe, and the role of temperature.

Directory of Open Access Journals (Sweden)

Gérard Liger-Belair

Full Text Available In champagne tasting, gaseous CO(2 and volatile organic compounds progressively invade the headspace above glasses, thus progressively modifying the chemical space perceived by the consumer. Simultaneous quantification of gaseous CO(2 and ethanol was monitored through micro-gas chromatography (μGC, all along the first 15 minutes following pouring, depending on whether a volume of 100 mL of champagne was served into a flute or into a coupe. The concentration of gaseous CO(2 was found to be significantly higher above the flute than above the coupe. Moreover, a recently developed gaseous CO(2 visualization technique based on infrared imaging was performed, thus confirming this tendency. The influence of champagne temperature was also tested. As could have been expected, lowering the temperature of champagne was found to decrease ethanol vapor concentrations in the headspace of a glass. Nevertheless, and quite surprisingly, this temperature decrease had no impact on the level of gaseous CO(2 found above the glass. Those results were discussed on the basis of a multiparameter model which describes fluxes of gaseous CO(2 escaping the liquid phase into the form of bubbles.

Monitoring gaseous CO2 and ethanol above champagne glasses: flute versus coupe, and the role of temperature.

Science.gov (United States)

Liger-Belair, Gérard; Bourget, Marielle; Pron, Hervé; Polidori, Guillaume; Cilindre, Clara

2012-01-01

In champagne tasting, gaseous CO(2) and volatile organic compounds progressively invade the headspace above glasses, thus progressively modifying the chemical space perceived by the consumer. Simultaneous quantification of gaseous CO(2) and ethanol was monitored through micro-gas chromatography (μGC), all along the first 15 minutes following pouring, depending on whether a volume of 100 mL of champagne was served into a flute or into a coupe. The concentration of gaseous CO(2) was found to be significantly higher above the flute than above the coupe. Moreover, a recently developed gaseous CO(2) visualization technique based on infrared imaging was performed, thus confirming this tendency. The influence of champagne temperature was also tested. As could have been expected, lowering the temperature of champagne was found to decrease ethanol vapor concentrations in the headspace of a glass. Nevertheless, and quite surprisingly, this temperature decrease had no impact on the level of gaseous CO(2) found above the glass. Those results were discussed on the basis of a multiparameter model which describes fluxes of gaseous CO(2) escaping the liquid phase into the form of bubbles.

Linear scleroderma en coup de sabre including abnormal dental development

DEFF Research Database (Denmark)

Hørberg, M; Lauesen, S R; Daugaard-Jensen, J

2015-01-01

BACKGROUND: Linear scleroderma en coup de sabre (SCS) is a rare skin condition, where dense collagen is deposited in a localised groove of the head and neck area resembling the stroke of a sabre. The SCS may involve the oral cavity, but the severity and relation to this skin abnormality is unknow...... with a left-sided skin defect (SCS) and a left-sided local malformation in her dentition. It is possible that there is a developmental connection between these two left-sided defects, both with an ectodermal origin.......-UP: The patient has been regularly controlled and treated since she was first diagnosed. A surgical and orthodontic treatment was performed to ensure optimal occlusion, space and alveolar bone development. The present age of the patient is 14 years and 10 months. CONCLUSION: This case demonstrated a patient...

Systematic Identification of Intracellular-Translocated Candidate Effectors in Edwardsiella piscicida

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Lingzhi Zhang

2018-02-01

Full Text Available Many bacterial pathogens inject effectors directly into host cells to target a variety of host cellular processes and promote bacterial dissemination and survival. Identifying the bacterial effectors and elucidating their functions are central to understanding the molecular pathogenesis of these pathogens. Edwardsiella piscicida is a pathogen with a wide host range, and very few of its effectors have been identified to date. Here, based on the genes significantly regulated by macrophage infection, we identified 25 intracellular translocation-positive candidate effectors, including all five previously reported effectors, namely EseG, EseJ, EseH, EseK, and EvpP. A subsequent secretion analysis revealed diverse secretion patterns for the 25 effector candidates, suggesting that multiple transport pathways were involved in the internalization of these candidate effectors. Further, we identified two novel type VI secretion system (T6SS putative effectors and three outer membrane vesicles (OMV-dependent putative effectors among the candidate effectors described above, and further analyzed their contribution to bacterial virulence in a zebrafish model. This work demonstrates an effective approach for screening bacterial effectors and expands the effectors repertoire in E. piscicida.

Peringkasan Sentimen Esktraktif di Twitter Menggunakan Hybrid TF-IDF dan Cosine Similarity

Directory of Open Access Journals (Sweden)

Devid Haryalesmana Wahid

2016-07-01

Full Text Available The using of Twitter by selebrities has become a new trend of impression management strategy. Mining public reaction in social media is a good strategy to obtain feedbacks, but extracting it are not trivial matter. Reads hundred of tweets while determine their sentiment polarity are time consuming. Extractive sentiment summarization machine are needed to address this issue. Previous research generally do not include sentiment information contained in a tweet as weight factor, as a results only general topics of discussion are extracted. This research aimed to do an extractive sentiment summarization on both positive and negative sentiment mentioning Indonesian selebrity, Agnes Monica, by combining SentiStrength, Hybrid TF-IDF, and Cosine Similarity. SentiStrength is used to obtain sentiment strength score and classify tweet as a positive, negative or neutral. The summarization of posisitve and negative sentiment can be done by rank tweets using Hybrid TF-IDF summarization and sentiment strength score as additional weight then removing similar tweet by using Cosine Similarity. The test results showed that the combination of SentiStrength, Hybrid TF-IDF, and Cosine Similarity perform better than using Hybrid TF-IDF only, given an average 60% accuracy and 62% f-measure. This is due to the addition of sentiment score as a weight factor in sentiment summ­ari­zation.

WISE TF: A MID-INFRARED, 3.4 {mu}m EXTENSION OF THE TULLY-FISHER RELATION USING WISE PHOTOMETRY

Energy Technology Data Exchange (ETDEWEB)

Lagattuta, David J.; Mould, Jeremy R. [Centre for Astrophysics and Supercomputing, Swinburne University of Technology, P.O. Box 218, Hawthorn, VIC 3122 (Australia); Staveley-Smith, Lister; Hong Tao; Springob, Christopher M. [ARC Centre of Excellence for All-sky Astrophysics (CAASTRO), Redfern, NSW (Australia); Masters, Karen L. [Institute for Cosmology and Gravitation, University of Portsmouth, Dennis Sciama Building, Burnaby Road, Portsmouth, PO1 3FX (United Kingdom); Koribalski, Baerbel S. [CSIRO Astronomy and Space Science, Australia Telescope National Facility (ATNF) P.O. Box 76, Epping, NSW 1710 (Australia); Jones, D. Heath, E-mail: dlagattu@astro.swin.edu.au [School of Physics, Monash University, Clayton, VIC 3800 (Australia)

2013-07-10

We present a mid-infrared Tully-Fisher (TF) relation using photometry from the 3.4 {mu}m W1 band of the Wide-field Infrared Survey Explorer (WISE) satellite. The WISE TF relation is formed from 568 galaxies taken from the all-sky 2MASS Tully-Fisher (2MTF) galaxy catalog, spanning a range of environments including field, group, and cluster galaxies. This constitutes the largest mid-infrared TF relation constructed to date. After applying a number of corrections to galaxy magnitudes and line widths, we measure a master TF relation given by M{sub corr} = -22.24 - 10.05[log (W{sub corr}) - 2.5], with an average dispersion of {sigma}{sub WISE} = 0.686 mag. There is some tension between WISE TF and a preliminary 3.6 {mu}m relation, which has a shallower slope and almost no intrinsic dispersion. However, our results agree well with a more recent relation constructed from a large sample of cluster galaxies. We additionally compare WISE TF to the near-infrared 2MTF template relations, finding a good agreement between the TF parameters and total dispersions of WISE TF and the 2MTF K-band template. This fact, coupled with typical galaxy colors of (K - W1) {approx} 0, suggests that these two bands are tracing similar stellar populations, including the older, centrally-located stars in the galactic bulge which can (for galaxies with a prominent bulge) dominate the light profile.

WISE TF: A MID-INFRARED, 3.4 μm EXTENSION OF THE TULLY-FISHER RELATION USING WISE PHOTOMETRY

International Nuclear Information System (INIS)

Lagattuta, David J.; Mould, Jeremy R.; Staveley-Smith, Lister; Hong Tao; Springob, Christopher M.; Masters, Karen L.; Koribalski, Bärbel S.; Jones, D. Heath

2013-01-01

We present a mid-infrared Tully-Fisher (TF) relation using photometry from the 3.4 μm W1 band of the Wide-field Infrared Survey Explorer (WISE) satellite. The WISE TF relation is formed from 568 galaxies taken from the all-sky 2MASS Tully-Fisher (2MTF) galaxy catalog, spanning a range of environments including field, group, and cluster galaxies. This constitutes the largest mid-infrared TF relation constructed to date. After applying a number of corrections to galaxy magnitudes and line widths, we measure a master TF relation given by M corr = –22.24 – 10.05[log (W corr ) – 2.5], with an average dispersion of σ WISE = 0.686 mag. There is some tension between WISE TF and a preliminary 3.6 μm relation, which has a shallower slope and almost no intrinsic dispersion. However, our results agree well with a more recent relation constructed from a large sample of cluster galaxies. We additionally compare WISE TF to the near-infrared 2MTF template relations, finding a good agreement between the TF parameters and total dispersions of WISE TF and the 2MTF K-band template. This fact, coupled with typical galaxy colors of (K – W1) ∼ 0, suggests that these two bands are tracing similar stellar populations, including the older, centrally-located stars in the galactic bulge which can (for galaxies with a prominent bulge) dominate the light profile.

Effector-Triggered Self-Replication in Coupled Subsystems.

Science.gov (United States)

Komáromy, Dávid; Tezcan, Meniz; Schaeffer, Gaël; Marić, Ivana; Otto, Sijbren

2017-11-13

In living systems processes like genome duplication and cell division are carefully synchronized through subsystem coupling. If we are to create life de novo, similar control over essential processes such as self-replication need to be developed. Here we report that coupling two dynamic combinatorial subsystems, featuring two separate building blocks, enables effector-mediated control over self-replication. The subsystem based on the first building block shows only self-replication, whereas that based on the second one is solely responsive toward a specific external effector molecule. Mixing the subsystems arrests replication until the effector molecule is added, resulting in the formation of a host-effector complex and the liberation of the building block that subsequently engages in self-replication. The onset, rate and extent of self-replication is controlled by the amount of effector present. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Application of [HMim][NTf2], [HMim][TfO] and [BMim][TfO] ionic liquids on the extraction of toluene from alkanes: Effect of the anion and the alkyl chain length of the cation on the LLE

International Nuclear Information System (INIS)

Corderí, Sandra; González, Emilio J.; Calvar, Noelia; Domínguez, Ángeles

2012-01-01

Highlights: ► Several ionic liquids were studied as solvent to extract toluene from heptane and cyclohexane. ► (Liquid + liquid) equilibrium data were measured at 298.15 K and atmospheric pressure. ► Selectivity and solute distribution ratio were calculated and compared with those found in literature for sulfolane. ► Experimental data were correlated using NRTL and UNIQUAC thermodynamic models. - Abstract: In this paper, the separation of toluene from the aliphatic hydrocarbons heptane and cyclohexane employing the ionic liquids 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [HMim][NTf 2 ], 1-hexyl-3-methylimidazolium trifluoromethanesulfonate, [HMim][TfO] and 1-butyl-3-methylimidazolium trifluoromethanesulfonate, [BMim][TfO], as solvents was studied and discussed. Liquid–liquid equilibrium data for the ternary systems {heptane, or cyclohexane + toluene + [HMim][NTf 2 ], or [HMim][TfO], or [BMim][TfO]} and {heptane + cyclohexane + [HMim][NTf 2 ], or [HMim][TfO], or [BMim][TfO]} were measured at T = 298.15 K and atmospheric pressure. The degree of consistency of the tie-lines was tested using the Othmer–Tobias equation. The solute distribution ratio and selectivity, derived from the experimental tie-lines, were used to determine if these ionic liquids can be used as potential solvents on the extraction of toluene from aliphatic hydrocarbons; a comparison with literature data where sulfolane is used as solvent was also included. Finally, the experimental data were correlated with the NRTL and UNIQUAC thermodynamic models.

A retinoic acid response element that overlaps an estrogen response element mediates multihormonal sensitivity in transcriptional activation of the lactoferrin gene.

Science.gov (United States)

Lee, M O; Liu, Y; Zhang, X K

1995-08-01

The lactoferrin gene is highly expressed in many different tissues, and its expression is controlled by different regulators. In this report, we have defined a retinoic acid response element (RARE) in the 5'-flanking region of the lactoferrin gene promoter. The lactoferrin-RARE is composed of two AGGTCA-like motifs arranged as a direct repeat with 1-bp spacing (DR-1). A gel retardation assay demonstrated that it bound strongly with retinoid X receptor (RXR) homodimers and RXR-retinoic acid receptor (RAR) heterodimers as well as chicken ovalbumin upstream promoter transcription factor (COUP-TF) orphan receptor. In CV-1 cells, the lactoferrin-RARE linked with a heterologous thymidine kinase promoter was strongly activated by RXR homodimers in response to 9-cis-retinoic acid (9-cis-RA) but not to all-trans-RA. When the COUP-TF orphan receptor was cotransfected, the 9-cis-RA-induced RXR homodimer activity was strongly repressed. A unique feature of the lactoferrin-RARE is that it has an AGGTCA-like motif in common with an estrogen-responsive element (ERE). The composite RARE/ERE contributes to the functional interaction between retinoid receptors and the estrogen receptor (ER) and their ligands. In CV-1 cells, cotransfection of the retinoid and estrogen receptors led to mutual inhibition of the other's activity, while an RA-dependent inhibition of ER activity was observed in breast cancer cells. Furthermore, the lactoferrin-RARE/ERE showed differential transactivation activity in different cell types. RAs could activate the lactoferrin-RARE/ERE in human leukemia HL-60 cells and U937 cells but not in human breast cancer cells. By gel retardation analyses, we demonstrated that strong binding of the endogenous COUP-TF in breast cancer cells to the composite element contributed to diminished RA response in these cells. Thus, the lactoferrin-RARE/ERE functions as a signaling switch module that mediates multihormonal responsiveness in the regulation of lactoferrin gene

SPRYSEC effector proteins in Globodera rostochiensis

NARCIS (Netherlands)

Rehman, S.

2008-01-01

Plant pathogens inject so-called effector molecules into the cells of a host plant to promote their growth and reproduction in these hosts. In plant parasitic nematodes, these effector molecules are produced in the salivary glands. The objective of this thesis was to identify and characterize

A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib.

Science.gov (United States)

Sun, Tianliang; Yang, Lida; Kaur, Harmandeep; Pestel, Jenny; Looso, Mario; Nolte, Hendrik; Krasel, Cornelius; Heil, Daniel; Krishnan, Ramesh K; Santoni, Marie-Josée; Borg, Jean-Paul; Bünemann, Moritz; Offermanns, Stefan; Swiercz, Jakub M; Worzfeld, Thomas

2017-01-02

Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A. We further show that binding of Plexin-B1 to Sema4A promotes the interaction of Sema4A with Scrib, thereby removing Scrib from its complex with the Rac/Cdc42 exchange factor βPIX and decreasing the activity of the small guanosine triphosphatase Rac1 and Cdc42. Our data unravel a role for Plexin-B1 as a ligand and Sema4A as a receptor and characterize a reverse signaling pathway downstream of Sema4A, which controls cell migration. © 2017 Sun et al.

Sidelining Democracy : Explaining the United States Response to Thailand’s 2006 and 2014 Coups D’etat

Science.gov (United States)

2016-06-01

force against extreme political corruption and unrest. A strong U.S. government pushback to the coups can result in Thailand pursuing an already...despite setbacks in Thailand’s democratization process , suggesting that the U.S. government values having a reliable, stable ally over a democratic...In the process , Thailand ceded territorial rights, forged alliances with great powers, and played alliances with great powers for its survival

A Method to Predict Compressor Stall in the TF34-100 Turbofan Engine Utilizing Real-Time Performance Data

Science.gov (United States)

2015-06-01

A METHOD TO PREDICT COMPRESSOR STALL IN THE TF34-100 TURBOFAN ENGINE UTILIZING REAL-TIME PERFORMANCE...THE TF34-100 TURBOFAN ENGINE UTILIZING REAL-TIME PERFORMANCE DATA THESIS Presented to the Faculty Department of Systems Engineering and...036 A METHOD TO PREDICT COMPRESSOR STALL IN THE TF34-100 TURBOFAN ENGINE UTILIZING REAL-TIME PERFORMANCE DATA Shuxiang ‘Albert’ Li, BS

Cobra-TF simulation of BWR bundle dry out experiments

Energy Technology Data Exchange (ETDEWEB)

Frepoli, C.; Ireland, A.; Hochreiter, L.; Ivanov, K. [Penn State Univ., Dept. of Mechanical and Nuclear Engineering, University Park, PA (United States); Velten, R. [Siemens Nuclear Power GmbH, Erlangen (Germany)

2001-07-01

The COBRA-TF computer code uses a two-fluid, three-field and three-dimensional formulation to model a two-phase flow field in a specific geometry. The liquid phase is divided in a continuous liquid field and a separate dispersed field, which is used to describe the entrained liquid drops. For each space dimension, the code solves three momentum equations, three mass conservation equations and two energy conservation equations. Entrainment and depositions models are implemented into the code to model the mass transfer between the two liquid fields. This study presents the results obtained with COBRA-TF for the simulation of the Siemens 9-9Q BWR Bundle Dryout experiments. The model includes 20 channels and 34 axial nodes in the heated section. The predicted critical power and dryout location is compared with the measured values. An assessment of the code entrainment and de-entrainment models is presented. (authors)

Uncovering the Legionella genus effector repertoire - strength in diversity and numbers

Science.gov (United States)

Burstein, David; Amaro, Francisco; Zusman, Tal; Lifshitz, Ziv; Cohen, Ofir; Gilbert, Jack A; Pupko, Tal; Shuman, Howard A; Segal, Gil

2016-01-01

Infection by the human pathogen Legionella pneumophila relies on the translocation of ~300 virulence proteins, termed effectors, which manipulate host-cell processes. However, almost no information exists regarding effectors in other Legionella pathogens. Here we sequenced, assembled and characterized the genomes of 38 Legionella species, and predicted their effector repertoire using a previously validated machine-learning approach. This analysis revealed a treasure trove of 5,885 predicted effectors. The effector repertoire of different Legionella species was found to be largely non-overlapping, and only seven core-effectors were shared among all species studied. Species-specific effectors had atypically low GC content, suggesting exogenous acquisition, possibly from their natural protozoan hosts. Furthermore, we detected numerous novel conserved effector domains, and discovered new domain combinations, which allowed inferring yet undescribed effector functions. The effector collection and network of domain architectures described here can serve as a roadmap for future studies of effector function and evolution. PMID:26752266

BOREAS TF-02 SSA-OA Tethersonde Meteorological and Ozone Data

Data.gov (United States)

National Aeronautics and Space Administration — ABSTRACT: The BOREAS TF-02 team collected various trace gas and energy flux data along with meteorological parameters at the SSA-OA site. This data set contains...

BOREAS TF-02 SSA-OA Tethersonde Meteorological and Ozone Data

Data.gov (United States)

National Aeronautics and Space Administration — The BOREAS TF-02 team collected various trace gas and energy flux data along with meteorological parameters at the SSA-OA site. This data set contains meteorological...

Effector proteins of rust fungi.

Science.gov (United States)

Petre, Benjamin; Joly, David L; Duplessis, Sébastien

2014-01-01

Rust fungi include many species that are devastating crop pathogens. To develop resistant plants, a better understanding of rust virulence factors, or effector proteins, is needed. Thus far, only six rust effector proteins have been described: AvrP123, AvrP4, AvrL567, AvrM, RTP1, and PGTAUSPE-10-1. Although some are well established model proteins used to investigate mechanisms of immune receptor activation (avirulence activities) or entry into plant cells, how they work inside host tissues to promote fungal growth remains unknown. The genome sequences of four rust fungi (two Melampsoraceae and two Pucciniaceae) have been analyzed so far. Genome-wide analyses of these species, as well as transcriptomics performed on a broader range of rust fungi, revealed hundreds of small secreted proteins considered as rust candidate secreted effector proteins (CSEPs). The rust community now needs high-throughput approaches (effectoromics) to accelerate effector discovery/characterization and to better understand how they function in planta. However, this task is challenging due to the non-amenability of rust pathosystems (obligate biotrophs infecting crop plants) to traditional molecular genetic approaches mainly due to difficulties in culturing these species in vitro. The use of heterologous approaches should be promoted in the future.

Lichen sclerosus et atrophicans, scleroderma en coup de sabre and Lyme borreliosis

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Serena Bonin

2011-09-01

Full Text Available Lichen sclerosus et atrophicans (LSA is a chronic, inflammatory skin disease of unknown etiology, characterized by atrophy. We report a case of LSA with frontoparietal distribution, mimicking scleroderma en coup de sabre, causing scarring alopecia. The case was associated with Borrelia infection. The lesion improved with 2 cycles of antibiotic therapy with ceftriaxone 2 gr /day i.v for 21 days associated with UVA-1 therapy and local and systemic vitamin E supply (400 mg 2x/day per os for 3 months. This case stresses the importance of identifying clinical manifestations associated with Lyme disease and the use of tissue PCR to detect borrelial DNA in patients with these lesions, but characterized by negative serology for Borrelia.

Tissue specific heterogeneity in effector immune cell response

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Saba eTufail

2013-08-01

Full Text Available Post pathogen invasion, migration of effector T-cell subsets to specific tissue locations is of prime importance for generation of robust immune response. Effector T cells are imprinted with distinct ‘homing codes’ (adhesion molecules and chemokine receptors during activation which regulate their targeted trafficking to specific tissues. Internal cues in the lymph node microenvironment along with external stimuli from food (vitamin A and sunlight (vitamin D3 prime dendritic cells, imprinting them to play centrestage in the induction of tissue tropism in effector T cells. B cells as well, in a manner similar to effector T cells, exhibit tissue tropic migration. In this review, we have focused on the factors regulating the generation and migration of effector T cells to various tissues alongwith giving an overview of tissue tropism in B cells.

Magnetic field shielding effect for CFETR TF coil-case

Energy Technology Data Exchange (ETDEWEB)

Xu, Weiwei; Liu, Xufeng, E-mail: Lxf@ipp.ac.cn; Du, Shuangsong; Zheng, Jinxing

2017-05-15

Highlights: • The eddy current of CFETR vacuum vessel can be calculated by using a series of ideal current loops. • The shielding effect with different eddy current is studied by decomposing the exciting magnetic field as two orthogonal components. • The shielding effect can be determined from the rate of eddy current magnetic field to the external magnetic field. - Abstract: The operation of superconducting magnet for fusion device is under the complex magnetic field condition, which affect the stabilization of superconductor. The coil-case of TF coil can shield the magnetic field to some extent. The shielding effect is related to the eddy current of coil-case. The shielding effect with different eddy current is studied by decomposing the exciting magnetic field as two orthogonal components, respectively. The results indicate that the shielding effect of CFETR TF coil-case has obvious different with the different directional magnetic field, and it’s larger for tangential magnetic compared with that for normal field.

Special-purpose multifingered robotic end-effectors

International Nuclear Information System (INIS)

Crowder, R.M.

1990-01-01

A number of advanced multifingered robotic end-effectors have been developed recently in which the finger joints are powered from external actuators. Although this gives dexterous performance, there are considerable problems with power transmission, due to the use of flexible tendons between the external actuators and the individual finger joints. If a multifingered robotic end-effector is to be operated in a confined space, local actuation of the fingers needs to be fully considered, even if there is a reduction in hand dexterity over that of an externally mounted actuator system. The University of Southampton has developed a number of end-effectors that incorporate integral finger actuators and mechanisms, two examples of which are discussed in this paper

RNAi effector diversity in nematodes.

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Johnathan J Dalzell

2011-06-01

Full Text Available While RNA interference (RNAi has been deployed to facilitate gene function studies in diverse helminths, parasitic nematodes appear variably susceptible. To test if this is due to inter-species differences in RNAi effector complements, we performed a primary sequence similarity survey for orthologs of 77 Caenorhabditis elegans RNAi pathway proteins in 13 nematode species for which genomic or transcriptomic datasets were available, with all outputs subjected to domain-structure verification. Our dataset spanned transcriptomes of Ancylostoma caninum and Oesophagostomum dentatum, and genomes of Trichinella spiralis, Ascaris suum, Brugia malayi, Haemonchus contortus, Meloidogyne hapla, Meloidogyne incognita and Pristionchus pacificus, as well as the Caenorhabditis species C. brenneri, C. briggsae, C. japonica and C. remanei, and revealed that: (i Most of the C. elegans proteins responsible for uptake and spread of exogenously applied double stranded (dsRNA are absent from parasitic species, including RNAi-competent plant-nematodes; (ii The Argonautes (AGOs responsible for gene expression regulation in C. elegans are broadly conserved, unlike those recruited during the induction of RNAi by exogenous dsRNA; (iii Secondary Argonautes (SAGOs are poorly conserved, and the nuclear AGO NRDE-3 was not identified in any parasite; (iv All five Caenorhabditis spp. possess an expanded RNAi effector repertoire relative to the parasitic nematodes, consistent with the propensity for gene loss in nematode parasites; (v In spite of the quantitative differences in RNAi effector complements across nematode species, all displayed qualitatively similar coverage of functional protein groups. In summary, we could not identify RNAi effector deficiencies that associate with reduced susceptibility in parasitic nematodes. Indeed, similarities in the RNAi effector complements of RNAi refractory and competent nematode parasites support the broad applicability of this research

Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency

Science.gov (United States)

Saul, Louise; Saul, Louise; Josephs, Debra H; Josephs, Debra H; Cutler, Keith; Cutler, Keith; Bradwell, Andrew; Bradwell, Andrew; Karagiannis, Panagiotis; Karagiannis, Panagiotis; Selkirk, Chris; Selkirk, Chris; Gould, Hannah J; Gould, Hannah J; Jones, Paul; Jones, Paul; Spicer, James F; Spicer, James F; Karagiannis, Sophia N; Karagiannis, Sophia N

2014-01-01

Background: Due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. IgE therapeutics in development depend upon engagement with the FcεRI and FcεRII receptors on immune effector cells for their function. Only limited knowledge of the primate IgE immune system is available to inform the choice of models for mechanistic and safety evaluations.   Methods: The recognition of human IgE by peripheral blood lymphocytes from cynomolgus monkey and man was compared. We used effector cells from each species in ex vivo affinity, dose-response, antibody-receptor dissociation and potency assays. Results: We report cross-reactivity of human IgE Fc with cynomolgus monkey cells, and comparable binding kinetics to peripheral blood lymphocytes from both species. In competition and dissociation assays, however, human IgE dissociated faster from cynomolgus monkey compared with human effector cells. Differences in association and dissociation kinetics were reflected in effector cell potency assays of IgE-mediated target cell killing, with higher concentrations of human IgE needed to elicit effector response in the cynomolgus monkey system. Additionally, human IgE binding on immune effector cells yielded significantly different cytokine release profiles in each species. Conclusion: These data suggest that human IgE binds with different characteristics to human and cynomolgus monkey IgE effector cells. This is likely to affect the potency of IgE effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies. PMID:24492303

Parallelized preconditioned BiCGStab solution of sparse linear system equations in F-COBRA-TF

International Nuclear Information System (INIS)

Geemert, Rene van; Glück, Markus; Riedmann, Michael; Gabriel, Harry

2011-01-01

Recently, the in-house development of a preconditioned and parallelized BiCGStab solver has been pursued successfully in AREVA’s advanced sub-channel code F-COBRA-TF. This solver can be run either in a sequential computation mode on a single CPU, or in a parallel computation mode on multiple parallel CPUs. The developed procedure enables the computation of several thousands of successive sparse linear system solutions in F-COBRA-TF with acceptable wall clock run times. The current paper provides general information about F-COBRA-TF in terms of modeling capabilities and application areas, and points out where the relevance arises for the efficient iterative solution of sparse linear systems. Furthermore, the preconditioning and parallelization strategies in the developed BiCGStab iterative solution approach are discussed. The paper is concluded with a number of verification examples. (author)

On the Sidelines of the Failed Coup d’ État in Turkey : Can Greece Extradite the Eight Turkish Military Officers to Turkey?

NARCIS (Netherlands)

Rachovitsa, Adamantia

2016-01-01

The article discusses the pending extradition case of eight Turkish military officers who, on the night of the recent failed coup d’ état in Turkey, defected and resorted to Greece. The analysis addresses the public emergency in Turkey, insofar it is relevant for the extradition case, against the

Robotic end-effector for rewaterproofing shuttle tiles

Science.gov (United States)

Manouchehri, Davoud; Hansen, Joseph M.; Wu, Cheng M.; Yamamoto, Brian S.; Graham, Todd

1992-11-01

This paper summarizes work by Rockwell International's Space Systems Division's Robotics Group at Downey, California. The work is part of a NASA-led team effort to automate Space Shuttle rewaterproofing in the Orbiter Processing Facility at the Kennedy Space Center and the ferry facility at the Ames-Dryden Flight Research Facility. Rockwell's effort focuses on the rewaterproofing end-effector, whose function is to inject hazardous dimethylethyloxysilane into thousands of ceramic tiles on the underside of the orbiter after each flight. The paper has five sections. First, it presents background on the present manual process. Second, end-effector requirements are presented, including safety and interface control. Third, a design is presented for the five end-effector systems: positioning, delivery, containment, data management, and command and control. Fourth, end-effector testing and integrating to the total system are described. Lastly, future applications for this technology are discussed.

Religion and politics in conflict: Paul Stuart Wright and the 1964 coup

Directory of Open Access Journals (Sweden)

Márcio Ananias Ferreira Vilela

2016-06-01

Full Text Available In this article, we seek to understand the implications of Paulo Stuart Wright´s political and religious action. Beginning with the civil and military coup of 1964, it suffered a strong reaction from majority sectors in the Presbyterian Church of Brazil that started to perceive him as a threat to the religious community and to society itself. The following period was marked by an intense political conflict in Brazil. This contributed for the person in question to be expelled from the Church, have his mandate as a state representative for Santa Catarina impeached, be exiled, live in clandestinity and, later on in the 1970s, be murdered by the organs of repression. Thus, his trajectory bears many similarities to those of others who marked the recent history of Brazil.

Partial Diversity Generates Effector Immunity Specificity of the Bac41-Like Bacteriocins of Enterococcus faecalis Clinical Strains.

Science.gov (United States)

Kurushima, Jun; Ike, Yasuyoshi; Tomita, Haruyoshi

2016-09-01

Bacteriocin 41 (Bac41) is the plasmid-encoded bacteriocin produced by the opportunistic pathogen Enterococcus faecalis Its genetic determinant consists of bacL1 (effector), bacL2 (regulator), bacA (effector), and bacI (immunity). The secreted effectors BacL1 and BacA coordinate to induce the lytic cell death of E. faecalis Meanwhile, the immunity factor BacI provides self-resistance to the Bac41 producer, E. faecalis, against the action of BacL1 and BacA. In this study, we demonstrated that more than half of the 327 clinical strains of E. faecalis screened had functional Bac41 genes. Analysis of the genetic structure of the Bac41 genes in the DNA sequences of the E. faecalis strains revealed that the Bac41-like genes consist of a relatively conserved region and a variable region located downstream from bacA Based on similarities in the variable region, the Bac41-like genes could be classified into type I, type IIa, and type IIb. Interestingly, the distinct Bac41 types had specific immunity factors for self-resistance, BacI1 or BacI2, and did not show cross-immunity to the other type of effector. We also demonstrated experimentally that the specificity of the immunity was determined by the combination of the C-terminal region of BacA and the presence of the unique BacI1 or BacI2 factor. These observations suggested that Bac41-like bacteriocin genes are extensively disseminated among E. faecalis strains in the clinical environment and can be grouped into at least three types. It was also indicated that the partial diversity results in specificity of self-resistance which may offer these strains a competitive advantage. Bacteriocins are antibacterial effectors produced by bacteria. In general, a bacteriocin-coding gene is accompanied by a cognate immunity gene that confers self-resistance on the bacteriocin-producing bacterium itself. We demonstrated that one of the bacteriocins, Bac41, is disseminated among E. faecalis clinical strains and the Bac41 subtypes with

Estimation of Theaflavins (TF) and Thearubigins (TR) Ratio in Black Tea Liquor Using Electronic Vision System

Science.gov (United States)

Akuli, Amitava; Pal, Abhra; Ghosh, Arunangshu; Bhattacharyya, Nabarun; Bandhopadhyya, Rajib; Tamuly, Pradip; Gogoi, Nagen

2011-09-01

Quality of black tea is generally assessed using organoleptic tests by professional tea tasters. They determine the quality of black tea based on its appearance (in dry condition and during liquor formation), aroma and taste. Variation in the above parameters is actually contributed by a number of chemical compounds like, Theaflavins (TF), Thearubigins (TR), Caffeine, Linalool, Geraniol etc. Among the above, TF and TR are the most important chemical compounds, which actually contribute to the formation of taste, colour and brightness in tea liquor. Estimation of TF and TR in black tea is generally done using a spectrophotometer instrument. But, the analysis technique undergoes a rigorous and time consuming effort for sample preparation; also the operation of costly spectrophotometer requires expert manpower. To overcome above problems an Electronic Vision System based on digital image processing technique has been developed. The system is faster, low cost, repeatable and can estimate the amount of TF and TR ratio for black tea liquor with accuracy. The data analysis is done using Principal Component Analysis (PCA), Multiple Linear Regression (MLR) and Multiple Discriminate Analysis (MDA). A correlation has been established between colour of tea liquor images and TF, TR ratio. This paper describes the newly developed E-Vision system, experimental methods, data analysis algorithms and finally, the performance of the E-Vision System as compared to the results of traditional spectrophotometer.

Mycobacterium tuberculosis effectors interfering host apoptosis signaling.

Science.gov (United States)

Liu, Minqiang; Li, Wu; Xiang, Xiaohong; Xie, Jianping

2015-07-01

Tuberculosis remains a serious human public health concern. The coevolution between its pathogen Mycobacterium tuberculosis and human host complicated the way to prevent and cure TB. Apoptosis plays subtle role in this interaction. The pathogen endeavors to manipulate the apoptosis via diverse effectors targeting key signaling nodes. In this paper, we summarized the effectors pathogen used to subvert the apoptosis, such as LpqH, ESAT-6/CFP-10, LAMs. The interplay between different forms of cell deaths, such as apoptosis, autophagy, necrosis, is also discussed with a focus on the modes of action of effectors, and implications for better TB control.

Epigenetic control of effectors in plant pathogens

Directory of Open Access Journals (Sweden)

Mark eGijzen

2014-11-01

Full Text Available Plant pathogens display impressive versatility in adapting to host immune systems. Pathogen effector proteins facilitate disease but can become avirulence (Avr factors when the host acquires discrete recognition capabilities that trigger immunity. The mechanisms that lead to changes to pathogen Avr factors that enable escape from host immunity are diverse, and include epigenetic switches that allow for reuse or recycling of effectors. This perspective outlines possibilities of how epigenetic control of Avr effector gene expression may have arisen and persisted in plant pathogens, and how it presents special problems for diagnosis and detection of specific pathogen strains or pathotypes.

TAL effectors and the executor R genes.

Science.gov (United States)

Zhang, Junli; Yin, Zhongchao; White, Frank

2015-01-01

Transcription activator-like (TAL) effectors are bacterial type III secretion proteins that function as transcription factors in plants during Xanthomonas/plant interactions, conditioning either host susceptibility and/or host resistance. Three types of TAL effector associated resistance (R) genes have been characterized-recessive, dominant non-transcriptional, and dominant TAL effector-dependent transcriptional based resistance. Here, we discuss the last type of R genes, whose functions are dependent on direct TAL effector binding to discrete effector binding elements in the promoters. Only five of the so-called executor R genes have been cloned, and commonalities are not clear. We have placed the protein products in two groups for conceptual purposes. Group 1 consists solely of the protein from pepper, BS3, which is predicted to have catalytic function on the basis of homology to a large conserved protein family. Group 2 consists of BS4C-R, XA27, XA10, and XA23, all of which are relatively short proteins from pepper or rice with multiple potential transmembrane domains. Group 2 members have low sequence similarity to proteins of unknown function in closely related species. Firm predictions await further experimentation on these interesting new members to the R gene repertoire, which have potential broad application in new strategies for disease resistance.

TAL effectors and the executor R genes

Directory of Open Access Journals (Sweden)

Junli eZhang

2015-08-01

Full Text Available Transcription activation-like (TAL effectors are bacterial type III secretion proteins that function as transcription factors in plants during Xanthomonas/plant interactions, conditioning either host susceptibility and/or host resistance. Three types of TAL effector associated resistance (R genes have been characterized - recessive, dominant non-transcriptional and dominant TAL effector-dependent transcriptional based resistance. Here, we discuss the last type of R genes, whose functions are dependent on direct TAL effector binding to discrete effector binding elements in the promoters. Only five of the so-called executor R genes have been cloned, and commonalities are not clear. We have placed the protein products in two groups for conceptual purposes. Group 1 consists solely of the protein from pepper, BS3, which is predicted to have catalytic function on the basis of homology to a large conserved protein family. Group 2 consists of BS4C-R, XA27, XA10, and XA23, all of which are relatively short proteins from pepper or rice with multiple potential transmembrane domains. Group 2 members have low sequence similarity to proteins of unknown function in closely related species. Firm predictions await further experimentation on these interesting new members to the R gene repertoire, which have potential broad application in new strategies for disease resistance.

Genome-scale identification of Legionella pneumophila effectors using a machine learning approach.

Directory of Open Access Journals (Sweden)

David Burstein

2009-07-01

Full Text Available A large number of highly pathogenic bacteria utilize secretion systems to translocate effector proteins into host cells. Using these effectors, the bacteria subvert host cell processes during infection. Legionella pneumophila translocates effectors via the Icm/Dot type-IV secretion system and to date, approximately 100 effectors have been identified by various experimental and computational techniques. Effector identification is a critical first step towards the understanding of the pathogenesis system in L. pneumophila as well as in other bacterial pathogens. Here, we formulate the task of effector identification as a classification problem: each L. pneumophila open reading frame (ORF was classified as either effector or not. We computationally defined a set of features that best distinguish effectors from non-effectors. These features cover a wide range of characteristics including taxonomical dispersion, regulatory data, genomic organization, similarity to eukaryotic proteomes and more. Machine learning algorithms utilizing these features were then applied to classify all the ORFs within the L. pneumophila genome. Using this approach we were able to predict and experimentally validate 40 new effectors, reaching a success rate of above 90%. Increasing the number of validated effectors to around 140, we were able to gain novel insights into their characteristics. Effectors were found to have low G+C content, supporting the hypothesis that a large number of effectors originate via horizontal gene transfer, probably from their protozoan host. In addition, effectors were found to cluster in specific genomic regions. Finally, we were able to provide a novel description of the C-terminal translocation signal required for effector translocation by the Icm/Dot secretion system. To conclude, we have discovered 40 novel L. pneumophila effectors, predicted over a hundred additional highly probable effectors, and shown the applicability of machine

Design and implementation of quench detection instrumentation for TF magnet system of SST-1

International Nuclear Information System (INIS)

Khristi, Y.; Sharma, A.N.; Doshi, K.; Banaudha, M.; Prasad, U.; Varmora, P.; Patel, D.; Pradhan, S.

2014-01-01

Steady State Superconducting Tokamak-1 (SST-1) at Institute for Plasma Research (IPR), India is now in engineering validation phase. The assembled Toroidal Field (TF) magnet system of SST-1 will be operated at 10 kA of nominal current at helium cooled condition of 4.5 K. A reliable and fail proof quench detection (QD) system is essential for the safety and the investment protection requirements of the magnets. This QD system needs to continuously monitor all the superconducting coils, which include 16 TF magnets, return-loop, bus bars and current leads. In case of any event initiating the normal resistive zone and reaching thermal run-away, the QD system needs to trigger the magnet protection circuits. Precision instrumentation and control system with 204 signal channels had been developed for detection of quench anywhere in the entire TF magnet system. In the present configuration of quench detection scheme, the voltage drop across each double pancake (DP) of each TF coil are compared with its two adjacent DPs for the detection of normal zone and cancelation of inductive couples. Two identical redundant systems with one out of two configurations are successfully commissioned and tested at IPR. This paper describes the design and implementation of the QD system, Installation experience, validation test and initial results from the recent SST-1 magnet system charging

Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and Regulate the Human TF Pathway in Vitro and in a Rodent Model

Directory of Open Access Journals (Sweden)

Hongchen Ji

2015-05-01

Full Text Available Background: The activation of tissue factor (TF is one of the major reasons for coagulation dysregulation after pig-to-primate xenotransplantation. Tissue factor pathway inhibitor (TFPI is the most important inhibitor of TF. Studies have demonstrated species incompatibility between pig TFPI and human TF. Methods: A pig-to-macaque heterotopic auxiliary liver transplantation model was established to determine the origin of activated TF. Chimeric proteins of human and pig TFPI were constructed to assess the role of Kunitz domains in species incompatibility. Immortalised pig bone marrow mesenchymal stem cells transfected with human TFPI were tested for their ability to inhibit clotting in vitro. Results: TF from recipient was activated early after liver xenotransplantation. Pig TFPI Kunitz domain 2 bound human FXa, but Kunitz domain 1 did not effectively inhibit human TF/FVIIa. Immortalised pig bone marrow mesenchymal cells (BMSCs transfected with human TFPI showed a prolonged recalcification time in vitro and in a rodent model. Conclusion: Recipient TF is relevant to dysregulated coagulation after xenotransplantation. Kunitz domain 1 plays the most important role in species incompatibility between pig TFPI and human TF, and clotting can be inhibited by human TFPI-transfected pig BMSCs. Our study shows a possible way to resolve the incompatibility of pig TFPI.

Effectors from Wheat Rust Fungi Suppress Multiple Plant Defense Responses.

Science.gov (United States)

Ramachandran, Sowmya R; Yin, Chuntao; Kud, Joanna; Tanaka, Kiwamu; Mahoney, Aaron K; Xiao, Fangming; Hulbert, Scot H

2017-01-01

Fungi that cause cereal rust diseases (genus Puccinia) are important pathogens of wheat globally. Upon infection, the fungus secretes a number of effector proteins. Although a large repository of putative effectors has been predicted using bioinformatic pipelines, the lack of available high-throughput effector screening systems has limited functional studies on these proteins. In this study, we mined the available transcriptomes of Puccinia graminis and P. striiformis to look for potential effectors that suppress host hypersensitive response (HR). Twenty small (wheat, confirming its activity in a homologous system. Overall, this study provides the first evidence for the presence of effectors in Puccinia species suppressing multiple plant defense responses.

Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice

Energy Technology Data Exchange (ETDEWEB)

Sur, Subhayan, E-mail: subhayansur18@gmail.com [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India); Pal, Debolina; Roy, Rituparna; Barua, Atish [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India); Roy, Anup [North Bengal Medical College and Hospital, West Bengal (India); Saha, Prosenjit [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India); Panda, Chinmay Kumar, E-mail: ckpanda.cnci@gmail.com [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India)

2016-06-01

The aim of this study is to understand the molecular mechanisms of N-nitrosodiethylamine (NDEA) induced multi-organ carcinogenesis in tongue and liver of the same mouse and restriction of carcinogenesis by Epigallocatechin gallate (EGCG) and Theaflavin (TF), if any. For that purpose, cellular proliferation/apoptosis, prevalence of CD44 positive stem cell population and expressions of some key regulatory genes of self renewal Wnt and Hedgehog (Hh) pathways and some of their associated genes were analyzed in the NDEA induced tongue and liver lesions in absence or presence of EGCG/TF. Chronic NDEA exposure in oral cavity could decrease mice body weights and induce tongue and liver carcinogenesis with similar histological stages (severe dysplasia up to 30th weeks of NDEA administration). Increasing mice body weights were seen in continuous and post EGCG/TF treated groups. EGCG/TF treatment could restrict both the carcinogenesis at similar histological stages showing potential chemopreventive effect in continuous treated groups (mild dysplasia) followed by pre treatment (moderate dysplasia) and therapeutic efficacy in post treated groups (mild dysplasia) up to 30th week. The mechanism of carcinogenesis by NDEA and restriction by the EGCG/TF in both tongue and liver were similar and found to be associated with modulation in cellular proliferation/apoptosis and prevalence of CD44 positive population. The up-regulation of self renewal Wnt/β-catenin, Hh/Gli1 pathways and their associated genes Cyclin D1, cMyc and EGFR along with down regulation of E-cadherin seen during the carcinogenesis processes were found to be modulated during the restriction processes by EGCG/TF. - Highlights: • Simultaneous tongue and liver carcinogenesis in mice by oral NDEA administration • Restriction of both carcinogenesis by EGCG and TF at early pre-malignant stages • The mechanisms of carcinogenesis and restriction were similar in both the organs. • Changes in proliferation

Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice

International Nuclear Information System (INIS)

Sur, Subhayan; Pal, Debolina; Roy, Rituparna; Barua, Atish; Roy, Anup; Saha, Prosenjit; Panda, Chinmay Kumar

2016-01-01

The aim of this study is to understand the molecular mechanisms of N-nitrosodiethylamine (NDEA) induced multi-organ carcinogenesis in tongue and liver of the same mouse and restriction of carcinogenesis by Epigallocatechin gallate (EGCG) and Theaflavin (TF), if any. For that purpose, cellular proliferation/apoptosis, prevalence of CD44 positive stem cell population and expressions of some key regulatory genes of self renewal Wnt and Hedgehog (Hh) pathways and some of their associated genes were analyzed in the NDEA induced tongue and liver lesions in absence or presence of EGCG/TF. Chronic NDEA exposure in oral cavity could decrease mice body weights and induce tongue and liver carcinogenesis with similar histological stages (severe dysplasia up to 30th weeks of NDEA administration). Increasing mice body weights were seen in continuous and post EGCG/TF treated groups. EGCG/TF treatment could restrict both the carcinogenesis at similar histological stages showing potential chemopreventive effect in continuous treated groups (mild dysplasia) followed by pre treatment (moderate dysplasia) and therapeutic efficacy in post treated groups (mild dysplasia) up to 30th week. The mechanism of carcinogenesis by NDEA and restriction by the EGCG/TF in both tongue and liver were similar and found to be associated with modulation in cellular proliferation/apoptosis and prevalence of CD44 positive population. The up-regulation of self renewal Wnt/β-catenin, Hh/Gli1 pathways and their associated genes Cyclin D1, cMyc and EGFR along with down regulation of E-cadherin seen during the carcinogenesis processes were found to be modulated during the restriction processes by EGCG/TF. - Highlights: • Simultaneous tongue and liver carcinogenesis in mice by oral NDEA administration • Restriction of both carcinogenesis by EGCG and TF at early pre-malignant stages • The mechanisms of carcinogenesis and restriction were similar in both the organs. • Changes in proliferation

BOREAS TF-06 SSA-YA Surface Energy Flux and Meteorological Data

Data.gov (United States)

National Aeronautics and Space Administration — ABSTRACT: Contains meteorology data collected at the SSA-YA tower flux site by the TF6 group. These data were reported at 10 minute intervals. The flux and ancillary...

Cryogenic analysis of forced-cooled, superconducting TF magnets for compact tokamak reactors

International Nuclear Information System (INIS)

Kerns, J.A.; Slack, D.S.; Miller, J.R.

1988-01-01

Current designs for compact tokamak reactors require the toroidal- field (TF) superconducting magnets to produce fields from 10 to 15 T at the winding pack, using high-current densities to high nuclear heat loads (greater than 1 kW/coil in some instances), which are significantly greater than the conduction and radiation heat loads for which cryogenic systems are usually designed. A cryogenic system for the TF winding pack for two such tokamak designs has been verified by performing a detailed, steady-state heat-removal analysis. Helium properties along the forced-cooled conductor flow path for a range of nuclear heat loads have been calculated. The results and implications of this analysis are presented. 12 refs., 6 figs

Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells*

Science.gov (United States)

Ali, Ramadan A.; Camick, Christina; Wiles, Katherine; Walseth, Timothy F.; Slama, James T.; Bhattacharya, Sumit; Giovannucci, David R.; Wall, Katherine A.

2016-01-01

Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca2+ mobilizing second messenger discovered to date, has been implicated in Ca2+ signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca2+ signaling or the identity of the Ca2+ stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca2+ signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca2+ signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca2+ stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca2+ signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca2+ release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. PMID:26728458

Comparative Evaluation of Tubex TF (Inhibition Magnetic Binding Immunoassay) for Typhoid Fever in Endemic Area.

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Khanna, Ashish; Khanna, Menka; Gill, Karamjit Singh

2015-11-01

Typhoid fever remains a significant health problem in endemic countries like India. Various serological tests for the diagnosis of typhoid fever are available commercially. We assessed the usefulness of rapid test based on magnetic particle separation to detect Immunoglobulin against Salmonella typhi O9 lipopolysaccharide. Aim of this study was to compare the sensitivity and specificity of widal test, typhidot and tubex TF test for the diagnosis of typhoid fever in an endemic country like India. Serum samples collected from 50 patients of typhoid fever, 50 patients of non typhoid fever and 100 normal healthy individuals residing in Amritsar were subjected to widal test, typhidot test and tubex TF test as per manufacturer's instructions. Data collected was assessed to find sensitivity and specificity of these tests in an endemic area. Significant widal test results were found positive in 68% of patients of typhoid fever and only 4% of non typhoid fever patients. Typhidot (IgM or IgG) was positive in 72% of typhoid fever patients and 10% and 6% in non typhoid fever and normal healthy individuals respectively. Tubex TF showed higher sensitivity of 76% and specificity of 96-99% which was higher than typhidot and comparable to widal test. This was the first evaluation of rapid tubex TF test in northern India. In countries which can afford high cost of test, tubex TF should be recommended for the diagnosis in acute stage of the disease in clinical setting. However, there is urgent need for a highly specific and sensitive test for the diagnosis of typhoid fever in clinical settings in endemic areas.

Localized scleroderma en coup de sabre in the Neurology Clinic.

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Pinho, João; Rocha, João; Sousa, Filipa; Macedo, Cristiana; Soares-Fernandes, João; Cerqueira, João; Maré, Ricardo; Lourenço, Esmeralda; Pereira, João

2016-07-01

Localized scleroderma en coup de sabre (LScs) is a form of localized scleroderma thought to be an autoimmune disorder. Central nervous system involvement is not rare and neurological manifestations include seizures, focal neurological deficits, headache and neuropsychiatric changes. Patients attending the Neurology Clinic with the final diagnosis of LScs with neurological manifestations were identified and clinical and imagiological records reviewed. Five patients (0.024%) had LScs with neurological involvement, presenting with transient focal neurologic deficits, seizures, headache or migraine with aura. Neuroimaging studies confirmed localized skin depression and showed bone thinning, white matter lesions, brain calcifications, sulcal effacement and meningeal enhancement. Three patients experienced clinical improvement after immunosuppressive therapy, and in two of these patients neuroimaging findings also improved. Recognizing typical dermatologic changes is keystone for the diagnosis of LScs with neurological involvement. It is a diagnosis of exclusion and extensive etiological diagnostic evaluation should be performed. Treatment options, including conservative follow-up or immunosuppressive therapy, should be carefully considered. Copyright © 2016 Elsevier B.V. All rights reserved.

DipoCoup: A versatile program for 3D-structure homology comparison based on residual dipolar couplings and pseudocontact shifts

International Nuclear Information System (INIS)

Meiler, Jens; Peti, Wolfgang; Griesinger, Christian

2000-01-01

A program, DipoCoup, is presented that allows to search the protein data bank for proteins which have a three dimensional fold that is at least partially homologous to a protein under investigation. The three dimensional homology search uses secondary structure alignment based on chemical shifts and dipolar couplings or pseudocontact shifts for the three dimensional orientation of secondary structure elements. Moreover, the program offers additional tools for handling and analyzing dipolar couplings

The chronic encephalopathy of Parry Romberg Syndrome and en coupe de sabre with a 31-year-history in a West Indian woman: clinical, immunologic and neuroimaging abnormalities

Directory of Open Access Journals (Sweden)

Karan Seegobin

2016-09-01

Full Text Available We describe a case of Parry Romberg syndrome/ en coupe de sabre in a woman whose disease started as seizures at age 8 but was diagnosed at the age 39. During these 31 years she got married, completed a first degree at university, had two successful pregnancies and has been gainfully employed. The features of generalized tonic-clonic seizures, autoimmune abnormalities, ocular abnormalities, morphea en coup de sabre and brain imaging abnormalities were present. Areas of parietal lobe cerebral calcification were encountered on the computed tomographic scan and bilateral periventricular white matter changes on the magnetic resonance imaging with frontal, temporal and parietal lobe brain atrophy ipsilateral to the facial hemiatrophy. Clinical, immunologic and neuroradiological abnormalities are discussed. In some cases, this illness can run a benign and stable course.

Transcriptional programming and functional interactions within the Phytophthora sojae RXLR effector repertoire.

Science.gov (United States)

Wang, Qunqing; Han, Changzhi; Ferreira, Adriana O; Yu, Xiaoli; Ye, Wenwu; Tripathy, Sucheta; Kale, Shiv D; Gu, Biao; Sheng, Yuting; Sui, Yangyang; Wang, Xiaoli; Zhang, Zhengguang; Cheng, Baoping; Dong, Suomeng; Shan, Weixing; Zheng, Xiaobo; Dou, Daolong; Tyler, Brett M; Wang, Yuanchao

2011-06-01

The genome of the soybean pathogen Phytophthora sojae contains nearly 400 genes encoding candidate effector proteins carrying the host cell entry motif RXLR-dEER. Here, we report a broad survey of the transcription, variation, and functions of a large sample of the P. sojae candidate effectors. Forty-five (12%) effector genes showed high levels of polymorphism among P. sojae isolates and significant evidence for positive selection. Of 169 effectors tested, most could suppress programmed cell death triggered by BAX, effectors, and/or the PAMP INF1, while several triggered cell death themselves. Among the most strongly expressed effectors, one immediate-early class was highly expressed even prior to infection and was further induced 2- to 10-fold following infection. A second early class, including several that triggered cell death, was weakly expressed prior to infection but induced 20- to 120-fold during the first 12 h of infection. The most strongly expressed immediate-early effectors could suppress the cell death triggered by several early effectors, and most early effectors could suppress INF1-triggered cell death, suggesting the two classes of effectors may target different functional branches of the defense response. In support of this hypothesis, misexpression of key immediate-early and early effectors severely reduced the virulence of P. sojae transformants.

Book Review: Chachavalpongpun, Pavin (ed. (2014, Good Coup Gone Bad: Thailand’s Political Developments since Thaksin’s Downfall

Directory of Open Access Journals (Sweden)

Hipolitus Yolisandry Ringgi Wangge

2016-01-01

Full Text Available Book Review of the edited volume: Chachavalpongpun, Pavin (ed. (2014, Good Coup Gone Bad: Thailand’s Political Developments since Thaksin’s Downfall. Singapore: Institute of Southeast Asian Studies (ISEAS Publishing, ISBN 979-981-4459-60-0, 290 pages

Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

Science.gov (United States)

Skikne, Barry S; Punnonen, Kari; Caldron, Paul H; Bennett, Michael T; Rehu, Mari; Gasior, Gail H; Chamberlin, Janna S; Sullivan, Linda A; Bray, Kurtis R; Southwick, Paula C

2011-11-01

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Copyright © 2011 Wiley-Liss, Inc.

