WorldWideScience

Sample records for noradrenergic cell group

  1. Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons

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    Vitor Fortuna

    2015-06-01

    Full Text Available The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs develop in close proximity to the dorsal aorta (DA and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA differentiation of SN precursors temporally coincides with vascular mural cell (VMC recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation.

  2. Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons.

    Science.gov (United States)

    Fortuna, Vitor; Pardanaud, Luc; Brunet, Isabelle; Ola, Roxana; Ristori, Emma; Santoro, Massimo M; Nicoli, Stefania; Eichmann, Anne

    2015-06-23

    The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs) develop in close proximity to the dorsal aorta (DA) and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA) differentiation of SN precursors temporally coincides with vascular mural cell (VMC) recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR) signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Noradrenergic deficits in Parkinson's disease

    DEFF Research Database (Denmark)

    Nahimi, A.; Sommerauer, M.; Ostergaard, K.

    2017-01-01

    Objectives: In vitro studies suggest that noradrenergic projections from locus coeruleus to subcortical and cortical brain structures, e.g., thalamus, undergo severe neurodegeneration in Parkinson’s disease (PD). Loss of noradrenergic projections may alter oscillatory activity that in turn may...... be associated with cognitive decline. To test this hypothesis of the origin of cognitive decline in this disease, we used positron emission tomography (PET) to quantify the density of noradrenergic projections in groups of PD patients and healthy controls (HC), in combination with neuropsychological assessment...... with cognitive performance, independent of premorbid cognitive function or disease. PD patients had significant slowing of qEEG, e.g., the background alpha rhythm, but only EEG reactivity upon eye opening correlated with thalamic 11C-MeNER BPND in PD patients. Conclusion: This is the first direct quantification...

  4. The central noradrenergic system: an overview | Viljoen | African ...

    African Journals Online (AJOL)

    The central noradrenergic system belongs to a group of brainstem neuromodulatory systems previously referred to as the ascending reticular activating system. In this article a heuristic model is presented of the central noradrenergic system depicting the major projections to other cerebral areas, its interactions with other ...

  5. Noradrenergic dysfunction in Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Mary eGannon

    2015-06-01

    Full Text Available The brain noradrenergic system supplies the neurotransmitter norepinephrine throughout the brain via widespread efferent projections, and plays a pivotal role in modulating cognitive activities in the cortex. Profound noradrenergic degeneration in Alzheimer’s disease (AD patients has been observed for decades, with recent research suggesting that the locus coeruleus (where noradrenergic neurons are mainly located is a predominant site where AD-related pathology begins. Mounting evidence indicate that the loss of noradrenergic innervation greatly exacerbates AD pathogenesis and progression, although the precise roles of noradrenergic components in AD pathogenesis remain unclear. The aim of this review is to summarize current findings on noradrenergic dysfunction in AD, as well as to point out deficiencies in our knowledge where more research is needed.

  6. Co-expression of Cholinergic and Noradrenergic Phenotypes in Human and Non-Human Autonomic Nervous System

    OpenAIRE

    Weihe, Eberhard; Schütz, Burkhard; Hartschuh, Wolfgang; Anlauf, Martin; Schäfer, Martin K.; Eiden, Lee E.

    2005-01-01

    It has long been known that the sympathetic innervation of the sweat glands is cholinergic in most mammalian species, and that during development, rodent sympathetic cholinergic sweat gland innervation transiently expresses noradrenergic traits. We show here that some noradrenergic traits persist in cholinergic sympathetic innervation of the sweat glands in rodents, but that lack of expression of the vesicular monoamine transporter renders these cells functionally non-noradrenergic. Adult hum...

  7. The inhibition of the dorsal paragigantocellular reticular nucleus induces waking and the activation of all adrenergic and noradrenergic neurons: a combined pharmacological and functional neuroanatomical study.

    Science.gov (United States)

    Clément, Olivier; Valencia Garcia, Sara; Libourel, Paul-Antoine; Arthaud, Sébastien; Fort, Patrice; Luppi, Pierre-Hervé

    2014-01-01

    GABAergic neurons specifically active during paradoxical sleep (PS) localized in the dorsal paragigantocellular reticular nucleus (DPGi) are known to be responsible for the cessation of activity of the noradrenergic neurons of the locus coeruleus during PS. In the present study, we therefore sought to determine the role of the DPGi in PS onset and maintenance and in the inhibition of the LC noradrenergic neurons during this state. The effect of the inactivation of DPGi neurons on the sleep-waking cycle was examined in rats by microinjection of muscimol, a GABAA agonist, or clonidine, an alpha-2 adrenergic receptor agonist. Combining immunostaining of the different populations of wake-inducing neurons with that of c-FOS, we then determined whether muscimol inhibition of the DPGi specifically induces the activation of the noradrenergic neurons of the LC. Slow wave sleep and PS were abolished during 3 and 5 h after muscimol injection in the DPGi, respectively. The application of clonidine in the DPGi specifically induced a significant decrease in PS quantities and delayed PS appearance compared to NaCl. We further surprisingly found out that more than 75% of the noradrenergic and adrenergic neurons of all adrenergic and noradrenergic cell groups are activated after muscimol treatment in contrast to the other wake active systems significantly less activated. These results suggest that, in addition to its already know inhibition of LC noradrenergic neurons during PS, the DPGi might inhibit the activity of noradrenergic and adrenergic neurons from all groups during PS, but also to a minor extent during SWS and waking.

  8. The inhibition of the dorsal paragigantocellular reticular nucleus induces waking and the activation of all adrenergic and noradrenergic neurons: a combined pharmacological and functional neuroanatomical study.

    Directory of Open Access Journals (Sweden)

    Olivier Clément

    Full Text Available GABAergic neurons specifically active during paradoxical sleep (PS localized in the dorsal paragigantocellular reticular nucleus (DPGi are known to be responsible for the cessation of activity of the noradrenergic neurons of the locus coeruleus during PS. In the present study, we therefore sought to determine the role of the DPGi in PS onset and maintenance and in the inhibition of the LC noradrenergic neurons during this state. The effect of the inactivation of DPGi neurons on the sleep-waking cycle was examined in rats by microinjection of muscimol, a GABAA agonist, or clonidine, an alpha-2 adrenergic receptor agonist. Combining immunostaining of the different populations of wake-inducing neurons with that of c-FOS, we then determined whether muscimol inhibition of the DPGi specifically induces the activation of the noradrenergic neurons of the LC. Slow wave sleep and PS were abolished during 3 and 5 h after muscimol injection in the DPGi, respectively. The application of clonidine in the DPGi specifically induced a significant decrease in PS quantities and delayed PS appearance compared to NaCl. We further surprisingly found out that more than 75% of the noradrenergic and adrenergic neurons of all adrenergic and noradrenergic cell groups are activated after muscimol treatment in contrast to the other wake active systems significantly less activated. These results suggest that, in addition to its already know inhibition of LC noradrenergic neurons during PS, the DPGi might inhibit the activity of noradrenergic and adrenergic neurons from all groups during PS, but also to a minor extent during SWS and waking.

  9. Drugs of abuse specifically sensitize noradrenergic and serotonergic neurons via a non-dopaminergic mechanism.

    Science.gov (United States)

    Lanteri, Christophe; Salomon, Lucas; Torrens, Yvette; Glowinski, Jacques; Tassin, Jean-Pol

    2008-06-01

    A challenge in drug dependence is to delineate long-term neurochemical modifications induced by drugs of abuse. Repeated d-amphetamine was recently shown to disrupt a mutual regulatory link between noradrenergic and serotonergic neurons, thus inducing long-term increased responses to d-amphetamine and para-chloroamphetamine, respectively. We show here that such a sensitization of noradrenergic and serotonergic neurons also occurs following repeated treatment with cocaine, morphine, or alcohol, three compounds belonging to main groups of addictive substances. In all cases, this sensitization is prevented by alpha 1b-adrenergic and 5-HT2A receptors blockade, indicating the critical role of these receptors on long-term effects of drugs of abuse. However, repeated treatments with two non-addictive antidepressants, venlafaxine, and clorimipramine, which nevertheless inhibit noradrenergic and serotonergic reuptake, do not induce noradrenergic and serotonergic neurons sensitization. Similarly, this sensitization does not occur following repeated treatments with a specific inhibitor of dopamine (DA) reuptake, GBR12783. Moreover, we show that the effects of SCH23390, a D1 receptor antagonist known to inhibit development of d-amphetamine behavioral sensitization, are due to its 5-HT2C receptor agonist property. SCH23390 blocks amphetamine-induced release of norepinephrine and RS102221, a 5-HT2C antagonist, can reverse this inhibition as well as inhibition of noradrenergic sensitization and development of behavioral sensitization induced by repeated d-amphetamine. We propose that noradrenergic/serotonergic uncoupling is a common neurochemical consequence of repeated consumption of drugs of abuse, unrelated with DA release. Our data also suggest that compounds able to restore the link between noradrenergic and serotonergic modulatory systems could represent important therapeutic targets for investigation.

  10. Modulation of limbic noradrenergic circuits by cannabinoids

    OpenAIRE

    Carvalho, Ana Raquel Franky Gomes

    2010-01-01

    Tese de doutoramento Medicina The endocannabinoid system has been implicated in the regulation of several physiological functions. The widespread distribution of the endocannabinoid system in the central nervous system (CNS) accounts for many effects attributed to cannabinoids. Importantly, cannabinoids have been shown to modulate mood, cognition and memory. There is growing evidence suggesting that cannabinoids can interact with the noradrenergic system. Noradrenergic trans...

  11. Chlorotoxin-mediated disinhibition of noradrenergic locus coeruleus neurons using a conditional transgenic approach.

    Science.gov (United States)

    Salbaum, J Michael; Cirelli, Chiara; Walcott, Elisabeth; Krushel, Les A; Edelman, Gerald M; Tononi, Giulio

    2004-07-30

    The noradrenergic locus coeruleus (LC) has been implicated in the promotion of arousal, in focused attention and learning, and in the regulation of the sleep/waking cycle. The complex biological functions of the central noradrenergic system have been investigated largely through electrophysiological recordings and neurotoxic lesions of LC neurons. Activation of LC neurons through electrical or chemical stimulation has also led to important insights, although these techniques have limited cellular specificity and short-term effects. Here, we describe a novel method aimed at stimulating the central noradrenergic system in a highly selective manner for prolonged periods of time. This was achieved through the conditional expression of a transgene for chlorotoxin (Cltx) in the LC of adult mice. Chlorotoxin is a component of scorpion venom that partially blocks small conductance chloride channels. In this manner, the influence of GABAergic and glycinergic inhibitory inputs on LC cells is greatly reduced, while their ability to respond to excitatory inputs is unaffected. We demonstrate that the unilateral induction of Cltx expression in the LC is associated with a concomitant ipsilateral increase in the expression of markers of noradrenergic activity in LC neurons. Moreover, LC disinhibition is associated with the ipsilateral induction of the immediate early gene NGFI-A in cortical and subcortical target areas. Unlike previous gain of function approaches, transgenic disinhibition of LC cells is highly selective and persists for at least several weeks. This method represents a powerful new tool to assess the long-term effects of LC activation and is potentially applicable to other neuronal systems.

  12. The central noradrenergic system

    African Journals Online (AJOL)

    2006-07-27

    Jul 27, 2006 ... recognition of a direct influence of the central noradrenergic system on peripheral ... influences on cerebral function and behavior it is impossible to imagine ... stimuli and to speed-up information processing.4. The influence of ...

  13. Noradrenergic Dysfunction in Alzheimer's and Parkinson's Diseases—An Overview of Imaging Studies

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    Andrew C. Peterson

    2018-05-01

    Full Text Available Noradrenergic dysfunction contributes to cognitive impairment in Alzheimer's Disease (AD and Parkinson's Disease (PD. Conventional therapeutic strategies seek to enhance cholinergic and dopaminergic neurotransmission in AD and PD, respectively, and few studies have examined noradrenergic dysfunction as a target for medication development. We review the literature of noradrenergic dysfunction in AD and PD with a focus on human imaging studies that implicate the locus coeruleus (LC circuit. The LC sends noradrenergic projections diffusely throughout the cerebral cortex and plays a critical role in attention, learning, working memory, and cognitive control. The LC undergoes considerable degeneration in both AD and PD. Advances in magnetic resonance imaging have facilitated greater understanding of how structural and functional alteration of the LC may contribute to cognitive decline in AD and PD. We discuss the potential roles of the noradrenergic system in the pathogenesis of AD and PD with an emphasis on postmortem anatomical studies, structural MRI studies, and functional MRI studies, where we highlight changes in LC connectivity with the default mode network (DMN. LC degeneration may accompany deficient capacity in suppressing DMN activity and increasing saliency and task control network activities to meet behavioral challenges. We finish by proposing potential and new directions of research to address noradrenergic dysfunction in AD and PD.

  14. 125I-[Tyr0,D-Trp8]somatostatin-14 binding sites in the locus coeruleus of the rat are located on both ascending and descending projecting noradrenergic cells

    International Nuclear Information System (INIS)

    Epelbaum, J.; Bluet-Pajot, M.T.; Llorens-Cortes, C.; Kordon, C.; Mounier, F.; Senut, M.C.; Videau, C.

    1990-01-01

    Radioautographic determinations of 125I-[Tyr0,D-Trp8]somatostatin-14 (125I-SRIF) binding sites were performed on frozen serial sections of the locus coeruleus (LC) of control rats and of rats subjected to either bilateral microinjections of 6 hydroxydopamine (6-OHDA) into the LC or unilateral microinjection into the ascending noradrenergic bundles. These experiments were performed in order to determine whether 125I-SRIF binding was localized to noradrenergic-containing cells and in which regions the cells which contain the binding sites are projecting. The extent of the lesions was assessed by measuring norepinephrine (NE) levels in the hippocampus (88% decrease as compared to sham-operated animals) for bilateral LC lesions and in the frontal cortex (87% reduction vs. contralateral side) for unilateral bundle lesions. In control rats, 125I-SRIF binding sites were restricted to the boundaries of the LC and followed closely the distribution of tyrosine hydroxylase-labeled cells. Three weeks after bilateral injections of 6-OHDA, 125I-SRIF binding decreased by 79% in all regions of the LC. In contrast, unilateral destruction of the ascending noradrenergic bundles resulted in a moderate decrease only in the middle part of the LC with a more important effect in the dorsal (55%) than in the ventral (24%) portion of the nucleus. These data demonstrate that: (1) most SRIF receptors in the LC are located in the vicinity of NE-containing cell bodies and (2) NE-containing cells bearing SRIF receptors project to the forebrain as well as to other terminal areas located more caudally in the brain. These data suggest a general role for SRIF in the control of the multiple functions of the LC

  15. The role of central noradrenergic dysregulation in anxiety disorders: evidence from clinical studies.

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    Kalk, N J; Nutt, D J; Lingford-Hughes, A R

    2011-01-01

    The nature of the noradrenergic dysregulation in clinical anxiety disorders remains unclear. In panic disorder, the predominant view has been that central noradrenergic neuronal networks and/or the sympathetic nervous system was normal in patients at rest, but hyper-reactive to specific stimuli, for example carbon dioxide. These ideas have been extended to other anxiety disorders, which share with panic disorder characteristic subjective anxiety and physiological symptoms of excess sympathetic activity. For example, Generalized Anxiety Disorder is characterized by chronic free-floating anxiety, muscle tension, palpitation and insomnia. It has been proposed that there is chronic central hypersecretion of noradrenaline in Generalized Anxiety Disorder, with consequent hyporesponsiveness of central post-synaptic receptors. With regards to other disorders, it has been suggested that there is noradrenergic involvement or derangement, but a more specific hypothesis has not been enunciated. This paper reviews the evidence for noradrenergic dysfunction in anxiety disorders, derived from indirect measures of noradrenergic function in clinical populations.

  16. Generation of Two Noradrenergic-Specific Dopamine-Beta-Hydroxylase-FLPo Knock-In Mice Using CRISPR/Cas9-Mediated Targeting in Embryonic Stem Cells.

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    Jenny J Sun

    Full Text Available CRISPR/Cas9 mediated DNA double strand cutting is emerging as a powerful approach to increase rates of homologous recombination of large targeting vectors, but the optimization of parameters, equipment and expertise required remain barriers to successful mouse generation by single-step zygote injection. Here, we sought to apply CRISPR/Cas9 methods to traditional embryonic stem (ES cell targeting followed by blastocyst injection to overcome the common issues of difficult vector construction and low targeting efficiency. To facilitate the study of noradrenergic function, which is implicated in myriad behavioral and physiological processes, we generated two different mouse lines that express FLPo recombinase under control of the noradrenergic-specific Dopamine-Beta-Hydroxylase (DBH gene. We found that by co-electroporating a circular vector expressing Cas9 and a locus-specific sgRNA, we could target FLPo to the DBH locus in ES cells with shortened 1 kb homology arms. Two different sites in the DBH gene were targeted; the translational start codon with 6-8% targeting efficiency, and the translational stop codon with 75% targeting efficiency. Using this approach, we established two mouse lines with DBH-specific expression of FLPo in brainstem catecholaminergic populations that are publically available on MMRRC (MMRRC_041575-UCD and MMRRC_041577-UCD. Altogether, this study supports simplified, high-efficiency Cas9/CRISPR-mediated targeting in embryonic stem cells for production of knock-in mouse lines in a wider variety of contexts than zygote injection alone.

  17. NORADRENERGIC AND ADRENERGIC FUNCTIONING IN AUTISM

    NARCIS (Netherlands)

    MINDERAA, RB; ANDERSON, GM; VOLKMAR, FR; AKKERHUIS, GW; COHEN, DJ

    1994-01-01

    A neurochemical assessment of noradrenergic and adrenergic functioning was carried out with autistic patients and normal control individuals. Norepinephrine and related compounds were measured in autistic (n = 17 unmedicated, 23 medicated; age range 9-29 years old) and normal controls (n = 27; age

  18. Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system

    DEFF Research Database (Denmark)

    Ádori, Csaba; Glück, Laura; Barde, Swapnali

    2015-01-01

    Alzheimer’s disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is n......Alzheimer’s disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites...... morphometry and mRNA profiling in a cohort of Alzheimer’s and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer’s disease, we found significantly....../IV and onwards, i.e., a process preceding advanced Alzheimer’s pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine β-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We modeled these pathogenic changes in Sstr2 −/− mice and...

  19. Contribution of the dorsal noradrenergic bundle to the effect of amphetamine on acetylcholine turnover

    International Nuclear Information System (INIS)

    Robinson, S.E.

    1986-01-01

    In order to determine the contribution of the noradrenergic projections of the locus coeruleus to the action of amphetamine on cholinergic neurons in several areas of the brain, the dorsal noradrenergic bundle was selectively lesioned by injection of the neurotoxin 6-hydroxydopamine. The bundles of Equithesin-anesthetized male rats were lesioned bilaterally by stereotaxically-placed injections of 6-OHDA. The animals were killed in the microwave and constant rate infusion with phosphoryl ( 2 H 9 )-choline was begun. Levels of ACh and choline and TR /SUB ACh/ were determined by a mass fragmentographic technique. Rats not exhibiting the proper decrease in NE were excluded from all data calculations. It is shown that noradrenergic neurons travelling in the dorsal noradrenergic bundle do not exert a tonic action on cholinergic neurons in the cortex, hippocampus or hypothalamus

  20. Noradrenergic Modulation of Cognition in Health and Disease

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    Olga Borodovitsyna

    2017-01-01

    Full Text Available Norepinephrine released by the locus coeruleus modulates cellular processes and synaptic transmission in the central nervous system through its actions at a number of pre- and postsynaptic receptors. This transmitter system facilitates sensory signal detection and promotes waking and arousal, processes which are necessary for navigating a complex and dynamic sensory environment. In addition to its effects on sensory processing and waking behavior, norepinephrine is now recognized as a contributor to various aspects of cognition, including attention, behavioral flexibility, working memory, and long-term mnemonic processes. Two areas of dense noradrenergic innervation, the prefrontal cortex and the hippocampus, are particularly important with regard to these functions. Due to its role in mediating normal cognitive function, it is reasonable to expect that noradrenergic transmission becomes dysfunctional in a number of neuropsychiatric and neurodegenerative diseases characterized by cognitive deficits. In this review, we summarize the unique role that norepinephrine plays in prefrontal cortical and hippocampal function and how its interaction with its various receptors contributes to cognitive behaviors. We further assess the changes that occur in the noradrenergic system in Alzheimer’s disease, Parkinson’s disease, attention-deficit/hyperactivity disorder, and schizophrenia and how these changes contribute to cognitive decline in these pathologies.

  1. Glucocorticoid enhancement of dorsolateral striatum-dependent habit memory requires concurrent noradrenergic activity.

    Science.gov (United States)

    Goodman, J; Leong, K-C; Packard, M G

    2015-12-17

    Previous findings indicate that post-training administration of glucocorticoid stress hormones can interact with the noradrenergic system to enhance consolidation of hippocampus- or amygdala-dependent cognitive/emotional memory. The present experiments were designed to extend these findings by examining the potential interaction of glucocorticoid and noradrenergic mechanisms in enhancement of dorsolateral striatum (DLS)-dependent habit memory. In experiment 1, different groups of adult male Long-Evans rats received training in two DLS-dependent memory tasks. In a cued water maze task, rats were released from various start points and were reinforced to approach a visibly cued escape platform. In a response-learning version of the water plus-maze task, animals were released from opposite starting positions and were reinforced to make a consistent egocentric body-turn to reach a hidden escape platform. Immediately post-training, rats received peripheral injections of the glucocorticoid corticosterone (1 or 3 mg/kg) or vehicle solution. In both tasks, corticosterone (3 mg/kg) enhanced DLS-dependent habit memory. In experiment 2, a separate group of animals received training in the response learning version of the water plus-maze task and were given peripheral post-training injections of corticosterone (3 mg/kg), the β-adrenoreceptor antagonist propranolol (3 mg/kg), corticosterone and propranolol concurrently, or control vehicle solution. Corticosterone injections again enhanced DLS-dependent memory, and this effect was blocked by concurrent administration of propranolol. Propranolol administration by itself (3 mg/kg) did not influence DLS-dependent memory. Taken together, the findings indicate an interaction between glucocorticoid and noradrenergic mechanisms in DLS-dependent habit memory. Propranolol administration may be useful in treating stress-related human psychopathologies associated with a dysfunctional DLS-dependent habit memory system. Copyright © 2015

  2. Noradrenergic enhancement of amygdala responses to fear

    NARCIS (Netherlands)

    Onur, Oezguer A; Walter, Henrik; Schlaepfer, Thomas E; Rehme, Anne K; Schmidt, Christoph; Keysers, Christian; Maier, Wolfgang; Hurlemann, René

    Multiple lines of evidence implicate the basolateral amygdala (BLA) and the noradrenergic (norepinephrine, NE) system in responding to stressful stimuli such as fear signals, suggesting hyperfunction of both in the development of stress-related pathologies including anxiety disorders. However, no

  3. Central serotonergic and noradrenergic receptors in functional dyspepsia

    Institute of Scientific and Technical Information of China (English)

    S O'Mahony; TG Dinan; PW Keeling; ASB Chua

    2006-01-01

    Functional dyspepsia is a symptom complex characterised by upper abdominal discomfort or pain, early satiety,motor abnormalities, abdominal bloating and nausea in the absence of organic disease. The central nervous system plays an important role in the conducting and processing of visceral signals. Alterations in brain processing of pain, perception and affective responses may be key factors in the pathogenesis of functional dyspepsia. Central serotonergic and noradrenergic receptor systems are involved in the processing of motor,sensory and secretory activities of the gastrointestinal tract. Visceral hypersensitivity is currently regarded as the mechanism responsible for both motor alterations and abdominal pain in functional dyspepsia. Some studies suggest that there are alterations in central serotonergic and noradrenergic systems which may partially explain some of the symptoms of functional dyspepsia. Alterations in the autonomic nervous system may be implicated in the motor abnormalities and increases in visceral sensitivity in these patients.Noradrenaline is the main neurotransmitter in the sympathetic nervous system and again alterations in the functioning of this system may lead to changes in motor function. Functional dyspepsia causes considerable burden on the patient and society. The pathophysiology of functional dyspepsia is not fully understood but alterations in central processing by the serotonergic and noradrenergic systems may provide plausible explanations for at least some of the symptoms and offer possible treatment targets for the future.

  4. Noradrenergic modulation of neural erotic stimulus perception.

    Science.gov (United States)

    Graf, Heiko; Wiegers, Maike; Metzger, Coraline Danielle; Walter, Martin; Grön, Georg; Abler, Birgit

    2017-09-01

    We recently investigated neuromodulatory effects of the noradrenergic agent reboxetine and the dopamine receptor affine amisulpride in healthy subjects on dynamic erotic stimulus processing. Whereas amisulpride left sexual functions and neural activations unimpaired, we observed detrimental activations under reboxetine within the caudate nucleus corresponding to motivational components of sexual behavior. However, broadly impaired subjective sexual functioning under reboxetine suggested effects on further neural components. We now investigated the same sample under these two agents with static erotic picture stimulation as alternative stimulus presentation mode to potentially observe further neural treatment effects of reboxetine. 19 healthy males were investigated under reboxetine, amisulpride and placebo for 7 days each within a double-blind cross-over design. During fMRI static erotic picture were presented with preceding anticipation periods. Subjective sexual functions were assessed by a self-reported questionnaire. Neural activations were attenuated within the caudate nucleus, putamen, ventral striatum, the pregenual and anterior midcingulate cortex and in the orbitofrontal cortex under reboxetine. Subjective diminished sexual arousal under reboxetine was correlated with attenuated neural reactivity within the posterior insula. Again, amisulpride left neural activations along with subjective sexual functioning unimpaired. Neither reboxetine nor amisulpride altered differential neural activations during anticipation of erotic stimuli. Our results verified detrimental effects of noradrenergic agents on neural motivational but also emotional and autonomic components of sexual behavior. Considering the overlap of neural network alterations with those evoked by serotonergic agents, our results suggest similar neuromodulatory effects of serotonergic and noradrenergic agents on common neural pathways relevant for sexual behavior. Copyright © 2017 Elsevier B.V. and

  5. Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone.

    Science.gov (United States)

    Patel, Ryan; Qu, Chaoling; Xie, Jennifer Y; Porreca, Frank; Dickenson, Anthony H

    2018-05-31

    Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of α2-adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. In contrast, clonidine, an α2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared to sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief.

  6. A1 noradrenergic neurons lesions reduce natriuresis and hypertensive responses to hypernatremia in rats.

    Directory of Open Access Journals (Sweden)

    Elaine Fernanda da Silva

    Full Text Available Noradrenergic neurons in the caudal ventrolateral medulla (CVLM; A1 group contribute to cardiovascular regulation. The present study assessed whether specific lesions in the A1 group altered the cardiovascular responses that were evoked by hypertonic saline (HS infusion in non-anesthetized rats. Male Wistar rats (280-340 g received nanoinjections of antidopamine-β-hydroxylase-saporin (A1 lesion, 0.105 ng.nL(-1 or free saporin (sham, 0.021 ng.nL(-1 into their CVLMs. Two weeks later, the rats were anesthetized (2% halothane in O2 and their femoral artery and vein were catheterized and led to exit subcutaneously between the scapulae. On the following day, the animals were submitted to HS infusion (3 M NaCl, 1.8 ml • kg(-1, b.wt., for longer than 1 min. In the sham-group (n = 8, HS induced a sustained pressor response (ΔMAP: 35±3.6 and 11±1.8 mmHg, for 10 and 90 min after HS infusion, respectively; P<0.05 vs. baseline. Ten min after HS infusion, the pressor responses of the anti-DβH-saporin-treated rats (n = 11were significantly smaller(ΔMAP: 18±1.4 mmHg; P<0.05 vs. baseline and vs. sham group, and at 90 min, their blood pressures reached baseline values (2±1.6 mmHg. Compared to the sham group, the natriuresis that was induced by HS was reduced in the lesioned group 60 min after the challenge (196±5.5 mM vs. 262±7.6 mM, respectively; P<0.05. In addition, A1-lesioned rats excreted only 47% of their sodium 90 min after HS infusion, while sham animals excreted 80% of their sodium. Immunohistochemical analysis confirmed a substantial destruction of the A1 cell group in the CVLM of rats that had been nanoinjected withanti-DβH-saporin. These results suggest that medullary noradrenergic A1 neurons are involved in the excitatory neural pathway that regulates hypertensive and natriuretic responses to acute changes in the composition of body fluid.

