Dual Role (dual + role)

Distribution by Scientific Domains
Distribution within Life Sciences


Selected Abstracts


Dual Role for Ethylene in Susceptibility of Tomato to Verticillium Wilt

JOURNAL OF PHYTOPATHOLOGY, Issue 7-8 2001
M. M. Robison
Abstract Ethylene has been observed to both inhibit and promote the symptoms of Verticillium wilt (caused by Verticillium dahliae) in tomato. To test the hypothesis that ethylene has different effects at different stages in the infection process, ethylene levels were manipulated in V. dahliae -infected tomato plants by the application of an ethylene synthesis inhibitor aminoethoxyvinylglycine (AVG) and/or ethylene's biosynthetic precursor 1-aminocyclopropane-1-carboxylate (ACC) and the effects on disease severity were examined. Statistically significant reductions in disease severity were consistently obtained for AVG-treated plants that had ACC added at the time of inoculation. A model is therefore proposed in which post-infection ethylene enhances Verticillium wilt development in tomato whereas its presence at the time of infection inhibits disease development. [source]


Pd-Catalyzed Stereoselective Oxidation of Methyl Groups by Inexpensive Oxidants under Mild Conditions: A Dual Role for Carboxylic Anhydrides in Catalytic C,H Bond Oxidation.

CHEMINFORM, Issue 12 2006
Ramesh Giri
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source]


ChemInform Abstract: Stereocontrol in Radical Processes Through the Exocyclic Effect: Dual Role of Triethylboron as Radical Initiator and in situ Derivatization Agent.

CHEMINFORM, Issue 34 2001
Jean-Pierre Bouvier
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]


Consequences of childhood abuse among male psychiatric inpatients: Dual roles as victims and perpetrators

JOURNAL OF TRAUMATIC STRESS, Issue 1 2001
Marylene Cloitre
Abstract The relationship between retrospective self-reports of childhood abuse and subsequent interpersonal violence was assessed among 354 consecutive male inpatient admissions. Three logistic regressions revealed that, controlling for sociodemo-graphic and diagnostic variables, the association between childhood abuse and three mutually exclusive adult negative outcomes were as follows: (1) being a perpetrator of violence (Odds Ratio [OR] = ns), (2) being a victim of violence (OR = 2.5), and (3) being a perpetrator and victim (OR = 4.9). The results suggest that, among men with significant psychiatric impairments and childhood abuse, rates of adult victimization are high, and the most frequent negative outcome reflects involvement in dual roles of perpetrator and victim. The possible dynamics of this relationship are discussed. [source]


The Macro-Economic Effects of Directed Credit Policies: A Real-Financial CGE Evaluation for India

DEVELOPMENT AND CHANGE, Issue 3 2001
C. W. M. Naastepad
The effectiveness of directed credit programmes as an instrument for economic development is the subject of considerable debate. However, the focus of this debate is almost exclusively on the intra-sectoral effects of directed credit and its adverse effects on financial sector performance, neglecting possible spillover effects on demand, production and investment in the rest of the economy. This article tries to fill this gap by examining the macro-economic effects of directed credit in India with the help of a novel real-financial computable general equilibrium (CGE) model. Focusing on credit rather than money, the model goes beyond earlier modelling approaches by (1) incorporating directed credit policy and credit rationing; (2) recognizing the dual role of credit for working capital and investment; and (3) allowing for switches between credit-constrained, capacity-constrained and demand-constrained regimes. The results from short- and medium-term simulation experiments with the model indicate that, when credit market failures result in rationing as in India's agricultural and small-scale industrial sectors, the macro-economic effects of directed credit are likely to be significant and positive. [source]


Initial stages of neural regeneration in Helisoma trivolvis are dependent upon PLA2 activity

DEVELOPMENTAL NEUROBIOLOGY, Issue 4 2003
Matthew S. Geddis
Abstract Neuronal regeneration after damage to an axon tract requires the rapid sealing of the injured plasma membrane and the subsequent formation of growth cones that can lead regenerating processes to their appropriate target. Membrane sealing and growth cone formation are Ca2+ -dependent processes, but the signaling pathways activated by Ca2+ to bring about these effects remain poorly understood. An in vitro injury model was employed in which neurites from identified snail neurons (Helisoma trivolvis) were transected with a glass microknife, and the formation of new growth cones from the distal portions of transected neurites was recorded at defined times after transection. This study presents three main results. First, phospholipase A2 (PLA2), a calcium-activated enzyme, is necessary for membrane sealing in vitro. Second, PLA2 activity is also required for the formation of a new growth cone after the membrane has sealed successfully. Thus, PLA2 plays a dual role by affecting both growth cone formation and membrane sealing. Third, the injury-induced activation of PLA2 by Ca2+ controls growth cone formation through the production of leukotrienes, secondary metabolites of PLA2 activity. Taken together, these results suggest that the injury-induced Ca2+ influx acts via PLA2 and leukotriene production to assure growth cone formation. These findings indicate that events that cause an inhibition of PLA2 or lipoxygenases, enzymes that produce leukotrienes, could result in the inability of neurites to regenerate. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 555,565, 2003 [source]