Searching for the annual modulation of dark matter signal with the GENIUS-TF experiment

International Nuclear Information System (INIS)

Tomei, C.; Dietz, A.; Krivosheina, I.; Klapdor-Kleingrothaus, H.V.

2003-01-01

The annual modulation of the recoil spectrum observed in an underground detector is well known as the main signature of a possible WIMP signal. The GENIUS-TF experiment, under construction in the Gran Sasso National Laboratory, can search for the annual modulation of the Dark Matter signal using 40 kg of naked-Ge detectors in liquid nitrogen. Starting from a set of data simulated under the hypothesis of modulation and using different methods, we show the potential of GENIUS-TF for extracting the modulated signal and the expected WIMP mass and WIMP cross-section

Redesigning pH optimum of Geobacillus sp. TF16 endoxylanase through in silico designed DNA swapping strategy.

Science.gov (United States)

Uzuner, Ugur; Canakci, Sabriye; Bektas, Kadriye Inan; Sapmaz, Merve Tuncel; Belduz, Ali Osman

2017-06-01

Thermoalkaliphilic xylanases are highly desired and of great importance due to their vast potential in paper pulp and bleaching processes. Here, we report rapid, cost-effective, and result-oriented combinatorial potential of in silico DNA swapping strategy to engineer the pH optimum of industrially crucial enzymes, particularly engineering of Geobacillus sp. TF16 endoxylanase for alkaline environments. The 3D structures of Geobacillus sp. TF16 and donor Bacillus halodurans C-125 endoxylanases were firstly predicted, analyzed, and compared for their similarities before any in silico design of mutants. Reasonably, to improve its alkaline pH tolerance, the corresponding regions in Geobacillus sp.TF16 endoxylanase were further engineered by swapping with negatively-charged amino acid-rich regions from B. halodurans C-125 endoxylanase. Through only two of four in silico-designed mutants, the optimum pH of GeoTF16 endoxylanase was improved from 8.5 to 10.0. Moreover, as compared to GeoTF16 parental enzyme, both GeoInt3 and GeoInt4 mutants revealed (i) enhanced biobleaching performance, (ii) improved adaptability to alkaline conditions, and (iii) better activity for broader pH range. Unlike GeoTF16 losing activity at pH 11.0 completely, GeoInt4 retained 60% and 40% of its activity at pH 11.0 and 12.0, respectively. Thus, GeoInt4 stands out as a more competent biocatalyst that is suitable for alkaline environments of diverse industrial applications. The current study represents an efficient protein engineering strategy to adapt industrial catalysts to diverse processing conditions. Further comprehensive and fine-tuned research efforts may result in biotechnologically more promising outcomes. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

The Genome Biology of Effector Gene Evolution in Filamentous Plant Pathogens.

Science.gov (United States)

Sánchez-Vallet, Andrea; Fouché, Simone; Fudal, Isabelle; Hartmann, Fanny E; Soyer, Jessica L; Tellier, Aurélien; Croll, Daniel

2018-05-16

Filamentous pathogens, including fungi and oomycetes, pose major threats to global food security. Crop pathogens cause damage by secreting effectors that manipulate the host to the pathogen's advantage. Genes encoding such effectors are among the most rapidly evolving genes in pathogen genomes. Here, we review how the major characteristics of the emergence, function, and regulation of effector genes are tightly linked to the genomic compartments where these genes are located in pathogen genomes. The presence of repetitive elements in these compartments is associated with elevated rates of point mutations and sequence rearrangements with a major impact on effector diversification. The expression of many effectors converges on an epigenetic control mediated by the presence of repetitive elements. Population genomics analyses showed that rapidly evolving pathogens show high rates of turnover at effector loci and display a mosaic in effector presence-absence polymorphism among strains. We conclude that effective pathogen containment strategies require a thorough understanding of the effector genome biology and the pathogen's potential for rapid adaptation. Expected final online publication date for the Annual Review of Phytopathology Volume 56 is August 25, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Nematode effector proteins: an emerging paradigm of parasitism

Science.gov (United States)

Phytonematodes use a stylet and secreted effectors to invade host tissues and extract nutrients to support their growth and development. The molecular function of nematode effectors is currently the subject of intense investigation. In this review, we summarize our current understanding of nematode ...

Identifying TF-MiRNA Regulatory Relationships Using Multiple Features.

Directory of Open Access Journals (Sweden)

Mingyu Shao

Full Text Available MicroRNAs are known to play important roles in the transcriptional and post-transcriptional regulation of gene expression. While intensive research has been conducted to identify miRNAs and their target genes in various genomes, there is only limited knowledge about how microRNAs are regulated. In this study, we construct a pipeline that can infer the regulatory relationships between transcription factors and microRNAs from ChIP-Seq data with high confidence. In particular, after identifying candidate peaks from ChIP-Seq data, we formulate the inference as a PU learning (learning from only positive and unlabeled examples problem. Multiple features including the statistical significance of the peaks, the location of the peaks, the transcription factor binding site motifs, and the evolutionary conservation are derived from peaks for training and prediction. To further improve the accuracy of our inference, we also apply a mean reciprocal rank (MRR-based method to the candidate peaks. We apply our pipeline to infer TF-miRNA regulatory relationships in mouse embryonic stem cells. The experimental results show that our approach provides very specific findings of TF-miRNA regulatory relationships.

Functional heterogeneity of human effector CD8+ T cells.

Science.gov (United States)

Takata, Hiroshi; Naruto, Takuya; Takiguchi, Masafumi

2012-02-09

Effector CD8(+) T cells are believed to be terminally differentiated cells having cytotoxic activity and the ability to produce effector cytokines such as INF-γ and TNF-α. We investigated the difference between CXCR1(+) and CXCR1(-) subsets of human effector CD27(-)CD28(-)CD8(+) T cells. The subsets expressed cytolytic molecules similarly and exerted substantial cytolytic activity, whereas only the CXCR1(-) subset had IL-2 productivity and self-proliferative activity and was more resistant to cell death than the CXCR1(+) subset. These differences were explained by the specific up-regulation of CAMK4, SPRY2, and IL-7R in the CXCR1(-) subset and that of pro-apoptotic death-associated protein kinase 1 (DAPK1) in the CXCR1(+) subset. The IL-2 producers were more frequently found in the IL-7R(+) subset of the CXCR1(-) effector CD8(+) T cells than in the IL-7R(-) subset. IL-7/IL-7R signaling promoted cell survival only in the CXCR1(-) subset. The present study has highlighted a novel subset of effector CD8(+) T cells producing IL-2 and suggests the importance of this subset in the homeostasis of effector CD8(+) T cells.

Principles and applications of TAL effectors for plant physiology and metabolism.

Science.gov (United States)

Bogdanove, Adam J

2014-06-01

Recent advances in DNA targeting allow unprecedented control over gene function and expression. Targeting based on TAL effectors is arguably the most promising for systems biology and metabolic engineering. Multiple, orthogonal TAL-effector reagents of different types can be used in the same cell. Furthermore, variation in base preferences of the individual structural repeats that make up the TAL effector DNA recognition domain makes targeting stringency tunable. Realized applications range from genome editing to epigenome modification to targeted gene regulation to chromatin labeling and capture. The principles that govern TAL effector DNA recognition make TAL effectors well suited for applications relevant to plant physiology and metabolism. TAL effector targeting has merits that are distinct from those of the RNA-based DNA targeting CRISPR/Cas9 system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intraspecies Competition in Serratia marcescens Is Mediated by Type VI-Secreted Rhs Effectors and a Conserved Effector-Associated Accessory Protein.

Science.gov (United States)

Alcoforado Diniz, Juliana; Coulthurst, Sarah J

2015-07-01

The type VI secretion system (T6SS) is widespread in Gram-negative bacteria and can deliver toxic effector proteins into eukaryotic cells or competitor bacteria. Antibacterial T6SSs are increasingly recognized as key mediators of interbacterial competition and may contribute to the outcome of many polymicrobial infections. Multiple antibacterial effectors can be delivered by these systems, with diverse activities against target cells and distinct modes of secretion. Polymorphic toxins containing Rhs repeat domains represent a recently identified and as-yet poorly characterized class of T6SS-dependent effectors. Previous work had revealed that the potent antibacterial T6SS of the opportunistic pathogen Serratia marcescens promotes intraspecies as well as interspecies competition (S. L. Murdoch, K. Trunk, G. English, M. J. Fritsch, E. Pourkarimi, and S. J. Coulthurst, J Bacteriol 193:6057-6069, 2011, http://dx.doi.org/10.1128/JB.05671-11). In this study, two new Rhs family antibacterial effectors delivered by this T6SS have been identified. One of these was shown to act as a DNase toxin, while the other contains a novel, cytoplasmic-acting toxin domain. Importantly, using S. marcescens, it has been demonstrated for the first time that Rhs proteins, rather than other T6SS-secreted effectors, can be the primary determinant of intraspecies competition. Furthermore, a new family of accessory proteins associated with T6SS effectors has been identified, exemplified by S. marcescens EagR1, which is specifically required for deployment of its associated Rhs effector. Together, these findings provide new insight into how bacteria can use the T6SS to deploy Rhs-family effectors and mediate different types of interbacterial interactions. Infectious diseases caused by bacterial pathogens represent a continuing threat to health and economic prosperity. To counter this threat, we must understand how such organisms survive and prosper. The type VI secretion system is a weapon that

Dendritic Cytoskeletal Architecture Is Modulated by Combinatorial Transcriptional Regulation in Drosophila melanogaster.

Science.gov (United States)

Das, Ravi; Bhattacharjee, Shatabdi; Patel, Atit A; Harris, Jenna M; Bhattacharya, Surajit; Letcher, Jamin M; Clark, Sarah G; Nanda, Sumit; Iyer, Eswar Prasad R; Ascoli, Giorgio A; Cox, Daniel N

2017-12-01

Transcription factors (TFs) have emerged as essential cell autonomous mediators of subtype specific dendritogenesis; however, the downstream effectors of these TFs remain largely unknown, as are the cellular events that TFs control to direct morphological change. As dendritic morphology is largely dictated by the organization of the actin and microtubule (MT) cytoskeletons, elucidating TF-mediated cytoskeletal regulatory programs is key to understanding molecular control of diverse dendritic morphologies. Previous studies in Drosophila melanogaster have demonstrated that the conserved TFs Cut and Knot exert combinatorial control over aspects of dendritic cytoskeleton development, promoting actin and MT-based arbor morphology, respectively. To investigate transcriptional targets of Cut and/or Knot regulation, we conducted systematic neurogenomic studies, coupled with in vivo genetic screens utilizing multi-fluor cytoskeletal and membrane marker reporters. These analyses identified a host of putative Cut and/or Knot effector molecules, and a subset of these putative TF targets converge on modulating dendritic cytoskeletal architecture, which are grouped into three major phenotypic categories, based upon neuromorphometric analyses: complexity enhancer, complexity shifter, and complexity suppressor. Complexity enhancer genes normally function to promote higher order dendritic growth and branching with variable effects on MT stabilization and F-actin organization, whereas complexity shifter and complexity suppressor genes normally function in regulating proximal-distal branching distribution or in restricting higher order branching complexity, respectively, with spatially restricted impacts on the dendritic cytoskeleton. Collectively, we implicate novel genes and cellular programs by which TFs distinctly and combinatorially govern dendritogenesis via cytoskeletal modulation. Copyright © 2017 by the Genetics Society of America.

Genomic characterisation of the effector complement of the potato cyst nematode Globodera pallida.

Science.gov (United States)

Thorpe, Peter; Mantelin, Sophie; Cock, Peter Ja; Blok, Vivian C; Coke, Mirela C; Eves-van den Akker, Sebastian; Guzeeva, Elena; Lilley, Catherine J; Smant, Geert; Reid, Adam J; Wright, Kathryn M; Urwin, Peter E; Jones, John T

2014-10-23

The potato cyst nematode Globodera pallida has biotrophic interactions with its host. The nematode induces a feeding structure - the syncytium - which it keeps alive for the duration of the life cycle and on which it depends for all nutrients required to develop to the adult stage. Interactions of G. pallida with the host are mediated by effectors, which are produced in two sets of gland cells. These effectors suppress host defences, facilitate migration and induce the formation of the syncytium. The recent completion of the G. pallida genome sequence has allowed us to identify the effector complement from this species. We identify 128 orthologues of effectors from other nematodes as well as 117 novel effector candidates. We have used in situ hybridisation to confirm gland cell expression of a subset of these effectors, demonstrating the validity of our effector identification approach. We have examined the expression profiles of all effector candidates using RNAseq; this analysis shows that the majority of effectors fall into one of three clusters of sequences showing conserved expression characteristics (invasive stage nematode only, parasitic stage only or invasive stage and adult male only). We demonstrate that further diversity in the effector pool is generated by alternative splicing. In addition, we show that effectors target a diverse range of structures in plant cells, including the peroxisome. This is the first identification of effectors from any plant pathogen that target this structure. This is the first genome scale search for effectors, combined to a life-cycle expression analysis, for any plant-parasitic nematode. We show that, like other phylogenetically unrelated plant pathogens, plant parasitic nematodes deploy hundreds of effectors in order to parasitise plants, with different effectors required for different phases of the infection process.

Fibre optic sensor on robot end effector for flexible assembly

International Nuclear Information System (INIS)

Yung, K.L.; Lau, W.S.; Choi, C.K.; Shan, Y.Y.

1995-01-01

A fibre optic sensor system was constructed for use on robot end effectors for flexible assembly. The sensor detected the deviations between robot end effector and the workpiece. The signal was fed back to robot controller to shift the end effector until the centre of end effector and the centre of workpiece were aligned at the correct orientation. Then workpiece can be grasped symmetrically. Sensor fusion concept was used to guard against sensor system failure. Fuzzy linguistic variable and control rule concept were introduced in the sensor integration. The experimental setup for the sensor integrated system was shown. The accuracy was also discussed

Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells.

Science.gov (United States)

Ali, Ramadan A; Camick, Christina; Wiles, Katherine; Walseth, Timothy F; Slama, James T; Bhattacharya, Sumit; Giovannucci, David R; Wall, Katherine A

2016-02-26

Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca(2+) mobilizing second messenger discovered to date, has been implicated in Ca(2+) signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca(2+) signaling or the identity of the Ca(2+) stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca(2+) signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca(2+) signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca(2+) stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca(2+) signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca(2+) release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

APPLICATION HYDRAULIQUE DE LA TECHNIQUE GRAPHIQUE DE BERGERON AUX ACCIDENTS VASCULAIRES CÉRÉBRAUX : LE COUP DE BÉLIER HYDRAULIQUE Á L’ORIGINE D’UNE CAVITATION ENGENDRANT UN PHÉNOMÈNE DE THIXOTROPIE. LE MIRACLE DE SAINT JANVIER : HYPOTHESE SUR L’ORIGINE DE L’HEMORRAGIE CEREBRALE DU SUJET HYPERTENDU.

OpenAIRE

Venet , Richard; Léger , Philippe; Pavie , Alain

2013-01-01

Un poète de l’entre deux guerres a décrit les circonstances de son accident vasculaire cérébral, nous évoquant « un coup de bélier hydraulique ». Pour Ahlqvist l’hémorragie cérébrale est secondaire à l’embolisation (occlusion instantanée) d’une artère cérébrale engendrant ainsi un coup de bélier responsable de la fissuration d’un micro-anévrisme de Charcot. Nous nous proposons dans cet article d’exposer le plus compendieusement possible la théorie du coup de bélier hydraulique. Appliquant cet...

Nanorobotic end-effectors: Design, fabrication, and in situ characterization

Science.gov (United States)

Fan, Zheng

Nano-robotic end-effectors have promising applications for nano-fabrication, nano-manufacturing, nano-optics, nano-medical, and nano-sensing; however, low performances of the conventional end-effectors have prevented the widespread utilization of them in various fields. There are two major difficulties in developing the end-effectors: their nano-fabrication and their advanced characterization in the nanoscale. Here we introduce six types of end-effectors: the nanotube fountain pen (NFP), the super-fine nanoprobe, the metal-filled carbon nanotube (m CNT)-based sphere-on-pillar (SOP) nanoantennas, the tunneling nanosensor, and the nanowire-based memristor. The investigations on the NFP are focused on nano-fluidics and nano-fabrications. The NFP could direct write metallic "inks" and fabricating complex metal nanostructures from 0D to 3D with a position servo control, which is critically important to future large-scale, high-throughput nanodevice production. With the help of NFP, we could fabricate the end-effectors such as super-fine nanoprobe and m CNT-based SOP nanoantennas. Those end-effectors are able to detect local flaws or characterize the electrical/mechanical properties of the nanostructure. Moreover, using electron-energy-loss-spectroscopy (EELS) technique during the operation of the SOP optical antenna opens a new basis for the application of nano-robotic end-effectors. The technique allows advanced characterization of the physical changes, such as carrier diffusion, that are directly responsible for the device's properties. As the device was coupled with characterization techniques of scanning-trasmission-electron-microscopy (STEM), the development of tunneling nanosensor advances this field of science into quantum world. Furthermore, the combined STEM-EELS technique plays an important role in our understanding of the memristive switching performance in the nanowire-based memristor. The developments of those nano-robotic end-effectors expend the study

GENIUS-TF: a test facility for the GENIUS project

OpenAIRE

Baudis, L.; Dietz, A.; Heusser, G.; Majorovits, B.; Strecker, H.; Klapdor--Kleingrothaus, H. V.

2000-01-01

GENIUS is a proposal for a large scale detector of rare events. As a first step of the experiment, a small test version, the GENIUS test facility, will be build up at the Laboratorio Nazionale del Gran Sasso (LNGS). With about 40 kg of natural Ge detectors operated in liquid nitrogen, GENIUS-TF could exclude (or directly confirm) the DAMA annual modulation signature within about two years of measurement.

Investigation of a bio-inspired lift-enhancing effector on a 2D airfoil.

Science.gov (United States)

Johnston, Joe; Gopalarathnam, Ashok

2012-09-01

A flap mounted on the upper surface of an airfoil, called a 'lift-enhancing effector', has been shown in wind tunnel tests to have a similar function to a bird's covert feathers, which rise off the wing's surface in response to separated flows. The effector, fabricated from a thin Mylar sheet, is allowed to rotate freely about its leading edge. The tests were performed in the NCSU subsonic wind tunnel at a chord Reynolds number of 4 × 10(5). The maximum lift coefficient with the effector was the same as that for the clean airfoil, but was maintained over an angle-of-attack range from 12° to almost 20°, resulting in a very gentle stall behavior. To better understand the aerodynamics and to estimate the deployment angle of the free-moving effector, fixed-angle effectors fabricated out of stiff wood were also tested. A progressive increase in the stall angle of attack with increasing effector angle was observed, with diminishing returns beyond the effector angle of 60°. Drag tests on both the free-moving and fixed effectors showed a marked improvement in drag at high angles of attack. Oil flow visualization on the airfoil with and without the fixed-angle effectors proved that the effector causes the separation point to move aft on the airfoil, as compared to the clean airfoil. This is thought to be the main mechanism by which an effector improves both lift and drag. A comparison of the fixed-effector results with those from the free-effector tests shows that the free effector's deployment angle is between 30° and 45°. When operating at and beyond the clean airfoil's stall angle, the free effector automatically deploys to progressively higher angles with increasing angles of attack. This slows down the rapid upstream movement of the separation point and avoids the severe reduction in the lift coefficient and an increase in the drag coefficient that are seen on the clean airfoil at the onset of stall. Thus, the effector postpones the stall by 4-8° and makes the

Design and Computational Fluid Dynamics Optimization of the Tube End Effector for Reactor Pressure Vessel Head Type VVER-1000

International Nuclear Information System (INIS)

Novosel, D.

2006-01-01

In this paper is presented development and optimization of the tube end effector design which should consist of 4 ultrasonic transducers, 4 Eddy Current's transducers and Radiation Proof Dot Camera. Basically, designing was conducted by main input requests, such as: inner diameter of a tested reactor pressure vessel head penetration tube, dimensions of a transducers and maximum allowable vertical movement of a manipulator connection rod in order to cover all inner tube surface. As is obvious, for ultrasonic testing should be provided the thin layer of liquid material (in our case water was chosen) which is necessary to make physical contact between transducer surface and investigated inner tube surface. By help of Computational Fluid Dynamics, determined were parameters of geometry, as the most important factor of transducer housing, hydraulically parameters for water supply and primary drain together implemented into this housing, movement of the end effectors (vertical and cylindrical) and finally, necessary equipment which has to provide all hydraulically and pneumatic requirements. As the cylindrical surface of the inner tube diameter was liquefied and contact between transducer housing and tested tube wasn't ideally covered, water leakage could occur in downstream direction. To reduce water leakage, which is highly contaminated, developed was second water drain by diffuser assembly which is driven by Venturi pipe, commercially called vacuum generator. Using the Computational Fluid Dynamic, obtained was optimized geometry of diffuser control volume with the highest efficiency, in other words, unobstructed fluid flux. Afterwards, the end effectors system was synchronized to the existing operable system for NDT methods all invented and designed by INETEC. (author)

Design and force analysis of end-effector for plug seedling transplanter.

Science.gov (United States)

Jiang, Zhuohua; Hu, Yang; Jiang, Huanyu; Tong, Junhua

2017-01-01

Automatic transplanters have been very important in greenhouses since the popularization of seedling nurseries. End-effector development is a key technology for transplanting plug seedlings. Most existing end-effectors have problems with holding root plugs or releasing plugs. An efficient end-effector driven by a linear pneumatic cylinder was designed in this study, which could hold root plugs firmly and release plugs easily. This end-effector with four needles could clamp the plug simultaneously while the needles penetrate into the substrate. The depth and verticality of the needles could be adjusted conveniently for different seedling trays. The effectiveness of this end-effector was tested by a combinational trial examining three seedling nursery factors (the moisture content of the substrate, substrate bulk density and the volume proportion of substrate ingredients). Results showed that the total transplanting success rate for the end-effector was 100%, and the root plug harm rate was below 17%. A force measure system with tension and pressure transducers was installed on the designed end-effector. The adhesive force FL between the root plug and the cell of seedling trays and the extrusion force FK on the root plug were measured and analyzed. The results showed that all three variable factors and their interactions had significant effects on the extrusion force. Each factor had a significant effect on adhesive force. Additionally, it was found that the end-effector did not perform very well when the value of FK/FL was beyond the range of 5.99~8.67. This could provide a scientific basis for end-effector application in transplanting.

Impact of maximum TF magnetic field on performance and cost of an advanced physics tokamak

International Nuclear Information System (INIS)

Reid, R.L.

1983-01-01

Parametric studies were conducted using the Fusion Engineering Design Center (FEDC) Tokamak Systems Code to investigate the impact of variation in the maximum value of the field at the toroidal field (TF) coils on the performance and cost of a low q/sub psi/, quasi-steady-state tokamak. Marginal ignition, inductive current startup plus 100 s of inductive burn, and a constant value of epsilon (inverse aspect ratio) times beta poloidal were global conditions imposed on this study. A maximum TF field of approximately 10 T was found to be appropriate for this device

New clues in the nucleus: Transcriptional reprogramming in effector-triggered immunity

Directory of Open Access Journals (Sweden)

SAIKAT eBHATTACHARJEE

2013-09-01

Full Text Available The robustness of plant effector-triggered immunity is correlated with massive alterations of the host transcriptome. Yet the molecular mechanisms that cause and underlie this reprogramming remain obscure. Here we will review recent advances in deciphering nuclear functions of plant immune receptors and of associated proteins. Important open questions remain, such as the identities of the primary transcription factors involved in control of effector-triggered immune responses, and indeed whether this can be generalized or whether particular effector-resistance protein interactions impinge on distinct sectors in the transcriptional response web. Multiple lines of evidence have implicated WRKY transcription factors at the core of responses to microbe-associated molecular patterns and in intersections with effector-triggered immunity. Recent findings from yeast two-hybrid studies suggest that members of the TCP transcription factor family are targets of several effectors from diverse pathogens. Additional transcription factor families that are directly or indirectly involved in effector-triggered immunity are likely to be identified.

Fatigue assessment of the ITER TF coil case based on JJ1 fatigue tests

International Nuclear Information System (INIS)

Hamada, K.; Nakajima, H.; Takano, K.; Kudo, Y.; Tsutsumi, F.; Okuno, K.; Jong, C.

2005-01-01

The material of the TF coil case in the ITER requires to withstand cyclic electromagnetic forces applied up to 3 x 10 4 cycles at 4.2 K. A cryogenic stainless steel, JJ1, is used in high stress region of TF coil case. The fatigue characteristics (S-N curve) of JJ1 base metal and welded joint at 4.2 K has been measured. The fatigue strength of base metal and welded joint at 3 x 10 4 cycles are measured as 1032 and 848 MPa, respectively. The design S-N curve is derived from the measured data taking account of the safety factor of 20 for cycle-to-failure and 2 for fatigue strength, and it indicates that an equivalent alternating stress of the case should be kept less than 516 MPa for the base metal and 424 MPa for the welded joint at 3 x 10 4 cycles. It is demonstrated that the TF coil case has enough margins for the cyclic operation. It is also shown the welded joint should be located in low cyclic stress region because a residual stress affects the fatigue life

Design and force analysis of end-effector for plug seedling transplanter.

Directory of Open Access Journals (Sweden)

Zhuohua Jiang

Full Text Available Automatic transplanters have been very important in greenhouses since the popularization of seedling nurseries. End-effector development is a key technology for transplanting plug seedlings. Most existing end-effectors have problems with holding root plugs or releasing plugs. An efficient end-effector driven by a linear pneumatic cylinder was designed in this study, which could hold root plugs firmly and release plugs easily. This end-effector with four needles could clamp the plug simultaneously while the needles penetrate into the substrate. The depth and verticality of the needles could be adjusted conveniently for different seedling trays. The effectiveness of this end-effector was tested by a combinational trial examining three seedling nursery factors (the moisture content of the substrate, substrate bulk density and the volume proportion of substrate ingredients. Results showed that the total transplanting success rate for the end-effector was 100%, and the root plug harm rate was below 17%. A force measure system with tension and pressure transducers was installed on the designed end-effector. The adhesive force FL between the root plug and the cell of seedling trays and the extrusion force FK on the root plug were measured and analyzed. The results showed that all three variable factors and their interactions had significant effects on the extrusion force. Each factor had a significant effect on adhesive force. Additionally, it was found that the end-effector did not perform very well when the value of FK/FL was beyond the range of 5.99~8.67. This could provide a scientific basis for end-effector application in transplanting.

Analysis of NSTX TF Joint Voltage Measurements

International Nuclear Information System (INIS)

Woolley R

2005-01-01

This report presents findings of analyses of recorded current and voltage data associated with 72 electrical joints operating at high current and high mechanical stress. The analysis goal was to characterize the mechanical behavior of each joint and thus evaluate its mechanical supports. The joints are part of the toroidal field (TF) magnet system of the National Spherical Torus Experiment (NSTX) pulsed plasma device operating at the Princeton Plasma Physics Laboratory (PPPL). Since there is not sufficient space near the joints for much traditional mechanical instrumentation, small voltage probes were installed on each joint and their voltage monitoring waveforms have been recorded on sampling digitizers during each NSTX ''shot''

Controlling transcription in human pluripotent stem cells using CRISPR-effectors.

Science.gov (United States)

Genga, Ryan M; Kearns, Nicola A; Maehr, René

2016-05-15

The ability to manipulate transcription in human pluripotent stem cells (hPSCs) is fundamental for the discovery of key genes and mechanisms governing cellular state and differentiation. Recently developed CRISPR-effector systems provide a systematic approach to rapidly test gene function in mammalian cells, including hPSCs. In this review, we discuss recent advances in CRISPR-effector technologies that have been employed to control transcription through gene activation, gene repression, and epigenome engineering. We describe an application of CRISPR-effector mediated transcriptional regulation in hPSCs by targeting a synthetic promoter driving a GFP transgene, demonstrating the ease and effectiveness of CRISPR-effector mediated transcriptional regulation in hPSCs. Copyright © 2015 Elsevier Inc. All rights reserved.

Non Nuclear Testing of Reactor Systems In The Early Flight Fission Test Facilities (EFF-TF)

International Nuclear Information System (INIS)

Van Dyke, Melissa; Martin, James

2004-01-01

The Early Flight Fission-Test Facility (EFF-TF) can assist in the design and development of systems through highly effective non-nuclear testing of nuclear systems when technical issues associated with near-term space fission systems are 'non-nuclear' in nature (e.g. system's nuclear operations are understood). For many systems, thermal simulators can be used to closely mimic fission heat deposition. Axial power profile, radial power profile, and fuel pin thermal conductivity can be matched. In addition to component and subsystem testing, operational and lifetime issues associated with the steady state and transient performance of the integrated reactor module can be investigated. Instrumentation at the EFF-TF allows accurate measurement of temperature, pressure, strain, and bulk core deformation (useful for accurately simulating nuclear behavior). Ongoing research at the EFF-TF is geared towards facilitating research, development, system integration, and system utilization via cooperative efforts with DOE laboratories, industry, universities, and other Nasa centers. This paper describes the current efforts for the latter portion of 2003 and beginning of 2004. (authors)

BOREAS TF-8 NSA-OJP Tower Flux, Meteorological, and Soil Temperature Data

Science.gov (United States)

Hall, Forrest G. (Editor); Huemmrich, Karl (Editor); Moore, Kathleen E.; Fitzjarrald, David R.

2000-01-01

The BOREAS TF-8 team collected energy, CO2, and water vapor flux data at the BOREAS NSA-OJP site during the growing season of 1994 and most of the year for 1996. The data are available in tabular ASCII files.

The value of Ret-Hb and sTfR in the diagnosis of iron depletion in healthy, young children

NARCIS (Netherlands)

Uijterschout, L.; Domellöf, M.; Vloemans, J.; Vos, R.; Hudig, C.; Bubbers, S.; Verbruggen, S.; Veldhorst, M.; de Leeuw, T.; Teunisse, P. P.; van Goudoever, J. B.; Brus, F.

2014-01-01

Reticulocyte hemoglobin (Ret-Hb) content and soluble transferrin receptor (sTfR) are described as promising biomarkers in the analysis of iron status. However, the value of Ret-Hb and sTfR in the early detection of iron depletion, as frequently observed in children in high-income countries, is

Immunohistochemical evalulation of activated Ras and Rac1 as potential downstream effectors of aquaporin-5 in breast cancer in vivo.

Science.gov (United States)

Jensen, Helene H; Login, Frédéric H; Park, Ji-Young; Kwon, Tae-Hwan; Nejsum, Lene N

2017-11-25

Aberrant levels of aquaporin-5 (AQP5) expression have been observed in several types of cancer, including breast cancer, where AQP5 overexpression is associated with metastasis and poor prognosis. In cultured cancer cells, AQP5 facilitates cell migration and activates Ras signaling. Both increased cell migration and Ras activation are associated with cancer metastasis, but so far it is unknown if AQP5 also affects these processes in vivo. Therefore, we investigated if high AQP5 expression in breast cancer tissue correlated with increased activation of Ras and of Rac1, which is a GTPase also involved in cell migration. This was accomplished by immunohistochemical analysis of invasive ductal carcinoma of breast tissue sections from human patients, followed by qualitative and quantitative correlation analysis between AQP5 and activated Ras and Rac1. Immunohistochemistry revealed that activation of Ras and Rac1 was positively correlated. There was, however, no correlation between high AQP5 expression and activation of Ras, whereas a nonsignificant, but positive, tendency between the levels of AQP5 and activated Rac1 levels was observed. In summary, this is the first report that correlates AQP5 expression levels to downstream signaling partners in breast cancer tissue sections. The results suggest Rac1 as a potential downstream signaling partner of AQP5 in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Test facility for PLT TF coils

International Nuclear Information System (INIS)

Hearney, J.; File, J.; Dreskin, S.

1975-01-01

Past experience with the model C stellerator and other toroidal field devices indicates that mechanical and electrical tests of a toroidal field coil prior to maximum field operation of the device is prudent and desirable. This paper describes a test program for the PLT-TF coils. The test stand consists of one test coil, two background coils and a steel supporting structure. The three coil configuration produces a 67.5 kG field at the inner conductor (38 kG at the bore center) and simulates a 1/R field distribution in the bore of the test coil. The resolution of the field force system and resultant stresses within the test structure are discussed. A test procedure is described which maximizes the information obtained from a 100,000 pulse program

Genome-Wide Analysis of Corynespora cassiicola Leaf Fall Disease Putative Effectors.

Science.gov (United States)

Lopez, David; Ribeiro, Sébastien; Label, Philippe; Fumanal, Boris; Venisse, Jean-Stéphane; Kohler, Annegret; de Oliveira, Ricardo R; Labutti, Kurt; Lipzen, Anna; Lail, Kathleen; Bauer, Diane; Ohm, Robin A; Barry, Kerrie W; Spatafora, Joseph; Grigoriev, Igor V; Martin, Francis M; Pujade-Renaud, Valérie

2018-01-01

Corynespora cassiicola is an Ascomycetes fungus with a broad host range and diverse life styles. Mostly known as a necrotrophic plant pathogen, it has also been associated with rare cases of human infection. In the rubber tree, this fungus causes the Corynespora leaf fall (CLF) disease, which increasingly affects natural rubber production in Asia and Africa. It has also been found as an endophyte in South American rubber plantations where no CLF outbreak has yet occurred. The C. cassiicola species is genetically highly diverse, but no clear relationship has been evidenced between phylogenetic lineage and pathogenicity. Cassiicolin, a small glycosylated secreted protein effector, is thought to be involved in the necrotrophic interaction with the rubber tree but some virulent C. cassiicola isolates do not have a cassiicolin gene. This study set out to identify other putative effectors involved in CLF. The genome of a highly virulent C. cassiicola isolate from the rubber tree (CCP) was sequenced and assembled. In silico prediction revealed 2870 putative effectors, comprising CAZymes, lipases, peptidases, secreted proteins and enzymes associated with secondary metabolism. Comparison with the genomes of 44 other fungal species, focusing on effector content, revealed a striking proximity with phylogenetically unrelated species ( Colletotrichum acutatum, Colletotrichum gloesporioides, Fusarium oxysporum, nectria hematococca , and Botrosphaeria dothidea ) sharing life style plasticity and broad host range. Candidate effectors involved in the compatible interaction with the rubber tree were identified by transcriptomic analysis. Differentially expressed genes included 92 putative effectors, among which cassiicolin and two other secreted singleton proteins. Finally, the genomes of 35 C. cassiicola isolates representing the genetic diversity of the species were sequenced and assembled, and putative effectors identified. At the intraspecific level, effector

Genome-Wide Analysis of Corynespora cassiicola Leaf Fall Disease Putative Effectors

Directory of Open Access Journals (Sweden)

David Lopez

2018-03-01

Full Text Available Corynespora cassiicola is an Ascomycetes fungus with a broad host range and diverse life styles. Mostly known as a necrotrophic plant pathogen, it has also been associated with rare cases of human infection. In the rubber tree, this fungus causes the Corynespora leaf fall (CLF disease, which increasingly affects natural rubber production in Asia and Africa. It has also been found as an endophyte in South American rubber plantations where no CLF outbreak has yet occurred. The C. cassiicola species is genetically highly diverse, but no clear relationship has been evidenced between phylogenetic lineage and pathogenicity. Cassiicolin, a small glycosylated secreted protein effector, is thought to be involved in the necrotrophic interaction with the rubber tree but some virulent C. cassiicola isolates do not have a cassiicolin gene. This study set out to identify other putative effectors involved in CLF. The genome of a highly virulent C. cassiicola isolate from the rubber tree (CCP was sequenced and assembled. In silico prediction revealed 2870 putative effectors, comprising CAZymes, lipases, peptidases, secreted proteins and enzymes associated with secondary metabolism. Comparison with the genomes of 44 other fungal species, focusing on effector content, revealed a striking proximity with phylogenetically unrelated species (Colletotrichum acutatum, Colletotrichum gloesporioides, Fusarium oxysporum, nectria hematococca, and Botrosphaeria dothidea sharing life style plasticity and broad host range. Candidate effectors involved in the compatible interaction with the rubber tree were identified by transcriptomic analysis. Differentially expressed genes included 92 putative effectors, among which cassiicolin and two other secreted singleton proteins. Finally, the genomes of 35 C. cassiicola isolates representing the genetic diversity of the species were sequenced and assembled, and putative effectors identified. At the intraspecific level, effector

Space-based multifunctional end effector systems functional requirements and proposed designs

Science.gov (United States)

Mishkin, A. H.; Jau, B. M.

1988-01-01

The end effector is an essential element of teleoperator and telerobot systems to be employed in space in the next decade. The report defines functional requirements for end effector systems to perform operations that are currently only feasible through Extra-Vehicular Activity (EVA). Specific tasks and functions that the end effectors must be capable of performing are delineated. Required capabilities for forces and torques, clearances, compliance, and sensing are described, using current EVA requirements as guidelines where feasible. The implications of these functional requirements on the elements of potential end effector systems are discussed. The systems issues that must be considered in the design of space-based manipulator systems are identified; including impacts on subsystems tightly coupled to the end effector, i.e., control station, information processing, manipulator arm, tool and equipment stowage. Possible end effector designs are divided into three categories: single degree-of-freedom end effectors, multiple degree of freedom end effectors, and anthropomorphic hands. Specific design alternatives are suggested and analyzed within the individual categories. Two evaluations are performed: the first considers how well the individual end effectors could substitute for EVA; the second compares how manipulator systems composed of the top performers from the first evaluation would improve the space shuttle Remote Manipulator System (RMS) capabilities. The analysis concludes that the anthropomorphic hand is best-suited for EVA tasks. A left- and right-handed anthropomorphic manipulator arm configuration is suggested as appropriate to be affixed to the RMS, but could also be used as part of the Smart Front End for the Orbital Maneuvering Vehicle (OMV). The technical feasibility of the anthropomorphic hand and its control are demonstrated. An evolutionary development approach is proposed and approximate scheduling provided for implementing the suggested

Quantitative comparison of MiTF, Melan-A, HMB-45 and Mel-5 in solar lentigines and melanoma in situ.

Science.gov (United States)

Kim, Jinah; Taube, Janis M; McCalmont, Timothy H; Glusac, Earl J

2011-10-01

It is often challenging to reliably assess the number of lesional melanocytes in intraepidermal melanocytic proliferations involving sun-damaged skin. Therefore, dermatopathologists routinely use immunostains to help differentiate melanocytes from surrounding keratinocytes. Forty-three cases of solar lentigo or melanoma in situ (of the lentigo maligna type) were retrospectively chosen (20 melanomas in situ and 23 solar lentigo). Microphthalmia transcription factor (MiTF), HMB-45, Melan-A and Mel-5 immunostains were performed with an Azure blue counterstain, and the mean melanocyte counts were calculated within a 1-mm segment of epidermis. In solar lentigines, the mean melanocyte counts were 27 (MiTF), 23 (HMB-45 and Mel-5) and 41 (Melan-A), as compared to hematoxylin and eosin (H&E) (25). In melanoma in situ, the mean melanocyte counts were 112 (MiTF), 149 (Melan-A), 111 (HMB-45) and 80 (Mel-5), as compared to H&E (109). These results show that Melan-A significantly overestimates the density of melanocytes within dermatoheliotic skin. Compared to other tested stains, nuclear staining MiTF allowed greater distinction of melanocytes from keratinocytes with melanized cytoplasm. These findings indicate that MiTF is a superior marker for quantification of melanocytes in the evaluation of subtle intraepidermal melanocytic proliferations and in the differential diagnosis of solar lentigo. Copyright © 2011 John Wiley & Sons A/S.

Identification and Characterisation CRN Effectors in Phytophthora capsici Shows Modularity and Functional Diversity.

Directory of Open Access Journals (Sweden)

Remco Stam

Full Text Available Phytophthora species secrete a large array of effectors during infection of their host plants. The Crinkler (CRN gene family encodes a ubiquitous but understudied class of effectors with possible but as of yet unknown roles in infection. To appreciate CRN effector function in Phytophthora, we devised a simple Crn gene identification and annotation pipeline to improve effector prediction rates. We predicted 84 full-length CRN coding genes and assessed CRN effector domain diversity in sequenced Oomycete genomes. These analyses revealed evidence of CRN domain innovation in Phytophthora and expansion in the Peronosporales. We performed gene expression analyses to validate and define two classes of CRN effectors, each possibly contributing to infection at different stages. CRN localisation studies revealed that P. capsici CRN effector domains target the nucleus and accumulate in specific sub-nuclear compartments. Phenotypic analyses showed that few CRN domains induce necrosis when expressed in planta and that one cell death inducing effector, enhances P. capsici virulence on Nicotiana benthamiana. These results suggest that the CRN protein family form an important class of intracellular effectors that target the host nucleus during infection. These results combined with domain expansion in hemi-biotrophic and necrotrophic pathogens, suggests specific contributions to pathogen lifestyles. This work will bolster CRN identification efforts in other sequenced oomycete species and set the stage for future functional studies towards understanding CRN effector functions.

Short initial length quench on CICC of ITER TF coils

Energy Technology Data Exchange (ETDEWEB)

Nicollet, S.; Ciazynski, D.; Duchateau, J.-L.; Lacroix, B. [CEA, IRFM, F-13108 Saint-Paul-lez-Durance (France); Bessette, D.; Rodriguez-Mateos, F. [ITER Organization, Route de Vinon sur Verdon, 13115 Saint Paul Lez Durance (France); Coatanea-Gouachet, M. [ELC Engineering, 350 chemin du Verladet, F-13290 Les Milles (France); Gauthier, F. [Soditech Ingenierie, 4 bis allée des Gabians, ZI La Frayère, 06150 Cannes (France)

2014-01-29

Previous quench studies performed for the International Thermonuclear Experimental Reactor (ITER) Toroidal Field (TF) Coils have led to identify two extreme families of quench: first 'severe' quenches over long initial lengths in high magnetic field, and second smooth quenches over short initial lengths in low field region. Detailed analyses and results on smooth quench propagation and detectability on one TF Cable In Conduit Conductor (CICC) with a lower propagation velocity are presented here. The influence of the initial quench energy is shown and results of computations with either a Fast Discharge (FD) of the magnet or without (failure of the voltage quench detection system) are reported. The influence of the central spiral of the conductor on the propagation velocity is also detailed. In the cases of a regularly triggered FD, the hot spot temperature criterion of 150 K (with helium and jacket) is fulfilled for an initial quench length of 1 m, whereas this criterion is exceed (Tmax ≈ 200 K) for an extremely short length of 5 cm. These analyses were carried out using both the Supermagnet(trade mark, serif) and Venecia codes and the comparisons of the results are also discussed.

Short initial length quench on CICC of ITER TF coils

International Nuclear Information System (INIS)

Nicollet, S.; Ciazynski, D.; Duchateau, J.-L.; Lacroix, B.; Bessette, D.; Rodriguez-Mateos, F.; Coatanea-Gouachet, M.; Gauthier, F.

2014-01-01

Previous quench studies performed for the International Thermonuclear Experimental Reactor (ITER) Toroidal Field (TF) Coils have led to identify two extreme families of quench: first 'severe' quenches over long initial lengths in high magnetic field, and second smooth quenches over short initial lengths in low field region. Detailed analyses and results on smooth quench propagation and detectability on one TF Cable In Conduit Conductor (CICC) with a lower propagation velocity are presented here. The influence of the initial quench energy is shown and results of computations with either a Fast Discharge (FD) of the magnet or without (failure of the voltage quench detection system) are reported. The influence of the central spiral of the conductor on the propagation velocity is also detailed. In the cases of a regularly triggered FD, the hot spot temperature criterion of 150 K (with helium and jacket) is fulfilled for an initial quench length of 1 m, whereas this criterion is exceed (Tmax ≈ 200 K) for an extremely short length of 5 cm. These analyses were carried out using both the Supermagnet(trade mark, serif) and Venecia codes and the comparisons of the results are also discussed

O après-coup e a reconsolidação da memória

Directory of Open Access Journals (Sweden)

Graziele Luiza Barizon Scopel Gerbasi

2015-04-01

Full Text Available Em diferentes áreas do conhecimento é reconhecido que a memória está sujeita a transformações ao longo do tempo. Partindo desse pressuposto, o objetivo do presente estudo é apresentar uma discussão compreendendo a ideia de que nossas recordações são suscetíveis a transformações e a concepção de après-coup. Há o delineamento de algumas ideias acerca da temporalidade em Psicanálise e do mecanismo de reconsolidação da memória segundo as Neurociências. Utilizando-se tais conceitos, evidenciou-se a viabilidade de se pensar uma interlocução entre a Psicanálise e as Neurociências.

Hippocampal atrophy and developmental regression as first sign of linear scleroderma "en coup de sabre".

Science.gov (United States)

Verhelst, Helene E; Beele, Hilde; Joos, Rik; Vanneuville, Benedicte; Van Coster, Rudy N

2008-11-01

An 8-year-old girl with linear scleroderma "en coup de sabre" is reported who, at preschool age, presented with intractable simple partial seizures more than 1 year before skin lesions were first noticed. MRI revealed hippocampal atrophy, controlaterally to the seizures and ipsilaterally to the skin lesions. In the following months, a mental and motor regression was noticed. Cerebral CT scan showed multiple foci of calcifications in the affected hemisphere. In previously reported patients the skin lesions preceded the neurological signs. To the best of our knowledge, hippocampal atrophy was not earlier reported as presenting symptom of linear scleroderma. Linear scleroderma should be included in the differential diagnosis in patients with unilateral hippocampal atrophy even when the typical skin lesions are not present.

Targeted delivery of siRNA to activated T cells via transferrin-polyethylenimine (Tf-PEI) as a potential therapy of asthma.

Science.gov (United States)

Xie, Yuran; Kim, Na Hyung; Nadithe, Venkatareddy; Schalk, Dana; Thakur, Archana; Kılıç, Ayşe; Lum, Lawrence G; Bassett, David J P; Merkel, Olivia M

2016-05-10

Asthma is a worldwide health problem. Activated T cells (ATCs) in the lung, particularly T helper 2 cells (Th2), are strongly associated with inducing airway inflammatory responses and chemoattraction of inflammatory cells in asthma. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence inflammation related genes in ATCs, however, lack of safe and efficient siRNA delivery systems limits the application of siRNA as a therapeutic molecule in asthma. Here, we designed a novel pulmonary delivery system of siRNA, transferrin-polyethylenimine (Tf-PEI), to selectively deliver siRNA to ATCs in the lung. Tf-PEI polyplexes demonstrated optimal physicochemical properties such as size, distribution, zeta-potential, and siRNA condensation efficiency. Moreover, in vitro studies showed significantly enhanced cellular uptake and gene knockdown mediated by Tf-PEI polyplexes in human primary ATCs. Biodistribution of polyplexes in a murine asthmatic model confirmed that Tf-PEI polyplexes can efficiently and selectively deliver siRNA to ATCs. In conclusion, the present work proves the feasibility to target ATCs in asthma via Tf receptor. This strategy could potentially be used to design an efficient siRNA delivery system for asthma therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of secretion prediction highlights differing approaches needed for oomycete and fungal effectors

Directory of Open Access Journals (Sweden)

Jana eSperschneider

2015-12-01

Full Text Available The steadily increasing number of sequenced fungal and oomycete genomes has enabled detailed studies of how these eukaryotic microbes infect plants and cause devastating losses in food crops. During infection, fungal and oomycete pathogens secrete effector molecules which manipulate host plant cell processes to the pathogen’s advantage. Proteinaceous effectors are synthesised intracellularly and must be externalised to interact with host cells. Computational prediction of secreted proteins from genomic sequences is an important technique to narrow down the candidate effector repertoire for subsequent experimental validation. In this study, we benchmark secretion prediction tools on experimentally validated fungal and oomycete effectors. We observe that for a set of fungal SwissProt protein sequences, SignalP 4 and the neural network predictors of SignalP 3 (D-score and SignalP 2 perform best. For effector prediction in particular, the use of a sensitive method can be desirable to obtain the most complete candidate effector set. We show that the neural network predictors of SignalP 2 and 3, as well as TargetP were the most sensitive tools for fungal effector secretion prediction, whereas the hidden Markov model predictors of SignalP 2 and 3 were the most sensitive tools for oomycete effectors. Thus, previous versions of SignalP retain value for oomycete effector prediction, as the current version, SignalP 4, was unable to reliably predict the signal peptide of the oomycete Crinkler effectors in the test set. Our assessment of subcellular localisation predictors shows that cytoplasmic effectors are often predicted as not extracellular. This limits the reliability of secretion predictions that depend on these tools. We present our assessment with a view to informing future pathogenomics studies and suggest revised pipelines for secretion prediction to obtain optimal effector predictions in fungi and oomycetes.

Effector profiles distinguish formae speciales of Fusarium oxysporum.

Science.gov (United States)

van Dam, Peter; Fokkens, Like; Schmidt, Sarah M; Linmans, Jasper H J; Kistler, H Corby; Ma, Li-Jun; Rep, Martijn

2016-11-01

Formae speciales (ff.spp.) of the fungus Fusarium oxysporum are often polyphyletic within the species complex, making it impossible to identify them on the basis of conserved genes. However, sequences that determine host-specific pathogenicity may be expected to be similar between strains within the same forma specialis. Whole genome sequencing was performed on strains from five different ff.spp. (cucumerinum, niveum, melonis, radicis-cucumerinum and lycopersici). In each genome, genes for putative effectors were identified based on small size, secretion signal, and vicinity to a "miniature impala" transposable element. The candidate effector genes of all genomes were collected and the presence/absence patterns in each individual genome were clustered. Members of the same forma specialis turned out to group together, with cucurbit-infecting strains forming a supercluster separate from other ff.spp. Moreover, strains from different clonal lineages within the same forma specialis harbour identical effector gene sequences, supporting horizontal transfer of genetic material. These data offer new insight into the genetic basis of host specificity in the F. oxysporum species complex and show that (putative) effectors can be used to predict host specificity in F. oxysporum. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Effector/memory CD4 T cells making either Th1 or Th2 cytokines commonly co-express T-bet and GATA-3.

Directory of Open Access Journals (Sweden)

Arundhoti Das

Full Text Available Naïve CD4 T (NCD4T cells post-activation undergo programming for inducible production of cytokines leading to generation of memory cells with various functions. Based on cytokine based polarization of NCD4T cells in vitro, programming for either 'Th1' (interferon-gamma [IFNg] or 'Th2' (interleukin [IL]-4/5/13 cytokines is thought to occur via mutually exclusive expression and functioning of T-bet or GATA-3 transcription factors (TFs. However, we show that a high proportion of mouse and human memory-phenotype CD4 T (MCD4T cells generated in vivo which expressed either Th1 or Th2 cytokines commonly co-expressed T-bet and GATA-3. While T-bet levels did not differ between IFNg-expressing and IL-4/5/13-expressing MCD4T cells, GATA-3 levels were higher in the latter. These observations were also confirmed in MCD4T cells from FVB/NJ or aged C57BL/6 or IFNg-deficient mice. While MCD4T cells from these strains showed greater Th2 commitment than those from young C57BL/6 mice, pattern of co-expression of TF was similar. Effector T cells generated in vivo following immunization also showed TF co-expression in Th1 or Th2 cytokine producing cells. We speculated that the difference in TF expression pattern of MCD4T cells generated in vivo and those generated in cytokine polarized cultures in vitro could be due to relative absence of polarizing conditions during activation in vivo. We tested this by NCD4T cell activation in non-polarizing conditions in vitro. Anti-CD3 and anti-CD28-mediated priming of polyclonal NCD4T cells in vitro without polarizing milieu generated cells that expressed either IFNg or IL-4/5/13 but not both, yet both IFNg- and IL-4/5/13-expressing cells showed upregulation of both TFs. We also tested monoclonal T cell populations activated in non-polarizing conditions. TCR-transgenic NCD4T cells primed in vitro by cognate peptide in non-polarizing conditions which expressed either IFNg or IL-4/5/13 also showed a high proportion of cells co

Effector-triggered immunity: from pathogen perception to robust defense.

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Cui, Haitao; Tsuda, Kenichi; Parker, Jane E

2015-01-01

In plant innate immunity, individual cells have the capacity to sense and respond to pathogen attack. Intracellular recognition mechanisms have evolved to intercept perturbations by pathogen virulence factors (effectors) early in host infection and convert it to rapid defense. One key to resistance success is a polymorphic family of intracellular nucleotide-binding/leucine-rich-repeat (NLR) receptors that detect effector interference in different parts of the cell. Effector-activated NLRs connect, in various ways, to a conserved basal resistance network in order to transcriptionally boost defense programs. Effector-triggered immunity displays remarkable robustness against pathogen disturbance, in part by employing compensatory mechanisms within the defense network. Also, the mobility of some NLRs and coordination of resistance pathways across cell compartments provides flexibility to fine-tune immune outputs. Furthermore, a number of NLRs function close to the nuclear chromatin by balancing actions of defense-repressing and defense-activating transcription factors to program cells dynamically for effective disease resistance.

Treatment processes and demographic variables as predictors of dropout from trauma-focused cognitive behavioral therapy (TF-CBT) for youth.

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Yasinski, Carly; Hayes, Adele M; Alpert, Elizabeth; McCauley, Thomas; Ready, C Beth; Webb, Charles; Deblinger, Esther

2018-05-22

Premature dropout is a significant concern in trauma-focused psychotherapy for youth. Previous studies have primarily examined pre-treatment demographic and symptom-related predictors of dropout, but few consistent findings have been reported. The current study examined demographic, symptom, and in-session process variables as predictors of dropout from Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) for youth. Participants were a diverse sample of Medicaid-eligible youth (ages 7-17; n = 108) and their nonoffending caregivers (n = 86), who received TF-CBT through an effectiveness study in a community setting. In-session process variables were coded from audio-recorded sessions, and these and pre-treatment demographic variables and symptom levels were examined as predictors of dropout prior to receiving an adequate dose of TF-CBT (parents or relatives. No other demographic or symptom-related factors predicted dropout. These findings highlight the importance of addressing avoidance and therapeutic relationship difficulties in early sessions of TF-CBT to help reduce dropout, and they have implications for improving efforts to disseminate evidence-based trauma-focused treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Spargel/dPGC-1 is a new downstream effector in the insulin-TOR signaling pathway in Drosophila.

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Mukherjee, Subhas; Duttaroy, Atanu

2013-10-01

Insulin and target of rapamycin (TOR) signaling pathways converge to maintain growth so a proportionate body form is attained. Insufficiency in either insulin or TOR results in developmental growth defects due to low ATP level. Spargel is the Drosophila homolog of PGC-1, which is an omnipotent transcriptional coactivator in mammals. Like its mammalian counterpart, Spargel/dPGC-1 is recognized for its role in energy metabolism through mitochondrial biogenesis. An earlier study demonstrated that Spargel/dPGC-1 is involved in the insulin-TOR signaling, but a comprehensive analysis is needed to understand exactly which step of this pathway Spargel/PGC-1 is essential. Using genetic epistasis analysis, we demonstrated that a Spargel gain of function can overcome the TOR and S6K mediated cell size and cell growth defects in a cell autonomous manner. Moreover, the tissue-restricted phenotypes of TOR and S6k mutants are rescued by Spargel overexpression. We have further elucidated that Spargel gain of function sets back the mitochondrial numbers in growth-limited TOR mutant cell clones, which suggests a possible mechanism for Spargel action on cells and tissue to attain normal size. Finally, excess Spargel can ameliorate the negative effect of FoxO overexpression only to a limited extent, which suggests that Spargel does not share all of the FoxO functions and consequently cannot significantly rescue the FoxO phenotypes. Together, our observation established that Spargel/dPGC-1 is indeed a terminal effector in the insulin-TOR pathway operating below TOR, S6K, Tsc, and FoxO. This led us to conclude that Spargel should be incorporated as a new member of this growth-signaling pathway.