  7. Complementary neural correlates of motivation in dopaminergic and noradrenergic neurons of monkeys.

    Directory of Open Access Journals (Sweden)

    Sebastien eBouret

    2012-07-01

    Full Text Available Rewards have many influences on learning, decision-making and performance. All seem to rely on complementary actions of two closely related catecholaminergic neuromodulators, dopamine and noradrenaline. We compared single unit activity of dopaminergic neurons of the substantia nigra pars compacta and noradrenergic neurons of the locus coeruleus in monkeys performing a reward schedule task. Their motivation, indexed using operant performance, increased as they progressed through schedules ending in reward delivery. The responses of dopaminergic and noradrenergic neurons around the time of major task events, visual cues predicting trial outcome and operant action to complete a trial, were similar, in that they occurred at the same time. They were also similar in that they both responded most strongly to the first cues in schedules, which are the most informative cues. The neuronal responses around the time of the monkeys’ actions were different, in that the response intensity profiles changed in opposite directions. Dopaminergic responses were stronger around predictably rewarded correct actions whereas noradrenergic responses were greater around predictably unrewarded correct actions. The complementary response profiles related to the monkeys operant actions suggest that dopamine neurons might relate to the value of the current action whereas the noradrenergic neurons relate to the psychological cost of that action.

  8. Noradrenergic activation of the basolateral amygdala modulates the consolidation of object-in-context recognition memory

    NARCIS (Netherlands)

    Barsegyan, Areg; McGaugh, James L.; Roozendaal, Benno

    2014-01-01

    Noradrenergic activation of the basolateral complex of the amygdala (BLA) is well known to enhance the consolidation of long-term memory of highly emotionally arousing training experiences. The present study investigated whether such noradrenergic activation of the BLA also influences the

  9. Evidence for a role of corticopetal, noradrenergic systems in the development of executive function.

    Science.gov (United States)

    Mokler, David J; Miller, Christine E; McGaughy, Jill A

    2017-09-01

    Adolescence is a period during which many aspects of executive function are maturing. Much of the literature has focused on discrepancies between sub-cortical and cortical development that is hypothesized to lead to over-processing of reinforcement related stimuli unchecked by fully matured response inhibition. Specifically, maturation of sub-cortical dopaminergic systems that terminate in the nucleus accumbens has been suggested to occur prior to the full maturation of corticopetal dopaminergic systems. However, converging evidence supports the hypothesis that many aspects of cognitive control are critically linked to cortical noradrenergic systems, that the effectiveness of drugs used to treat disorders of executive function, e.g. ADHD, may result primarily from increases in cortical norepinephrine (NE) and that cortical noradrenergic systems mature across adolescence. However, little attention has been given to the development of this system during adolescence or to its influence in executive function. In the present paper, we discuss the developmental trajectory of the noradrenergic system of the forebrain, highlight the interactions between noradrenergic and dopaminergic systems, and highlight the contribution of the immature corticopetal noradrenergic systems in the ontogeny of several aspects of executive function. Finally we compare data from adolescent rats to those gathered after selective depletion of NE in sub-regions of the prefrontal cortex with an emphasis on the similarities in performance of NE lesioned rats and adolescents. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Statins Promote Long-Term Recovery after Ischemic Stroke by Reconnecting Noradrenergic Neuronal Circuitry

    Directory of Open Access Journals (Sweden)

    Kyoung Joo Cho

    2015-01-01

    Full Text Available Inhibitors of HMG-CoA reductase (statins, widely used to lower cholesterol in coronary heart and vascular disease, are effective drugs in reducing the risk of stroke and improving its outcome in the long term. After ischemic stroke, cardiac autonomic dysfunction and psychological problems are common complications related to deficits in the noradrenergic (NA system. This study investigated the effects of statins on the recovery of NA neuron circuitry and its function after transient focal cerebral ischemia (tFCI. Using the wheat germ agglutinin (WGA transgene technique combined with the recombinant adenoviral vector system, NA-specific neuronal pathways were labeled, and were identified in the locus coeruleus (LC, where NA neurons originate. NA circuitry in the atorvastatin-treated group recovered faster than in the vehicle-treated group. The damaged NA circuitry was partly reorganized with the gradual recovery of autonomic dysfunction and neurobehavioral deficit. Newly proliferated cells might contribute to reorganizing NA neurons and lead anatomic and functional recovery of NA neurons. Statins may be implicated to play facilitating roles in the recovery of the NA neuron and its function.

  11. Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation of Genioglossus in Chronic Intermittent Hypoxic Rats

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2017-05-01

    Full Text Available Neuromuscular compensation of the genioglossus muscle can be induced by chronic intermittent hypoxia (CIH in obstructive sleep apnea to maintain upper airway stability. Noradrenergic activation of hypoglossal nucleus plays a critical role in the central control of the genioglossus. However, it remains unknown whether norepinephrine takes part in the central regulation of the genioglossus during CIH. Adult male Wistar rats (n = 32 were studied to explore the influence of noradrenergic activation of hypoglossal nucleus on the central control of the genioglossus at different stages of CIH. The rats were divided into four groups: normal control or normoxic (NO group, CIH group, CIH + normal saline (NS group, and CIH + prazosin (PZ, α1-adrenergic antagonist group. PZ (0.2 mM, 60 nl and NS (0.9%, 60 nl were microinjected into the hypoglossal nucleus. The responses of the genioglossus corticomotor area to transcranial magnetic stimulation (TMS were recorded on the 1st, 7th, 14th, and 21st day of CIH. The CIH group showed significantly shorter TMS latencies on days 1, 7, and 14 (3.85 ± 0.37 vs. 4.58 ± 0.42, 3.93 ± 0.17 vs. 4.49 ± 0.55, 3.79 ± 0.38 vs. 4.39 ± 0.30 ms, P < 0.05, and higher TMS amplitudes on day 1 (2.74 ± 0.87 vs. 1.60 ± 0.52 mV, P < 0.05 of CIH than the NO group. Compared to the CIH + NS group, the CIH + PZ group showed decreased TMS responses (longer latencies and lower amplitudes only on the 14th day of CIH (3.99 ± 0.28 vs. 4.61 ± 0.48 ms, 2.51 ± 0.67 vs. 1.18 ± 0.62 mV, P < 0.05. These results indicated that noradrenergic activation of the hypoglossal nucleus played a role in the central compensation of genioglossus through α1-adrenoceptor on the 14th day of CIH.

  12. Noradrenergic enhancement of associative fear memory in humans

    NARCIS (Netherlands)

    Soeter, M.; Kindt, M.

    2011-01-01

    Ample evidence in animals and humans supports the noradrenergic modulation in the formation of emotional memory. However, in humans the effects of stress on emotional memory are traditionally investigated by declarative memory tests (e.g., recall, recognition) for non-associative emotional stimuli

  13. Noradrenergic Stimulation Impairs Memory Generalization in Women.

    Science.gov (United States)

    Kluen, Lisa Marieke; Agorastos, Agorastos; Wiedemann, Klaus; Schwabe, Lars

    2017-07-01

    Memory generalization is essential for adaptive decision-making and action. Our ability to generalize across past experiences relies on medial-temporal lobe structures, known to be highly sensitive to stress. Recent evidence suggests that stressful events may indeed interfere with memory generalization. Yet, the mechanisms involved in this generalization impairment are unknown. We tested here whether a pharmacological elevation of major stress mediators-noradrenaline and glucocorticoids-is sufficient to disrupt memory generalization. In a double-blind, placebo-controlled design, healthy men and women received orally a placebo, hydrocortisone, the α2-adrenoceptor antagonist yohimbine that leads to increased noradrenergic stimulation, or both drugs, before they completed an associative learning task probing memory generalization. Drugs left learning performance intact. Yohimbine, however, led to a striking generalization impairment in women, but not in men. Hydrocortisone, in turn, had no effect on memory generalization, neither in men nor in women. The present findings indicate that increased noradrenergic activity, but not cortisol, is sufficient to disrupt memory generalization in a sex-specific manner, with relevant implications for stress-related mental disorders characterized by generalization deficits.

  14. The noradrenergic paradox: implications in the management of depression and anxiety

    Directory of Open Access Journals (Sweden)

    Montoya A

    2016-03-01

    Full Text Available Alonso Montoya,1 Robert Bruins,1 Martin A Katzman,2 Pierre Blier3 1Eli Lilly Canada Inc, 2START Clinic for the Mood and Anxiety Disorders, Toronto, 3Mood Disorders Research Unit, Institute of Mental Health Research, University of Ottawa, Ottawa, ON, Canada Abstract: Both major depressive disorder and the anxiety disorders are major causes of ­disability and markedly contribute to a significant global burden of the disease worldwide. In part because of the significant socioeconomic burden associated with these disorders, theories have been developed to specifically build clinical treatment approaches. One such theory, the monoaminergic hypothesis, has led to the development of several generations of selective and nonselective inhibitors of transporters of serotonin and norepinephrine, with the goal of augmenting monoaminergic transmission. These efforts have led to considerable success in the development of antidepressant therapeutics. However, there is a strong correlation between enhanced noradrenergic activity and fear and anxiety. Consequently, some physicians have expressed concerns that the same enhanced noradrenergic activity that alleviates depression could also promote anxiety. The fact that the serotonergic and noradrenergic reuptake inhibitors are successfully used in the treatment of anxiety and panic disorders seems paradoxical. This review was undertaken to determine if any clinical evidence exists to show that serotonergic and noradrenergic reuptake inhibitors can cause anxiety. The PubMed, EMBASE, and Cochrane Library databases were searched, and the results limited to randomized, double-blind, placebo-controlled studies performed in nongeriatric adults and with clear outcome measures were reported. Based on these criteria, a total of 52 studies were examined. Patients in these studies suffered from depression or anxiety disorders (generalized and social anxiety disorders, panic disorder, and posttraumatic stress disorder. The

  15. Dibutyryl cyclic AMP induces differentiation of human neuroblastoma SH-SY5Y cells into a noradrenergic phenotype.

    Science.gov (United States)

    Kume, Toshiaki; Kawato, Yuka; Osakada, Fumitaka; Izumi, Yasuhiko; Katsuki, Hiroshi; Nakagawa, Takayuki; Kaneko, Shuji; Niidome, Tetsuhiro; Takada-Takatori, Yuki; Akaike, Akinori

    2008-10-10

    Dibutyryl cyclic AMP (dbcAMP) and retinoic acid (RA) have been demonstrated to be the inducers of morphological differentiation in SH-SY5Y cells, a human catecholaminergic neuroblastoma cell line. However, it remains unclear whether morphologically differentiated SH-SY5Y cells by these compounds acquire catecholaminergic properties. We focused on the alteration of tyrosine hydroxylase (TH) expression and intracellular content of noradrenaline (NA) as the indicators of functional differentiation. Three days treatment with dbcAMP (1mM) and RA (10microM) induced morphological changes and an increase of TH-positive cells using immunocytochemical analysis in SH-SY5Y cells. The percentage of TH-expressing cells in dbcAMP (1mM) treatment was larger than that in RA (10microM) treatment. In addition, dbcAMP increased intracellular NA content, whereas RA did not. The dbcAMP-induced increase in TH-expressing cells is partially inhibited by KT5720, a protein kinase A (PKA) inhibitor. We also investigated the effect of butyrate on SH-SY5Y cells, because dbcAMP is enzymatically degraded by intracellular esterase, thereby resulting in the formation of butyrate. Butyrate induced the increase of NA content at lower concentrations than dbcAMP, although the increase in TH-expressing cells by butyrate was smaller than that by dbcAMP. The dbcAMP (1mM)- and butyrate (0.3mM)-induced increase in NA content was completely suppressed by alpha-methyl-p-tyrosine (1mM), an inhibitor of TH. These results suggest that dbcAMP induces differentiation into the noradrenergic phenotype through both PKA activation and butyrate.

  16. Noradrenergic lesioning with an anti-dopamine beta-hydroxylase immunotoxin

    Science.gov (United States)

    Picklo, M. J.; Wiley, R. G.; Lappi, D. A.; Robertson, D.

    1994-01-01

    Sympathectomy has been achieved by a variety of methods but each has its limitations. These include lack of tissue specificity, incomplete lesioning, and the age range of susceptibility to the lesioning. To circumvent these drawbacks, an immunotoxin was constructed using a monoclonal antibody against the noradrenergic specific enzyme dopamine beta-hydroxylase (D beta H) coupled via a disulfide bond to saporin, a ribosomal inactivating protein. Three days after intravenous injection of the anti-D beta H immunotoxin (50 micrograms) into adult Sprague-Dawley rats, 66% of neurons in the superior cervical ganglia were chromatolytic. Superior cervical ganglia neurons were poisoned in 1 day old and 1 week old (86% of neurons) neonatal rats following subcutaneous injection of 3.75 and 15 micrograms, respectively. The anti-D beta H immunotoxin will be a useful tool in the study of the peripheral noradrenergic system in adult and neonatal animals.

  17. Stimulation of the noradrenergic system during memory formation impairs extinction learning but not the disruption of reconsolidation

    NARCIS (Netherlands)

    Soeter, M.; Kindt, M.

    2012-01-01

    The noradrenergic system plays a critical role in the ‘consolidation’ of emotional memory. If we are to target ‘reconsolidation’ in patients with anxiety disorders, the noradrenergic strengthening of fear memory should not impair the disruption of reconsolidation. In Experiment I, we addressed this

  18. Functional neuroanatomy of the central noradrenergic system.

    Science.gov (United States)

    Szabadi, Elemer

    2013-08-01

    The central noradrenergic neurone, like the peripheral sympathetic neurone, is characterized by a diffusely arborizing terminal axonal network. The central neurones aggregate in distinct brainstem nuclei, of which the locus coeruleus (LC) is the most prominent. LC neurones project widely to most areas of the neuraxis, where they mediate dual effects: neuronal excitation by α₁-adrenoceptors and inhibition by α₂-adrenoceptors. The LC plays an important role in physiological regulatory networks. In the sleep/arousal network the LC promotes wakefulness, via excitatory projections to the cerebral cortex and other wakefulness-promoting nuclei, and inhibitory projections to sleep-promoting nuclei. The LC, together with other pontine noradrenergic nuclei, modulates autonomic functions by excitatory projections to preganglionic sympathetic, and inhibitory projections to preganglionic parasympathetic neurones. The LC also modulates the acute effects of light on physiological functions ('photomodulation'): stimulation of arousal and sympathetic activity by light via the LC opposes the inhibitory effects of light mediated by the ventrolateral preoptic nucleus on arousal and by the paraventricular nucleus on sympathetic activity. Photostimulation of arousal by light via the LC may enable diurnal animals to function during daytime. LC neurones degenerate early and progressively in Parkinson's disease and Alzheimer's disease, leading to cognitive impairment, depression and sleep disturbance.

  19. Noradrenergic activation of the basolateral amygdala modulates the consolidation of object-in-context recognition memory

    OpenAIRE

    Barsegyan, Areg; McGaugh, James L.; Roozendaal, Benno

    2014-01-01

    Noradrenergic activation of the basolateral complex of the amygdala (BLA) is well known to enhance the consolidation of long-term memory of highly emotionally arousing training experiences. The present study investigated whether such noradrenergic activation of the BLA also influences the consolidation of object-in-context recognition memory, a low-arousing training task assessing episodic-like memory. Male Sprague-Dawley rats were exposed to two identical objects in one context for either 3 ...

  20. Hindbrain medulla catecholamine cell group involvement in lactate-sensitive hypoglycemia-associated patterns of hypothalamic norepinephrine and epinephrine activity.

    Science.gov (United States)

    Shrestha, P K; Tamrakar, P; Ibrahim, B A; Briski, K P

    2014-10-10

    Cell-type compartmentation of glucose metabolism in the brain involves trafficking of the oxidizable glycolytic end product, l-lactate, by astrocytes to fuel neuronal mitochondrial aerobic respiration. Lactate availability within the hindbrain medulla is a monitored function that regulates systemic glucostasis as insulin-induced hypoglycemia (IIH) is exacerbated by lactate repletion of that brain region. A2 noradrenergic neurons are a plausible source of lactoprivic input to the neural gluco-regulatory circuit as caudal fourth ventricular (CV4) lactate infusion normalizes IIH-associated activation, e.g. phosphorylation of the high-sensitivity energy sensor, adenosine 5'-monophosphate-activated protein kinase (AMPK), in these cells. Here, we investigated the hypothesis that A2 neurons are unique among medullary catecholamine cells in directly screening lactate-derived energy. Adult male rats were injected with insulin or vehicle following initiation of continuous l-lactate infusion into the CV4. Two hours after injections, A1, C1, A2, and C2 neurons were collected by laser-microdissection for Western blot analysis of AMPKα1/2 and phosphoAMPKα1/2 proteins. Results show that AMPK is expressed in each cell group, but only a subset, e.g. A1, C1, and A2 neurons, exhibit increased sensor activity in response to IIH. Moreover, hindbrain lactate repletion reversed hypoglycemic augmentation of pAMPKα1/2 content in A2 and C1 but not A1 cells, and normalized hypothalamic norepinephrine and epinephrine content in a site-specific manner. The present evidence for discriminative reactivity of AMPK-expressing medullary catecholamine neurons to the screened energy substrate lactate implies that that lactoprivation is selectively signaled to the hypothalamus by A2 noradrenergic and C1 adrenergic cells. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Noradrenergic control of gene expression and long-term neuronal adaptation evoked by learned vocalizations in songbirds.

    Directory of Open Access Journals (Sweden)

    Tarciso A F Velho

    Full Text Available Norepinephrine (NE is thought to play important roles in the consolidation and retrieval of long-term memories, but its role in the processing and memorization of complex acoustic signals used for vocal communication has yet to be determined. We have used a combination of gene expression analysis, electrophysiological recordings and pharmacological manipulations in zebra finches to examine the role of noradrenergic transmission in the brain's response to birdsong, a learned vocal behavior that shares important features with human speech. We show that noradrenergic transmission is required for both the expression of activity-dependent genes and the long-term maintenance of stimulus-specific electrophysiological adaptation that are induced in central auditory neurons by stimulation with birdsong. Specifically, we show that the caudomedial nidopallium (NCM, an area directly involved in the auditory processing and memorization of birdsong, receives strong noradrenergic innervation. Song-responsive neurons in this area express α-adrenergic receptors and are in close proximity to noradrenergic terminals. We further show that local α-adrenergic antagonism interferes with song-induced gene expression, without affecting spontaneous or evoked electrophysiological activity, thus dissociating the molecular and electrophysiological responses to song. Moreover, α-adrenergic antagonism disrupts the maintenance but not the acquisition of the adapted physiological state. We suggest that the noradrenergic system regulates long-term changes in song-responsive neurons by modulating the gene expression response that is associated with the electrophysiological activation triggered by song. We also suggest that this mechanism may be an important contributor to long-term auditory memories of learned vocalizations.

  2. Neuropeptide S interacts with the basolateral amygdala noradrenergic system in facilitating object recognition memory consolidation.

    Science.gov (United States)

    Han, Ren-Wen; Xu, Hong-Jiao; Zhang, Rui-San; Wang, Pei; Chang, Min; Peng, Ya-Li; Deng, Ke-Yu; Wang, Rui

    2014-01-01

    The noradrenergic activity in the basolateral amygdala (BLA) was reported to be involved in the regulation of object recognition memory. As the BLA expresses high density of receptors for Neuropeptide S (NPS), we investigated whether the BLA is involved in mediating NPS's effects on object recognition memory consolidation and whether such effects require noradrenergic activity. Intracerebroventricular infusion of NPS (1nmol) post training facilitated 24-h memory in a mouse novel object recognition task. The memory-enhancing effect of NPS could be blocked by the β-adrenoceptor antagonist propranolol. Furthermore, post-training intra-BLA infusions of NPS (0.5nmol/side) improved 24-h memory for objects, which was impaired by co-administration of propranolol (0.5μg/side). Taken together, these results indicate that NPS interacts with the BLA noradrenergic system in improving object recognition memory during consolidation. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Noradrenergic deficits in Parkinson's disease imaged with (11)C-MeNER

    DEFF Research Database (Denmark)

    Nahimi, Adjmal; Sommerauer, Michael; Kinnerup, Martin B

    2017-01-01

    significant declines in the thalamus, hypothalamus, and nucleus ruber. Tremor was significantly associated with preserved tracer binding. Conclusion: This is first specific quantification of noradrenergic denervation in Parkinsonńs disease patients in vivo. In agreement with predictions from determinations...

  4. Human amygdala reactivity is diminished by the beta-noradrenergic antagonist propranolol

    NARCIS (Netherlands)

    Hurlemann, R.; Walter, H.; Rehme, A. K.; Kukolja, J.; Santoro, S. C.; Schmidt, C.; Schnell, K.; Musshoff, F.; Keysers, C.; Maier, W.; Kendrick, K. M.; Onur, O. A.

    Background. Animal models of anxiety disorders emphasize the crucial role of locus ceruleus-noradrenergic (norepinephrine, NE) signaling, the basolateral amygdala (BLA) and their interactions in the expression of anxiety-like behavioral responses to stress. Despite clinical evidence for the efficacy

  5. Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

    Science.gov (United States)

    Boeva, Valentina; Louis-Brennetot, Caroline; Peltier, Agathe; Durand, Simon; Pierre-Eugène, Cécile; Raynal, Virginie; Etchevers, Heather C; Thomas, Sophie; Lermine, Alban; Daudigeos-Dubus, Estelle; Geoerger, Birgit; Orth, Martin F; Grünewald, Thomas G P; Diaz, Elise; Ducos, Bertrand; Surdez, Didier; Carcaboso, Angel M; Medvedeva, Irina; Deller, Thomas; Combaret, Valérie; Lapouble, Eve; Pierron, Gaelle; Grossetête-Lalami, Sandrine; Baulande, Sylvain; Schleiermacher, Gudrun; Barillot, Emmanuel; Rohrer, Hermann; Delattre, Olivier; Janoueix-Lerosey, Isabelle

    2017-09-01

    Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

  6. Peripheral markers of serotonergic and noradrenergic function in post-pubertal, caucasian males with autistic disorder.

    Science.gov (United States)

    Croonenberghs, J; Delmeire, L; Verkerk, R; Lin, A H; Meskal, A; Neels, H; Van der Planken, M; Scharpe, S; Deboutte, D; Pison, G; Maes, M

    2000-03-01

    Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline may play a role in the pathophysiology of autistic disorder. This study examines serotonergic and noradrenergic markers in a study group of 13 male, post-pubertal, caucasian autistic patients (age 12-18 y; I.Q. > 55) and 13 matched volunteers. [3H]-paroxetine binding Kd values were significantly higher in patients with autism than in healthy volunteers. Plasma concentrations of tryptophan, the precursor of 5-HT, were significantly lower in autistic patients than in healthy volunteers. There were no significant differences between autistic and normal children in the serum concentrations of 5-HT, or the 24-hr urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA), adrenaline, noradrenaline, and dopamine. There were no significant differences in [3H]-rauwolscine binding Bmax or Kd values, or in the serum concentrations of tyrosine, the precursor of noradrenaline, between both study groups. There were highly significant positive correlations between age and 24-hr urinary excretion of 5-HIAA and serum tryptophan. The results suggest that: 1) serotonergic disturbances, such as defects in the 5-HT transporter system and lowered plasma tryptophan, may play a role in the pathophysiology of autism; 2) autism is not associated with alterations in the noradrenergic system; and 3) the metabolism of serotonin in humans undergoes significant changes between the ages of 12 and 18 years.

  7. Combined Effects of Glucocorticoid and Noradrenergic Activity on Loss Aversion.

    Science.gov (United States)

    Margittai, Zsofia; Nave, Gideon; Van Wingerden, Marijn; Schnitzler, Alfons; Schwabe, Lars; Kalenscher, Tobias

    2018-01-01

    Loss aversion is a well-known behavioral regularity in financial decision making, describing humans' tendency to overweigh losses compared to gains of the same amount. Recent research indicates that stress and associated hormonal changes affect loss aversion, yet the underlying neuroendocrine mechanisms are still poorly understood. Here, we investigated the causal influence of two major stress neuromodulators, cortisol and noradrenaline, on loss aversion during financial decision making. In a double-blind, placebo-controlled between-subject design, we orally administered either the α2-adrenergic antagonist yohimbine (increasing noradrenergic stimulation), hydrocortisone, both substances, or a placebo to healthy young men. We tested the treatments' influence on a financial decision-making task measuring loss aversion and risk attitude. We found that both drugs combined, relative to either drug by itself, reduced loss aversion in the absence of an effect on risk attitude or choice consistency. Our data suggest that concurrent glucocorticoid and noradrenergic activity prompts an alignment of reward- with loss-sensitivity, and thus diminishes loss aversion. Our results have implications for the understanding of the susceptibility to biases in decision making.

  8. Noradrenergic stimulation modulates activation of extinction-related brain regions and enhances contextual extinction learning without affecting renewal

    Directory of Open Access Journals (Sweden)

    Silke eLissek

    2015-02-01

    Full Text Available Renewal in extinction learning describes the recovery of an extinguished response if the extinction context differs from the context present during acquisition and recall. Attention may have a role in contextual modulation of behavior and contribute to the renewal effect, while noradrenaline is involved in attentional processing. In this functional magnetic resonance imaging (fMRI study we investigated the role of the noradrenergic system for behavioral and brain activation correlates of contextual extinction and renewal, with a particular focus upon hippocampus and ventromedial PFC, which have crucial roles in processing of renewal. Healthy human volunteers received a single dose of the NA reuptake inhibitor atomoxetine prior to extinction learning. During extinction of previously acquired cue-outcome associations, cues were presented in a novel context (ABA or in the acquisition context (AAA. In recall, all cues were again presented in the acquisition context. Atomoxetine participants (ATO showed significantly faster extinction compared to placebo (PLAC. However, atomoxetine did not affect renewal. Hippocampal activation was higher in ATO during extinction and recall, as was ventromedial PFC activation, except for ABA recall. Moreover, ATO showed stronger recruitment of insula, anterior cingulate, and dorsolateral/orbitofrontal PFC. Across groups, cingulate, hippocampus and vmPFC activity during ABA extinction correlated with recall performance, suggesting high relevance of these regions for processing the renewal effect. In summary, the noradrenergic system appears to be involved in the modification of established associations during extinction learning and thus has a role in behavioral flexibility. The assignment of an association to a context and the subsequent decision on an adequate response, however, presumably operate largely independently of noradrenergic mechanisms.

  9. Noradrenergic and GABAergic systems in the medial hypothalamus are activated during hypoglycemia

    NARCIS (Netherlands)

    Beverly, JL; De Vries, MG; Bouman, SD; Arseneau, LM

    Noradrenergic and GABAergic systems in the medial hypothalamus influence plasma glucose and may be activated during glucoprivation. Microdialysis probes were placed into the ventromedial nucleus (VMH), lateral hypothalamus (LHA), and paraventricular nucleus (PVH) of male Sprague-Dawley rats to

  10. Prenatal drug exposures sensitize noradrenergic circuits to subsequent disruption by chlorpyrifos.

    Science.gov (United States)

    Slotkin, Theodore A; Skavicus, Samantha; Seidler, Frederic J

    2015-12-02

    We examined whether nicotine or dexamethasone, common prenatal drug exposures, sensitize the developing brain to chlorpyrifos. We gave nicotine to pregnant rats throughout gestation at a dose (3mg/kg/day) producing plasma levels typical of smokers; offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1mg/kg) that produces minimally-detectable inhibition of brain cholinesterase activity. In a parallel study, we administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2mg/kg) used in the management of preterm labor, followed by postnatal chlorpyrifos. We evaluated cerebellar noradrenergic projections, a known target for each agent, and contrasted the effects with those in the cerebral cortex. Either drug augmented the effect of chlorpyrifos, evidenced by deficits in cerebellar β-adrenergic receptors; the receptor effects were not due to increased systemic toxicity or cholinesterase inhibition, nor to altered chlorpyrifos pharmacokinetics. Further, the deficits were not secondary adaptations to presynaptic hyperinnervation/hyperactivity, as there were significant deficits in presynaptic norepinephrine levels that would serve to augment the functional consequence of receptor deficits. The pretreatments also altered development of cerebrocortical noradrenergic circuits, but with a different overall pattern, reflecting the dissimilar developmental stages of the regions at the time of exposure. However, in each case the net effects represented a change in the developmental trajectory of noradrenergic circuits, rather than simply a continuation of an initial injury. Our results point to the ability of prenatal drug exposure to create a subpopulation with heightened vulnerability to environmental neurotoxicants. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Disinhibition by propranolol and chlordiazepoxide of nonrewarded lever-pressing in the rat is unaffected by dorsal noradrenergic bundle lesion.