Orexin B/hypocretin 2 increases glutamatergic transmission to ventral tegmental area neurons

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2008
S. L. Borgland
Abstract The orexins (hypocretins) play a crucial role in arousal, feeding and reward. Highly relevant to these functions, orexin-containing neurons from the lateral hypothalamus project densely to the ventral tegmental area (VTA), which is the origin of dopamine projections implicated in motivation and reward. Orexin A/hypocretin 1 (oxA/hcrt-1) can enable long-term changes associated with drugs of abuse; however, the effects of orexin B/hypocretin 2 (oxB/hcrt-2) on excitatory synaptic transmission in the VTA are unknown. We used whole-cell patch-clamp electrophysiology in rat horizontal midbrain slices to examine the effects of oxB/hcrt-2 on excitatory synaptic transmission. We observed that oxB/hcrt-2 has distinct effects from oxA/hcrt-1 in the VTA. oxB/Hcrt-2 (100 nm) increased presynaptic glutamate release in addition to a postsynaptic potentiation of NMDA receptors (NMDARs). The oxB/hcrt-2-mediated postsynaptic potentiation of NMDARs was mediated via activation of orexin/hypocretin 2 (OX2/Hcrt-2) receptors and protein kinase C (PKC). Furthermore, the increase in transmitter release probability was also PKC-dependent, but not through activation of orexin/hypocretin 1 (OX1/Hcrt-1) or OX2/Hcrt-2 receptors. Finally, oxB/hcrt-2 or the selective OX2/Hcrt-2 receptor agonist ala11 - d -leu15 -orexin B, significantly reduced spike-timing-induced long-term potentiation. Taken together, these results support a dual role for oxB/hcrt-2 in mediating enhanced glutamatergic transmission in the VTA, and suggest that oxA/hcrt-1 and oxB/hcrt-2 exert different functional roles in modulating the enhancement of the motivational components of arousal and feeding. [source]


Dual effects of NMDA receptor activation on polysialylated neural cell adhesion molecule expression during brainstem postnatal development

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2001
Farima Bouzioukh
Abstract Here we show a dual role of N -methyl- d -aspartate receptor (NMDAR) activation in controlling polysialylated neural cell adhesion molecule (PSA-NCAM) dynamic expression in the dorsal vagal complex (DVC), a gateway for many primary afferent fibres. In this structure the overall expression of PSA-NCAM decreases during the first 2 weeks after birth to persist only at synapses in the adult. Electrical stimulation of the vagal afferents causes a rapid increase of PSA-NCAM expression both in vivo and in acute slices before postnatal day (P) 14 whereas a similar stimulation induces a decrease after P15. Inhibition of NMDAR activity in vitro completely prevented these changes. These regulations depend on calmodulin activation and cGMP production at all stages. By contrast, blockade of neuronal nitric oxide synthase (nNOS) prevented these changes only after P10 in agreement with its late expression in the DVC. The pivotal role of NMDAR is also supported by the observation that chronic blockade induces a dramatic decrease in PSA-NCAM expression. [source]


Dual effect of ecdysone on adult cricket mushroom bodies

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2000
Myriam Cayre
Abstract Mushroom bodies, which are the main integrative centre for insect sensorial information, play a critical role in associative olfactory learning and memory. This paired brain structure contains interneurons grouped in a cortex, sending their axons into organized neuropiles. In the house cricket (Acheta domesticus) brain, persistent neuroblasts proliferate throughout adult life. Juvenile hormone (JH) has been shown to stimulate this proliferation [Cayre, M., Strambi, C. & Strambi, A. (1994) Nature, 368, 57,59]. In the present study, the effect of morphogenetic hormones on mushroom body cells maintained in primary culture was examined. Whereas JH did not significantly affect neurite growth, ecdysone significantly stimulated neurite elongation. Moreover, ecdysone also acted on neuroblast proliferation, as demonstrated by the reduced number of cells labelled with 5-bromodeoxyuridine following ecdysone application. Heterospecific antibodies raised against ecdysone receptor protein and ultraspiracle protein, the two heterodimers of ecdysteroid receptors, showed positive immunoreactivity in nervous tissue extracts and in nuclei of mushroom body cells, indicating the occurrence of putative ecdysteroid receptors in cricket mushroom body cells. These data indicate a dual role for ecdysone in adult cricket mushroom bodies: this hormone inhibits neuroblast proliferation and stimulates interneuron differentiation. These results suggest that a constant remodelling of mushroom body structure could result from physiological changes in hormone titres during adult life. [source]