L'échographie, alternative à la coupe de carcasses dans le testage des aptitudes bouchères

OpenAIRE

Praud, J.P.; Bouix, Jacques; Perret, Gilles

2007-01-01

Une noix de côtelette bien développée est un élément important dans la valorisation des carcasses ovines. Ce caractère a été mesuré pendant plus de 20 ans, dans le cadre des programmes d’évaluation sur descendance des races ovines à viande, par la station nationale de Berry-Test, sur photographies de coupes transversales d’un échantillon de carcasses. Après l’arrêt d’activité de cette station en 2002, le maintien de cette mesure coûteuse en terme de dépréciation de la carcasse et exigeant de ...

The twenty-four/four hour ratio (T/F ratio) of Tc-99m MDP uptake in patients with bone metastases and degenerative changes

International Nuclear Information System (INIS)

Israel, O.; Kleinhaus, U.; Keren, R.; Frankel, A.; Front, D.

1984-01-01

Normal and metastatic bone differ in their histological structure. Normal bone is mainly lamellar while metastatic bone formation is made in a large part out of new woven bone. The woven bone has a much larger surface area than the more stable lamellar bone and it is lined with metabolically active osteoblasts. The crystalline structures in the woven bone are smaller and have a larger surface area available for absorption. Uptake of bone seeking radiopharmaceuticals continues in new woven bone longer than in the lamellar bone. Bone scintigraphy was performed in 89 patients at four hours and 24 hours using a digital camera. The lesion to non lesion (L/N) ratio was determined using the camera computer. The T/F ratio was calculated: T/F=((L/N)-24)/((L/N)-4). Three groups were investigated. In 15 patients with metastatic bone carcinoma, T/F ratio was 1.46 +- 0.4. In 47 patients with degenerative joint disease the T/F ratio was 1.05 +- 0.06. In 27 patients with treated metastatic bone carcinoma the T/F ratio was 1.12 +- 0.13. The T/F ratio is significantly (p<0.001) different in patients with metastases compared to patients with benign degenerative disease. Chemotherapeutic and hormonal treatment cause significant (p<0.001) reduction in the T/F ratio. The T/F ratio may have a potential in differentiating degenerative from neoplastic diseases and in the evaluation of patients with bone metastases undergoing treatment

Preliminary power supply design for the TF coil system of CIT

International Nuclear Information System (INIS)

Neumeyer, C.; Bronner, G.; Huttar, D.

1989-01-01

Initial operation of the Compact Ignition Tokamak (CIT) is planned with a Toroidal Field (TF) of 8 Tesla and a flat top duration of 5 seconds. Ultimately, operation will be extended beyond 8 Tesla. The power supply to be used for the initial phase of operation has been modeled using the parameters of the thyristor rectifier power supplies which are now in service for the Tokamak Fusion Test Reactor (TFTR). A subset of these existing units, or perhaps new units with similar ratings, are envisioned to be connected to the existing 138kV transmission line serving PPPL so as to take advantage of this power source for CIT. For the extended operation phase the equipment used for the initial phase of TF operation will be augmented with new equipment to permit operation up to 11 Tesla. This paper describes the preliminary design for the 8 Tesla power supply and presents results from simulation studies. In addition, issues concerning transient behavior and fault modes are discussed. 4 refs., 12 figs

Detailed design studies at CEA for JT-60SA TF coils

International Nuclear Information System (INIS)

Decool, P.; Marechal, J.L.; Portafaix, C.; Lacroix, B.; Gros, G.; Verger, J.M.

2011-01-01

Following a first conceptual design activity in which the general design of the JT-60SA TF system was defined and frozen in agreement with all the participants in the project (CEA, ENEA, F4E), a second phase had to be launched to deal with the detailed design. In this paper, we present the work performed at CEA on the TF coil design during this second phase. Part of this work, concerns the determination of conductor hydraulic performances during operation as well as in factory. The thermohydraulic of the conductor was also assessed to confirm the need of helium inlets and a specific design was developed and qualified to be compatible with the available hydraulic performance of the cryoplant. The mechanical behavior is still to be assessed and qualified. Last but not least, the inner electrical joints of the coil have been modified with respect to the original twin-box design developed by CEA for the ITER coils in order to simplify the fabrication process. A dedicated qualification program for their manufacture is ongoing.

AC loss, interstrand resistance and mechanical properties of prototype EU DEMO TF conductors up to 30 000 load cycles

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Yagotintsev, K.; Nijhuis, A.

2018-07-01

Two prototype Nb3Sn cable-in-conduit conductors conductors were designed and manufactured for the toroidal field (TF) magnet system of the envisaged European DEMO fusion reactor. The AC loss, contact resistance and mechanical properties of two sample conductors were tested in the Twente Cryogenic Cable Press under cyclic load up to 30 000 cycles. Though both conductors were designed to operate at 82 kA in a background magnetic field of 13.6 T, they reflect different approaches with respect to the magnet winding pack assembly. The first approach is based on react and wind technology while the second is the more common wind and react technology. Each conductor was tested first for AC loss in virgin condition without handling. The impact of Lorentz load during magnet operation was simulated using the cable press. In the press each conductor specimen was subjected to transverse cyclic load up to 30 000 cycles in liquid helium bath at 4.2 K. Here a summary of results for AC loss, contact resistance, conductor deformation, mechanical heat production and conductor stiffness evolution during cycling of the load is presented. Both conductors showed similar mechanical behaviour but quite different AC loss. In comparison with previously tested ITER TF conductors, both DEMO TF conductors possess very low contact resistance resulting in high coupling loss. At the same time, load cycling has limited impact on properties of DEMO TF conductors in comparison with ITER TF conductors.

Type VI secretion system MIX-effectors carry both antibacterial and anti-eukaryotic activities.

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Ray, Ann; Schwartz, Nika; de Souza Santos, Marcela; Zhang, Junmei; Orth, Kim; Salomon, Dor

2017-11-01

Most type VI secretion systems (T6SSs) described to date are protein delivery apparatuses that mediate bactericidal activities. Several T6SSs were also reported to mediate virulence activities, although only few anti-eukaryotic effectors have been described. Here, we identify three T6SSs in the marine bacterium Vibrio proteolyticus and show that T6SS1 mediates bactericidal activities under warm marine-like conditions. Using comparative proteomics, we find nine potential T6SS1 effectors, five of which belong to the polymorphic MIX-effector class. Remarkably, in addition to six predicted bactericidal effectors, the T6SS1 secretome includes three putative anti-eukaryotic effectors. One of these is a MIX-effector containing a cytotoxic necrotizing factor 1 domain. We demonstrate that T6SS1 can use this MIX-effector to target phagocytic cells, resulting in morphological changes and actin cytoskeleton rearrangements. In conclusion, the V. proteolyticus T6SS1, a system homologous to one found in pathogenic vibrios, uses a suite of polymorphic effectors that target both bacteria and eukaryotic neighbors. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Full scale trials for qualification of the manufacture of the ITER TF coils in Japan

Energy Technology Data Exchange (ETDEWEB)

Matsui, Kunihiro, E-mail: matsui.kunihiro@jaea.go.jp; Hemmi, Tsutomu; Kajitani, Hideki; Yamane, Minoru; Mizutani, Takumi; Nakano, Toshihide; Takano, Katsutoshi; Ando, Shinji; Koizumi, Norikiyo

2016-11-01

Highlights: • High accuracy conductor winding of 0.1% was achieved in TF coil fabrication. • Conductor elongation due to heat treatment satisfied with the expected value of 0.06% ± 0.02%. • Commissioning of a transfer tooling without adding strain to conductor was completed. • Commissioning of a conductor insulation and CP welding was successfully completed. - Abstract: JAEA performed full-scale trials to qualify and optimize manufacturing procedure of TF coil fabrication prior to series production. In the full-scale trials, conductor winding, heat treatment, conductor transfer, conductor insulation and cover plate (CP) welding trials were performed to resolve some technical issues and to demonstrate the fabrication procedure. The followings are major achievement. (1) High accuracy conductor winding of 0.01%, (2) the evaluation of 0.06% conductor elongation due to heat treatment, (3) conductor transfer in a radial plate (RP) groove with addition strain under 0.1%, (4) conductor insulation without breakage of the insulation tape and (5) flatness of 2 mm of the double pancake (DP) by CP welding. Then JAEA started the 1st TF coil fabrication from March 2014, and has already completed ten conductor windings and heat treatment of nine windings.

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants.

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Jwa, Nam-Soo; Hwang, Byung Kook

2017-01-01

Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants.

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants

Directory of Open Access Journals (Sweden)

Nam-Soo Jwa

2017-09-01

Full Text Available Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP-triggered immunity (PTI and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants.

GENIUS and the Genius TF: A New Observatory for WIMP Dark Matter and Neutrinoless Double Beta Decay

OpenAIRE

Klapdor-Kleingrothaus, H. V.; Majorovits, B.

2001-01-01

The GENIUS proposal is described and some of it's physics potential is outlined. Also in the light of the contradictive results from the DAMA and CDMS experiments the Genius TF, a new experimental setup is proposed. The Genius TF could probe the DAMA evidence region using the WIMP nucleus recoil signal and WIMP annual modulation signature simultaneously. Besides that it can prove the long term feasibility of the detector technique to be implemented into the GENIUS setup and will in this sense...

Characterization of the largest effector gene cluster of Ustilago maydis.

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Thomas Brefort

2014-07-01

Full Text Available In the genome of the biotrophic plant pathogen Ustilago maydis, many of the genes coding for secreted protein effectors modulating virulence are arranged in gene clusters. The vast majority of these genes encode novel proteins whose expression is coupled to plant colonization. The largest of these gene clusters, cluster 19A, encodes 24 secreted effectors. Deletion of the entire cluster results in severe attenuation of virulence. Here we present the functional analysis of this genomic region. We show that a 19A deletion mutant behaves like an endophyte, i.e. is still able to colonize plants and complete the infection cycle. However, tumors, the most conspicuous symptoms of maize smut disease, are only rarely formed and fungal biomass in infected tissue is significantly reduced. The generation and analysis of strains carrying sub-deletions identified several genes significantly contributing to tumor formation after seedling infection. Another of the effectors could be linked specifically to anthocyanin induction in the infected tissue. As the individual contributions of these genes to tumor formation were small, we studied the response of maize plants to the whole cluster mutant as well as to several individual mutants by array analysis. This revealed distinct plant responses, demonstrating that the respective effectors have discrete plant targets. We propose that the analysis of plant responses to effector mutant strains that lack a strong virulence phenotype may be a general way to visualize differences in effector function.

Effector candidates in the secretome of Piriformospora indica, a ubiquitous plant-associated fungus

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Maryam eRafiqi

2013-07-01

Full Text Available One of the emerging systems in plant-microbe interaction is the study of proteins, referred to as effectors, secreted by microbes in order to modulate host cells function and structure and to promote microbial growth on plant tissue. Current knowledge on fungal effectors derives mainly from biotrophic and hemibiotrophic plant fungal pathogens that have a limited host range. Here, we focus on effectors of Piriformospora indica, a soil borne endophyte forming intimate associations with roots of a wide range of plant species. Complete genome sequencing provides an opportunity to investigate the role of effectors during the interaction of this mutualistic fungus with plants. We describe in silico analyses to predict effectors of P. indica and we explore effector features considered here to mine a high priority protein list for functional analysis.

BOREAS TF-3 NSA-OBS Tower Flux, Meteorological, and Soil Temperature Data

Science.gov (United States)

Wofsy, Steven; Sutton, Doug; Goulden, Mike; Hall, Forrest G. (Editor); Huemmrich, Karl (Editor)

2000-01-01

The BOReal Ecosystem-Atmosphere Study Tower Flux (BOREAS TF-3) team collected tower flux, surface meteorological, and soil temperature data at the BOREAS Northern Study Area-Old Black Spruce (NSA-OBS) site continuously from the March 1994 through October 1996. The data are available in tabular ASCII files.

CardioTF, a database of deconstructing transcriptional circuits in the heart system.

Science.gov (United States)

Zhen, Yisong

2016-01-01

Information on cardiovascular gene transcription is fragmented and far behind the present requirements of the systems biology field. To create a comprehensive source of data for cardiovascular gene regulation and to facilitate a deeper understanding of genomic data, the CardioTF database was constructed. The purpose of this database is to collate information on cardiovascular transcription factors (TFs), position weight matrices (PWMs), and enhancer sequences discovered using the ChIP-seq method. The Naïve-Bayes algorithm was used to classify literature and identify all PubMed abstracts on cardiovascular development. The natural language learning tool GNAT was then used to identify corresponding gene names embedded within these abstracts. Local Perl scripts were used to integrate and dump data from public databases into the MariaDB management system (MySQL). In-house R scripts were written to analyze and visualize the results. Known cardiovascular TFs from humans and human homologs from fly, Ciona, zebrafish, frog, chicken, and mouse were identified and deposited in the database. PWMs from Jaspar, hPDI, and UniPROBE databases were deposited in the database and can be retrieved using their corresponding TF names. Gene enhancer regions from various sources of ChIP-seq data were deposited into the database and were able to be visualized by graphical output. Besides biocuration, mouse homologs of the 81 core cardiac TFs were selected using a Naïve-Bayes approach and then by intersecting four independent data sources: RNA profiling, expert annotation, PubMed abstracts and phenotype. The CardioTF database can be used as a portal to construct transcriptional network of cardiac development. Database URL: http://www.cardiosignal.org/database/cardiotf.html.

Wash functions downstream of Rho1 GTPase in a subset of Drosophila immune cell developmental migrations

Science.gov (United States)

Verboon, Jeffrey M.; Rahe, Travis K.; Rodriguez-Mesa, Evelyn; Parkhurst, Susan M.

2015-01-01

Drosophila immune cells, the hemocytes, undergo four stereotypical developmental migrations to populate the embryo, where they provide immune reconnoitering, as well as a number of non–immune-related functions necessary for proper embryogenesis. Here, we describe a role for Rho1 in one of these developmental migrations in which posteriorly located hemocytes migrate toward the head. This migration requires the interaction of Rho1 with its downstream effector Wash, a Wiskott–Aldrich syndrome family protein. Both Wash knockdown and a Rho1 transgene harboring a mutation that prevents Wash binding exhibit the same developmental migratory defect as Rho1 knockdown. Wash activates the Arp2/3 complex, whose activity is needed for this migration, whereas members of the WASH regulatory complex (SWIP, Strumpellin, and CCDC53) are not. Our results suggest a WASH complex–independent signaling pathway to regulate the cytoskeleton during a subset of hemocyte developmental migrations. PMID:25739458

Target selection biases from recent experience transfer across effectors.

Science.gov (United States)

Moher, Jeff; Song, Joo-Hyun

2016-02-01

Target selection is often biased by an observer's recent experiences. However, not much is known about whether these selection biases influence behavior across different effectors. For example, does looking at a red object make it easier to subsequently reach towards another red object? In the current study, we asked observers to find the uniquely colored target object on each trial. Randomly intermixed pre-trial cues indicated the mode of action: either an eye movement or a visually guided reach movement to the target. In Experiment 1, we found that priming of popout, reflected in faster responses following repetition of the target color on consecutive trials, occurred regardless of whether the effector was repeated from the previous trial or not. In Experiment 2, we examined whether an inhibitory selection bias away from a feature could transfer across effectors. While priming of popout reflects both enhancement of the repeated target features and suppression of the repeated distractor features, the distractor previewing effect isolates a purely inhibitory component of target selection in which a previewed color is presented in a homogenous display and subsequently inhibited. Much like priming of popout, intertrial suppression biases in the distractor previewing effect transferred across effectors. Together, these results suggest that biases for target selection driven by recent trial history transfer across effectors. This indicates that representations in memory that bias attention towards or away from specific features are largely independent from their associated actions.

Proliferation requirements of cytomegalovirus-specific, effector-type human CD8+ T cells

NARCIS (Netherlands)

van Leeuwen, Ester M.; Gamadia, Laila E.; Baars, Paul A.; Remmerswaal, Ester B.; ten Berge, Ineke J.; van Lier, René A.

2002-01-01

Two prototypic types of virus-specific CD8(+) T cells can be found in latently infected individuals: CD45R0(+)CD27(+)CCR7(-) effector-memory, and CD45RA(+)CD27(-)CCR7(-) effector-type cells. It has recently been implied that CD45RA(+)CD27(-)CCR7(-) T cells are terminally differentiated effector

Identification of Anaplasma marginale type IV secretion system effector proteins.

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Svetlana Lockwood

Full Text Available Anaplasma marginale, an obligate intracellular alphaproteobacterium in the order Rickettsiales, is a tick-borne pathogen and the leading cause of anaplasmosis in cattle worldwide. Complete genome sequencing of A. marginale revealed that it has a type IV secretion system (T4SS. The T4SS is one of seven known types of secretion systems utilized by bacteria, with the type III and IV secretion systems particularly prevalent among pathogenic Gram-negative bacteria. The T4SS is predicted to play an important role in the invasion and pathogenesis of A. marginale by translocating effector proteins across its membrane into eukaryotic target cells. However, T4SS effector proteins have not been identified and tested in the laboratory until now.By combining computational methods with phylogenetic analysis and sequence identity searches, we identified a subset of potential T4SS effectors in A. marginale strain St. Maries and chose six for laboratory testing. Four (AM185, AM470, AM705 [AnkA], and AM1141 of these six proteins were translocated in a T4SS-dependent manner using Legionella pneumophila as a reporter system.The algorithm employed to find T4SS effector proteins in A. marginale identified four such proteins that were verified by laboratory testing. L. pneumophila was shown to work as a model system for A. marginale and thus can be used as a screening tool for A. marginale effector proteins. The first T4SS effector proteins for A. marginale have been identified in this work.

System for exchanging tools and end effectors on a robot

International Nuclear Information System (INIS)

Burry, D.B.; Williams, P.M.

1991-01-01

A system and method for exchanging tools and end effectors on a robot permits exchange during a programmed task. The exchange mechanism is located off the robot, thus reducing the mass of the robot arm and permitting smaller robots to perform designated tasks. A simple spring/collet mechanism mounted on the robot is used which permits the engagement and disengagement of the tool or end effector without the need for a rotational orientation of the tool to the end effector/collet interface. As the tool changing system is not located on the robot arm no umbilical cords are located on robot. 12 figures

The genome sequence and effector complement of the flax rust pathogen Melampsora lini

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Adnane eNemri

2014-03-01

Full Text Available Rust fungi cause serious yield reductions on crops, including wheat, barley, soybean, coffee, and represent real threats to global food security. Of these fungi, the flax rust pathogen Melampsora lini has been developed extensively over the past 80 years as a model to understand the molecular mechanisms that underpin pathogenesis. During infection, M. lini secretes virulence effectors to promote disease. The number of these effectors, their function and their degree of conservation across rust fungal species is unknown. To assess this, we sequenced and assembled de novo the genome of M. lini isolate CH5 into 21,130 scaffolds spanning 189 Mbp (scaffold N50 of 31 kbp. Global analysis of the DNA sequence revealed that repetitive elements, primarily retrotransposons, make up at least 45% of the genome. Using ab initio predictions, transcriptome data and homology searches, we identified 16,271 putative protein-coding genes. An analysis pipeline was then implemented to predict the effector complement of M. lini and compare it to that of the poplar rust, wheat stem rust and wheat stripe rust pathogens to identify conserved and species-specific effector candidates. Previous knowledge of four cloned M. lini avirulence effector proteins and two basidiomycete effectors was used to optimise parameters of the effector prediction pipeline. Markov clustering based on sequence similarity was performed to group effector candidates from all four rust pathogens. Clusters containing at least one member from M. lini were further analysed and prioritized based on features including expression in isolated haustoria and infected leaf tissue and conservation across rust species. Herein, we describe 200 of 940 clusters that ranked highest on our priority list, representing 725 flax rust candidate effectors. Our findings on this important model rust species provide insight into how effectors of rust fungi are conserved across species and how they may act to promote

The genome sequence and effector complement of the flax rust pathogen Melampsora lini.

Science.gov (United States)

Nemri, Adnane; Saunders, Diane G O; Anderson, Claire; Upadhyaya, Narayana M; Win, Joe; Lawrence, Gregory J; Jones, David A; Kamoun, Sophien; Ellis, Jeffrey G; Dodds, Peter N

2014-01-01

Rust fungi cause serious yield reductions on crops, including wheat, barley, soybean, coffee, and represent real threats to global food security. Of these fungi, the flax rust pathogen Melampsora lini has been developed most extensively over the past 80 years as a model to understand the molecular mechanisms that underpin pathogenesis. During infection, M. lini secretes virulence effectors to promote disease. The number of these effectors, their function and their degree of conservation across rust fungal species is unknown. To assess this, we sequenced and assembled de novo the genome of M. lini isolate CH5 into 21,130 scaffolds spanning 189 Mbp (scaffold N50 of 31 kbp). Global analysis of the DNA sequence revealed that repetitive elements, primarily retrotransposons, make up at least 45% of the genome. Using ab initio predictions, transcriptome data and homology searches, we identified 16,271 putative protein-coding genes. An analysis pipeline was then implemented to predict the effector complement of M. lini and compare it to that of the poplar rust, wheat stem rust and wheat stripe rust pathogens to identify conserved and species-specific effector candidates. Previous knowledge of four cloned M. lini avirulence effector proteins and two basidiomycete effectors was used to optimize parameters of the effector prediction pipeline. Markov clustering based on sequence similarity was performed to group effector candidates from all four rust pathogens. Clusters containing at least one member from M. lini were further analyzed and prioritized based on features including expression in isolated haustoria and infected leaf tissue and conservation across rust species. Herein, we describe 200 of 940 clusters that ranked highest on our priority list, representing 725 flax rust candidate effectors. Our findings on this important model rust species provide insight into how effectors of rust fungi are conserved across species and how they may act to promote infection on their

Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model

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Kidwai, Afshan S.; Mushamiri, Ivy T.; Niemann, George; Brown, Roslyn N.; Adkins, Joshua N.; Heffron, Fred

2013-08-12

Salmonella enterica serovar Typhimurium causes typhoid-like disease in mice and is a model of typhoid fever in humans. One of the hallmarks of typhoid is persistence, the ability of the bacteria to survive in the host weeks after infection. Virulence factors called effectors facilitate this process by direct transfer to the cytoplasm of infected cells thereby subverting cellular processes. Secretion of effectors to the cell cytoplasm takes place through multiple routes, including two separate type III secretion (T3SS) apparati as well as outer membrane vesicles. The two T3SS are encoded on separate pathogenicity islands, SPI-1 and -2, with SPI-1 more strongly associated with the intestinal phase of infection, and SPI-2 with the systemic phase. Both T3SS are required for persistence, but the effectors required have not been systematically evaluated. In this study, mutations in 48 described effectors were tested for persistence. We replaced each effector with a specific DNA barcode sequence by allelic exchange and co-infected with a wild-type reference to calculate the ratio of wild-type parent to mutant at different times after infection. The competitive index (CI) was determined by quantitative PCR in which primers that correspond to the barcode were used for amplification. Mutations in all but seven effectors reduced persistence demonstrating that most effectors were required. One exception was CigR, a recently discovered effector that is widely conserved throughout enteric bacteria. Deletion of cigR increased lethality, suggesting that it may be an anti-virulence factor. The fact that almost all Salmonella effectors are required for persistence argues against redundant functions. This is different from effector repertoires in other intracellular pathogens such as Legionella.

Diacylglycerol kinases in T cell tolerance and effector function

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Shelley S Chen

2016-11-01

Full Text Available Diacylglycerol kinases (DGKs are a family of enzymes that regulate the relative levels of diacylglycerol (DAG and phosphatidic acid (PA in cells by phosphorylating DAG to produce PA. Both DAG and PA are important second messengers cascading T cell receptor (TCR signal by recruiting multiple effector molecules such as RasGRP1, PKC, and mTOR. Studies have revealed important physiological functions of DGKs in the regulation of receptor signaling and the development and activation of immune cells. In this review, we will focus on recent progresses in our understanding of two DGK isoforms,  and , in CD8 T effector and memory cell differentiation, regulatory T cell development and function, and invariant NKT cell development and effector lineage differentiation.

Epigenetic landscapes reveal transcription factors regulating CD8+ T cell differentiation

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Yu, Bingfei; Zhang, Kai; Milner, J. Justin; Toma, Clara; Chen, Runqiang; Scott-Browne, James P.; Pereira, Renata M.; Crotty, Shane; Chang, John T.; Pipkin, Matthew E.; Wang, Wei; Goldrath, Ananda W.

2017-01-01

Dynamic changes in the expression of transcription factors (TFs) can influence specification of distinct CD8+ T cell fates, but the observation of equivalent expression of TF among differentially-fated precursor cells suggests additional underlying mechanisms. Here, we profiled genome-wide histone modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8+ T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that TF expression and binding contributed to establishment of subset-specific enhancers during differentiation. We developed a new bioinformatics method using the PageRank algorithm to reveal novel TFs influencing the generation of effector and memory populations. The TFs YY1 and Nr3c1, both constitutively expressed during CD8+ T cell differentiation, regulated the formation of terminal-effector and memory-precursor cell-fates, respectively. Our data define the epigenetic landscape of differentiation intermediates, facilitating identification of TFs with previously unappreciated roles in CD8+ T cell differentiation. PMID:28288100

A new meshless approach to map electromagnetic loads for FEM analysis on DEMO TF coil system

International Nuclear Information System (INIS)

Biancolini, Marco Evangelos; Brutti, Carlo; Giorgetti, Francesco; Muzzi, Luigi; Turtù, Simonetta; Anemona, Alessandro

2015-01-01

Graphical abstract: - Highlights: • Generation and mapping of magnetic load on DEMO using radial basis function. • Good agreement between RBF interpolation and EM TOSCA computations. • Resultant forces are stable with respect to the target mesh used. • Stress results are robust and accurate even if a coarse cloud is used for RBF interpolation. - Abstract: Demonstration fusion reactors (DEMO) are being envisaged to be able to produce commercial electrical power. The design of the DEMO magnets and of the constituting conductors is a crucial issue in the overall engineering design of such a large fusion machine. In the frame of the EU roadmap of the so-called fast track approach, mechanical studies of preliminary DEMO toroidal field (TF) coil system conceptual designs are being enforced. The magnetic field load acting on the DEMO TF coil conductor has to be evaluated as input in the FEM model mesh, in order to evaluate the stresses on the mechanical structure. To gain flexibility, a novel approach based on the meshless method of radial basis functions (RBF) has been implemented. The present paper describes this original and flexible approach for the generation and mapping of magnetic load on DEMO TF coil system.

The Shigella flexneri OspB effector: an early immunomodulator.

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Ambrosi, Cecilia; Pompili, Monica; Scribano, Daniela; Limongi, Dolores; Petrucca, Andrea; Cannavacciuolo, Sonia; Schippa, Serena; Zagaglia, Carlo; Grossi, Milena; Nicoletti, Mauro

2015-01-01

Through the action of the type three secretion system (T3SS) Shigella flexneri delivers several effectors into host cells to promote cellular invasion, multiplication and to exploit host-cell signaling pathways to modulate the host innate immune response. Although much progress has been made in the understanding of many type III effectors, the molecular and cellular mechanism of the OspB effector is still poorly characterized. In this study we present new evidence that better elucidates the role of OspB as pro-inflammatory factor at very early stages of infection. Indeed, we demonstrate that, during the first hour of infection, OspB is required for full activation of ERK1/2 and p38 MAPKs and the cytosolic phospholipase A(2) (cPLA(2)). Activation of cPLA(2) ultimately leads to the production and secretion of PMN chemoattractant metabolite(s) uncoupled with release of IL-8. Moreover, we also present evidence that OspB is required for the development of the full and promptly inflammatory reaction characteristic of S. flexneri wild-type infection in vivo. Based on OspB and OspF similarity (both effectors share similar transcription regulation, temporal secretion into host cells and nuclear localization) we hypothesized that OspB and OspF effectors may form a pair aimed at modulating the host cell response throughout the infection process, with opposite effects. A model is presented to illustrate how OspB activity would promote S. flexneri invasion and bacterial dissemination at early critical phases of infection. Copyright © 2014 Elsevier GmbH. All rights reserved.

Stability of [MeBu3N][Tf2N] under gamma irradiation

International Nuclear Information System (INIS)

Bosse, Emilie; Berthon, Laurence; Zorz, Nicole; Monget, Julie; Berthon, Claude; Bisel, Isabelle; Legand, Solene; Moisy, Philippe

2008-01-01

The stability of the ionic liquid [MeBu 3 N][Tf 2 N], dry or after contact with water (where [MeBu 3 N] + is the methyl-tributyl-ammonium cation and [Tf 2 N] - is the bistriflimide anion), was studied under 137 Cs gamma irradiation in argon and in air. In a quantitative study with an absorbed dose of 2 MGy this ionic liquid was highly stable regardless of the radiolysis conditions. The radiolytic disappearance yields determined by ESI-MS were -0.38 and -0.25 μmol*J -1 for the cation and anion, respectively. ESI-MS, NMR, and liquid chromatography coupled with ESI-MS identified a large number of degradation products in very small quantities for the same dose. The cation radicals were formed by the loss of a Bu . group, the Me . group, or two H . atoms to form a double bond with the butyl chain. Radiolysis of the anion produced mainly F . and CF 3 . radicals. The anion radicals recombined with the cation to form a wide range of secondary degradation products regardless of the radiolysis conditions. (authors)

Yersinia type III effectors perturb host innate immune responses

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Pha, Khavong; Navarro, Lorena

2016-01-01

The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type III secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp. (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gram-negative bacteria that share in common a 70 kb virulence plasmid which encodes the T3SS. Translocation of the Yersinia effector proteins (YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia

Modular Study of the Type III Effector Repertoire in Pseudomonas syringae pv. tomato DC3000 Reveals a Matrix of Effector Interplay in Pathogenesis

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Hai-Lei Wei

2018-05-01

Full Text Available Summary: The bacterial pathogen Pseudomonas syringae pv. tomato DC3000 suppresses the two-tiered innate immune system of Nicotiana benthamiana and other plants by injecting a complex repertoire of type III secretion effector (T3E proteins. Effectorless polymutant DC3000D36E was used with a modularized system for native delivery of the 29 DC3000 T3Es singly and in pairs. Assays of the performance of this T3E library in N. benthamiana leaves revealed a matrix of T3E interplay, with six T3Es eliciting death and eight others variously suppressing the death activity of the six. The T3E library was also interrogated for effects on DC3000D36E elicitation of a reactive oxygen species burst, for growth in planta, and for T3Es that reversed these effects. Pseudomonas fluorescens and Agrobacterium tumefaciens heterologous delivery systems yielded notably different sets of death-T3Es. The DC3000D36E T3E library system highlights the importance of 13 T3Es and their interplay in interactions with N. benthamiana. : Wei et al. used a Pseudomonas syringae strain lacking all known type III effectors with a modularized library expressing the 29 active effectors in the strain’s native repertoire, individually and in pairs, to comprehensively determine effector actions and interplay in inducing and suppressing responses associated with plant pathogenesis and immunity. Keywords: effector-triggered-immunity, pattern-triggered-immunity, Hop proteins, plant immunity, mini-Tn7

Design considerations for the TF center conductor post for the Ignition Spherical Torus (IST)

International Nuclear Information System (INIS)

Dalton, G.R.; Haines, J.R.

1986-01-01

A trade-off study has been carried out to compare the differential costs of using high-strength alloy copper versus oxygen-free, high-conductivity (OFHC) copper for the center legs of the toroidal field (TF) coils of an Ignition Spherical Torus (IST). The electrical heating, temperatures, stresses, cooling requirements, material costs, pump costs, and power to drive the TF coils and pumps are all assessed for both materials for a range of compact tokamak reactors. The alloy copper material is found to result in a more compact reactor and to allow use of current densities of up to 170 MA/m 2 versus 40 MA/m 2 for the OFHC copper. The OFHC conductor system with high current density is $24 million less expensive than more conventional copper systems with 30 MA/m 2 . The alloy copper system costs $32 million less than conventional systems. Therefore, the alloy system offers a net savings of $8 million compared to the 50% cold-worked OFHC copper system. Although the savings are a significant fraction of the center conductor post cost, they are relatively insignificant in terms of the total device cost. It is concluded that the use of alloy copper contributes very little to the economic or technical viability of the compact IST. It is recommended that a similar systematic approach be applied to evaluating coil material and current density trade-offs for other compact copper-TF-coil tokamak designs. 9 refs., 13 figs., 13 tabs

The Alpha-Melanocyte Stimulating Hormone Induces Conversion of Effector T Cells into Treg Cells

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Andrew W. Taylor

2011-01-01

Full Text Available The neuropeptide alpha-melanocyte stimulating hormone (α-MSH has an important role in modulating immunity and homeostasis. The production of IFN-γ by effector T cells is suppressed by α-MSH, while TGF-β production is promoted in the same cells. Such α-MSH-treated T cells have immune regulatory activity and suppress hypersensitivity, autoimmune diseases, and graft rejection. Previous characterizations of the α-MSH-induced Treg cells showed that the cells are CD4+ T cells expressing the same levels of CD25 as effector T cells. Therefore, we further analyzed the α-MSH-induced Treg cells for expression of effector and regulatory T-cell markers. Also, we examined the potential for α-MSH-induced Treg cells to be from the effector T-cell population. We found that the α-MSH-induced Treg cells are CD25+  CD4+ T cells that share similar surface markers as effector T cells, except that they express on their surface LAP. Also, the α-MSH treatment augments FoxP3 message in the effector T cells, and α-MSH induction of regulatory activity was limited to the effector CD25+ T-cell population. Therefore, α-MSH converts effector T cells into Treg cells, which suppress immunity targeting specific antigens and tissues.

In Planta Functional Analysis and Subcellular Localization of the Oomycete Pathogen Plasmopara viticola Candidate RXLR Effector Repertoire

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Yunxiao Liu

2018-04-01

Full Text Available Downy mildew is one of the most destructive diseases of grapevine, causing tremendous economic loss in the grape and wine industry. The disease agent Plasmopara viticola is an obligate biotrophic oomycete, from which over 100 candidate RXLR effectors have been identified. In this study, 83 candidate RXLR effector genes (PvRXLRs were cloned from the P. viticola isolate “JL-7-2” genome. The results of the yeast signal sequence trap assay indicated that most of the candidate effectors are secretory proteins. The biological activities and subcellular localizations of all the 83 effectors were analyzed via a heterologous Agrobacterium-mediated Nicotiana benthamiana expression system. Results showed that 52 effectors could completely suppress cell death triggered by elicitin, 10 effectors could partially suppress cell death, 11 effectors were unable to suppress cell death, and 10 effectors themselves triggered cell death. Live-cell imaging showed that the majority of the effectors (76 of 83 could be observed with informative fluorescence signals in plant cells, among which 34 effectors were found to be targeted to both the nucleus and cytosol, 29 effectors were specifically localized in the nucleus, and 9 effectors were targeted to plant membrane system. Interestingly, three effectors PvRXLR61, 86 and 161 were targeted to chloroplasts, and one effector PvRXLR54 was dually targeted to chloroplasts and mitochondria. However, western blot analysis suggested that only PvRXLR86 carried a cleavable N-terminal transit peptide and underwent processing in planta. Many effectors have previously been predicted to target organelles, however, to the best of our knowledge, this is the first study to provide experimental evidence of oomycete effectors targeted to chloroplasts and mitochondria.

TAL effectors: highly adaptable phytobacterial virulence factors and readily engineered DNA targeting proteins

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Doyle, Erin L.; Stoddard, Barry L.; Voytas, Daniel F.; Bogdanove, Adam J.

2013-01-01

Transcription activator-like (TAL) effectors are transcription factors injected into plant cells by pathogenic bacteria in the genus Xanthomonas. They function as virulence factors by activating host genes important for disease, or as avirulence factors by turning on genes that provide resistance. DNA binding specificity is encoded by polymorphic repeats in each protein that correspond one-to-one with different nucleotides. This code has facilitated target identification and opened new avenues for engineering disease resistance. It has also enabled TAL effector customization for targeted gene control, genome editing, and other applications. This article reviews the structural basis for TAL effector-DNA specificity, the impact of the TAL effector-DNA code on plant pathology and engineered resistance, and recent accomplishments and future challenges in TAL effector-based DNA targeting. PMID:23707478

Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling

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Ashton, Gabrielle H.; Morton, Jennifer P.; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.

2012-01-01

SUMMARY The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein within the intestinal epithelium. Following Apc loss, FAK expression increased in a c-Myc-dependent manner. Codeletion of Apc and Fak strongly reduced proliferation normally induced following Apc loss, and this was associated with reduced levels of phospho-Akt and suppression of intestinal tumorigenesis in Apc heterozygous mice. Thus, FAK is required downstream of Wnt Signaling, for Akt/mTOR activation, intestinal regeneration, and tumorigenesis. Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer. PMID:20708588

SPRYSEC effectors: a versatile protein-binding platform to disrupt plant innate immunity

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Amalia Diaz-Granados

2016-10-01

Full Text Available Persistent infections by sedentary plant-parasitic nematodes are a major threat to important food crops all over the world. These round worms manipulate host plant cell morphology and physiology to establish sophisticated feeding structures. Key modifications to plant cells during their transition into feeding structures are largely attributed to the activity of effectors secreted by the nematodes. The SPRYSEC effectors were initially identified in the potato cyst nematodes Globodera rostochiensis and G. pallida, and are characterized by a single SPRY domain, a non-catalytic domain present in modular proteins with different functions. The SPRY domain is wide-spread among eukaryotes and thought to be involved in mediating protein-protein interactions. Thus far, the SPRY domain is only reported as a functional domain in effectors of plant-parasitic nematodes, but not of other plant pathogens. SPRYSEC effectors have been implicated in both suppression and activation of plant immunity, but other possible roles in nematode virulence remain undefined. Here, we review the latest reports on the structure, function, and sequence diversity of SPRYSEC effectors, which provide support for a model featuring these effectors as a versatile protein-binding platform for the nematodes to target a wide range of host proteins during parasitism.

Advances in therapeutic Fc engineering - modulation of IgG associated effector functions and serum half-life

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Abhishek Saxena

2016-12-01

Full Text Available Today monoclonal immunoglobulin gamma (IgG antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs are achieved through both its antigen binding fragment (Fab and crystallizable fragment (Fc. Fab can specifically recognize tumor associated antigen (TAA and thus modulate TAA-linked downstream signaling pathways that may lead to inhibition of tumor growth, induction of tumor apoptosis and differentiation. The Fc region can further improve mAbs’ efficacy by mediating effector functions such as antibody-dependent cellular cytotoxicity (ADCC, complement-dependent cytotoxicity (CDC and antibody dependent cell-mediated phagocytosis (ADCP. Moreover, Fc is the region interacting with the neonatal Fc receptor (FcRn in a pH-dependent manner that can slow down IgG’s degradation and extend its serum half-life. Loss of the antibody Fc region dramatically shortens its serum half-life and weakens its anti-cancer effects. Given the essential roles that the Fc region plays in the modulation of the efficacy of mAb in cancer treatment, Fc engineering has been extensively studied in the past years. This review focuses on the recent advances in therapeutic Fc engineering that modulates its related effector functions and serum half-life. We also discuss the progress made in aglycosylated mAb development that may substantially reduce cost of manufacture but maintain similar efficacies as conventional glycosylated mAb. Finally, we highlight several Fc engineering based mAbs under clinical trials.

Development and testing of the cooling coil cleaning end effector

International Nuclear Information System (INIS)

Johnson, K.I.; Mullen, O.D.; Powell, M.R.; Daly, D.S.; Engel, D.W.

1997-01-01

The Retrieval Process Development and Enhancement (KPD ampersand E) program has developed and tested an end effector to support the waste retrieval mission at the Idaho National Engineering and Environmental Laboratory (INEEL). The end effector was developed specifically to remove a sticky waste material from the cooling coils in the High Level Liquid Waste (HLLW) tank, and to vacuum up a sediment layer that has settled beneath the cooling coils. An extensive testing program was conducted in the hydraulic test bed (HTB) at the Pacific Northwest National Laboratory (PNNL) to evaluate the performance of the end effector under simulated in-tank conditions. A mock up of the cooling coils was installed in the test bed tank, and simulated waste materials were included to represent the sticky waste on the tubes and the particulate waste settled beneath them. The testing program focused on assessing long-duration mining strategies for cleaning the cooling coils and removing the particulate waste forms. The report describes the results of the end effector testing program at PNNL. Section 2 describes the physical characteristics of the HLLW tanks, including the layout of the cooling coils, and it also describes what is known of the waste forms in the tanks. Section 3 describes the cleaning and retrieval strategy that was used in developing the end effector design. Section 4 describes the cooling coil mockup in the hydraulic test bed. Section 5 discusses the rationale used in selecting the simulants for the tarry waste and particulate waste forms. Section 6 describes the tests that were performed to evaluate cleaning of the cooling coils and retrieval of the particulate simulant. Section 7 summarizes the cleaning and retrieval tests, assesses the relative importance of cleaning the cooling coils and retrieving the particulate waste, and suggests modifications that would simplify the end effector design

Identification and functional analysis of secreted effectors from phytoparasitic nematodes.

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Rehman, Sajid; Gupta, Vijai K; Goyal, Aakash K

2016-03-21

Plant parasitic nematodes develop an intimate and long-term feeding relationship with their host plants. They induce a multi-nucleate feeding site close to the vascular bundle in the roots of their host plant and remain sessile for the rest of their life. Nematode secretions, produced in the oesophageal glands and secreted through a hollow stylet into the host plant cytoplasm, are believed to play key role in pathogenesis. To combat these persistent pathogens, the identity and functional analysis of secreted effectors can serve as a key to devise durable control measures. In this review, we will recapitulate the knowledge over the identification and functional characterization of secreted nematode effector repertoire from phytoparasitic nematodes. Despite considerable efforts, the identity of genes encoding nematode secreted proteins has long been severely hampered because of their microscopic size, long generation time and obligate biotrophic nature. The methodologies such as bioinformatics, protein structure modeling, in situ hybridization microscopy, and protein-protein interaction have been used to identify and to attribute functions to the effectors. In addition, RNA interference (RNAi) has been instrumental to decipher the role of the genes encoding secreted effectors necessary for parasitism and genes attributed to normal development. Recent comparative and functional genomic approaches have accelerated the identification of effectors from phytoparasitic nematodes and offers opportunities to control these pathogens. Plant parasitic nematodes pose a serious threat to global food security of various economically important crops. There is a wealth of genomic and transcriptomic information available on plant parasitic nematodes and comparative genomics has identified many effectors. Bioengineering crops with dsRNA of phytonematode genes can disrupt the life cycle of parasitic nematodes and therefore holds great promise to develop resistant crops against plant

Political and economic conjuncture in Brazil (1950-1964: a fertile land for the 1964 coup d'État

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FABIANO FARIAS DE SOUZA

2013-01-01

Full Text Available The years preceding the 1964 coup d’état in Brazil were marked by turbulent political moments that contributed to the accomplishment of joints and conspiracies that were plotting the overthrow of President João Goulart, seen as a solution to the end of the economic, political and social crises taking place successively in the country. In this period, society was divided between the proposals of the left and right of the political debate in effect at that time. Thus, we analyze the circumstances that forged an enabling environment for identified civil and military that communed common interest in replacing the ruling power by taking control of the Brazilian State.

A Novel Demountable TF Joint Design for Low Aspect Ratio Spherical Torus Tokamaks

International Nuclear Information System (INIS)

Woolley, R.D.

2009-01-01

A novel shaped design for the radial conductors and demountable electrical joints connecting inner and outer legs of copper TF system conductors in low aspect ratio tokamaks is described and analysis results are presented. Specially shaped designs can optimize profiles of electrical current density, magnetic force, heating, and mechanical stress

A Novel Demountable TF Joint Design for Low Aspect Ratio Spherical Torus Tokamaks

International Nuclear Information System (INIS)

Woolley, Robert D.

2009-01-01

A novel shaped design for the radial conductors and demountable electrical joints connecting inner and outer legs of copper TF system conductors in low aspect ratio tokamaks is described and analysis results are presented. Specially shaped designs can optimize profiles of electrical current density, magnetic force, heating, and mechanical stress.

Qualification of the US Made Conductors for ITER TF Magnet System

International Nuclear Information System (INIS)

Martovetsky, Nicolai N.; Hatfield, Daniel R.; Miller, John R.; Bruzzone, P.; Stepanov, B.; Seber, B.

2010-01-01

The US Domestic Agency (USDA) is one of the six suppliers of the Toroidal Field (TF) conductor for the International Thermonuclear Experimental Reactor (ITER). In order to qualify conductors according to ITER requirements we prepared several lengths of the CICC and short samples for testing in the SULTAN facility in CRPP, Switzerland. We also fully characterized the strands that were used in these SULTAN samples. Fabrication experience and test results are presented and discussed.

Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3

Science.gov (United States)

Zhao, Li-Hua; Zhou, X Edward; Yi, Wei; Wu, Zhongshan; Liu, Yue; Kang, Yanyong; Hou, Li; de Waal, Parker W; Li, Suling; Jiang, Yi; Scaffidi, Adrian; Flematti, Gavin R; Smith, Steven M; Lam, Vinh Q; Griffin, Patrick R; Wang, Yonghong; Li, Jiayang; Melcher, Karsten; Xu, H Eric

2015-01-01

Strigolactones (SLs) are endogenous hormones and exuded signaling molecules in plant responses to low levels of mineral nutrients. Key mediators of the SL signaling pathway in rice include the α/β-fold hydrolase DWARF 14 (D14) and the F-box component DWARF 3 (D3) of the ubiquitin ligase SCFD3 that mediate ligand-dependent degradation of downstream signaling repressors. One perplexing feature is that D14 not only functions as the SL receptor but is also an active enzyme that slowly hydrolyzes diverse natural and synthetic SLs including GR24, preventing the crystallization of a binary complex of D14 with an intact SL as well as the ternary D14/SL/D3 complex. Here we overcome these barriers to derive a structural model of D14 bound to intact GR24 and identify the interface that is required for GR24-mediated D14-D3 interaction. The mode of GR24-mediated signaling, including ligand recognition, hydrolysis by D14, and ligand-mediated D14-D3 interaction, is conserved in structurally diverse SLs. More importantly, D14 is destabilized upon the binding of ligands and D3, thus revealing an unusual mechanism of SL recognition and signaling, in which the hormone, the receptor, and the downstream effectors are systematically destabilized during the signal transduction process. PMID:26470846

In-Session Caregiver Behavior Predicts Symptom Change in Youth Receiving Trauma-Focused Cognitive Behavioral Therapy (TF-CBT)

Science.gov (United States)

Yasinski, Carly; Hayes, Adele; Ready, C. Beth; Cummings, Jorden A.; Berman, Ilana S.; McCauley, Thomas; Webb, Charles; Deblinger, Esther

2016-01-01

Objective Involving caregivers in trauma-focused treatments for youth has been shown to result in better outcomes, but it is not clear which in-session caregiver behaviors enhance or inhibit this effect. The current study examined the associations between caregiver behaviors during Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) and youth cognitive processes and symptoms. Method Participants were a racially diverse sample of Medicaid-eligible youth (ages 7–17) and their non-offending caregivers (N= 71 pairs) who received TF-CBT through an effectiveness study in a community setting. Caregiver and youth processes were coded from audio-recorded sessions, and outcomes were measured using the Child Behavior Checklist (CBCL) and UCLA PTSD Reaction Index for DSM-IV (UPID) at 3, 6, 9, and 12 months post-intake. Results Piecewise linear growth curve modeling revealed that during the trauma narrative phase of TF-CBT, caregivers’ cognitive-emotional processing of their own and their child's trauma-related reactions predicted decreases in youth internalizing and externalizing symptoms over treatment. Caregiver support predicted lower internalizing symptoms over follow-up. In contrast, caregiver avoidance and blame of the child predicted worsening of youth internalizing and externalizing symptoms over follow-up. Caregiver avoidance early in treatment also predicted worsening of externalizing symptoms over follow-up. During the narrative phase, caregiver blame and avoidance were correlated with more child overgeneralization of trauma beliefs, and blame was also associated with less child accommodation of balanced beliefs. Conclusions The association between in-session caregiver behaviors and youth symptomatology during and after TF-CBT highlights the importance of assessing and targeting these behaviors to improve clinical outcomes. PMID:27618641

Structure and evolution of barley powdery mildew effector candidates

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Pedersen Carsten

2012-12-01

Full Text Available Abstract Background Protein effectors of pathogenicity are instrumental in modulating host immunity and disease resistance. The powdery mildew pathogen of grasses Blumeria graminis causes one of the most important diseases of cereal crops. B. graminis is an obligate biotrophic pathogen and as such has an absolute requirement to suppress or avoid host immunity if it is to survive and cause disease. Results Here we characterise a superfamily predicted to be the full complement of Candidates for Secreted Effector Proteins (CSEPs in the fungal barley powdery mildew parasite B. graminis f.sp. hordei. The 491 genes encoding these proteins constitute over 7% of this pathogen’s annotated genes and most were grouped into 72 families of up to 59 members. They were predominantly expressed in the intracellular feeding structures called haustoria, and proteins specifically associated with the haustoria were identified by large-scale mass spectrometry-based proteomics. There are two major types of effector families: one comprises shorter proteins (100–150 amino acids, with a high relative expression level in the haustoria and evidence of extensive diversifying selection between paralogs; the second type consists of longer proteins (300–400 amino acids, with lower levels of differential expression and evidence of purifying selection between paralogs. An analysis of the predicted protein structures underscores their overall similarity to known fungal effectors, but also highlights unexpected structural affinities to ribonucleases throughout the entire effector super-family. Candidate effector genes belonging to the same family are loosely clustered in the genome and are associated with repetitive DNA derived from retro-transposons. Conclusions We employed the full complement of genomic, transcriptomic and proteomic analyses as well as structural prediction methods to identify and characterize the members of the CSEPs superfamily in B. graminis f

T3SEdb: data warehousing of virulence effectors secreted by the bacterial Type III Secretion System.

Science.gov (United States)

Tay, Daniel Ming Ming; Govindarajan, Kunde Ramamoorthy; Khan, Asif M; Ong, Terenze Yao Rui; Samad, Hanif M; Soh, Wei Wei; Tong, Minyan; Zhang, Fan; Tan, Tin Wee

2010-10-15

Effectors of Type III Secretion System (T3SS) play a pivotal role in establishing and maintaining pathogenicity in the host and therefore the identification of these effectors is important in understanding virulence. However, the effectors display high level of sequence diversity, therefore making the identification a difficult process. There is a need to collate and annotate existing effector sequences in public databases to enable systematic analyses of these sequences for development of models for screening and selection of putative novel effectors from bacterial genomes that can be validated by a smaller number of key experiments. Herein, we present T3SEdb http://effectors.bic.nus.edu.sg/T3SEdb, a specialized database of annotated T3SS effector (T3SE) sequences containing 1089 records from 46 bacterial species compiled from the literature and public protein databases. Procedures have been defined for i) comprehensive annotation of experimental status of effectors, ii) submission and curation review of records by users of the database, and iii) the regular update of T3SEdb existing and new records. Keyword fielded and sequence searches (BLAST, regular expression) are supported for both experimentally verified and hypothetical T3SEs. More than 171 clusters of T3SEs were detected based on sequence identity comparisons (intra-cluster difference up to ~60%). Owing to this high level of sequence diversity of T3SEs, the T3SEdb provides a large number of experimentally known effector sequences with wide species representation for creation of effector predictors. We created a reliable effector prediction tool, integrated into the database, to demonstrate the application of the database for such endeavours. T3SEdb is the first specialised database reported for T3SS effectors, enriched with manual annotations that facilitated systematic construction of a reliable prediction model for identification of novel effectors. The T3SEdb represents a platform for inclusion of

T3SEdb: data warehousing of virulence effectors secreted by the bacterial Type III Secretion System

Directory of Open Access Journals (Sweden)

Tong Minyan

2010-10-01

Full Text Available Abstract Background Effectors of Type III Secretion System (T3SS play a pivotal role in establishing and maintaining pathogenicity in the host and therefore the identification of these effectors is important in understanding virulence. However, the effectors display high level of sequence diversity, therefore making the identification a difficult process. There is a need to collate and annotate existing effector sequences in public databases to enable systematic analyses of these sequences for development of models for screening and selection of putative novel effectors from bacterial genomes that can be validated by a smaller number of key experiments. Results Herein, we present T3SEdb http://effectors.bic.nus.edu.sg/T3SEdb, a specialized database of annotated T3SS effector (T3SE sequences containing 1089 records from 46 bacterial species compiled from the literature and public protein databases. Procedures have been defined for i comprehensive annotation of experimental status of effectors, ii submission and curation review of records by users of the database, and iii the regular update of T3SEdb existing and new records. Keyword fielded and sequence searches (BLAST, regular expression are supported for both experimentally verified and hypothetical T3SEs. More than 171 clusters of T3SEs were detected based on sequence identity comparisons (intra-cluster difference up to ~60%. Owing to this high level of sequence diversity of T3SEs, the T3SEdb provides a large number of experimentally known effector sequences with wide species representation for creation of effector predictors. We created a reliable effector prediction tool, integrated into the database, to demonstrate the application of the database for such endeavours. Conclusions T3SEdb is the first specialised database reported for T3SS effectors, enriched with manual annotations that facilitated systematic construction of a reliable prediction model for identification of novel effectors

Stability of [MeBu3N][Tf2N] under gamma irradiation

International Nuclear Information System (INIS)

Bosse, E.; Berthon, L.; Zorz, N.; Monget, J.; Berthon, C.; Bisel, I.; Legand, S.; Moisy, P.

2008-01-01

The stability of the ionic liquid [MeBu 3 N][Tf 2 N], dry or after contact with water (where [MeBu 3 N] + is the methyl-tributyl-ammonium cation and [Tf 2 N] - is the bistriflimide anion), was studied under 137 Cs gamma irradiation in argon and in air. In a quantitative study with an absorbed dose of 2 MGy this ionic liquid was highly stable regardless of the radiolysis conditions. The radiolytic disappearance yields determined by ESI-MS were -0.38 and -0.25 μmolJ -1 for the cation and anion, respectively. ESI-MS, NMR, and liquid chromatography coupled with ESI-MS identified a large number of degradation products in very small quantities for the same dose. The cation radicals were formed by the loss of a Bu-radical group, the Me-radical group, or two H-radical atoms to form a double bond with the butyl chain. Radiolysis of the anion produced mainly F-radical and CF 3 -radicals. The anion radicals recombined with the cation to form a wide range of secondary degradation products regardless of the radiolysis conditions. (authors)

Hitting the Sweet Spot: Glycans as Targets of Fungal Defense Effector Proteins

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Markus Künzler

2015-05-01

Full Text Available Organisms which rely solely on innate defense systems must combat a large number of antagonists with a comparatively low number of defense effector molecules. As one solution of this problem, these organisms have evolved effector molecules targeting epitopes that are conserved between different antagonists of a specific taxon or, if possible, even of different taxa. In order to restrict the activity of the defense effector molecules to physiologically relevant taxa, these target epitopes should, on the other hand, be taxon-specific and easily accessible. Glycans fulfill all these requirements and are therefore a preferred target of defense effector molecules, in particular defense proteins. Here, we review this defense strategy using the example of the defense system of multicellular (filamentous fungi against microbial competitors and animal predators.

BOREAS TF-8 NSA-OJP and SSA-OBS Ceilometer Data

Science.gov (United States)

Moore, Kathleen E.; Hall, Forrest G. (Editor); Huemmrich, Karl (Editor); Fitzjarrald, David R.

2000-01-01

The BOREAS TF-8 team used ceilometers to collect data on the fraction of the sky covered with clouds and the cloud height. Included with these data is the surface-based lifting condensation level, derived from temperature and humidity values acquired at the flux tower at the NSA-OJP site. Ceilo-meter data were collected at the NSA-OJP site in 1994 and at the NSA-OJP and SSA-OBS sites in 1996. The data are available in tabular ASCII files. The data files are available on a CD-ROM (see document number 20010000884).