    Science.gov (United States)

    Salmon, P; Tsaltas, E; Gray, J A

    1989-03-01

    Ten male Sprague-Dawley rats received 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle and 10 others underwent control operations. The lesion depleted levels of noradrenaline in the hippocampus to 2% of those in the controls. All rats were then trained for 16 sessions to lever-press in a Skinner box on a variable interval 18 sec schedule of food-reinforcement, then for 42 days on a successive discrimination between periods of variable interval (VI 18 sec) food-reinforcement and periods of extinction. This report describes the effects of chlordiazepoxide (CDP; 5 mg/kg) and propranolol (5 and 10 mg/kg) injected intraperitoneally in both groups on modified ABBA designs after this training. Both drugs increased the response rates in extinction periods. The effect of propranolol was similar at each dose and smaller than that of CDP. Although CDP and propranolol (5 mg/kg) increased variable interval response rates also, this could not account for the effect on extinction response rates. Responding did not differ between the lesioned and control animals and the effects of drugs were similar in each group. It is unlikely that CDP or propranolol release nonrewarded responding by disrupting transmission in the dorsal noradrenergic bundle.

  12. Autoradiographic analysis of alpha 1-noradrenergic receptors in the human brain postmortem. Effect of suicide

    International Nuclear Information System (INIS)

    Gross-Isseroff, R.; Dillon, K.A.; Fieldust, S.J.; Biegon, A.

    1990-01-01

    In vitro quantitative autoradiography of alpha 1-noradrenergic receptors, using tritiated prazosin as a ligand, was performed on 24 human brains postmortem. Twelve brains were obtained from suicide victims and 12 from matched controls. We found significant lower binding to alpha 1 receptors in several brain regions of the suicide group as compared with matched controls. This decrease in receptor density was evident in portions of the prefrontal cortex, as well as the temporal cortex and in the caudate nucleus. Age, sex, presence of alcohol, and time of death to autopsy did not affect prazosin binding, in our sample, as measured by autoradiography

  13. Modulation of the noradrenergic receptor at uterine level by the 17 β-estradiol influence

    International Nuclear Information System (INIS)

    Vanderlei, F.H.F.; Catanho, M.T.J.

    1991-01-01

    The present study was undertaken to asses the regulation of the noradrenergic receptor, by estrogens. We measured the uterotrophic response and the binding capacity of the noradrenergic receptor after the administration of 17 β-estradiol (E sub(2); 132 nmol/kg b.w., i.p.) to immature rats. The results showed that 2 and 4 hs after E sub(2) treatment, the total number of NA-receptors enhanced significantly (6 fold). Similarly, it was observed a significant increase in uterine weight, 24 h after E sub(2) administration. The results indicate that NA-receptors present in the uterus may be under a direct E sub(2) regulation, which suggests a possible participation on the uterotropic response induced by E sub(2). (author)

  14. Noradrenergic action in prefrontal cortex in the late stage of memory consolidation

    NARCIS (Netherlands)

    Tronel, Sophie; Feenstra, Matthijs G. P.; Sara, Susan J.

    2004-01-01

    These experiments investigated the role of the noradrenergic system in the late stage of memory consolidation and in particular its action at beta receptors in the prelimbic region (PL) of the prefrontal cortex in the hours after training. Rats were trained in a rapidly acquired, appetitively

  15. One-single physical exercise session after object recognition learning promotes memory persistence through hippocampal noradrenergic mechanisms.

    Science.gov (United States)

    da Silva de Vargas, Liane; Neves, Ben-Hur Souto das; Roehrs, Rafael; Izquierdo, Iván; Mello-Carpes, Pâmela

    2017-06-30

    Previously we showed the involvement of the hippocampal noradrenergic system in the consolidation and persistence of object recognition (OR) memory. Here we show that one-single physical exercise session performed immediately after learning promotes OR memory persistence and increases norepinephrine levels in the hippocampus. Additionally, effects of exercise on memory are avoided by an intra-hippocampal beta-adrenergic antagonist infusion. Taken together, these results suggest that exercise effects on memory can be related to noradrenergic mechanisms and acute physical exercise can be a non-pharmacological intervention to assist memory consolidation and persistence, with few or no side effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Noradrenergic Action in Prefrontal Cortex in the Late Stage of Memory Consolidation

    Science.gov (United States)

    Tronel, Sophie; Feenstra, Matthijs G. P.; Sara, Susan J.

    2004-01-01

    These experiments investigated the role of the noradrenergic system in the late stage of memory consolidation and in particular its action at beta receptors in the prelimbic region (PL) of the prefrontal cortex in the hours after training. Rats were trained in a rapidly acquired, appetitively motivated foraging task based on olfactory…

  17. Paraquat and maneb co-exposure induces noradrenergic locus coeruleus neurodegeneration through NADPH oxidase-mediated microglial activation

    International Nuclear Information System (INIS)

    Hou, Liyan; Zhang, Cong; Wang, Ke; Liu, Xiaofang; Wang, Hongwei; Che, Yuning; Sun, Fuqiang; Zhou, Xueying; Zhao, Xiulan; Wang, Qingshan

    2017-01-01

    Highlights: • Microglial activation induced by paraquat and maneb precedes noradrenergic neurodegeneration in locus coeruleus. • NADPH oxidase activation contributes to microglia-mediated neuroinflammation and related noradrenergic neurodegeneration. • Inhibition of NADPH oxidase by apocynin protects noradrenergic neurons against paraquat and maneb-induced toxicity. - Abstract: Co-exposure to paraquat (PQ) and maneb (Mb) has been shown to increase the risk of Parkinson’s disease (PD) and dopaminergic (DA) neurodegeneration in the substantia nigra pars compacta (SNpc) is observed in PQ and Mb-treated experimental animals. The loss of noradrenergic locus coeruleus (LC/NE) neurons in brainstem is a common feature shared by multiple neurodegenerative diseases, including PD. However, whether PQ and Mb is able to damage LC/NE neurons remains undefined. In this study, mice treated with combined PQ and Mb displayed progressive LC/NE neurodegeneration. Time course studies revealed that the activation of microglia preceded LC/NE neurodegeneration. Mechanistically, the activation of NADPH oxidase contributed to microglial activation and subsequent LC/NE neurodegeneration. We found that PQ and Mb co-exposure induced activation of NADPH oxidase as shown by increased superoxide production and membrane translocation of p47 phox , a cytosolic subunit of NADPH oxidase. Inhibition of NADPH oxidase by apocynin, a widely used NADPH oxidase inhibitor, suppressed microglial activation and gene expressions of proinflammatory factors. Furthermore, reduced activation of nuclear factor-κB (NF-κB) pathway was observed in apocynin-treated mice. More importantly, inhibition of NADPH oxidase by apocynin afforded LC/NE neuroprotection against PQ and Mb-induced neurotoxicity. Thus, our findings revealed the critical role NADPH oxidase-mediated microglial activation in driving LC/NE neurodegeneration induced by PQ and Mb, providing new insights into the pathogenesis of environmental

  18. Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling.

    Science.gov (United States)

    Skelly, M J; Chappell, A E; Carter, E; Weiner, J L

    2015-10-01

    Alcohol use disorder, anxiety disorders, and post-traumatic stress disorder (PTSD) are highly comorbid, and exposure to chronic stress during adolescence may increase the incidence of these conditions in adulthood. Efforts to identify the common stress-related mechanisms driving these disorders have been hampered, in part, by a lack of reliable preclinical models that replicate their comorbid symptomatology. Prior work by us, and others, has shown that adolescent social isolation increases anxiety-like behaviors and voluntary ethanol consumption in adult male Long-Evans rats. Here we examined whether social isolation also produces deficiencies in extinction of conditioned fear, a hallmark symptom of PTSD. Additionally, as disrupted noradrenergic signaling may contribute to alcoholism, we examined the effect of anxiolytic medications that target noradrenergic signaling on ethanol intake following adolescent social isolation. Our results confirm and extend previous findings that adolescent social isolation increases anxiety-like behavior and enhances ethanol intake and preference in adulthood. Additionally, social isolation is associated with a significant deficit in the extinction of conditioned fear and a marked increase in the ability of noradrenergic therapeutics to decrease ethanol intake. These results suggest that adolescent social isolation not only leads to persistent increases in anxiety-like behaviors and ethanol consumption, but also disrupts fear extinction, and as such may be a useful preclinical model of stress-related psychopathology. Our data also suggest that disrupted noradrenergic signaling may contribute to escalated ethanol drinking following social isolation, thus further highlighting the potential utility of noradrenergic therapeutics in treating the deleterious behavioral sequelae associated with early life stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. The dorsal tegmental noradrenergic projection: an analysis of its role in maze learning.

    Science.gov (United States)

    Roberts, D C; Price, M T; Fibiger, H C

    1976-04-01

    The hypothesis that the noradrenergic projection from the locus coeruleus (LC) to the cerebral cortex and hippocampus is an important neural substrate for learning was evaluated. Maze performance was studied in rats receiving either electrolytic lesions of LC or 6-hydroxydopamine (6-OHDA) lesions of the dorsal tegmental noradrenergic projection. The LC lesions did not disrupt the acquisition of a running response for food reinforcement in an L-shaped runway, even though hippocampal-cortical norepinephrine (NE) was reduced to 29%. Greater telencephalic NE depletions (to 6% of control levels) produced by 6-OHDA also failed to disrupt the acquisition of this behavior or to impair the acquisition of a food-reinforced position habit in a T-maze. Neither locomotor activity nor habituation to a novel environment was affected by the 6-OHDA lesions. Rats with such lesions were, however, found to be significantly more distractible than were controls during the performance of a previously trained response. The hypothesis that telencephalic NE is of fundamental importance in learning was not supported. The data suggest that this system may participate in attentional mechanisms.

  20. Selective Serotonergic (SSRI) Versus Noradrenergic (SNRI) Reuptake Inhibitors with and without Acetylsalicylic Acid in Major Depressive Disorder.

    Science.gov (United States)

    Zdanowicz, Nicolas; Reynaert, Christine; Jacques, Denis; Lepiece, Brice; Dubois, Thomas

    2017-09-01

    Antidepressant medication efficacy remains a major research challenge. Here, we explored four questions: whether noradrenergic antidepressants are more effective than serotonergic antidepressants; whether the addition of 100 mg acetylsalicylic acid (ASA) changes antidepressant efficacy; whether the long-term efficacy differs depending on the antidepressant and the addition of ASA; and whether serum levels of brain-derived neurotrophic factor (BDNF) are clinically informative. In a two-year study, forty people with major depressive disorder were randomly assigned to groups that received an SSRI (escitalopram) or an SNRI (duloxetine), each group received concomitant ASA (100 mg) or a placebo. Sociodemographic data were recorded and patients under went regular assessments with the Hamilton depression scale (HDS) and clinical global impression (CGI) scale. Serum levels of BDNF were measured four times per year. There was no significant difference in efficacy between the two antidepressants or between antidepressant treatment with and without ASA. However, subgroup comparisons revealed that the duloxetine + ASA (DASA) subgroup showed a more rapid improvement in HDS score as early as 2 months (t=-3.114, p=0.01), in CGI score at 5 months (t=-2.119, p=0.05), and a better remission rate (χ 2 =6.296, p 0.012) than the escitalopram + placebo (EP) subgroup. Serum BDNF before treatment was also higher in the DASA subgroup than in the EP subgroup (t=3.713; p=0.002). This suggest two hypotheses: either a noradrenergic agent combined with ASA is more effective in treating depression than a serotonergic agent alone, or the level of serum BDNF before treatment is a precursor marker of the response to antidepressants. Further research is needed to test these hypotheses.

  1. Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

    NARCIS (Netherlands)

    Ronzoni, G.; Arco, A. Del; Mora, F.; Segovia, G.

    2016-01-01

    Increased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats

  2. Localization of endogenous amyloid-β to the coeruleo-cortical pathway: consequences of noradrenergic depletion.

    Science.gov (United States)

    Ross, Jennifer A; Reyes, Beverly A S; Thomas, Steven A; Van Bockstaele, Elisabeth J

    2018-01-01

    The locus coeruleus (LC)-norepinephrine (NE) system is an understudied circuit in the context of Alzheimer's disease (AD), and is thought to play an important role in neurodegenerative and neuropsychiatric diseases involving catecholamine neurotransmitters. Understanding the expression and distribution of the amyloid beta (Aβ) peptide, a primary component of AD, under basal conditions and under conditions of NE perturbation within the coeruleo-cortical pathway may be important for understanding its putative role in pathological states. Thus, the goal of this study is to define expression levels and the subcellular distribution of endogenous Aβ with respect to noradrenergic profiles in the rodent LC and medial prefrontal cortex (mPFC) and, further, to determine the functional relevance of NE in modulating endogenous Aβ 42 levels. We report that endogenous Aβ 42 is localized to tyrosine hydroxylase (TH) immunoreactive somatodendritic profiles of the LC and dopamine-β-hydroxylase (DβH) immunoreactive axon terminals of the infralimbic mPFC (ILmPFC). Male and female naïve rats have similar levels of amyloid precursor protein (APP) cleavage products demonstrated by western blot, as well as similar levels of endogenous Aβ 42 as determined by enzyme-linked immunosorbent assay. Two models of NE depletion, DSP-4 lesion and DβH knockout (KO) mice, were used to assess the functional relevance of NE on endogenous Aβ 42 levels. DSP-4 lesioned rats and DβH-KO mice show significantly lower levels of endogenous Aβ 42 . Noradrenergic depletion did not change APP-cleavage products resulting from β-secretase processing. Thus, resultant decreases in endogenous Aβ 42 may be due to decreased neuronal activity of noradrenergic neurons, or, by decreased stimulation of adrenergic receptors which are known to contribute to Aβ 42 production by enhancing γ-secretase processing under normal physiological conditions.

  3. Noradrenergic Control of Odor Recognition in a Nonassociative Olfactory Learning Task in the Mouse

    Science.gov (United States)

    Veyrac, Alexandra; Nguyen, Veronique; Marien, Marc; Didier, Anne; Jourdan, Francois

    2007-01-01

    The present study examined the influence of pharmacological modulations of the locus coeruleus noradrenergic system on odor recognition in the mouse. Mice exposed to a nonrewarded olfactory stimulation (training) were able to memorize this odor and to discriminate it from a new odor in a recall test performed 15 min later. At longer delays (30 or…

  4. Projection specificity in heterogeneous locus coeruleus cell populations: implications for learning and memory

    Science.gov (United States)

    Uematsu, Akira; Tan, Bao Zhen

    2015-01-01

    Noradrenergic neurons in the locus coeruleus (LC) play a critical role in many functions including learning and memory. This relatively small population of cells sends widespread projections throughout the brain including to a number of regions such as the amygdala which is involved in emotional associative learning and the medial prefrontal cortex which is important for facilitating flexibility when learning rules change. LC noradrenergic cells participate in both of these functions, but it is not clear how this small population of neurons modulates these partially distinct processes. Here we review anatomical, behavioral, and electrophysiological studies to assess how LC noradrenergic neurons regulate these different aspects of learning and memory. Previous work has demonstrated that subpopulations of LC noradrenergic cells innervate specific brain regions suggesting heterogeneity of function in LC neurons. Furthermore, noradrenaline in mPFC and amygdala has distinct effects on emotional learning and cognitive flexibility. Finally, neural recording data show that LC neurons respond during associative learning and when previously learned task contingencies change. Together, these studies suggest a working model in which distinct and potentially opposing subsets of LC neurons modulate particular learning functions through restricted efferent connectivity with amygdala or mPFC. This type of model may provide a general framework for understanding other neuromodulatory systems, which also exhibit cell type heterogeneity and projection specificity. PMID:26330494

  5. Noradrenergic activation of the basolateral amygdala modulates the consolidation of object-in-context recognition memory

    Directory of Open Access Journals (Sweden)

    Areg eBarsegyan

    2014-05-01

    Full Text Available Noradrenergic activation of the basolateral complex of the amygdala (BLA is well known to enhance the consolidation of long-term memory of highly emotionally arousing training experiences. The present study investigated whether such noradrenergic activation of the BLA also influences the consolidation of object-in-context recognition memory, a low-arousing training task assessing episodic-like memory. Male Sprague–Dawley rats were exposed to two identical objects in one context for either 3 or 10 min, immediately followed by exposure to two other identical objects in a distinctly different context. Immediately after the training they received bilateral intra-BLA infusions of norepinephrine (0.3, 1.0 or 3.0 μg or the β-adrenoceptor antagonist propranolol (0.1, 0.3 or 1.0 μg. On the 24-h retention test, rats were placed back into one of the training contexts with one copy of each of the two training objects. Thus, although both objects were familiar, one of the objects had not previously been encountered in this particular test context. Hence, if the animal generated a long-term memory for the association between an object and its context, it would spend significantly more time exploring the object that was not previously experienced in this context. Saline-infused control rats exhibited poor 24-h retention when given 3 min of training and good retention when given 10 min of training. Norepinephrine administered after 3 min of object-in-context training induced a dose-dependent memory enhancement, whereas propranolol administered after 10 min of training produced memory impairment. These findings provide evidence that posttraining noradrenergic activation of the BLA also enhances the consolidation of memory of object-in-context recognition training, enabling accuracy of episodic-like memories.

  6. Tonic noradrenergic activity modulates explorative behavior and attentional set shifting: Evidence from pupillometry and gaze pattern analysis.

    Science.gov (United States)

    Pajkossy, Péter; Szőllősi, Ágnes; Demeter, Gyula; Racsmány, Mihály

    2017-12-01

    A constant task for every living organism is to decide whether to exploit rewards associated with current behavior or to explore the environment for more rewarding options. Current empirical evidence indicates that exploitation is related to phasic whereas exploration is related to tonic firing mode of noradrenergic neurons in the locus coeruleus. In humans, this exploration-exploitation trade-off is subserved by the ability to flexibly switch attention between task-related and task-irrelevant information. Here, we investigated whether this function, called attentional set shifting, is related to exploration and tonic noradrenergic discharge. We measured pretrial baseline pupil dilation, proved to be strongly correlated with the activity of the locus coeruleus, while human participants took part in well-known tasks of attentional set shifting. Study 1 used the Wisconsin Card Sorting Task, whereas in Study 2, the Intra/Extradimensional Set Shifting Task was used. Both tasks require participants to choose between different compound stimuli based on feedback provided for their previous decisions. During the task, stimulus-reward contingencies change periodically, thus participants are repeatedly required to reassess which stimulus features are relevant (i.e., they shift their attentional set). Our results showed that baseline pupil diameter steadily decreased when the stimulus-reward contingencies were stable, whereas they suddenly increased when these contingencies changed. Analysis of looking patterns also confirmed the presence of exploratory behavior during attentional set shifting. Thus, our results suggest that tonic firing mode of noradrenergic neurons in the locus coeruleus is implicated in attentional set shifting, as it regulates the amount of exploration. © 2017 Society for Psychophysiological Research.

  7. CHOLINERGIC AND NORADRENERGIC MODULATION OF LONG-TERM EXPLICIT MEMORY ARE ALTERED BY CHRONIC LOW-LEVEL LEAD EXPOSURE. (U915393)

    Science.gov (United States)

    Recent evidence suggests that septohippocampal cholinergic activity is suppressed in rats exposed to low levels of lead (Pb). As a result, noradrenergic activity may be elevated due to compensatory sympathetic sprouting. Therefore, the goals of this study were to (a) determine...

  8. Noradrenergic α1 Receptor Antagonist Treatment Attenuates Positive Subjective Effects of Cocaine in Humans: A Randomized Trial

    Science.gov (United States)

    Newton, Thomas F.; De La Garza, Richard; Brown, Gregory; Kosten, Thomas R.; Mahoney, James J.; Haile, Colin N.

    2012-01-01

    Background Preclinical research implicates dopaminergic and noradrenergic mechanisms in mediating the reinforcing effects of drugs of abuse, including cocaine. The objective of this study was to evaluate the impact of treatment with the noradrenergic α1 receptor antagonist doxazosin on the positive subjective effects of cocaine. Methods Thirteen non-treatment seeking, cocaine-dependent volunteers completed this single-site, randomized, placebo-controlled, within-subjects study. In one study phase volunteers received placebo and in the other they received doxazosin, with the order counterbalanced across participants. Study medication was masked by over-encapsulating doxazosin tablets and matched placebo lactose served as the control. Study medication treatment was initiated at 1 mg doxazosin or equivalent number of placebo capsules PO/day and increased every three days by 1 mg. After receiving 4 mg doxazosin or equivalent number of placebo capsules participants received masked doses of 20 and 40 mg cocaine IV in that order with placebo saline randomly interspersed to maintain the blind. Results Doxazosin treatment was well tolerated and doxazosin alone produced minimal changes in heart rate and blood pressure. During treatment with placebo, cocaine produced dose-dependent increases in subjective effect ratings of “high”, “stimulated”, “like cocaine”, “desire cocaine”, “any drug effect”, and “likely to use cocaine if had access” (p<.001). Doxazosin treatment significantly attenuated the effects of 20 mg cocaine on ratings of “stimulated”, “like cocaine”, and “likely to use cocaine if had access” (p<.05). There were trends for doxazosin to reduce ratings of “stimulated”, “desire cocaine”, and “likely to use cocaine if had access” (p<.10). Conclusions Medications that block noradrenergic α1 receptors, such as doxazosin, may be useful as treatments for cocaine dependence, and should be evaluated further. Trial

  9. Noradrenergic Activation of the Basolateral Amygdala Enhances Object Recognition Memory and Induces Chromatin Remodeling in the Insular Cortex

    Directory of Open Access Journals (Sweden)

    Hassiba eBeldjoud

    2015-04-01

    Full Text Available It is well established that arousal-induced memory enhancement requires noradrenergic activation of the basolateral complex of the amygdala (BLA and modulatory influences on information storage processes in its many target regions. While this concept is well accepted, the molecular basis of such BLA effects on neural plasticity changes within other brain regions remains to be elucidated. The present study investigated whether noradrenergic activation of the BLA after object recognition training induces chromatin remodeling through histone post-translational modifications in the insular cortex (IC, a brain region that is importantly involved in object recognition memory. Male Sprague–Dawley rats were trained on an object recognition task, followed immediately by bilateral microinfusions of norepinephrine (1.0 µg or saline administered into the BLA. Saline-treated control rats exhibited poor 24-h retention, whereas norepinephrine treatment induced robust 24-h object recognition memory. Most importantly, this memory-enhancing dose of norepinephrine induced a global reduction in the acetylation levels of histone H3 at lysine 14, H2B and H4 in the IC 1 h later, whereas it had no effect on the phosphorylation of histone H3 at serine 10 or tri-methylation of histone H3 at lysine 27. Norepinephrine administered into the BLA of non-trained control rats did not induce any changes in the histone marks investigated in this study. These findings indicate that noradrenergic activation of the BLA induces training-specific effects on chromatin remodeling mechanisms, and presumably gene transcription, in its target regions, which may contribute to the understanding of the molecular mechanisms of stress and emotional arousal effects on memory consolidation.

  10. Both a Nicotinic Single Nucleotide Polymorphism (SNP) and a Noradrenergic SNP Modulate Working Memory Performance when Attention Is Manipulated

    Science.gov (United States)

    Greenwood, Pamela M.; Sundararajan, Ramya; Lin, Ming-Kuan; Kumar, Reshma; Fryxell, Karl J.; Parasuraman, Raja

    2009-01-01

    We investigated the relation between the two systems of visuospatial attention and working memory by examining the effect of normal variation in cholinergic and noradrenergic genes on working memory performance under attentional manipulation. We previously reported that working memory for location was impaired following large location precues,…

  11. Effects of lesions to the dorsal noradrenergic bundle on counterconditioning of punished barpressing.

    Science.gov (United States)

    Tsaltas, E; Gray, J A; Preston, G C

    1987-01-01

    The possible contribution of the dorsal noradrenergic bundle (DB) to the development of a simple form of counterconditioning (an associative mechanism leading to behavioural tolerance for stress) was assessed by comparison of the performance of animals with 6-hydroxydopamine-induced lesions of the DB to that of sham-operated (SH) animals. Animals engaging in barpressing for food reward on a random-interval (RI) 64 sec schedule were presented with a stimulus signalling the concurrent operation of an RI-64 sec schedule of response-contingent shock. In the control condition (punishment), shock and reward never occurred as a result of the same barpress. In the experimental condition (counterconditioning), the frequency of shock and reward were the same as for the punishment condition but the two events always occurred in succession, with food following shock, as a consequence of the same barpress. DB lesions had no effect on the acquisition of rewarded barpressing or on the initial acquisition of the discrimination between the shock-free and shock-containing (signalled) components of the schedule. However, once performance on the discrimination had reached asymptote, DB animals in the punishment control group showed significantly less suppression to the signal than SH animals. The counterconditioning schedule used was effective, leading to significantly reduced response suppression in the SH animals in comparison to the SH group subjected to punishment. The pattern of findings in the DB groups was consistent with a blockade by the lesion of the development of counterconditioning. These results suggest, therefore, that the DB is involved in at least one associative mechanism leading to tolerance for stress.

  12. Ilex paraguariensis Promotes Orofacial Pain Relief After Formalin Injection: Involvement of Noradrenergic Pathway.

    Science.gov (United States)

    de Carvalho, Eudislaine Fonseca; de Oliveira, Simone Kobe; Nardi, Viviane Koepp; Gelinski, Tathiana Carla; Bortoluzzi, Marcelo Carlos; Maraschin, Marcelo; Nardi, Geisson Marcos

    2016-03-01

    Drinking mate or chimarrão, a hot infusion of Ilex paraguariensis (ILEX) leaves, is a common habit in Southern South America that has a social and almost ritualistic role. It has been used as a stimulant beverage in South America and analgesic in regions of Argentina for treatment of headache and others painful inflammatory conditions such as arthritis and rheumatism. The aim of this study was to evaluate the pharmacological activity of I. paraguariensis infusion (ILEX) on orofacial nociception model induced by formalin, and study its mechanism of action. The analgesic effect of ILEX was assessed through writhing test, paw formalin test, paw edema induced by carrageenan, and orofacial pain induced by formalin. To study the action mechanism of ILEX, opioidergic, dopaminergic, nitrergic, and adrenergic pathways were investigated. The high-performance liquid chromatography analysis of ILEX infusion revealed caffeine and theobromine. The treatment with ILEX reduced the number of writhing. However, it was effective neither in the formalin paw test nor in the paw edema induced by carrageenan. Different from formalin paw test, ILEX was able to reduce the orofacial reactivity to formalin in 31.8% (70.4 ± 2.5 s; first phase), and 20% (127.3 ± 18.9 s; second phase). The analgesic effect of ILEX results from the modulation of noradrenergic pathways since prazosin (α1-adrenoceptor antagonist, 0.15 mg/kg; intraperitoneal) reversed the analgesic effect of ILEX. The present report demonstrates that analgesic effect of ILEX in orofacial formalin test is due mainly to modulation of noradrenergic pathways. Ilex paraguariensis (ILEX) has been used as a stimulant beverage in South America and analgesic in regions of Argentina for the treatment of headache and others painful inflammatory conditions such arthritis and rheumatism.The aim of this study was to evaluate the pharmacological activity of ILEX on orofacial nociception model induced by formalin, and study its mechanism of

  13. Dopamine modulates male sexual behavior in Japanese quail in part via actions on noradrenergic receptors.

    Science.gov (United States)

    Cornil, Charlotte A; Dejace, Christel; Ball, Gregory F; Balthazart, Jacques

    2005-08-30

    In rats, dopamine (DA) facilitates male sexual behavior through its combined action on D1- and D2-like receptors, in the medial preoptic area (MPOA) as well as other brain areas. In Japanese quail, systemic injections of dopaminergic drugs suggested a similar pharmacology but central injections have never been performed. Recent electrophysiological experiments demonstrated that DA effects in the MPOA of quail are mediated mainly through the activation of alpha2-noradrenergic receptors. Previous studies of DA action on behavior used specific dopaminergic agonists/antagonists and therefore unintentionally avoided the potential cross-reaction with alpha2-receptors. The present study was thus designed to investigate directly the effects of DA on male sexual behavior and to test whether the interaction of DA with heterologous receptors affects this behavior. Intracerebroventricular (i.c.v.) injection of DA or NE inhibited copulation in a dose-dependent manner. Systemic injections of yohimbine, an alpha2-noradrenergic antagonist, modulated copulation in a bimodal manner depending on the dose injected. Interestingly, a behaviorally ineffective dose of yohimbine markedly reduced the inhibitory effects of DA when injected 15min before. Together, these results show for the first time that i.c.v. injections of DA itself inhibit male sexual behavior in quail and suggest that the interaction of DA with alpha2-receptors has behavioral significance.