A Facile and Efficient One-Pot Synthesis of Substituted Quinolines from ,-Arylamino Ketones Under Vilsmeier Conditions

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 24 2009
Yan Wang
Abstract An efficient one-pot synthesis of substituted quinolines from ,-arylamino ketones in the presence of PBr3 in DMF has been developed. This general protocol provides a novel and facile access to substituted quinolines by sequential Vilsmeier,Haack reaction, intramolecular cyclization and aromatization reactions of ,-arylamino ketones. PBr3 plays a dual role in the quinoline synthesis: as a key component of the Vilsmeier reagent (PBr3/DMF) and as a reducing reagent. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]


MICRO- AND MACROEVOLUTIONARY DECOUPLING OF CICHLID JAWS: A TEST OF LIEM'S KEY INNOVATION HYPOTHESIS

EVOLUTION, Issue 10 2006
C. D. Hulsey
Abstract The extent to which elements of functional systems can change independently (modularity) likely influences the diversification of lineages. Major innovations in organismal design, like the pharyngeal jaw in cichlid fishes, may be key to a group's success when they relax constraints on diversification by increasing phenotypic modularity. In cichlid fishes, pharyngeal jaw modifications that enhanced the ability to breakdown prey may have freed their oral jaws from serving their ancestral dual role as a site of both prey capture and prey processing. This functional decoupling that allowed the oral jaws to become devoted solely to prey capture has been hypothesized to have permitted the two sets of cichlid jaws to evolve independently. We tested the hypothesis that oral and pharyngeal jaw mechanics are evolutionarily decoupled both within and among Neotropical Heroine cichlids. In the trophically polymorphic species Herichthys minckleyi, molariforms that exhibit enlarged molarlike pharyngeal jaw teeth were found to have approximately 400% greater lower jaw mass compared to H. minckleyi with the alternative papilliform pharyngeal morphology. However, oral jaw gape, lower jaw velocity ratios, anterior jaw linkage mechanics, and jaw protrusion did not differ between the morphotypes. In 40 other Heroine species, there was a weak correlation between oral jaw mechanics and pharyngeal jaw mass when phylogenetic history was ignored. Yet, after expansion of the cytochrome b phylogeny for Heroines, change in oral jaw mechanics was found to be independent of evolutionary change in pharyngeal jaw mass based on independent contrasts. Evolutionary decoupling of oral and pharyngeal jaw mechanics has likely played a critical role in the unparalleled trophic diversification of cichlid fishes. [source]


Angiotensin-(1,7) has a dual role on growth-promoting signalling pathways in rat heart in vivo by stimulating STAT3 and STAT5a/b phosphorylation and inhibiting angiotensin II-stimulated ERK1/2 and Rho kinase activity

EXPERIMENTAL PHYSIOLOGY, Issue 5 2008
Jorge F. Giani
Angiotensin (ANG) II contributes to cardiac remodelling by inducing the activation of several signalling molecules, including ERK1/2, Rho kinase and members of the STAT family of proteins. Angiotensin-(1,7) is produced in the heart and inhibits the proliferative actions of ANG II, although the mechanisms of this inhibition are poorly understood. Accordingly, in the present study we examined whether ANG-(1,7) affects the ANG II-mediated activation of ERK1/2 and Rho kinase, STAT3 and STAT5a/b in rat heart in vivo. We hypothesized that ANG-(1,7) inhibits these growth-promoting pathways, counterbalancing the trophic action of ANG II. Solutions of normal saline (0.9% NaCl) containing ANG II (8 pmol kg,1) plus ANG-(1,7) in increasing doses (from 0.08 to 800 pmol kg,1) were administered via the inferior vena cava to anaesthetized male Sprague,Dawley rats. After 5 min, hearts were removed and ERK1/2, Rho kinase, STAT3 and STAT5a/b phosphorylation was determined by Western blotting using phosphospecific antibodies. Angiotensin II stimulated ERK1/2 and Rho kinase phosphorylation (2.3 ± 0.2- and 2.1 ± 0.2-fold increase over basal values, respectively), while ANG-(1,7) was without effect. The ANG II-mediated phosphorylation of ERK1/2 and Rho kinase was prevented in a dose-dependent manner by ANG-(1,7) and disappeared in the presence of the Mas receptor antagonist d -Ala7 -ANG-(1,7). Both ANG II and ANG-(1,7) increased STAT3 and STAT5a/b phosphorylation to a similar extent (130,140% increase). The ANG-(1,7)-stimulated STAT phosphorylation was blocked by the AT1 receptor antagonist losartan and not by d -Ala7 -ANG-(1,7). Our results show a dual action of ANG-(1,7), that is, a stimulatory effect on STAT3 and 5a/b phosphorylation through AT1 receptors and a blocking action on ANG II-stimulated ERK1/2 and Rho kinase phosphorylation through Mas receptor activation. The latter effect could be representative of a mechanism for a protective role of ANG-(1,7) in the heart by counteracting the effects of locally generated ANG II. [source]