Type IV Secretion System of Brucella spp. and its Effectors

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Yuehua eKe

2015-10-01

Full Text Available Brucella spp. cause brucellosis in domestic and wild animals. They are intracellular bacterial pathogens and used as model organisms to study intracellular bacterial infections. Brucella VirB T4SS is a key virulence factor that plays important roles in mediating intracellular survival and manipulating host immune response to infection. In this review, we will discuss roles of Brucella VirB T4SS and in more detail of all 15 identified effectors, which may be crucial for Brucella pathogenesis. VirB T4SS regulates the inflammation response and manipulates vesicle trafficking inside host cells, suggesting that it plays crucial roles in the inhibition of the host immune response and intracellular survival during infection. So, we listed some key molecular events in the intracellular life cycle of Brucella potentially targeted by the VirB T4SS effectors. Elucidating functions of the effectors secreted will be crucial to clarifying mechanism of T4SS during infection. Studying the effectors secreted by Brucella spp. might provide insights into the mechanisms by which the bacteria hijack the host signaling pathways, which help us to develop better vaccines and therapies against brucellosis.

Type IV secretion system of Brucella spp. and its effectors.

Science.gov (United States)

Ke, Yuehua; Wang, Yufei; Li, Wengfeng; Chen, Zeliang

2015-01-01

Brucella spp. are intracellular bacterial pathogens that cause infection in domestic and wild animals. They are often used as model organisms to study intracellular bacterial infections. Brucella VirB T4SS is a key virulence factor that plays important roles in mediating intracellular survival and manipulating host immune response to infection. In this review, we discuss the roles of Brucella VirB T4SS and 15 effectors that are proposed to be crucial for Brucella pathogenesis. VirB T4SS regulates the inflammation response and manipulates vesicle trafficking inside host cells. VirB T4SS also plays crucial roles in the inhibition of the host immune response and intracellular survival during infection. Here, we list the key molecular events in the intracellular life cycle of Brucella that are potentially targeted by the VirB T4SS effectors. Elucidating the functions of these effectors will help clarify the molecular role of T4SS during infection. Furthermore, studying the effectors secreted by Brucella spp. might provide insights into the mechanisms used by the bacteria to hijack the host signaling pathways and aid in the development of better vaccines and therapies against brucellosis.

An overlap case of Parry–Romberg syndrome and en coup de sabre with striking ocular involvement and anti-double-stranded DNA positivity

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Hatice Atas

2018-01-01

Full Text Available Parry–Romberg syndrome (PRS may overlap localized scleroderma (morphea lesions with linear depression (en coup de sabre [ECDS]. Overlap case with PRS and ECDS was presented. Enophthalmos, uveitis, ocular torticollis, keratic linear precipitates, and anti-double-stranded DNA positivity were identified. Subendothelial keratic precipitates detected by an in vivo laser scanning confocal microscopy were the first profiled in the literature. Patients must be evaluated and followed up carefully by their clinics to prevent misdiagnosis and unnecessary procedures such as surgery of ocular torticollis as muscular torticollis.

High-Pressure Phase Equilibria in Systems Containing CO2 and Ionic Liquid of the [Cnmim][Tf2N] Type

OpenAIRE

Sedláková, Z. (Zuzana); Wagner, Z. (Zdeněk)

2012-01-01

In this review, we present a comparison of the high-pressure phase behaviour of binary systems constituted of CO2 and ionic liquids of the [Cn(m)mim][Tf2N] type. The comparative study shows that the solubility of CO2 in ionic liquids of the [Cnmim][Tf2N] type generally increases with increasing pressure and decreasing temperature, but some peculiarities have been observed. The solubility of CO2 in ionic liquid solvents was correlated using the Soave–Redlich–Kwong equation of state. The result...

TF-finder: A software package for identifying transcription factors involved in biological processes using microarray data and existing knowledge base

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Cui Xiaoqi

2010-08-01

Full Text Available Abstract Background Identification of transcription factors (TFs involved in a biological process is the first step towards a better understanding of the underlying regulatory mechanisms. However, due to the involvement of a large number of genes and complicated interactions in a gene regulatory network (GRN, identification of the TFs involved in a biology process remains to be very challenging. In reality, the recognition of TFs for a given a biological process can be further complicated by the fact that most eukaryotic genomes encode thousands of TFs, which are organized in gene families of various sizes and in many cases with poor sequence conservation except for small conserved domains. This poses a significant challenge for identification of the exact TFs involved or ranking the importance of a set of TFs to a process of interest. Therefore, new methods for recognizing novel TFs are desperately needed. Although a plethora of methods have been developed to infer regulatory genes using microarray data, it is still rare to find the methods that use existing knowledge base in particular the validated genes known to be involved in a process to bait/guide discovery of novel TFs. Such methods can replace the sometimes-arbitrary process of selection of candidate genes for experimental validation and significantly advance our knowledge and understanding of the regulation of a process. Results We developed an automated software package called TF-finder for recognizing TFs involved in a biological process using microarray data and existing knowledge base. TF-finder contains two components, adaptive sparse canonical correlation analysis (ASCCA and enrichment test, for TF recognition. ASCCA uses positive target genes to bait TFS from gene expression data while enrichment test examines the presence of positive TFs in the outcomes from ASCCA. Using microarray data from salt and water stress experiments, we showed TF-finder is very efficient in recognizing

GENIUS-TF: a test facility for the GENIUS project

International Nuclear Information System (INIS)

Klapdor-Kleingrothaus, H.V.; Baudis, L.; Dietz, A.; Heusser, G.; Krivosheina, I.; Majorovits, B.; Strecker, H.

2002-01-01

GENIUS is a proposal for a large scale detector of rare events. As a first step of the experiment, a small test version, the Genius Test-Facility will be built at the Laboratori Nazionali del Gran Sasso. With about 40 kg of natural Ge detectors operated in liquid nitrogen, GENIUS-TF could exclude (or directly confirm) the DAMA annual modulation seasonal modulation signature within about 2 yr of measurement using both, signal and signature of the claimed WIMP Dark Matter. The construction of the experiment has already been started, and four 2.5 kg germanium detectors with an extreme low threshold of 500 eV have been produced

Identification of Novel Host Interactors of Effectors Secreted by Salmonella and Citrobacter

Energy Technology Data Exchange (ETDEWEB)

Sontag, Ryan L.; Nakayasu, Ernesto S.; Brown, Roslyn N.; Niemann, George S.; Sydor, Michael A.; Sanchez, Octavio; Ansong, Charles; Lu, Shao-Yeh; Choi, Hyungwon; Valleau, Dylan; Weitz, Karl K.; Savchenko, Alexei; Cambronne, Eric D.; Adkins, Joshua N.; McFall-Ngai, Margaret J.

2016-07-12

Many pathogenic bacteria of the familyEnterobacteriaceaeuse type III secretion systems to inject virulence proteins, termed “effectors,” into the host cell cytosol. Although host-cellular activities of several effectors have been demonstrated, the function and host-targeted pathways of most of the effectors identified to date are largely undetermined. To gain insight into host proteins targeted by bacterial effectors, we performed coaffinity purification of host proteins from cell lysates using recombinant effectors from theEnterobacteriaceaeintracellular pathogensSalmonella entericaserovar Typhimurium andCitrobacter rodentium. We identified 54 high-confidence host interactors for theSalmonellaeffectors GogA, GtgA, GtgE, SpvC, SrfH, SseL, SspH1, and SssB collectively and 21 interactors for theCitrobactereffectors EspT, NleA, NleG1, and NleK. We biochemically validated the interaction between the SrfHSalmonellaprotein and the extracellular signal-regulated kinase 2 (ERK2) host protein kinase, which revealed a role for this effector in regulating phosphorylation levels of this enzyme, which plays a central role in signal transduction.

IMPORTANCEDuring infection, pathogenic bacteria face an adverse environment of factors driven by both cellular and humoral defense mechanisms. To help evade the immune response and ultimately proliferate inside the host, many bacteria evolved specialized secretion systems to deliver effector proteins directly into host cells. Translocated effector proteins function to subvert host defense mechanisms. Numerous pathogenic bacteria use a specialized secretion system called type III secretion to deliver effectors into the host cell cytosol. Here, we identified 75 new host targets ofSalmonellaandCitrobactereffectors, which will help elucidate their mechanisms of

The Soviet Union and the Third World. Part 1. Coups D’Etat: Lessons of the Past, Prospects for the Future and a Guide for Action

Science.gov (United States)

1984-01-01

which most of the Arab states supported the Eritreans) while Ismail readily agreed to the Soviet request. More fundementally , the dispute revolved around... investment , United Fruit controlled much of the Guatemalan economy and was virtually a state within a state. In June 1953 Arbenz issued an agrarian...CIA continued its efforts to create a coup climate in Chile. President Nixon ordered the end to private investment guarantees to American firms doing

Shear strength of the ASDEX upgrade TF coil insulation: Rupture, fatigue and creep behaviour

International Nuclear Information System (INIS)

Streibl, B.; Maier, E.A.; Perchermeier, J.; Cimbrico, P.L.; Varni, G.; Pisani, D.; Deska, R.; Endreat, J.

1987-03-01

This report is concerned with the interlaminar shear strength of the insulation system for the 16 toroidal field (TF) coils of ASDEX upgrade. The interlaminar shear properties of the glass-epoxy insulation are primarily determined by the resin system (ARALDIT-F, HT 907, DZ 40) and its curing procedure. The pure resin was therefore tested first in tension. The results were taken into account for setting up the method of curing the TF coils. Shear tests of the complete glass-epopxy system were then conducted with tubular torque specimens providing a nearly homogeneous stress distribution. In particular, the influence of the amount of flexibilizer (5, 10, 15 parts of resin weight = PoW) on the rupture and fatigue strengths was assessed at a temperature T=60 C, as also was the temperature dependence of the creep rate (40 C, 60 C, 80 C). The results obtained are not based on safe statistics. Nevertheless, they show clear trends. (orig.)

Phytoplasma effector SAP54 induces indeterminate leaf-like flower development in Arabidopsis plants.

Science.gov (United States)

MacLean, Allyson M; Sugio, Akiko; Makarova, Olga V; Findlay, Kim C; Grieve, Victoria M; Tóth, Réka; Nicolaisen, Mogens; Hogenhout, Saskia A

2011-10-01

Phytoplasmas are insect-transmitted bacterial plant pathogens that cause considerable damage to a diverse range of agricultural crops globally. Symptoms induced in infected plants suggest that these phytopathogens may modulate developmental processes within the plant host. We report herein that Aster Yellows phytoplasma strain Witches' Broom (AY-WB) readily infects the model plant Arabidopsis (Arabidopsis thaliana) ecotype Columbia, inducing symptoms that are characteristic of phytoplasma infection, such as the production of green leaf-like flowers (virescence and phyllody) and increased formation of stems and branches (witches' broom). We found that the majority of genes encoding secreted AY-WB proteins (SAPs), which are candidate effector proteins, are expressed in Arabidopsis and the AY-WB insect vector Macrosteles quadrilineatus (Hemiptera; Cicadellidae). To identify which of these effector proteins induce symptoms of phyllody and virescence, we individually expressed the effector genes in Arabidopsis. From this screen, we have identified a novel AY-WB effector protein, SAP54, that alters floral development, resulting in the production of leaf-like flowers that are similar to those produced by plants infected with this phytoplasma. This study offers novel insight into the effector profile of an insect-transmitted plant pathogen and reports to our knowledge the first example of a microbial pathogen effector protein that targets flower development in a host.

Meta-analytic approach to the accurate prediction of secreted virulence effectors in gram-negative bacteria

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Sato Yoshiharu

2011-11-01

Full Text Available Abstract Background Many pathogens use a type III secretion system to translocate virulence proteins (called effectors in order to adapt to the host environment. To date, many prediction tools for effector identification have been developed. However, these tools are insufficiently accurate for producing a list of putative effectors that can be applied directly for labor-intensive experimental verification. This also suggests that important features of effectors have yet to be fully characterized. Results In this study, we have constructed an accurate approach to predicting secreted virulence effectors from Gram-negative bacteria. This consists of a support vector machine-based discriminant analysis followed by a simple criteria-based filtering. The accuracy was assessed by estimating the average number of true positives in the top-20 ranking in the genome-wide screening. In the validation, 10 sets of 20 training and 20 testing examples were randomly selected from 40 known effectors of Salmonella enterica serovar Typhimurium LT2. On average, the SVM portion of our system predicted 9.7 true positives from 20 testing examples in the top-20 of the prediction. Removal of the N-terminal instability, codon adaptation index and ProtParam indices decreased the score to 7.6, 8.9 and 7.9, respectively. These discrimination features suggested that the following characteristics of effectors had been uncovered: unstable N-terminus, non-optimal codon usage, hydrophilic, and less aliphathic. The secondary filtering process represented by coexpression analysis and domain distribution analysis further refined the average true positive counts to 12.3. We further confirmed that our system can correctly predict known effectors of P. syringae DC3000, strongly indicating its feasibility. Conclusions We have successfully developed an accurate prediction system for screening effectors on a genome-wide scale. We confirmed the accuracy of our system by external validation

In-session caregiver behavior predicts symptom change in youth receiving trauma-focused cognitive behavioral therapy (TF-CBT).

Science.gov (United States)

Yasinski, Carly; Hayes, Adele M; Ready, C Beth; Cummings, Jorden A; Berman, Ilana S; McCauley, Thomas; Webb, Charles; Deblinger, Esther

2016-12-01

Involving caregivers in trauma-focused treatments for youth has been shown to result in better outcomes, but it is not clear which in-session caregiver behaviors enhance or inhibit this effect. The current study examined the associations between caregiver behaviors during Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) and youth cognitive processes and symptoms. Participants were a racially diverse sample of Medicaid-eligible youth (ages 7-17) and their nonoffending caregivers (N = 71 pairs) who received TF-CBT through an effectiveness study in a community setting. Caregiver and youth processes were coded from audio-recorded sessions, and outcomes were measured using the Child Behavior Checklist (CBCL) and UCLA PTSD Reaction Index for Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition (DSM-IV; UPID) at 3, 6, 9, and 12 months postintake. Piecewise linear growth curve modeling revealed that during the trauma narrative phase of TF-CBT, caregivers' cognitive-emotional processing of their own and their child's trauma-related reactions predicted decreases in youth internalizing and externalizing symptoms over treatment. Caregiver support predicted lower internalizing symptoms over follow-up. In contrast, caregiver avoidance and blame of the child predicted worsening of youth internalizing and externalizing symptoms over follow-up. Caregiver avoidance early in treatment also predicted worsening of externalizing symptoms over follow-up. During the narrative phase, caregiver blame and avoidance were correlated with more child overgeneralization of trauma beliefs, and blame was also associated with less child accommodation of balanced beliefs. The association between in-session caregiver behaviors and youth symptomatology during and after TF-CBT highlights the importance of assessing and targeting these behaviors to improve clinical outcomes. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Subtle variation within conserved effector operon gene products contributes to T6SS-mediated killing and immunity.

Science.gov (United States)

Alteri, Christopher J; Himpsl, Stephanie D; Zhu, Kevin; Hershey, Haley L; Musili, Ninette; Miller, Jessa E; Mobley, Harry L T

2017-11-01

Type VI secretion systems (T6SS) function to deliver lethal payloads into target cells. Many studies have shown that protection against a single, lethal T6SS effector protein requires a cognate antidote immunity protein, both of which are often encoded together in a two-gene operon. The T6SS and an effector-immunity pair is sufficient for both killing and immunity. HereIn this paper we describe a T6SS effector operon that differs from conventional effector-immunity pairs in that eight genes are necessary for lethal effector function, yet can be countered by a single immunity protein. In this study, we investigated the role that the PefE T6SS immunity protein plays in recognition between two strains harboring nearly identical effector operons. Interestingly, despite containing seven of eight identical effector proteins, the less conserved immunity proteins only provided protection against their native effectors, suggesting that specificity and recognition could be dependent on variation within an immunity protein and one effector gene product. The variable effector gene product, PefD, is encoded upstream from pefE, and displays toxic activity that can be countered by PefE independent of T6SS-activity. Interestingly, while the entire pef operon was necessary to exert toxic activity via the T6SS in P. mirabilis, production of PefD and PefE alone was unable to exert this effector activity. Chimeric PefE proteins constructed from two P. mirabilis strains were used to localize immunity function to three amino acids. A promiscuous immunity protein was created using site-directed mutagenesis to change these residues from one variant to another. These findings support the notion that subtle differences between conserved effectors are sufficient for T6SS-mediated kin discrimination and that PefD requires additional factors to function as a T6SS-dependent effector.

Study for Manufacturing of ITER TF Coil Radial Plates

International Nuclear Information System (INIS)

Fietz, W.H.; Muetzel, W.

2006-01-01

During the previous design phase of ITER the ITER Toroidal Field Model Coil (TFMC) has been built to verify the TF coil concept of ITER and to proof the feasibility of an industrial fabrication of such a coil. In April 2004, Forschungszentrum and BNG, started a Manufacturing Study for the full scale Radial Plates (RP) of the TF Coils in the frame of an EFDA task. The main part of the Study was to develop feasible concepts of the technology for the manufacturing of the Full Scale Radial Plates starting with the raw material until final testing. The Feasibility Study has covered all manufacturing steps that are necessary for production of the RP. It has included as well a basic layout for the manufacturing process. During the work several proposals for the single manufacturing work steps have been developed. After that an evaluation of the found proposals has taken place. The most feasible proposals have been combined to manufacturing concepts. Finally two main Concepts were elaborated and evaluated: Concept 1 includes the premachining of segments with grooves, the welding of the segments and the final machining of the RP. Concept 2 includes the welding of not machined small segments to the D-shape of the RP and the following machining of the surface and grooves. Both Concepts will be described in detail with a comparison of tooling and manufacturing details, achievement of technological requirements as well as with the requirements coming from the overall time schedule. Based on the results of the assessment of the different concepts and manufacturing techniques Concept 1 shows some advantages compared to Concept 2. These will be described in the paper. In addition a proposal about additional R(and)D in front of the later manufacturing will be made. (author)

Development of manufacturing technology for ITER TF Coil Structure

Energy Technology Data Exchange (ETDEWEB)

Sakurai, Takeru, E-mail: sakurai.takeru@jaea.go.jp; Iguchi, Masahide; Nakahira, Masataka; Inagaki, Takashi; Matsui, Kunihiro; Koizumi, Norikiyo

2016-11-01

Highlights: • Heavy thick welding (Max. 287 mm) was performed by balance welding. • Figured out Attachment welding deformation including heavy thick welding. • The deformation of Segments welding was suppressed to 1/3 of previous method. • Based on this study, JAEA started actual ITER TF coil structure manufacturing. - Abstract: Japan Atomic Energy Agency (JAEA) performed a trial of A1 Segment manufacturing of Toroidal Field (TF) coil structure, which is a piece with a radius of curvature 3 m with square channel for coil. Even though both-side welding (balance welding) was preferred to one-side welding considering the welding deformation, it could not be applied to the previous trial due to the difficulty of overhead or horizontal welding by machine. Hence, one-side welding with strong restriction jig was applied in the previous trials. In the latest trial, JAEA adopted a manual balance welding with a development of manufacturing technology. As the result of A1 Segment Mainbody welding trial, welding deformation of the Outer Plate and the Side Plate could have been controlled closer to the target value. JAEA also tried Attachments welding, in which Pre-Compression Flange (PCF) and Extension are welded to A1 Segment Mainbody, and a Segments welding trial, which is a weld between A1 Segment and a part of A2 Segment. A2 Segment is a 3 m straight part with square channel for coil. The inclination of A1 Segment and A2 Segment due to the welding was 2.7 mm. By applying balance welding, the deformation by Segments welding was suppressed to about 1/3 of the one-side welding. The views and opinions expressed herein do not necessarily reflect those of the ITER Organization.

Structural modelling and molecular dynamics of a multi-stress responsive WRKY TF-DNA complex towards elucidating its role in stress signalling mechanisms in chickpea.

Science.gov (United States)

Konda, Aravind Kumar; Farmer, Rohit; Soren, Khela Ram; P S, Shanmugavadivel; Setti, Aravind

2017-07-28

Chickpea is a premier food legume crop with high nutritional quality and attains prime importance in the current era of 795 million people being undernourished worldwide. Chickpea production encounters setbacks due to various stresses and understanding the role of key transcription factors (TFs) involved in multiple stresses becomes inevitable. We have recently identified a multi-stress responsive WRKY TF in chickpea. The present study was conducted to predict the structure of WRKY TF to identify the DNA-interacting residues and decipher DNA-protein interactions. Comparative modelling approach produced 3D model of the WRKY TF with good stereochemistry, local/global quality and further revealed W19, R20, K21, and Y22 motifs within a vicinity of 5 Å to the DNA amongst R18, G23, Q24, K25, Y36, Y37, R38 and K47 and these positions were equivalent to the 2LEX WRKY domain of Arabidopsis. Molecular simulations analysis of reference protein -PDB ID 2LEX, along with Car-WRKY TF modelled structure with the DNA coordinates derived from PDB ID 2LEX and docked using HADDOCK were executed. Root Mean Square (RMS) Deviation and RMS Fluctuation values yielded consistently stable trajectories over 50 ns simulation. Strengthening the obtained results, neither radius of gyration, distance and total energy showed any signs of DNA-WRKY complex falling apart nor any significant dissociation event over 50 ns run. Therefore, the study provides first insights into the structural properties of multi-stress responsive WRKY TF-DNA complex in chickpea, enabling genome wide identification of TF binding sites and thereby deciphers their gene regulatory networks.

The barley powdery mildew effector candidates CSEP0081 and CSEP0254 promote fungal infection success

DEFF Research Database (Denmark)

Ahmed, Ali Abdurehim; Pedersen, Carsten; Thordal-Christensen, Hans

2016-01-01

Effectors play significant roles in the success of pathogens. Recent advances in genome sequencing have revealed arrays of effectors and effector candidates from a wide range of plant pathogens. Yet, the vast majority of them remain uncharacterized. Among the ~500 Candidate Secreted Effector...... independent silencing of the transcripts for these CSEPs significantly reduced the fungal penetration and haustoria formation rate. Both CSEPs are likely required during and after the formation of haustoria, in which their transcripts were found to be differentially expressed, rather than in epiphytic tissue...

Functions and requirements for the INEL light duty utility arm gripper end effector

International Nuclear Information System (INIS)

Pace, D.P.; Barnes, G.E.

1995-02-01

This gripper end effector system functions and requirements document defines the system functions that the end effector must perform as well as the requirements the design must meet. Safety, quality assurance, operations, environmental conditions, and regulatory requirements have been considered. The main purpose of this document is to provide a basis for the end effector engineering, design, and fabrication activities. The document shall be the living reference document to initiate the development activities and will be updated as system technologies are finalized

Functions and requirements for the INEL light duty utility arm sampler end effector

International Nuclear Information System (INIS)

Pace, D.P.; Barnes, G.E.

1995-02-01

This sampler end effector system functions and requirements document defines the system functions that the end effector must perform as well as the requirements the design must meet. Safety, quality assurance, operations, environmental conditions, and regulatory requirements have been considered. The main purpose of this document is to provide a basis for the end effector engineering, design, and fabrication activities. The document shall be the living reference document to initiate the development activities and will be updated as system technologies are finalized

Uji Unjuk Kerja Traktor Yanmar Tipe TF 85 pada Lahan Basah dan Lahan Kering di Desa Dolok Hataran, Kabupaten Simalungun

OpenAIRE

Tobing, Toman Harry Duga L.

2010-01-01

TOMAN H D L. TOBING: Performance of Yanmar TF 85 Tractor on Wet land and Dry land at Desa Dolok Hataran Kabupaten Simalungun. Under the supervision of TAUFIK RIZALDI and AINUN ROHANAH. The performance test of tractor is its ability to prepare land using implements to know the work capacity, efficiency, work velocity, and wheel skid. The objective of this research is to know the capacity of Yanmar TF 85 tractor on wet land and dry land at Desa Dolok Hataran Kabupaten Simalungun. This rese...

Establishment of an inducing medium for type III effector secretion in Xanthomonas campestris pv. campestris

Directory of Open Access Journals (Sweden)

Guo-Feng Jiang

2013-09-01

Full Text Available It is well known that the type III secretion system (T3SS and type III (T3 effectors are essential for the pathogenicity of most bacterial phytopathogens and that the expression of T3SS and T3 effectors is suppressed in rich media but induced in minimal media and plants. To facilitate in-depth studies on T3SS and T3 effectors, it is crucial to establish a medium for T3 effector expression and secretion. Xanthomonas campestris pv. campestris (Xcc is a model bacterium for studying plant-pathogen interactions. To date no medium for Xcc T3 effector secretion has been defined. Here, we compared four minimal media (MME, MMX, XVM2, and XOM2 which are reported for T3 expression induction in Xanthomonas spp. and found that MME is most efficient for expression and secretion of Xcc T3 effectors. By optimization of carbon and nitrogen sources and pH value based on MME, we established XCM1 medium, which is about 3 times stronger than MME for Xcc T3 effectors secretion. We further optimized the concentration of phosphate, calcium, and magnesium in XCM1 and found that XCM1 with a lower concentration of magnesium (renamed as XCM2 is about 10 times as efficient as XCM1 (meanwhile, about 30 times stronger than MME. Thus, we established an inducing medium XCM2 which is preferred for T3 effector secretion in Xcc.

The Legionella pneumophila IcmSW complex interacts with multiple Dot/Icm effectors to facilitate type IV translocation.

Directory of Open Access Journals (Sweden)

Eric D Cambronne

2007-12-01

Full Text Available Many gram-negative pathogens use a type IV secretion system (T4SS to deliver effector proteins into eukaryotic host cells. The fidelity of protein translocation depends on the efficient recognition of effector proteins by the T4SS. Legionella pneumophila delivers a large number of effector proteins into eukaryotic cells using the Dot/Icm T4SS. How the Dot/Icm system is able to recognize and control the delivery of effectors is poorly understood. Recent studies suggest that the IcmS and IcmW proteins interact to form a stable complex that facilitates translocation of effector proteins by the Dot/Icm system by an unknown mechanism. Here we demonstrate that the IcmSW complex is necessary for the productive translocation of multiple Dot/Icm effector proteins. Effector proteins that were able to bind IcmSW in vitro required icmS and icmW for efficient translocation into eukaryotic cells during L. pneumophila infection. We identified regions in the effector protein SidG involved in icmSW-dependent translocation. Although the full-length SidG protein was translocated by an icmSW-dependent mechanism, deletion of amino terminal regions in the SidG protein resulted in icmSW-independent translocation, indicating that the IcmSW complex is not contributing directly to recognition of effector proteins by the Dot/Icm system. Biochemical and genetic studies showed that the IcmSW complex interacts with a central region of the SidG protein. The IcmSW interaction resulted in a conformational change in the SidG protein as determined by differences in protease sensitivity in vitro. These data suggest that IcmSW binding to effectors could enhance effector protein delivery by mediating a conformational change that facilitates T4SS recognition of a translocation domain located in the carboxyl region of the effector protein.

tf_unet: Generic convolutional neural network U-Net implementation in Tensorflow

Science.gov (United States)

Akeret, Joel; Chang, Chihway; Lucchi, Aurelien; Refregier, Alexandre

2016-11-01

tf_unet mitigates radio frequency interference (RFI) signals in radio data using a special type of Convolutional Neural Network, the U-Net, that enables the classification of clean signal and RFI signatures in 2D time-ordered data acquired from a radio telescope. The code is not tied to a specific segmentation and can be used, for example, to detect radio frequency interference (RFI) in radio astronomy or galaxies and stars in widefield imaging data. This U-Net implementation can outperform classical RFI mitigation algorithms.

Identification and characterisation of a hyper-variable apoplastic effector gene family of the potato cyst nematodes.

Science.gov (United States)

Eves-van den Akker, Sebastian; Lilley, Catherine J; Jones, John T; Urwin, Peter E

2014-09-01

Sedentary endoparasitic nematodes are obligate biotrophs that modify host root tissues, using a suite of effector proteins to create and maintain a feeding site that is their sole source of nutrition. Using assumptions about the characteristics of genes involved in plant-nematode biotrophic interactions to inform the identification strategy, we provide a description and characterisation of a novel group of hyper-variable extracellular effectors termed HYP, from the potato cyst nematode Globodera pallida. HYP effectors comprise a large gene family, with a modular structure, and have unparalleled diversity between individuals of the same population: no two nematodes tested had the same genetic complement of HYP effectors. Individuals vary in the number, size, and type of effector subfamilies. HYP effectors are expressed throughout the biotrophic stages in large secretory cells associated with the amphids of parasitic stage nematodes as confirmed by in situ hybridisation. The encoded proteins are secreted into the host roots where they are detectable by immunochemistry in the apoplasm, between the anterior end of the nematode and the feeding site. We have identified HYP effectors in three genera of plant parasitic nematodes capable of infecting a broad range of mono- and dicotyledon crop species. In planta RNAi targeted to all members of the effector family causes a reduction in successful parasitism.

Effector-independent motor sequence representations exist in extrinsic and intrinsic reference frames.

Science.gov (United States)

Wiestler, Tobias; Waters-Metenier, Sheena; Diedrichsen, Jörn

2014-04-02

Many daily activities rely on the ability to produce meaningful sequences of movements. Motor sequences can be learned in an effector-specific fashion (such that benefits of training are restricted to the trained hand) or an effector-independent manner (meaning that learning also facilitates performance with the untrained hand). Effector-independent knowledge can be represented in extrinsic/world-centered or in intrinsic/body-centered coordinates. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to determine the distribution of intrinsic and extrinsic finger sequence representations across the human neocortex. Participants practiced four sequences with one hand for 4 d, and then performed these sequences during fMRI with both left and right hand. Between hands, these sequences were equivalent in extrinsic or intrinsic space, or were unrelated. In dorsal premotor cortex (PMd), we found that sequence-specific activity patterns correlated higher for extrinsic than for unrelated pairs, providing evidence for an extrinsic sequence representation. In contrast, primary sensory and motor cortices showed effector-independent representations in intrinsic space, with considerable overlap of the two reference frames in caudal PMd. These results suggest that effector-independent representations exist not only in world-centered, but also in body-centered coordinates, and that PMd may be involved in transforming sequential knowledge between the two. Moreover, although effector-independent sequence representations were found bilaterally, they were stronger in the hemisphere contralateral to the trained hand. This indicates that intermanual transfer relies on motor memories that are laid down during training in both hemispheres, but preferentially draws upon sequential knowledge represented in the trained hemisphere.

Downstream Toll-like receptor signaling mediates adaptor-specific cytokine expression following focal cerebral ischemia

Directory of Open Access Journals (Sweden)

Bolanle Famakin

2012-07-01

Full Text Available Abstract Background Deletion of some Toll-like receptors (TLRs affords protection against cerebral ischemia, but disruption of their known major downstream adaptors does not. To determine whether compensation in the production of downstream effectors by one pathway when the other is disrupted can explain these findings, we examined cytokine/chemokine expression and inflammatory infiltrates in wild-type (WT, MyD88−/− and TRIF-mutant mice following permanent middle cerebral artery occlusion (pMCAO. Methods Cytokine/chemokine expression was measured with a 25-plex bead array in the serum and brains of all three groups of mice at baseline (no surgery/naïve and at 3 hours and 24 hours following pMCAO. Brain inflammatory and neutrophil infiltrates were examined 24 hours following pMCAO. Results IL-6, keratinocyte chemoattractant (KC, granulocyte colony-stimulating factor (G-CSF and IL-10 were significantly decreased in MyD88−/− mice compared to WT mice following pMCAO. Significantly, decreased levels of the neutrophil chemoattractants KC and G-CSF corresponded with a trend toward fewer neutrophils in the brains of MyD88−/− mice. IP-10 was significantly decreased when either pathway was disrupted. MIP-1α was significantly decreased in TRIF-mutant mice, consistent with TRIF-dependent production. MyD88−/− mice showed elevations of a number of Th2 cytokines, such as IL-13, at baseline, which became significantly decreased following pMCAO. Conclusions Both MyD88 and TRIF mediate pathway-specific cytokine production following focal cerebral ischemia. Our results also suggest a compensatory Th2-type skew at baseline in MyD88−/− mice and a paradoxical switch to a Th1 phenotype following focal cerebral ischemia. The MyD88 pathway directs the expression of neutrophil chemoattractants following cerebral ischemia.

TIBER-II TF [toroidal-field] winding pack design

International Nuclear Information System (INIS)

Kerns, J.A.; Miller, J.R.; Slack, D.S.; Summers, L.T.

1987-01-01

The superconducting, toroidal-field (TF) coils in the Tokamak Ignition/Burn Engineering Reactor (TIBER II) are designed with cable-in-conduit conductor (CICC) using Nb 3 Sn composite strands. To design the CICC winding pack, we used an optimization technique that maximizes the conductor stability without violating the constraints imposed by the structure, electrical insulation, quench protection, and fabrication technique. Detailed helium-properties codes calculate the heat removal along a flow path, and detailed field calculations determine the temperature, current, and stability margins. The conductor sheath is designed as distributed structure to partially support the combined in-plane and out-of-plane loads generated within the winding pack. Pancakes of the coil are wound, reacted, and insulated before being potted in the case. This design is aggressive but fully consistent with good engineering practice. 5 refs., 4 figs., 2 tabs

TFTR D and D Project: Final Examination and Testing of the TFTR TF-Coils

International Nuclear Information System (INIS)

Zatz, Irving J.

2003-01-01

In operation for nearly 15 years, TFTR (Tokamak Fusion Test Reactor) was not only a fusion science milestone, but a milestone of achievement in engineering as well. The TFTR DandD (Decommissioning and Decontamination) program provided a rare opportunity to examine machine components that had been exposed to a unique performance environment of greater than 100,000 mechanical and thermal load cycles. In particular, the possible examination of the TFTR toroidal-field (TF) coils, which met, then exceeded, the 5.2 Tesla magnetic field machine specification, could supply the answers to many questions that have been asked and debated since the coils were originally designed and built. A test program conducted in parallel with the DandD effort was the chance to look inside and examine, in detail, the TFTR TF coils for the first time since they were delivered encased to PPPL (Princeton Plasma Physics Laboratory). The results from such a program would provide data and insight that would not only be nefit PPPL and the fusion community, but the broader scientific community as well

Identification of proteins similar to AvrE type III effector proteins from ...

African Journals Online (AJOL)

Type III effector proteins are injected into host cells through type III secretion systems. Some effectors are similar to host proteins to promote pathogenicity, while others lead to the activation of disease resistance. We used partial least squares alignment-free bioinformatics methods to identify proteins similar to AvrE proteins ...

Shigella IpaH Family Effectors as a Versatile Model for Studying Pathogenic Bacteria.

Science.gov (United States)

Ashida, Hiroshi; Sasakawa, Chihiro

2015-01-01

Shigella spp. are highly adapted human pathogens that cause bacillary dysentery (shigellosis). Via the type III secretion system (T3SS), Shigella deliver a subset of virulence proteins (effectors) that are responsible for pathogenesis, with functions including pyroptosis, invasion of the epithelial cells, intracellular survival, and evasion of host immune responses. Intriguingly, T3SS effector activity and strategies are not unique to Shigella, but are shared by many other bacterial pathogens, including Salmonella, Yersinia, and enteropathogenic Escherichia coli (EPEC). Therefore, studying Shigella T3SS effectors will not only improve our understanding of bacterial infection systems, but also provide a molecular basis for developing live bacterial vaccines and antibacterial drugs. One of Shigella T3SS effectors, IpaH family proteins, which have E3 ubiquitin ligase activity and are widely conserved among other bacterial pathogens, are very relevant because they promote bacterial survival by triggering cell death and modulating the host immune responses. Here, we describe selected examples of Shigella pathogenesis, with particular emphasis on the roles of IpaH family effectors, which shed new light on bacterial survival strategies and provide clues about how to overcome bacterial infections.

Shigella IpaH family effectors as a versatile model for studying pathogenic bacteria

Directory of Open Access Journals (Sweden)

Hiroshi eAshida

2016-01-01

Full Text Available Shigella spp. are highly adapted human pathogens that cause bacillary dysentery (shigellosis. Via the type III secretion system (T3SS, Shigella deliver a subset of virulence proteins (effectors that are responsible for pathogenesis, with functions including pyroptosis, invasion of the epithelial cells, intracellular survival, and evasion of host immune responses. Intriguingly, T3SS effector activity and strategies are not unique to Shigella, but are shared by many other bacterial pathogens, including Salmonella, Yersinia, and enteropathogenic Escherichia coli (EPEC. Therefore, studying Shigella T3SS effectors will not only improve our understanding of bacterial infection systems, but also provide a molecular basis for developing live bacterial vaccines and antibacterial drugs. One of Shigella T3SS effectors, IpaH family proteins, which have E3 ubiquitin ligase activity and are widely conserved among other bacterial pathogens, are very relevant because they promote bacterial survival by triggering cell death and modulating the host immune responses. Here, we describe selected examples of Shigella pathogenesis, with particular emphasis on the roles of IpaH family effectors, which shed new light on bacterial survival strategies and provide clues about how to overcome bacterial infections.

Using hierarchical clustering of secreted protein families to classify and rank candidate effectors of rust fungi.

Directory of Open Access Journals (Sweden)

Diane G O Saunders

Full Text Available Rust fungi are obligate biotrophic pathogens that cause considerable damage on crop plants. Puccinia graminis f. sp. tritici, the causal agent of wheat stem rust, and Melampsora larici-populina, the poplar leaf rust pathogen, have strong deleterious impacts on wheat and poplar wood production, respectively. Filamentous pathogens such as rust fungi secrete molecules called disease effectors that act as modulators of host cell physiology and can suppress or trigger host immunity. Current knowledge on effectors from other filamentous plant pathogens can be exploited for the characterisation of effectors in the genome of recently sequenced rust fungi. We designed a comprehensive in silico analysis pipeline to identify the putative effector repertoire from the genome of two plant pathogenic rust fungi. The pipeline is based on the observation that known effector proteins from filamentous pathogens have at least one of the following properties: (i contain a secretion signal, (ii are encoded by in planta induced genes, (iii have similarity to haustorial proteins, (iv are small and cysteine rich, (v contain a known effector motif or a nuclear localization signal, (vi are encoded by genes with long intergenic regions, (vii contain internal repeats, and (viii do not contain PFAM domains, except those associated with pathogenicity. We used Markov clustering and hierarchical clustering to classify protein families of rust pathogens and rank them according to their likelihood of being effectors. Using this approach, we identified eight families of candidate effectors that we consider of high value for functional characterization. This study revealed a diverse set of candidate effectors, including families of haustorial expressed secreted proteins and small cysteine-rich proteins. This comprehensive classification of candidate effectors from these devastating rust pathogens is an initial step towards probing plant germplasm for novel resistance components.

Preliminary LOCA analysis of the westinghouse small modular reactor using the WCOBRA/TRAC-TF2 thermal-hydraulics code

Energy Technology Data Exchange (ETDEWEB)

Liao, J.; Kucukboyaci, V. N.; Nguyen, L.; Frepoli, C. [Westinghouse Electric Company, 1000 Westinghouse Drive, Cranberry Township, PA 16066 (United States)

2012-07-01

The Westinghouse Small Modular Reactor (SMR) is an 800 MWt (> 225 MWe) integral pressurized water reactor (iPWR) with all primary components, including the steam generator and the pressurizer located inside the reactor vessel. The reactor core is based on a partial-height 17x17 fuel assembly design used in the AP1000{sup R} reactor core. The Westinghouse SMR utilizes passive safety systems and proven components from the AP1000 plant design with a compact containment that houses the integral reactor vessel and the passive safety systems. A preliminary loss of coolant accident (LOCA) analysis of the Westinghouse SMR has been performed using the WCOBRA/TRAC-TF2 code, simulating a transient caused by a double ended guillotine (DEG) break in the direct vessel injection (DVI) line. WCOBRA/TRAC-TF2 is a new generation Westinghouse LOCA thermal-hydraulics code evolving from the US NRC licensed WCOBRA/TRAC code. It is designed to simulate PWR LOCA events from the smallest break size to the largest break size (DEG cold leg). A significant number of fluid dynamics models and heat transfer models were developed or improved in WCOBRA/TRAC-TF2. A large number of separate effects and integral effects tests were performed for a rigorous code assessment and validation. WCOBRA/TRAC-TF2 was introduced into the Westinghouse SMR design phase to assist a quick and robust passive cooling system design and to identify thermal-hydraulic phenomena for the development of the SMR Phenomena Identification Ranking Table (PIRT). The LOCA analysis of the Westinghouse SMR demonstrates that the DEG DVI break LOCA is mitigated by the injection and venting from the Westinghouse SMR passive safety systems without core heat up, achieving long term core cooling. (authors)

End-Effector Development for the PIP Puck Handling Robot

International Nuclear Information System (INIS)

Fowley, M.D.

2001-01-01

It has been decided that excess, weapons-grade plutonium shall be immobilized to prevent nuclear proliferation. The method of immobilization is to encapsulate the plutonium in a ceramic puck, roughly the size of a hockey puck, using a sintering process. This method has been officially identified as the Plutonium Immobilization Process (PIP). A Can-in-Canister storage method will be used to further immobilize the plutonium. The Can-in-Canister method uses the existing design of a Defense Waste Processing Facility (DWPF) canister to house the plutonium pucks. the process begins with several pucks being stacked in a stainless steel can. Several of the stainless steel cans are stacked in a cage-like magazine. Several of the magazines are then placed in a DWPF canister. The DWPF canister is then filled with molten glass containing high-level, radioactive waste from the DWPF vitrification process. The Can-in-Canister method makes reclamation of plutonium from the pucks technically difficult and highly undesirable. The mechanical requirements of the Can-in-Canister process, in conjunction with the amount of time required to immobilize the vast quantities of weapons-grade plutonium, will expose personnel to unnecessarily high levels of radiation if the processes were completed manually, in glove boxes. Therefore, automated equipment is designed into the process to reduce or eliminate personnel exposure. Robots are used whenever the automated handling operations become complicated. There are two such operations in the initial stages of the Can-in-Canister process, which required a six-axis robot. The first operation is a press unloading process. The second operation is a tray transfer process. To successfully accomplish the operational tasks described in the two operations, the end-effector of the robot must be versatile, lightweight, and rugged. As a result of these demands, an extensive development process was undertaken to design the optimum end-effector for these puck

Identification and characterisation of a hyper-variable apoplastic effector gene family of the potato cyst nematodes.

Directory of Open Access Journals (Sweden)

Sebastian Eves-van den Akker

2014-09-01

Full Text Available Sedentary endoparasitic nematodes are obligate biotrophs that modify host root tissues, using a suite of effector proteins to create and maintain a feeding site that is their sole source of nutrition. Using assumptions about the characteristics of genes involved in plant-nematode biotrophic interactions to inform the identification strategy, we provide a description and characterisation of a novel group of hyper-variable extracellular effectors termed HYP, from the potato cyst nematode Globodera pallida. HYP effectors comprise a large gene family, with a modular structure, and have unparalleled diversity between individuals of the same population: no two nematodes tested had the same genetic complement of HYP effectors. Individuals vary in the number, size, and type of effector subfamilies. HYP effectors are expressed throughout the biotrophic stages in large secretory cells associated with the amphids of parasitic stage nematodes as confirmed by in situ hybridisation. The encoded proteins are secreted into the host roots where they are detectable by immunochemistry in the apoplasm, between the anterior end of the nematode and the feeding site. We have identified HYP effectors in three genera of plant parasitic nematodes capable of infecting a broad range of mono- and dicotyledon crop species. In planta RNAi targeted to all members of the effector family causes a reduction in successful parasitism.

Downstream-based Scheduling for Energy Conservation in Green EPONs

KAUST Repository

Chen, Shen

2012-05-01

Maximizing the optical network unit’s (ONU) sleep time is an effective approach for achieving maximum energy conservation in green Ethernet passive optical networks (EPONs). While overlapping downstream and upstream ONU transmissions can maximize the ONU sleep time, it jeopardizes the quality of service (QoS) performance of the network, especially for downstream traffic in case the overlapping is based on the upstream time slot. In this paper, we study the downstream traffic performance in green EPONs under the limited service discipline and the upstream-based overlapped time window. Specifically, we first derive the expected mean packet delay, and then present a closed-form expression of the ONU sleep time, setting identical upstream/downstream transmission cycle times based on a maximum downstream traffic delay re-quirement. With the proposed system model, we present a novel downstream bandwidth allocation scheme for energy conservation in green EPONs. Simulation results verify the proposed model and highlight the advantages of our scheme over conventional approaches.

Two-phase interfacial area and flow regime modeling in FLOWTRAN-TF code

International Nuclear Information System (INIS)

Smith, F.G. III; Lee, S.Y.; Flach, G.P.; Hamm, L.L.

1992-01-01

FLOWTRAN-TF is a new two-component, two-phase thermal-hydraulics code to capture the detailed assembly behavior associated with loss-of-coolant accident analyses in multichannel assemblies of the SRS reactors. The local interfacial area of the two-phase mixture is computed by summing the interfacial areas contributed by each of three flow regimes. For smooth flow regime transitions, the code uses an interpolation technique in terms of component void fraction for each basic flow regime

Double-stranded RNA transcribed from vector-based oligodeoxynucleotide acts as transcription factor decoy

International Nuclear Information System (INIS)

Xiao, Xiao; Gang, Yi; Wang, Honghong; Wang, Jiayin; Zhao, Lina; Xu, Li; Liu, Zhiguo

2015-01-01

Highlights: • A shRNA vector based transcription factor decoy, VB-ODN, was designed. • VB-ODN for NF-κB inhibited cell viability in HEK293 cells. • VB-ODN inhibited expression of downstream genes of target transcription factors. • VB-ODN may enhance nuclear entry ratio for its feasibility of virus production. - Abstract: In this study, we designed a short hairpin RNA vector-based oligodeoxynucleotide (VB-ODN) carrying transcription factor (TF) consensus sequence which could function as a decoy to block TF activity. Specifically, VB-ODN for Nuclear factor-κB (NF-κB) could inhibit cell viability and decrease downstream gene expression in HEK293 cells without affecting expression of NF-κB itself. The specific binding between VB-ODN produced double-stranded RNA and NF-κB was evidenced by electrophoretic mobility shift assay. Moreover, similar VB-ODNs designed for three other TFs also inhibit their downstream gene expression but not that of themselves. Our study provides a new design of decoy for blocking TF activity

Double-stranded RNA transcribed from vector-based oligodeoxynucleotide acts as transcription factor decoy

Energy Technology Data Exchange (ETDEWEB)

Xiao, Xiao [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Gang, Yi [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi Province (China); Wang, Honghong [No. 518 Hospital of Chinese People’s Liberation Army, Xi’an 710043, Shaanxi Province (China); Wang, Jiayin [The Genome Institute, Washington University in St. Louis, St. Louis, MO 63108 (United States); Zhao, Lina [Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Xu, Li, E-mail: lxuhelen@163.com [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Liu, Zhiguo, E-mail: liuzhiguo@fmmu.edu.cn [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China)

2015-02-06

Highlights: • A shRNA vector based transcription factor decoy, VB-ODN, was designed. • VB-ODN for NF-κB inhibited cell viability in HEK293 cells. • VB-ODN inhibited expression of downstream genes of target transcription factors. • VB-ODN may enhance nuclear entry ratio for its feasibility of virus production. - Abstract: In this study, we designed a short hairpin RNA vector-based oligodeoxynucleotide (VB-ODN) carrying transcription factor (TF) consensus sequence which could function as a decoy to block TF activity. Specifically, VB-ODN for Nuclear factor-κB (NF-κB) could inhibit cell viability and decrease downstream gene expression in HEK293 cells without affecting expression of NF-κB itself. The specific binding between VB-ODN produced double-stranded RNA and NF-κB was evidenced by electrophoretic mobility shift assay. Moreover, similar VB-ODNs designed for three other TFs also inhibit their downstream gene expression but not that of themselves. Our study provides a new design of decoy for blocking TF activity.

X-linked inhibitor of apoptosis regulates T cell effector function

DEFF Research Database (Denmark)

Zehntner, Simone P; Bourbonnière, Lyne; Moore, Craig S

2007-01-01

To understand how the balance between pro- and anti-apoptotic signals influences effector function in the immune system, we studied the X-linked inhibitor of apoptosis (XIAP), an endogenous regulator of cellular apoptosis. Real-time PCR showed increased XIAP expression in blood of mice with exper......To understand how the balance between pro- and anti-apoptotic signals influences effector function in the immune system, we studied the X-linked inhibitor of apoptosis (XIAP), an endogenous regulator of cellular apoptosis. Real-time PCR showed increased XIAP expression in blood of mice...... dramatically reduced within the CNS. Flow cytometry showed an 88-93% reduction in T cells. The proportion of TUNEL(+) apoptotic CD4(+) T cells in the CNS was increased from Neurons...... and oligodendrocytes were not affected; neither did apoptosis increase in liver, where XIAP knockdown also occurred. ASO-XIAP increased susceptibility of T cells to activation-induced apoptosis in vitro. Our results identify XIAP as a critical controller of apoptotic susceptibility of effector T cell function...

A Plant Immune Receptor Detects Pathogen Effectors that Target WRKY Transcription Factors.

Science.gov (United States)

Sarris, Panagiotis F; Duxbury, Zane; Huh, Sung Un; Ma, Yan; Segonzac, Cécile; Sklenar, Jan; Derbyshire, Paul; Cevik, Volkan; Rallapalli, Ghanasyam; Saucet, Simon B; Wirthmueller, Lennart; Menke, Frank L H; Sohn, Kee Hoon; Jones, Jonathan D G

2015-05-21

Defense against pathogens in multicellular eukaryotes depends on intracellular immune receptors, yet surveillance by these receptors is poorly understood. Several plant nucleotide-binding, leucine-rich repeat (NB-LRR) immune receptors carry fusions with other protein domains. The Arabidopsis RRS1-R NB-LRR protein carries a C-terminal WRKY DNA binding domain and forms a receptor complex with RPS4, another NB-LRR protein. This complex detects the bacterial effectors AvrRps4 or PopP2 and then activates defense. Both bacterial proteins interact with the RRS1 WRKY domain, and PopP2 acetylates lysines to block DNA binding. PopP2 and AvrRps4 interact with other WRKY domain-containing proteins, suggesting these effectors interfere with WRKY transcription factor-dependent defense, and RPS4/RRS1 has integrated a "decoy" domain that enables detection of effectors that target WRKY proteins. We propose that NB-LRR receptor pairs, one member of which carries an additional protein domain, enable perception of pathogen effectors whose function is to target that domain. Copyright © 2015 Elsevier Inc. All rights reserved.

Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection.

Directory of Open Access Journals (Sweden)

Eva Rothmeier

2013-09-01

Full Text Available The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS to form in phagocytes a distinct "Legionella-containing vacuole" (LCV, which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed the presence of the small GTPase Ran and its effector RanBP1 on purified LCVs. Here we validate that Ran and RanBP1 localize to LCVs and promote intracellular growth of L. pneumophila. Moreover, the L. pneumophila protein LegG1, which contains putative RCC1 Ran guanine nucleotide exchange factor (GEF domains, accumulates on LCVs in an Icm/Dot-dependent manner. L. pneumophila wild-type bacteria, but not strains lacking LegG1 or a functional Icm/Dot T4SS, activate Ran on LCVs, while purified LegG1 produces active Ran(GTP in cell lysates. L. pneumophila lacking legG1 is compromised for intracellular growth in macrophages and amoebae, yet is as cytotoxic as the wild-type strain. A downstream effect of LegG1 is to stabilize microtubules, as revealed by conventional and stimulated emission depletion (STED fluorescence microscopy, subcellular fractionation and Western blot, or by microbial microinjection through the T3SS of a Yersinia strain lacking endogenous effectors. Real-time fluorescence imaging indicates that LCVs harboring wild-type L. pneumophila rapidly move along microtubules, while LCVs harboring ΔlegG1 mutant bacteria are stalled. Together, our results demonstrate that Ran activation and RanBP1 promote LCV formation, and the Icm/Dot substrate LegG1 functions as a bacterial Ran activator, which localizes to LCVs and promotes microtubule stabilization, LCV motility as well as intracellular replication of L. pneumophila.

Activation of Ran GTPase by a Legionella Effector Promotes Microtubule Polymerization, Pathogen Vacuole Motility and Infection

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Rothmeier, Eva; Pfaffinger, Gudrun; Hoffmann, Christine; Harrison, Christopher F.; Grabmayr, Heinrich; Repnik, Urska; Hannemann, Mandy; Wölke, Stefan; Bausch, Andreas; Griffiths, Gareth; Müller-Taubenberger, Annette; Itzen, Aymelt; Hilbi, Hubert

2013-01-01

The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS) to form in phagocytes a distinct “Legionella-containing vacuole” (LCV), which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed the presence of the small GTPase Ran and its effector RanBP1 on purified LCVs. Here we validate that Ran and RanBP1 localize to LCVs and promote intracellular growth of L. pneumophila. Moreover, the L. pneumophila protein LegG1, which contains putative RCC1 Ran guanine nucleotide exchange factor (GEF) domains, accumulates on LCVs in an Icm/Dot-dependent manner. L. pneumophila wild-type bacteria, but not strains lacking LegG1 or a functional Icm/Dot T4SS, activate Ran on LCVs, while purified LegG1 produces active Ran(GTP) in cell lysates. L. pneumophila lacking legG1 is compromised for intracellular growth in macrophages and amoebae, yet is as cytotoxic as the wild-type strain. A downstream effect of LegG1 is to stabilize microtubules, as revealed by conventional and stimulated emission depletion (STED) fluorescence microscopy, subcellular fractionation and Western blot, or by microbial microinjection through the T3SS of a Yersinia strain lacking endogenous effectors. Real-time fluorescence imaging indicates that LCVs harboring wild-type L. pneumophila rapidly move along microtubules, while LCVs harboring ΔlegG1 mutant bacteria are stalled. Together, our results demonstrate that Ran activation and RanBP1 promote LCV formation, and the Icm/Dot substrate LegG1 functions as a bacterial Ran activator, which localizes to LCVs and promotes microtubule stabilization, LCV motility as well as intracellular replication of L. pneumophila. PMID:24068924

An Aphid Effector Targets Trafficking Protein VPS52 in a Host-Specific Manner to Promote Virulence.

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Rodriguez, Patricia A; Escudero-Martinez, Carmen; Bos, Jorunn I B

2017-03-01

Plant- and animal-feeding insects secrete saliva inside their hosts, containing effectors, which may promote nutrient release and suppress immunity. Although for plant pathogenic microbes it is well established that effectors target host proteins to modulate host cell processes and promote disease, the host cell targets of herbivorous insects remain elusive. Here, we show that the existing plant pathogenic microbe effector paradigm can be extended to herbivorous insects in that effector-target interactions inside host cells modify critical host processes to promote plant susceptibility. We showed that the effector Mp1 from Myzus persicae associates with the host Vacuolar Protein Sorting Associated Protein52 (VPS52). Using natural variants, we provide a strong link between effector virulence activity and association with VPS52, and show that the association is highly specific to M persicae -host interactions. Also, coexpression of Mp1, but not Mp1-like variants, specifically with host VPS52s resulted in effector relocalization to vesicle-like structures that associate with prevacuolar compartments. We show that high VPS52 levels negatively impact virulence, and that aphids are able to reduce VPS52 levels during infestation, indicating that VPS52 is an important virulence target. Our work is an important step forward in understanding, at the molecular level, how a major agricultural pest promotes susceptibility during infestation of crop plants. We give evidence that an herbivorous insect employs effectors that interact with host proteins as part of an effective virulence strategy, and that these effectors likely function in a species-specific manner. © 2017 American Society of Plant Biologists. All Rights Reserved.

Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis.

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Abdelsamed, Hossam A; Moustaki, Ardiana; Fan, Yiping; Dogra, Pranay; Ghoneim, Hazem E; Zebley, Caitlin C; Triplett, Brandon M; Sekaly, Rafick-Pierre; Youngblood, Ben

2017-06-05

Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell-mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (T EM ), and longer-lived central memory (T CM ) and stem cell memory (T SCM ) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7- and IL-15-mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of T CM and T SCM memory cells resulted in phenotypic conversion into T EM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired T EM -associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells. © 2017 Abdelsamed et al.

Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted).

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Ark, B; Gummere, G; Bennett, D; Artzt, K

1991-06-01

Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses. Pim-1 was previously mapped to chromosome 17 by somatic cell hybrids, and subsequently to the region between the hemoglobin alpha-chain pseudogene 4 (Hba-4ps) and the alpha-crystalline gene (Crya-1) by Southern blot analysis of DNA obtained from panels of recombinant inbred strains. We have now mapped Pim-1 more accurately in t-haplotypes by analysis of recombinant t-chromosomes. The recombinants were derived from Tts6tf/t12 parents backcrossed to + tf/ + tf, and scored for recombination between the loci of T and tf. For simplicity all t-complex lethal genes properly named tcl-tx are shortened to tx. The Pim-1 gene was localized 0.6 cM proximal to the tw12 lethal gene, thus placing the Pim-1 gene 5.2 cM distal to the H-2 region in t-haplotypes. Once mapped, the Pim-1 gene was used as a marker for further genetic analysis of t-haplotypes. tw12 is so close to tf that even with a large number of recombinants it was not possible to determine whether it is proximal or distal to tf. Southern blot analysis of DNA from T-tf recombinants with a separation of tw12 and tf indicated that tw12 is proximal to tf. The mapping of two allelic t-lethals, t0 and t6 with respect to tw12 and tf has also been a problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification, structure, and function of a novel type VI secretion peptidoglycan glycoside hydrolase effector-immunity pair.

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Whitney, John C; Chou, Seemay; Russell, Alistair B; Biboy, Jacob; Gardiner, Taylor E; Ferrin, Michael A; Brittnacher, Mitchell; Vollmer, Waldemar; Mougous, Joseph D

2013-09-13

Bacteria employ type VI secretion systems (T6SSs) to facilitate interactions with prokaryotic and eukaryotic cells. Despite the widespread identification of T6SSs among Gram-negative bacteria, the number of experimentally validated substrate effector proteins mediating these interactions remains small. Here, employing an informatics approach, we define novel families of T6S peptidoglycan glycoside hydrolase effectors. Consistent with the known intercellular self-intoxication exhibited by the T6S pathway, we observe that each effector gene is located adjacent to a hypothetical open reading frame encoding a putative periplasmically localized immunity determinant. To validate our sequence-based approach, we functionally investigate a representative family member from the soil-dwelling bacterium Pseudomonas protegens. We demonstrate that this protein is secreted in a T6SS-dependent manner and that it confers a fitness advantage in growth competition assays with Pseudomonas putida. In addition, we determined the 1.4 Å x-ray crystal structure of this effector in complex with its cognate immunity protein. The structure reveals the effector shares highest overall structural similarity to a glycoside hydrolase family associated with peptidoglycan N-acetylglucosaminidase activity, suggesting that T6S peptidoglycan glycoside hydrolase effector families may comprise significant enzymatic diversity. Our structural analyses also demonstrate that self-intoxication is prevented by the immunity protein through direct occlusion of the effector active site. This work significantly expands our current understanding of T6S effector diversity.

Identification, Structure, and Function of a Novel Type VI Secretion Peptidoglycan Glycoside Hydrolase Effector-Immunity Pair*

Science.gov (United States)

Whitney, John C.; Chou, Seemay; Russell, Alistair B.; Biboy, Jacob; Gardiner, Taylor E.; Ferrin, Michael A.; Brittnacher, Mitchell; Vollmer, Waldemar; Mougous, Joseph D.

2013-01-01

Bacteria employ type VI secretion systems (T6SSs) to facilitate interactions with prokaryotic and eukaryotic cells. Despite the widespread identification of T6SSs among Gram-negative bacteria, the number of experimentally validated substrate effector proteins mediating these interactions remains small. Here, employing an informatics approach, we define novel families of T6S peptidoglycan glycoside hydrolase effectors. Consistent with the known intercellular self-intoxication exhibited by the T6S pathway, we observe that each effector gene is located adjacent to a hypothetical open reading frame encoding a putative periplasmically localized immunity determinant. To validate our sequence-based approach, we functionally investigate a representative family member from the soil-dwelling bacterium Pseudomonas protegens. We demonstrate that this protein is secreted in a T6SS-dependent manner and that it confers a fitness advantage in growth competition assays with Pseudomonas putida. In addition, we determined the 1.4 Å x-ray crystal structure of this effector in complex with its cognate immunity protein. The structure reveals the effector shares highest overall structural similarity to a glycoside hydrolase family associated with peptidoglycan N-acetylglucosaminidase activity, suggesting that T6S peptidoglycan glycoside hydrolase effector families may comprise significant enzymatic diversity. Our structural analyses also demonstrate that self-intoxication is prevented by the immunity protein through direct occlusion of the effector active site. This work significantly expands our current understanding of T6S effector diversity. PMID:23878199

Avaliação do kit "TF-Test" para o diagnóstico das infecções por parasitas gastrintestinais em ovinos

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Giuliano Lumina

2006-08-01

Full Text Available Este estudo teve como objetivos padronizar o kit TF-Test para a quantificação de ovos de parasitas gastrintestinais de ovinos e compará-lo ao método de Gordon & Whitlock modificado (G&W. Vinte quatro cordeiros confinados foram infectados artificialmente com Haemonchus contortus, durante 12 semanas, até o abate, quando foram colhidas amostras fecais e realizada a identificação e contagem dos parasitas abomasais. Nestes animais, ovos de H. contortus foram detectados em 95,8% das amostras fecais por ambos os testes (P>;0,05. Os coeficientes de correlação (r entre a carga parasitária (CP e os valores de OPG obtidos pelos métodos de G&W e TF-Test foram, respectivamente, de r=0,52 e r=0,51 (dados não transformados e r=0,85 e r=0,87 (dados transformados em log. Outras 100 amostras fecais foram colhidas de ovinos naturalmente infectados. Nas amostras destes animais, os testes G&W e TF-Test propiciaram o diagnóstico de ovos de estrongilídeos em 85% e 86% das amostras, respectivamente (P>;0,05. Pelo TF-Test e pelo G&W, oocistos de Eimeria foram detectados em 33% e em 12% das amostras (P<0,001 e ovos de Strongyloides spp. em 15% e 5% das amostras, respectivamente (P<0,05. Ambos os testes foram precisos para o diagnóstico de estrongilídeos gastrintestinais, porém, o TF-Test foi superior para o diagnóstico de oocistos de Eimeria spp. e de ovos de Strongyloides spp., mas, por outro lado, subestimou o número de ovos de estrongilídeos presente nas amostras.

Intrinsic disorder in pathogen effectors: protein flexibility as an evolutionary hallmark in a molecular arms race.

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Marín, Macarena; Uversky, Vladimir N; Ott, Thomas

2013-09-01

Effector proteins represent a refined mechanism of bacterial pathogens to overcome plants' innate immune systems. These modular proteins often manipulate host physiology by directly interfering with immune signaling of plant cells. Even if host cells have developed efficient strategies to perceive the presence of pathogenic microbes and to recognize intracellular effector activity, it remains an open question why only few effectors are recognized directly by plant resistance proteins. Based on in-silico genome-wide surveys and a reevaluation of published structural data, we estimated that bacterial effectors of phytopathogens are highly enriched in long-disordered regions (>50 residues). These structurally flexible segments have no secondary structure under physiological conditions but can fold in a stimulus-dependent manner (e.g., during protein-protein interactions). The high abundance of intrinsic disorder in effectors strongly suggests positive evolutionary selection of this structural feature and highlights the dynamic nature of these proteins. We postulate that such structural flexibility may be essential for (1) effector translocation, (2) evasion of the innate immune system, and (3) host function mimicry. The study of these dynamical regions will greatly complement current structural approaches to understand the molecular mechanisms of these proteins and may help in the prediction of new effectors.

Effector Regulatory T Cell Differentiation and Immune Homeostasis Depend on the Transcription Factor Myb.

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Dias, Sheila; D'Amico, Angela; Cretney, Erika; Liao, Yang; Tellier, Julie; Bruggeman, Christine; Almeida, Francisca F; Leahy, Jamie; Belz, Gabrielle T; Smyth, Gordon K; Shi, Wei; Nutt, Stephen L

2017-01-17

FoxP3-expressing regulatory T (Treg) cells are essential for maintaining immune homeostasis. Activated Treg cells undergo further differentiation into an effector state that highly expresses genes critical for Treg cell function, although how this process is coordinated on a transcriptional level is poorly understood. Here, we demonstrate that mice lacking the transcription factor Myb in Treg cells succumbed to a multi-organ inflammatory disease. Myb was specifically expressed in, and required for the differentiation of, thymus-derived effector Treg cells. The combination of transcriptome and genomic footprint analyses revealed that Myb directly regulated a large proportion of the gene expression specific to effector Treg cells, identifying Myb as a critical component of the gene regulatory network controlling effector Treg cell differentiation and function. Copyright © 2017 Elsevier Inc. All rights reserved.

Improvements to the COBRA-TF (EPRI) computer code for steam generator analysis. Final report

International Nuclear Information System (INIS)

Stewart, C.W.; Barnhart, J.S.; Koontz, A.S.

1980-09-01

The COBRA-TF (EPRI) code has been improved and extended for pressurized water reactor steam generator analysis. New features and models have been added in the areas of subcooled boiling and heat transfer, turbulence, numerics, and global steam generator modeling. The code's new capabilities are qualified against selected experimental data and demonstrated for typical global and microscale steam generator analysis

Exact positioning of the robotic arm end effector

Science.gov (United States)

Korepanov, Valery; Dudkin, Fedir

2016-07-01

Orbital service becomes a new challenge of space exploration. The necessity to introduce it is connected first of all with an attractive opportunity to prolong the exploitation terms of expensive commercial satellites by, e.g., refilling of fuel or changing batteries. Other application area is a fight with permanently increasing amount of space litter - defunct satellites, burnt-out rocket stages, discarded trash and other debris. Now more than few tens of thousands orbiting objects larger than 5-10 cm (or about 1 million junks larger than 1 cm) are a huge problem for crucial and costly satellites and manned vehicles. For example, in 2014 the International Space Station had to change three times its orbit to avoid collision with space debris. So the development of the concepts and actions related to removal of space debris or non-operational satellites with use of robotic arm of a servicing satellite is very actual. Such a technology is also applicable for unmanned exploratory missions in solar system, for example for collecting a variety of samples from a celestial body surface. Naturally, the robotic arm movements should be controlled with great accuracy at influence of its non-rigidity, thermal and other factors. In these circumstances often the position of the arm end effector has to be controlled with high accuracy. The possibility of coordinate determination for the robotic arm end effector with use of a low frequency active electromagnetic system has been considered in the presented report. The proposed design of such a system consists of a small magnetic dipole source, which is mounted inside of the arm end effector and two or three 3-component magnetic field sensors mounted on a servicing satellite body. The data from this set of 3-component magnetic field sensors, which are fixed relatively to the satellite body, allows use of the mathematical approach for determination of position and orientation of the magnetic dipole source. The theoretical

Chloroplastic protein NRIP1 mediates innate immune receptor recognition of a viral effector

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Caplan, Jeffrey L.; Mamillapalli, Padmavathi; Burch-Smith, Tessa M.; Czymmek, Kirk; Dinesh-Kumar, S.P.

2008-01-01

Summary Plant innate immunity relies on the recognition of pathogen effector molecules by nucleotide-binding-leucine-rich repeat (NB-LRR) immune receptor families. Previously we have shown the N immune receptor, a member of TIR-NB-LRR family, indirectly recognizes the 50-kDa helicase (p50) domain of Tobacco mosaic virus (TMV) through its TIR domain. We have identified an N receptor-interacting protein, NRIP1, that directly interacts with both N's TIR domain and p50. NRIP1 is a functional rhodanese sulfurtransferase and is required for N to provide complete resistance to TMV. Interestingly, NRIP1 that normally localizes to the chloroplasts is recruited to the cytoplasm and nucleus by the p50 effector. As a consequence, NRIP1 interacts with N only in the presence of the p50 effector. Our findings show that a chloroplastic protein is intimately involved in pathogen recognition. We propose that N's activation requires a pre-recognition complex containing the p50 effector and NRIP1. PMID:18267075

Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement

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Seung-Hye Lee

2016-08-01

Full Text Available The spread of tau pathology correlates with cognitive decline in Alzheimer’s disease. In vitro, tau antibodies can block cell-to-cell tau spreading. Although mechanisms of anti-tau function in vivo are unknown, effector function might promote microglia-mediated clearance. In this study, we investigated whether antibody effector function is required for targeting tau. We compared efficacy in vivo and in vitro of two versions of the same tau antibody, with and without effector function, measuring tau pathology, neuron health, and microglial function. Both antibodies reduced accumulation of tau pathology in Tau-P301L transgenic mice and protected cultured neurons against extracellular tau-induced toxicity. Only the full-effector antibody enhanced tau uptake in cultured microglia, which promoted release of proinflammatory cytokines. In neuron-microglia co-cultures, only effectorless anti-tau protected neurons, suggesting full-effector tau antibodies can induce indirect toxicity via microglia. We conclude that effector function is not required for efficacy, and effectorless tau antibodies may represent a safer approach to targeting tau.

Stability of [MeBu{sub 3}N][Tf{sub 2}N] under gamma irradiation

Energy Technology Data Exchange (ETDEWEB)

Bosse, Emilie; Berthon, Laurence; Zorz, Nicole; Monget, Julie; Berthon, Claude; Bisel, Isabelle; Legand, Solene; Moisy, Philippe [CEA Marcoule, DCRP/SCPS, BP 17171, 30207 Bagnols sur Ceze Cedex (France)

2008-07-01

The stability of the ionic liquid [MeBu{sub 3}N][Tf{sub 2}N], dry or after contact with water (where [MeBu{sub 3}N]{sup +} is the methyl-tributyl-ammonium cation and [Tf{sub 2}N]{sup -} is the bistriflimide anion), was studied under {sup 137}Cs gamma irradiation in argon and in air. In a quantitative study with an absorbed dose of 2 MGy this ionic liquid was highly stable regardless of the radiolysis conditions. The radiolytic disappearance yields determined by ESI-MS were -0.38 and -0.25 {mu}mol*J{sup -1} for the cation and anion, respectively. ESI-MS, NMR, and liquid chromatography coupled with ESI-MS identified a large number of degradation products in very small quantities for the same dose. The cation radicals were formed by the loss of a Bu{sup .} group, the Me{sup .} group, or two H{sup .} atoms to form a double bond with the butyl chain. Radiolysis of the anion produced mainly F{sup .} and CF{sub 3}{sup .} radicals. The anion radicals recombined with the cation to form a wide range of secondary degradation products regardless of the radiolysis conditions. (authors)

Effector gene birth in plant parasitic nematodes: Neofunctionalization of a housekeeping glutathione synthetase gene

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Lilley, Catherine J.; Maqbool, Abbas; Wu, Duqing; Yusup, Hazijah B.; Jones, Laura M.; Birch, Paul R. J.; Urwin, Peter E.

2018-01-01

Plant pathogens and parasites are a major threat to global food security. Plant parasitism has arisen four times independently within the phylum Nematoda, resulting in at least one parasite of every major food crop in the world. Some species within the most economically important order (Tylenchida) secrete proteins termed effectors into their host during infection to re-programme host development and immunity. The precise detail of how nematodes evolve new effectors is not clear. Here we reconstruct the evolutionary history of a novel effector gene family. We show that during the evolution of plant parasitism in the Tylenchida, the housekeeping glutathione synthetase (GS) gene was extensively replicated. New GS paralogues acquired multiple dorsal gland promoter elements, altered spatial expression to the secretory dorsal gland, altered temporal expression to primarily parasitic stages, and gained a signal peptide for secretion. The gene products are delivered into the host plant cell during infection, giving rise to “GS-like effectors”. Remarkably, by solving the structure of GS-like effectors we show that during this process they have also diversified in biochemical activity, and likely represent the founding members of a novel class of GS-like enzyme. Our results demonstrate the re-purposing of an endogenous housekeeping gene to form a family of effectors with modified functions. We anticipate that our discovery will be a blueprint to understand the evolution of other plant-parasitic nematode effectors, and the foundation to uncover a novel enzymatic function. PMID:29641602

Subversion of the Endocytic and Secretory Pathways by Bacterial Effector Proteins

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Mary M. Weber

2018-01-01

Full Text Available Intracellular bacteria have developed numerous strategies to hijack host vesicular trafficking pathways to form their unique replicative niches. To promote intracellular replication, the bacteria must interact with host organelles and modulate host signaling pathways to acquire nutrients and membrane for the growing parasitophorous vacuole all while suppressing activation of the immune response. To facilitate host cell subversion, bacterial pathogens use specialized secretion systems to deliver bacterial virulence factors, termed effectors, into the host cell that mimic, agonize, and/or antagonize the function of host proteins. In this review we will discuss how bacterial effector proteins from Coxiella burnetii, Brucella abortus, Salmonella enterica serovar Typhimurium, Legionella pneumophila, Chlamydia trachomatis, and Orientia tsutsugamushi manipulate the endocytic and secretory pathways. Understanding how bacterial effector proteins manipulate host processes not only gives us keen insight into bacterial pathogenesis, but also enhances our understanding of how eukaryotic membrane trafficking is regulated.

Structural basis for sequence-specific recognition of DNA by TAL effectors

KAUST Repository

Deng, Dong

2012-01-05

TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats. Each repeat comprises 33 to 35 conserved amino acids and targets a specific base pair by using two hypervariable residues [known as repeat variable diresidues (RVDs)] at positions 12 and 13. Here, we report the crystal structures of an 11.5-repeat TAL effector in both DNA-free and DNA-bound states. Each TAL repeat comprises two helices connected by a short RVD-containing loop. The 11.5 repeats form a right-handed, superhelical structure that tracks along the sense strand of DNA duplex, with RVDs contacting the major groove. The 12th residue stabilizes the RVD loop, whereas the 13th residue makes a base-specific contact. Understanding DNA recognition by TAL effectors may facilitate rational design of DNA-binding proteins with biotechnological applications.

Engineering, Manufacture and Preliminary Testing of the ITER Toroidal Field (TF) Magnet Helium Cold Circulator

Science.gov (United States)

Rista, P. E. C.; Shull, J.; Sargent, S.

2015-12-01

The ITER cryodistribution system provides the supercritical Helium (SHe) forced flow cooling to the magnet system using cold circulators. The cold circulators are located in each of five separate auxiliary cold boxes planned for use in the facility. Barber-Nichols Inc. has been awarded a contract from ITER-India for engineering, manufacture and testing of the Toroidal Field (TF) Magnet Helium Cold Circulator. The cold circulator will be extensively tested at Barber-Nichols’ facility prior to delivery for qualification testing at the Japan Atomic Energy Agency's (JAEA) test facility at Naka, Japan. The TF Cold Circulator integrates features and technical requirements which Barber-Nichols has utilized when supplying helium cold circulators worldwide over a period of 35 years. Features include a vacuum-jacketed hermetically sealed design with a very low helium leak rate, a heat shield for use with both nitrogen & helium cold sources, a broad operating range with a guaranteed isentropic efficiency over 70%, and impeller design features for high efficiency. The cold circulator will be designed to meet MTBM of 17,500 hours and MTBF of 36,000 hours. Vibration and speed monitoring are integrated into a compact package on the rotating assembly with operation and health monitoring in a multi-drop PROFIBUS communication environment using an electrical cabinet with critical features and full local and network PLC interface and control. For the testing in Japan and eventual installation in Europe, the cold circulator must be certified to the Japanese High Pressure Gas Safety Act (JHPGSA) and CE marked in compliance with the European Pressure Equipment Directive (PED) including Essential Safety Requirements (ESR). The test methodology utilized at Barber-Nichols’ facility and the resulting test data, validating the high efficiency of the TF Cold Circulator across a broad operating range, are important features of this paper.

Engineering, Manufacture and Preliminary Testing of the ITER Toroidal Field (TF) Magnet Helium Cold Circulator

International Nuclear Information System (INIS)

C Rista, P E; Shull, J; Sargent, S

2015-01-01

The ITER cryodistribution system provides the supercritical Helium (SHe) forced flow cooling to the magnet system using cold circulators. The cold circulators are located in each of five separate auxiliary cold boxes planned for use in the facility. Barber-Nichols Inc. has been awarded a contract from ITER-India for engineering, manufacture and testing of the Toroidal Field (TF) Magnet Helium Cold Circulator. The cold circulator will be extensively tested at Barber-Nichols’ facility prior to delivery for qualification testing at the Japan Atomic Energy Agency's (JAEA) test facility at Naka, Japan. The TF Cold Circulator integrates features and technical requirements which Barber-Nichols has utilized when supplying helium cold circulators worldwide over a period of 35 years. Features include a vacuum-jacketed hermetically sealed design with a very low helium leak rate, a heat shield for use with both nitrogen and helium cold sources, a broad operating range with a guaranteed isentropic efficiency over 70%, and impeller design features for high efficiency. The cold circulator will be designed to meet MTBM of 17,500 hours and MTBF of 36,000 hours. Vibration and speed monitoring are integrated into a compact package on the rotating assembly with operation and health monitoring in a multi-drop PROFIBUS communication environment using an electrical cabinet with critical features and full local and network PLC interface and control. For the testing in Japan and eventual installation in Europe, the cold circulator must be certified to the Japanese High Pressure Gas Safety Act (JHPGSA) and CE marked in compliance with the European Pressure Equipment Directive (PED) including Essential Safety Requirements (ESR). The test methodology utilized at Barber-Nichols’ facility and the resulting test data, validating the high efficiency of the TF Cold Circulator across a broad operating range, are important features of this paper. (paper)

Brucella Modulates Secretory Trafficking via Multiple Type IV Secretion Effector Proteins

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Myeni, Sebenzile; Child, Robert; Ng, Tony W.; Kupko, John J.; Wehrly, Tara D.; Porcella, Stephen F.; Knodler, Leigh A.; Celli, Jean

2013-01-01

The intracellular pathogenic bacterium Brucella generates a replicative vacuole (rBCV) derived from the endoplasmic reticulum via subversion of the host cell secretory pathway. rBCV biogenesis requires the expression of the Type IV secretion system (T4SS) VirB, which is thought to translocate effector proteins that modulate membrane trafficking along the endocytic and secretory pathways. To date, only a few T4SS substrates have been identified, whose molecular functions remain unknown. Here, we used an in silico screen to identify putative T4SS effector candidate proteins using criteria such as limited homology in other bacterial genera, the presence of features similar to known VirB T4SS effectors, GC content and presence of eukaryotic-like motifs. Using β-lactamase and CyaA adenylate cyclase reporter assays, we identified eleven proteins translocated into host cells by Brucella, five in a VirB T4SS-dependent manner, namely BAB1_0678 (BspA), BAB1_0712 (BspB), BAB1_0847 (BspC), BAB1_1671 (BspE) and BAB1_1948 (BspF). A subset of the translocated proteins targeted secretory pathway compartments when ectopically expressed in HeLa cells, and the VirB effectors BspA, BspB and BspF inhibited protein secretion. Brucella infection also impaired host protein secretion in a process requiring BspA, BspB and BspF. Single or combined deletions of bspA, bspB and bspF affected Brucella ability to replicate in macrophages and persist in the liver of infected mice. Taken together, these findings demonstrate that Brucella modulates secretory trafficking via multiple T4SS effector proteins that likely act coordinately to promote Brucella pathogenesis. PMID:23950720

Opioid and GABAB receptors differentially couple to an adenylyl cyclase/protein kinase A downstream effector after chronic morphine treatment.

Directory of Open Access Journals (Sweden)

Elena Elizabeth Bagley

2014-06-01

effector.

Parametric system studies of candidate TF coil system options for the Tokamak Fusion Core Experiment (TFCX)

International Nuclear Information System (INIS)

Reiersen, W.T.; Flanagan, C.A.; Miller, J.B.

1983-01-01

System studies were performed to determine the sensitivity of hybrid and superconducting toroidal field (TF) coil system options to maximum field at the TF coil and to field enhancement due to resistive insert coils. The studies were performed using Tokamak Fusion Core Experiment (TFCX) design assumptions, guidelines, and criteria and involved iterative execution of the Fusion Engineering Design Center (FEDC) systems code, magnetohydrodynamics (MHD) equilibrium code, and EFFI (a code to evaluate magnetic field strength). The results indicate that for TFCX with no minimum wall loading specified, a design point chosen solely on the basis of cost would likely be in the low-field region of design space where the cost advantage of hybrids is least apparent. However, as the desired neutron wall loading increases, the hybrid option suggests an increasing cost advantage over the all-superconducting option; this cost advantage is countered by increased complexity in design -- particularly in assembly and maintenance

Parametric system studies of candidate TF coil system options for the Tokamak Fusion Core Experiment (TFCX)

International Nuclear Information System (INIS)

Reiersen, W.T.; Flanagan, C.A.; Miller, J.B.

1983-01-01

System studies were performed to determine the sensitivity of hybrid and superconducting toroidal field (TF) coil system options to maximum field at the TF coil and to field enhancement due to resistive insert coils. The studies were performed using Tokamak Fusion Core Experiment (TFCX) design assumptions, guidelines, and criteria and involved iterative execution of the Fusion Engineering Design Center (FEDC) systems code, magnetohydrodynamics (MHD) equilibrium code, and EFFI (a code to evaluate magnetic field strength). The results indicate that for TFCX with no minimum wall loading specified, a design point chosen solely on the basis of cost would likely be in the low-field region of design space where the cost advantage of hybrids is least apparent. However, as the desired neutron wall loading increases, the hybrid option suggests an increasing cost advantage over the all-superconducting option; this cost advantage is countered by increased complexity in design - particularly in assembly and maintenance

Analysis and tests of TF magnet insulation samples for the JET upgrade to 4 tesla

CERN Document Server

Miele, P; Bettinali, L; Kaye, A; Last, J; Papastergiou, S; Riccardo, V; Visca, E

2000-01-01

The JET Toroidal Field (TF) coils were originally designed for operation at 3.4 tesla. In order to upgrade the field to 4 tesla and thus improve the performance of the JET machine, new mechanical tests and analysis were carried out on the insulation of TF coil samples. They are aimed at investigating the mechanical properties and the status of the insulation in order to set allowable stresses and force limits. In particular since the shear stress in the insulation is strongly affected by the shear modulus of elasticity G, it is important to measure this parameter. A method for the measurement of G in glass-resin fibres, the V-notched beam method (Iosipescu method) , was applied. The particular shape of the rectangular Iosipescu V- notched sample and the particular modality of force application produce pure shear stress for a reliable measurement of the G value and of the shear strength of the insulation. The effect of temperature on these mechanical properties was also investigated. Results show higher averag...

Autoreactive T effector memory differentiation mirrors β-cell function in type 1 diabetes.

Science.gov (United States)

Yeo, Lorraine; Woodwyk, Alyssa; Sood, Sanjana; Lorenc, Anna; Eichmann, Martin; Pujol-Autonell, Irma; Melchiotti, Rossella; Skowera, Ania; Fidanis, Efthymios; Dolton, Garry M; Tungatt, Katie; Sewell, Andrew K; Heck, Susanne; Saxena, Alka; Beam, Craig A; Peakman, Mark

2018-05-31

In type 1 diabetes, cytotoxic CD8 T cells with specificity for β-cell autoantigens are found in the pancreatic islets where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β-cell-reactive CD8 T cells that are detectable in the circulation, and their relationship to β-cell function, are not known. Here, we tracked multiple, circulating β-cell-reactive CD8 T cell subsets and measured β-cell function longitudinally for two years, starting immediately after diagnosis of type 1 diabetes. We found that change in β-cell-specific effector memory CD8 T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8 T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer specific protein 37 and CD16, and reduced expression of CD28) compared with their CD57-negative counterparts, and network association modelling indicated that the dynamics of β-cell-reactive CD57+ effector memory CD8 T cell subsets were strongly linked. Thus, coordinated changes in circulating β-cell-specific CD8 T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.

Identification of antibody glycosylation structures that predict monoclonal antibody Fc-effector function.

Science.gov (United States)

Chung, Amy W; Crispin, Max; Pritchard, Laura; Robinson, Hannah; Gorny, Miroslaw K; Yu, Xiaojie; Bailey-Kellogg, Chris; Ackerman, Margaret E; Scanlan, Chris; Zolla-Pazner, Susan; Alter, Galit

2014-11-13

To determine monoclonal antibody (mAb) features that predict fragment crystalizable (Fc)-mediated effector functions against HIV. Monoclonal antibodies, derived from Chinese hamster ovary cells or Epstein-Barr virus-immortalized mouse heteromyelomas, with specificity to key regions of the HIV envelope including gp120-V2, gp120-V3 loop, gp120-CD4(+) binding site, and gp41-specific antibodies, were functionally profiled to determine the relative contribution of the variable and constant domain features of the antibodies in driving robust Fc-effector functions. Each mAb was assayed for antibody-binding affinity to gp140(SR162), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and for the ability to bind to FcγRIIa, FcγRIIb and FcγRIIIa receptors. Antibody glycan profiles were determined by HPLC. Neither the specificity nor the affinity of the mAbs determined the potency of Fc-effector function. FcγRIIIa binding strongly predicted ADCC and decreased galactose content inversely correlated with ADCP, whereas N-glycolylneuraminic acid-containing structures exhibited enhanced ADCP. Additionally, the bi-antenary glycan arm onto which galactose was added predicted enhanced binding to FcγRIIIa and ADCC activity, independent of the specificity of the mAb. Our studies point to the specific Fc-glycan structures that can selectively promote Fc-effector functions independently of the antibody specificity. Furthermore, we demonstrated antibody glycan structures associated with enhanced ADCP activity, an emerging Fc-effector function that may aid in the control and clearance of HIV infection.

High immunosuppressive burden in advanced hepatocellular carcinoma patients: Can effector functions be restored?

Science.gov (United States)

Lugade, Amit A; Kalathil, Suresh; Miller, Austin; Iyer, Renuka; Thanavala, Yasmin

2013-07-01

The accumulation of immunosuppressive cells and exhausted effector T cells highlight an important immune dysfunction in advanced stage hepatocellular carcinoma (HCC) patients. These cells significantly hamper the efficacy immunotherapies and facilitate HCC progression. We have recently demonstrated that the multipronged depletion of immunosuppressive cells potentially restores effector T-cell function in HCC.

Control of Delta Avulsion by Downstream Sediment Sinks

Science.gov (United States)

Salter, Gerard; Paola, Chris; Voller, Vaughan R.

2018-01-01

Understanding how fluxes are partitioned at delta bifurcations is critical for predicting patterns of land loss and gain in deltas worldwide. Although the dynamics of river deltas are influenced from both upstream and downstream, previous studies of bifurcations have focused on upstream controls. Using a quasi-1-D bifurcation model, we show that flow switching in bifurcations is strongly influenced by downstream sediment sinks. We find that coupling between upstream and downstream feedbacks can lead to oscillations in water and sediment flux partitioning. The frequency and initial rate of growth/decay of the oscillations depend on both upstream and downstream conditions, with dimensionless bifurcate length and bypass fraction emerging as key downstream parameters. With a strong offshore sink, causing bypass in the bifurcate branches, we find that bifurcation dynamics become "frozen"; that is, the bifurcation settles on a permanent discharge ratio. In contrast, under depositional conditions, we identify three dynamical regimes: symmetric; soft avulsion, where both branches remain open but the dominant branch switches; and full avulsion. Finally, we show that differential subsidence alters these regimes, with the difference in average sediment supply to each branch exactly compensating for the difference in accommodation generation. Additionally, the model predicts that bifurcations with shorter branches are less asymmetric than bifurcations with longer branches, all else equal, providing a possible explanation for the difference between backwater length distributaries, which tend to be avulsive, and relatively stable mouth-bar-scale networks. We conclude that bifurcations are sensitive both quantitatively and qualitatively to downstream sinks.

Electromagnetic and structural global model of the TF magnet system in ASDEX Upgrade

Energy Technology Data Exchange (ETDEWEB)

Zammuto, I., E-mail: irene.zammuto@ipp.mpg.de [Max-Planck-Institut für Plasmaphysik, EURATOM Association, D-85740 Garching (Germany); Streibl, B.; Giannone, L.; Herrmann, A.; Kallenbach, A.; Mertens, V. [Max-Planck-Institut für Plasmaphysik, EURATOM Association, D-85740 Garching (Germany)

2013-10-15

Highlights: ► An electromagnetic and structural FE 3D model is set up for ASDEX Upgrade. ► The model is benchmarked against the old design results, present displacement measurements. ► The benchmarked model is applied to the present plasma configurations, which have a different poloidal field distribution with respect to the design case. ► The different poloidal field influences the out-of-plane force distribution, thus requiring an update of the TF safety system. -- Abstract: The enhancements carried out in the tokamak ASDEX Upgrade (AUG) are oriented toward the preparation of the future physics-related activities of ITER and DEMO. To address the main ITER issues, plasma configurations with a wider operational limit (e.g. higher triangularity) are planned for the future experimental campaigns in AUG. To evaluate the mechanical impact on the toroidal field (TF) magnet system a combined electromagnetic and structural finite element model was set up. At first extensive benchmarks of the models are carried out against the AUG reference design configurations with respect to stress [1–3], lateral displacement measurements and poloidal flux pattern. The numerical model was then applied to a set of actual high triangularity (HT) configurations generated by a more favorable poloidal field (PF) current distribution made possible by an extension of the power supply system. The resulting change of the poloidal flux pattern and the lateral force distribution has consequences for the coil shear stress and vault stability. Both aspects are monitored by a safety system measuring the PF flux placed on top and bottom of the outer surface of two TF coils (TFCs) between vault and the TFC supporting structure, so called Turn Over Structure (TOS). The range of the new HT configurations has induced a modification of the flux pattern, so that an adaptation of safety system is required to protect the TFCs system. Following the same criteria of the old safety system [4,5], a new

The pore-forming bacterial effector, VopQ, halts autophagic turnover.

Science.gov (United States)

Sreelatha, Anju; Orth, Kim; Starai, Vincent J

2013-12-01

Vibrio parahemolyticus Type III effector VopQ is both necessary and sufficient to induce autophagy within one hour of infection. We demonstrated that VopQ interacts with the Vo domain of the conserved vacuolar H(+)-ATPase. Membrane-associated VopQ subsequently forms pores in the membranes of acidic compartments, resulting in immediate release of protons without concomitant release of lumenal protein contents. These studies show how a bacterial pathogen can compromise host ion potentials using a gated pore-forming effector to equilibrate levels of small molecules found in endolysosomal compartments and disrupt cellular processes such as autophagy.

Association study between four polymorphisms in the HFE, TF and TFR genes and Parkinson's disease in southern Italy.

Science.gov (United States)

Greco, Valentina; De Marco, Elvira Valeria; Rocca, Francesca Emanuela; Annesi, Ferdinanda; Civitelli, Donatella; Provenzano, Giovanni; Tarantino, Patrizia; Scornaienchi, Vittorio; Pucci, Franco; Salsone, Maria; Novellino, Fabiana; Morelli, Maurizio; Paglionico, Sandra; Gambardella, Antonio; Quattrone, Aldo; Annesi, Grazia

2011-06-01

Iron overload may lead to neurodegenerative disorders such as Parkinson's disease (PD) and alterations of iron-related genes might be involved in the pathogenesis of this disease. The gene of haemochromatosis (HFE) encodes the HFE protein which interacts with the transferrin receptor (TFR), lowering its affinity for iron-bound transferrin (TF). We examined four known polymorphisms, C282Y and H63D in the HFE gene, G258S in the TF gene and S82G in the TFR gene, in 181 sporadic PD patients and 180 controls from Southern Italy to investigate their possible role in susceptibility to PD. No significant differences were found in genotype and allele frequencies between PD and controls for all the polymorphisms studied, suggesting that these variants do not contribute significantly to the risk of PD.

Modulating Cytotoxic Effector Functions by Fc Engineering to Improve Cancer Therapy.

Science.gov (United States)

Kellner, Christian; Otte, Anna; Cappuzzello, Elisa; Klausz, Katja; Peipp, Matthias

2017-09-01

In the last two decades, monoclonal antibodies have revolutionized the therapy of cancer patients. Although antibody therapy has continuously been improved, still a significant number of patients do not benefit from antibody therapy. Therefore, rational optimization of the antibody molecule by Fc engineering represents a major area of translational research to further improve this potent therapeutic option. Monoclonal antibodies are able to trigger a variety of effector mechanisms. Especially Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement- dependent cytotoxicity (CDC) are considered important in antibody therapy of cancer. Novel mechanistic insights into the action of monoclonal antibodies allowed the development of various Fc engineering approaches to modulate antibodies' effector functions. Strategies in modifying the Fc glycosylation profile (Fc glyco-engineering) or approaches in engineering the protein backbone (Fc protein engineering) have been intensively evaluated. In the current review, Fc engineering strategies resulting in improved ADCC, ADCP and CDC activity are summarized and discussed.

Role of Rab family GTPases and their effectors in melanosomal logistics.

Science.gov (United States)

Ohbayashi, Norihiko; Fukuda, Mitsunori

2012-04-01

Rab GTPases constitute a family of small GTPases that regulate a variety of membrane trafficking events in all eukaryotic cells by recruiting their specific effector molecules. Recent accumulating evidence indicates that members of the mammalian Rab small GTPase family are involved in certain physiological and pathological processes. In particular, functional impairments of specific Rab proteins, e.g. Rab38 and Rab27A, their regulators or their effectors cause pigmentation disorders in humans and coat colour variations in mice because such impairments cause defects in melanosomal logistics, i.e. defects in melanosome biogenesis and transport. Genetic and biochemical analyses of the gene products responsible for mammalian pigmentation disorders in the past decade have revealed that Rab-mediated endosomal transport systems and melanosome transport systems play crucial roles in the efficient darkening of mammalian hair and skin. In this article, we review current knowledge regarding melanosomal logistics, with particular focus on the roles of Rab small GTPases and their effectors.

Conference on heat mass transfer and properties of liquid metals TF-2002

International Nuclear Information System (INIS)

Efanov, A.D.; Kozlov, F.A.

2003-01-01

Results of the conference TF-2002 devoted to the combined approach to problems of harnessing liquid metals as coolants for NPU are presented. The conference takes place in Obninsk, 29 - 31 October, 2002. Papers of the conference involve items on thermal hydraulics, mass transfer and safety of NPU with liquid metal coolants, structure, physical and chemical properties of liquid metal and liquid metal solutions, decommissioning of units and ecology, application of liquid metals divorced with NPU. Most of the papers of the conference are devoted to the investigation into lead and lead-bismuth coolants [ru

Cell volume homeostatic mechanisms: effectors and signalling pathways

DEFF Research Database (Denmark)

Hoffmann, E K; Pedersen, Stine Helene Falsig

2011-01-01

. Later work addressed the mechanisms through which cellular signalling pathways regulate the volume regulatory effectors or flux pathways. These studies were facilitated by the molecular identification of most of the relevant channels and transporters, and more recently also by the increased...

The Salmonella effector protein SpvC, a phosphothreonine lyase is functional in plant cells

Directory of Open Access Journals (Sweden)

Christina eNeumann

2014-10-01

Full Text Available Salmonella is one of the most prominent causes of food poisoning and growing evidence indicates that contaminated fruits and vegetables are an increasing concern for human health. Successful infection demands the suppression of the host immune system, which is often achieved via injection of bacterial effector proteins into host cells. In this report we present the function of Salmonella effector protein in plant cell, supporting the new concept of trans-kingdom competence of this bacterium. We screened a range of Salmonella Typhimurium effector proteins for interference with plant immunity. Among these, the phosphothreonine lyase SpvC attenuated the induction of immunity-related genes when present in plant cells. Using in vitro and in vivo systems we show that this effector protein interacts with and dephosphorylates activated Arabidopsis Mitogen-activated Protein Kinase 6 (MPK6, thereby inhibiting defense signaling. Moreover, the requirement of Salmonella SpvC was shown by the decreased proliferation of the ΔspvC mutant in Arabidopsis plants. These results suggest that some Salmonella effector proteins could have a conserved function during proliferation in different hosts. The fact that Salmonella and other Enterobacteriaceae use plants as hosts strongly suggests that plants represent a much larger reservoir for animal pathogens than so far estimated.

The Salmonella effector protein SpvC, a phosphothreonine lyase is functional in plant cells

KAUST Repository

Neumann, Christina

2014-10-17

Salmonella is one of the most prominent causes of food poisoning and growing evidence indicates that contaminated fruits and vegetables are an increasing concern for human health. Successful infection demands the suppression of the host immune system, which is often achieved via injection of bacterial effector proteins into host cells. In this report we present the function of Salmonella effector protein in plant cell, supporting the new concept of trans-kingdom competence of this bacterium. We screened a range of Salmonella Typhimurium effector proteins for interference with plant immunity. Among these, the phosphothreonine lyase SpvC attenuated the induction of immunity-related genes when present in plant cells. Using in vitro and in vivo systems we show that this effector protein interacts with and dephosphorylates activated Arabidopsis Mitogen-activated Protein Kinase 6 (MPK6), thereby inhibiting defense signaling. Moreover, the requirement of Salmonella SpvC was shown by the decreased proliferation of the ΔspvC mutant in Arabidopsis plants. These results suggest that some Salmonella effector proteins could have a conserved function during proliferation in different hosts. The fact that Salmonella and other Enterobacteriaceae use plants as hosts strongly suggests that plants represent a much larger reservoir for animal pathogens than so far estimated.

Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes.

Science.gov (United States)

Chaudhary, Natasha; Gonzalez, Eva; Chang, Sung-Hee; Geng, Fuqiang; Rafii, Shahin; Altorki, Nasser K; McGraw, Timothy E

2016-12-20

Insulin activation of phosphatidylinositol 3-kinase (PI3K) regulates metabolism, including the translocation of the Glut4 glucose transporter to the plasma membrane and inactivation of the FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth-factor activation of PI3K. We have used E4-ORF1 as a tool to dissect PI3K-mediated signaling in adipocytes. E4-ORF1 activation of PI3K in adipocytes recapitulates insulin regulation of FoxO1 but not regulation of Glut4. This uncoupling of PI3K effects occurs despite E4-ORF1 activating PI3K and downstream signaling to levels achieved by insulin. Although E4-ORF1 does not fully recapitulate insulin's effects on Glut4, it enhances insulin-stimulated insertion of Glut4-containing vesicles to the plasma membrane independent of Rab10, a key regulator of Glut4 trafficking. E4-ORF1 also stimulates plasma membrane translocation of ubiquitously expressed Glut1 glucose transporter, an effect that is likely essential for E4-ORF1 to promote an anabolic metabolism in a broad range of cell types. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes

Directory of Open Access Journals (Sweden)

Natasha Chaudhary

2016-12-01

Full Text Available Insulin activation of phosphatidylinositol 3-kinase (PI3K regulates metabolism, including the translocation of the Glut4 glucose transporter to the plasma membrane and inactivation of the FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth-factor activation of PI3K. We have used E4-ORF1 as a tool to dissect PI3K-mediated signaling in adipocytes. E4-ORF1 activation of PI3K in adipocytes recapitulates insulin regulation of FoxO1 but not regulation of Glut4. This uncoupling of PI3K effects occurs despite E4-ORF1 activating PI3K and downstream signaling to levels achieved by insulin. Although E4-ORF1 does not fully recapitulate insulin’s effects on Glut4, it enhances insulin-stimulated insertion of Glut4-containing vesicles to the plasma membrane independent of Rab10, a key regulator of Glut4 trafficking. E4-ORF1 also stimulates plasma membrane translocation of ubiquitously expressed Glut1 glucose transporter, an effect that is likely essential for E4-ORF1 to promote an anabolic metabolism in a broad range of cell types.

Actin Cytoskeleton Manipulation by Effector Proteins Secreted by Diarrheagenic Escherichia coli Pathotypes

Directory of Open Access Journals (Sweden)

Fernando Navarro-Garcia

2013-01-01

Full Text Available The actin cytoskeleton is a dynamic structure necessary for cell and tissue organization, including the maintenance of epithelial barriers. Disruption of the epithelial barrier coincides with alterations of the actin cytoskeleton in several disease states. These disruptions primarily affect the paracellular space, which is normally regulated by tight junctions. Thereby, the actin cytoskeleton is a common and recurring target of bacterial virulence factors. In order to manipulate the actin cytoskeleton, bacteria secrete and inject toxins and effectors to hijack the host cell machinery, which interferes with host-cell pathways and with a number of actin binding proteins. An interesting model to study actin manipulation by bacterial effectors is Escherichia coli since due to its genome plasticity it has acquired diverse genetic mobile elements, which allow having different E. coli varieties in one bacterial species. These E. coli pathotypes, including intracellular and extracellular bacteria, interact with epithelial cells, and their interactions depend on a specific combination of virulence factors. In this paper we focus on E. coli effectors that mimic host cell proteins to manipulate the actin cytoskeleton. The study of bacterial effector-cytoskeleton interaction will contribute not only to the comprehension of the molecular causes of infectious diseases but also to increase our knowledge of cell biology.

An Aphid Effector Targets Trafficking Protein VPS52 in a Host-Specific Manner to Promote Virulence1[OPEN

Science.gov (United States)

2017-01-01

Plant- and animal-feeding insects secrete saliva inside their hosts, containing effectors, which may promote nutrient release and suppress immunity. Although for plant pathogenic microbes it is well established that effectors target host proteins to modulate host cell processes and promote disease, the host cell targets of herbivorous insects remain elusive. Here, we show that the existing plant pathogenic microbe effector paradigm can be extended to herbivorous insects in that effector-target interactions inside host cells modify critical host processes to promote plant susceptibility. We showed that the effector Mp1 from Myzus persicae associates with the host Vacuolar Protein Sorting Associated Protein52 (VPS52). Using natural variants, we provide a strong link between effector virulence activity and association with VPS52, and show that the association is highly specific to M. persicae-host interactions. Also, coexpression of Mp1, but not Mp1-like variants, specifically with host VPS52s resulted in effector relocalization to vesicle-like structures that associate with prevacuolar compartments. We show that high VPS52 levels negatively impact virulence, and that aphids are able to reduce VPS52 levels during infestation, indicating that VPS52 is an important virulence target. Our work is an important step forward in understanding, at the molecular level, how a major agricultural pest promotes susceptibility during infestation of crop plants. We give evidence that an herbivorous insect employs effectors that interact with host proteins as part of an effective virulence strategy, and that these effectors likely function in a species-specific manner. PMID:28100451

Learning-based position control of a closed-kinematic chain robot end-effector

Science.gov (United States)

Nguyen, Charles C.; Zhou, Zhen-Lei

1990-01-01

A trajectory control scheme whose design is based on learning theory, for a six-degree-of-freedom (DOF) robot end-effector built to study robotic assembly of NASA hardwares in space is presented. The control scheme consists of two control systems: the feedback control system and the learning control system. The feedback control system is designed using the concept of linearization about a selected operating point, and the method of pole placement so that the closed-loop linearized system is stabilized. The learning control scheme consisting of PD-type learning controllers, provides additional inputs to improve the end-effector performance after each trial. Experimental studies performed on a 2 DOF end-effector built at CUA, for three tracking cases show that actual trajectories approach desired trajectories as the number of trials increases. The tracking errors are substantially reduced after only five trials.

GENIUS-TF - a test facility for the GENIUS project. Proposal

International Nuclear Information System (INIS)

Klapdor-Kleingrothaus, H.V.; Dietz, A.; Heusser, G.

2001-02-01

GENIUS is a proposal for a large scale detector of rare events. As a first step of the experiment, a small test version, the Genius Test-Facility is proposed to be built up at the Laboratori Nazionali del Gran Sasso (LNGS). With about 40 kg of natural Ge detectors operated in liquid nitrogen, Genius-TF could exclude (or directly confirm) the DAMA annual modulation signature within about two years of measurement using both, signal and signature of the claimed WIMP Dark matter. The funding of the experiment has already been approved and four 2.5 kg germanium detectors with an extreme low treshold of 500 eV have been produced. The installation can be started immediately. No additional space in the Underground Laboratory is required. (orig.)

Plant parasitic nematode effectors target host defence and nuclear functions to establish feeding cells

Directory of Open Access Journals (Sweden)

Michaël eQuentin

2013-03-01

Full Text Available Plant parasitic nematodes are microscopic worms, the most damaging species of which have adopted a sedentary lifestyle within their hosts. These obligate endoparasites have a biotrophic relationship with plants, in which they induce the differentiation of root cells into hypertrophied, multinucleate feeding cells. Effectors synthesised in the oesophageal glands of the nematode are injected into the plant cells via the syringe-like stylet and play a key role in manipulating the host machinery. The establishment of specialized feeding cells requires these effectors to modulate many aspects of plant cell morphogenesis and physiology, including defence responses. This cell reprogramming requires changes to host nuclear processes. Some proteins encoded by parasitism genes target host nuclei. Several of these proteins were immunolocalised within feeding cell nuclei or shown to interact with host nuclear proteins. Comparative genomics and functional analyses are gradually revealing the roles of nematode effectors. We describe here these effectors and their hypothesised roles in the unique feeding behaviour of these pests.

Bacterial effector HopF2 interacts with AvrPto and suppresses Arabidopsis innate immunity at the plasma membrane

Science.gov (United States)

Plant pathogenic bacteria inject a cocktail of effector proteins into host plant cells to modulate the host immune response, thereby promoting pathogenicity. How or whether these effectors work cooperatively is largely unknown. The Pseudomonas syringae DC3000 effector HopF2 suppresses the host plan...

Philippines' downstream sector poised for growth

International Nuclear Information System (INIS)

Anon.

1992-01-01

This paper reports that the Philippines' downstream sector is poised for sharp growth. Despite a slip in refined products demand in recent years, Philippines products demand will rebound sharply by 2000, East-West Center (EWC), Honolulu, predicts. Philippines planned refinery expansions are expected to meet that added demand, EWC Director Fereidun Fesharaki says. Like the rest of the Asia-Pacific region, product specifications are changing, but major refiners in the area expect to meet the changes without major case outlays. At the same time, Fesharaki says, push toward deregulation will further bolster the outlook for the Philippines downstream sector

Continuous downstream processing of biopharmaceuticals.

Science.gov (United States)

Jungbauer, Alois

2013-08-01

Continuous manufacturing has been applied in many different industries but has been pursued reluctantly in biotechnology where the batchwise process is still the standard. A shift to continuous operation can improve productivity of a process and substantially reduce the footprint. Continuous operation also allows robust purification of labile biomolecules. A full set of unit operations is available to design continuous downstream processing of biopharmaceuticals. Chromatography, the central unit operation, is most advanced in respect to continuous operation. Here, the problem of 'batch' definition has been solved. This has also paved the way for implementation of continuous downstream processing from a regulatory viewpoint. Economic pressure, flexibility, and parametric release considerations will be the driving force to implement continuous manufacturing strategies in future. Copyright © 2013 Elsevier Ltd. All rights reserved.

CXCR3 Directs Antigen-Specific Effector CD4+ T Cell Migration to the Lung During Parainfluenza Virus Infection

DEFF Research Database (Denmark)

Kohlmeier, Jacob E; Cookenham, Tres; Miller, Shannon C

2009-01-01

effector CD4(+) T cell migration to the lungs. To assess the role of CCR5 and CXCR3 in vivo, we directly compared the migration of Ag-specific wild-type and chemokine receptor-deficient effector T cells in mixed bone marrow chimeric mice during a parainfluenza virus infection. CXCR3-deficient effector CD4......(+) T cells were 5- to 10-fold less efficient at migrating to the lung compared with wild-type cells, whereas CCR5-deficient effector T cells were not impaired in their migration to the lung. In contrast to its role in trafficking, CXCR3 had no impact on effector CD4(+) T cell proliferation, phenotype......, or function in any of the tissues examined. These findings demonstrate that CXCR3 controls virus-specific effector CD4(+) T cell migration in vivo, and suggest that blocking CXCR3-mediated recruitment may limit T cell-induced immunopathology during respiratory virus infections....

Implementation of non-condensable gases condensation suppression model into the WCOBRA/TRAC-TF2 LOCA safety evaluation code

Energy Technology Data Exchange (ETDEWEB)

Liao, J.; Cao, L.; Ohkawa, K.; Frepoli, C. [LOCA Integrated Services I, Westinghouse Electric Company, 1000 Westinghouse Drive, Cranberry Township, PA 16066 (United States)

2012-07-01

The non-condensable gases condensation suppression model is important for a realistic LOCA safety analysis code. A condensation suppression model for direct contact condensation was previously developed by Westinghouse using first principles. The model is believed to be an accurate description of the direct contact condensation process in the presence of non-condensable gases. The Westinghouse condensation suppression model is further revised by applying a more physical model. The revised condensation suppression model is thus implemented into the WCOBRA/TRAC-TF2 LOCA safety evaluation code for both 3-D module (COBRA-TF) and 1-D module (TRAC-PF1). Parametric study using the revised Westinghouse condensation suppression model is conducted. Additionally, the performance of non-condensable gases condensation suppression model is examined in the ACHILLES (ISP-25) separate effects test and LOFT L2-5 (ISP-13) integral effects test. (authors)

A floating trap for sampling downstream migrant fishes.

Science.gov (United States)

Carl E. McLemore; Fred H. Everest; William R. Humphreys; Mario F. Solazzi

1989-01-01

Fishery scientists and managers are interested in obtaining information about downstream movements of fish species for biological and economic reasons. Different types of nets and traps have been used for this purpose with only partial success. The floating, self-cleaning downstream migrant trap described here proved successful for sampling several salmoniform and...

IgG-Fc-mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation.

Science.gov (United States)

Jefferis, R; Lund, J; Pound, J D

1998-06-01

The Fc region of human IgG expresses interaction sites for many effector ligands. In this review the topographical distributions of ten of these sites are discussed in relation to functional requirement. It is apparent that interaction sites localised to the inter-CH2-CH3 domain region of the Fc allow for functional divalency, whereas sites localised to the hinge proximal region of the CH2 domain are functionally monovalent, with expression of the latter sites being particularly dependent on glycosylation. All x-ray crystal structures for Fc and Fc-ligand complexes report that the protein structure of the hinge proximal region of the CH2 domain is "disordered", suggesting "internal mobility". We propose a model in which such "internal mobility" results in the generation of a dynamic equilibrium between multiple conformers, certain of which express interaction sites specific to individual ligands. The emerging understanding of the influence of oligosaccharide/protein interactions on protein conformation and biological function of IgG antibodies suggests a potential to generate novel glycoforms of antibody molecules having unique profiles of effector functions.

DMPD: MyDths and un-TOLLed truths: sensor, instructive and effector immunity totuberculosis. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18191460 MyDths and un-TOLLed truths: sensor, instructive and effector immunity totuberculosis...g) (.svg) (.html) (.csml) Show MyDths and un-TOLLed truths: sensor, instructive and effector immunity totuberculosis...e and effector immunity totuberculosis. Authors Reiling N, Ehlers S, Holscher C. Publication Immunol Lett. 2

Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted mice

International Nuclear Information System (INIS)

Liu, Guozheng; Dou, Shuping; He, Jiang; Liu, Xinrong; Rusckowski, Mary; Hnatowich, Donald J.