  14. A computational psychiatry approach identifies how alpha-2a noradrenergic agonist guanfacine affects feature-based reinforcement learning in the macaque

    NARCIS (Netherlands)

    Hassani, S.A.; Oemisch, M.; Balcarras, M.; Westendorff, S.; Ardid, S.; van der Meer, M.A.; Tiesinga, P.H.E.; Womelsdorf, T.

    2017-01-01

    Noradrenaline is believed to support cognitive flexibility through the alpha 2A noradrenergic receptor (a2A-NAR) acting in prefrontal cortex. Enhanced flexibility has been inferred from improved working memory with the a2A-NA agonist Guanfacine. But it has been unclear whether Guanfacine improves

  15. Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex.

    Science.gov (United States)

    Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Frau, Roberto; Gessa, Gian L

    2015-10-01

    Disulfiram has been claimed to be useful in cocaine addiction therapy, its efficacy being attributed to dopamine-beta-hydroxylase (DBH) inhibition. Our previous results indicate that disulfiram and the selective DBH inhibitor nepicastat increase extracellular dopamine (DA) in the rat medial prefrontal cortex (mPFC), and markedly potentiated cocaine-induced increase. Concomitantly, in rats with cocaine self-administration history, cocaine-seeking behavior induced by drug priming was prevented, probably through overstimulation of D1 receptors due to the DA increase. The present research was aimed at studying the neurochemical mechanisms originating the enhanced DA release. Noradrenergic system ablation was attained by intracerebroventricular (i.c.v.) administration of the neurotoxin anti-DBH-saporin (aDBH-sap). DA, noradrenaline (NA), and DOPAC were assessed by HPLC after ex vivo tissue extraction or in vivo microdialysis. Control and denervated rats were subjected to microdialysis in the mPFC and caudate nucleus to evaluate the effect of nepicastat-cocaine combination on extracellular DA levels and their regulation by α2-adrenoceptors. Fifteen days after neurotoxin or its vehicle administration, tissue and extracellular NA were reduced to less than 2% the control value, while extracellular DA was increased by approximately 100%. In control rats, nepicastat given alone and in combination with cocaine increased extracellular DA by about 250% and 1100%, respectively. In denervated rats, nepicastat slightly affected extracellular DA, while in combination with cocaine increased extracellular DA by 250%. No differences were found in the caudate nucleus. Clonidine almost totally reversed the extracellular DA elevation produced by nepicastat-cocaine combination, while it was ineffective in denervated rats. This research shows that the increase of extracellular DA produced by nepicastat alone or in combination with cocaine was prevented by noradrenergic denervation. The

  16. Short-term serotonergic but not noradrenergic antidepressant administration reduces attentional vigilance to threat in healthy volunteers

    OpenAIRE

    Murphy, Susannah E; Yiend, Jenny; Lester, Kathryn J; Cowen, Philip J; Harmer, Catherine J

    2009-01-01

    Anxiety is associated with threat-related biases in information processing such as heightened attentional vigilance to potential threat. Such biases are an important focus of psychological treatments for anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of a range of anxiety disorders. The aim of this study was to assess the effect of an SSRI on the processing of threat in healthy volunteers. A selective noradrenergic reuptake inhibitor (SNRI), ...

  17. The antidepressant-like effect of ethynyl estradiol is mediated by both serotonergic and noradrenergic systems in the forced swimming test.

    Science.gov (United States)

    Vega-Rivera, N M; López-Rubalcava, C; Estrada-Camarena, E

    2013-10-10

    17α-Ethynyl-estradiol (EE2, a synthetic steroidal estrogen) induces antidepressant-like effects in the forced swimming test (FST) similar to those induced by 5-HT and noradrenaline reuptake inhibitors (dual antidepressants). However, the precise mechanism of action of EE2 has not been studied. In the present study, the participation of estrogen receptors (ERs) and the serotonergic and the noradrenergic presynaptic sites in the antidepressant-like action of EE2 was evaluated in the FST. The effects of the ER antagonist ICI 182,780 (10 μg/rat; i.c.v.), the serotonergic and noradrenergic terminal destruction with 5,7-dihydroxytryptamine (5,7-DHT; 200 μg/rat, i.c.v.), and N-(2-chloro-ethyl)-N-ethyl-2-bromobenzylamine (DSP4; 10mg/kg, i.p.) were studied in ovariectomized rats treated with EE2 and subjected to the FST. In addition, the participation of α2-adrenergic receptors in the antidepressant-like action of EE2 was explored using the selective α2-receptor antagonist idazoxan (0.25, 0.5 and 1.0mg/kg, i.p.). EE2 induced an antidepressant-like action characterized by a decrease in immobility behavior with a concomitant increase in swimming and climbing behaviors. The ER antagonist, 5,7-DHT, DSP4, and idazoxan blocked the effects of EE2 on the immobility behavior, whereas ICI 182,780 and 5,7-DHT affected swimming behavior. The noradrenergic compound DSP4 altered climbing behavior, while Idazoxan inhibited the increase of swimming and climbing behaviors induced by EE2. Our results suggest that the antidepressant-like action of EE2 implies a complex mechanism of action on monoaminergic systems and estrogen receptors. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma.

    Science.gov (United States)

    Ikram, Fakhera; Ackermann, Sandra; Kahlert, Yvonne; Volland, Ruth; Roels, Frederik; Engesser, Anne; Hertwig, Falk; Kocak, Hayriye; Hero, Barbara; Dreidax, Daniel; Henrich, Kai-Oliver; Berthold, Frank; Nürnberg, Peter; Westermann, Frank; Fischer, Matthias

    2016-02-01

    Neuroblastoma is an embryonal pediatric tumor that originates from the developing sympathetic nervous system and shows a broad range of clinical behavior, ranging from fatal progression to differentiation into benign ganglioneuroma. In experimental neuroblastoma systems, retinoic acid (RA) effectively induces neuronal differentiation, and RA treatment has been therefore integrated in current therapies. However, the molecular mechanisms underlying differentiation are still poorly understood. We here investigated the role of transcription factor activating protein 2 beta (TFAP2B), a key factor in sympathetic nervous system development, in neuroblastoma pathogenesis and differentiation. Microarray analyses of primary neuroblastomas (n = 649) demonstrated that low TFAP2B expression was significantly associated with unfavorable prognostic markers as well as adverse patient outcome. We also found that low TFAP2B expression was strongly associated with CpG methylation of the TFAP2B locus in primary neuroblastomas (n = 105) and demethylation with 5-aza-2'-deoxycytidine resulted in induction of TFAP2B expression in vitro, suggesting that TFAP2B is silenced by genomic methylation. Tetracycline inducible re-expression of TFAP2B in IMR-32 and SH-EP neuroblastoma cells significantly impaired proliferation and cell cycle progression. In IMR-32 cells, TFAP2B induced neuronal differentiation, which was accompanied by up-regulation of the catecholamine biosynthesizing enzyme genes DBH and TH, and down-regulation of MYCN and REST, a master repressor of neuronal genes. By contrast, knockdown of TFAP2B by lentiviral transduction of shRNAs abrogated RA-induced neuronal differentiation of SH-SY5Y and SK-N-BE(2)c neuroblastoma cells almost completely. Taken together, our results suggest that TFAP2B is playing a vital role in retaining RA responsiveness and mediating noradrenergic neuronal differentiation in neuroblastoma. Copyright © 2015 Federation of European Biochemical Societies

  19. Noradrenergic mechanisms and high blood pressure maintenance in genetic hypertension: The role of Gi proteins and voltage-dependent calcium channels

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Pintérová, Mária; Líšková, Silvia; Dobešová, Zdenka; Kuneš, Jaroslav

    2007-01-01

    Roč. 29, č. 4 (2007), s. 229-229 ISSN 1064-1963. [International symposium on SHR /12./. 20.10.2006-21.10.2006, Kyoto] R&D Projects: GA MZd(CZ) NR7786 Institutional research plan: CEZ:AV0Z50110509 Keywords : genetic hypertension * noradrenergic mechanisms * Gi proteins * voltage-dependent calcium channels Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  20. Does Growth Impairment Underlie the Adverse Effects of Dexamethasone on Development of Noradrenergic Systems?

    Science.gov (United States)

    Slotkin, Theodore A; Ko, Ashley; Seidler, Frederic J

    2018-06-20

    Glucocorticoids are given in preterm labor to prevent respiratory distress but these agents evoke neurobehavioral deficits in association with reduced brain region volumes. To determine whether the neurodevelopmental effects are distinct from growth impairment, we gave developing rats dexamethasone at doses below or within the therapeutic range (0.05, 0.2 or 0.8 mg/kg) at different stages: gestational days (GD) 17-19, postnatal days (PN) 1-3 or PN7-9. In adolescence and adulthood, we assessed the impact on noradrenergic systems in multiple brain regions, comparing the effects to those on somatic growth or on brain region growth. Somatic growth was reduced with exposure in all three stages, with greater sensitivity for the postnatal regimens; brain region growth was impaired to a lesser extent. Norepinephrine content and concentration were reduced depending on the treatment regimen, with a rank order of deficits of PN7-9 > PN1-3 > GD17-19. However, brain growth impairment did not parallel reduced norepinephrine content in magnitude, dose threshold, sex or regional selectivity, or temporal pattern, and even when corrected for reduced brain region weights (norepinephrine per g tissue), the dexamethasone-exposed animals showed subnormal values. Regression analysis showed that somatic growth impairment accounted for an insubstantial amount of the reduction in norepinephrine content, and brain growth impairment accounted for only 12%, whereas specific effects on norepinephrine accounted for most of the effect. The adverse effects of dexamethasone on noradrenergic system development are not simply related to impaired somatic or brain region growth, but rather include specific targeting of neurodifferentiation. Copyright © 2018. Published by Elsevier B.V.

  1. Inferior frontal gyrus preserves working memory and emotional learning under conditions of impaired noradrenergic signaling

    Directory of Open Access Journals (Sweden)

    Benjamin eBecker

    2013-12-01

    Full Text Available Compensation has been widely applied to explain neuroimaging findings in neuropsychiatric patients. Functional compensation is often invoked when patients display equal performance and increased neural activity in comparison to healthy controls. According to the compensatory hypothesis increased activity allows the brain to maintain cognitive performance despite underlying neuropathological changes. Due to methodological and pathology-related issues, however, the functional relevance of the increased activity and the specific brain regions involved in the compensatory response remain unclear. An experimental approach that allows a transient induction of compensatory responses in the healthy brain could help to overcome these issues. To this end we used the nonselective beta-blocker propranolol to pharmacologically induce sub-optimal noradrenergic signaling in healthy participants. In two independent fMRI experiments participants received either placebo or propranolol before they underwent a cognitive challenge (experiment 1: working memory; experiment 2: emotional learning: Pavlovian fear conditioning. In experiment 1 propranolol had no effects on working memory performance, but evoked stronger activity in the left inferior frontal gyrus (IFG. In experiment 2 propranolol produced no effects on emotional memory formation, but evoked stronger activity in the right IFG. The present finding that sub-optimal beta-adrenergic signaling did not disrupt performance and concomitantly increased IFG activity is consistent with, and extends, current perspectives on functional compensation. Together, our findings suggest that under conditions of impaired noradrenergic signaling, heightened activity in brain regions located within the cognitive control network, particularly the IFG, may reflect compensatory operations subserving the maintenance of behavioral performance.

  2. The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats.

    Directory of Open Access Journals (Sweden)

    Sebastián eHormigo

    2012-06-01

    Full Text Available The inferior colliculus (IC and the locus coeruleus (LC are two midbrain nuclei that integrate multimodal information and play a major role in novelty detection to elicit an orienting response. Despite the reciprocal connections between these two structures, the projection pattern and target areas of the LC within the subdivisions of the rat IC are still unknown. Here, we used tract-tracing approaches combined with immunohistochemistry, densitometry and confocal microscopy analysis to describe a projection from the LC to the IC. Biotinylated dextran amine (BDA injections into the LC showed that the LC-IC projection is mainly ipsilateral (90% and reaches, to a major extent, the dorsal and lateral part of the IC and the intercollicular commissure. Additionally, some LC fibers extend into the central nucleus of the IC. The neurochemical nature of this projection is noradrenergic, given that tyrosine hydroxylase (TH and dopamine beta hydroxylase (DBH colocalize with the BDA-labeled fibers from the LC. To determine the total field of the LC innervations in the IC, we destroyed the LC neurons and fibers using a highly selective neurotoxin, DSP-4, and then studied the distribution and density of TH- and DBH-immunolabeled axons in the IC. In the DSP-4 treated animals, the number of axonal fibers immunolabeled for TH and DBH were deeply decreased throughout the entire rostrocaudal extent of the IC and its subdivisions compared to controls. Our densitometry results showed that the IC receives up to 97% of its noradrenergic innervations from the LC neurons and only 3% from non-coeruleus neurons. Our results also indicate that TH immunoreactivity in the IC was less impaired than the immunoreactivity for DBH after DSP-4 administration. This is consistent with the existence of an important dopaminergic projection from the substantia nigra to the IC. In conclusion, our study demonstrates and quantifies the noradrenergic projection from the LC to the IC and its

  3. Too much of a good thing: blocking noradrenergic facilitation in medial prefrontal cortex prevents the detrimental effects of chronic stress on cognition.

    Science.gov (United States)

    Jett, Julianne D; Morilak, David A

    2013-03-01

    Cognitive impairments associated with dysfunction of the medial prefrontal cortex (mPFC) are prominent in stress-related psychiatric disorders. We have shown that enhancing noradrenergic tone acutely in the rat mPFC facilitated extra-dimensional (ED) set-shifting on the attentional set-shifting test (AST), whereas chronic unpredictable stress (CUS) impaired ED. In this study, we tested the hypothesis that the acute facilitatory effect of norepinephrine (NE) in mPFC becomes detrimental when activated repeatedly during CUS. Using microdialysis, we showed that the release of NE evoked in mPFC by acute stress was unchanged at the end of CUS treatment. Thus, to then determine if repeated elicitation of this NE activity in mPFC during CUS may have contributed to the ED deficit, we infused a cocktail of α(1)-, β(1)-, and β(2)-adrenergic receptor antagonists into the mPFC prior to each CUS session, then tested animals drug free on the AST. Antagonist treatment prevented the CUS-induced ED deficit, suggesting that NE signaling during CUS compromised mPFC function. We confirmed that this was not attributable to sensitization of adrenergic receptor function following chronic antagonist treatment, by administering an additional microinjection into the mPFC immediately prior to ED testing. Acute antagonist treatment did not reverse the beneficial effects of chronic drug treatment during CUS, nor have any effect on baseline ED performance in chronic vehicle controls. Thus, we conclude that blockade of noradrenergic receptors in mPFC protected against the detrimental cognitive effects of CUS, and that repeated elicitation of noradrenergic facilitatory activity is one mechanism by which chronic stress may promote mPFC cognitive dysfunction.

  4. Localisation of NG2 immunoreactive neuroglia cells in the rat locus coeruleus and their plasticity in response to stress

    Directory of Open Access Journals (Sweden)

    Mohsen eSeifi

    2014-05-01

    Full Text Available The locus coeruleus (LC nucleus modulates adaptive behavioural responses to stress and dysregulation of LC neuronal activity is implicated in stress-induced mental illnesses. The LC is composed primarily of noradrenergic neurons together with various glial populations. A neuroglia cell-type largely unexplored within the LC is the NG2 cell. NG2 cells serve primarily as oligodendrocyte precursor cells throughout the brain. However, some NG2 cells are in synaptic contact with neurons suggesting a role in information processing. The aim of this study was to neurochemically and anatomically characterise NG2 cells within the rat LC. Furthermore, since NG2 cells have been shown to proliferate in response to traumatic brain injury, we investigated whether such NG2 cells plasticity also occurs in response to emotive insults such as stress. Immunohistochemistry and confocal microscopy revealed that NG2 cells were enriched within the pontine region occupied by the LC. Close inspection revealed that a sub-population of NG2 cells were located within unique indentations of LC noradrenergic somata and were immunoreactive for the neuronal marker NeuN whilst NG2 cell processes formed close appositions with clusters immunoreactive for the inhibitory synaptic marker proteins gephyrin and the GABA-A receptor alpha3-subunit, on noradrenergic dendrites. In addition, LC NG2 cell processes were decorated with vesicular glutamate transporter 2 immunoreactive puncta. Finally, ten days of repeated restraint stress significantly increased the density of NG2 cells within the LC. The study demonstrates that NG2 IR cells are integral components of the LC cellular network and they exhibit plasticity as a result of emotive challenges.

  5. Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior.

    Science.gov (United States)

    McCall, Jordan G; Siuda, Edward R; Bhatti, Dionnet L; Lawson, Lamley A; McElligott, Zoe A; Stuber, Garret D; Bruchas, Michael R

    2017-07-14

    Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural activity and behavior, the downstream receptors and anatomical projections that mediate these acute risk aversive behavioral states via the LC-NE system remain unresolved. Here we use a combination of retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, and in vivo optogenetics with localized pharmacology to identify neural substrates downstream of increased tonic LC-NE activity in mice. We demonstrate that photostimulation of LC-NE fibers in the BLA evokes norepinephrine release in the basolateral amygdala (BLA), alters BLA neuronal activity, conditions aversion, and increases anxiety-like behavior. Additionally, we report that β-adrenergic receptors mediate the anxiety-like phenotype of increased NE release in the BLA. These studies begin to illustrate how the complex efferent system of the LC-NE system selectively mediates behavior through distinct receptor and projection-selective mechanisms.

  6. Both a Nicotinic Single Nucleotide Polymorphism (SNP) and a Noradrenergic SNP Modulate Working Memory Performance when Attention is Manipulated

    OpenAIRE

    Greenwood, Pamela M.; Sundararajan, Ramya; Lin, Ming-Kuan; Kumar, Reshma; Fryxell, Karl J.; Parasuraman, Raja

    2009-01-01

    We investigated the relation between the two systems of visuospatial attention and working memory by examining the effect of normal variation in cholinergic and noradrenergic genes on working memory performance under attentional manipulation. We previously reported that working memory for location was impaired following large location precues, indicating the scale of visuospatial attention has a role in forming the mental representation of the target. In one of the first studies to compare ef...

  7. Noradrenergic System in Down Syndrome and Alzheimer's Disease A Target for Therapy.

    Science.gov (United States)

    Phillips, Cristy; Fahimi, Atoossa; Das, Devsmita; Mojabi, Fatemeh S; Ponnusamy, Ravikumar; Salehi, Ahmad

    2016-01-01

    Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimer's disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regions vital for cognition, mood, and executive function. While the mechanisms by which NE-ergic abnormalities contribute to cognitive dysfunction are not fully understood, emergent evidence suggests that rescue of NE-ergic system can attenuate neuropathology and cognitive decline in both AD and DS. Therapeutic strategies to enhance NE neurotransmission have undergone limited testing. Among those deployed to date are NE reuptake inhibitors, presynaptic α-adrenergic receptor antagonists, NE prodrugs, and β-adrenergic agonists. Here we examine alterations in the NE-ergic system in AD and DS and suggest that NE-ergic system rescue is a plausible treatment strategy for targeting cognitive decline in both disorders.

  8. Noradrenergic facilitation of shock-probe defensive burying in lateral septum of rats, and modulation by chronic treatment with desipramine.

    Science.gov (United States)

    Bondi, Corina O; Barrera, Gabriel; Lapiz, M Danet S; Bedard, Tania; Mahan, Amy; Morilak, David A

    2007-03-30

    We have previously shown that acute stress-induced release of norepinephrine (NE) facilitates anxiety-like behavioral responses to stress, such as reduction in open-arm exploration on the elevated-plus maze and in social behavior on the social interaction test. Since these responses represent inhibition of ongoing behavior, it is important to also address whether NE facilitates a response that represents an activation of behavior. Correspondingly, it is unknown how a chronic elevation in tonic steady-state noradrenergic (NA) neurotransmission induced by NE reuptake blockade might alter this acute modulatory function, a regulatory process that may be pertinent to the anxiolytic effects of NE reuptake blockers such as desipramine (DMI). Therefore, in this study, we investigated noradrenergic modulation of the shock-probe defensive burying response in the lateral septum (LS). In experiment 1, shock-probe exposure induced an acute 3-fold increase in NE levels measured in LS of male Sprague-Dawley rats by microdialysis. Shock-probe exposure also induced a modest rise in plasma ACTH, taken as an indicator of perceived stress, that returned to baseline more rapidly in rats that were allowed to bury the probe compared to rats prevented from burying by providing them with minimal bedding, indicating that the active defensive burying behavior is an effective coping strategy that reduces the impact of acute shock probe-induced stress. In experiment 2, blockade of either alpha(1)- or beta-adrenergic receptors in LS by local antagonist microinjection immediately before testing reduced defensive burying and increased immobility. In the next experiment, chronic DMI treatment increased basal extracellular NE levels in LS, and attenuated the acute shock probe-induced increase in NE release in LS relative to baseline. Chronic DMI treatment decreased shock-probe defensive burying behavior in a time-dependent manner, apparent only after 2 weeks or more of drug treatment. Moreover

  9. Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities.

    Science.gov (United States)

    Katayama, K; Yamada, K; Ornthanalai, V G; Inoue, T; Ota, M; Murphy, N P; Aruga, J

    2010-02-01

    Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an alpha2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plus-maze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.

  10. Changes of the rats’ heart rate variability caused by chlorpromazine modulation of central noradrenergic neurotransmission during prolonged stress

    Directory of Open Access Journals (Sweden)

    O. Z. Мelnikova

    2012-03-01

    Full Text Available It’s established that under the prolonged stress there were changes of geometric and spectral indices of the rats’ heart rate variability (HRV, manifestations of which depended on duration of stressful factors acting and represented the stress reaction development from the stage of anxiety to the exhaustion phase. Application of chlorpromazine at the beginning and against the background of stress blocked the central alpha adrenoceptors and contributed to renewal of the most HRV indices into the limits of control values at the end of experiment. The results of research show that the modulation of functional state of central noradrenergic system plays a great role in the changes of HRV during prolonged stress.

  11. Dissociable roles of glucocorticoid and noradrenergic activation on social discounting.

    Science.gov (United States)

    Margittai, Zsofia; van Wingerden, Marijn; Schnitzler, Alfons; Joëls, Marian; Kalenscher, Tobias

    2018-04-01

    People often exhibit prosocial tendencies towards close kin and friends, but generosity decreases as a function of increasing social distance between donor and recipient, a phenomenon called social discounting. Evidence suggests that acute stress affects prosocial behaviour in general and social discounting in particular. We tested the causal role of the important stress neuromodulators cortisol (CORT) and noradrenaline (NA) in this effect by considering two competing hypotheses. On the one hand, it is possible that CORT and NA act in concert to increase generosity towards socially close others by reducing the aversiveness of the cost component in costly altruism and enhancing the emotional salience of vicarious reward. Alternatively, it is equally plausible that CORT and NA exert dissociable, opposing effects on prosocial behaviour based on prior findings implicating CORT in social affiliation, and NA in aggressive and antagonistic tendencies. We pharmacologically manipulated CORT and NA levels in a sample of men (N = 150) and found that isolated hydrocortisone administration promoted prosocial tendencies towards close others, reflected in an altered social discount function, but this effect was offset by concurrent noradrenergic activation brought about by simultaneous yohimbine administration. These results provide inceptive evidence for causal, opposing roles of these two important stress neuromodulators on prosocial behaviour, and give rise to the possibility that, depending on the neuroendocrine response profile, stress neuromodulator action can foster both tend-and-befriend and fight-or-flight tendencies at the same time. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Glucocorticoids interact with the noradrenergic arousal system in the nucleus accumbens shell to enhance memory consolidation of both appetitive and aversive taste learning.

    Science.gov (United States)

    Wichmann, Romy; Fornari, Raquel V; Roozendaal, Benno

    2012-09-01

    It is well established that glucocorticoid hormones strengthen the consolidation of long-term memory of emotionally arousing experiences but have little effect on memory of low-arousing experiences. Although both positive and negative emotionally arousing events tend to be well remembered, studies investigating the neural mechanism underlying glucocorticoid-induced memory enhancement focused primarily on negatively motivated training experiences. In the present study we show an involvement of glucocorticoids within the nucleus accumbens (NAc) in enhancing memory consolidation of both an appetitive and aversive form of taste learning. The specific glucocorticoid receptor (GR) agonist RU 28362 (1 or 3ng) administered bilaterally into the NAc shell, but not core, of male Sprague-Dawley rats immediately after an appetitive saccharin drinking experience dose-dependently enhanced 24-h retention of the safe taste, resulting in a facilitated attenuation of neophobia. Similarly, GR agonist infusions given into the NAc shell immediately after pairing of the saccharin taste with a malaise-inducing agent enhanced memory of this negative experience, resulting in an intensified conditioned aversion. Importantly, a suppression of noradrenergic activity within the NAc shell with the β-adrenoceptor antagonist propranolol blocked the facilitating effect of a concurrently administered GR agonist on memory consolidation in both the appetitive and aversive learning task. Thus, these findings indicate that GR activation interacts with the noradrenergic arousal system within the NAc to enhance memory consolidation of emotionally arousing training experiences regardless of valence. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Opioid and noradrenergic contributions of tapentadol to the inhibition of locus coeruleus neurons in the streptozotocin rat model of polyneuropathic pain.