Experimental and steady-state analysis of the GAL regulatory system in Kluyveromyces lactis

FEBS JOURNAL, Issue 14 2010
Venkat R. Pannala
The galactose uptake mechanism in yeast is a well-studied regulatory network. The regulatory players in the galactose regulatory mechanism (GAL system) are conserved in Saccharomyces cerevisiae and Kluyveromyces lactis, but the molecular mechanisms that occur as a result of the molecular interactions between them are different. The key differences in the GAL system of K. lactis relative to that of S. cerevisiae are: (a) the autoregulation of KlGAL4; (b) the dual role of KlGal1p as a metabolizing enzyme as well as a galactose-sensing protein; (c) the shuttling of KlGal1p between nucleus and cytoplasm; and (d) the nuclear confinement of KlGal80p. A steady-state model was used to elucidate the roles of these molecular mechanisms in the transcriptional response of the GAL system. The steady-state results were validated experimentally using measurements of ,-galactosidase to represent the expression for genes having two binding sites. The results showed that the autoregulation of the synthesis of activator KlGal4p is responsible for the leaky expression of GAL genes, even at high glucose concentrations. Furthermore, GAL gene expression in K. lactis shows low expression levels because of the limiting function of the bifunctional protein KlGal1p towards the induction process in order to cope with the need for the metabolism of lactose/galactose. The steady-state model of the GAL system of K. lactis provides an opportunity to compare with the design prevailing in S. cerevisiae. The comparison indicates that the existence of a protein, Gal3p, dedicated to the sensing of galactose in S. cerevisiae as a result of genome duplication has resulted in a system which metabolizes galactose efficiently. [source]


Members of the IclR family of bacterial transcriptional regulators function as activators and/or repressors

FEMS MICROBIOLOGY REVIEWS, Issue 2 2006
Antonio J. Molina-Henares
Abstract Members of the IclR family of regulators are proteins with around 250 residues. The IclR family is best defined by a profile covering the effector binding domain. This is supported by structural data and by a number of mutants showing that effector specificity lies within a pocket in the C-terminal domain. These regulators have a helix-turn-helix DNA binding motif in the N-terminal domain and bind target promoters as dimers or as a dimer of dimers. This family comprises regulators acting as repressors, activators and proteins with a dual role. Members of the IclR family control genes whose products are involved in the glyoxylate shunt in Enterobacteriaceae, multidrug resistance, degradation of aromatics, inactivation of quorum-sensing signals, determinants of plant pathogenicity and sporulation. No clear consensus exists on the architecture of DNA binding sites for IclR activators: the MhpR binding site is formed by a 15-bp palindrome, but the binding sites of PcaU and PobR are three perfect 10-bp sequence repetitions forming an inverted and a direct repeat. IclR-type positive regulators bind their promoter DNA in the absence of effector. The mechanism of repression differs among IclR-type regulators. In most of them the binding sites of RNA polymerase and the repressor overlap, so that the repressor occludes RNA polymerase binding. In other cases the repressor binding site is distal to the RNA polymerase, so that the repressor destabilizes the open complex. [source]


Neural circuit-dependent odor adaptation in C. elegans is regulated by the Ras-MAPK pathway

GENES TO CELLS, Issue 6 2005
Takaaki Hirotsu
The molecular machinery that mediates odor adaptation in the olfactory neurons is well documented in various animal species. However, types of adaptation that depend on neural circuits are mostly unexplored. We report here that the Ras-MAPK pathway is essential for such a type of odor adaptation, called early adaptation, in C. elegans. Early adaptation requires a pair of AIY interneurons, which receive synaptic inputs from olfactory neurons. Mutants of the Ras-MAPK pathway show defects in early adaptation. Continued exposure to an odorant causes activation of MAP kinase not only in the olfactory neurons, but also in the AIY interneurons. While activity of the Ras-MAPK pathway in the olfactory neurons is important for odor perception, its activity in the AIY interneurons is important for odor adaptation. Our results thus reveal a dual role of the Ras-MAPK pathway in sensory processing in the nervous system of C. elegans. [source]


Central role for Cdc45 in establishing an initiation complex of DNA replication in Xenopus egg extracts