2007-01-01

Pretargeting with phosphorodiamidate morpholino oligomers (MORFs) involves administration of a MORF-conjugated anti-tumor antibody such as MN14 as a pretargeting agent before that of the radiolabeled complementary MORF (cMORF) as the effector. The dosages of the pretargeting agent and effector, the pretargeting interval, and the detection time are the four pretargeting variables. The goal of this study was to develop a semiempirical description capable of predicting the biodistribution of the radiolabeled effector in pretargeted mice and then to compare predictions with experimental results from pretargeting studies in tumored animals in which the pretargeting interval and the detection time were both fixed but the dosages of both the effector and the pretargeting agent were separately varied. Pretargeting studies in LS174T tumored mice were performed using the anti-CEA antibody MN14 conjugated with MORF and the cMORF radiolabeled with 99m Tc. A description was developed based on our previous observations in the same mouse model of the blood and tumor levels of MORF-MN14, accessibility of MORF-MN14 to labeled cMORF, the tumor accumulation of labeled cMORF relative to MORF-MN14 levels therein, and the kidney accumulation of labeled cMORF. The predicted values were then compared with the experimental values. The predicted biodistribution of the radiolabeled effector and the experimental data were in gratifying agreement in normal organs, suggesting that the description of the pretargeting process was reliable. The tumor accumulations occasionally fell outside two standard deviations of that predicted, but after tumor size correction, good agreement between predicted and experimental values was observed here as well. A semiempirical description of the biodistribution of labeled cMORF was capable of predicting the biodistribution of the radiolabeled effector in the pretargeted tumored mouse model, demonstrating that the underlying pretargeting concepts are correct. We

Fusion of Potentiometric & Voltammetric Electronic Tongue for Classification of Black Tea Taste based on Theaflavins (TF) Content

Science.gov (United States)

Bhattacharyya, Nabarun; Legin, Andrey; Papieva, Irina; Sarkar, Subrata; Kirsanov, Dmitry; Kartsova, Anna; Ghosh, Arunangshu; Bandyopadhyay, Rajib

2011-09-01

Black tea is an extensively consumed beverage worldwide with an expanding market. The final quality of black tea depends upon number of chemical compounds present in the tea. Out of these compounds, theaflavins (TF), which is responsible for astringency in black tea, plays an important role in determining the final taste of the finished black tea. The present paper reports our effort to correlate the theaflavins contents with the voltammetric and potentiometric electronic tongue (e-tongue) data. Noble metal-based electrode array has been used for collecting data though voltammetric electronic tongue where as liquid filled membrane based electrodes have been used for potentiometric electronic tongue. Black tea samples with tea taster score and biochemical results have been collected from Tea Research Association, Tocklai, India for the analysis purpose. In this paper, voltammetric and potentiometric e-tongue responses are combined to demonstrate improvement of cluster formation among tea samples with different ranges of TF values.

Effector Gene Suites in Some Soil Isolates of Fusarium oxysporum Are Not Sufficient Predictors of Vascular Wilt in Tomato.

Science.gov (United States)

Jelinski, Nicolas A; Broz, Karen; Jonkers, Wilfried; Ma, Li-Jun; Kistler, H Corby

2017-07-01

Seventy-four Fusarium oxysporum soil isolates were assayed for known effector genes present in an F. oxysporum f. sp. lycopersici race 3 tomato wilt strain (FOL MN-25) obtained from the same fields in Manatee County, Florida. Based on the presence or absence of these genes, four haplotypes were defined, two of which represented 96% of the surveyed isolates. These two most common effector haplotypes contained either all or none of the assayed race 3 effector genes. We hypothesized that soil isolates with all surveyed effector genes, similar to FOL MN-25, would be pathogenic toward tomato, whereas isolates lacking all effectors would be nonpathogenic. However, inoculation experiments revealed that presence of the effector genes alone was not sufficient to ensure pathogenicity on tomato. Interestingly, a nonpathogenic isolate containing the full suite of unmutated effector genes (FOS 4-4) appears to have undergone a chromosomal rearrangement yet remains vegetatively compatible with FOL MN-25. These observations confirm the highly dynamic nature of the F. oxysporum genome and support the conclusion that pathogenesis among free-living populations of F. oxysporum is a complex process. Therefore, the presence of effector genes alone may not be an accurate predictor of pathogenicity among soil isolates of F. oxysporum.

Mechanism of host substrate acetylation by a YopJ family effector.

Science.gov (United States)

Zhang, Zhi-Min; Ma, Ka-Wai; Gao, Linfeng; Hu, Zhenquan; Schwizer, Simon; Ma, Wenbo; Song, Jikui

2017-07-24

The Yersinia outer protein J (YopJ) family of bacterial effectors depends on a novel acetyltransferase domain to acetylate signalling proteins from plant and animal hosts. However, the underlying mechanism is unclear. Here, we report the crystal structures of PopP2, a YopJ effector produced by the plant pathogen Ralstonia solanacearum, in complex with inositol hexaphosphate (InsP 6 ), acetyl-coenzyme A (AcCoA) and/or substrate Resistance to Ralstonia solanacearum 1 (RRS1-R) WRKY . PopP2 recognizes the WRKYGQK motif of RRS1-R WRKY to position a targeted lysine in the active site for acetylation. Importantly, the PopP2-RRS1-R WRKY association is allosterically regulated by InsP 6 binding, suggesting a previously unidentified role of the eukaryote-specific cofactor in substrate interaction. Furthermore, we provide evidence for the reaction intermediate of PopP2-mediated acetylation, an acetyl-cysteine covalent adduct, lending direct support to the 'ping-pong'-like catalytic mechanism proposed for YopJ effectors. Our study provides critical mechanistic insights into the virulence activity of YopJ class of acetyltransferases.

Bio-effectors from waste materials as growth promoters for tomato plants, an agronomic and metabolomic study

Science.gov (United States)

Abou Chehade, Lara; Chami, Ziad Al; De Pascali, Sandra; Cavoski, Ivana; Fanizzi, Francesco Paolo

2015-04-01

In organic farming, where nutrient management is constrained and sustainability is claimed, bio-effectors pave their way. Considering selected bio-effectors, this study integrates metabolomics to agronomy in depicting induced relevant phenomena. Extracts of three agro-industrial wastes (Lemon processing residues, Fennel processing residues and Brewer's spent grain) are being investigated as sources of bio-effectors for the third trial consequently. Corresponding individual and mixture aqueous extracts are assessed for their synergistic and/or single agronomic and qualitative performances on soil-grown tomato, compared to both a control and humic acid treatments. A metabolomic profiling of tomato fruits via the Proton Nuclear Magnetic Resonance (NMR) spectroscopy, as holistic indicator of fruit quality and extract-induced responses, complements crop productivity and organoleptic/nutritional qualitative analyses. Results are expected to show mainly an enhancement of the fruit qualitative traits, and to confirm partly the previous results of better crop productivity and metabolism enhancement. Waste-derived bio-effectors could be, accordingly, demonstrated as potential candidates of plant-enhancing substances. Keywords: bio-effectors, organic farming, agro-industrial wastes, nuclear magnetic resonance (NMR), tomato.

Wave and particle evolution downstream of quasi-perpendicular shocks

Science.gov (United States)

Mckean, M. E.; Omidi, N.; Krauss-Varban, D.; Karimabadi, H.

1995-01-01

Distributions of ions heated in quasi-perpendicular bow shocks have large perpendicular temperature anisotropies that provide free energy for the growth of Alfven ion cyclotron (AIC) and mirror waves. These modes are often obsreved in the Earth's magnetosheath. Using two-dimensional hybrid simulations, we show that these waves are produced near the shock front and convected downstream rather than being produced locally downstream. The wave activity reduces the proton anisotropy to magnetosheath levels within a few tens of gyroradii of the shock but takes significantly longer to reduce the anisotropy of He(++) ions. The waves are primarily driven by proton anisotropy and the dynamics of the helium ions is controlled by the proton waves. Downstream of high Mach number shocks, mirror waves compete effectively with AIC waves. Downstream of low Mach number shocks, AIC waves dominate.

The study of hard microporous material using the ultrafine section technique (1961); Etude des materiaux microporeux durs par la technique des coupes ultraminces (1961)

Energy Technology Data Exchange (ETDEWEB)

Magdalena, Th [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1961-07-01

The conventional replica techniques for the examination of surfaces or fractures with the electron microscope are unsuitable for refractories or microporous bodies. The method of cutting ultrafine sections with a diamond cutter, the sample being impregnated with methyl methacrylate, has the advantage of making possible the direct examination by transmission of the sample. (author) [French] Les techniques classiques de repliques pour l'examen de surfaces ou de fractures au microscope electronique sont difficilement applicables aux refractaires et aux microporeux. Les coupes ultraminces au couteau de diamant d'echantillons enrobes dans le methyl-methacrylate ont l'avantage de permettre l'examen direct par transmission des corps etudies. (auteur)

Qualification tests for ITER TF conductors in SULTAN

International Nuclear Information System (INIS)

Bruzzone, P.; Stepanov, B.; Wesche, R.

2009-01-01

From February 2007 to May 2008, 18 short length conductor sections have been tested in SULTAN for design verification and manufacturer qualification of the ITER Toroidal Field (TF) conductor. The test program is focussed on the current sharing temperature, T cs , at the nominal operating conditions, 68 kA current and 11.15 T effective field, which can be fully reproduced in the SULTAN test facility. A broad range of results was observed, with over 2 K difference among the T cs of the conductors. In average, the results are poorer compared to the potential performance estimated from the strand scaling law. The key parameters to mitigate the degradation are not yet clearly identified. The experimental challenges to test conductors with performance degradation are highlighted, including enhanced instrumentation sets, the application of gas flow calorimetry to sense the current sharing power and the post-processing of voltage data to cancel the transverse potential across the cable. The updated schedule of the tests in SULTAN is presented with the short-term action plan for conductor test.

APT Blanket Detailed Bin Model Based on Initial Plate-Type Design -3D FLOWTRAN-TF Model

International Nuclear Information System (INIS)

Hamm, L.L.

1998-01-01

This report provides background information for a series of reports documenting accident scenario simulations for the Accelerator Production of Tritium (APT) blanket heat removal systems. The simulations were performed in support of the Preliminary Safety Analysis Report for the APT. This report gives a brief description of the FLOWTRAN-TF code which was used for detailed blanket bin modeling

Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR)

DEFF Research Database (Denmark)

Christensen, Anders; Kiss, Katalin; Lelkaitis, Giedrius

2017-01-01

Background: Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhib...... with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer....

Imbalanced expression of functional surface molecules in regulatory and effector T cells in systemic lupus erythematosus

International Nuclear Information System (INIS)

Mesquita Júnior, D.; Cruvinel, W.M.; Araujo, J.A.P.; Salmazi, K.C.; Kallas, E.G.; Andrade, L.E.C.

2014-01-01

Regulatory T (TREG) cells play an important role in maintaining immune tolerance and avoiding autoimmunity. We analyzed the expression of membrane molecules in TREG and effector T cells in systemic lupus erythematosus (SLE). TREG and effector T cells were analyzed for the expression of CTLA-4, PD1, CD28, CD95, GITR, HLA-DR, OX40, CD40L, and CD45RO in 26 patients with active disease, 31 with inactive disease, and 26 healthy controls. TREG cells were defined as CD25 +/high CD127 Ø/low FoxP3 + , and effector T cells were defined as CD25 + CD127 + FoxP3 Ø . The ratio of TREG to effector T cells expressing GITR, PD1, HLA-DR, OX40, CD40L, and CD45RO was determined in the three groups. The frequency of TREG cells was similar in patients with SLE and controls. However, SLE patients had a decreased frequency of CTLA-4 + TREG and CD28 + TREG cells and an increased frequency of CD40L + TREG cells. There was a decrease in the TREG/effector-T ratio for GITR + , HLA-DR + , OX40 + , and CD45RO + cells, and an increased ratio of TREG/effector-T CD40L + cells in patients with SLE. In addition, CD40L + TREG cell frequency correlated with the SLE disease activity index (P=0.0163). In conclusion, our findings showed several abnormalities in the expression of functionally critical surface molecules in TREG and effector T cells in SLE that may be relevant to the pathogenesis of this disease

Imbalanced expression of functional surface molecules in regulatory and effector T cells in systemic lupus erythematosus

Energy Technology Data Exchange (ETDEWEB)

Mesquita Júnior, D. [Disciplina de Reumatologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Cruvinel, W.M. [Disciplina de Reumatologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Departamento de Biomedicina, Universidade Católica de Goiás, Goiânia, GO (Brazil); Araujo, J.A.P. [Disciplina de Reumatologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Salmazi, K.C.; Kallas, E.G. [Disciplina de Imunologia Clínica e Alergia, Departamento de Clínica Médica, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Andrade, L.E.C. [Disciplina de Reumatologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

2014-08-22

Regulatory T (TREG) cells play an important role in maintaining immune tolerance and avoiding autoimmunity. We analyzed the expression of membrane molecules in TREG and effector T cells in systemic lupus erythematosus (SLE). TREG and effector T cells were analyzed for the expression of CTLA-4, PD1, CD28, CD95, GITR, HLA-DR, OX40, CD40L, and CD45RO in 26 patients with active disease, 31 with inactive disease, and 26 healthy controls. TREG cells were defined as CD25{sup +/high}CD127{sup Ø/low}FoxP3{sup +}, and effector T cells were defined as CD25{sup +}CD127{sup +}FoxP3{sup Ø}. The ratio of TREG to effector T cells expressing GITR, PD1, HLA-DR, OX40, CD40L, and CD45RO was determined in the three groups. The frequency of TREG cells was similar in patients with SLE and controls. However, SLE patients had a decreased frequency of CTLA-4{sup +}TREG and CD28{sup +}TREG cells and an increased frequency of CD40L{sup +}TREG cells. There was a decrease in the TREG/effector-T ratio for GITR{sup +}, HLA-DR{sup +}, OX40{sup +}, and CD45RO{sup +} cells, and an increased ratio of TREG/effector-T CD40L{sup +} cells in patients with SLE. In addition, CD40L{sup +}TREG cell frequency correlated with the SLE disease activity index (P=0.0163). In conclusion, our findings showed several abnormalities in the expression of functionally critical surface molecules in TREG and effector T cells in SLE that may be relevant to the pathogenesis of this disease.

A generalized quantitative antibody homeostasis model: maintenance of global antibody equilibrium by effector functions.

Science.gov (United States)

Prechl, József

2017-11-01

The homeostasis of antibodies can be characterized as a balanced production, target-binding and receptor-mediated elimination regulated by an interaction network, which controls B-cell development and selection. Recently, we proposed a quantitative model to describe how the concentration and affinity of interacting partners generates a network. Here we argue that this physical, quantitative approach can be extended for the interpretation of effector functions of antibodies. We define global antibody equilibrium as the zone of molar equivalence of free antibody, free antigen and immune complex concentrations and of dissociation constant of apparent affinity: [Ab]=[Ag]=[AbAg]= K D . This zone corresponds to the biologically relevant K D range of reversible interactions. We show that thermodynamic and kinetic properties of antibody-antigen interactions correlate with immunological functions. The formation of stable, long-lived immune complexes correspond to a decrease of entropy and is a prerequisite for the generation of higher-order complexes. As the energy of formation of complexes increases, we observe a gradual shift from silent clearance to inflammatory reactions. These rules can also be applied to complement activation-related immune effector processes, linking the physicochemical principles of innate and adaptive humoral responses. Affinity of the receptors mediating effector functions shows a wide range of affinities, allowing the continuous sampling of antibody-bound antigen over the complete range of concentrations. The generation of multivalent, multicomponent complexes triggers effector functions by crosslinking these receptors on effector cells with increasing enzymatic degradation potential. Thus, antibody homeostasis is a thermodynamic system with complex network properties, nested into the host organism by proper immunoregulatory and effector pathways. Maintenance of global antibody equilibrium is achieved by innate qualitative signals modulating a

Fructose 1-phosphate is the preferred effector of the metabolic regulator Cra of Pseudomonas putida.

Science.gov (United States)

Chavarría, Max; Santiago, César; Platero, Raúl; Krell, Tino; Casasnovas, José M; de Lorenzo, Víctor

2011-03-18

The catabolite repressor/activator (Cra) protein is a global sensor and regulator of carbon fluxes through the central metabolic pathways of gram-negative bacteria. To examine the nature of the effector (or effectors) that signal such fluxes to the protein of Pseudomonas putida, the Cra factor of this soil microorganism has been purified and characterized and its three-dimensional structure determined. Analytical ultracentrifugation, gel filtration, and mobility shift assays showed that the effector-free Cra is a dimer that binds an operator DNA sequence in the promoter region of the fruBKA cluster. Furthermore, fructose 1-phosphate (F1P) was found to most efficiently dissociate the Cra-DNA complex. Thermodynamic parameters of the F1P-Cra-DNA interaction calculated by isothermal titration calorimetry revealed that the factor associates tightly to the DNA sequence 5'-TTAAACGTTTCA-3' (K(D) = 26.3 ± 3.1 nM) and that F1P binds the protein with an apparent stoichiometry of 1.06 ± 0.06 molecules per Cra monomer and a K(D) of 209 ± 20 nM. Other possible effectors, like fructose 1,6-bisphosphate, did not display a significant affinity for the regulator under the assay conditions. Moreover, the structure of Cra and its co-crystal with F1P at a 2-Å resolution revealed that F1P fits optimally the geometry of the effector pocket. Our results thus single out F1P as the preferred metabolic effector of the Cra protein of P. putida.

Fructose 1-Phosphate Is the Preferred Effector of the Metabolic Regulator Cra of Pseudomonas putida*

Science.gov (United States)

Chavarría, Max; Santiago, César; Platero, Raúl; Krell, Tino; Casasnovas, José M.; de Lorenzo, Víctor

2011-01-01

The catabolite repressor/activator (Cra) protein is a global sensor and regulator of carbon fluxes through the central metabolic pathways of Gram-negative bacteria. To examine the nature of the effector (or effectors) that signal such fluxes to the protein of Pseudomonas putida, the Cra factor of this soil microorganism has been purified and characterized and its three-dimensional structure determined. Analytical ultracentrifugation, gel filtration, and mobility shift assays showed that the effector-free Cra is a dimer that binds an operator DNA sequence in the promoter region of the fruBKA cluster. Furthermore, fructose 1-phosphate (F1P) was found to most efficiently dissociate the Cra-DNA complex. Thermodynamic parameters of the F1P-Cra-DNA interaction calculated by isothermal titration calorimetry revealed that the factor associates tightly to the DNA sequence 5′-TTAAACGTTTCA-3′ (KD = 26.3 ± 3.1 nm) and that F1P binds the protein with an apparent stoichiometry of 1.06 ± 0.06 molecules per Cra monomer and a KD of 209 ± 20 nm. Other possible effectors, like fructose 1,6-bisphosphate, did not display a significant affinity for the regulator under the assay conditions. Moreover, the structure of Cra and its co-crystal with F1P at a 2-Å resolution revealed that F1P fits optimally the geometry of the effector pocket. Our results thus single out F1P as the preferred metabolic effector of the Cra protein of P. putida. PMID:21239488

Defining essential processes in plant pathogenesis with Pseudomonas syringae pv. tomato DC3000 disarmed polymutants and a subset of key type III effectors.

Science.gov (United States)

Wei, Hai-Lei; Collmer, Alan

2017-12-25

Pseudomonas syringae pv. tomato DC3000 and its derivatives cause disease in tomato, Arabidopsis and Nicotiana benthamiana. The primary virulence factors include a repertoire of 29 effector proteins injected into plant cells by the type III secretion system and the phytotoxin coronatine. The complete repertoire of effector genes and key coronatine biosynthesis genes have been progressively deleted and minimally reassembled to reconstitute basic pathogenic ability in N. benthamiana, and in Arabidopsis plants that have mutations in target genes that mimic effector actions. This approach and molecular studies of effector activities and plant immune system targets have highlighted a small subset of effectors that contribute to essential processes in pathogenesis. Most notably, HopM1 and AvrE1 redundantly promote an aqueous apoplastic environment, and AvrPtoB and AvrPto redundantly block early immune responses, two conditions that are sufficient for substantial bacterial growth in planta. In addition, disarmed DC3000 polymutants have been used to identify the individual effectors responsible for specific activities of the complete repertoire and to more effectively study effector domains, effector interplay and effector actions on host targets. Such work has revealed that AvrPtoB suppresses cell death elicitation in N. benthamiana that is triggered by another effector in the DC3000 repertoire, highlighting an important aspect of effector interplay in native repertoires. Disarmed DC3000 polymutants support the natural delivery of test effectors and infection readouts that more accurately reveal effector functions in key pathogenesis processes, and enable the identification of effectors with similar activities from a broad range of other pathogens that also defeat plants with cytoplasmic effectors. © 2017 BSPP AND JOHN WILEY & SONS LTD.

Quickly Planning TF/TA2 Trajectory by Artificial Immune Algorithm

Directory of Open Access Journals (Sweden)

LIU Lifeng

2015-04-01

Full Text Available Flight path planning by artificial immune algorithm approach met the requirements of aircraft's flyability and operation is proposed for the problem of single and double TF/TA2 flight path planning. Punishment function (affinity function with comprehensive 3D threat information is designed. A comprehensive threat model is formed including dynamic and static threats and no-fly-zone. Accordingly, single and dual flight paths are planned by AIA, which have been compared with the paths by GA. The results show that, GA's planned a quick and longer path compared under simple threat environment; in complex environments, GA has high failure rate (greater than 95% for single aircraft, but it is failed for double aircrafts. For the single and double aircrafts, AIA can provides one optimal and more candidate optimal flight paths.

EU ITER TF coil: Dimensional metrology, a key player in the Double Pancake integration

International Nuclear Information System (INIS)

Poncet, L.; Bellesia, B.; Oliva, A. Bonito; Boter Rebollo, E.; Cornelis, M.; Cornella Medrano, J.; Harrison, R.; Bue, A. Lo; Moreno, A.; Foussat, A.; Felipe, A.; Echeandia, A.; Barutti, A.; Caserza, B.; Barbero, P.; Stenca, S.; Da Re, A.; Silva Ribeiro, J.; Brocot, C.; Benaoun, S.

2015-01-01

Highlights: • Development and qualification of a dimensional metrology procedure on wound superconductor trajectory based on Laser scanning system. • Dimensional control of the conductor centreline during winding, before and after heat treatment. • Radial Plate groove centreline length controlled using Laser Trackers. • Full scale wound Double Pancake prototype transferred inside Radial Plate prototype without any issues. - Abstract: The ITER Toroidal Field (TF) magnet system consists of 18 “D” shaped coils. Fusion for Energy (F4E), the European Domestic Agency for ITER, is responsible for the supply of 10 out the 19 TF coils (18 installed plus one spare coil). Each TF coil, about 300 t in weight, is made of a stainless steel case containing a Winding Pack (WP). The European manufacturing of the Radial Plates (RPs) and WPs has been awarded to two different industrial partners, whose activities are strongly linked with each other. In order to manufacture a Double Pancake (DP), first, the conductor has to be bent onto a D-shaped double spiral trajectory, then heat treated and inserted in the grooves of the RP. This represents the most challenging manufacturing step: in order to fit inside the groove, the double spiral trajectory of the conductor must match almost perfectly the trajectory of the groove, over a length above 700 m. In order to achieve this, the conductor trajectory length must be controlled with an accuracy of 1 mm over a length of 350 m while the radial plate groove has to be machined with tolerances of ±0.2 mm over dimensions of more than 10 m. In order to succeed, it has been essential to develop a metrology process capable to control with high accuracy both the DP conductor and the RP groove trajectories. This paper reports on the work carried out on the development and qualification of the dimensional metrology to monitor the manufacturing of the conductor. Reference is made to the final dimensional check of the RP focusing on the

Identifying Cancer Subtypes from miRNA-TF-mRNA Regulatory Networks and Expression Data.

Directory of Open Access Journals (Sweden)

Taosheng Xu

Full Text Available Identifying cancer subtypes is an important component of the personalised medicine framework. An increasing number of computational methods have been developed to identify cancer subtypes. However, existing methods rarely use information from gene regulatory networks to facilitate the subtype identification. It is widely accepted that gene regulatory networks play crucial roles in understanding the mechanisms of diseases. Different cancer subtypes are likely caused by different regulatory mechanisms. Therefore, there are great opportunities for developing methods that can utilise network information in identifying cancer subtypes.In this paper, we propose a method, weighted similarity network fusion (WSNF, to utilise the information in the complex miRNA-TF-mRNA regulatory network in identifying cancer subtypes. We firstly build the regulatory network where the nodes represent the features, i.e. the microRNAs (miRNAs, transcription factors (TFs and messenger RNAs (mRNAs and the edges indicate the interactions between the features. The interactions are retrieved from various interatomic databases. We then use the network information and the expression data of the miRNAs, TFs and mRNAs to calculate the weight of the features, representing the level of importance of the features. The feature weight is then integrated into a network fusion approach to cluster the samples (patients and thus to identify cancer subtypes. We applied our method to the TCGA breast invasive carcinoma (BRCA and glioblastoma multiforme (GBM datasets. The experimental results show that WSNF performs better than the other commonly used computational methods, and the information from miRNA-TF-mRNA regulatory network contributes to the performance improvement. The WSNF method successfully identified five breast cancer subtypes and three GBM subtypes which show significantly different survival patterns. We observed that the expression patterns of the features in some miRNA-TF

Design criteria for the light duty utility arm system end effectors

International Nuclear Information System (INIS)

Pardini, A.F.

1995-01-01

This document provides the criteria for the design of end effectors that will be used as part of the Light Duty Utility Arm (LDUA) System. The LDUA System consists of a deployment vehicle, a vertical positioning mast, a light duty multi-axis robotic arm, a tank riser interface and confinement, a tool interface plate, a control system, and an operations control trailer. The criteria specified in this document will apply to all end effector systems being developed for use on or with the LDUA system at the Hanford site. The requirement stipulated in this document are mandatory

The Coding and Effector Transfer of Movement Sequences

Science.gov (United States)

Kovacs, Attila J.; Muhlbauer, Thomas; Shea, Charles H.

2009-01-01

Three experiments utilizing a 14-element arm movement sequence were designed to determine if reinstating the visual-spatial coordinates, which require movements to the same spatial locations utilized during acquisition, results in better effector transfer than reinstating the motor coordinates, which require the same pattern of homologous muscle…

Dynamic transcription factor networks in epithelial-mesenchymal transition in breast cancer models.

Science.gov (United States)

Siletz, Anaar; Schnabel, Michael; Kniazeva, Ekaterina; Schumacher, Andrew J; Shin, Seungjin; Jeruss, Jacqueline S; Shea, Lonnie D

2013-01-01

The epithelial-mesenchymal transition (EMT) is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs) are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy.

Dynamic transcription factor networks in epithelial-mesenchymal transition in breast cancer models.

Directory of Open Access Journals (Sweden)

Anaar Siletz

Full Text Available The epithelial-mesenchymal transition (EMT is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy.

Global study of holistic morphological effectors in the budding yeast Saccharomyces cerevisiae.

Science.gov (United States)

Suzuki, Godai; Wang, Yang; Kubo, Karen; Hirata, Eri; Ohnuki, Shinsuke; Ohya, Yoshikazu

2018-02-20

The size of the phenotypic effect of a gene has been thoroughly investigated in terms of fitness and specific morphological traits in the budding yeast Saccharomyces cerevisiae, but little is known about gross morphological abnormalities. We identified 1126 holistic morphological effectors that cause severe gross morphological abnormality when deleted, and 2241 specific morphological effectors with weak holistic effects but distinctive effects on yeast morphology. Holistic effectors fell into many gene function categories and acted as network hubs, affecting a large number of morphological traits, interacting with a large number of genes, and facilitating high protein expression. Holistic morphological abnormality was useful for estimating the importance of a gene to morphology. The contribution of gene importance to fitness and morphology could be used to efficiently classify genes into functional groups. Holistic morphological abnormality can be used as a reproducible and reliable gene feature for high-dimensional morphological phenotyping. It can be used in many functional genomic applications.

Abstract and Effector-Selective Decision Signals Exhibit Qualitatively Distinct Dynamics before Delayed Perceptual Reports.

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Twomey, Deirdre M; Kelly, Simon P; O'Connell, Redmond G

2016-07-13

Electrophysiological research has isolated neural signatures of decision formation in a variety of brain regions. Studies in rodents and monkeys have focused primarily on effector-selective signals that translate the emerging decision into a specific motor plan, but, more recently, research on the human brain has identified an abstract signature of evidence accumulation that does not appear to play any direct role in action preparation. The functional dissociations between these distinct signal types have only begun to be characterized, and their dynamics during decisions with deferred actions with or without foreknowledge of stimulus-effector mapping, a commonly studied task scenario in single-unit and functional imaging investigations, have not been established. Here we traced the dynamics of distinct abstract and effector-selective decision signals in the form of the broad-band centro-parietal positivity (CPP) and limb-selective β-band (8-16 and 18-30 Hz) EEG activity, respectively, during delayed-reported motion direction decisions with and without foreknowledge of direction-response mapping. With foreknowledge, the CPP and β-band signals exhibited a similar gradual build-up following evidence onset, but whereas choice-predictive β-band activity persisted up until the delayed response, the CPP dropped toward baseline after peaking. Without foreknowledge, the CPP exhibited identical dynamics, whereas choice-selective β-band activity was eliminated. These findings highlight qualitative functional distinctions between effector-selective and abstract decision signals and are of relevance to the assumptions founding functional neuroimaging investigations of decision-making. Neural signatures of evidence accumulation have been isolated in numerous brain regions. Although animal neurophysiology has largely concentrated on effector-selective decision signals that translate the emerging decision into a specific motor plan, recent research on the human brain has

CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis

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McNally, Alice; Hill, Geoffrey R.; Sparwasser, Tim; Thomas, Ranjeny; Steptoe, Raymond J.

2011-01-01

CD4+CD25+ regulatory T cells (Treg) play a crucial role in the regulation of immune responses. Although many mechanisms of Treg suppression in vitro have been described, the mechanisms by which Treg modulate CD8+ T cell differentiation and effector function in vivo are more poorly defined. It has been proposed, in many instances, that modulation of cytokine homeostasis could be an important mechanism by which Treg regulate adaptive immunity; however, direct experimental evidence is sparse. Here we demonstrate that CD4+CD25+ Treg, by critically regulating IL-2 homeostasis, modulate CD8+ T-cell effector differentiation. Expansion and effector differentiation of CD8+ T cells is promoted by autocrine IL-2 but, by competing for IL-2, Treg limit CD8+ effector differentiation. Furthermore, a regulatory loop exists between Treg and CD8+ effector T cells, where IL-2 produced during CD8+ T-cell effector differentiation promotes Treg expansion. PMID:21502514

The effector repertoire of Fusarium oxysporum determines the tomato xylem proteome composition following infection

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Fleur eGawehns

2015-11-01

Full Text Available Plant pathogens secrete small proteins, of which some are effectors that promote infection. During colonization of the tomato xylem vessels the fungus Fusarium oxysporum f. sp. lycopersici (Fol secretes small proteins that are referred to as SIX (Secreted In Xylem proteins. Of these, Six1 (Avr3, Six3 (Avr2, Six5 and Six6 are required for full virulence, denoting them as effectors. To investigate their activities in the plant, the xylem sap proteome of plants inoculated with Fol wild-type or either AVR2, AVR3, SIX2, SIX5 or SIX6 knockout strains was analyzed with nano-Liquid Chromatography-Mass Spectrometry (nLC-MSMS. Compared to mock-inoculated sap 12 additional plant proteins appeared while 45 proteins were no longer detectable in the xylem sap of Fol-infected plants. Of the 285 proteins found in both uninfected and infected plants the abundance of 258 proteins changed significantly following infection. The xylem sap proteome of plants infected with four Fol effector knockout strains differed significantly from plants infected with wild-type Fol, while that of the SIX2-knockout inoculated plants remained unchanged. Besides an altered abundance of a core set of 24 differentially accumulated proteins (DAPs, each of the four effector knockout strains affected specifically the abundance of a subset of DAPs. Hence, Fol effectors have both unique and shared effects on the composition of the tomato xylem sap proteome.

Small-angle neutron scattering from the reconstituted TF sub 1 of H sup + -ATPase from thermophilic bacterium PS3 with deuterated subunits

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Ito, Yuji [Univ. of Tokyo (Japan) Brookhaven National Lab., Upton, NY (United States); Harada, Mitsuo [Univ. of Tokyo (Japan); Ohta, Shigeo; Kagawa, Yasuo; Aono, Osamu [Jichi Medical School, Tochigi (Japan); Schefer, J; Schoenborn, B P [Brookhaven National Lab., Upton (United States)

1990-01-01

Subunits {alpha}, {beta} and {gamma} of adenosine triphosphatase (H{sup +}-ATPase) from the thermophilic bacterium PS3 (TF{sub 1}) have been over-expressed in Escherichia coli. {alpha} and {beta} subunits deuterated to the level of 90% were obtained by culturing E. coli in {sup 2}H{sub 2}O medium. Both the subunits and the reconstituted {alpha}{beta}{gamma} complex, TF{sub 1}, which contain the deuterated components in various combinations, were studied in solution by small-angle neutron scattering. The individual shapes of the subunits and their organization in the {alpha}{beta}{gamma}-TF{sub 1} complex were examined using the techniques of selective deuteration and contrast variation. The {alpha} and {beta} subunits are well approximated as ellipsoids of revolution having minor semi-axes of 20{center dot}4({plus minus}0{center dot}4) and 20{center dot}0({plus minus}0{center dot}2) {angstrom}, and major semi-axes of 53{center dot}0({plus minus}1{center dot}4) and 55{center dot}8({plus minus}0{center dot}9) {angstrom}, respectively. In the TF{sub 1} complex, three {beta} subunits are aligned to form an equilateral triangle, with their major axes tilted by 35{degree} with respect to the 3-fold axis of the complex. The {beta}-{beta} distance is about 53 {angstrom}. Three {alpha} subunits are similarly arranged, positioned between the {beta} subunits, and with their direction of tilt opposite to that of the {beta} subunits. The centers of the {alpha} and {beta} subunits lie in the same plane, forming a hexagon. Adjacent subunits overlap in this model, suggesting that they are not simple ellipsoids of revolution.

Downstream-based Scheduling for Energy Conservation in Green EPONs

KAUST Repository

Chen, Shen; Dhaini, Ahmad R.; Ho, Pin-Han; Shihada, Basem; Shen, Gangxiang; Lin, Chih-Hao

2012-01-01

the ONU sleep time, it jeopardizes the quality of service (QoS) performance of the network, especially for downstream traffic in case the overlapping is based on the upstream time slot. In this paper, we study the downstream traffic performance in green

Evidence of end-effector based gait machines in gait rehabilitation after CNS lesion.

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Hesse, S; Schattat, N; Mehrholz, J; Werner, C

2013-01-01

A task-specific repetitive approach in gait rehabilitation after CNS lesion is well accepted nowadays. To ease the therapists' and patients' physical effort, the past two decades have seen the introduction of gait machines to intensify the amount of gait practice. Two principles have emerged, an exoskeleton- and an endeffector-based approach. Both systems share the harness and the body weight support. With the end-effector-based devices, the patients' feet are positioned on two foot plates, whose movements simulate stance and swing phase. This article provides an overview on the end-effector based machine's effectiveness regarding the restoration of gait. For the electromechanical gait trainer GT I, a meta analysis identified nine controlled trials (RCT) in stroke subjects (n = 568) and were analyzed to detect differences between end-effector-based locomotion + physiotherapy and physiotherapy alone. Patients practising with the machine effected in a superior gait ability (210 out of 319 patients, 65.8% vs. 96 out of 249 patients, 38.6%, respectively, Z = 2.29, p = 0.020), due to a larger training intensity. Only single RCTs have been reported for other devices and etiologies. The introduction of end-effector based gait machines has opened a new succesful chapter in gait rehabilitation after CNS lesion.

Phytophthora suppressor of RNA silencing 2 is a conserved RxLR effector that promotes infection in soybean and Arabidopsis thaliana.

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Xiong, Qin; Ye, Wenwu; Choi, Duseok; Wong, James; Qiao, Yongli; Tao, Kai; Wang, Yuanchao; Ma, Wenbo

2014-12-01

The genus Phytophthora consists of notorious and emerging pathogens of economically important crops. Each Phytophthora genome encodes several hundreds of cytoplasmic effectors, which are believed to manipulate plant immune response inside the host cells. However, the majority of Phytophthora effectors remain functionally uncharacterized. We recently discovered two effectors from the soybean stem and root rot pathogen Phytophthora sojae with the activity to suppress RNA silencing in plants. These effectors are designated Phytophthora suppressor of RNA silencing (PSRs). Here, we report that the P. sojae PSR2 (PsPSR2) belongs to a conserved and widespread effector family in Phytophthora. A PsPSR2-like effector produced by P. infestans (PiPSR2) can also suppress RNA silencing in plants and promote Phytophthora infection, suggesting that the PSR2 family effectors have conserved functions in plant hosts. Using Agrobacterium rhizogenes-mediated hairy roots induction, we demonstrated that the expression of PsPSR2 rendered hypersusceptibility of soybean to P. sojae. Enhanced susceptibility was also observed in PsPSR2-expressing Arabidopsis thaliana plants during Phytophthora but not bacterial infection. These experiments provide strong evidence that PSR2 is a conserved Phytophthora effector family that performs important virulence functions specifically during Phytophthora infection of various plant hosts.

Investigation of wall mass transfer characteristics downstream of an orifice

International Nuclear Information System (INIS)

El-Gammal, M.; Ahmed, W.H.; Ching, C.Y.

2012-01-01

Highlights: ► Numerical simulations were performed for the mass transfer downstream of an orifice. ► The Low Reynolds Number K-ε turbulence model was used. ► The numerical results were in good agreement with existing experimental results. ► The maximum Sherwood number downstream of the orifice was significantly affected by the Reynolds number. ► The Sherwood number profile was well correlated with the turbulence kinetic energy profile close to the wall. - Abstract: Numerical simulations were performed to determine the effect of Reynolds number and orifice to pipe diameter ratio (d o /d) on the wall mass transfer rate downstream of an orifice. The simulations were performed for d o /d of 0.475 for Reynolds number up to 70,000. The effect of d o /d was determined by performing simulations at a Reynolds number of 70,000 for d o /d of 0.375, 0.475 and 0.575. The momentum and mass transport equations were solved using the Low Reynolds Number (LRN) K-ε turbulence model. The Sherwood number (Sh) profile downstream of the orifice was in relatively good agreement with existing experimental results. The Sh increases sharply downstream of the orifice, reaching a maximum within 1–2 diameters downstream of the orifice, before relaxing back to the fully developed pipe flow value. The Sh number well downstream of the orifice was in good agreement with results for fully developed pipe flow estimated from the correlation of . The peak Sh numbers from the simulations were higher than that predicted from and .

Rho-GTPase effector ROCK phosphorylates cofilin in actin-meditated cytokinesis during mouse oocyte meiosis.

Science.gov (United States)

Duan, Xing; Liu, Jun; Dai, Xiao-Xin; Liu, Hong-Lin; Cui, Xiang-Shun; Kim, Nam-Hyung; Wang, Zhen-Bo; Wang, Qiang; Sun, Shao-Chen

2014-02-01

During oocyte meiosis, a spindle forms in the central cytoplasm and migrates to the cortex. Subsequently, the oocyte extrudes a small body and forms a highly polarized egg; this process is regulated primarily by actin. ROCK is a Rho-GTPase effector that is involved in various cellular functions, such as stress fiber formation, cell migration, tumor cell invasion, and cell motility. In this study, we investigated possible roles for ROCK in mouse oocyte meiosis. ROCK was localized around spindles after germinal vesicle breakdown and was colocalized with cytoplasmic actin and mitochondria. Disrupting ROCK activity by RNAi or an inhibitor resulted in cell cycle progression and polar body extrusion failure. Time-lapse microscopy showed that this may have been due to spindle migration and cytokinesis defects, as chromosomes segregated but failed to extrude a polar body and then realigned. Actin expression at oocyte membranes and in cytoplasm was significantly decreased after these treatments. Actin caps were also disrupted, which was confirmed by a failure to form cortical granule-free domains. The mitochondrial distribution was also disrupted, which indicated that mitochondria were involved in the ROCK-mediated actin assembly. In addition, the phosphorylation levels of Cofilin, a downstream molecule of ROCK, decreased after disrupting ROCK activity. Thus, our results indicated that a ROCK-Cofilin-actin pathway regulated meiotic spindle migration and cytokinesis during mouse oocyte maturation.

Human reinforcement learning subdivides structured action spaces by learning effector-specific values.

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Gershman, Samuel J; Pesaran, Bijan; Daw, Nathaniel D

2009-10-28

Humans and animals are endowed with a large number of effectors. Although this enables great behavioral flexibility, it presents an equally formidable reinforcement learning problem of discovering which actions are most valuable because of the high dimensionality of the action space. An unresolved question is how neural systems for reinforcement learning-such as prediction error signals for action valuation associated with dopamine and the striatum-can cope with this "curse of dimensionality." We propose a reinforcement learning framework that allows for learned action valuations to be decomposed into effector-specific components when appropriate to a task, and test it by studying to what extent human behavior and blood oxygen level-dependent (BOLD) activity can exploit such a decomposition in a multieffector choice task. Subjects made simultaneous decisions with their left and right hands and received separate reward feedback for each hand movement. We found that choice behavior was better described by a learning model that decomposed the values of bimanual movements into separate values for each effector, rather than a traditional model that treated the bimanual actions as unitary with a single value. A decomposition of value into effector-specific components was also observed in value-related BOLD signaling, in the form of lateralized biases in striatal correlates of prediction error and anticipatory value correlates in the intraparietal sulcus. These results suggest that the human brain can use decomposed value representations to "divide and conquer" reinforcement learning over high-dimensional action spaces.

Virus-specific regulatory T cells ameliorate encephalitis by repressing effector T cell functions from priming to effector stages.

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Jingxian Zhao

2014-08-01

Full Text Available Several studies have demonstrated the presence of pathogen-specific Foxp3+ CD4 regulatory T cells (Treg in infected animals, but little is known about where and how these cells affect the effector T cell responses and whether they are more suppressive than bulk Treg populations. We recently showed the presence of both epitope M133-specific Tregs (M133 Treg and conventional CD4 T cells (M133 Tconv in the brains of mice with coronavirus-induced encephalitis. Here, we provide new insights into the interactions between pathogenic Tconv and Tregs responding to the same epitope. M133 Tregs inhibited the proliferation but not initial activation of M133 Tconv in draining lymph nodes (DLN. Further, M133 Tregs inhibited migration of M133 Tconv from the DLN. In addition, M133 Tregs diminished microglia activation and decreased the number and function of Tconv in the infected brain. Thus, virus-specific Tregs inhibited pathogenic CD4 T cell responses during priming and effector stages, particularly those recognizing cognate antigen, and decreased mortality and morbidity without affecting virus clearance. These cells are more suppressive than bulk Tregs and provide a targeted approach to ameliorating immunopathological disease in infectious settings.

A Legionella pneumophila effector protein encoded in a region of genomic plasticity binds to Dot/Icm-modified vacuoles.

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Shira Ninio

2009-01-01

Full Text Available Legionella pneumophila is an opportunistic pathogen that can cause a severe pneumonia called Legionnaires' disease. In the environment, L. pneumophila is found in fresh water reservoirs in a large spectrum of environmental conditions, where the bacteria are able to replicate within a variety of protozoan hosts. To survive within eukaryotic cells, L. pneumophila require a type IV secretion system, designated Dot/Icm, that delivers bacterial effector proteins into the host cell cytoplasm. In recent years, a number of Dot/Icm substrate proteins have been identified; however, the function of most of these proteins remains unknown, and it is unclear why the bacterium maintains such a large repertoire of effectors to promote its survival. Here we investigate a region of the L. pneumophila chromosome that displays a high degree of plasticity among four sequenced L. pneumophila strains. Analysis of GC content suggests that several genes encoded in this region were acquired through horizontal gene transfer. Protein translocation studies establish that this region of genomic plasticity encodes for multiple Dot/Icm effectors. Ectopic expression studies in mammalian cells indicate that one of these substrates, a protein called PieA, has unique effector activities. PieA is an effector that can alter lysosome morphology and associates specifically with vacuoles that support L. pneumophila replication. It was determined that the association of PieA with vacuoles containing L. pneumophila requires modifications to the vacuole mediated by other Dot/Icm effectors. Thus, the localization properties of PieA reveal that the Dot/Icm system has the ability to spatially and temporally control the association of an effector with vacuoles containing L. pneumophila through activities mediated by other effector proteins.

Generation of knockout rabbits using transcription activator-like effector nucleases.

Science.gov (United States)

Wang, Yu; Fan, Nana; Song, Jun; Zhong, Juan; Guo, Xiaogang; Tian, Weihua; Zhang, Quanjun; Cui, Fenggong; Li, Li; Newsome, Philip N; Frampton, Jon; Esteban, Miguel A; Lai, Liangxue

2014-01-01

Zinc-finger nucleases and transcription activator-like effector nucleases are novel gene-editing platforms contributing to redefine the boundaries of modern biological research. They are composed of a non-specific cleavage domain and a tailor made DNA-binding module, which enables a broad range of genetic modifications by inducing efficient DNA double-strand breaks at desired loci. Among other remarkable uses, these nucleases have been employed to produce gene knockouts in mid-size and large animals, such as rabbits and pigs, respectively. This approach is cost effective, relatively quick, and can produce invaluable models for human disease studies, biotechnology or agricultural purposes. Here we describe a protocol for the efficient generation of knockout rabbits using transcription activator-like effector nucleases, and a perspective of the field.

Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells

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Shiming Ye

2017-01-01

Full Text Available Enavatuzumab is a humanized IgG1 anti-TWEAK receptor monoclonal antibody that was evaluated in a phase I clinical study for the treatment of solid malignancies. The current study was to determine whether and how myeloid effector cells were involved in postulated mechanisms for its potent antitumor activity in xenograft models. The initial evidence for a role of effector cells was obtained in a subset of tumor xenograft mouse models whose response to enavatuzumab relied on the binding of Fc of the antibody to Fcγ receptor. The involvement of effector cells was further confirmed by immunohistochemistry, which revealed strong infiltration of CD45+ effector cells into tumor xenografts in responding models, but minimal infiltration in nonresponders. Consistent with the xenograft studies, human effector cells preferentially migrated toward in vivo-responsive tumor cells treated by enavatuzumab in vitro, with the majority of migratory cells being monocytes. Conditioned media from enavatuzumab-treated tumor cells contained elevated levels of chemokines, which might be responsible for enavatuzumab-triggered effector cell migration. These preclinical studies demonstrate that enavatuzumab can exert its potent antitumor activity by actively recruiting and activating myeloid effectors to kill tumor cells. Enavatuzumab-induced chemokines warrant further evaluation in clinical studies as potential biomarkers for such activity.

Structure of the effector-binding domain of the arabinose repressor AraR from Bacillus subtilis

Energy Technology Data Exchange (ETDEWEB)

Procházková, Kateřina; Čermáková, Kateřina [Academy of Sciences of the Czech Republic, Flemingovo nam. 2, Prague 6 (Czech Republic); Pachl, Petr; Sieglová, Irena [Academy of Sciences of the Czech Republic, Flemingovo nam. 2, Prague 6 (Czech Republic); Academy of Sciences of the Czech Republic, Videnska 1083, Prague 4 (Czech Republic); Fábry, Milan [Academy of Sciences of the Czech Republic, Videnska 1083, Prague 4 (Czech Republic); Otwinowski, Zbyszek [UT Southwestern Medical Center, Dallas, Texas (United States); Řezáčová, Pavlína, E-mail: rezacova@uochb.cas.cz [Academy of Sciences of the Czech Republic, Flemingovo nam. 2, Prague 6 (Czech Republic); Academy of Sciences of the Czech Republic, Videnska 1083, Prague 4 (Czech Republic)

2012-02-01

The crystal structure of the effector-binding domain of the transcriptional repressor AraR from B. subtilis in complex with the effector molecule (l-arabinose) was determined at 2.2 Å resolution. A detailed analysis of the crystal identified a dimer organization that is distinctive from that of other members of the GalR/LacI family. In Bacillus subtilis, the arabinose repressor AraR negatively controls the expression of genes in the metabolic pathway of arabinose-containing polysaccharides. The protein is composed of two domains of different phylogenetic origin and function: an N-terminal DNA-binding domain belonging to the GntR family and a C-terminal effector-binding domain that shows similarity to members of the GalR/LacI family. The crystal structure of the C-terminal effector-binding domain of AraR in complex with the effector l-arabinose has been determined at 2.2 Å resolution. The l-arabinose binding affinity was characterized by isothermal titration calorimetry and differential scanning fluorimetry; the K{sub d} value was 8.4 ± 0.4 µM. The effect of l-arabinose on the protein oligomeric state was investigated in solution and detailed analysis of the crystal identified a dimer organization which is distinctive from that of other members of the GalR/LacI family.

DARHT-II Downstream Transport Beamline

International Nuclear Information System (INIS)

Westenskow, G A; Bertolini, L R; Duffy, P T; Paul, A C

2001-01-01

This paper describes the mechanical design of the downstream beam transport line for the second axis of the Dual Axis Radiographic Hydrodynamic Test (DARHT II) Facility. The DARHT-II project is a collaboration between LANL, LBNL and LLNL. DARHT II is a 18.4-MeV, 2000-Amperes, 2-(micro)sec linear induction accelerator designed to generate short bursts of x-rays for the purpose of radiographing dense objects. The downstream beam transport line is approximately 22-meter long region extending from the end of the accelerator to the bremsstrahlung target. Within this proposed transport line there are 12 conventional solenoid, quadrupole and dipole magnets; as well as several specialty magnets, which transport and focus the beam to the target and to the beam dumps. There are two high power beam dumps, which are designed to absorb 80-kJ per pulse during accelerator start-up and operation. Aspects of the mechanical design of these elements are presented

Yeast as a Heterologous Model System to Uncover Type III Effector Function.

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Crina Popa

2016-02-01

Full Text Available Type III effectors (T3E are key virulence proteins that are injected by bacterial pathogens inside the cells of their host to subvert cellular processes and contribute to disease. The budding yeast Saccharomyces cerevisiae represents an important heterologous system for the functional characterisation of T3E proteins in a eukaryotic environment. Importantly, yeast contains eukaryotic processes with low redundancy and are devoid of immunity mechanisms that counteract T3Es and mask their function. Expression in yeast of effectors from both plant and animal pathogens that perturb conserved cellular processes often resulted in robust phenotypes that were exploited to elucidate effector functions, biochemical properties, and host targets. The genetic tractability of yeast and its amenability for high-throughput functional studies contributed to the success of this system that, in recent years, has been used to study over 100 effectors. Here, we provide a critical view on this body of work and describe advantages and limitations inherent to the use of yeast in T3E research. "Favourite" targets of T3Es in yeast are cytoskeleton components and small GTPases of the Rho family. We describe how mitogen-activated protein kinase (MAPK signalling, vesicle trafficking, membrane structures, and programmed cell death are also often altered by T3Es in yeast and how this reflects their function in the natural host. We describe how effector structure-function studies and analysis of candidate targeted processes or pathways can be carried out in yeast. We critically analyse technologies that have been used in yeast to assign biochemical functions to T3Es, including transcriptomics and proteomics, as well as suppressor, gain-of-function, or synthetic lethality screens. We also describe how yeast can be used to select for molecules that block T3E function in search of new antibacterial drugs with medical applications. Finally, we provide our opinion on the limitations

Phytoplasma Effector SAP54 Induces Indeterminate Leaf-Like Flower Development in Arabidopsis Plants1[C][W][OA

Science.gov (United States)

MacLean, Allyson M.; Sugio, Akiko; Makarova, Olga V.; Findlay, Kim C.; Grieve, Victoria M.; Tóth, Réka; Nicolaisen, Mogens; Hogenhout, Saskia A.

2011-01-01

Phytoplasmas are insect-transmitted bacterial plant pathogens that cause considerable damage to a diverse range of agricultural crops globally. Symptoms induced in infected plants suggest that these phytopathogens may modulate developmental processes within the plant host. We report herein that Aster Yellows phytoplasma strain Witches’ Broom (AY-WB) readily infects the model plant Arabidopsis (Arabidopsis thaliana) ecotype Columbia, inducing symptoms that are characteristic of phytoplasma infection, such as the production of green leaf-like flowers (virescence and phyllody) and increased formation of stems and branches (witches’ broom). We found that the majority of genes encoding secreted AY-WB proteins (SAPs), which are candidate effector proteins, are expressed in Arabidopsis and the AY-WB insect vector Macrosteles quadrilineatus (Hemiptera; Cicadellidae). To identify which of these effector proteins induce symptoms of phyllody and virescence, we individually expressed the effector genes in Arabidopsis. From this screen, we have identified a novel AY-WB effector protein, SAP54, that alters floral development, resulting in the production of leaf-like flowers that are similar to those produced by plants infected with this phytoplasma. This study offers novel insight into the effector profile of an insect-transmitted plant pathogen and reports to our knowledge the first example of a microbial pathogen effector protein that targets flower development in a host. PMID:21849514

Depigmented-polymerised allergoids favour regulatory over effector T cells: enhancement by 1α, 25-dihydroxyvitamin D3.

Science.gov (United States)

Urry, Zoe L; Richards, David F; Black, Cheryl; Morales, Maria; Carnés, Jerónimo; Hawrylowicz, Catherine M; Robinson, Douglas S

2014-05-29

Allergen immunotherapy (SIT) is the only treatment for allergic disease capable of modifying disease long term. To reduce the risk of anaphylaxis from SIT, allergen-extracts have been modified by polymerisation with glutaraldehyde to reduce IgE binding. It is suggested that these allergoid extracts also have reduced T cell activity, which could compromise clinical efficacy. Effective SIT is thought to act through regulatory T cells (Tregs) rather than activation of effector T cells. There is no published data on the activity of modified extracts on Tregs. We compared the capacity of modified (depigmented-polymerised) versus unmodified (native) allergen extracts of grass pollen and house dust mite to stimulate proliferation/cytokine production and to modulate Treg/effector T cell frequency in cultures of peripheral blood mononuclear cells (PBMC), from volunteers sensitised to both allergens in vitro. Depigmented-polymerised allergen extracts stimulated less proliferation of PBMC, and reduced effector cell numbers after 7 days in culture than did native extracts. However, the frequency of Foxp3+ Tregs in cultures were similar to those seen with native extract so that ratios of regulatory to effector T cells were significantly increased in cultures stimulated with depigmented-polymerised extracts. Addition of 1α, 25-dihydroxyvitamin D3 further favoured Treg, and reduced effector cytokine production, but not interleukin-10. Depigmented-polymerised allergen extracts appear to favour Treg expansion over activation of effector T cells and this may relate to their demonstrated efficacy and safety in SIT. 1α, 25-dihydroxyvitamin D3 further reduces effector T cell activation by allergen extracts and may be a useful adjuvant for SIT.

Impact of sodium butyrate and mild hypothermia on metabolic and physiological behaviour of CHO TF 70R cells

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Veronica Avello

2017-05-01

Conclusions: The combination of NaBu addition and mild hypothermic condition causes an impact on physiological and metabolic state of CHO TF 70R cells, decreasing cell growth rate and improving glucose consumption efficiency. These results therefore provide a promising strategy to increase specific productivity of rh-tPA.

A bacterial toxin-antitoxin module is the origin of inter-bacterial and inter-kingdom effectors of Bartonella.