    Science.gov (United States)

    Torres-Sanchez, Sonia; Borges, Gisela Da Silva; Mico, Juan A; Berrocoso, Esther

    2018-06-01

    Tapentadol is an analgesic that acts as an agonist of µ opioid receptors (MOR) and that inhibits noradrenaline reuptake. Data from healthy rats show that tapentadol inhibits neuronal activity in the locus coeruleus (LC), a nucleus regulated by both the noradrenergic and opioid systems. Thus, we set out to investigate the effect of tapentadol on LC activity in streptozotocin (STZ)-induced diabetic rats, a model of diabetic polyneuropathy, by analyzing single-unit extracellular recordings of LC neurons. Four weeks after inducing diabetes, tapentadol dose-response curves were obtained from animals pre-treated with RX821002 or naloxone (alpha2-adrenoceptors and opioid receptors antagonists, respectively). In STZ rats, the spontaneous activity of LC neurons (0.9 ± 0.1 Hz) was lower than in naïve animals (1.5 ± 0.1 Hz), and tapentadol's inhibitory effect was also weaker. Alpha2-adrenoceptors blockade by RX821002 (100 μg/kg i.v.) in STZ animals significantly increased the spontaneous activity (from 0.8 ± 0.1 to 1.4 ± 0.2 Hz) and it dampened the inhibition of LC neurons produced by tapentadol. However, opioid receptors blockade following naloxone pre-treatment (5 mg/kg i.v.) did not alter the spontaneous firing rate (0.9 ± 0.2 vs 0.9 ± 0.2 Hz) or the inhibitory effect of tapentadol on LC neurons in STZ animals. Thus, diabetic polyneuropathy appears to exert neuroplastic changes in LC neurotransmission, enhancing the sensitivity of alpha2-adrenoceptors and dampening opioid receptors expression. Tapentadol's activity seems to be predominantly mediated through its noradrenergic effects rather than its influence on opioid receptors in the STZ model of diabetic polyneuropathy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Evaluation of the noradrenergic pathway and alpha-2 and beta-receptors in the modulation of the analgesia induced by transcutaneous electric nerve stimulation of high and low frequencies

    OpenAIRE

    Vasconcellos, Thiago Henrique Ferreira; Pantaleão, Patricia de Fátima; Teixeira, Dulcinéa Gonçalves; Santos, Ana Paula; Ferreira, Célio Marcos dos Reis

    2014-01-01

    Transcutaneous electric nerve stimulation is a noninvasive method used in clinical Physiotherapy to control acute or chronic pain. Different theories have been proposed to explain the mechanism of the analgesic action of transcutaneous electric nerve stimulation, as the participation of central and peripheral neurotransmitters. The aim of this study was to evaluate the involvement of noradrenergic pathway and of the receptors alfa-2 and beta in the modulation of analgesia produced by transcut...

  15. Chronic treatment with prazosin or duloxetine lessens concurrent anxiety-like behavior and alcohol intake: evidence of disrupted noradrenergic signaling in anxiety-related alcohol use.

    Science.gov (United States)

    Skelly, Mary J; Weiner, Jeff L

    2014-07-01

    Alcohol use disorders have been linked to increased anxiety, and enhanced central noradrenergic signaling may partly explain this relationship. Pharmacological interventions believed to reduce the excitatory effects of norepinephrine have proven effective in attenuating ethanol intake in alcoholics as well as in rodent models of ethanol dependence. However, most preclinical investigations into the effectiveness of these drugs in decreasing ethanol intake have been limited to acute observations, and none have concurrently assessed their anxiolytic effects. The purpose of these studies was to examine the long-term effectiveness of pharmacological interventions presumed to decrease norepinephrine signaling on concomitant ethanol self-administration and anxiety-like behavior in adult rats with relatively high levels of antecedent anxiety-like behavior. Adult male Long-Evans rats self-administered ethanol on an intermittent access schedule for eight to ten weeks prior to being implanted with osmotic minipumps containing either an a1-adrenoreceptor antagonist (prazosin, 1.5 mg/kg/day), a β1/2-adrenoreceptor antagonist (propranolol, 2.5 mg/kg/day), a serotonin/norepinephrine reuptake inhibitor (duloxetine, 1.5 mg/kg/day) or vehicle (10% dimethyl sulfoxide). These drugs were continuously delivered across four weeks, during which animals continued to have intermittent access to ethanol. Anxiety-like behavior was assessed on the elevated plus maze before treatment and again near the end of the drug delivery period. Our results indicate that chronic treatment with a low dose of prazosin or duloxetine significantly decreases ethanol self-administration (P chronic treatment with putative inhibitors of central noradrenergic signaling may attenuate ethanol intake via a reduction in anxiety-like behavior.

  16. Presynaptic beta-adrenoceptors in guinea pig papillary muscle: evidence for adrenaline-mediated positive feedback on noradrenergic transmission

    International Nuclear Information System (INIS)

    Valenta, B.; Singer, E.A.

    1991-01-01

    Guinea pig papillary muscles were preincubated in the presence of 5 x 10 - 9 mol/L unlabeled noradrenaline or adrenaline then incubated with ( 3 H)-noradrenaline and superfused. Electrical field stimulation with 180 pulses delivered at 1 or 3 Hz was used to induce overflow of radioactivity. Comparison of the effects of preexposure of the tissue to adrenaline or noradrenaline revealed that adrenaline incubation caused an enhancement of stimulation-evoked overflow of ( 3 H)noradrenaline and a reduction of the effect of exogenously added isoprenaline. Furthermore, the selective beta 2-adrenoceptor antagonist ICI 118,551 (10 - 7 mol/L), but not the selective beta 1-adrenoceptor antagonist ICI 89,406 (10 - 7 mol/L), reduced electrically evoked overflow of ( 3 H)noradrenaline in tissue preincubated with adrenaline but not in tissue preincubated with noradrenaline. The overflow-reducing effect of ICI 118.551 occurred at stimulation with 3 Hz but not at stimulation with 1 Hz. The present results support the hypothesis that noradrenergic transmission in guinea pig papillary muscle is facilitated via beta 2-adrenoceptors, and that adrenaline may serve as transmitter in this positive feedback mechanism after its incorporation into sympathetic nerves

  17. Performance of 12Ah aerospace nickel-cadmium cells of design variable groups

    Science.gov (United States)

    Vasanth, K. L.

    1985-01-01

    The design variable program of NASA is a systematic approach to evaluate the performance of 12Ah aerospace nickel-cadmium cells of 9 important cell designs. These cells were life cycled in a Low-Earth Orbit (LEO) regime for 3 to 4 years. Representative cells taken from the design variable groups after different cycling periods have been examined. The results show that: (1) positive swelling and carbonate content in the electrolyte increases as a function of the number of cycles, (2) electrolyte distribution follows the order NEG greater than POS greater than SEP, 3) control and no PQ groups outperformed the rest of the groups and (4) the polypropylene group shows very heavy cadmium migration and poor performance.

  18. Alleviation of response suppression to conditioned aversive stimuli by lesions of the dorsal noradrenergic bundle.

    Science.gov (United States)

    Tsaltas, E; Gray, J A; Fillenz, M

    1984-08-01

    Rats with neurotoxic lesions of the dorsal ascending noradrenergic bundle (DB) were compared with sham-operated (SH) controls on the acquisition, steady state and extinction of response suppression maintained by a classical (conditioned suppression) or an instrumental (discriminated punishment) contingency. DB lesions interfered neither with the acquisition of the reference response of sucrose-rewarded barpressing nor with unconditioned responding to the overhead flashing light subsequently used as a signal of shock. The acquisition of discriminated response suppression was also unaffected by the lesion under both types of contingency. However, once discriminated suppression had stabilized, both the conditioned and the discriminative stimulus used were significantly less effective in maintaining suppression in DB animals than in SH controls provided that low intensity footshock (0.2 mA) was used as the unconditioned stimulus (UCS). Upon increase of UCS intensity (to 0.5 mA) normal suppression was observed in the DB group under both contingencies. Extinction of the classical contingency reinstated the difference between DB and SH performance: DB lesion resulted in significantly faster extinction of fear. In contrast, extinction of the discriminated punishment contingency was unaffected by the lesion, although generalized response suppression dissipated faster in the DB than in the SH animals trained under this condition. Our results offer no support for the reinforcement hypothesis of DB function (normal acquisition of barpressing and of discriminated suppression of barpressing); mixed support (greater initial generalization of suppression in DB animals) and contradiction (more rapid extinction of conditioned suppression in DB animals) for the attentional hypothesis; and weak support (reduced suppression and more rapid extinction of suppression in DB animals, but only within limited experimental parameters) for the anxiety hypothesis of DB function. Hence none of

  19. Two-group Current-equivalent Parameters for Control Rod Cells. Autocode Programme CRCC

    Energy Technology Data Exchange (ETDEWEB)

    Norinder, O; Nyman, K

    1962-06-15

    In two-group neutron diffusion calculations there is mostly necessary to describe the influence of control rods by equivalent homogeneous two-group parameters in regions about the control rods. The problem is solved for a control rod in a medium characterized by two-group parameters. The property of fast and thermal neutr. on current equivalence is selected to obtain equivalent two-group parameters for a homogeneous cell with the same radius as the control rod cell. For the parameters determined one obtains the same fast and thermal neutron current into the rod cell and the equivalent cell independent of the fast and thermal flux amplitudes on the cell boundaries. The equivalent parameters are obtained as a solution of a system of transcendental equations. A Ferranti Mercury Autocode performing the solution is described. Calculated equivalent parameters for control rods in a heavy water lattice are given for some representative cases.

  20. Involvement of noradrenergic and corticoid receptors in the consolidation of the lasting anxiogenic effects of predator stress.

    Science.gov (United States)

    Adamec, R; Muir, C; Grimes, M; Pearcey, K

    2007-05-16

    The roles of beta-NER (beta-noradrenergic receptor), GR (glucocorticoid) and mineral corticoid receptors (MR) in the consolidation of anxiogenic effects of predator stress were studied. One minute after predator stress, different groups of rats were injected (ip) with vehicle, propranolol (beta-NER blocker, 5 and 10 mg/kg), mifepristone (RU486, GR blocker, 20 mg/kg), spironolactone (MR blocker, 50 mg/kg), propranolol (5 mg/kg) plus RU486 (20 mg/kg) or the anxiolytic, chloradiazepoxide (CPZ, 10 mg/kg). One week later, rodent anxiety was assessed in elevated plus maze, hole board, light/dark box, social interaction and acoustic startle. Considering all tests except startle, propranolol dose dependently blocked consolidation of lasting anxiogenic effects of predator stress in all tests. GR receptor block alone was ineffective. However, GR block in combination with an ineffective dose of propranolol did blocked consolidation of predator stress effects in all tests, suggesting a synergism between beta-NER and GR. Surprisingly, MR block prevented consolidation of anxiogenic effects in all tests except the light/dark box. CPZ post stress was ineffective against the anxiogenic impact of predator stress. Study of startle was complicated by the fact that anxiogenic effects of stress on startle amplitude manifested as both an increase and a decrease in startle amplitude. Suppression of startle occurred in stressed plus vehicle injected groups handled three times prior to predator stress. In contrast, stressed plus vehicle rats handled five times prior to predator stress showed increases in startle, as did all predator stressed only groups. Mechanisms of consolidation of the different startle responses appear to differ. CPZ post stress blocked startle suppression but not enhancement of startle. Propranolol post stress had no effect on either suppression or enhancement of startle. GR block alone post stress prevented suppression of startle, but not enhancement. In contrast

  1. Effects of lesions of the dorsal noradrenergic bundle on conditioned suppression to a CS and to a contextual background stimulus.

    Science.gov (United States)

    Tsaltas, E; Schugens, M M; Gray, J A

    1989-01-01

    The aim of the experiment was to determine whether the dorsal noradrenergic bundle (DB) plays a role in conditioning to context. Rats received either bilateral lesions of the DB by local injection of 6-hydroxydopamine, vehicle injections only, or sham operations. All animals were then trained to barpress for food on a variable interval (VI) schedule. Two 5-min intrusion periods were superimposed on the VI baseline during each session. An 'envelope' stimulus (flashing light) was on throughout each intrusion period. In addition, embedded in the two intrusion periods of each session, there occurred 8 presentations of a 'punctate' conditioned stimulus (CS) (a 15-s clicker), and 8 presentations of a 0.5-s footshock. Within each surgical condition rats were randomly allocated to one of three conditioning groups, receiving 100%, 50% or 0% temporal association between CS and shock. Conditioning to the punctate CS and to the context provided by the envelope stimulus was assessed by the degree of suppression of the barpress response relative to the VI baseline. Responding was most suppressed in the punctate CS in the 100 and 50% conditions, and most suppressed in the envelope stimulus in the 0% condition. DB lesions released response suppression to the punctate CS, had no effect on suppression to the envelope stimulus, and reduced sensitivity to CS-shock probability as measured by response suppression during the punctate CS. These results confirm previous reports that DB lesions alleviate response suppression to shock-associated cues, identify some of the parameters that affect this phenomenon, but fail to support a role for the DB in contextual conditioning.

  2. Host-cell reactivation of ultraviolet-irradiated SV 40 DNA in five complementation groups of xeroderma pigmentosum

    International Nuclear Information System (INIS)

    Abrahams, P.J.; Eb, A.J. van der

    1976-01-01

    Host-cell reactivation of UV-irradiated double-stranded SV40 DNA was studied in BSC-1 monkey cells, normal human cells, heterozygous Xeroderma pigmentosum xp cells, representative cell strains of the five complemention groups of XP and in XP 'variant' cells. The following percentages of survival of the plaque-forming ability of double-stranded SV40 DNA were found in XP cells compared with the value found in normal monkey and human cells: groupA, 13%; group B, 30%; group C, 18%; group D, 14%; group E, 59%; and in the heterozygous XP cells almost 100%. The survival in XP 'variant' cells was 66%. The survival of single-stranded SV40 DNA in BSC-1 cells was much lower than that of double-stranded SV40 DNA in XP cells of complementation group A, which possibly indicates that some repair of UV damage occurs even in XP cells of group A

  3. Pattern of distribution of blood group antigens on human epidermal cells during maturation

    DEFF Research Database (Denmark)

    Dabelsteen, Erik; Buschard, Karsten; Hakomori, Sen-Itiroh

    1984-01-01

    The distribution in human epidermis of A, B, and H blood group antigens and of a precursor carbohydrate chain, N-acetyl-lactosamine, was examined using immunofluorescence staining techniques. The material included tissue from 10 blood group A, 4 blood group B, and 9 blood group O persons. Murine...... on the lower spinous cells whereas H antigen was seen predominantly on upper spinous cells or on the granular cells. Epithelia from blood group A or B persons demonstrated A or B antigens, respectively, but only if the tissue sections were trypsinized before staining. In such cases A or B antigens were found...... monoclonal antibodies were used to identify H antigen (type 2 chain) and N-acetyl-lactosamine. Human antisera were used to identify A and B antigens. In all groups N-acetyl-lactosamine and H antigen were found on the cell membranes of the spinous cell layer. N-acetyl-lactosamine was present mainly...

  4. mCell: Facilitating Mobile Communication of Small Groups

    OpenAIRE

    Mikko T. Tarkiainen; Jonna Häkkilä; Jan Blom; Merja Haveri; Jyri Virtanen

    2008-01-01

    Mobile communication technology offers a potential platform for new types of communication applications. Here, we describe the development and experiences with a mobile group communication application, mCell, that runs on a mobile phone. We present the underlying design implications, the application implementation, and a user study, where three groups used the application for one month. The findings of the user study reveal general user experiences with the application and show different patt...

  5. Stabilization of Transfected Cells Expressing Low-Incidence Blood Group Antigens: Novel Methods Facilitating Their Use as Reagent-Cells.

    Directory of Open Access Journals (Sweden)

    Cecilia González

    Full Text Available The identification of erythrocyte antibodies in the serum of patients rely on panels of human red blood cells (RBCs, which coexpress many antigens and are not easily available for low-incidence blood group phenotypes. These problems have been addressed by generating cell lines expressing unique blood group antigens, which may be used as an alternative to human RBCs. However, the use of cell lines implies several drawbacks, like the requirement of cell culture facilities and the high cost of cryopreservation. The application of cell stabilization methods could facilitate their use as reagent cells in clinical laboratories.We generated stably-transfected cells expressing low-incidence blood group antigens (Dia and Lua. High-expresser clones were used to assess the effect of TransFix® treatment and lyophilization as cell preservation methods. Cells were kept at 4°C and cell morphology, membrane permeability and antigenic properties were evaluated at several time-points after treatment.TransFix® addition to cell suspensions allows cell stabilization and proper antigen detection for at least 120 days, despite an increase in membrane permeability and a reduction in antigen expression levels. Lyophilized cells showed minor morphological changes and antigen expression levels were rather conserved at days 1, 15 and 120, indicating a high stability of the freeze-dried product. These stabilized cells have been proved to react specifically with human sera containing alloantibodies.Both stabilization methods allow long-term preservation of the transfected cells antigenic properties and may facilitate their distribution and use as reagent-cells expressing low-incidence antigens, overcoming the limited availability of such rare RBCs.

  6. Calcium-independent phospholipase A₂, group VIA, is critical for RPE cell survival

    DEFF Research Database (Denmark)

    Kolko, Miriam; Vohra, Rupali; Westlund, Barbro S.

    2014-01-01

    PURPOSE: To investigate the significance of calcium-independent phospholipase A₂, group VIA (iPLA2-VIA), in RPE cell survival following responses to sodium iodate (SI) in cell cultures. METHODS: The human retinal pigment epithelium (RPE) cell line (ARPE-19) cells and primary mouse-RPE cultures were...

  7. Homogenisation of a Wigner-Seitz cell in two group diffusion theory

    International Nuclear Information System (INIS)

    Allen, F.R.

    1968-02-01

    Two group diffusion theory is used to develop a theory for the homogenisation of a Wigner-Seitz cell, neglecting azimuthal flux components of higher order than dipoles. An iterative method of solution is suggested for linkage with reactor calculations. The limiting theory for no cell leakage leads to cell edge flux normalisation of cell parameters, the current design method for SGHW reactor design calculations. Numerical solutions are presented for a cell-plus-environment model with monopoles only. The results demonstrate the exact theory in comparison with the approximate recipes of normalisation to cell edge, moderator average, or cell average flux levels. (author)

  8. Lysis of cells infected with typhus group rickettsiae by a human cytotoxic T cell clone

    International Nuclear Information System (INIS)

    Carl, M.; Robbins, F.; Hartzman, R.J.; Dasch, G.A.

    1987-01-01

    Cytolytic human T cells clones generated in response to the intracellular bacterium Rickettsia typhi were characterized. Growing clones were tested for their ability to proliferate specifically in response to antigens derived from typhus group rickettsiae or to lyse targets infected with R. typhi or Rickettsia prowazekii, as measured by 51 Cr-release from target cells. Two clones were able to lyse targets infected with typhus group rickettsiae. One of these clones was more fully characterized because of its rapid growth characteristics. This cytolytic clone was capable of lysing an autologous infected target as well as a target matched for class I and II histocompatibility leukocyte antigens (HLA). It was not capable, however, of lysing either a target mismatched for both class I and II HLA or a target partially matched for class I HLA. In addition, the clone exhibited specificity in that it was able to lyse an autologous target infected with typhus group rickettsiae, but did not lyse an autologous target infected with an antigenically distinct rickettsial species, Rickettsia tsutsugamushi. These results demonstrate, for the first time, that cells infected with intracellular bacteria can be lysed by human cytotoxic T lymphocytes

  9. Norepinephrine stimulates progesterone production in highly estrogenic bovine granulosa cells cultured under serum-free, chemically defined conditions.

    Science.gov (United States)

    Piccinato, Carla A; Montrezor, Luis H; Collares, Cristhianna A V; Vireque, Alessandra A; Rosa e Silva, Alzira A M

    2012-11-22

    Since noradrenergic innervation was described in the ovarian follicle, the actions of the intraovarian catecholaminergic system have been the focus of a variety of studies. We aimed to determine the gonadotropin-independent effects of the catecholamine norepinephrine (NE) in the steroid hormone profile of a serum-free granulosa cell (GC) culture system in the context of follicular development and dominance. Primary bovine GCs were cultivated in a serum-free, chemically defined culture system supplemented with 0.1% polyvinyl alcohol. The culture features were assessed by hormone measurements and ultrastructural characteristics of GCs. GCs produced increasing amounts of estradiol and pregnenolone for 144h and maintained ultrastructural features of healthy steroidogenic cells. Progesterone production was also detected, although it significantly increased only after 96h of culture. There was a highly significant positive correlation between estradiol and pregnenolone production in high E2-producing cultures. The effects of NE were further evaluated in a dose-response study. The highest tested concentration of NE (10 (-7) M) resulted in a significant increase in progesterone production, but not in estradiol or pregnenolone production. The specificity of NE effects on progesterone production was further investigated by incubating GCs with propranolol (10 (-8) M), a non-selective beta-adrenergic antagonist. The present culture system represents a robust model to study the impact of intrafollicular factors, such as catecholamines, in ovarian steroidogenesis and follicular development. The results of noradrenergic effects in the steroidogenesis of GC have implications on physiological follicular fate and on certain pathological ovarian conditions such as cyst formation and anovulation.

  10. Development of end group for 1.3 GHZ nine cell SCRF cavity

    International Nuclear Information System (INIS)

    Yedle, Ajay; Bagre, Manish; Maurya, Tilak; Yadav, Anand; Puntambekar, Avinash; Mahawar, Ashish; Mohania, Praveen; Shrivastava, Purushottam; Joshi, Satish Chandra

    2013-01-01

    Raja Ramanna Centre for Advanced Technology (RRCAT) is developing 1.3 GHz superconducting radio frequency (SCRF) cavities as part of SCRF technology development. The 1.3 GHz nine cell SCRF cavities comprise of multiple cells and end groups at each end. These end groups are important parts of a multi-cell cavity. They serve as interface for putting RF power to cavity, pick up the signal for various RF control and have higher order modes (HOM) coupler. The multiple parts with intricate shape, complex weld geometry and stringent RF requirements pose various challenges in their manufacturing. This paper presents the efforts on development of end groups comprising of manufacturing of various parts, their fabrication by electron beam welding process and pre-qualification including mechanical measurement, vacuum leak testing RF measurement. (author)

  11. Group 1 innate lymphoid cells in Toxoplasma gondii infection.

    Science.gov (United States)

    Dunay, I R; Diefenbach, A

    2018-02-01

    Innate lymphoid cells (ILCs) are a group of lymphocytes that carry out important functions in immunity to infections and in organ homeostasis at epithelial barrier surfaces. ILCs are innate immune cells that provide an early source of cytokines to initiate immune responses against pathogens. Cytotoxic ILCs (i.e. conventional (c)NK cells) and several subsets of helper-like ILCs are the major branches of the ILC family. Conventional NK cells and group 1 ILCs share several characteristics such as surface receptors and the ability to produce IFN-γ upon activation, but they differ in their developmental paths and in their dependence on specific transcription factors. Infection of mice with the intracellular parasite Toxoplasma gondii is followed by a strong Th1-mediated immune response. Previous studies indicate that NK1.1 + cells contribute to the production of IFN-γ and TNF and cytotoxicity during acute T. gondii infection. Upon oral infection, the parasite infects intestinal enterocytes, and within the lamina propria, innate immune responses lead to initial parasite control although the infection disseminates widely and persists long-term in immune privileged sites despite adaptive immunity. Upon parasite entry into the small intestine, during the acute stage, ILC1 produce high levels of IFN-γ and TNF protecting barrier surfaces, thus essentially contributing to early parasite control. We will discuss here the role of innate lymphocytes during T. gondii infection in the context of the only recently appreciated diversity of ILC subsets. © 2018 John Wiley & Sons Ltd.

  12. A consistent homogenization procedure to obtain few-group cell parameters

    International Nuclear Information System (INIS)

    Pierini, G.

    1979-01-01

    The criterion, according to which one heterogeneous and one homogeneous cell are equivalent if they have the same boundary values of both the flux and the normal components of the current, is used to homogenize radially an axially infinite cylindrical cell, with azimuth independent properties and moderatur adequately described by diffusion theory. The method, which leads to the definition of a full matrix of diffusion coefficients, provides a new and simple definition of the few-group cell parameters, which are nearly independent of the environment. (orig.) [de

  13. Beta adrenergic blockade reduces utilitarian judgement

    Science.gov (United States)

    Sylvia, Terbeck; Guy, Kahane; Sarah, McTavish; Julian, Savulescu; Neil, Levy; Miles, Hewstone; Cowen, Philip J.

    2013-01-01

    Noradrenergic pathways are involved in mediating the central and peripheral effects of physiological arousal. The aim of the present study was to investigate the role of noradrenergic transmission in moral decision-making. We studied the effects in healthy volunteers of propranolol (a noradrenergic beta-adrenoceptor antagonist) on moral judgement in a set of moral dilemmas pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person) in a double-blind, placebo-controlled, parallel group design. Propranolol (40 mg orally) significantly reduced heart rate, but had no effect on self-reported mood. Importantly, propranolol made participants more likely to judge harmful actions as morally unacceptable, but only in dilemmas where harms were ‘up close and personal’. In addition, longer response times for such personal dilemmas were only found for the placebo group. Finally, judgments in personal dilemmas by the propranolol group were more decisive. These findings indicate that noradrenergic pathways play a role in responses to moral dilemmas, in line with recent work implicating emotion in moral decision-making. However, contrary to current theorising, these findings also suggest that aversion to harming is not driven by emotional arousal. Our findings are also of significant practical interest given that propranolol is a widely used drug in different settings, and is currently being considered as a potential treatment for post-traumatic stress disorder in military and rescue service personnel. PMID:23085134

  14. Noradrenaline decreases spike voltage threshold and induces electrographic sharp waves in turtle medial cortex in vitro.

    Science.gov (United States)

    Lorenzo, Daniel; Velluti, Julio C

    2004-01-01

    The noradrenergic modulation of neuronal properties has been described at different levels of the mammalian brain. Although the anatomical characteristics of the noradrenergic system are well known in reptiles, functional data are scarce. In our study the noradrenergic modulation of cortical electrogenesis in the turtle medial cortex was studied in vitro using a combination of field and intracellular recordings. Turtle EEG consists of a low voltage background interspersed by spontaneous large sharp waves (LSWs). Noradrenaline (NA, 5-40 microM) induced (or enhanced) the generation of LSWs in a dose-dependent manner. Pharmacological experiments suggest the participation of alpha and beta receptors in this effect. In medial cortex neurons NA induced a hyperpolarization of the resting potential and a decrease of input resistance. Both effects were observed also after TTX treatment. Noradrenaline increased the response of the cells to depolarizing pulses, resulting in an upward shift of the frequency/current relation. In most cells the excitability change was mediated by a decrease of the spike voltage threshold resulting in the reduction of the amount of depolarization needed to fire the cell (voltage threshold minus resting potential). As opposed to the mechanisms reported in mammalian neurons, no changes in the frequency adaptation or the post-train afterhyperpolarization were observed. The NA effects at the cellular level were not reproduced by noradrenergic agonists. Age- and species-dependent properties in the pharmacology of adrenergic receptors could be involved in this result. Cellular effects of NA in turtle cortex are similar to those described in mammals, although the increase in cellular excitability seems to be mediated by a different mechanism. Copyright 2004 S. Karger AG, Basel

  15. Short-term serotonergic but not noradrenergic antidepressant administration reduces attentional vigilance to threat in healthy volunteers.

    Science.gov (United States)

    Murphy, Susannah E; Yiend, Jenny; Lester, Kathryn J; Cowen, Philip J; Harmer, Catherine J

    2009-03-01

    Anxiety is associated with threat-related biases in information processing such as heightened attentional vigilance to potential threat. Such biases are an important focus of psychological treatments for anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of a range of anxiety disorders. The aim of this study was to assess the effect of an SSRI on the processing of threat in healthy volunteers. A selective noradrenergic reuptake inhibitor (SNRI), which is not generally used in the treatment of anxiety, was used as a contrast to assess the specificity of SSRI effects on threat processing. Forty-two healthy volunteers were randomly assigned to 7 d double-blind intervention with the SSRI citalopram (20 mg/d), the SNRI reboxetine (8 mg/d), or placebo. On the final day, attentional and interpretative bias to threat was assessed using the attentional probe and the homograph primed lexical decision tasks. Citalopram reduced attentional vigilance towards fearful faces but did not affect the interpretation of ambiguous homographs as threatening. Reboxetine had no significant effect on either of these measures. Citalopram reduces attentional orienting to threatening stimuli, which is potentially relevant to its clinical use in the treatment of anxiety disorders. This finding supports a growing literature suggesting that an important mechanism through which pharmacological agents may exert their effects on mood is by reversing the cognitive biases that characterize the disorders that they treat. Future studies are needed to clarify the neural mechanisms through which these effects on threat processing are mediated.

  16. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells

    Science.gov (United States)

    Hepworth, Matthew R.; Fung, Thomas C.; Masur, Samuel H.; Kelsen, Judith R.; McConnell, Fiona M.; Dubrot, Juan; Withers, David R.; Hugues, Stephanie; Farrar, Michael A.; Reith, Walter; Eberl, Gerard; Baldassano, Robert N.; Laufer, Terri M.; Elson, Charles O.; Sonnenberg, Gregory F.