GENES TO CELLS, Issue 6 2000
Satoru Mimura
Background In eukaryotes, chromosomal DNA is licensed to be replicated through the sequential loading of the origin recognition complex, Cdc6 and mini-chromosome maintenance protein complex (MCM) onto chromatin. However, how the replication machinery is assembled onto the licensed chromatin during initiation of replication is poorly understood. Results Using Xenopus egg extracts, we have investigated the role of Cdc45 in the loading of various replication proteins onto chromatin at the onset of S phase, and found that Cdc45, which required MCM for its loading, was essential for the sequential loading of replication protein A (RPA), DNA polymerase , and proliferating cell nuclear antigen (PCNA) onto chromatin. The assembly of DNA polymerase , onto chromatin required Cdc45 but did not require DNA polymerase ,. Analysis of nuclease-digested chromatin fractions shows that Cdc45 formed a stable complex with either MCM or DNA polymerase , on chromatin. Conclusions These results demonstrate a central role for Cdc45 in activation of the licensed chromatin to form replication complexes at the onset of S phase, and suggest that Cdc45 has a dual role in the initiation of DNA replication: the unwinding of DNA and the recruiting of DNA polymerases onto DNA. [source]


Genetic and molecular aspects of Alzheimer's disease shed light on new mechanisms of transcriptional regulation

GENES, BRAIN AND BEHAVIOR, Issue 3 2005
P. Marambaud
Rapid advances made in biological research aimed at understanding the molecular basis of the pathogenesis of Alzheimer's disease have led to the characterization of a novel catalytic activity termed ,-secretase. First described for its ,-amyloid-producing function, ,-secretase is now actively studied for its role in a novel signal transduction paradigm, which implicates cell-surface receptor proteolysis and direct surface-to-nucleus signal transduction. ,-Secretase targets numerous type I protein receptors involved in diverse functions ranging from normal development to neurodegeneration. In this Review we discuss how the study of the genetic and molecular aspects of Alzheimer's disease has revealed a dual role of ,-secretase in transcriptional regulation and in the pathogenesis of familial Alzheimer's disease. [source]


Investor Protections and Concentrated Ownership: Assessing Corporate Control Mechanisms in the Netherlands

GERMAN ECONOMIC REVIEW, Issue 2 2004
Robert Chirinko
Corporate governance; legal approach; the Netherlands Abstract. The Berle,Means problem , information and incentive asymmetries disrupting relations between knowledgeable managers and remote investors , has remained a durable issue engaging researchers since the 1930s. However, the Berle,Means paradigm , widely dispersed, helpless investors facing strong, entrenched managers , is under stress in the wake of the cross-country evidence presented by La Porta, Lopez-de-Silanes, Shleifer and Vishny, and their legal approach to corporate control. This paper continues to investigate the roles of investor protections and concentrated ownership by examining firm behaviour in the Netherlands. Our within-country analysis generates two key results. First, the role of investor protections emphasized in the legal approach is not sustained. Rather, firm performance is enhanced when the firm is freed of equity market constraints. Second, ownership concentration does not have a discernible impact on firm performance, which may reflect large shareholders' dual role in lowering the costs of managerial agency problems but raising the agency costs of expropriation. [source]


Astrocytes,Friends or foes in multiple sclerosis?

GLIA, Issue 13 2007
Anna Williams
Abstract In multiple sclerosis (MS), the presence of demyelinating plaques has concentrated researchers' minds on the role of the oligodendrocyte in its pathophysiology. Recently, with the rediscovery of early and widespread loss of axons in the disease, new emphasis has been put on the role of axons and axon-oligodendrocyte interactions in MS. Despite the fact that, in 1904, Müller claimed that MS was a disease of astrocytes, more recently, astrocytes have taken a back seat, except as the cells that form the final glial scar after all hope of demyelination is over. However, perhaps it is time for the return of the astrocyte to popularity in the pathogenesis of MS, with recent reports on the dual role of astrocytes in aiding degeneration and demyelination, by promoting inflammation, damage of oligodendrocytes and axons, and glial scarring, but also in creating a permissive environment for remyelination by their action on oligodendrocyte precursor migration, oligodendrocyte proliferation, and differentiation. We review these findings to try to provide a cogent view of astrocytes in the pathology of MS. © 2007 Wiley-Liss, Inc. [source]


Covance's global mentoring initiative develops people through exceptional partnerships

GLOBAL BUSINESS AND ORGANIZATIONAL EXCELLENCE, Issue 1 2006
Miriam Darmstadter
The global mentoring program at Covance plays a dual role as a diversity initiative and a resource-efficient developmental tool, providing a powerful developmental experience that enriches worklife for all participants. After studying successful programs in leading companies, the Covance team crafted a program that includes selection criteria and a careful matching process, training and tools for mentoring pairs, ongoing support, and close monitoring and evaluation. The company has also tackled the challenges of long-distance mentoring relationships to make the program more accessible to its global workforce. As the program continues to grow and receive rave reviews, the Covance team continues to refine it for even greater effectiveness. © 2006 Wiley Periodicals, Inc. [source]