Science.gov (United States)

Harms, Alexander; Liesch, Marius; Körner, Jonas; Québatte, Maxime; Engel, Philipp; Dehio, Christoph

2017-10-01

Host-targeting type IV secretion systems (T4SS) evolved from conjugative T4SS machineries that mediate interbacterial plasmid transfer. However, the origins of effectors secreted by these virulence devices have remained largely elusive. Previous work showed that some effectors exhibit homology to toxins of bacterial toxin-antitoxin modules, but the evolutionary trajectories underlying these ties had not been resolved. We previously reported that FicT toxins of FicTA toxin-antitoxin modules disrupt cellular DNA topology via their enzymatic FIC (filamentation induced by cAMP) domain. Intriguingly, the FIC domain of the FicT toxin VbhT of Bartonella schoenbuchensis is fused to a type IV secretion signal-the BID (Bep intracellular delivery) domain-similar to the Bartonella effector proteins (Beps) that are secreted into eukaryotic host cells via the host-targeting VirB T4SS. In this study, we show that the VbhT toxin is an interbacterial effector protein secreted via the conjugative Vbh T4SS that is closely related to the VirB T4SS and encoded by plasmid pVbh of B. schoenbuchensis. We therefore propose that the Vbh T4SS together with its effector VbhT represent an evolutionary missing link on a path that leads from a regular conjugation system and FicTA toxin-antitoxin modules to the VirB T4SS and the Beps. Intriguingly, phylogenetic analyses revealed that the fusion of FIC and BID domains has probably occurred independently in VbhT and the common ancestor of the Beps, suggesting parallel evolutionary paths. Moreover, several other examples of TA module toxins that are bona fide substrates of conjugative T4SS indicate that their recruitment as interbacterial effectors is prevalent and serves yet unknown biological functions in the context of bacterial conjugation. We propose that the adaptation for interbacterial transfer favors the exaptation of FicT and other TA module toxins as inter-kingdom effectors and may thus constitute an important stepping stone in the

A bacterial toxin-antitoxin module is the origin of inter-bacterial and inter-kingdom effectors of Bartonella.

Directory of Open Access Journals (Sweden)

Alexander Harms

2017-10-01

Full Text Available Host-targeting type IV secretion systems (T4SS evolved from conjugative T4SS machineries that mediate interbacterial plasmid transfer. However, the origins of effectors secreted by these virulence devices have remained largely elusive. Previous work showed that some effectors exhibit homology to toxins of bacterial toxin-antitoxin modules, but the evolutionary trajectories underlying these ties had not been resolved. We previously reported that FicT toxins of FicTA toxin-antitoxin modules disrupt cellular DNA topology via their enzymatic FIC (filamentation induced by cAMP domain. Intriguingly, the FIC domain of the FicT toxin VbhT of Bartonella schoenbuchensis is fused to a type IV secretion signal-the BID (Bep intracellular delivery domain-similar to the Bartonella effector proteins (Beps that are secreted into eukaryotic host cells via the host-targeting VirB T4SS. In this study, we show that the VbhT toxin is an interbacterial effector protein secreted via the conjugative Vbh T4SS that is closely related to the VirB T4SS and encoded by plasmid pVbh of B. schoenbuchensis. We therefore propose that the Vbh T4SS together with its effector VbhT represent an evolutionary missing link on a path that leads from a regular conjugation system and FicTA toxin-antitoxin modules to the VirB T4SS and the Beps. Intriguingly, phylogenetic analyses revealed that the fusion of FIC and BID domains has probably occurred independently in VbhT and the common ancestor of the Beps, suggesting parallel evolutionary paths. Moreover, several other examples of TA module toxins that are bona fide substrates of conjugative T4SS indicate that their recruitment as interbacterial effectors is prevalent and serves yet unknown biological functions in the context of bacterial conjugation. We propose that the adaptation for interbacterial transfer favors the exaptation of FicT and other TA module toxins as inter-kingdom effectors and may thus constitute an important stepping

India's Downstream Petroleum Sector

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-07-01

This study provides a holistic examination of pricing and investment dynamics in India's downstream petroleum sector. It analyses the current pricing practices, highlights the tremendous fiscal cost of current pricing and regulatory arrangements, and examines the sectoral investment dynamics. It also looks at potential paths towards market-based reform along which the Indian government may move, while at the same time protecting energy market access for India's large poor population.

Repertoire Development and the Control of Cytotoxic/Effector Function in Human γδ T Cells

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Elizabeth M. Urban

2010-01-01

Full Text Available T cells develop into two major populations distinguished by their T cell receptor (TCR chains. Cells with the αβ TCR generally express CD4 or CD8 lineage markers and mostly fall into helper or cytotoxic/effector subsets. Cells expressing the alternate γδ TCR in humans generally do not express lineage markers, do not require MHC for antigen presentation, and recognize nonpeptidic antigens. We are interested in the dominant Vγ2Vδ2+ T cell subset in human peripheral blood and the control of effector function in this population. We review the literature on γδ T cell generation and repertoire selection, along with recent work on CD56 expression and defining a cytotoxic/effector lineage within the phosphoantigen-reactive Vγ2Vδ2 cells. A unique mechanism for MHC-independent repertoire selection is linked to the control of effector function that is vital to the role for γδ T cells in tumor surveillance. Better understanding of these mechanisms will improve our ability to exploit this population for tumor immunotherapy.

A translocator-specific export signal establishes the translocator-effector secretion hierarchy that is important for type III secretion system function

Science.gov (United States)

Tomalka, Amanda G.; Stopford, Charles M.; Lee, Pei-Chung; Rietsch, Arne

2012-01-01

Summary Type III secretion systems are used by many Gram-negative pathogens to directly deliver effector proteins into the cytoplasm of host cells. To accomplish this, bacteria secrete translocator proteins that form a pore in the host-cell membrane through which the effector proteins are then introduced into the host cell. Evidence from multiple systems indicates that the pore-forming translocator proteins are exported before effectors, but how this secretion hierarchy is established is unclear. Here we used the P. aeruginosa translocator protein PopD as a model to identify its export signals. The amino-terminal secretion signal and chaperone, PcrH, are required for export under all conditions. Two novel signals in PopD, one proximal to the chaperone-binding site and one at the very C-terminus of the protein, are required for export of PopD before effector proteins. These novel export signals establish the translocator-effector secretion hierarchy, which in turn, is critical for the delivery of effectors into host cells. PMID:23121689

Structure and evolution of barley powdery mildew effector candidates

DEFF Research Database (Denmark)

Pedersen, Carsten; Themaat, Emiel Ver Loren van; McGuffin, Liam J.

2012-01-01

Protein effectors of pathogenicity are instrumental in modulating host immunity and disease resistance. The powdery mildew pathogen of grasses Blumeria graminis causes one of the most important diseases of cereal crops. B. graminis is an obligate biotrophic pathogen and as such has an absolute...

Solvent extraction of Pu(IV) with TODGA in C6mimTf2N

International Nuclear Information System (INIS)

Xiaohong Huang; Qiuyue Zhang; Jinping Liu; Hui He; Wenbin Zhu; Xiaorong Wang

2013-01-01

Studies on the solvent extraction of Plutonium(Pu(IV)) from aqueous nitric acid by N,N,N'N'tetraoctyl-diglycolamide (TODGA) in 1-hexyl-3-methylimidazolium-bis(trifluoromethylsulfonyl) imide (C 6 mimTf 2 N) room temperature ionic liquid (RTIL) were carried out. It was found that Pu(IV) is extracted into RTIL phase as [Pu(NO 3 )(TODGA)] 3+ through cation exchange mechanism. Extraction reaction equation is obtained by the influence of acidity and extractant concentration, and the parameters of thermodynamic equilibrium constant was calculated. (author)

Generation of knockout rabbits using transcription activator-like effector nucleases

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Yu Wang

2014-01-01

Full Text Available Zinc-finger nucleases and transcription activator-like effector nucleases are novel gene-editing platforms contributing to redefine the boundaries of modern biological research. They are composed of a non-specific cleavage domain and a tailor made DNA-binding module, which enables a broad range of genetic modifications by inducing efficient DNA double-strand breaks at desired loci. Among other remarkable uses, these nucleases have been employed to produce gene knockouts in mid-size and large animals, such as rabbits and pigs, respectively. This approach is cost effective, relatively quick, and can produce invaluable models for human disease studies, biotechnology or agricultural purposes. Here we describe a protocol for the efficient generation of knockout rabbits using transcription activator-like effector nucleases, and a perspective of the field.

Test plan for the remote conveyance and innovative end effector demonstration

Energy Technology Data Exchange (ETDEWEB)

Rice, P.; Smith, A.M. [EG& G Idaho, Inc., Idaho Falls, ID (United States). Idaho National Engineering Lab.; Peterson, R.

1994-08-01

This test plan describes the demonstration of innovative equipment and processes specifically designed to be superior to currently employed technology for buried waste retrieval. The dumping of dry soil into a funnel/dumpster arrangement has been found to be the primary mechanism for dust generation during the retrieval of buried transuranic waste. The primary goal of the innovative end effector is to reduce dust generation and the potential spread of airborne contaminants during the dumping operation. In addition, regardless of the excavation technique, exhumed waste will have to be conveyed away from the retrieval area to a packaging area or directly to a treatment facility. The remote conveyance system is aimed at developing a remotely controlled vehicle to convey retrieved waste that will operate on variable terrain and remove workers from the hazardous zone. To demonstrate the remote conveyance system and the innovative end effector, the Buried Waste Integrated Demonstration (BWID) Program has subcontracted with RAHCO International to provide equipment and services to perform a demonstration of the technologies. The demonstration will be performed in two phases. In Phase I, the subcontractor will perform a full scale demonstration to assess the ability of the innovative end effector to control dust generation and the potential spread of contamination during dumping operations. Phase II includes performing a retrieval/conveyance demonstration. This demonstration will excavate, dump, and convey simulated waste to demonstrate the functionality of the system (e.g., maneuverability, retrieval rates, and system integration). Phase II of the demonstration will include all elements of the remote conveyance and end effector system. This test plan will describe the demonstration objectives, data quality objectives, equipment operation, and methods for collecting data during the demonstration.

Test plan for the remote conveyance and innovative end effector demonstration

International Nuclear Information System (INIS)

Rice, P.; Smith, A.M.; Peterson, R.

1994-08-01

This test plan describes the demonstration of innovative equipment and processes specifically designed to be superior to currently employed technology for buried waste retrieval. The dumping of dry soil into a funnel/dumpster arrangement has been found to be the primary mechanism for dust generation during the retrieval of buried transuranic waste. The primary goal of the innovative end effector is to reduce dust generation and the potential spread of airborne contaminants during the dumping operation. In addition, regardless of the excavation technique, exhumed waste will have to be conveyed away from the retrieval area to a packaging area or directly to a treatment facility. The remote conveyance system is aimed at developing a remotely controlled vehicle to convey retrieved waste that will operate on variable terrain and remove workers from the hazardous zone. To demonstrate the remote conveyance system and the innovative end effector, the Buried Waste Integrated Demonstration (BWID) Program has subcontracted with RAHCO International to provide equipment and services to perform a demonstration of the technologies. The demonstration will be performed in two phases. In Phase I, the subcontractor will perform a full scale demonstration to assess the ability of the innovative end effector to control dust generation and the potential spread of contamination during dumping operations. Phase II includes performing a retrieval/conveyance demonstration. This demonstration will excavate, dump, and convey simulated waste to demonstrate the functionality of the system (e.g., maneuverability, retrieval rates, and system integration). Phase II of the demonstration will include all elements of the remote conveyance and end effector system. This test plan will describe the demonstration objectives, data quality objectives, equipment operation, and methods for collecting data during the demonstration

Interaction of barley powdery mildew effector candidate CSEP0055 with the defence protein PR17c

DEFF Research Database (Denmark)

Zhang, Wenjing; Pedersen, Carsten; Kwaaitaal, Mark Adrianus Cornelis J

2012-01-01

A large number of effector candidates have been identified recently in powdery mildew fungi. However, their roles and how they perform their functions remain unresolved. In this study, we made use of host-induced gene silencing and confirmed that the secreted barley powdery mildew effector candid...

The role of headwater streams in downstream water quality

Science.gov (United States)

Alexander, R.B.; Boyer, E.W.; Smith, R.A.; Schwarz, G.E.; Moore, R.B.

2007-01-01

Knowledge of headwater influences on the water-quality and flow conditions of downstream waters is essential to water-resource management at all governmental levels; this includes recent court decisions on the jurisdiction of the Federal Clean Water Act (CWA) over upland areas that contribute to larger downstream water bodies. We review current watershed research and use a water-quality model to investigate headwater influences on downstream receiving waters. Our evaluations demonstrate the intrinsic connections of headwaters to landscape processes and downstream waters through their influence on the supply, transport, and fate of water and solutes in watersheds. Hydrological processes in headwater catchments control the recharge of subsurface water stores, flow paths, and residence times of water throughout landscapes. The dynamic coupling of hydrological and biogeochemical processes in upland streams further controls the chemical form, timing, and longitudinal distances of solute transport to downstream waters. We apply the spatially explicit, mass-balance watershed model SPARROW to consider transport and transformations of water and nutrients throughout stream networks in the northeastern United States. We simulate fluxes of nitrogen, a primary nutrient that is a water-quality concern for acidification of streams and lakes and eutrophication of coastal waters, and refine the model structure to include literature observations of nitrogen removal in streams and lakes. We quantify nitrogen transport from headwaters to downstream navigable waters, where headwaters are defined within the model as first-order, perennial streams that include flow and nitrogen contributions from smaller, intermittent and ephemeral streams. We find that first-order headwaters contribute approximately 70% of the mean-annual water volume and 65% of the nitrogen flux in second-order streams. Their contributions to mean water volume and nitrogen flux decline only marginally to about 55% and

On design and development of additional End-Effectors for the Cassette Multifunctional Mover

Energy Technology Data Exchange (ETDEWEB)

Valkama, Peetu, E-mail: peetu.valkama@tut.fi [Department of Intelligent Hydraulics and Automation, Tampere University of Technology, P.O. Box 589, FI-33720 Tampere (Finland); Mattila, J.; Amjad, F.; Vaeyrynen, J.; Vilenius, M. [Department of Intelligent Hydraulics and Automation, Tampere University of Technology, P.O. Box 589, FI-33720 Tampere (Finland); Siuko, M. [VTT Technical Research Centre of Finland, P.O. Box 1300, FI-33101 Tampere (Finland); Semeraro, L.; Esque, S. [F4E, Fusion for Energy, Torres Diagonal Litoral B3, Josep Pla 2, 08019 Barcelona (Spain)

2011-10-15

The divertor area of ITER Vacuum Vessel (VV) consists of 54 modular cassettes which must be replaced three times during the estimated 20 years of operation of the ITER. Cassette Multifunctional Mover (CMM) and Cassette Toroidal Mover (CTM) are used in the cassette remote handling (RH). In this paper we discuss the design and development process for the RH equipment to be used in the ITER environment. Design concepts for the Standard Cassette End-Effector and Central Cassette End-Effector are described and the conceptual design phase methodology is presented. The main improvements of the new End-Effector concept designs are more robust and reliable assembly process with reduced CMM mover assembly accuracy requirement. New Central Cassette locking system was developed to address the high forces and contact pressures emerging during the Central Cassette installation. The chosen design concepts are verified with virtual reality simulations and are fulfilling the requirements defined in the concept design phase, including structural, assembly sequence, safety and reliability.

Identification and Initial Characterization of the Effectors of an Anther Smut Fungus and Potential Host Target Proteins

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Venkata S. Kuppireddy

2017-11-01

Full Text Available (1 Background: Plant pathogenic fungi often display high levels of host specificity and biotrophic fungi; in particular, they must manipulate their hosts to avoid detection and to complete their obligate pathogenic lifecycles. One important strategy of such fungi is the secretion of small proteins that serve as effectors in this process. Microbotryum violaceum is a species complex whose members infect members of the Caryophyllaceae; M. lychnidis-dioicae, a parasite on Silene latifolia, is one of the best studied interactions. We are interested in identifying and characterizing effectors of the fungus and possible corresponding host targets; (2 Methods: In silico analysis of the M. lychnidis-dioicae genome and transcriptomes allowed us to predict a pool of small secreted proteins (SSPs with the hallmarks of effectors, including a lack of conserved protein family (PFAM domains and also localized regions of disorder. Putative SSPs were tested for secretion using a yeast secretion trap method. We then used yeast two-hybrid analyses for candidate-secreted effectors to probe a cDNA library from a range of growth conditions of the fungus, including infected plants; (3 Results: Roughly 50 SSPs were identified by in silico analysis. Of these, 4 were studied further and shown to be secreted, as well as examined for potential host interactors. One of the putative effectors, MVLG_01732, was found to interact with Arabidopsis thaliana calcium-dependent lipid binding protein (AtCLB and with cellulose synthase interactive protein 1 orthologues; and (4 Conclusions: The identification of a pool of putative effectors provides a resource for functional characterization of fungal proteins that mediate the delicate interaction between pathogen and host. The candidate targets of effectors, e.g., AtCLB, involved in pollen germination suggest tantalizing insights that could drive future studies.

Downstream Yangtze River levels impacted by Three Gorges Dam

International Nuclear Information System (INIS)

Wang, Jida; Sheng, Yongwei; Gleason, Colin J; Wada, Yoshihide

2013-01-01

Changes in the Yangtze River level induced by large-scale human water regulation have profound implications on the inundation dynamics of surrounding lakes/wetlands and the integrity of related ecosystems. Using in situ measurements and hydrological simulation, this study reveals an altered Yangtze level regime downstream from the Three Gorges Dam (TGD) to the Yangtze estuary in the East China Sea as a combined result of (i) TGD’s flow regulation and (ii) Yangtze channel erosion due to reduced sediment load. During the average annual cycle of TGD’s regular flow control in 2009–2012, downstream Yangtze level variations were estimated to have been reduced by 3.9–13.5% at 15 studied gauging stations, manifested as evident level decrease in fall and increase in winter and spring. The impacts on Yangtze levels generally diminished in a longitudinal direction from the TGD to the estuary, with a total time lag of ∼9–12 days. Chronic Yangtze channel erosion since the TGD closure has lowered water levels in relation to flows at most downstream stations, which in turn counteracts the anticipated level increase by nearly or over 50% in winter and spring while reinforcing the anticipated level decrease by over 20% in fall. Continuous downstream channel erosion in the near future may further counteract the benefit of increased Yangtze levels during TGD’s water supplement in winter and accelerate the receding of inundation areas/levels of downstream lakes in fall. (letter)

Evidence for acquisition of virulence effectors in pathogenic chytrids

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Summers Kyle

2011-07-01

Full Text Available Abstract Background The decline in amphibian populations across the world is frequently linked to the infection of the chytrid fungus Batrachochytrium dendrobatidis (Bd. This is particularly perplexing because Bd was only recently discovered in 1999 and no chytrid fungus had previously been identified as a vertebrate pathogen. Results In this study, we show that two large families of known virulence effector genes, crinkler (CRN proteins and serine peptidases, were acquired by Bd from oomycete pathogens and bacteria, respectively. These two families have been duplicated after their acquisition by Bd. Additional selection analyses indicate that both families evolved under strong positive selection, suggesting that they are involved in the adaptation of Bd to its hosts. Conclusions We propose that the acquisition of virulence effectors, in combination with habitat disruption and climate change, may have driven the Bd epidemics and the decline in amphibian populations. This finding provides a starting point for biochemical investigations of chytridiomycosis.

DENSITY FLUCTUATIONS UPSTREAM AND DOWNSTREAM OF INTERPLANETARY SHOCKS

Energy Technology Data Exchange (ETDEWEB)

Pitňa, A.; Šafránková, J.; Němeček, Z.; Goncharov, O.; Němec, F.; Přech, L. [Charles University, Faculty of Mathematics and Physics, V Holešovičkách 2, 180 00 Prague 8 (Czech Republic); Chen, C. H. K. [Department of Physics, Imperial College London, London SW7 2AZ (United Kingdom); Zastenker, G. N., E-mail: jana.safrankova@mff.cuni.cz [Space Research Institute of Russian Academy of Sciences, Moscow, Russia, Profsoyuznaya ul. 84/32, Moscow 117997 (Russian Federation)

2016-03-01

Interplanetary (IP) shocks as typical large-scale disturbances arising from processes such as stream–stream interactions or Interplanetary Coronal Mass Ejection (ICME) launching play a significant role in the energy redistribution, dissipation, particle heating, acceleration, etc. They can change the properties of the turbulent cascade on shorter scales. We focus on changes of the level and spectral properties of ion flux fluctuations upstream and downstream of fast forward oblique shocks. Although the fluctuation level increases by an order of magnitude across the shock, the spectral slope in the magnetohydrodynamic range is conserved. The frequency spectra upstream of IP shocks are the same as those in the solar wind (if not spoiled by foreshock waves). The spectral slopes downstream are roughly proportional to the corresponding slopes upstream, suggesting that the properties of the turbulent cascade are conserved across the shock; thus, the shock does not destroy the shape of the spectrum as turbulence passes through it. Frequency spectra downstream of IP shocks often exhibit “an exponential decay” in the ion kinetic range that was earlier reported at electron scales in the solar wind or at ion scales in the interstellar medium. We suggest that the exponential shape of ion flux spectra in this range is caused by stronger damping of the fluctuations in the downstream region.

Field performance of the waste retrieval end effectors in the Oak Ridge gunite tanks

International Nuclear Information System (INIS)

Mullen, O.D.

1997-09-01

Waterjet-based tank waste retrieval end effectors have been developed by Retrieval Process Development and Enhancements through several generations of test articles targeted at deployment in Hanford underground storage tanks with a large robotic arm. The basic technology has demonstrated effectiveness for retrieval of simulants bounding a wide range of waste properties and compatibility with foreseen deployment systems. The Oak Ridge National Laboratory (ORNL) selected the waterjet scarifying end effector, the jet pump conveyance system, and the Modified Light Duty Utility Arm and Houdini Remotely Operated Vehicle deployment and manipulator systems for evaluation in the Gunite and Associated Tanks Treatability Study (GAAT-TS). The Retrieval Process Development and Enhancements (RPD ampersand E) team was tasked with developing a version of the retrieval end effector tailored to the Oak Ridge tanks, waste, and deployment platforms. The conceptual design was done by the University of Missouri-Rolla in FY 1995-96. The university researchers conducted separate effects tests of the component concepts, scaled the basic design features, and constructed a full-scale test article incorporating their findings in early FY 1996. The test article was extensively evaluated in the Hanford Hydraulic Testbed and the design features were further refined. Detail design of the prototype item was started at Waterjet Technology, Inc. before the development testing was finished, and two of the three main subassemblies were substantially complete before final design of the waterjet manifold was determined from the Hanford hydraulic testbed (HTB) testing. The manifold on the first prototype was optimized for sludge retrieval; assembled with that manifold, the end effector is termed the Sludge Retrieval End Effector (SREE)

Modulation of innate immune responses by Yersinia type III secretion system translocators and effectors.

Science.gov (United States)

Bliska, James B; Wang, Xiaoying; Viboud, Gloria I; Brodsky, Igor E

2013-10-01

The innate immune system of mammals responds to microbial infection through detection of conserved molecular determinants called 'pathogen-associated molecular patterns' (PAMPs). Pathogens use virulence factors to counteract PAMP-directed responses. The innate immune system can in turn recognize signals generated by virulence factors, allowing for a heightened response to dangerous pathogens. Many Gram-negative bacterial pathogens encode type III secretion systems (T3SSs) that translocate effector proteins, subvert PAMP-directed responses and are critical for infection. A plasmid-encoded T3SS in the human-pathogenic Yersinia species translocates seven effectors into infected host cells. Delivery of effectors by the T3SS requires plasma membrane insertion of two translocators, which are thought to form a channel called a translocon. Studies of the Yersinia T3SS have provided key advances in our understanding of how innate immune responses are generated by perturbations in plasma membrane and other signals that result from translocon insertion. Additionally, studies in this system revealed that effectors function to inhibit innateimmune responses resulting from insertion of translocons into plasma membrane. Here, we review these advances with the goal of providing insight into how a T3SS can activate and inhibit innate immune responses, allowing a virulent pathogen to bypass host defences. © 2013 John Wiley & Sons Ltd.

A massive expansion of effector genes underlies gall-formation in the wheat pest Mayetiola destructor

DEFF Research Database (Denmark)

Zhao, Chaoyang; Escalante, Lucio Navarro; Chen, Hang

2015-01-01

Gall-forming arthropods are highly specialized herbivores that, in combination with their hosts, produce extended phenotypes with unique morphologies [1]. Many are economically important, and others have improved our understanding of ecology and adaptive radiation [2]. However, the mechanisms...... in plants and E3-ligase-mimicking effectors in plant pathogenic bacteria. SSGP-71 proteins and wheat Skp proteins interact in vivo. Mutations in different SSGP-71 genes avoid the effector-triggered immunity that is directed by the wheat resistance genes H6 and H9. Results point to effectors as the agents...

Effector protein translocation by the Coxiella burnetii Dot/Icm type IV secretion system requires endocytic maturation of the pathogen-occupied vacuole.

Directory of Open Access Journals (Sweden)

Hayley J Newton

Full Text Available The human pathogen Coxiella burnetii encodes a type IV secretion system called Dot/Icm that is essential for intracellular replication. The Dot/Icm system delivers bacterial effector proteins into the host cytosol during infection. The effector proteins delivered by C. burnetii are predicted to have important functions during infection, but when these proteins are needed during infection has not been clearly defined. Here, we use a reporter system consisting of fusion proteins that have a β-lactamase enzyme (BlaM fused to C. burnetii effector proteins to study protein translocation by the Dot/Icm system. Translocation of BlaM fused to the effector proteins CBU0077, CBU1823 and CBU1524 was not detected until 8-hours after infection of HeLa cells, which are permissive for C. burnetii replication. Translocation of these effector fusion proteins by the Dot/Icm system required acidification of the Coxiella-containing vacuole. Silencing of the host genes encoding the membrane transport regulators Rab5 or Rab7 interfered with effector translocation, which indicates that effectors are not translocated until bacteria traffic to a late endocytic compartment in the host cell. Similar requirements for effector translocation were discerned in bone marrow macrophages derived from C57BL/6 mice, which are primary cells that restrict the intracellular replication of C. burnetii. In addition to requiring endocytic maturation of the vacuole for Dot/Icm-mediated translocation of effectors, bacterial transcription was required for this process. Thus, translocation of effector proteins by the C. burnetii Dot/Icm system occurs after acidification of the CCV and maturation of this specialized organelle to a late endocytic compartment. This indicates that creation of the specialized vacuole in which C. burnetii replicates represents a two-stage process mediated initially by host factors that regulate endocytic maturation and then by bacterial effectors delivered into

Critical effects of downstream boundary conditions on vortex breakdown

Science.gov (United States)

Kandil, Osama; Kandil, Hamdy A.; Liu, C. H.

1992-01-01

The unsteady, compressible, full Navier-Stokes (NS) equations are used to study the critical effects of the downstream boundary conditions on the supersonic vortex breakdown. The present study is applied to two supersonic vortex breakdown cases. In the first case, quasi-axisymmetric supersonic swirling flow is considered in a configured circular duct, and in the second case, quasi-axisymmetric supersonic swirling jet, that is issued from a nozzle into a supersonic jet of lower Mach number, is considered. For the configured duct flow, four different types of downstream boundary conditions are used, and for the swirling jet flow from the nozzle, two types of downstream boundary conditions are used. The solutions are time accurate which are obtained using an implicit, upwind, flux-difference splitting, finite-volume scheme.

A Legionella Effector Disrupts Host Cytoskeletal Structure by Cleaving Actin.

Directory of Open Access Journals (Sweden)

Yao Liu

2017-01-01

Full Text Available Legionella pneumophila, the etiological agent of Legionnaires' disease, replicates intracellularly in protozoan and human hosts. Successful colonization and replication of this pathogen in host cells requires the Dot/Icm type IVB secretion system, which translocates approximately 300 effector proteins into the host cell to modulate various cellular processes. In this study, we identified RavK as a Dot/Icm substrate that targets the host cytoskeleton and reduces actin filament abundance in mammalian cells upon ectopic expression. RavK harbors an H95EXXH99 motif associated with diverse metalloproteases, which is essential for the inhibition of yeast growth and for the induction of cell rounding in HEK293T cells. We demonstrate that the actin protein itself is the cellular target of RavK and that this effector cleaves actin at a site between residues Thr351 and Phe352. Importantly, RavK-mediated actin cleavage also occurs during L. pneumophila infection. Cleavage by RavK abolishes the ability of actin to form polymers. Furthermore, an F352A mutation renders actin resistant to RavK-mediated cleavage; expression of the mutant in mammalian cells suppresses the cell rounding phenotype caused by RavK, further establishing that actin is the physiological substrate of RavK. Thus, L. pneumophila exploits components of the host cytoskeleton by multiple effectors with distinct mechanisms, highlighting the importance of modulating cellular processes governed by the actin cytoskeleton in the intracellular life cycle of this pathogen.

Parametric thermo-hydraulic analysis of the TF system of JT-60SA during fast discharge

International Nuclear Information System (INIS)

Polli, Gian Mario; Lacroix, Benoit; Zani, Louis; Besi Vetrella, Ugo; Cucchiaro, Antonio

2013-01-01

Highlights: • We modeled the central clock-wise pancake of JT-60SA TF magnet at the EOB. • We simulated a quench followed by a fast discharge. • We evaluated the temperature and pressure rises in the nominal configuration. • We evaluated the effect of several parameter changes on the thermal-hydraulic response of the system. -- Abstract: The evolution of the conductor temperature and of the helium pressure of the central pancake of the TF superconducting magnet of the JT-60SA tokamak in a quench scenario are here discussed. The quench is triggered by a heat disturbance applied at the end of burning and followed by a fast safety discharge. A parametric study aimed at assessing the robustness of the calculation is also addressed with special regard to the voltage threshold, used to define the occurrence of the quench, and to the time delay, that cover all the possible delays in the fast discharge after quench detection. Finally, due to sensitivity analyses the influences of different parameters were assessed: the material properties of the strands (RRR, copper fraction), the magnitude and the spatial length of the triggering disturbance and the magnetic field distribution. The numerical evaluations were performed in the framework of the Broader Approach Agreement in collaboration with CEA, ENEA and the JT-60SA European Home Team using the 1D code Gandalf [1

Cladding Heatup Prediction between Spacer Grids for the Downstream Effect Evaluation

International Nuclear Information System (INIS)

Park, J. Y.; Kim, M. W.

2009-01-01

Since a recirculation sump clogging issue by debris generated from high energy pipe line break had been invoked as GSI-191 in the US, many researches on this issue have been undertaken. Previous researches on this topic are well summarized in Bang et al. Due to comprehensive nature of the issue, it includes many area of research and one of them is the area of downstream effect evaluation. The downstream effect is involved with adverse effects of debris passing the sump screen on the downstream systems, components and piping including core and it can be further divided into an ex-vessel downstream effect and an in-vessel downstream effect. In the ex-vessel downstream effect, focus is laid on plugging of spray nozzle, wearing and abrasion of moving parts of pump and valve and etc. Otherwise, a debris effect on reactor core is focused in the in-vessel downstream effect. Since debris can be ingested in the core or the systems of downstream of sump screen during recirculation, basically the downstream effect influences long-term core cooling phase. With respect to the in-vessel downstream effect, an up-to-date evaluation methodology is well summarized in a topical report submitted to the US nuclear regulatory commission by the pressurized water reactor owners group (PWROG). The report evaluates various aspects of debris ingestion in the core such as blockage at the core inlet, collection of debris on fuel grids, plating-out of fuel, chemical precipitants, protective coatings effect and etc. Most of them are evaluated qualitative manner based on previous research results and geometrical consideration on fuel rod bundles but some of them are also backed up by quantitative calculations to corroborate the qualitative decisions. One of them is a cladding heatup calculation between spacer grids. This is done to demonstrate that the cladding temperature of a fuel rod between grids with debris deposited on the clad surface in a post- LOCA recirculation environment is below

Orbital maneuvering vehicle end effectors

Science.gov (United States)

Myers, W. Neill (Inventor); Forbes, John C. (Inventor); Barnes, Wayne L. (Inventor)

1988-01-01

An end effector device (A) for grasping and holding an article such as a handle (18) of a space telescope is disclosed. The device includes a V-shaped capture window (74) defined as inclined surfaces (76, 78) in parallel face plates (22, 24) which converge toward a retainer recess (54) in which the handle is retained. A pivotal finger (30) meshes with a pair of pivoted fingers (26, 28) which rotate in counterrotation. The fingers rotate to pull a handle within the capture window into recess (54) where latches (50) lock handle (18) in the recess. To align the capture window, plates (22, 24) may be cocked plus or minus five degrees on base (64).

An engineered tale-transcription factor rescues transcription of factor VII impaired by promoter mutations and enhances its endogenous expression in hepatocytes.

Science.gov (United States)

Barbon, Elena; Pignani, Silvia; Branchini, Alessio; Bernardi, Francesco; Pinotti, Mirko; Bovolenta, Matteo

2016-06-24

Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.

Tomato Cf resistance proteins mediate recognition of cognate homologous effectors from fungi pathogenic on diots and monocots

NARCIS (Netherlands)

Stergiopoulos, I.; Burg, van den H.A.; Ökmen, B.; Beenen, H.G.; Liere, van S.; Kema, G.H.J.; Wit, de P.J.G.M.

2010-01-01

Most fungal effectors characterized so far are species-specific and facilitate virulence on a particular host plant. During infection of its host tomato, Cladosporium fulvum secretes effectors that function as virulence factors in the absence of cognate Cf resistance proteins and induce

Mortality of zebra mussel, Dreissena polymorpha, veligers during downstream transport

Science.gov (United States)

Horvath, T.G.; Lamberti, G.A.

1999-01-01

1. Streams flowing from lakes which contain zebra mussels, Dreissena polymorpha, provide apparently suitable habitats for mussel colonization and downstream range expansion, yet most such streams contain few adult mussels. We postulated that mussel veligers experience high mortality during dispersal via downstream transport. They tested this hypothesis in Christiana Creek, a lake-outlet stream in south-western Michigan, U.S.A., in which adult mussel density declined exponentially with distance downstream. 2. A staining technique using neutral red was developed and tested to distinguish quickly live and dead veligers. Live and dead veligers were distinguishable after an exposure of fresh samples to 13.3 mg L-1 of neutral red for 3 h. 3. Neutral red was used to determine the proportion of live veligers in samples taken longitudinally along Christiana Creek. The proportion of live veligers (mean ?? SE) declined from 90 ?? 3% at the lake outlet to 40 ?? 8% 18 km downstream. 4. Veligers appear to be highly susceptible to damage by physical forces (e.g. shear), and therefore, mortality in turbulent streams could be an important mechanism limiting zebra mussel dispersal to downstream reaches. Predictions of zebra mussel spread and population growth should consider lake-stream linkages and high mortality in running waters.

Mercury exposure in terrestrial birds far downstream of an historical point source

Energy Technology Data Exchange (ETDEWEB)

Jackson, Allyson K., E-mail: allyson.jackson@briloon.org [Biodiversity Research Institute, 19 Flaggy Meadow Road, Gorham, ME 04038 (United States); Institute for Integrative Bird Behavior Studies, Department of Biology, College of William and Mary, PO Box 8795, Williamsburg, VA 23187 (United States); Evers, David C.; Folsom, Sarah B. [Biodiversity Research Institute, 19 Flaggy Meadow Road, Gorham, ME 04038 (United States); Condon, Anne M. [U.S. Fish and Wildlife Service, 6669 Short Lane, Gloucester, VA 23061 (United States); Diener, John; Goodrick, Lizzie F. [Biodiversity Research Institute, 19 Flaggy Meadow Road, Gorham, ME 04038 (United States); McGann, Andrew J. [Institute for Integrative Bird Behavior Studies, Department of Biology, College of William and Mary, PO Box 8795, Williamsburg, VA 23187 (United States); Schmerfeld, John [U.S. Fish and Wildlife Service, 6669 Short Lane, Gloucester, VA 23061 (United States); Cristol, Daniel A. [Institute for Integrative Bird Behavior Studies, Department of Biology, College of William and Mary, PO Box 8795, Williamsburg, VA 23187 (United States)

2011-12-15

Mercury (Hg) is a persistent environmental contaminant found in many freshwater and marine ecosystems. Historical Hg contamination in rivers can impact the surrounding terrestrial ecosystem, but there is little known about how far downstream this contamination persists. In 2009, we sampled terrestrial forest songbirds at five floodplain sites up to 137 km downstream of an historical source of Hg along the South and South Fork Shenandoah Rivers (Virginia, USA). We found that blood total Hg concentrations remained elevated over the entire sampling area and there was little evidence of decline with distance. While it is well known that Hg is a pervasive and long-lasting aquatic contaminant, it has only been recently recognized that it also biomagnifies effectively in floodplain forest food webs. This study extends the area of concern for terrestrial habitats near contaminated rivers for more than 100 km downstream from a waterborne Hg point source. - Highlights: > We report blood mercury levels for terrestrial songbirds downstream of contamination. > Blood mercury levels remain elevated above reference for at least 137 km downstream. > Trends vary based on foraging guild and migration strategy. > Mercury affects terrestrial biota farther downstream than previously documented. - Blood mercury levels of forest songbirds remain elevated above reference levels for at least 137 km downstream of historical point source.

Separation of toluene from n-heptane by liquid–liquid extraction using binary mixtures of [bpy][BF4] and [4bmpy][Tf2N] ionic liquids as solvent

International Nuclear Information System (INIS)

García, Silvia; Larriba, Marcos; García, Julián; Torrecilla, José S.; Rodríguez, Francisco

2012-01-01

Highlights: ► Binary mixtures of ionic liquids as extraction solvents of aromatics. ► [4bmpy][Tf 2 N] shows higher capacity but lower selectivity than sulfolane. ► [bpy][BF 4 ] shows lower capacity but higher selectivity than sulfolane. ► Mixed {[4bmpy][Tf 2 N] + [bpy][BF 4 ]} improves both extractive properties. - Abstract: The use of binary mixture of ionic liquids N-butylpyridinium tetrafluoroborate ([bpy][BF 4 ]), and 1-butyl-4-methylpyridinium bis(trifluoromethylsulfonyl)imide ([4bmpy][Tf 2 N]) in the liquid–liquid extraction of toluene from n-heptane has been investigated at 313.2 K and atmospheric pressure. The experimental capacity of extraction and selectivity for this binary mixture has proved to be intermediate to those corresponding to the pure ionic liquids, and they can be predicted using a logarithmic–linear model of solubility. Furthermore, the results showed that the use of binary mixture of {[bpy][BF 4 ] + [4bmpy][Tf 2 N]} at a mole solvent composition around 0.7 for [bpy][BF 4 ] improves both the capacity of extraction of toluene and the selectivity with respect to those of sulfolane, the organic solvent taken as a benchmark. Thus, this mixed ionic liquid could be likely to be used in the extraction of aromatic from aliphatic in replacement to sulfolane.

Protecting and rescuing the effectors: roles of differentiation and survival in the control of memory T cell development

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Sema eKurtulus

2013-01-01

Full Text Available Vaccines, arguably the single most important intervention in improving human health, have exploited the phenomenon of immunological memory. The elicitation of memory T cells is often an essential part of successful long-lived protective immunity. Our understanding of T cell memory has been greatly aided by the development of TCR Tg mice and MHC tetrameric staining reagents that have allowed the precise tracking of antigen-specific T cell responses. Indeed, following acute infection or immunization, naïve T cells undergo a massive expansion culminating in the generation of a robust effector T cell population. This peak effector response is relatively short-lived and, while most effector T cells die by apoptosis, some remain and develop into memory cells. Although the molecular mechanisms underlying this cell fate decision remain incompletely defined, substantial progress has been made, particularly with regards to CD8+ T cells. For example, the effector CD8+ T cells generated during a response are heterogeneous, consisting of cells with more or less potential to develop into full-fledged memory cells. Development of CD8+ T cell memory is regulated by the transcriptional programs that control the differentiation and survival of effector T cells. While the type of antigenic stimulation and level of inflammation control effector CD8+ T cell differentiation, availability of cytokines and their ability to control expression and function of Bcl-2 family members governs their survival. These distinct differentiation and survival programs may allow for finer therapeutic intervention to control both the quality and quantity of CD8+ T cell memory. Effector to memory transition of CD4+ T cells is less well characterized than CD8+ T cells, emerging details will be discussed. This review will focus on the recent progress made in our understanding of the mechanisms underlying the development of T cell memory with an emphasis on factors controlling survival of

Normal hematopoietic stem cell function in mice with enforced expression of the Hippo signaling effector YAP1.

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Lina Jansson

Full Text Available The Hippo pathway has recently been implicated in the regulation of organ size and stem cells in multiple tissues. The transcriptional cofactor yes-associated protein 1 (Yap1 is the most downstream effector of Hippo signaling and is functionally repressed by the upstream components of the pathway. Overexpression of YAP1 stimulates proliferation of stem and progenitor cells in many tissues, consistent with inhibition of Hippo signaling. To study the role of Hippo signaling in hematopoietic stem cells (HSCs, we created a transgenic model with inducible YAP1 expression exclusively within the hematopoietic system. Following 3 months induction, examination of blood and bone marrow in the induced mice revealed no changes in the distribution of the hematopoietic lineages compared to control mice. Moreover, the progenitor cell compartment was unaltered as determined by colony forming assays and immunophenotyping. To address whether YAP1 affects the quantity and function of HSCs we performed competitive transplantation experiments. We show that ectopic YAP1 expression does not influence HSC function neither during steady state nor in situations of hematopoietic stress. This is in sharp contrast to effects seen on stem- and progenitor cells in other organs and suggests highly tissue specific functions of the Hippo pathway in regulation of stem cells.

Role of Soluble Innate Effector Molecules in Pulmonary Defense against Fungal Pathogens

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Soledad R. Ordonez

2017-10-01

Full Text Available Fungal infections of the lung are life-threatening but rarely occur in healthy, immunocompetent individuals, indicating efficient clearance by pulmonary defense mechanisms. Upon inhalation, fungi will first encounter the airway surface liquid which contains several soluble effector molecules that form the first barrier of defense against fungal infections. These include host defense peptides, like LL-37 and defensins that can neutralize fungi by direct killing of the pathogen, and collectins, such as surfactant protein A and D, that can aggregate fungi and stimulate phagocytosis. In addition, these molecules have immunomodulatory activities which can aid in fungal clearance from the lung. However, existing observations are based on in vitro studies which do not reflect the complexity of the lung and its airway surface liquid. Ionic strength, pH, and the presence of mucus can have strong detrimental effects on antifungal activity, while the potential synergistic interplay between soluble effector molecules is largely unknown. In this review, we describe the current knowledge on soluble effector molecules that contribute to antifungal activity, the importance of environmental factors and discuss the future directions required to understand the innate antifungal defense in the lung.

Role of Soluble Innate Effector Molecules in Pulmonary Defense against Fungal Pathogens

Science.gov (United States)

Ordonez, Soledad R.; Veldhuizen, Edwin J. A.; van Eijk, Martin; Haagsman, Henk P.

2017-01-01

Fungal infections of the lung are life-threatening but rarely occur in healthy, immunocompetent individuals, indicating efficient clearance by pulmonary defense mechanisms. Upon inhalation, fungi will first encounter the airway surface liquid which contains several soluble effector molecules that form the first barrier of defense against fungal infections. These include host defense peptides, like LL-37 and defensins that can neutralize fungi by direct killing of the pathogen, and collectins, such as surfactant protein A and D, that can aggregate fungi and stimulate phagocytosis. In addition, these molecules have immunomodulatory activities which can aid in fungal clearance from the lung. However, existing observations are based on in vitro studies which do not reflect the complexity of the lung and its airway surface liquid. Ionic strength, pH, and the presence of mucus can have strong detrimental effects on antifungal activity, while the potential synergistic interplay between soluble effector molecules is largely unknown. In this review, we describe the current knowledge on soluble effector molecules that contribute to antifungal activity, the importance of environmental factors and discuss the future directions required to understand the innate antifungal defense in the lung. PMID:29163395

Innovative technology summary report: Confined sluicing end effector

International Nuclear Information System (INIS)

1998-09-01

A Confined Sluicing End-Effector (CSEE) was field tested during the summer of 1997 in Tank W-3, one of the Gunite and Associated Tanks (GAAT) at the Oak Ridge Reservation (ORR). It should be noted that the specific device used at the Oak Ridge Reservation demonstration was the Sludge Retrieval End-Effector (SREE), although in common usage it is referred to as the CSEE. Deployed by the Modified Light-Duty Utility Arm (MLDUA) and the Houdini remotely operated vehicle (ROV), the CSEE was used to mobilize and retrieve waste from the tank. After removing the waste, the CSEE was used to scarify the gunite walls of Tank W-3, removing approximately 0.1 in of material. The CSEE uses three rotating water-jets to direct a short-range pressurized jet of water to effectively mobilize the waste. Simultaneously, the water and dislodged tank waste, or scarified materials, are aspirated using a water-jet pump-driven conveyance system. The material is then pumped outside of the tank, where it can be stored for treatment. The technology, its performance, uses, cost, and regulatory issues are discussed

Multiple candidate effectors from the oomycete pathogen Hyaloperonospora arabidopsidis suppress host plant immunity.

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Georgina Fabro

2011-11-01

Full Text Available Oomycete pathogens cause diverse plant diseases. To successfully colonize their hosts, they deliver a suite of effector proteins that can attenuate plant defenses. In the oomycete downy mildews, effectors carry a signal peptide and an RxLR motif. Hyaloperonospora arabidopsidis (Hpa causes downy mildew on the model plant Arabidopsis thaliana (Arabidopsis. We investigated if candidate effectors predicted in the genome sequence of Hpa isolate Emoy2 (HaRxLs were able to manipulate host defenses in different Arabidopsis accessions. We developed a rapid and sensitive screening method to test HaRxLs by delivering them via the bacterial type-three secretion system (TTSS of Pseudomonas syringae pv tomato DC3000-LUX (Pst-LUX and assessing changes in Pst-LUX growth in planta on 12 Arabidopsis accessions. The majority (~70% of the 64 candidates tested positively contributed to Pst-LUX growth on more than one accession indicating that Hpa virulence likely involves multiple effectors with weak accession-specific effects. Further screening with a Pst mutant (ΔCEL showed that HaRxLs that allow enhanced Pst-LUX growth usually suppress callose deposition, a hallmark of pathogen-associated molecular pattern (PAMP-triggered immunity (PTI. We found that HaRxLs are rarely strong avirulence determinants. Although some decreased Pst-LUX growth in particular accessions, none activated macroscopic cell death. Fewer HaRxLs conferred enhanced Pst growth on turnip, a non-host for Hpa, while several reduced it, consistent with the idea that turnip's non-host resistance against Hpa could involve a combination of recognized HaRxLs and ineffective HaRxLs. We verified our results by constitutively expressing in Arabidopsis a sub-set of HaRxLs. Several transgenic lines showed increased susceptibility to Hpa and attenuation of Arabidopsis PTI responses, confirming the HaRxLs' role in Hpa virulence. This study shows TTSS screening system provides a useful tool to test whether

MicroRNA-34a promotes genomic instability by a broad suppression of genome maintenance mechanisms downstream of the oncogene KSHV-vGPCR.

Science.gov (United States)

Krause, Claudia J; Popp, Oliver; Thirunarayanan, Nanthakumar; Dittmar, Gunnar; Lipp, Martin; Müller, Gerd

2016-03-01

The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded chemokine receptor vGPCR acts as an oncogene in Kaposi's sarcomagenesis. Until now, the molecular mechanisms by which the vGPCR contributes to tumor development remain incompletely understood. Here, we show that the KSHV-vGPCR contributes to tumor progression through microRNA (miR)-34a-mediated induction of genomic instability. Large-scale analyses on the DNA, gene and protein level of cell lines derived from a mouse model of vGPCR-driven tumorigenesis revealed that a vGPCR-induced upregulation of miR-34a resulted in a broad suppression of genome maintenance genes. A knockdown of either the vGPCR or miR-34a largely restored the expression of these genes and confirmed miR-34a as a downstream effector of the KSHV-vGPCR that compromises genome maintenance mechanisms. This novel, protumorigenic role of miR-34a questions the use of miR-34a mimetics in cancer therapy as they could impair genome stability.

High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors.

Science.gov (United States)

Koizume, Shiro; Ito, Shin; Yoshioka, Yusuke; Kanayama, Tomohiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Yamada, Roppei; Ochiya, Takahiro; Ruf, Wolfram; Miyagi, Etsuko; Hirahara, Fumiki; Miyagi, Yohei

2016-01-01

Thromboembolic events occur frequently in ovarian cancer patients. Tissue factor (TF) is often overexpressed in tumours, including ovarian clear-cell carcinoma (CCC), a subtype with a generally poor prognosis. TF-coagulation factor VII (fVII) complexes on the cell surface activate downstream coagulation mechanisms. Moreover, cancer cells secrete extracellular vesicles (EVs), which act as vehicles for TF. We therefore examined the characteristics of EVs produced by ovarian cancer cells of various histological subtypes. CCC cells secreted high levels of TF within EVs, while the high-TF expressing breast cancer cell line MDA-MB-231 shed fewer TF-positive EVs. We also found that CCC tumours with hypoxic tissue areas synthesised TF and fVII in vivo, rendering the blood of xenograft mice bearing these tumours hypercoagulable compared with mice bearing MDA-MB-231 tumours. Incorporation of TF into EVs and secretion of EVs from CCC cells exposed to hypoxia were both dependent on the actin-binding protein, filamin-A (filA). Furthermore, production of these EVs was dependent on different protease-activated receptors (PARs) on the cell surface. These results show that CCC cells could produce large numbers of TF-positive EVs dependent upon filA and PARs. This phenomenon may be the mechanism underlying the increased incidence of venous thromboembolism in ovarian cancer patients.

The Chlamydia type III secretion system C-ring engages a chaperone-effector protein complex.

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Kris E Spaeth

2009-09-01

Full Text Available In Gram-negative bacterial pathogens, specialized chaperones bind to secreted effector proteins and maintain them in a partially unfolded form competent for translocation by type III secretion systems/injectisomes. How diverse sets of effector-chaperone complexes are recognized by injectisomes is unclear. Here we describe a new mechanism of effector-chaperone recognition by the Chlamydia injectisome, a unique and ancestral line of these evolutionarily conserved secretion systems. By yeast two-hybrid analysis we identified networks of Chlamydia-specific proteins that interacted with the basal structure of the injectisome, including two hubs of protein-protein interactions that linked known secreted effector proteins to CdsQ, the putative cytoplasmic C-ring component of the secretion apparatus. One of these protein-interaction hubs is defined by Ct260/Mcsc (Multiple cargo secretion chaperone. Mcsc binds to and stabilizes at least two secreted hydrophobic proteins, Cap1 and Ct618, that localize to the membrane of the pathogenic vacuole ("inclusion". The resulting complexes bind to CdsQ, suggesting that in Chlamydia, the C-ring of the injectisome mediates the recognition of a subset of inclusion membrane proteins in complex with their chaperone. The selective recognition of inclusion membrane proteins by chaperones may provide a mechanism to co-ordinate the translocation of subsets of inclusion membrane proteins at different stages in infection.

Tomato immune receptor Ve1 recognizes effector of multiple fungal pathogens uncovered by genome and RNA sequencing

NARCIS (Netherlands)

Jonge, de R.; Esse, van H.P.; Maruthachalam, K.; Bolton, M.D.; Santhanam, P.; Keykha Saber, M.; Zhang, Z.; Usami, T.; Lievens, B.; Subbarao, K.V.; Thomma, B.

2012-01-01

Fungal plant pathogens secrete effector molecules to establish disease on their hosts, and plants in turn use immune receptors to try to intercept these effectors. The tomato immune receptor Ve1 governs resistance to race 1 strains of the soil-borne vascular wilt fungi Verticillium dahliae and

Mercury exposure in terrestrial birds far downstream of an historical point source

International Nuclear Information System (INIS)

Jackson, Allyson K.; Evers, David C.; Folsom, Sarah B.; Condon, Anne M.; Diener, John; Goodrick, Lizzie F.; McGann, Andrew J.; Schmerfeld, John; Cristol, Daniel A.

2011-01-01

Mercury (Hg) is a persistent environmental contaminant found in many freshwater and marine ecosystems. Historical Hg contamination in rivers can impact the surrounding terrestrial ecosystem, but there is little known about how far downstream this contamination persists. In 2009, we sampled terrestrial forest songbirds at five floodplain sites up to 137 km downstream of an historical source of Hg along the South and South Fork Shenandoah Rivers (Virginia, USA). We found that blood total Hg concentrations remained elevated over the entire sampling area and there was little evidence of decline with distance. While it is well known that Hg is a pervasive and long-lasting aquatic contaminant, it has only been recently recognized that it also biomagnifies effectively in floodplain forest food webs. This study extends the area of concern for terrestrial habitats near contaminated rivers for more than 100 km downstream from a waterborne Hg point source. - Highlights: → We report blood mercury levels for terrestrial songbirds downstream of contamination. → Blood mercury levels remain elevated above reference for at least 137 km downstream. → Trends vary based on foraging guild and migration strategy. → Mercury affects terrestrial biota farther downstream than previously documented. - Blood mercury levels of forest songbirds remain elevated above reference levels for at least 137 km downstream of historical point source.

Code-assisted discovery of TAL effector targets in bacterial leaf streak of rice reveals contrast with bacterial blight and a novel susceptibility gene.

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Raul A Cernadas

2014-02-01

Full Text Available Bacterial leaf streak of rice, caused by Xanthomonas oryzae pv. oryzicola (Xoc is an increasingly important yield constraint in this staple crop. A mesophyll colonizer, Xoc differs from X. oryzae pv. oryzae (Xoo, which invades xylem to cause bacterial blight of rice. Both produce multiple distinct TAL effectors, type III-delivered proteins that transactivate effector-specific host genes. A TAL effector finds its target(s via a partially degenerate code whereby the modular effector amino acid sequence identifies nucleotide sequences to which the protein binds. Virulence contributions of some Xoo TAL effectors have been shown, and their relevant targets, susceptibility (S genes, identified, but the role of TAL effectors in leaf streak is uncharacterized. We used host transcript profiling to compare leaf streak to blight and to probe functions of Xoc TAL effectors. We found that Xoc and Xoo induce almost completely different host transcriptional changes. Roughly one in three genes upregulated by the pathogens is preceded by a candidate TAL effector binding element. Experimental analysis of the 44 such genes predicted to be Xoc TAL effector targets verified nearly half, and identified most others as false predictions. None of the Xoc targets is a known bacterial blight S gene. Mutational analysis revealed that Tal2g, which activates two genes, contributes to lesion expansion and bacterial exudation. Use of designer TAL effectors discriminated a sulfate transporter gene as the S gene. Across all targets, basal expression tended to be higher than genome-average, and induction moderate. Finally, machine learning applied to real vs. falsely predicted targets yielded a classifier that recalled 92% of the real targets with 88% precision, providing a tool for better target prediction in the future. Our study expands the number of known TAL effector targets, identifies a new class of S gene, and improves our ability to predict functional targeting.

Manipulation of host membranes by bacterial effectors.

Science.gov (United States)

Ham, Hyeilin; Sreelatha, Anju; Orth, Kim

2011-07-18

Bacterial pathogens interact with host membranes to trigger a wide range of cellular processes during the course of infection. These processes include alterations to the dynamics between the plasma membrane and the actin cytoskeleton, and subversion of the membrane-associated pathways involved in vesicle trafficking. Such changes facilitate the entry and replication of the pathogen, and prevent its phagocytosis and degradation. In this Review, we describe the manipulation of host membranes by numerous bacterial effectors that target phosphoinositide metabolism, GTPase signalling and autophagy.