    2015-01-01

    Inflammatory CD4+ T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. While selection of self-specific T cells in the thymus limits responses to tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells, and that MHCII+ ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on human colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4+ T cells in the intestine, and suggest that this process is dysregulated in human IBD. PMID:25908663

  17. solving the cell formation problem in group technology

    Directory of Open Access Journals (Sweden)

    Prafulla Joglekar

    2001-01-01

    Full Text Available Over the last three decades, numerous algorithms have been proposed to solve the work-cell formation problem. For practicing manufacturing managers it would be nice to know as to which algorithm would be most effective and efficient for their specific situation. While several studies have attempted to fulfill this need, most have not resulted in any definitive recommendations and a better methodology of evaluation of cell formation algorithms is urgently needed. Prima facie, the methodology underlying Miltenburg and Zhang's (M&Z (1991 evaluation of nine well-known cell formation algorithms seems very promising. The primary performance measure proposed by M&Z effectively captures the objectives of a good solution to a cell formation problem and is worthy of use in future studies. Unfortunately, a critical review of M&Z's methodology also reveals certain important flaws in M&Z's methodology. For example, M&Z may not have duplicated each algorithm precisely as the developer(s of that algorithm intended. Second, M&Z's misrepresent Chandrasekharan and Rajagopalan's [C&R's] (1986 grouping efficiency measure. Third, M&Z's secondary performance measures lead them to unnecessarily ambivalent results. Fourth, several of M&Z's empirical conclusions can be theoretically deduced. It is hoped that future evaluations of cell formation algorithms will benefit from both the strengths and weaknesses of M&Z's work.

  18. Norepinephrine stimulates progesterone production in highly estrogenic bovine granulosa cells cultured under serum-free, chemically defined conditions

    Directory of Open Access Journals (Sweden)

    Piccinato Carla A

    2012-11-01

    Full Text Available Abstract Background Since noradrenergic innervation was described in the ovarian follicle, the actions of the intraovarian catecholaminergic system have been the focus of a variety of studies. We aimed to determine the gonadotropin-independent effects of the catecholamine norepinephrine (NE in the steroid hormone profile of a serum-free granulosa cell (GC culture system in the context of follicular development and dominance. Methods Primary bovine GCs were cultivated in a serum-free, chemically defined culture system supplemented with 0.1% polyvinyl alcohol. The culture features were assessed by hormone measurements and ultrastructural characteristics of GCs. Results GCs produced increasing amounts of estradiol and pregnenolone for 144h and maintained ultrastructural features of healthy steroidogenic cells. Progesterone production was also detected, although it significantly increased only after 96h of culture. There was a highly significant positive correlation between estradiol and pregnenolone production in high E2-producing cultures. The effects of NE were further evaluated in a dose–response study. The highest tested concentration of NE (10 (−7 M resulted in a significant increase in progesterone production, but not in estradiol or pregnenolone production. The specificity of NE effects on progesterone productio n was further investigated by incubating GCs with propranolol (10 (−8 M, a non-selective beta-adrenergic antagonist. Conclusions The present culture system represents a robust model to study the impact of intrafollicular factors, such as catecholamines, in ovarian steroidogenesis and follicular development. The results of noradrenergic effects in the steroidogenesis of GC have implications on physiological follicular fate and on certain pathological ovarian conditions such as cyst formation and anovulation.

  19. Dual-cell reduction and group effect in an internal microelectrolysis reactor

    International Nuclear Information System (INIS)

    Ying, Diwen; Peng, Juan; Li, Kan; Wang, Yalin; Pan, Siwen; Jia, JinPing

    2013-01-01

    Highlights: ► 2,4-DCP was removed simultaneously in cathode and anode cells in IME reactor. ► Mechanism of dual-cell reduction gave an insight of cathode and anode cells. ► Significant V oc increase with one/two electrodes couples being installed in series. ► Group effect reveals possible high redox potential in IME reactor. -- Abstract: To address some of the fundamental questions regarding the functions of cathodes and anodes (e.g., iron and granular active carbon) and what happens when numerous particles (microscopic galvanic cells) are combined in the widely used and efficient wastewater treatment of an internal microelectrolysis (IME) reactor, we employed a specifically designed dual-cell IME reactor with single-couple electrodes and a narrow cell IME reactor with multi-couple electrodes. The simultaneous removal of 6.36 mg L −1 and 2.93 mg L −1 of 2,4-dichlorophenol within 30 min from the graphite cathode and the iron anode cells, respectively, was observed in the dual-cell reactor. The innovative concept behind this phenomenon is that the anode, which is generally believed to be oxidative, could probably be reductive in an IME reactor. Thus, it is important to understand the unique performance of IME reactors. The group effect, which provides a 45% increase of open-circuit potential with just two additional electrode couples in aqueous solution, was tested and verified in a multi-couple electrode reactor. It suggests a complex potential distribution in the IME reactor and that compounds even with high redox potential could possibly be reduced, which was generally believed to be difficult to accomplish

  20. Do ABO blood group antigens hamper the therapeutic efficacy of mesenchymal stromal cells?

    Science.gov (United States)

    Moll, Guido; Hult, Annika; von Bahr, Lena; Alm, Jessica J; Heldring, Nina; Hamad, Osama A; Stenbeck-Funke, Lillemor; Larsson, Stella; Teramura, Yuji; Roelofs, Helene; Nilsson, Bo; Fibbe, Willem E; Olsson, Martin L; Le Blanc, Katarina

    2014-01-01

    Investigation into predictors for treatment outcome is essential to improve the clinical efficacy of therapeutic multipotent mesenchymal stromal cells (MSCs). We therefore studied the possible harmful impact of immunogenic ABO blood groups antigens - genetically governed antigenic determinants - at all given steps of MSC-therapy, from cell isolation and preparation for clinical use, to final recipient outcome. We found that clinical MSCs do not inherently express or upregulate ABO blood group antigens after inflammatory challenge or in vitro differentiation. Although antigen adsorption from standard culture supplements was minimal, MSCs adsorbed small quantities of ABO antigen from fresh human AB plasma (ABP), dependent on antigen concentration and adsorption time. Compared to cells washed in non-immunogenic human serum albumin (HSA), MSCs washed with ABP elicited stronger blood responses after exposure to blood from healthy O donors in vitro, containing high titers of ABO antibodies. Clinical evaluation of hematopoietic stem cell transplant (HSCT) recipients found only very low titers of anti-A/B agglutination in these strongly immunocompromised patients at the time of MSC treatment. Patient analysis revealed a trend for lower clinical response in blood group O recipients treated with ABP-exposed MSC products, but not with HSA-exposed products. We conclude, that clinical grade MSCs are ABO-neutral, but the ABP used for washing and infusion of MSCs can contaminate the cells with immunogenic ABO substance and should therefore be substituted by non-immunogenic HSA, particularly when cells are given to immunocompentent individuals.

  1. A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups

    Science.gov (United States)

    Randolph, Matthew E.; Pavlath, Grace K.

    2015-01-01

    The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies (MDs), such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some MDs. The biology of muscle stem cells varies depending on the muscles with which they are associated. Here we review the biology of skeletal muscle stem cell populations of eight different muscle groups. Understanding the biological variation of skeletal muscles and their resident stem cells could provide valuable insight into mechanisms underlying the susceptibility of certain muscles to myopathic disease. PMID:26500547

  2. HAMMER, 1-D Multigroup Neutron Transport Infinite System Cell Calculation for Few-Group Diffusion Calculation

    International Nuclear Information System (INIS)

    Honeck, H.C.

    1984-01-01

    1 - Description of problem or function: HAMMER performs infinite lattice, one-dimensional cell multigroup calculations, followed (optionally) by one-dimensional, few-group, multi-region reactor calculations with neutron balance edits. 2 - Method of solution: Infinite lattice parameters are calculated by means of multigroup transport theory, composite reactor parameters by few-group diffusion theory. 3 - Restrictions on the complexity of the problem: - Cell calculations - maxima of: 30 thermal groups; 54 epithermal groups; 20 space points; 20 regions; 18 isotopes; 10 mixtures; 3 thermal up-scattering mixtures; 200 resonances per group; no overlap or interference; single level only. - Reactor calculations - maxima of : 40 regions; 40 mixtures; 250 space points; 4 groups

  3. Effects of atomoxetine on attention and impulsivity in the five-choice serial reaction time task in rats with lesions of dorsal noradrenergic ascending bundle.

    Science.gov (United States)

    Liu, Yia-Ping; Huang, Teng-Shun; Tung, Che-Se; Lin, Chen-Cheng

    2015-01-02

    Atomoxetine, a noradrenaline reuptake inhibitor (NRI), which is a non-stimulating medicine that is used for the treatment of patients with attention deficit hyperactivity disorder (ADHD), has been found to be effective in reducing behavioral impulsivity in rodents, but its efficacy in a dorsal noradrenergic ascending bundle (DNAB)-lesioned condition has not been examined. The present study aimed to investigate the effects of DNAB lesions on attention and impulsive control in the five-choice serial reaction time task (5-CSRTT) in rats treated with atomoxetine. The drug-induced changes in noradrenaline efflux in the medial prefrontal cortex were also measured. 5-CSRTT-trained rats were included in one of the following groups: N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)/Atomoxetine, Sham/Atomoxetine, DSP-4/Saline, or Sham/Saline. Acute atomoxetine (0.3 mg/kg) was administered 14 days after the DSP-4 regime. The behavioral testing included manipulations of the inter-trial interval (ITI), stimulation duration and food satiety. In vivo microdialysis of the noradrenaline efflux in the medial prefrontal cortex and the expression of the noradrenaline transporter (NAT) in the DNAB areas were examined. Atomoxetine reduced impulsivity and perseveration in the long-ITI condition with no effects on any other variables. This phenomenon was not influenced by DSP-4 pre-treatment. The DNAB-lesioned rats had lower noradrenaline efflux in the medial prefrontal cortex. DSP-4 caused no change in NAT expression in the DNAB areas. These findings suggested that noradrenaline reuptake may not be exclusively responsible for the atomoxetine effects in adjusting impulsivity. The role of DNAB should also be considered, particularly in conditions requiring greater behavioral inhibition. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells

    Science.gov (United States)

    Benoit, Danielle S. W.; Schwartz, Michael P.; Durney, Andrew R.; Anseth, Kristi S.

    2008-10-01

    Cell-matrix interactions have critical roles in regeneration, development and disease. The work presented here demonstrates that encapsulated human mesenchymal stem cells (hMSCs) can be induced to differentiate down osteogenic and adipogenic pathways by controlling their three-dimensional environment using tethered small-molecule chemical functional groups. Hydrogels were formed using sufficiently low concentrations of tether molecules to maintain constant physical characteristics, encapsulation of hMSCs in three dimensions prevented changes in cell morphology, and hMSCs were shown to differentiate in normal growth media, indicating that the small-molecule functional groups induced differentiation. To our knowledge, this is the first example where synthetic matrices are shown to control induction of multiple hMSC lineages purely through interactions with small-molecule chemical functional groups tethered to the hydrogel material. Strategies using simple chemistry to control complex biological processes would be particularly powerful as they could make production of therapeutic materials simpler, cheaper and more easily controlled.

  5. Effect of runway training on rat brain tyrosine hydroxylase: differential effect of continuous and partial reinforcement schedules.

    Science.gov (United States)

    Boarder, M R; Feldon, J; Gray, J A; Fillenz, M

    1979-12-01

    Previous experiments have implicated ascending noradrenergic systems in the development of the behavioural responses to different patterns of reward. In this report food deprived male Sprague--Dawley rats were trained to run a straight alley for good reward on a continuous reinforcement (CRF) or a partial reinforcement (PRF) schedule. Tyrosine hydroxylase measured in a partially solubilized preparation from hippocampus and hypothalamus at the end of acquisition was not different from controls, indicating that enzyme induction does not occur during either training schedules. However, hippocampal synaptosomal tyrosine hydroxylation rates from the CRF group was significantly higher than from either the PRF group or the handled controls. This indicates that at the end of the acquisition schedule the noradrenergic projection to hippocampus was more active in the CRF group than with the PRF group or the handled control.

  6. Polycomb-group genes sustaining the stem cell activity

    International Nuclear Information System (INIS)

    Takihara, Yoshihiro

    2006-01-01

    Polycomb-group genes (PcG) have a role in constituting the cellular memory mechanisms through which the once expressed phenotypes during development are transmitted thereafter and this review describes, together with authors' findings of sustaining hematopoietic stem cell activity by the PcG products, what molecular bases, involving the control of histone code, are concerned in the memory. Recent investigations have gradually elucidated the outline of epigenetic control mechanisms of the memory: messages are set up as a histone code in the chromatin and the PcG complex recruited by recognition of the code regulates the chromatin structure leading to DNA transcription and maintenance of the phenotype. Proliferation of hematopoietic stem cells ex vivo will be possible if exact and detailed mechanisms for PcG are made clear in future. Such ex vivo techniques are especially awaited for marrow remodeling treatment of hematopoietic failure induced by radiation exposure. (T.I.)

  7. Relevance of blood groups in transfusion of sickle cell disease patients.

    Science.gov (United States)

    Noizat-Pirenne, France

    2013-03-01

    Blood groups are clinically significant in sickle cell disease (SCD) as transfusion remains a key treatment in this pathology. The occurrence of a delayed haemolytic transfusion reaction (DHTR) is not rare and is a life-threatening event. The main cause of DHTR is the production of alloantibodies against red blood cell antigens. The high rate of alloimmunization in SCD patients is mainly due to the differences of red blood groups between patients of African descent, and the frequently Caucasian donors. From an immuno-haematological point of view, DHTR in SCD patients has specific features: classical antibodies known to be haemolytic can be encountered, but otherwise non significant antibodies, autoantibodies and antibodies related to partial and rare blood groups are also frequently found in individuals of African descent. In some cases, there are no detectable antibodies. As alloimmunization remains the main cause of DHTR, it is extremely important to promote blood donation by individuals of African ancestry to make appropriate blood available. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  8. Homophilic and Heterophilic Interactions of Type II Cadherins Identify Specificity Groups Underlying Cell-Adhesive Behavior

    Directory of Open Access Journals (Sweden)

    Julia Brasch

    2018-05-01

    Full Text Available Summary: Type II cadherins are cell-cell adhesion proteins critical for tissue patterning and neuronal targeting but whose molecular binding code remains poorly understood. Here, we delineate binding preferences for type II cadherin cell-adhesive regions, revealing extensive heterophilic interactions between specific pairs, in addition to homophilic interactions. Three distinct specificity groups emerge from our analysis with members that share highly similar heterophilic binding patterns and favor binding to one another. Structures of adhesive fragments from each specificity group confirm near-identical dimer topology conserved throughout the family, allowing interface residues whose conservation corresponds to specificity preferences to be identified. We show that targeted mutation of these residues converts binding preferences between specificity groups in biophysical and co-culture assays. Our results provide a detailed understanding of the type II cadherin interaction map and a basis for defining their role in tissue patterning and for the emerging importance of their heterophilic interactions in neural connectivity. : Type II cadherins are a family of vertebrate cell adhesion proteins expressed primarily in the CNS. Brasch et al. measure binding between adhesive fragments, revealing homophilic and extensive selective heterophilic binding with specificities that define groups of similar cadherins. Structures reveal common adhesive dimers, with residues governing cell-adhesive specificity. Keywords: cell adhesion, crystal structure, hemophilic specificity, heterophilic specificity, neural patterning, synaptic targeting, cadherin

  9. Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells.

    Science.gov (United States)

    Cautivo, Kelly M; Molofsky, Ari B

    2016-06-01

    Adipose tissue (AT) is home to an abundance of immune cells. With chronic obesity, inflammatory immune cells accumulate and promote insulin resistance and the progression to type 2 diabetes mellitus. In contrast, recent studies have highlighted the regulation and function of immune cells in lean, healthy AT, including those associated with type 2 or "allergic" immunity. Although traditionally activated by infection with multicellular helminthes, AT type 2 immunity is active independently of infection, and promotes tissue homeostasis, AT "browning," and systemic insulin sensitivity, protecting against obesity-induced metabolic dysfunction and type 2 diabetes mellitus. In particular, group 2 innate lymphoid cells (ILC2s) are integral regulators of AT type 2 immunity, producing the cytokines interleukin-5 and IL-13, promoting eosinophils and alternatively activated macrophages, and cooperating with and promoting AT regulatory T (Treg) cells. In this review, we focus on the recent developments in our understanding of group 2 innate lymphoid cell cells and type 2 immunity in AT metabolism and homeostasis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Metformin normalizes the structural changes in glycogen preceding prediabetes in mice overexpressing neuropeptide Y in noradrenergic neurons.

    Science.gov (United States)

    Ailanen, Liisa; Bezborodkina, Natalia N; Virtanen, Laura; Ruohonen, Suvi T; Malova, Anastasia V; Okovityi, Sergey V; Chistyakova, Elizaveta Y; Savontaus, Eriika

    2018-04-01

    Hepatic insulin resistance and increased gluconeogenesis are known therapeutic targets of metformin, but the role of hepatic glycogen in the pathogenesis of diabetes is less clear. Mouse model of neuropeptide Y (NPY) overexpression in noradrenergic neurons (OE-NPY D βH ) with a phenotype of late onset obesity, hepatosteatosis, and prediabetes was used to study early changes in glycogen structure and metabolism preceding prediabetes. Furthermore, the effect of the anti-hyperglycemic agent, metformin (300 mg/kg/day/4 weeks in drinking water), was assessed on changes in glycogen metabolism, body weight, fat mass, and glucose tolerance. Glycogen structure was characterized by cytofluorometric analysis in isolated hepatocytes and mRNA expression of key enzymes by qPCR. OE-NPY D βH mice displayed decreased labile glycogen fraction relative to stabile fraction (the intermediate form of glycogen) suggesting enhanced glycogen cycling. This was supported by decreased filling of glucose residues in the 10th outer tier of the glycogen molecule, which suggests accelerated glycogen phosphorylation. Metformin reduced fat mass gain in both genotypes, but glucose tolerance was improved mostly in wild-type mice. However, metformin inhibited glycogen accumulation and normalized the ratio between glycogen structures in OE-NPY D βH mice indicating decreased glycogen synthesis. Furthermore, the presence of glucose residues in the 11th tier together with decreased glycogen phosphorylase expression suggested inhibition of glycogen degradation. In conclusion, structural changes in glycogen of OE-NPY D βH mice point to increased glycogen metabolism, which may predispose them to prediabetes. Metformin treatment normalizes these changes and suppresses both glycogen synthesis and phosphorylation, which may contribute to its preventive effect on the onset of diabetes.

  11. Surface grafting of carboxylic groups onto thermoplastic polyurethanes to reduce cell adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Alves, P., E-mail: palves@eq.uc.pt [CIEPQPF, Departamento de Engenharia Química, Universidade de Coimbra, Polo II, Pinhal de Marrocos, 3030-790 Coimbra (Portugal); Ferreira, P. [CIEPQPF, Departamento de Engenharia Química, Universidade de Coimbra, Polo II, Pinhal de Marrocos, 3030-790 Coimbra (Portugal); Kaiser, Jean-Pierre [EMPA, St. Gallen, Lerchenfeldstrasse 5, CH-9014 St. Gallen (Switzerland); Salk, Natalie [Mikrofertigung – Micro Engineering, Fraunhofer IFAM, Wiener Strasse 12, D-288359 Bremen (Germany); Bruinink, Arie [EMPA, St. Gallen, Lerchenfeldstrasse 5, CH-9014 St. Gallen (Switzerland); Sousa, Hermínio C. de; Gil, M.H. [CIEPQPF, Departamento de Engenharia Química, Universidade de Coimbra, Polo II, Pinhal de Marrocos, 3030-790 Coimbra (Portugal)

    2013-10-15

    The interaction of polymers with other materials is an important issue, being their surface properties clearly crucial. For some important polymer applications, their surfaces have to be modified. Surface modification aims to tailor the surface characteristics of a material for a specific application without affecting its bulk properties. Materials can be surface modified by using biological, chemical or physical methods. The aim of this work was to improve the reactivity of the thermoplastic polyurethane (TPU) material (Elastollan{sup ®}) surface and to make its surface cell repellent by grafting carboxylic groups onto its surface. Two TPU materials were studied: a polyether-based TPU and a polyester-based TPU. The grafting efficiency was evaluated by contact angle measurements and by analytical determination of the COOH groups. Scanning electron microscopy (SEM) of the membranes surface was performed as well as cell adhesion tests. It was proved that the surfaces of the TPUs membranes were successfully modified and that cell adhesion was remarkably reduced.

  12. Noradrenergic and cholinergic innervation of the bone marrow.

    Science.gov (United States)

    Artico, Marco; Bosco, Sandro; Cavallotti, Carlo; Agostinelli, Enzo; Giuliani-Piccari, Gabriella; Sciorio, Salvatore; Cocco, Lucio; Vitale, Marco

    2002-07-01

    Bone marrow is supplied by sensory and autonomic innervation. Although it is well established that hematopoiesis is regulated by cytokines and cell-to-cell contacts, the role played by neuromediators on the proliferation, differentiation and release of hematopoietic cells is still controversial. We studied the innervation of rat femur bone marrow by means of fluorescence histochemistry and immunohistochemistry. Glyoxylic acid-induced fluorescence was used to demonstrate catecholaminergic nerve fibers. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. Our results show the presence of an extensive network of innervation in the rat bone marrow, providing a morphological basis for the neural modulation of hemopoiesis.

  13. Neonatal co-lesion by DSP-4 and 5,7-DHT produces adulthood behavioral sensitization to dopamine D(2) receptor agonists.

    Science.gov (United States)

    Nowak, Przemysław; Nitka, Dariusz; Kwieciński, Adam; Jośko, Jadwiga; Drab, Jacek; Pojda-Wilczek, Dorota; Kasperski, Jacek; Kostrzewa, Richard M; Brus, Ryszard

    2009-01-01

    To assess the possible modulatory effects of noradrenergic and serotoninergic neurons on dopaminergic neuronal activity, the noradrenergic and serotoninergic neurotoxins DSP-4 N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine (50.0 mg/kg, sc) and 5,7-dihydroxytryptamine (5,7-DHT) (37.5 microg icv, half in each lateral ventricle), respectively, were administered toWistar rats on the first and third days of postnatal ontogeny, and dopamine (DA) agonist-induced behaviors were assessed in adulthood. At eight weeks, using an HPLC/ED technique, DSP-4 treatment was associated with a reduction in NE content of the corpus striatum (> 60%), hippocampus (95%), and frontal cortex (> 85%), while 5,7-DHT was associated with an 80-90% serotonin reduction in the same brain regions. DA content was unaltered in the striatum and the cortex. In the group lesioned with both DSP-4 and 5,7-DHT, quinpirole-induced (DA D(2) agonist) yawning, 7-hydroxy-DPAT-induced (DA D(3) agonist) yawning, and apomorphine-induced (non-selective DA agonist) stereotypies were enhanced. However, SKF 38393-induced (DA D(1) agonist) oral activity was reduced in the DSP-4 + 5,7-DHT group. These findings demonstrate that DA D(2)- and D(3)-agonist-induced behaviors are enhanced while DA D(1)-agonist-induced behaviors are suppressed in adult rats in which brain noradrenergic and serotoninergic innervation of the brain has largely been destroyed. This study indicates that noradrenergic and serotoninergic neurons have a great impact on the development of DA receptor reactivity (sensitivity).

  14. Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

    Science.gov (United States)

    Stine, S M; Grillon, C G; Morgan, C A; Kosten, T R; Charney, D S; Krystal, J H

    2001-03-01

    Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the

  15. Automated grouping of action potentials of human embryonic stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Gorospe, Giann; Zhu, Renjun; Millrod, Michal A; Zambidis, Elias T; Tung, Leslie; Vidal, Rene

    2014-09-01

    Methods for obtaining cardiomyocytes from human embryonic stem cells (hESCs) are improving at a significant rate. However, the characterization of these cardiomyocytes (CMs) is evolving at a relatively slower rate. In particular, there is still uncertainty in classifying the phenotype (ventricular-like, atrial-like, nodal-like, etc.) of an hESC-derived cardiomyocyte (hESC-CM). While previous studies identified the phenotype of a CM based on electrophysiological features of its action potential, the criteria for classification were typically subjective and differed across studies. In this paper, we use techniques from signal processing and machine learning to develop an automated approach to discriminate the electrophysiological differences between hESC-CMs. Specifically, we propose a spectral grouping-based algorithm to separate a population of CMs into distinct groups based on the similarity of their action potential shapes. We applied this method to a dataset of optical maps of cardiac cell clusters dissected from human embryoid bodies. While some of the nine cell clusters in the dataset are presented with just one phenotype, the majority of the cell clusters are presented with multiple phenotypes. The proposed algorithm is generally applicable to other action potential datasets and could prove useful in investigating the purification of specific types of CMs from an electrophysiological perspective.

  16. Growth hormone response to guanfacine in boys with attention deficit hyperactivity disorder: a preliminary study.

    Science.gov (United States)

    Halperin, Jeffrey M; Newcorn, Jeffrey H; McKay, Kathleen E; Siever, Larry J; Sharma, Vanshdeep

    2003-01-01

    This preliminary study evaluated a method for assessing central noradrenergic function in children via the growth hormone response to a single dose of the alpha-2 adrenergic receptor agonist guanfacine and examined whether this measure distinguishes between attention deficit hyperactivity disorder (ADHD) boys with and without reading disabilities (RD). Plasma growth hormone was assessed before and after the oral administration of guanfacine and placebo in boys with ADHD who were divided into subgroups based on the presence (n = 3) or absence (n = 5) of RD. Guanfacine and placebo conditions did not differ at baseline, but peak growth hormone was significantly higher following guanfacine. The increase in growth hormone following guanfacine was significantly greater in boys without RD as compared to those with RD, with no overlap between the groups. Consistent with findings using peripheral measures of noradrenergic function, these preliminary data suggest that ADHD boys with and without RD may differ in central noradrenergic function.

  17. Sodium butyrate stimulates cellular recovery from UV damage in xeroderma pigmentosum cells belonging to complementation group F

    International Nuclear Information System (INIS)

    Nishigori, Chikako; Takebe, Hiraku

    1987-01-01

    Possible stimulation of the DNA repair capacity by sodium butyrate in normal and xeroderma pigmentosum (XP) cells was investigated. XP cells belonging to the complementation group F showed considerable stimulation of DNA repair by sodium butyrate in terms of both the amount of unscheduled DNA synthesis (UDS) and the colony-forming ability after UV irradiation. UDS in XP cells belonging to the complementation group A was not enhanced, while normal cells showed slight enhancement, but less than that of XP F cells. In XP A, XP C, and normal cells, sodium butyrate treatment enhanced the killing effect of UV irradiation. The residual repair capacity in XP F cells appeared to be stimulated by sodium butyrate. (author)

  18. Self-assembled monolayers with different chemical group substrates for the study of MCF-7 breast cancer cell line behavior

    International Nuclear Information System (INIS)

    Yan, Hongji; Yin, Yanbin; Li, Yu; Tian, Weiming; Zhang, Song; Nie, Yongzhan; He, Jin; Wang, Xiumei; Cui, Fuzhai; Chen, Xiongbiao

    2013-01-01

    The interactions between cancer cells and the extracellular matrix (ECM) are important with respect to a number of cell behavoirs, yet remain unclear. In this study, self-assembled monolayers with different terminal chemical groups (hydroxyl (-OH), carboxyl (-COOH), animo (-NH 2 ), mercapto (-SH), and methyl (-CH 3 )) were employed as substrates for the culture of MCF-7 cells to examine effects on cell behavior. Cell spreading was investigated by scanning electron microscopy, tallin expression by immunofluorescence, proliferation rate by counting cell numbers, cell cycle by flow cytometry, metabolism by high-performance liquid chromatography and cell migration by live cell imaging. Annexin V-FITC (fluorescein isothiocyanate) and JC-1 assays were performed to determine cell apoptosis and mitochondrial membrane potential, respectively. Our results demonstrate the varied behaviors of MCF-7 cells in response to different chemical groups. Specifically, NH 2 and COOH terminal functional groups promote proliferation, the production of lactic acid and mobility of MCF-7 cells; SH and OH terminal groups enhance the expression and distribution of tallin but result in weak cell proliferation, metabolism, spreading and mobility. These results are meaningful for uncovering the interactions between the ECM and cancer cells; they are potentially useful for designing novel cancer treatment strategies. (paper)

  19. Polymerase chain reaction assay for the detection of Bacillus cereus group cells

    DEFF Research Database (Denmark)

    Hansen, Bjarne Munk; Leser, Thomas D.; Hendriksen, Niels Bohse

    2001-01-01

    of the B. cereus group in food and in the environment. Using 16S rDNA as target, a PCR assay for the detection of B. cereus group cells has been developed. Primers specific for the 16S rDNA of the B. cereus group bacteria were selected and used in combination with consensus primers for 165 rDNA as internal...... PCR procedure control. The PCR procedure was optimized with respect to annealing temperature. When DNA from the B. cereus group bacteria was present, the PCR assay yielded a B. cereus specific fragment, while when non-B. cereus prokaryotic DNA was present, the consensus 165 rDNA primers directed...