Liver stem cells and hepatocellular carcinoma,

HEPATOLOGY, Issue 1 2009
Lopa Mishra
Although the existence of cancer stem cells (CSCs) was first proposed over 40 years ago, only in the past decade have these cells been identified in hematological malignancies, and more recently in solid tumors that include liver, breast, prostate, brain, and colon. Constant proliferation of stem cells is a vital component in liver tissues. In these renewing tissues, mutations will most likely result in expansion of the altered stem cells, perpetuating and increasing the chances of additional mutations and tumor progression. However, many details about hepatocellular cancer stem cells that are important for early detection remain poorly understood, including the precise cell(s) of origin, molecular genetics, and the mechanisms responsible for the highly aggressive clinical picture of hepatocellular carcinoma (HCC). Exploration of the difference between CSCs from normal stem cells is crucial not only for the understanding of tumor biology but also for the development of specific therapies that effectively target these cells in patients. These ideas have drawn attention to control of stem cell proliferation by the transforming growth factor beta (TGF-,), Notch, Wnt, and Hedgehog pathways. Recent evidence also suggests a key role for the TGF-, signaling pathway in both hepatocellular cancer suppression and endoderm formation, suggesting a dual role for this pathway in tumor suppression as well as progression of differentiation from a stem or progenitor stage. This review provides a rationale for detecting and analyzing tumor stem cells as one of the most effective ways to treat cancers such as HCC. (HEPATOLOGY 2009;49:318,329.) [source]


Biological role of NHERF1 protein expression in breast cancer

HISTOPATHOLOGY, Issue 5 2009
Anita Mangia
Aims:, To determine the role of Na+/H+ exchanger regulatory factor (NHERF1) in breast cancerogenesis and progression. Methods and results:, NHERF1 expression was examined in normal tissue, ductal carcinoma in situ (DCIS), invasive carcinoma (IBC), synchronous metastatic lymph node and metachronous distant metastases of a retrospective series of breast cancers. Fifty-one IBC, 42 DCIS and normal tissues were examined immunohistochemically, and the colocalization between NHERF1 and HER2/neu was studied by immunofluorescence. NHERF1 showed a different localization and pattern of expression in the different compartments of the breast. The mean value of cytoplasmic NHERF1 expression in paired samples was significantly higher in DCIS, IBC, distant metastases and metastatic lymph nodes with respect to normal tissues. Moreover, in metastatic lymph nodes NHERF1 was exclusively cytoplasmic. In the membrane NHERF1 was colocalized with overexpressed HER2/neu in DCIS, IBC and distant metastases. Conclusions:, Breast cancerogenesis is characterized by increased cytoplasmic expression of NHERF1 as the tumour progresses, suggesting a role in this process. The switch from apical membranous to cytoplasmic expression is compatible with a dual role for NHERF1 as a tumour suppressor or tumour promoter dependent on its subcellular localization. [source]


Pathways of murine mast cell development and trafficking: tracking the roots and routes of the mast cell

IMMUNOLOGICAL REVIEWS, Issue 1 2007
Jenny Hallgren
Summary:, The appreciation of the role of the mast cell (MC) in inflammatory processes has expanded dramatically during the last decade. Many of these processes, especially more prolonged responses, are accompanied by an increase in the number of MCs, and much of this increase is likely because of recruitment of immature progenitors with subsequent maturation under the control of the tissue microenvironment. We have begun to identify many of the cell-surface molecules that control this influx and have traced the development of these cells back to their hematopoietic roots. This development proceeds along the myelomonocytic pathway with distinct intermediates having been identified in both bone marrow and spleen. The expression of ,4,7 integrins has played a prominent role in this process, as it helped identify a bipotent basophil MC precursor in the spleens of C57BL/6 mice. This integrin also controls basal influx into the intestine and, along with ,4,1 integrins, plays a critical role in recruitment to inflamed lungs. Investigation of chemokines and chemokine receptors in these processes led to the identification of a dual role for the murine interleukin-8 receptor CXCR2. This ,-chemokine receptor affects MC progenitor trafficking by its expression by MC progenitors and by its expression on stromal cells, likely endothelium, affecting trafficking to both intestine under basal conditions and lung during inflammatory recruitment. [source]


Kinetics and simulations of reaction between safranine- O and acidic bromate and role of bromide therein

INTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 9 2002
S. B. Jonnalagadda
Safranine- O, a dye of the phenazinium class, was found to exhibit intricate kinetics during its reaction with bromate at low pH conditions. Under conditions of excess concentrations of acid and bromate, safranine- O (SA+) initially depleted very slowly (k = (3.9 ± 0.3) × 10,4 M,3 s,1) but after an induction time, the reaction occurred swiftly. Bromide exhibited a dual role in the reaction mechanism, both as an autocatalyst and as an inhibitor. The added bromide increased the initial rate of depletion of SA+, but delayed the transition to rapid reaction. The overall stiochiometric reaction was found to be 6SA+ + 4 BrO3, = 6SP + 3N2O + 3H2O + 6H+ + 4Br,, where SP is 3-amino-7-oxo-2,8-dimethyl-5-phenylphenazine. The fast kinetics of the reaction between aqueous bromine and safranine- O (k = (2.2 ± 0.1) × 103 M,1 s,1) are also reported in this paper A 17-step mechanism, consistent with the overall reaction dynamics and supported by simulations, is proposed and the role of various bromo and oxybromo species is also discussed. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 542,549, 2002 [source]