Development of an optimum end-effector with a nano-scale uneven surface for non-adhesion cell manipulation using a micro-manipulator

International Nuclear Information System (INIS)

Horade, M; Kojima, M; Kamiyama, K; Kurata, T; Mae, Y; Arai, T

2015-01-01

In order to realize effective micro-manipulation using a micro-manipulator system, an optimum end-effector is proposed. Cell-manipulation experiments using mouse fibroblast cells are conducted, and the usability of the proposed end-effector is confirmed. A key advantage of the micro-manipulator is high-accuracy, high-speed 3D micro- and nano-scale positioning. Micro-manipulation has often been used in research involving biological cells. However, there are two important concerns with the micro-manipulator system: gripping efficiency and the release of gripped objects. When it is not possible to grip a micro-object, such as a cell, near its center, the object may be dropped during manipulation. Since the acquisition of exact position information for a micro-object in the vertical direction is difficult using a microscope, the gripping efficiency of the end-effector should be improved. Therefore, technical skill or operational support is required. Since, on the micro-scale, surface forces such as the adsorption force are greater than body forces, such as the gravitational force, the adhesion force between the end-effector and the object is strong. Therefore, manipulation techniques without adhesion are required for placed an object at an arbitrary position. In the present study, we consider direct physical contact between the end-effector and objects. First, the design and materials of the end-effector for micro-scale manipulation were optimized, and an end-effector with an optimum shape to increase the grip force was fabricated. Second, the surface of the end-effector tip was made uneven, and the adhesion force from increasing on the micro-scale was prevented. When an end-effector with an uneven surface was used, release without adhesion was successful 85.0% of the time. On the other hand, when an end-effector without an uneven surface was used, release without adhesion was successful 6.25% of the time. Therefore, the superiority of a structure with an uneven

Demonstration of NK cell-mediated lysis of varicella-zoster virus (VZV)-infected cells: characterization of the effector cells

Energy Technology Data Exchange (ETDEWEB)

Tilden, A.B.; Cauda, R.; Grossi, C.E.; Balch, C.M.; Lakeman, A.D.; Whitley, R.J.

1986-06-01

Infection with varicella-zoster virus (VZV) rendered RAJI cells more susceptible to lysis by non-adherent blood lymphocytes. At an effector to target ratio of 80:1 the mean percentage of /sup 51/Cr release of VZV-infected RAJI cells was 41 +/- 12%, whereas that of uninfected RAJI cells was 15 +/- 6%. The increased susceptibility to lysis was associated with increased effector to target conjugate formation in immunofluorescence binding assays. The effector cells cytotoxic for VZV-infected RAJI cells were predominantly Leu-11a/sup +/ Leu-4/sup -/ granular lymphocytes as demonstrated by fluorescence-activated cell sorting. The effector cell active against VZV-infected RAJI cells appeared similar to those active against herpes simplex virus (HSV)-infected cells, because in cold target competition experiments the lysis of /sup 51/Cr-labeled VZV-infected RAJI cells was efficiently inhibited by either unlabeled VZV-infected RAJI cells (mean 71% inhibition, 2:1 ratio unlabeled to labeled target) or HSV-infected RAJI cells (mean 69% inhibition) but not by uninfected RAJI cells (mean 10% inhibition). In contrast, competition experiments revealed donor heterogeneity in the overlap between effector cells for VZV- or HSV-infected RAJI vs K-562 cells.

The Role of CD39 in Modulating Effector Immune Responses in Inflammatory Bowel Disease

OpenAIRE

Huang, Huang

2015-01-01

Inflammatory bowel disease is associated with excessive inflammation of the bowel and intestinal tissues in genetically susceptible individuals. IBD can manifest in two major forms, ulcerative colitis and Crohn’s disease. T helper type 17 cells (Th17) are effector lymphocytes that have been linked to intestinal inflammation in both mice and humans. Effector Th17 cells and regulatory T cells (Treg) – a subset pivotal to immune-tolerance maintenance – derive from the same CD4 progenitors. Our i...

A translocated effector required for Bartonella dissemination from derma to blood safeguards migratory host cells from damage by co-translocated effectors.

Science.gov (United States)

Okujava, Rusudan; Guye, Patrick; Lu, Yun-Yueh; Mistl, Claudia; Polus, Florine; Vayssier-Taussat, Muriel; Halin, Cornelia; Rolink, Antonius G; Dehio, Christoph

2014-06-01

Numerous bacterial pathogens secrete multiple effectors to modulate host cellular functions. These effectors may interfere with each other to efficiently control the infection process. Bartonellae are Gram-negative, facultative intracellular bacteria using a VirB type IV secretion system to translocate a cocktail of Bartonella effector proteins (Beps) into host cells. Based on in vitro infection models we demonstrate here that BepE protects infected migratory cells from injurious effects triggered by BepC and is required for in vivo dissemination of bacteria from the dermal site of inoculation to blood. Human endothelial cells (HUVECs) infected with a ΔbepE mutant of B. henselae (Bhe) displayed a cell fragmentation phenotype resulting from Bep-dependent disturbance of rear edge detachment during migration. A ΔbepCE mutant did not show cell fragmentation, indicating that BepC is critical for triggering this deleterious phenotype. Complementation of ΔbepE with BepEBhe or its homologues from other Bartonella species abolished cell fragmentation. This cyto-protective activity is confined to the C-terminal Bartonella intracellular delivery (BID) domain of BepEBhe (BID2.EBhe). Ectopic expression of BID2.EBhe impeded the disruption of actin stress fibers by Rho Inhibitor 1, indicating that BepE restores normal cell migration via the RhoA signaling pathway, a major regulator of rear edge retraction. An intradermal (i.d.) model for B. tribocorum (Btr) infection in the rat reservoir host mimicking the natural route of infection by blood sucking arthropods allowed demonstrating a vital role for BepE in bacterial dissemination from derma to blood. While the Btr mutant ΔbepDE was abacteremic following i.d. inoculation, complementation with BepEBtr, BepEBhe or BIDs.EBhe restored bacteremia. Given that we observed a similar protective effect of BepEBhe on infected bone marrow-derived dendritic cells migrating through a monolayer of lymphatic endothelial cells we propose that

A translocated effector required for Bartonella dissemination from derma to blood safeguards migratory host cells from damage by co-translocated effectors.

Directory of Open Access Journals (Sweden)

Rusudan Okujava

2014-06-01

Full Text Available Numerous bacterial pathogens secrete multiple effectors to modulate host cellular functions. These effectors may interfere with each other to efficiently control the infection process. Bartonellae are Gram-negative, facultative intracellular bacteria using a VirB type IV secretion system to translocate a cocktail of Bartonella effector proteins (Beps into host cells. Based on in vitro infection models we demonstrate here that BepE protects infected migratory cells from injurious effects triggered by BepC and is required for in vivo dissemination of bacteria from the dermal site of inoculation to blood. Human endothelial cells (HUVECs infected with a ΔbepE mutant of B. henselae (Bhe displayed a cell fragmentation phenotype resulting from Bep-dependent disturbance of rear edge detachment during migration. A ΔbepCE mutant did not show cell fragmentation, indicating that BepC is critical for triggering this deleterious phenotype. Complementation of ΔbepE with BepEBhe or its homologues from other Bartonella species abolished cell fragmentation. This cyto-protective activity is confined to the C-terminal Bartonella intracellular delivery (BID domain of BepEBhe (BID2.EBhe. Ectopic expression of BID2.EBhe impeded the disruption of actin stress fibers by Rho Inhibitor 1, indicating that BepE restores normal cell migration via the RhoA signaling pathway, a major regulator of rear edge retraction. An intradermal (i.d. model for B. tribocorum (Btr infection in the rat reservoir host mimicking the natural route of infection by blood sucking arthropods allowed demonstrating a vital role for BepE in bacterial dissemination from derma to blood. While the Btr mutant ΔbepDE was abacteremic following i.d. inoculation, complementation with BepEBtr, BepEBhe or BIDs.EBhe restored bacteremia. Given that we observed a similar protective effect of BepEBhe on infected bone marrow-derived dendritic cells migrating through a monolayer of lymphatic endothelial cells we

Immune Effector Recovery in Chronic Myeloid Leukemia and Treatment-Free Remission

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Agnes S. M. Yong

2017-04-01

Full Text Available Chronic myeloid leukemia (CML is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 ≤ 0.01% in CML patients. As a result, the more recent goal of therapy in CML treatment is to induce a durable DMR as a prelude to successful treatment-free remission (TFR, which occurs in approximately half of all CML patients who cease TKI therapy. The lack of overt relapse in such patients has been attributed to immunological control of CML. In this review, we discuss an immunological timeline to successful TFR, focusing on the immunology of CML during TKI treatment; an initial period of immune suppression, limiting antitumor immune effector responses in newly diagnosed CML patients, linked to an expansion of immature myeloid-derived suppressor cells and regulatory T cells and aberrant expression of immune checkpoint signaling pathways, including programmed death-1/programmed death ligand-1. Commencement of TKI treatment is associated with immune system re-activation and restoration of effector-mediated [natural killer (NK cell and T cell] immune surveillance in CML patients, albeit with differing frequencies in concert with differing levels of molecular response achieved on TKI. DMR is associated with maximal restoration of immune recovery in CML patients on TKI. Current data suggest a net balance between both the effector and suppressor arms of the immune system, at a minimum involving mature, cytotoxic CD56dim NK cells may be important

Stimulation over primary motor cortex during action observation impairs effector recognition.

Science.gov (United States)

Naish, Katherine R; Barnes, Brittany; Obhi, Sukhvinder S

2016-04-01

Recent work suggests that motor cortical processing during action observation plays a role in later recognition of the object involved in the action. Here, we investigated whether recognition of the effector making an action is also impaired when transcranial magnetic stimulation (TMS) - thought to interfere with normal cortical activity - is applied over the primary motor cortex (M1) during action observation. In two experiments, single-pulse TMS was delivered over the hand area of M1 while participants watched short clips of hand actions. Participants were then asked whether an image (experiment 1) or a video (experiment 2) of a hand presented later in the trial was the same or different to the hand in the preceding video. In Experiment 1, we found that participants' ability to recognise static images of hands was significantly impaired when TMS was delivered over M1 during action observation, compared to when no TMS was delivered, or when stimulation was applied over the vertex. Conversely, stimulation over M1 did not affect recognition of dot configurations, or recognition of hands that were previously presented as static images (rather than action movie clips) with no object. In Experiment 2, we found that effector recognition was impaired when stimulation was applied part way through (300ms) and at the end (500ms) of the action observation period, indicating that 200ms of action-viewing following stimulation was not long enough to form a new representation that could be used for later recognition. The findings of both experiments suggest that interfering with cortical motor activity during action observation impairs subsequent recognition of the effector involved in the action, which complements previous findings of motor system involvement in object memory. This work provides some of the first evidence that motor processing during action observation is involved in forming representations of the effector that are useful beyond the action observation period

Immune Effector Recovery in Chronic Myeloid Leukemia and Treatment-Free Remission

Science.gov (United States)

Hughes, Amy; Yong, Agnes S. M.

2017-01-01

Chronic myeloid leukemia (CML) is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs) represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 ≤ 0.01%) in CML patients. As a result, the more recent goal of therapy in CML treatment is to induce a durable DMR as a prelude to successful treatment-free remission (TFR), which occurs in approximately half of all CML patients who cease TKI therapy. The lack of overt relapse in such patients has been attributed to immunological control of CML. In this review, we discuss an immunological timeline to successful TFR, focusing on the immunology of CML during TKI treatment; an initial period of immune suppression, limiting antitumor immune effector responses in newly diagnosed CML patients, linked to an expansion of immature myeloid-derived suppressor cells and regulatory T cells and aberrant expression of immune checkpoint signaling pathways, including programmed death-1/programmed death ligand-1. Commencement of TKI treatment is associated with immune system re-activation and restoration of effector-mediated [natural killer (NK) cell and T cell] immune surveillance in CML patients, albeit with differing frequencies in concert with differing levels of molecular response achieved on TKI. DMR is associated with maximal restoration of immune recovery in CML patients on TKI. Current data suggest a net balance between both the effector and suppressor arms of the immune system, at a minimum involving mature, cytotoxic CD56dim NK cells may be important in mediating

Tomato Cf resistance proteins mediate recognition of cognate homologous effectors from fungi pathogenic on dicots and monocots.

Science.gov (United States)

Stergiopoulos, Ioannis; van den Burg, Harrold A; Okmen, Bilal; Beenen, Henriek G; van Liere, Sabine; Kema, Gert H J; de Wit, Pierre J G M

2010-04-20

Most fungal effectors characterized so far are species-specific and facilitate virulence on a particular host plant. During infection of its host tomato, Cladosporium fulvum secretes effectors that function as virulence factors in the absence of cognate Cf resistance proteins and induce effector-triggered immunity in their presence. Here we show that homologs of the C. fulvum Avr4 and Ecp2 effectors are present in other pathogenic fungi of the Dothideomycete class, including Mycosphaerella fijiensis, the causal agent of black Sigatoka disease of banana. We demonstrate that the Avr4 homolog of M. fijiensis is a functional ortholog of C. fulvum Avr4 that protects fungal cell walls against hydrolysis by plant chitinases through binding to chitin and, despite the low overall sequence homology, triggers a Cf-4-mediated hypersensitive response (HR) in tomato. Furthermore, three homologs of C. fulvum Ecp2 are found in M. fijiensis, one of which induces different levels of necrosis or HR in tomato lines that lack or contain a putative cognate Cf-Ecp2 protein, respectively. In contrast to Avr4, which acts as a defensive virulence factor, M. fijiensis Ecp2 likely promotes virulence by interacting with a putative host target causing host cell necrosis, whereas Cf-Ecp2 could possibly guard the virulence target of Ecp2 and trigger a Cf-Ecp2-mediated HR. Overall our data suggest that Avr4 and Ecp2 represent core effectors that are collectively recognized by single cognate Cf-proteins. Transfer of these Cf genes to plant species that are attacked by fungi containing these cognate core effectors provides unique ways for breeding disease-resistant crops.

Influence of Upstream and Downstream Compressor Stators on Rotor Exit Flow Field

Directory of Open Access Journals (Sweden)

Nicole L. Key

2014-01-01

Full Text Available Measurements acquired at the rotor exit plane illuminate the interaction of the rotor with the upstream vane row and the downstream vane row. The relative phase of the upstream and downstream vane rows is adjusted using vane clocking so that the effect of the upstream propagating potential field from the downstream stator can be distinguished from the effects associated with the wakes shed from the upstream stator. Unsteady absolute flow angle information shows that the downstream potential field causes the absolute flow angle to increase in the vicinity of the downstream stator leading edge. The presence of Stator 1 wake is also detected at this measurement plane using unsteady total pressure data. The rotor wakes are measured at different circumferential locations across the vane passage, and the influence of Stator 1 wake on the suction side of the rotor wake is evident. Also, the influence of the downstream stator is detected on the pressure side of the rotor wake for a particular clocking configuration. Understanding the role of the surrounding vane rows on rotor wake development will lead to improved comparison between experimental data and results from computational models.

Trauma-Focused Early Intensive Cognitive Behavioral Intervention (TF-EICBI) in children and adolescent survivors of suicide bombing attacks (SBAs). A preliminary study.

Science.gov (United States)

Leor, Agnes; Dolberg, Orna T; Eshel, Shira Pagorek; Yagil, Yaron; Schreiber, Shaul

2013-01-01

To describe and evaluate the impact of an early intervention (Trauma-Focused Early Intensive Cognitive Behavioral Intervention, TF-EICBI) in children and adolescents who were victims of suicide bombing attacks (SBAs) in Israel. Description of an intervention and preliminary experience in its use. An acute trauma center of a Child and Adolescent Psychiatric Unit in a Department of Psychiatry of a university-affiliated medical center. Ten children and adolescents who were victims of SBAs and underwent early interventions (EIG) were compared to 11 adolescent victims who received no intervention (NEIG). The EIG included all the children and adolescent survivors of various SBAs that had occurred during 1 year who presented to our hospital after the TF-EICBI was implemented (June 2001). The NEIG comprised all adolescents girls children and adolescents after SBAs.

Allelic barley MLA immune receptors recognize sequence-unrelated avirulence effectors of the powdery mildew pathogen.

Science.gov (United States)

Lu, Xunli; Kracher, Barbara; Saur, Isabel M L; Bauer, Saskia; Ellwood, Simon R; Wise, Roger; Yaeno, Takashi; Maekawa, Takaki; Schulze-Lefert, Paul

2016-10-18

Disease-resistance genes encoding intracellular nucleotide-binding domain and leucine-rich repeat proteins (NLRs) are key components of the plant innate immune system and typically detect the presence of isolate-specific avirulence (AVR) effectors from pathogens. NLR genes define the fastest-evolving gene family of flowering plants and are often arranged in gene clusters containing multiple paralogs, contributing to copy number and allele-specific NLR variation within a host species. Barley mildew resistance locus a (Mla) has been subject to extensive functional diversification, resulting in allelic resistance specificities each recognizing a cognate, but largely unidentified, AVR a gene of the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh). We applied a transcriptome-wide association study among 17 Bgh isolates containing different AVR a genes and identified AVR a1 and AVR a13 , encoding candidate-secreted effectors recognized by Mla1 and Mla13 alleles, respectively. Transient expression of the effector genes in barley leaves or protoplasts was sufficient to trigger Mla1 or Mla13 allele-specific cell death, a hallmark of NLR receptor-mediated immunity. AVR a1 and AVR a13 are phylogenetically unrelated, demonstrating that certain allelic MLA receptors evolved to recognize sequence-unrelated effectors. They are ancient effectors because corresponding loci are present in wheat powdery mildew. AVR A1 recognition by barley MLA1 is retained in transgenic Arabidopsis, indicating that AVR A1 directly binds MLA1 or that its recognition involves an evolutionarily conserved host target of AVR A1 Furthermore, analysis of transcriptome-wide sequence variation among the Bgh isolates provides evidence for Bgh population structure that is partially linked to geographic isolation.

Downstream anastomotic hyperplasia. A mechanism of failure in Dacron arterial grafts.

Science.gov (United States)

LoGerfo, F W; Quist, W C; Nowak, M D; Crawshaw, H M; Haudenschild, C C

1983-01-01

The precise location and progression of anastomotic hyperplasia and its possible relationship to flow disturbances was investigated in femoro-femoral Dacron grafts in 28 dogs. In 13 grafts, the outflow from the end-to-side downstream anastomosis was bidirectional (BDO), and in 15 it was unidirectional (UDO) (distally). Grafts were electively removed at intervals of two to 196 days or at the time of thrombosis. Each anastomosis and adjacent artery was perfusion-fixed and sectioned sagittally. The mean sagittal section was projected onto a digitized pad, and the total area of hyperplasia internal to the arterial internal elastic lamina and within the adjacent graft was integrated by computer. The location of the hyperplasia was compared with previously established sites of flow separation and stagnation. The observation was made that hyperplasia is significantly greater at the downstream, as compared with the upstream, anastomosis in both groups (BDO = p less than 0.001 and UDO = p less than 0.001) (analysis of variance for independent groups). Furthermore, this downstream hyperplasia was progressive with time (BDO p less than 0.01) (UDO p less than 0.01); Spearman Rank Correlation. There was no significant increase in the extent of downstream hyperplasia where flow separation was known to be greater (BDO). Five grafts failed (three BDO, two UDO), as a result of complete occlusion of the downstream anastomosis by fibrous hyperplasia. Transmission electron microscopy showed the hyperplasia to consist of collagen-producing smooth muscle cells. Anastomotic hyperplasia is significantly greater at the downstream anastomosis, is progressive with time, and is the primary cause of failure of Dacron arterial grafts in this model. Quantitative analysis of downstream anastomotic hyperplasia may be a valuable measure of the biocompatibility of Dacron grafts. Images Fig. 2. Fig. 3. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:6219641

Application of calorimetry to the assessment of the performance of ITER Nb3Sn TF conductor samples in SULTAN tests

International Nuclear Information System (INIS)

Richard, L Savoldi; Zanino, R

2008-01-01

In the frame of the International Thermonuclear Experimental Reactor (ITER), several short full-size Nb 3 Sn samples of candidate toroidal field (TF) conductors were tested in 2007 at the SULTAN facility, PSI Villigen, Switzerland, in conditions relevant to the ITER TF (background magnetic field of 10.78 T and transport current of 68 kA). The performance of a SULTAN sample is determined by the current sharing temperature T CS . This can be obtained in principle from voltage measurements along the conductor sample, but the procedure is not free of issues and ambiguities. Here a complementary approach, based on the calorimetric assessment of the Joule heating due to current sharing, is critically discussed. Suitable algorithms are defined and the respective error bars are estimated, also based on numerical thermal-hydraulic modeling. The calorimetric approach is then applied to assess the performance of the samples tested in 2007 and compared with the results of the standard (electrical) approach

Structural basis for sequence-specific recognition of DNA by TAL effectors

KAUST Repository

Deng, Dong; Yan, Chuangye; Pan, Xiaojing; Mahfouz, Magdy M.; Wang, Jiawei; Zhu, Jiankang; Shi, Yi Gong; Yan, Nieng

2012-01-01

TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats. Each repeat comprises 33 to 35 conserved amino acids and targets a specific base pair

Development of position control of end-effector for CS-113 robot based on three degree of freedom motions

International Nuclear Information System (INIS)

Iqbal, Muhammad; Setiawan, Widi; Arif, Agus

2003-01-01

A software development for three degrees of freedom motions of CS-113 robot arm has been done. This software, which was based on inverse kinematic, can be used to control position of D and D (decontamination and Dismantlement) robot. A preliminary construction of robot arm (three degrees of freedom) has been constructed also to study the mechanic aspects. The scope of this research consist of direct kinematic and inverse kinematic implementation. The direct kinematic implementation developed according to following steps: (1) assigning kinematic parameters of CS-113 robot arm using Denavit-Hertenberg methods, (2) formulating kinematic equation for all joint. The inverse kinematic implementation developed by transforming position in Cartesian coordinates into joint angle in angle coordinates. Both direct and inverse kinematic were implemented with computer software which is written in the VISUAL BASIC. This software was tested on CS-113 robot. The theoretically calculation was done on MATLAB. Input of direct kinematic were joint angles (5 o , 10 o , -20 o , 15 o , 25 o , 30 o , -50 o , and 60 o ), whereas the input of inverse kinematic were the position on Cartesian coordinate, with the duration for moving end-effector testing 4 seconds. The test results of direct kinematic implementation on CS-113 robot were the position of end-effector on Cartesian coordinates. The position of end-effector which was measured experimentally on CS-113 robot compared with position of end-effector which was calculated on MATLAB. This comparison showed that static performance of CS-113 robot manipulator, bias (systematic error) that different from the end-effector position change within 8,9%, 12,3% and 27,3% on X, Y, Z axes, respectively, the measurements repeatability (precision) of end-effector position were ± 0,031 cm to ±0,183 cm. The test results of inverse kinematic implementation on CS-113 robot showed that the accuracy of end-effector position varied on all axes, the bias

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

Science.gov (United States)

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

2016-01-01

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

Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy.

Science.gov (United States)

Golubovskaya, Vita; Wu, Lijun

2016-03-15

This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy--a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4⁺ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) and CD8⁺ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.); intracellular markers (FOXP3); epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic); and these differences can be modulated to improve CAR-T therapy. In addition, CD4⁺ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.

Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy

Directory of Open Access Journals (Sweden)

Vita Golubovskaya

2016-03-01

Full Text Available This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy––a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4+ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh and CD8+ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.; intracellular markers (FOXP3; epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic; and these differences can be modulated to improve CAR-T therapy. In addition, CD4+ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.

Quench propagation and quench detection in the TF system of JT-60SA

International Nuclear Information System (INIS)

Lacroix, Benoit; Duchateau, Jean-Luc; Meuris, Chantal; Ciazynski, Daniel; Nicollet, Sylvie; Zani, Louis; Polli, Gian-Mario

2013-01-01

Highlights: • The JT-60SA primary quench detection system will be based on voltage measurements. • The early quench propagation was studied in the JT-60SA TF conductor. • The impact of the conductor jacket on the hot spot criterion was quantified. • The detection parameters were investigated for different quench initiations. -- Abstract: In the framework of the JT-60SA project, France and Italy will provide to JAEA 18 Toroidal Field (TF) coils including NbTi cable-in-conduit conductors. During the tokamak operation, these coils could experience a quench, an incidental event corresponding to the irreversible transition from superconducting state to normal resistive state. Starting from a localized disturbance, the normal zone propagates along the conductor and dissipates a large energy due to Joule heating, which can cause irreversible damages. The detection has to be fast enough (a few seconds) to trigger the current discharge, so as to dump the stored magnetic energy into an external resistor. The JT-60SA primary quench detection system will be based on voltage measurements, which are the most rapid technology. The features of the detection system must be adjusted so as to detect the most probable quenches, while avoiding inopportune fast safety discharges. This requires a reliable simulation of the early quench propagation, performed in this study with the Gandalf code. The conductor temperature reached during the current discharge must be kept under a maximal value, according to the hot spot criterion. In the present study, a hot spot criterion temperature of 150 K was taken into account and the role of each conductor component (strands, helium and conduit) was analyzed. The detection parameters were then investigated for different hypotheses regarding the quench initiation

How to conquer a tomato plant? Fusarium oxysporum effector targets

NARCIS (Netherlands)

de Sain, M.

2016-01-01

Pathogens secrete small proteins, called effectors, to alter the environment in their host to facilitate infection. The causal agent of Fusarium wilt on tomato, Fusarium oxysporum f. sp. lycopersici (Fol), secretes these proteins in the xylem sap of infected plants and hence they have been called

BOREAS TF-3 Automated Chamber CO2 Flux Data from the NSA-OBS

Science.gov (United States)

Goulden, Michael L.; Crill, Patrick M.; Hall, Forrest G. (Editor); Conrad, Sara (Editor)

2000-01-01

The BOReal Ecosystem Atmosphere Study Tower Flux (BOREAS TF-3) and Trace Gas Biogeochemistry (TGB-1) teams collected automated CO2 chamber flux data in their efforts to fully describe the CO2 flux at the Northern Study Area-Old Black Spruce (NSA-OBS) site. This data set contains fluxes of CO2 at the NSA-OBS site measured using automated chambers. In addition to reporting the CO2 flux, it reports chamber air temperature, moss temperature, and light levels during each measurement. The data set covers the period from 23-Sep-1995 through 26-Oct-1995 and from 28-May-1996 through 21-Oct-1996. The data are stored in tabular ASCII files.

Orbital maneuvering end effectors

Science.gov (United States)

Myers, W. Neill (Inventor); Forbes, John C. (Inventor); Barnes, Wayne L. (Inventor)

1986-01-01

This invention relates to an end effector device for grasping and maneuvering objects such as berthing handles of a space telescope. The device includes a V-shaped capture window defined as inclined surfaces in parallel face plates which converge toward a retainer recess in which the handle is retained. A pivotal finger (30) meshes with a pair of pivoted fingers which rotate in counterrotation. The fingers rotate to pull a handle within the capture window into recess where latches lock handle in the recess. To align the capture window, plates may be cocked plus or minus five degrees on base. Drive means is included in the form of a motor coupled with a harmonic drive speed reducer, which provides for slow movement of the fingers at a high torque so that large articles may be handled. Novelty of the invention is believed to reside in the combined intermeshing finger structure, drive means and the harmonic drive speed reducer, which features provide the required maneuverability and strength.

Transcription Factors Encoded on Core and Accessory Chromosomes of Fusarium oxysporum Induce Expression of Effector Genes

Science.gov (United States)

van der Does, H. Charlotte; Schmidt, Sarah M.; Langereis, Léon; Hughes, Timothy R.

2016-01-01

Proteins secreted by pathogens during host colonization largely determine the outcome of pathogen-host interactions and are commonly called ‘effectors’. In fungal plant pathogens, coordinated transcriptional up-regulation of effector genes is a key feature of pathogenesis and effectors are often encoded in genomic regions with distinct repeat content, histone code and rate of evolution. In the tomato pathogen Fusarium oxysporum f. sp. lycopersici (Fol), effector genes reside on one of four accessory chromosomes, known as the ‘pathogenicity’ chromosome, which can be exchanged between strains through horizontal transfer. The three other accessory chromosomes in the Fol reference strain may also be important for virulence towards tomato. Expression of effector genes in Fol is highly up-regulated upon infection and requires Sge1, a transcription factor encoded on the core genome. Interestingly, the pathogenicity chromosome itself contains 13 predicted transcription factor genes and for all except one, there is a homolog on the core genome. We determined DNA binding specificity for nine transcription factors using oligonucleotide arrays. The binding sites for homologous transcription factors were highly similar, suggesting that extensive neofunctionalization of DNA binding specificity has not occurred. Several DNA binding sites are enriched on accessory chromosomes, and expression of FTF1, its core homolog FTF2 and SGE1 from a constitutive promoter can induce expression of effector genes. The DNA binding sites of only these three transcription factors are enriched among genes up-regulated during infection. We further show that Ftf1, Ftf2 and Sge1 can activate transcription from their binding sites in yeast. RNAseq analysis revealed that in strains with constitutive expression of FTF1, FTF2 or SGE1, expression of a similar set of plant-responsive genes on the pathogenicity chromosome is induced, including most effector genes. We conclude that the Fol

ROBOTIC TANK INSPECTION END EFFECTOR

International Nuclear Information System (INIS)

Rachel Landry

1999-01-01

The objective of this contract between Oceaneering Space Systems (OSS) and the Department of Energy (DOE) was to provide a tool for the DOE to inspect the inside tank walls of underground radioactive waste storage tanks in their tank farms. Some of these tanks are suspected to have leaks, but the harsh nature of the environment within the tanks precludes human inspection of tank walls. As a result of these conditions only a few inspection methods can fulfill this task. Of the methods available, OSS chose to pursue Alternating Current Field Measurement (ACFM), because it does not require clean surfaces for inspection, nor any contact with the Surface being inspected, and introduces no extra by-products in the inspection process (no coupling fluids or residues are left behind). The tool produced by OSS is the Robotic Tank Inspection End Effector (RTIEE), which is initially deployed on the tip of the Light Duty Utility Arm (LDUA). The RTEE combines ACFM with a color video camera for both electromagnetic and visual inspection The complete package consists of an end effector, its corresponding electronics and software, and a user's manual to guide the operator through an inspection. The system has both coarse and fine inspection modes and allows the user to catalog defects and suspected areas of leakage in a database for further examination, which may lead to emptying the tank for repair, decommissioning, etc.. The following is an updated report to OSS document OSS-21100-7002, which was submitted in 1995. During the course of the contract, two related sub-tasks arose, the Wall and Coating Thickness Sensor and the Vacuum Scarifying and Sampling Tool Assembly. The first of these sub-tasks was intended to evaluate the corrosion and wall thinning of 55-gallon steel drums. The second was retrieved and characterized the waste material trapped inside the annulus region of the underground tanks on the DOE's tank farms. While these sub-tasks were derived from the original intent

Cultural and communicative memories: contrasting Argentina's 1976 coup d'état and the 2001 economic-political-social crisis.

Science.gov (United States)

Muller, Felipe; Bermejo, Federico; Hirst, William

2018-08-01

Studies on collective memory have recently addressed the distinction between cultural and communicative memory as a way to understand how the source of a memory affects its structure or form. When a groups' memory is mediated by memorials, documentaries or any other cultural artifacts, collective memory is shaped by cultural memory. When it is based mostly in communication with other people, its source is communicative memory. We address this distinction by studying two recent events in Argentinean history: the 2001 economic-political-social crisis (communicative memory) and the 1976 coup (cultural memory). We also examine the political ideology and the type of memory involved in collective memory. The memory of the studied events may occur during the lifetime of the rememberer (Lived Memory) or refer to distant events (Distant Memory). 100 participants responded to a Free Recall task about the events of 2001 in Argentina. Narrative analysis allowed comparing these recalls with our 1976 study. Results show: 1) Cultural memories are more contextualised, more impersonal and less affective. 2) Communicative memories are more personal and affective. Study shows how collective memory form changes when it has a different prevalent source.

Photoperiod control of downstream movements of Atlantic salmon Salmo salar smolts

Science.gov (United States)

Zydlewski, Gayle B.; Stich, Daniel S.; McCormick, Stephen D.

2014-01-01

This study provides the first direct observations that photoperiod controls the initiation of downstream movement in Atlantic salmon Salmo salar smolts. Under simulated natural day length (LDN) conditions and seasonal increases in temperature, smolts increased their downstream movements five-fold for a period of 1 month in late spring. Under the same conditions, parr did not show changes in downstream movement behaviour. When given a shortened day length (10L:14D) beginning in late winter, smolts did not increase the number of downstream movements. An early increase in day length (16L:8D) in late winter resulted in earlier initiation and termination of downstream movements compared to the LDN group. Physiological status and behaviour were related but not completely coincident: gill Na+/K+-ATPase activity increased in all treatments and thyroid hormone was elevated prior to movement in 16L:8D treatment. The most parsimonious model describing downstream movement of smolts included synergistic effects of photoperiod treatment and temperature, indicating that peak movements occurred at colder temperatures in the 16L:8D treatment than in LDN, and temperature did not influence movement of smolts in the 10L:14D treatment. The complicated interactions of photoperiod and temperature are not surprising since many organisms have evolved to rely on correlations among environmental cues and windows of opportunity to time behaviours associated with life-history transitions. These complicated interactions, however, have serious implications for phenological adjustments and persistence ofS. salar populations in response to climate change.

Generation mechanism of RANKL(+) effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis.

Science.gov (United States)

Ota, Yuri; Niiro, Hiroaki; Ota, Shun-Ichiro; Ueki, Naoko; Tsuzuki, Hirofumi; Nakayama, Tsuyoshi; Mishima, Koji; Higashioka, Kazuhiko; Jabbarzadeh-Tabrizi, Siamak; Mitoma, Hiroki; Akahoshi, Mitsuteru; Arinobu, Yojiro; Kukita, Akiko; Yamada, Hisakata; Tsukamoto, Hiroshi; Akashi, Koichi

2016-03-16

The efficacy of B cell-depleting therapies for rheumatoid arthritis underscores antibody-independent functions of effector B cells such as cognate T-B interactions and production of pro-inflammatory cytokines. Receptor activator of nuclear factor κB ligand (RANKL) is a key cytokine involved in bone destruction and is highly expressed in synovial fluid B cells in patients with rheumatoid arthritis. In this study we sought to clarify the generation mechanism of RANKL(+) effector B cells and their impacts on osteoclast differentiation. Peripheral blood and synovial fluid B cells from healthy controls and patients with rheumatoid arthritis were isolated using cell sorter. mRNA expression of RANKL, osteoprotegerin, tumor necrosis factor (TNF)-α, and Blimp-1 was analyzed by quantitative real-time polymerase chain reaction. Levels of RANKL, CD80, CD86, and CXCR3 were analyzed using flow cytometry. Functional analysis of osteoclastogenesis was carried out in the co-culture system using macrophage RAW264 reporter cells. RANKL expression was accentuated in CD80(+)CD86(+) B cells, a highly activated B-cell subset more abundantly observed in patients with rheumatoid arthritis. Upon activation via B-cell receptor and CD40, switched-memory B cells predominantly expressed RANKL, which was further augmented by interferon-γ (IFN-γ) but suppressed by interleukin-21. Strikingly, IFN-γ also enhanced TNF-α expression, while it strongly suppressed osteoprotegerin expression in B cells. IFN-γ increased the generation of CXCR3(+)RANKL(+) effector B cells, mimicking the synovial B cell phenotype in patients with rheumatoid arthritis. Finally, RANKL(+) effector B cells in concert with TNF-α facilitated osteoclast differentiation in vitro. Our current findings have shed light on the generation mechanism of pathogenic RANKL(+) effector B cells that would be an ideal therapeutic target for rheumatoid arthritis in the future.

Operational optimization in the downstream; Otimizacao operacional no downstream

Energy Technology Data Exchange (ETDEWEB)

Silberman, Luis; Cunha, Filipe Silveira Ramos da [Petroleo Ipiranga, Porto Alegre, RS (Brazil)

2004-07-01

On the present competitive down stream's market, there is a great necessity of optimization aiming to guarantee the best price and quality of our clients. Our goal is to attend these expectations while we guarantee an efficient operation. The greatest question is how far we are from the ideal model. This way, a lot of projects have been executed during the last years aiming the operational optimization of all our activities. We divide the projects in 4 areas: Logistic (new modals distribution), Transport (transport optimization - quality and more deliveries with less trucks), Client Support (Internet Ipiranga and Support Center), Distribution Terminals Productivity (automation and environment). This work intend to present our ideal, perfect and complete Downstream Operation model. We will talk about how close we are of this ideal model and we will present the projects that we had already developed and implanted on the automation of the terminals and the logistics area. (author)

Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient

DEFF Research Database (Denmark)

Pudasaini, Nawin; Upadhyay, Pratik Pankaj; Parker, Christian Richard

2017-01-01

Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability and tablet......Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability...

Improvements, enhancements, and optimizations of COBRA-TF

International Nuclear Information System (INIS)

Salko, R. K.; Avramova, M. N.; Hooper, R.; Palmtag, S.; Popov, E.; Turner, J.

2013-01-01

The Reactor Dynamics and Fuel Management Group (RDFMG) at The Pennsylvania State University (PSU) has become active in the Consortium for Advanced Simulation of Light Water Reactors (CASL) program by delivering, supporting, and further developing CTF, the PSU version of the Coolant Boiling in Rod Arrays - Two Fluids (COBRA-TF) Thermal/Hydraulic (T/H), sub-channel program. New development work on CTF was primarily geared towards decreasing the execution time of the code so that it may eventually be used for performing pin-by-pin, full-core simulations. Great gains have been made through targeting sections of source code for optimization. For example, wall clock time has been reduced for a one-assembly, three-dimensional model, containing ∼9,400 mesh cells, from 9.2 min to 1 min. A further improvement has been reduction in code memory usage, which was previously prohibitive for large models. In conjunction with the run time speedups, this has enabled the simulation of a refined quarter-core model (∼460,000 mesh cells), which saw a reduction in memory usage from over 130 GB to less than 3 GB. In addition to the optimization work, RDFMG has also created a preprocessor utility for the fast and less error-prone generation of CTF input decks. Furthermore, basic post-processing capabilities have been implemented by creating a CTF subroutine for producing Visualization Tool-Kit (VTK) files that output mesh data and associated simulation results. These VTK files can be opened with visualization software. (authors)

System design description for the LDUA common video end effector system (CVEE)

International Nuclear Information System (INIS)

Pardini, A.F.

1998-01-01

The Common Video End Effector System (CVEE), system 62-60, was designed by the Idaho National Engineering Laboratory (INEL) to provide the control interface of the various video end effectors used on the LDUA. The CVEE system consists of a Support Chassis which contains the input and output Opto-22 modules, relays, and power supplies and the Power Chassis which contains the bipolar supply and other power supplies. The combination of the Support Chassis and the Power Chassis make up the CVEE system. The CVEE system is rack mounted in the At Tank Instrument Enclosure (ATIE). Once connected it is controlled using the LDUA supervisory data acquisition system (SDAS). Video and control status will be displayed on monitors within the LDUA control center

Le Dix-huit Brumaire de Napoléon Bonaparte : retour sur un coup d'État [Review of: P. Gueniffey. Le Dix-huit Brumaire : l’épilogue de la Révolution française, 9-10 novembre 1799

NARCIS (Netherlands)

Jourdan, A.

2008-01-01

Patrice Gueniffey propose une nouvelle histoire du Dix-huit Brumaire, coup d’État par lequel Napoléon Bonaparte prit le pouvoir le 9 novembre 1799. Il voit dans cet évènement « une manière un peu tendue de résoudre les crises graves de l’État » et dresse un parallèle avec la journée du 13 mai 1958

Upstream-downstream cooperation approach in Guanting Reservoir watershed.

Science.gov (United States)

Yang, Zhi-Feng; Zhang, Wen-Guo

2005-01-01

A case study is introduced and discussed concerning water dispute of misuse and pollution between up- and down-stream parts. The relations between water usage and local industrial structures are analyzed. Results show it is important to change industrial structures of the target region along with controlling water pollution by technical and engineering methods. Three manners of upstream-downstream cooperation are presented and discussed based on the actual conditions of Guangting Reservoir watershed. Two typical scenarios are supposed and studied along with the local plan on water resources development. The best solution for this cooperation presents a good way to help the upstream developing in a new pattern of eco-economy.

Analysis of Petroleum Downstream Industry Potential in Riau Province

Directory of Open Access Journals (Sweden)

Tomi Erfando

2017-06-01

Full Text Available Petroleum downstream industry in Riau Province is still not optimal. The data shows that from 98,892,755 barrels lifting oil each year only 62,050,000 barrels could be processed in refinery unit II Dumai operated by PT Pertamina. There is a potential of 35-40% of downstream industry. Indonesian Government through The Ministry of Energy and Mineral Resources declared the construction of a mini refinery to boost oil processing output in the downstream sector. A feasibility study of development plan mini refinery is needed. The study includes production capacity analysis, product analysis, development & operational refinery  analysis and economic analysis. The results obtained by the mini refinery capacity is planned to process crude oil 6000 BOPD with the products produced are gasoline, kerosene, diesel and oil. Investment cost consist of is capital cost US $ 104419784 and operating cost US $ 13766734 each year with net profit earned US $ 12330063/year and rate of return from investment 11.63%

Hydrodynamic properties and distribution of bait downstream of a zooplankton trap

DEFF Research Database (Denmark)

Selander, Erik; Heuschele, Jan; Larsson, Ann I.

2017-01-01

The flow regime around a chemically baited trap is crucial for the trapping process and distribution of bait downstream of traps. We measured the flow field downstream of a trap prototype in flume experiments and mapped the distribution of bait using laser induced fluorescence. The trap produced ...

p21-ras effector domain mutants constructed by "cassette" mutagenesis

DEFF Research Database (Denmark)

Stone, J C; Vass, W C; Willumsen, B M

1988-01-01

A series of mutations encoding single-amino-acid substitutions within the v-rasH effector domain were constructed, and the ability of the mutants to induce focal transformation of NIH 3T3 cells was studied. The mutations, which spanned codons 32 to 40, were made by a "cassette" mutagenesis...

Aminoacyl-tRNA-charged eukaryotic elongation factor 1A is a bona fide substrate for Legionelle pneumophila effector glucosyltransferases

DEFF Research Database (Denmark)

Tzivelekidis, Tina; Jank, Thomas; Pohl, Corinna

2011-01-01

Legionella pneumophila, which is the causative organism of Legionnaires disease, translocates numerous effector proteins into the host cell cytosol by a type IV secretion system during infection. Among the most potent effector proteins of Legionella are glucosyltransferases (Lgt’s), which...

The "Revolution" is a tree of secular life: The Jornal do Brasil and the invention of democracy and legality of civil-military coup and the military government (1964-1968.

Directory of Open Access Journals (Sweden)

Dayane Cristina Guarnieri

2014-12-01

Full Text Available The research intends to analyze the editorials published by “Jornal do Brasil” (representative of the great press during the military-civil coup until 1968. The objective is to understand the justification for the military civil coup and the military government considering the speech changes of this newspaper in regard to the everyday politics. As “Jornal do Brasil” defended the intervention into Goulart´s constitutional government, like the most of the press, it´s conjectured that it continued to support the military government. The newspaper stressed that democracy should be preserved through democracy institutions and legality and their continuity in association with the military power. Even saying that democracy wasn’t practiced in that context, “JB” stated that the military government had it as the objective of its acts. It has been noticed that in spite of a contradiction in the editorial opinion, which varies between joining and criticism, it is always willing to guide the government actions. Therefore, “Jornal do Brasil” helped the military group to legitimate themselves before society through legalistic democratic speeches, but also in many occasions accused the government pointing out the political farces, for example the Constitution of 1967 and the indirect election, or criticizing the governmental immobility reminding, in several moments, promises made in 1964 that were not fulfilled – these promises intended to benefit the social group to which the newspaper integrated and represented. In other words, it preserves the democratic speech but also elaborates the conception that an arbitrary regime could improve the democracy and the development of capitalism.

The downstream externalities of harvesting rainwater in semi-arid watersheds: an Indian case study

NARCIS (Netherlands)

Bouma, J.A.; Biggs, T.W.; Bouwer, L.M.

2011-01-01

Water-related investment projects affect downstream water availability, and therefore should account for these externalities. Few projects do, however, owing to lack of awareness, lack of data and difficulty in linking upstream investments to downstream effects. This article assesses the downstream

Functional differences between PD-1+ and PD-1- CD4+ effector T cells in healthy donors and patients with glioblastoma multiforme.

Directory of Open Access Journals (Sweden)

Brittany A Goods

Full Text Available Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1 have been highly successful in the treatment of cancer. While PD-1 expression has been widely investigated, its role in CD4+ effector T cells in the setting of health and cancer remains unclear, particularly in the setting of glioblastoma multiforme (GBM, the most aggressive and common form of brain cancer. We examined the functional and molecular features of PD-1+CD4+CD25-CD127+Foxp3-effector cells in healthy subjects and in patients with GBM. In healthy subjects, we found that PD-1+CD4+ effector cells are dysfunctional: they do not proliferate but can secrete large quantities of IFNγ. Strikingly, blocking antibodies against PD-1 did not rescue proliferation. RNA-sequencing revealed features of exhaustion in PD-1+ CD4 effectors. In the context of GBM, tumors were enriched in PD-1+ CD4+ effectors that were similarly dysfunctional and unable to proliferate. Furthermore, we found enrichment of PD-1+TIM-3+ CD4+ effectors in tumors, suggesting that co-blockade of PD-1 and TIM-3 in GBM may be therapeutically beneficial. RNA-sequencing of blood and tumors from GBM patients revealed distinct differences between CD4+ effectors from both compartments with enrichment in multiple gene sets from tumor infiltrating PD-1-CD4+ effectors cells. Enrichment of these gene sets in tumor suggests a more metabolically active cell state with signaling through other co-receptors. PD-1 expression on CD4 cells identifies a dysfunctional subset refractory to rescue with PD-1 blocking antibodies, suggesting that the influence of immune checkpoint inhibitors may involve recovery of function in the PD-1-CD4+ T cell compartment. Additionally, co-blockade of PD-1 and TIM-3 in GBM may be therapeutically beneficial.

Methylation of Hg downstream from the Bonanza Hg mine, Oregon

Science.gov (United States)

Gray, John E.; Hines, Mark E.; Krabbenhoft, David P.; Thoms, Bryn

2012-01-01

Speciation of Hg and conversion to methyl-Hg were evaluated in stream sediment, stream water, and aquatic snails collected downstream from the Bonanza Hg mine, Oregon. Total production from the Bonanza mine was >1360t of Hg, during mining from the late 1800s to 1960, ranking it as an intermediate sized Hg mine on an international scale. The primary objective of this study was to evaluate the distribution, transport, and methylation of Hg downstream from a Hg mine in a coastal temperate climatic zone. Data shown here for methyl-Hg, a neurotoxin hazardous to humans, are the first reported for sediment and water from this area. Stream sediment collected from Foster Creek flowing downstream from the Bonanza mine contained elevated Hg concentrations that ranged from 590 to 71,000ng/g, all of which (except the most distal sample) exceeded the probable effect concentration (PEC) of 1060ng/g, the Hg concentration above which harmful effects are likely to be observed in sediment-dwelling organisms. Concentrations of methyl-Hg in stream sediment collected from Foster Creek varied from 11 to 62ng/g and were highly elevated compared to regional baseline concentrations (0.11-0.82ng/g) established in this study. Methyl-Hg concentrations in stream sediment collected in this study showed a significant correlation with total organic C (TOC, R2=0.62), generally indicating increased methyl-Hg formation with increasing TOC in sediment. Isotopic-tracer methods indicated that several samples of Foster Creek sediment exhibited high rates of Hg-methylation. Concentrations of Hg in water collected downstream from the mine varied from 17 to 270ng/L and were also elevated compared to baselines, but all were below the 770ng/L Hg standard recommended by the USEPA to protect against chronic effects to aquatic wildlife. Concentrations of methyl-Hg in the water collected from Foster Creek ranged from 0.17 to 1.8ng/L, which were elevated compared to regional baseline sites upstream and downstream

Macrophages are critical effectors of antibody therapies for cancer.

Science.gov (United States)

Weiskopf, Kipp; Weissman, Irving L

2015-01-01

Macrophages are innate immune cells that derive from circulating monocytes, reside in all tissues, and participate in many states of pathology. Macrophages play a dichotomous role in cancer, where they promote tumor growth but also serve as critical immune effectors of therapeutic antibodies. Macrophages express all classes of Fcγ receptors, and they have immense potential to destroy tumors via the process of antibody-dependent phagocytosis. A number of studies have demonstrated that macrophage phagocytosis is a major mechanism of action of many antibodies approved to treat cancer. Consequently, a number of approaches to augment macrophage responses to therapeutic antibodies are under investigation, including the exploration of new targets and development of antibodies with enhanced functions. For example, the interaction of CD47 with signal-regulatory protein α (SIRPα) serves as a myeloid-specific immune checkpoint that limits the response of macrophages to antibody therapies, and CD47-blocking agents overcome this barrier to augment phagocytosis. The response of macrophages to antibody therapies can also be enhanced with engineered Fc variants, bispecific antibodies, or antibody-drug conjugates. Macrophages have demonstrated success as effectors of cancer immunotherapy, and further investigation will unlock their full potential for the benefit of patients.

Cancer resistance of SR/CR mice in the genetic knockout backgrounds of leukocyte effector mechanisms: determinations for functional requirements.

Science.gov (United States)

Sanders, Anne M; Stehle, John R; Blanks, Michael J; Riedlinger, Gregory; Kim-Shapiro, Jung W; Monjazeb, Arta M; Adams, Jonathan M; Willingham, Mark C; Cui, Zheng

2010-03-31

Spontaneous Regression/Complete Resistant (SR/CR) mice are a colony of cancer-resistant mice that can detect and rapidly destroy malignant cells with innate cellular immunity, predominately mediated by granulocytes. Our previous studies suggest that several effector mechanisms, such as perforin, granzymes, or complements, may be involved in the killing of cancer cells. However, none of these effector mechanisms is known as critical for granulocytes. Additionally, it is unclear which effector mechanisms are required for the cancer killing activity of specific leukocyte populations and the survival of SR/CR mice against the challenges of lethal cancer cells. We hypothesized that if any of these effector mechanisms was required for the resistance to cancer cells, its functional knockout in SR/CR mice should render them sensitive to cancer challenges. This was tested by cross breeding SR/CR mice into the individual genetic knockout backgrounds of perforin (Prf-/-), superoxide (Cybb-/), or inducible nitric oxide (Nos2-/). SR/CR mice were bred into individual Prf-/-, Cybb-/-, or Nos2-/- genetic backgrounds and then challenged with sarcoma 180 (S180). Their overall survival was compared to controls. The cancer killing efficiency of purified populations of macrophages and neutrophils from these immunodeficient mice was also examined. When these genetically engineered mice were challenged with cancer cells, the knockout backgrounds of Prf-/-, Cybb-/-, or Nos2-/- did not completely abolish the SR/CR cancer resistant phenotype. However, the Nos2-/- background did appear to weaken the resistance. Incidentally, it was also observed that the male mice in these immunocompromised backgrounds tended to be less cancer-resistant than SR/CR controls. Despite the previously known roles of perforin, superoxide or nitric oxide in the effector mechanisms of innate immune responses, these effector mechanisms were not required for cancer-resistance in SR/CR mice. The resistance was

The downstream industry compared to market

International Nuclear Information System (INIS)

Chevallier, B.

2010-01-01

J.L. Schilansky introduces here the difficult question of the downstream industry compared to market in recalling the recent structural changes (behaviour of customers, behaviour of the USA- and China-governments), the increase of the European and French regulations, the climatic change and the conjectural impact of the crisis on the refining industry. (O.M.)

Rac1-induced cell migration requires membrane recruitment of the nuclear oncogene SET

NARCIS (Netherlands)

ten Klooster, Jean Paul; Leeuwen, Ingrid v; Scheres, Nina; Anthony, Eloise C.; Hordijk, Peter L.

2007-01-01

The Rho GTPase Rac1 controls cell adhesion and motility. The effector loop of Rac1 mediates interactions with downstream effectors, whereas its C-terminus binds the exchange factor beta-Pix, which mediates Rac1 targeting and activation. Here, we report that Rac1, through its C-terminus, also binds

Philips Gemini TF64 PET/CT Acceptance Testing

International Nuclear Information System (INIS)

González Gonzalez, Joaquín J.; Calderón Marin, Carlos F.; Varela Corona, Consuelo; Machado Tejeda, Adalberto; González Correa, Héctor J.

2016-01-01

The Philips Gemini TF64 is the first PET/CT scanner installed in Cuba at the Institute of Oncology and Radiobiology in 2014. It is a third generation fully tridimensional whole body PET scanner with time-of-flight (TOF) technology combined with a 64-slice Brilliance CT scanner. The CT detector module contains 672x64 solid state detector, incorporating GOS scintillators, optical diodes and electronic signal channels arranged in 64 side by side arcs, with 672 detectors in each arc. There are sixteen 0.75 mm individual detector elements around the center and four 1.5 mm elements at each end, resulting in a 24 mm total detection length. The PET detector consists of 28 pixelar modules of a 23x44 array of 4x4x22 mm3 of LYSO crystals arranged in an Anger-logic detector design. The hardware coincidence-timing window for this scanner is set at 4 ns and delayed coincidence window technique is used to estimate the random coincidences in collected data. In this study the performance characteristics of PET/CT scanner were measured as part of the program tests of acceptance for clinical use.Methodology. The performance characteristics of CT scanner were evaluated by manufacturer protocol using Philips system performance phantom. Some additional geometrical tests were performed by the user. The intrinsic measurements of energy resolution as well as timing resolution, which define the TOF performance of PET scanner, were performed following the recommendations of manufacturer using 18 F. Spatial resolution, sensitivity, scatter fraction, counting rate performance, image quality and accuracy were measured according to the NEMA NU-2 2007 procedures. Additionally, to characterize the effect of TOF reconstruction on lesion contrast and noise, the standard NEMA torso phantom was reconstructed with and without TOF capability. The accuracy of PET/CT image registration was tested according to the manufacturer protocol using an image alignment calibration holder with 6 point sources of 22

From gravel to sand. Downstream fining of bed sediments in the lower river Rhine

NARCIS (Netherlands)

Frings, R.M.

2007-01-01

A common characteristic of many rivers is the tendency for bed sediments to become finer in downstream direction. This phenomenon, which is generally known as downstream fining, has a strong effect on the morphologic and hydrodynamic behaviour of a river. The fundamental causes of downstream

Ion energy characteristics downstream of a high power helicon

International Nuclear Information System (INIS)

Prager, James; Winglee, Robert; Ziemba, Tim; Roberson, B Race; Quetin, Gregory

2008-01-01

The High Power Helicon eXperiment operates at higher powers (37 kW) and lower background neutral pressure than other helicon experiments. The ion velocity distribution function (IVDF) has been measured at multiple locations downstream of the helicon source and a mach 3-6 flowing plasma was observed. The helicon antenna has a direct effect in accelerating the plasma downstream of the source. Also, the IVDF is affected by the cloud of neutrals from the initial gas puff, which keeps the plasma speed low at early times near the source.

Ion energy characteristics downstream of a high power helicon

Energy Technology Data Exchange (ETDEWEB)

Prager, James; Winglee, Robert; Ziemba, Tim; Roberson, B Race; Quetin, Gregory [University of Washington, Johnson Hall 070, Box 351310, 4000 15th Avenue NE, Seattle, WA 98195-1310 (United States)], E-mail: jprager@u.washington.edu

2008-05-01

The High Power Helicon eXperiment operates at higher powers (37 kW) and lower background neutral pressure than other helicon experiments. The ion velocity distribution function (IVDF) has been measured at multiple locations downstream of the helicon source and a mach 3-6 flowing plasma was observed. The helicon antenna has a direct effect in accelerating the plasma downstream of the source. Also, the IVDF is affected by the cloud of neutrals from the initial gas puff, which keeps the plasma speed low at early times near the source.

Lessons after 3 years of running GENIUS-TF in Gran Sasso