  20. Monoamine re-uptake sites in the human brain evaluated in vivo by means of /sup 11/C-nomifensine and positron emission tomography: the effects of age and Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Tedroff, J; Aquilonius, S -M; Hartvig, P; Lundqvist, H; Gee, A G; Uhlin, J; Laangstroem, B

    1988-01-01

    Six patients with Parkinson's disease, selected to cover a range of clinical features, and 7 healthy volunteers aged 24-81 years, were examined by positron emission tomography after i.v. injection of racemic /sup 11/C-nomifensine, a catecholamine re-uptake blocking drug. After injection the radiotracer, radioactivity was rapidly distributed to the brain. The highest accumulation of radioactivity was found in areas rich in dopamineric and noradrenergic innervation, such as the striatum and the thalamus. In regions with negible dopaminergic and noradrenergic innervation, such as the cerebellum, radioactivity was lower and evenly distributed. In all investigated brain regions a marked age-related decline in /sup 11/C-nomifensinederived radioactivity relative to the cerebellum was observed in the group of healthy volunteers. Parkinsonian patients did not show such a decline with age. In the group of parkinsonian patients with mainly unilateral involvement, the contralateral putamen exhibited the most pronounced decrease. Only the 3 parkinsonian patients aged 63 and younger showed markedly lower /sup 11/C-nomifensine binding in striatal areas than age-matched healthy volunteers. /sup 11/C-nomifensine seems to be a valuable tool for investigating noradrenergic and dopaminergic re-uptake sites in vivo. Further achievements will most likely be made when the active enantioimer becomes available.

  1. Nucleus retroambiguous projections to lumbosacral motoneuronal cell groups in the male cat

    NARCIS (Netherlands)

    Vanderhorst, VGJM; Holstege, G

    1997-01-01

    Recently, in the female cat, nucleus retroambiguus (NRA) projections have been described as distinct motoneuronal cell groups in the lumbar enlargement, possibly involved in lordosis behavior. The present study deals with the NRA-lumbosacral pathway in the male cat, Lumbosacral injections of wheat

  2. Algebras of functions on compact quantum groups, Schubert cells and quantum tori

    International Nuclear Information System (INIS)

    Levendorskij, S.; Soibelman, Ya.

    1991-01-01

    The structure of Poisson Lie groups on a simple compact group are parametrized by pairs (a, u), where aelement ofR, uelement ofΛ 2 f R , and f R is a real Cartan subalgebra of complexification of Lie algebra of the group in question. In the present article the description of the symplectic leaves for all pairs (a, u) is given. Also, the corresponding quantized algebras of functions are constructed and their irreducible representations are described. In the course of investigation Schubert cells and quantum tori appear. At the end of the article the quantum analog of the Weyl group is constructed and some of its applications, among them the formula for the universal R-matrix, are given. (orig.)

  3. A discrete dopaminergic projection from the incertohypothalamic A13 cell group to the dorsolateral periaqueductal gray in rat

    Directory of Open Access Journals (Sweden)

    Fany eMessanvi

    2013-12-01

    Full Text Available Several findings have indicated an involvement of dopamine in panic and defensive behaviors. The dorsolateral column of the periaqueductal gray (dlPAG is crucially involved in the expression of panic attacks in humans and defensive behaviors, also referred to as panic-like behaviors, in animals. Although the dlPAG is known to receive a specific innervation of dopaminergic fibers and abundantly expresses dopamine receptors, the origin of this dopaminergic input is largely unknown. This study aimed at mapping the dopaminergic projections to the dlPAG in order to provide further insight into the panic-like related behavior circuitry of the dlPAG. For this purpose, the retrograde tracer cholera toxin subunit b (CTb was injected into the dlPAG of male Wistar rats and double immunofluorescence for CTb and tyrosine hydroxylase (TH, the rate-limiting enzyme in the synthesis of dopamine, was performed. Neurons labeled for both CTb and TH were counted in different dopaminergic cell groups. The findings indicate that the dopaminergic nerve terminals present in the dlPAG originate from multiple dopamine-containing cell groups in the hypothalamus and mesencephalon. Interestingly, the A13 cell group is the main source of dopaminergic afferents to the dlPAG and contains at least 45% of the total number of CTb/TH-positive neurons. Anterograde tracing with biotinylated dextran amine (BDA combined with double immunofluorescence for BDA and TH confirmed the projections from the A13 cell group to the dlPAG. The remainder of the dopamine-positive terminals present in the dlPAG was found to originate from the extended A10 cell group and the A11 group. The A13 cell group is known to send dopaminergic efferents to several other brain regions implicated in defensive behavior, including the central amygdala and ventromedial hypothalamus. Therefore, although direct behavioral evidence is lacking, our finding that the A13 cell group is also the main source of dopaminergic

  4. Letter of professional groups. Energies and fuel cells; La lettre des Groupe Professionnels, energies et piles a combustible

    Energy Technology Data Exchange (ETDEWEB)

    Meunier, M. [Supelec, 91 - Gif sur Yvette (France); Serre Combe, P. [CEA Grenoble, 38 (France); Sartorelli, G. [Maxwell Technologie, San Diego, CA (United States); Lafont, G. [PILLER France S.A., 92 - Nanterre (France); Green, A. [SAFT, 93170 Bagnolet (France); Perrin, M. [CEA Cadarache, 13 - Saint Paul lez Durance (France); Fregere, J.P.

    2004-07-01

    These proceedings of the 'Arts et Metiers' professional groups treats of energy storage solutions for delocalized power generation units. Four types of energy storage systems are presented with their operation principle, advantages and drawbacks: fuel cells and hydrogen, super-capacitors, flywheels, conventional batteries (lithium-ion, lead, redox, nickel-cadmium, zinc-air), and comparison between the different energy storage solutions including compressed air. (J.S.)

  5. Cellular characterization of cells from the Fanconi anemia complementation group, FA-D1/BRCA2

    Energy Technology Data Exchange (ETDEWEB)

    Godthelp, Barbara C. [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Buul, Paul P.W. van [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Jaspers, Nicolaas G.J. [Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam (Netherlands); Elghalbzouri-Maghrani, Elhaam [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Duijn-Goedhart, Annemarie van [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands); Arwert, Fre [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Amsterdam (Netherlands); Joenje, Hans [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Amsterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Center, Building 2, Postzone S-6-P, P.O. Box 9600, 2300 RC, Leiden (Netherlands) and Department of Molecular Cell Genetics, Collegium Medicum, N.Copernicus University, Bydgoszcz (Poland)]. E-mail: M.Z.Zdzienicka@LUMC.nl

    2006-10-10

    Fanconi anemia (FA) is an inherited cancer-susceptibility disorder, characterized by genomic instability and hypersensitivity to DNA cross-linking agents. The discovery of biallelic BRCA2 mutations in the FA-D1 complementation group allows for the first time to study the characteristics of primary BRCA2-deficient human cells. FANCD1/BRCA2-deficient fibroblasts appeared hypersensitive to mitomycin C (MMC), slightly sensitive to methyl methane sulfonate (MMS), and like cells derived from other FA complementation groups, not sensitive to X-ray irradiation. However, unlike other FA cells, FA-D1 cells were slightly sensitive to UV irradiation. Despite the observed lack of X-ray sensitivity in cell survival, significant radioresistant DNA synthesis (RDS) was observed in the BRCA2-deficient fibroblasts but also in the FANCA-deficient fibroblasts, suggesting an impaired S-phase checkpoint. FA-D1/BRCA2 cells displayed greatly enhanced levels of spontaneous as well as MMC-induced chromosomal aberrations (Canada), similar to cells deficient in homologous recombination (HR) and non-D1 FA cells. In contrast to Brca2-deficient rodent cells, FA-D1/BRCA2 cells showed normal sister chromatid exchange (SCE) levels, both spontaneous as well as after MMC treatment. Hence, these data indicate that human cells with biallelic BRCA2 mutations display typical features of both FA- and HR-deficient cells, which suggests that FANCD1/BRCA2 is part of the integrated FA/BRCA DNA damage response pathway but also controls other functions outside the FA pathway.

  6. Cellular characterization of cells from the Fanconi anemia complementation group, FA-D1/BRCA2

    International Nuclear Information System (INIS)

    Godthelp, Barbara C.; Buul, Paul P.W. van; Jaspers, Nicolaas G.J.; Elghalbzouri-Maghrani, Elhaam; Duijn-Goedhart, Annemarie van; Arwert, Fre; Joenje, Hans; Zdzienicka, Malgorzata Z.

    2006-01-01

    Fanconi anemia (FA) is an inherited cancer-susceptibility disorder, characterized by genomic instability and hypersensitivity to DNA cross-linking agents. The discovery of biallelic BRCA2 mutations in the FA-D1 complementation group allows for the first time to study the characteristics of primary BRCA2-deficient human cells. FANCD1/BRCA2-deficient fibroblasts appeared hypersensitive to mitomycin C (MMC), slightly sensitive to methyl methane sulfonate (MMS), and like cells derived from other FA complementation groups, not sensitive to X-ray irradiation. However, unlike other FA cells, FA-D1 cells were slightly sensitive to UV irradiation. Despite the observed lack of X-ray sensitivity in cell survival, significant radioresistant DNA synthesis (RDS) was observed in the BRCA2-deficient fibroblasts but also in the FANCA-deficient fibroblasts, suggesting an impaired S-phase checkpoint. FA-D1/BRCA2 cells displayed greatly enhanced levels of spontaneous as well as MMC-induced chromosomal aberrations (Canada), similar to cells deficient in homologous recombination (HR) and non-D1 FA cells. In contrast to Brca2-deficient rodent cells, FA-D1/BRCA2 cells showed normal sister chromatid exchange (SCE) levels, both spontaneous as well as after MMC treatment. Hence, these data indicate that human cells with biallelic BRCA2 mutations display typical features of both FA- and HR-deficient cells, which suggests that FANCD1/BRCA2 is part of the integrated FA/BRCA DNA damage response pathway but also controls other functions outside the FA pathway

  7. Group cell phones are feasible and acceptable for promoting optimal breastfeeding practices in a women's microcredit program in Nigeria.

    Science.gov (United States)

    Flax, Valerie L; Ibrahim, Alawiyatu Usman; Negerie, Mekebeb; Yakubu, Danjuma; Leatherman, Sheila; Bentley, Margaret E

    2017-01-01

    As part of a breastfeeding promotion intervention trial in Nigeria, we provided one cell phone per group of 5-7 microcredit clients and instructed the group's cell phone recipient to share weekly breastfeeding voice and text messages with group members. We measured the feasibility and acceptability of using group cell phones by conducting semi-structured exit interviews with 195 microcredit clients whose babies were born during the intervention (target group), in-depth interviews with eight phone recipients and nine non-phone recipients, and 16 focus group discussions with other microcredit clients. Women in the target group said the group phone worked well or very well (64%). They were motivated to try the recommended practices because they trusted the information (58%) and had support from others (35%). Approximately 44% of target women reported that their groups met and shared messages at least once a week. Women in groups that met at least weekly had higher odds of exclusive breastfeeding up to 6 months (OR 5.6, 95% CI 1.6, 19.7) than women in groups that never met. In-depth interviews and focus group discussions indicated that non-phone recipients had positive feelings towards phone recipients, the group phone met participants' needs, and messages were often shared outside the group. In conclusion, group cell phone messaging to promote breastfeeding among microcredit clients is feasible and acceptable and can be part of an effective behaviour change package. © 2016 John Wiley & Sons Ltd.

  8. Acquisition and extinction of continuously and partially reinforced running in rats with lesions of the dorsal noradrenergic bundle.

    Science.gov (United States)

    Owen, S; Boarder, M R; Gray, J A; Fillenz, M

    1982-05-01

    Local injection of 6-hydroxydopamine was used to selectively destroy the dorsal ascending noradrenergic bundle (DB) in rats. Two lesion procedures were used, differing in the extent of depletion of forebrain noradrenaline they produced (greater than 90% or 77%). In Experiments 1-3 the rats were run in a straight alley for food reward on continuous (CR) or partial (PR) reinforcement schedules. The smaller lesion reduced and the larger lesion eliminated the partial reinforcement acquisition effect (i.e. the faster start and run speeds produced by PR during training) and the partial reinforcement extinction effect (PREE, i.e. the greater resistance to extinction produced by PR training); these changes were due to altered performance only in the PR condition. Abolition of the PREE by the larger DB lesion occurred with 50 acquisition trials, but with 100 trials the lesion had no effect. In Experiment 4 rats were run in a double runway with food reward on CR in the second goal box, and on CR, PR or without reinforcement in the first. The larger lesion again eliminated the PREE in the first runway, but did not block the frustration effect in the second runway (i.e. the faster speeds observed in the PR condition after non-reward than after reward in the first goal box). These results are consistent with the hypothesis that DB lesions alter behavioural responses to signals of non-reward, but not to non-reward itself. They cannot be predicted from two other hypotheses: that the DB mediates responses to reward or that it subserves selective attention. Since septal and hippocampal, but not amygdalar, lesions have been reported to produced similar behavioural changes, it is proposed that the critical DB projection for the effects observed in these experiments is to the septo-hippocampal system.

  9. Role of nucleus of the solitary tract noradrenergic neurons in post-stress cardiovascular and hormonal control in male rats.

    Science.gov (United States)

    Bundzikova-Osacka, Jana; Ghosal, Sriparna; Packard, Benjamin A; Ulrich-Lai, Yvonne M; Herman, James P

    2015-01-01

    Chronic stress causes hypothalamo-pituitary-adrenal (HPA) axis hyperactivity and cardiovascular dyshomeostasis. Noradrenergic (NA) neurons in the nucleus of the solitary tract (NTS) are considered to play a role in these changes. In this study, we tested the hypothesis that NTS NA A2 neurons are required for cardiovascular and HPA axis responses to both acute and chronic stress. Adult male rats received bilateral microinjection into the NTS of 6-hydroxydopamine (6-OHDA) to lesion A2 neurons [cardiovascular study, n = 5; HPA study, n = 5] or vehicle [cardiovascular study, n = 6; HPA study, n = 4]. Rats were exposed to acute restraint stress followed by 14 d of chronic variable stress (CVS). On the last day of testing, rats were placed in a novel elevated plus maze (EPM) to test post-CVS stress responses. Lesions of NTS A2 neurons reduced the tachycardic response to acute restraint, confirming that A2 neurons promote sympathetic activation following acute stress. In addition, CVS increased the ratio of low-frequency to high-frequency power for heart rate variability, indicative of sympathovagal imbalance, and this effect was significantly attenuated by 6-OHDA lesion. Lesions of NTS A2 neurons reduced acute restraint-induced corticosterone secretion, but did not affect the corticosterone response to the EPM, indicating that A2 neurons promote acute HPA axis responses, but are not involved in CVS-mediated HPA axis sensitization. Collectively, these data indicate that A2 neurons promote both cardiovascular and HPA axis responses to acute stress. Moreover, A2 catecholaminergic neurons may contribute to the potentially deleterious enhancement of sympathetic drive following chronic stress.

  10. High Glucose-Induced PC12 Cell Death by Increasing Glutamate Production and Decreasing Methyl Group Metabolism

    Directory of Open Access Journals (Sweden)

    Minjiang Chen

    2016-01-01

    Full Text Available Objective. High glucose- (HG- induced neuronal cell death is responsible for the development of diabetic neuropathy. However, the effect of HG on metabolism in neuronal cells is still unclear. Materials and Methods. The neural-crest derived PC12 cells were cultured for 72 h in the HG (75 mM or control (25 mM groups. We used NMR-based metabolomics to examine both intracellular and extracellular metabolic changes in HG-treated PC12 cells. Results. We found that the reduction in intracellular lactate may be due to excreting more lactate into the extracellular medium under HG condition. HG also induced the changes of other energy-related metabolites, such as an increased succinate and creatine phosphate. Our results also reveal that the synthesis of glutamate from the branched-chain amino acids (isoleucine and valine may be enhanced under HG. Increased levels of intracellular alanine, phenylalanine, myoinositol, and choline were observed in HG-treated PC12 cells. In addition, HG-induced decreases in intracellular dimethylamine, dimethylglycine, and 3-methylhistidine may indicate a downregulation of methyl group metabolism. Conclusions. Our metabolomic results suggest that HG-induced neuronal cell death may be attributed to a series of metabolic changes, involving energy metabolism, amino acids metabolism, osmoregulation and membrane metabolism, and methyl group metabolism.

  11. Polybenzimidazole Membranes Containing Benzimidazole Side Groups for High Temprature Polymer Electrolyte Membrane Fuel Cells

    DEFF Research Database (Denmark)

    Yang, Jingshuai; Li, Xueyuan; Xu, Yizin

    2013-01-01

    Polybenzimidazole (PBI) with a high molecular weight of 69,000 was first synthesized. It was afterwards grafted with benzimidazole pendant groups on the backbones. The acid doped benzimidaozle grafted PBI membranes were investigated and characterized including fuel cell tests at elevated temperat......Polybenzimidazole (PBI) with a high molecular weight of 69,000 was first synthesized. It was afterwards grafted with benzimidazole pendant groups on the backbones. The acid doped benzimidaozle grafted PBI membranes were investigated and characterized including fuel cell tests at elevated...... temperatures without humidification. At an acid doping level of 13.1 mol H3PO4 per average molar repeat unit, the PBI membranes with a benzimidazole grafting degree of 10.6% demonstrated a conductivity of 0.15 S cm-1 and a H2-air fuel cell peak power density of 378 mW cm-2 at 180 oC at ambient pressure without...

  12. Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis

    Directory of Open Access Journals (Sweden)

    Barbara C. Mindt

    2018-04-01

    Full Text Available Group 2 innate lymphoid cells (ILC2 represent an evolutionary rather old but only recently identified member of the family of innate lymphoid cells and have received much attention since their detailed description in 2010. They can orchestrate innate as well as adaptive immune responses as they interact with and influence several immune and non-immune cell populations. Moreover, ILC2 are able to rapidly secrete large amounts of type 2 cytokines that can contribute to protective but also detrimental host immune responses depending on timing, location, and physiological context. Interestingly, ILC2, despite their scarcity, are the dominant innate lymphoid cell population in the lung, indicating a key role as first responders and amplifiers upon immune challenge at this site. In addition, the recently described tissue residency of ILC2 further underlines the importance of their respective microenvironment. In this review, we provide an overview of lung physiology including a description of the most prominent pulmonary resident cells together with a review of known and potential ILC2 interactions within this unique environment. We will further outline recent observations regarding pulmonary ILC2 during immune challenge including respiratory infections and discuss different models and approaches to study ILC2 biology in the lung.

  13. Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis.

    Science.gov (United States)

    Mindt, Barbara C; Fritz, Jörg H; Duerr, Claudia U

    2018-01-01

    Group 2 innate lymphoid cells (ILC2) represent an evolutionary rather old but only recently identified member of the family of innate lymphoid cells and have received much attention since their detailed description in 2010. They can orchestrate innate as well as adaptive immune responses as they interact with and influence several immune and non-immune cell populations. Moreover, ILC2 are able to rapidly secrete large amounts of type 2 cytokines that can contribute to protective but also detrimental host immune responses depending on timing, location, and physiological context. Interestingly, ILC2, despite their scarcity, are the dominant innate lymphoid cell population in the lung, indicating a key role as first responders and amplifiers upon immune challenge at this site. In addition, the recently described tissue residency of ILC2 further underlines the importance of their respective microenvironment. In this review, we provide an overview of lung physiology including a description of the most prominent pulmonary resident cells together with a review of known and potential ILC2 interactions within this unique environment. We will further outline recent observations regarding pulmonary ILC2 during immune challenge including respiratory infections and discuss different models and approaches to study ILC2 biology in the lung.

  14. Repair of ultraviolet radiation damage in xeroderma pigmentosum cells belonging to complementation group F

    International Nuclear Information System (INIS)

    Hayakawa, H.; Ishizaki, K.; Yagi, T.; Takebe, H.; Inoue, M.; Sekiguchi, M.; Kyoto Univ.

    1981-01-01

    DNA-repair characteristics of xeroderma pigmentosum belonging to complementation group F were investigated. The cells exhibited an intermediate level of repair as measured in terms of (1) disappearance of T4 endonuclease-V-susceptible sites from DNA, (2) formation of ultraviolet-induced strand breaks in DNA, and (3) ultraviolet-induced unscheduled DNA synthesis during post-irradiation incubation. The impaired ability of XP3YO to perform unscheduled DNA synthesis was restored, to half the normal level, by the concomitant treatment with T4 endonuclease V and ultraviolet-inactivated Sendai virus. It is suggested that xeroderma pigmentosum cells of group F may be defective, at least in part, in the incision step of excision repair. (orig.)

  15. Behavioral correlates of cerebrospinal fluid amino acid and biogenic amine neurotransmitter alterations in dementia

    NARCIS (Netherlands)

    Vermeiren, Yannick; Le Bastard, Nathalie; Van Hemelrijck, An; Drinkenburg, Wilhelmus H.; Engelborghs, Sebastiaan; De Deyn, Peter P.

    Background: Behavioral and psychological signs and symptoms of dementia (BPSD) are a heterogeneous group of behavioral and psychiatric disturbances occurring in dementia patients of any etiology. Research suggests that altered activities of dopaminergic, serotonergic, (nor)adrenergic, as well as

  16. Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine.

    Science.gov (United States)

    Fitzgerald, Paul J

    2013-10-13

    A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general.

  17. Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine

    Directory of Open Access Journals (Sweden)

    Paul J. Fitzgerald

    2013-01-01

    Full Text Available A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general.

  18. Loss of Sympathetic Nerves in Spleens from Patients with End Stage Sepsis

    Directory of Open Access Journals (Sweden)

    Donald B. Hoover

    2017-12-01

    Full Text Available The spleen is an important site for central regulation of immune function by noradrenergic sympathetic nerves, but little is known about this major region of neuroimmune communication in humans. Experimental studies using animal models have established that sympathetic innervation of the spleen is essential for cholinergic anti-inflammatory responses evoked by vagal nerve stimulation, and clinical studies are evaluating this approach for treating inflammatory diseases. Most data on sympathetic nerves in spleen derive from rodent studies, and this work has established that remodeling of sympathetic innervation can occur during inflammation. However, little is known about the effects of sepsis on spleen innervation. Our primary goals were to (i localize noradrenergic nerves in human spleen by immunohistochemistry for tyrosine hydroxylase (TH, a specific noradrenergic marker, (ii determine if nerves occur in close apposition to leukocytes, and (iii determine if splenic sympathetic innervation is altered in patients who died from end stage sepsis. Staining for vesicular acetylcholine transporter (VAChT was done to screen for cholinergic nerves. Archived paraffin tissue blocks were used. Control samples were obtained from trauma patients or patients who died after hemorrhagic stroke. TH + nerves were associated with arteries and arterioles in all control spleens, occurring in bundles or as nerve fibers. Individual TH + nerve fibers entered the perivascular region where some appeared in close apposition to leukocytes. In marked contrast, spleens from half of the septic patients lacked TH + nerves fibers and the average abundance of TH + nerves for the septic group was only 16% of that for the control group (control: 0.272 ± 0.060% area, n = 6; sepsis: 0.043 ± 0.026% area, n = 8; P < 0.005. All spleens lacked cholinergic innervation. Our results provide definitive evidence for the distribution of noradrenergic

  19. Noradrenergic neurotransmission within the bed nucleus of the stria terminalis modulates the retention of immobility in the rat forced swimming test.

    Science.gov (United States)

    Nagai, Michelly M; Gomes, Felipe V; Crestani, Carlos C; Resstel, Leonardo B M; Joca, Sâmia R L

    2013-06-01

    The bed nucleus of the stria terminalis (BNST) is a limbic structure that has a direct influence on the autonomic, neuroendocrine, and behavioral responses to stress. It was recently reported that reversible inactivation of synaptic transmission within this structure causes antidepressant-like effects, indicating that activation of the BNST during stressful situations would facilitate the development of behavioral changes related to the neurobiology of depression. Moreover, noradrenergic neurotransmission is abundant in the BNST and has an important role in the regulation of emotional processes related to the stress response. Thus, this study aimed to test the hypothesis that activation of adrenoceptors within the BNST facilitates the development of behavioral consequences of stress. To investigate this hypothesis, male Wistar rats were stressed (forced swimming, 15 min) and 24 h later received intra-BNST injections of vehicle, WB4101, RX821002, CGP20712, or ICI118,551, which are selective α(1), α(2), β(1), and β(2) adrenoceptor antagonists, respectively, 10 min before a 5-min forced swimming test. It was observed that administration of WB4101 (10 and 15 nmol), CGP20712 (5 and 10 nmol), or ICI118,551 (5 nmol) into the BNST reduced the immobility time of rats subjected to forced swimming test, indicating an antidepressant-like effect. These findings suggest that activation of α(1), β(1), and β(2) adrenoceptors in the BNST could be involved in the development of the behavioral consequences of stress. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

  20. Development of a fine and ultra-fine group cell calculation code SLAROM-UF for fast reactor analyses

    International Nuclear Information System (INIS)

    Hazama, Taira; Chiba, Go; Sugino, Kazuteru

    2006-01-01

    A cell calculation code SLAROM-UF has been developed for fast reactor analyses to produce effective cross sections with high accuracy in practical computing time, taking full advantage of fine and ultra-fine group calculation schemes. The fine group calculation covers the whole energy range in a maximum of 900-group structure. The structure is finer above 52.5 keV with a minimum lethargy width of 0.008. The ultra-fine group calculation solves the slowing down equation below 52.5 keV to treat resonance structures directly and precisely including resonance interference effects. Effective cross sections obtained in the two calculations are combined to produce effective cross sections over the entire energy range. Calculation accuracy and improvements from conventional 70-group cell calculation results were investigated through comparisons with reference values obtained with continuous energy Monte Carlo calculations. It was confirmed that SLAROM-UF reduces the difference in k-infinity from 0.15 to 0.01% for a JOYO MK-I fuel subassembly lattice cell calculation, and from - 0.21% to less than a statistical uncertainty of the reference calculation of 0.03% for a ZPPR-10A core criticality calculation. (author)

  1. Group 3 innate lymphoid cells (ILC3s): Origin, differentiation, and plasticity in humans and mice.

    Science.gov (United States)

    Montaldo, Elisa; Juelke, Kerstin; Romagnani, Chiara

    2015-08-01

    Since their discovery, innate lymphoid cells (ILCs) have been the subject of intense research. As their name implies, ILCs are innate cells of lymphoid origin, and can be grouped into subsets based on their cytotoxic activity, cytokine profile, and the transcriptional requirements during ILC differentiation. The main ILC groups are "killer" ILCs, comprising NK cells, and "helper-like" ILCs (including ILC1s, ILC2s, and ILC3s). This review examines the origin, differentiation stages, and plasticity of murine and human ILC3s. ILC3s express the retinoic acid receptor (RAR) related orphan receptor RORγt and the signature cytokines IL-22 and IL-17. Fetal ILC3s or lymphoid tissue inducer cells are required for lymphoid organogenesis, while postnatally developing ILC3s are important for the generation of intestinal cryptopatches and isolated lymphoid follicles as well as for the defence against pathogens and epithelial homeostasis. Here, we discuss the transcription factors and exogenous signals (including cytokines, nutrients and cell-to-cell interaction) that drive ILC3 lineage commitment and acquisition of their distinctive effector program. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. High mobility group A1 protein modulates autophagy in cancer cells.