Palladium(II)-Catalyzed Domino Reaction of 2-(1-Alkynyl)-2-alken-1-ones with Nucleophiles: Scope, Mechanism and Synthetic Application in the Synthesis of 3,4-Fused Bicyclic Tetrasubstituted Furans

ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 4 2009
Yuanjing Xiao
Abstract Described herein is the development of a palladium(II)-catalyzed two- or three-component reaction of 2-(1-alkynyl)-2-alken-1-ones with nucleophiles and allylic chlorides. Various types of nucleophiles such as O- , N- , C -based nucleophiles and olefin-tethered O- , N- , C -based nucleophiles were investigated. The scope, mechanism and application of this Pd(II)-catalyzed domino reaction were studied. In these transformations, the palladium catalyst exhibits a dual role, serving simultaneously as a Lewis acid and a transition metal. Two possible reaction pathways (cross-coupling reaction vs. Heck reaction) from the same intermediate furanylpalladium species were observed. The reaction pathway is dependent on the property of the nucleophile and the length of the tethered chain as well. When olefin-tethered O -based nucleophiles were used, only the cross-coupling reaction pathway was observed, in contrast, both reaction pathways were observed when olefin-tethered C -based nucleophiles were employed. The product ratio is dependent on the length of the tethered chain. Furthermore, ring-closing metathesis (RCM) of corresponding furans with CC bonds provides an easy method for the preparation of functionalized oxygen-heterocycles , 3,4-fused bicyclic furans. It is also noteworthy that allylic chloride can be as an oxidant besides its well known function as an alkylating reagent. [source]


Putative dual role of ephrin-Eph receptor interactions in inflammation

IUBMB LIFE, Issue 7 2006
Andrei I. Ivanov
Abstract Inflammation is associated with a decreased adhesion between endothelial cells in blood vessels and an increased adhesion of circulating leukocytes to vascular endothelium and to epithelia of internal organs. These changes lead to leukocyte extravasation and tissue transmigration. We propose that ephrins and Eph receptors play important, but underappreciated, signaling roles in these processes. At early stages of inflammation, EphA2 receptor and ephrin-B2 are overexpressed in endothelial and epithelial cells, thus leading to those events (expression of adhesion molecules on the cell surface and reorganization of the intracellular cytoskeleton) that cause cell repulsion and disruption of endothelial and epithelial barriers. At later stages of inflammation, expression of EphA1, EphA3, EphB3, and EphB4 on leukocytes and endothelial cells decreases, thus promoting adhesion of leukocytes to endothelial cells. Taking into consideration the abundance of ephrins and Eph receptors in tissues and the robustness of their signaling effects, the proposed involvement is likely to be substantial and may constitute a novel therapeutic target. iubmb Life, 58: 389-394, 2006 [source]


Warrior nurse: duality and complementarity of role in the operational environment

JOURNAL OF ADVANCED NURSING, Issue 1 2008
Lauren Griffiths
Abstract Title.,Warrior nurse: duality and complementarity of role in the operational environment Aim., This paper is a report of a study to explore the nature of military nursing in an environment of war, in particular the union of personal, professional and organizational tenets and to identify the actual or potential effect this had on the nursing role in this unique environment. Background., The history of nursing is intrinsically linked with war. There is an irony to this relationship. Active involvement with military activities has provided a vehicle in which nursing has developed, albeit through fostering war, which itself destroys health and contravenes the ethos of nursing. Military nurses, one would assume, are able to reconcile the dichotomy existing between their caring role and being a member of an organization associated with conflict. Methods., A grounded theory design was adopted and the data were collected from 1999 to 2002 using a series of in-depth interviews and focus group with of 24 military nurses. Findings., Three categories were identified: ,It's Just Different Levels', ,That Double Hat' and ,It's Who We Are!' The first illustrates the reality of conflict. ,That Double Hat' outlines the military nurses dual role: those of caring and the military. ,It's Who We Are!' demonstrates the transition from nurse-to-warrior. These integrate to create the core category: ,Caring for War: Transition to Warrior'. Conclusion., The symbiotic relationship of carer and warrior arises as a consequence of strategies used by military nurses to embrace their dual role. Further research is needed to explore the essence of the caring role within a conflict zone from military and civilian perspectives. [source]


c-Jun NH2 -terminal kinase (JNK)-dependent nuclear translocation of apoptosis-inducing factor (AIF) following engagement of membrane immunoglobulin on WEHI-231 B lymphoma cells

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2008
Eiko Takada
Abstract WEHI-231 B lymphoma cells have been employed for analysis of antigen-induced B cell unresponsiveness because these cells undergo cell cycle arrest in G1, accompanied by induction of apoptosis. In the present study, we examined the requirement for toxic small molecules apoptosis-inducing factor (AIF) and cytochrome c, and subsequent caspase activation in apoptotic cell death in WEHI-231 and CH31 B lymphoma cells following engagement of membrane immunoglobulin (mIg). Pan-caspase inhibitor BD-fmk blocked mIg-mediated increase in cells with sub-G1 DNA content, whereas it did not affect mIg-mediated loss of mitochondrial membrane potential and phosphatidylserine exposure on B cell membrane. Dominant-negative form of c-Jun NH2 -terminal kinase1 (JNK1) blocked the translocation of AIF into the nuclei and cytosol from the mitochondria in the WEHI-231 and CH31 cells following mIg engagement, whereas constitutively active form of JNK1 enhanced it. This AIF translocation was also blocked by Bcl-xL, but not by BD-fmk. Moreover, AIF-deficient clones via small interfering RNA (siRNA)-mediated method showed small increase in loss of mitochondrial membrane potential. After mIg engagement, the AIF-deficient clones displayed an enhanced sensitivity to mIg-mediated apoptosis, concomitant with translocation of a residual AIF into the nuclei, compared with control clone. Our findings are compatible with the notion that AIF has dual role, with a proapoptotic function in the nuclei and a distinct anti-apoptotic function in the mitochondria. These observations would be valuable for analysis of B cell unresponsiveness and hopefully for treatment of diseases involving B cell dysfunction. J. Cell. Biochem. 104: 1927,1936, 2008. © 2008 Wiley-Liss, Inc. [source]


Paradoxical roles for lysyl oxidases in cancer,A prospect

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2007
Stacey L. Payne
Abstract Lysyl oxidase (LOX) is an extracellular matrix (ECM) enzyme that catalyzes the cross-linking of collagens or elastin in the extracellular compartment, thereby regulating the tensile strength of tissues. However, recent reports have demonstrated novel roles for LOX, including the ability to regulate gene transcription, motility/migration, and cell adhesion. These diverse functions have led researchers to hypothesize that LOX may have multiple roles affecting both extra- and intracellular cell function(s). Particularly noteworthy is aberrant LOX expression and activity that have been observed in various cancerous tissues and neoplastic cell lines. Both down and upregulation of LOX in tumor tissues and cancer cell lines have been described, suggesting a dual role for LOX as a tumor suppressor, as well as a metastasis promoter gene,creating a conundrum within the LOX research field. Here, we review the body of evidence on LOX gene expression, regulation, and function(s) in various cancer cell types and tissues, as well as stromal,tumor cell interactions. Lastly, we will examine putative mechanisms in which LOX facilitates breast cancer invasion and metastasis. Taken together, the literature demonstrates the increasingly important role(s) that LOX may play in regulating tumor progression and the necessity to elucidate its myriad mechanisms of action in order to identify potentially novel therapeutics. J. Cell. Biochem. 101: 1338,1354, 2007. © 2007 Wiley-Liss, Inc. [source]


Cleavage of p130Cas in anoikis

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2004
Lin Wei
Abstract p130Cas is a multifunctional signaling adaptor protein. It integrates and relays signals generated from a variety of extracellular stimuli and regulates a number of cellular activities including cell death. In this study, we analyzed the regulation and function of p130Cas in anoikis, a type of apoptosis caused by disruption of cell-matrix interactions. We found that p130Cas was specifically cleaved during anoikis in anoikis-sensitive epithelial cells, but not in anoikis-resistant tumor cells. There is a close correlation between p130Cas cleavage and anoikis. Furthermore, we found that the cleavage of p130Cas, as well as another focal adhesion component FAK, is different from that of caspase substrate PARP and spectrin. Although caspases and calpain were found to be involved in the cleavage of p130Cas, there appear to be other unidentified proteases that are mainly responsible for the cleavage of p130Cas, particularly at the early stage of anoikis. Overexpression of the p130Cas cleavage product induced apoptosis. Taken together, these data suggest that there are novel proteases involved in the cleavage of p130Cas during anoikis, which may be functionally involved in the onset of anoikis. p130Cas may have a dual role in the regulation of anoikis. On one hand, it mediates a survival signal from cell-matrix interactions when cells are attached to the extracellular matrix. On the other hand, it participates in executing cell death when cell-matrix interactions are disrupted. These observations provide new insights into the understanding of the function of p130Cas and the molecular mechanism of anoikis. © 2003 Wiley-Liss, Inc. [source]