    Science.gov (United States)

    Conte, Andrea; Paladino, Simona; Bianco, Gaia; Fasano, Dominga; Gerlini, Raffaele; Tornincasa, Mara; Renna, Maurizio; Fusco, Alfredo; Tramontano, Donatella; Pierantoni, Giovanna Maria

    2017-11-01

    High Mobility Group A1 (HMGA1) is an architectural chromatin protein whose overexpression is a feature of malignant neoplasias with a causal role in cancer initiation and progression. HMGA1 promotes tumor growth by several mechanisms, including increase of cell proliferation and survival, impairment of DNA repair and induction of chromosome instability. Autophagy is a self-degradative process that, by providing energy sources and removing damaged organelles and misfolded proteins, allows cell survival under stress conditions. On the other hand, hyper-activated autophagy can lead to non-apoptotic programmed cell death. Autophagy deregulation is a common feature of cancer cells in which has a complex role, showing either an oncogenic or tumor suppressor activity, depending on cellular context and tumor stage. Here, we report that depletion of HMGA1 perturbs autophagy by different mechanisms. HMGA1-knockdown increases autophagosome formation by constraining the activity of the mTOR pathway, a major regulator of autophagy, and transcriptionally upregulating the autophagy-initiating kinase Unc-51-like kinase 1 (ULK1). Consistently, functional experiments demonstrate that HMGA1 binds ULK1 promoter region and negatively regulates its transcription. On the other hand, the increase in autophagosomes is not associated to a proportionate increase in their maturation. Overall, the effects of HMGA1 depletion on autophagy are associated to a decrease in cell proliferation and ultimately impact on cancer cells viability. Importantly, silencing of ULK1 prevents the effects of HMGA1-knockdown on cellular proliferation, viability and autophagic activity, highlighting how these effects are, at least in part, mediated by ULK1. Interestingly, this phenomenon is not restricted to skin cancer cells, as similar results have been observed also in HeLa cells silenced for HMGA1. Taken together, these results clearly indicate HMGA1 as a key regulator of the autophagic pathway in cancer cells

  3. Cell population data in neonates: differences by age group and associations with perinatal factors.

    Science.gov (United States)

    Lee, J; Kim, S Y; Lee, W; Han, K; Sung, I K

    2015-10-01

    Cell population data (CPD) describe physical parameters of white blood cell subpopulations and are reported to be of some value in the diagnosis of sepsis in neonates. Before using the CPD for diagnosing sepsis, the baseline features of the CPD distribution in healthy neonates should be clarified. The aim of this study was to compare the CPD distributions of healthy neonates and other age groups and to identify perinatal factors that are associated with changes in the CPD distribution of healthy neonates. The CPD distribution of 69 samples from term neonates was compared with adolescents and adults. The CPD distribution of 163 samples from healthy neonates was analyzed in association with perinatal factors, including gestational age, chronologic age, birthweight, delivery mode, premature rupture of membranes, diabetes, and pregnancy-induced hypertension. The CPD distribution for term neonates was significantly different from those in adolescents and adults. The mean lymphocyte volume showed a negative correlation with gestational age at birth (r = -0.305; P group than in the normal delivery group. The small for gestational age (SGA) group had smaller mean neutrophil volume and mean monocyte volume than the appropriate for gestational age group. The CPD distribution of healthy neonates differed from those of adolescents or adults, and the differences were associated with gestational age, delivery mode, and being SGA. © 2015 John Wiley & Sons Ltd.

  4. Hand-held cell phone use while driving legislation and observed driver behavior among population sub-groups in the United States.

    Science.gov (United States)

    Rudisill, Toni M; Zhu, Motao

    2017-05-12

    Cell phone use behaviors are known to vary across demographic sub-groups and geographic locations. This study examined whether universal hand-held calling while driving bans were associated with lower road-side observed hand-held cell phone conversations across drivers of different ages (16-24, 25-59, ≥60 years), sexes, races (White, African American, or other), ruralities (suburban, rural, or urban), and regions (Northeast, Midwest, South, and West). Data from the 2008-2013 National Occupant Protection Use Survey were merged with states' cell phone use while driving legislation. The exposure was presence of a universal hand-held cell phone ban at time of observation. Logistic regression was used to assess the odds of drivers having a hand-held cell phone conversation. Sub-groups differences were assessed using models with interaction terms. When universal hand-held cell phone bans were effective, hand-held cell phone conversations were lower across all driver demographic sub-groups and regions. Sub-group differences existed among the sexes (p-value, phone bans, the adjusted odds ratio (aOR) of a driver hand-held phone conversation was 0.34 [95% confidence interval (CI): 0.28, 0.41] for females versus 0.47 (CI 0.40, 0.55) for males and 0.31 (CI 0.25, 0.38) for drivers in Western states compared to 0.47 (CI 0.30, 0.72) in the Northeast and 0.50 (CI 0.38, 0.66) in the South. The presence of universal hand-held cell phone bans were associated lower hand-held cell phone conversations across all driver sub-groups and regions. Hand-held phone conversations were particularly lower among female drivers and those from Western states when these bans were in effect. Public health interventions concerning hand-held cell phone use while driving could reasonably target all drivers.

  5. SMIM1 underlies the Vel blood group and influences red blood cell traits

    DEFF Research Database (Denmark)

    Cvejic, Ana; Haer-Wigman, Lonneke; Stephens, Jonathan C

    2013-01-01

    The blood group Vel was discovered 60 years ago, but the underlying gene is unknown. Individuals negative for the Vel antigen are rare and are required for the safe transfusion of patients with antibodies to Vel. To identify the responsible gene, we sequenced the exomes of five individuals negative...... and expression of the Vel antigen on SMIM1-transfected cells confirm SMIM1 as the gene underlying the Vel blood group. An expression quantitative trait locus (eQTL), the common SNP rs1175550 contributes to variable expression of the Vel antigen (P = 0.003) and influences the mean hemoglobin concentration of red...... blood cells (RBCs; P = 8.6 × 10(-15)). In vivo, zebrafish with smim1 knockdown showed a mild reduction in the number of RBCs, identifying SMIM1 as a new regulator of RBC formation. Our findings are of immediate relevance, as the homozygous presence of the deletion allows the unequivocal identification...

  6. Human chromosome 9 can complement UV sensitivity of xeroderma pigmentosum group A cells

    International Nuclear Information System (INIS)

    Ishizaki, Kanji; Sasaki, Masao S.; Ikenaga, Mituo; Nakamura, Yusuke

    1990-01-01

    A single human chromosome derived from normal human fibroblasts and tagged with the G418 resistance gene was transferred into SV40-transformed xeroderma pigmentosum group A (XP-A) cells via microcell fusion. When chromosome 1 or 12 was transferred, UV sensitivity of microcell hybrid cells was not changed. By contrast, after transferring chromosome 9,7 of 11 reipient clones were as UV-resistant as normal human cells. Four other clones were still as UV-sensitive as the parental XP-A cells. Southern hybridization analysis using a polymorphic probe, pEKZ19.3, which is homologous to a sequence of the D9S17 locus on chromosome 9, has confirmed that at least a part of normal human chromosome 9 was transferred into the recipient clones. However, amounts iof UV-induced unscheduled DNA synthesis in the UV-resistant clones were only one-third of those in normal human cells. These results indicate that a gene on chromosome 9 can confer complementation of high UV sensitivity of XP-A cells although it is still possible that 2 or more genes might be involved in the defective-repair phenotypes of XP-A. (author). 20 refs.; 3 figs.; 1 tab

  7. Preliminary evaluation of two radioiodinated maleimide derivatives targeting peripheral and membrane sulfhydryl groups for in vitro cell labeling

    Energy Technology Data Exchange (ETDEWEB)

    Amartey, John K., E-mail: amarjk48@hotmail.co [Cyclotron and Radiopharmaceuticals Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Parhar, Ranjit S. [Biological and Medical Research Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Shi, Yufei [Genetics Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Al-Mohanna, Futwan [Biological and Medical Research Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia)

    2011-01-15

    A factor impeding the advancement of cell mediated therapy is the inability to track these cells in vivo by noninvasive techniques. It has been shown that cells express high levels of sulfhydryl groups. We sought to explore these groups to covalently label cells with radiolabeled maleimide derivatives. Two maleimide derivatives; N-[2-(2,5-dioxoazolinyl)ethyl](5-iodo(3-pyridyl))carboxamide and N-[2-(2,5-dioxoazolinyl)ethyl](3-iodophenyl)carboxamide ([{sup 125}I]-4 and [{sup 125}I]-8) were synthesized and radioiodinated. These compounds were evaluated for in vitro binding to neutrophils, endothelial and mesenchymal stem cells, and biodistribution of the radiolabeled stem cells in nude mice. These radiotracers were obtained in moderate to high radiochemical yields. Binding to cells were moderate (20-60%/10{sup 6} cells) and the label was retained, although washout (an average of 18-55%) was observed depending on the cell type and the tracer used. The labeled cells initially localized in well perfused organs and at a later time showed a general distribution as expected. The novel tracers labeled several cell types and shown that the stability of the label and viability of the cells were maintained in vitro and in vivo for a reasonable period and warrant further in vivo investigation.

  8. Group 5 allergens of timothy grass (Phl p 5) bear cross-reacting T cell epitopes with group 1 allergens of rye grass (Lol p 1).

    Science.gov (United States)

    Müller, W D; Karamfilov, T; Bufe, A; Fahlbush, B; Wolf, I; Jäger, L

    1996-04-01

    Selected human T cell clones reactive with group 5 allergens of timothy grass (Phl p 5) were cross-stimulated in specific proliferation assays with group 1 allergens of rye grass (Lol p 1). Such interspecies cross-reactivities result obviously from structural motifs presented on defined Phl p 5 fragments as shown with recombinant Phl p 5 products.

  9. Protective effect of Sestrin2 on apoptosis of dendritic cells induced by high mobility group box-1 protein

    Directory of Open Access Journals (Sweden)

    Li-xue WANG

    2018-04-01

    Full Text Available Objective To investigate the potential role of Sestrin2 (SESN2 in regulating the apoptosis of dendritic cells (DCs induced by high mobility group box-1 protein (HMGB1. Methods DCs (the murine DC cell line DC2.4 were cultured with or without HMGB1 stimulation (cultured with 10ng/ml HMGB1 for 8, 24 and 48 hours, or cultured with HMGB1 for 48 hours at different concentrations of 1, 10 and 100ng/ml, respectively, n=4. The protein level of SESN2, cleaved-caspase-3 and Bcl-2 were analyzed with Western blotting. Localization of SESN2 in cells was observed under confocal laser microscope (LSCM. Cell apoptosis was analyzed with flow cytometry. In addition, DC2.4 cells were transfected with lentivirus containing SESN2 LV-RNA, SESN2 siRNA sequence expressing plasmids or blank vector (NC, NS, n=4. These cells were then stimulated with HMGB1 (100ng/ml for 48 hours, and the apoptosis was accessed as mentioned above. Results Compared with the control group, the expression of SESN2 was obviously up-regulated after HMGB1 (10ng/ml stimulation for 24 and 48 hours (P<0.05. In a dose-dependent response, the expression of SESN2 was markedly enhanced in treatment with 1, 10, 100ng/ml HMGB1 for 48 hours (P<0.05. Compared with the control group (7.35%±1.33%, the percentage of apoptosis was significantly increased with 10, 100ng/ml HMGB1 for 48 hours [(17.02%±4.85%, 17.48%±4.04%, respectively, P<0.05 or P<0.01]. After transfection, compared with blank vector group, the apoptosis of SESN2 siRNA group obviously elevated [(65.96%±2.50% vs. (50.01%±2.07%, P<0.05], and cleaved-caspase-3 expression significantly increased while Bcl-2 expression obviously decreased. In SESN2 LV-RNA group, the apoptosis significantly decreased [(35.57%±1.69% vs. (49.04%±4.87%, P<0.05], and cleaved-caspase-3 expression decreased and Bcl-2 expression obviously increased compared with blank vector group (P<0.05. Conclusion SESN2 has a protective effect against HMGB1 induced apoptosis of DC2

  10. Opposing Effects of α2- and β-Adrenergic Receptor Stimulation on Quiescent Neural Precursor Cell Activity and Adult Hippocampal Neurogenesis

    Science.gov (United States)

    Prosper, Boris W.; Marathe, Swanand; Husain, Basma F. A.; Kernie, Steven G.; Bartlett, Perry F.; Vaidya, Vidita A.

    2014-01-01

    Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In this study, we used transgenic Nestin-GFP mice and neurosphere assays to show that modulation of α2- and β-adrenergic receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell population albeit in an opposing fashion. While selective stimulation of α2-adrenergic receptors decreases precursor cell activation, proliferation and immature neuron number, stimulation of β-adrenergic receptors activates the quiescent precursor pool and enhances their proliferation in the adult hippocampus. Furthermore, our data indicate no major role for α1-adrenergic receptors, as we did not observe any change in either the activation and proliferation of hippocampal precursors following selective stimulation or blockade of α1-adrenergic receptors. Taken together, our data suggest that under physiological as well as under conditions that lead to enhanced norepinephrine release, the balance between α2- and β-adrenergic receptor activity regulates precursor cell activity and hippocampal neurogenesis. PMID:24922313

  11. Hand-held cell phone use while driving legislation and observed driver behavior among population sub-groups in the United States

    Directory of Open Access Journals (Sweden)

    Toni M. Rudisill

    2017-05-01

    Full Text Available Abstract Background Cell phone use behaviors are known to vary across demographic sub-groups and geographic locations. This study examined whether universal hand-held calling while driving bans were associated with lower road-side observed hand-held cell phone conversations across drivers of different ages (16–24, 25–59, ≥60 years, sexes, races (White, African American, or other, ruralities (suburban, rural, or urban, and regions (Northeast, Midwest, South, and West. Methods Data from the 2008–2013 National Occupant Protection Use Survey were merged with states’ cell phone use while driving legislation. The exposure was presence of a universal hand-held cell phone ban at time of observation. Logistic regression was used to assess the odds of drivers having a hand-held cell phone conversation. Sub-groups differences were assessed using models with interaction terms. Results When universal hand-held cell phone bans were effective, hand-held cell phone conversations were lower across all driver demographic sub-groups and regions. Sub-group differences existed among the sexes (p-value, <0.0001 and regions (p-value, 0.0003. Compared to states without universal hand-held cell phone bans, the adjusted odds ratio (aOR of a driver hand-held phone conversation was 0.34 [95% confidence interval (CI: 0.28, 0.41] for females versus 0.47 (CI 0.40, 0.55 for males and 0.31 (CI 0.25, 0.38 for drivers in Western states compared to 0.47 (CI 0.30, 0.72 in the Northeast and 0.50 (CI 0.38, 0.66 in the South. Conclusions The presence of universal hand-held cell phone bans were associated lower hand-held cell phone conversations across all driver sub-groups and regions. Hand-held phone conversations were particularly lower among female drivers and those from Western states when these bans were in effect. Public health interventions concerning hand-held cell phone use while driving could reasonably target all drivers.

  12. Challenges and opportunities for international cooperative studies in pediatric hematopoeitic cell transplantation: priorities of the Westhafen Intercontinental Group.

    Science.gov (United States)

    Schultz, Rudolph Kirk R; Baker, Kevin Scott; Boelens, Jaap J; Bollard, Catherine M; Egeler, R Maarten; Cowan, Mort; Ladenstein, Ruth; Lankester, Arjan; Locatelli, Franco; Lawitschka, Anita; Levine, John E; Loh, Mignon; Nemecek, Eneida; Niemeyer, Charlotte; Prasad, Vinod K; Rocha, Vanderson; Shenoy, Shalini; Strahm, Brigitte; Veys, Paul; Wall, Donna; Bader, Peter; Grupp, Stephan A; Pulsipher, Michael A; Peters, Christina

    2013-09-01

    More than 20% of allogeneic hematopoietic cell transplantations (HCTs) are performed in children and adolescents at a large number of relatively small centers. Unlike adults, at least one-third of HCTs in children are performed for rare, nonmalignant indications. Clinical trials to improve HCT outcomes in children have been limited by small numbers and these pediatric-specific features. The need for a larger number of pediatric HCT centers to participate in trials has led to the involvement of international collaborative groups. Representatives of the Pediatric Blood and Marrow Transplant Consortium, European Group for Blood and Marrow Transplantation's Pediatric Working Group, International Berlin-Frankfurt-Munster (iBFm) Stem Cell Transplantation Committee, and Children's Oncology Group's Hematopoietic Stem Cell Transplantation Discipline Committee met on October 3, 2012, in Frankfurt, Germany to develop a consensus on the highest priorities in pediatric HCT. In addition, it explored the creation of an international consortium to develop studies focused on HCT in children and adolescents. This meeting led to the creation of an international HCT network, dubbed the Westhafen Intercontinental Group, to develop worldwide priorities and strategies to address pediatric HCT issues. This review outlines the priorities of need as identified by this consensus group. Copyright © 2013 American Society for Blood and Marrow Transplantation. All rights reserved.

  13. cell-derived IFN-γ downregulates protective group 2 innate lymphoid cells in murine lupus erythematosus.

    Science.gov (United States)

    Düster, Mathis; Becker, Martina; Gnirck, Ann-Christin; Wunderlich, Malte; Panzer, Ulf; Turner, Jan-Eric

    2018-04-19

    Innate lymphoid cells (ILCs) are important regulators of the immune response and play a crucial role in the restoration of tissue homeostasis after injury. GATA-3 + IL-13- and IL-5-producing group 2 innate lymphoid cells (ILC2s) have been shown to promote tissue repair in barrier organs, but despite extensive research on ILCs in the recent years, their potential role in autoimmune diseases is still incompletely understood. In the present study, we investigate the role of ILC2s in the MRL/MpJ-Fas lpr (MRL-lpr) mouse model for severe organ manifestation of systemic lupus erythematosus (SLE). We show that in these MRL-lpr mice, progression of lupus nephritis is accompanied with a reduction of ILC2 abundance in the inflamed renal tissue. Proliferation/survival and cytokine production of kidney-residing ILC2s was suppressed by IFN-γ and, to a lesser extent, by IL-27 which were produced by activated T cells and myeloid cells in the nephritic kidney, respectively. Most importantly, restoration of ILC2 numbers by IL-33-mediated expansion ameliorated lupus nephritis and prevented mortality in MRL-lpr mice. In summary, we show here that development of SLE-like kidney inflammation leads to a downregulation of the renal ILC2 response and identify an ILC2-expanding therapy as a promising treatment approach for autoimmune diseases. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Polycomb Group Protein YY1 Is an Essential Regulator of Hematopoietic Stem Cell Quiescence

    Directory of Open Access Journals (Sweden)

    Zhanping Lu

    2018-02-01

    Full Text Available Yin yang 1 (YY1 is a ubiquitous transcription factor and mammalian polycomb group protein (PcG with important functions to regulate embryonic development, lineage differentiation, and cell proliferation. YY1 mediates stable PcG-dependent transcriptional repression via recruitment of PcG proteins that catalyze histone modifications. Many questions remain unanswered regarding how cell- and tissue-specificity is achieved by PcG proteins. Here, we demonstrate that a conditional knockout of Yy1 in hematopoietic stem cells (HSCs decreases long-term repopulating activity and ectopic YY1 expression expands HSCs. Although the YY1 PcG domain is required for Igκ chain rearrangement in B cells, the YY1 mutant lacking the PcG domain retained the capacity to stimulate HSC self-renewal. YY1 deficiency deregulated the genetic network governing HSC cell proliferation and impaired stem cell factor/c-Kit signaling, disrupting mechanisms conferring HSC quiescence. These results reveal a mechanism for how a ubiquitously expressed transcriptional repressor mediates lineage-specific functions to control adult hematopoiesis.

  15. Genetic and epigenetic alterations of the blood group ABO gene in oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Gao, Shan; Worm, Jesper; Guldberg, Per

    2004-01-01

    Loss of histo-blood group A and B antigen expression is a frequent event in oral carcinomas and is associated with decreased activity of glycosyltransferases encoded by the ABO gene. We examined 30 oral squamous cell carcinomas for expression of A and B antigens and glycosyltransferases. We also....... Collectively, we have identified molecular events that may account for loss of A/B antigen expression in 67% of oral squamous cell carcinomas....

  16. Monkey Adrenal Chromaffin Cells Express α6β4* Nicotinic Acetylcholine Receptors

    Science.gov (United States)

    Scadden, Mick´l; Carmona-Hidalgo, Beatriz; McIntosh, J. Michael; Albillos, Almudena

    2014-01-01

    Nicotinic acetylcholine receptors (nAChRs) that contain α6 and β4 subunits have been demonstrated functionally in human adrenal chromaffin cells, rat dorsal root ganglion neurons, and on noradrenergic terminals in the hippocampus of adolescent mice. In human adrenal chromaffin cells, α6β4* nAChRs (the asterisk denotes the possible presence of additional subunits) are the predominant subtype whereas in rodents, the predominant nAChR is the α3β4* subtype. Here we present molecular and pharmacological evidence that chromaffin cells from monkey (Macaca mulatta) also express α6β4* receptors. PCR was used to show the presence of transcripts for α6 and β4 subunits and pharmacological characterization was performed using patch-clamp electrophysiology in combination with α-conotoxins that target the α6β4* subtype. Acetylcholine-evoked currents were sensitive to inhibition by BuIA[T5A,P6O] and MII[H9A,L15A]; α-conotoxins that inhibit α6-containing nAChRs. Two additional agonists were used to probe for the expression of α7 and β2-containing nAChRs. Cells with currents evoked by acetylcholine were relatively unresponsive to the α7-selctive agonist choline but responded to the agonist 5-I-A-85380. These studies provide further insights into the properties of natively expressed α6β4* nAChRs. PMID:24727685

  17. Introduction of functionalizable groups via radiation grafting into polymer electrolyte membranes for fuel cells

    International Nuclear Information System (INIS)

    Buchmueller, Y.; Scherer, G.G.; Wokaun, A.; Gubler, L.

    2011-01-01

    Complete text of publication follows. Our work is focused on the introduction of functionalizable groups, so called linkers, to polymer electrolyte membranes. The aim is to attach antioxidant groups to the linkers to enhance the durability of the proton conducting membrane in a fuel cell. The synthetic route we chose is radiation cografting of functionalizable monomers and precursor monomers of a protogenic group into ETFE base film (thickness 25 μm) with subsequent amination. Typically, we performed cografting of styrene with different linkers, such as acryloyl chloride, vinylbenzyl chloride, and glycidyl methacrylate. Styrene is readily sulfonated to introduce proton conductivity. The cografting behavior of the linkers and styrene was investigated to target the desired molar fraction of the monomers in the grafted polymer. All films were characterized by Fourier transform infrared (FTIR) spectroscopy and elemental analysis. Using these data the graft polymerization kinetics of these systems have been determined. The cografted films were first functionalized with amines, such as thyramine and dopamine, and then sulfonated or vice-versa, depending on the stability of the compounds in acidic environment. The synthesized membranes were characterized for conductivity and ion exchange capacity (IEC). Promising membranes were tested in a fuel cell.

  18. Reduced Sympathetic Innervation in Endometriosis is Associated to Semaphorin 3C and 3F Expression.

    Science.gov (United States)

    Scheerer, Claudia; Frangini, Sergio; Chiantera, Vito; Mechsner, Sylvia

    2017-09-01

    Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic innervation and the expression of the specific semaphorins and receptors possibly involved in the neuroimmunomodulation in endometriosis. Our studies revealed an affected innervation and a significant increase of semaphorins and their receptors in peritoneal endometriotic tissue. Thereby, the expression of the receptors was identified on the membrane of noradrenergic nerve fibers and vessels. Macrophages and activated fibroblasts were found in higher density levels and additionally express semaphorins in peritoneal endometriotic tissue. Inflammation leads to an increased release of immune cells, which secrete a variety of inflammatory factors capable of affecting innervation. Therefore, our data suggests that the chronic inflammatory condition in endometriosis might contribute to the increase of semaphorins, which could possibly affect the innervation in peritoneal endometriosis.

  19. High-efficiency organic solar cells based on end-functional-group-modified poly(3-hexylthiophene)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Soo; Lee, Ji Hwang [School of Environmental Science and Engineering Polymer Research Institute, Pohang University of Science and Engineering Pohang, 790-784 (Korea); Lee, Youngmin; Park, Jong Hwan; Kim, Jin Kon; Cho, Kilwon [Department of Chemical Engineering Polymer Research Institute, Pohang University of Science and Engineering Pohang, 790-784 (Korea)

    2010-03-26

    Photovoltaic devices of end-functional-group-modified poly 3-(hexylthiophene)/[6,6]-phenyl-C{sub 61} butyric acid methyl ester (P3HT:PCBM) are fabricated with thermal annealing. The surface energies between donor and acceptor were matched by varying the end group, which can be used to control vertical and horizontal phase separation in the active layer, leading mixed nanomorphology with optimized phase separation, low series resistance, and high performance for solar cell devices. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  20. "Spider"-shaped porphyrins with conjugated pyridyl anchoring groups as efficient sensitizers for dye-sensitized solar cells.

    Science.gov (United States)

    Stangel, Christina; Bagaki, Anthi; Angaridis, Panagiotis A; Charalambidis, Georgios; Sharma, Ganesh D; Coutsolelos, Athanasios G

    2014-11-17

    Two novel "spider-shaped" porphyrins, meso-tetraaryl-substituted 1PV-Por and zinc-metalated 1PV-Zn-Por, bearing four oligo(p-phenylenevinylene) (oPPV) pyridyl groups with long dodecyloxy chains on the phenyl groups, have been synthesized. The presence of four pyridyl groups in both porphyrins, which allow them to act as anchoring groups upon coordination to various Lewis acid sites, the conjugated oPPV bridges, which offer the possibility of electronic communication between the porphyrin core and the pyridyl groups, and the dodecyloxy groups, which offer the advantage of high solubility in a variety of organic solvents of different polarities and could prevent porphyrin aggregation, renders porphyrins 1PV-Por and 1PV-Zn-Por very promising sensitizers for dye-sensitized solar cells (DSSCs). Photophysical measurements, together with electrochemistry experiments and density functional theory calculations, suggest that both porphyrins have frontier molecular orbital energy levels that favor electron injection and dye regeneration in DSSCs. Solar cells sensitized by 1PV-Por and 1PV-Zn-Por were fabricated, and it was found that they show power conversion efficiencies (PCEs) of 3.28 and 5.12%, respectively. Photovoltaic measurements (J-V curves) together with incident photon-to-electron conversion efficiency spectra of the two cells reveal that the higher PCE value of the DSSC based on 1PV-Zn-Por is ascribed to higher short-circuit current (Jsc), open-circuit voltage (Voc), and dye loading values. Emission spectra and electrochemistry experiments suggest a greater driving force for injection of the photogenerated electrons into the TiO2 conduction band for 1PV-Zn-Por rather than its free-base analogue. Furthermore, electrochemical impedance spectroscopy measurements prove that the utilization of 1PV-Zn-Por as a sensitizer offers a high charge recombination resistance and, therefore, leads to a longer electron lifetime.

  1. Ordered self-assembled monolayers terminated with different chemical functional groups direct neural stem cell linage behaviours

    International Nuclear Information System (INIS)

    Yao, Shenglian; Liu, Xi; He, Jin; Wang, Xiumei; Wang, Ying; Cui, Fu-Zhai

    2016-01-01

    Neural stem cells (NSCs) have been a promising candidate for stem cell-based nerve tissue regeneration. Therefore, the design of idea biomaterials that deliver precise regulatory signals to control stem cell fate is currently a crucial issue that depends on a profound understanding of the interactions between NSCs with the surrounding micro-environment. In this work, self-assembled monolayers of alkanethiols on gold with different chemical groups, including hydroxyl (−OH), amino (−NH 2 ), carboxyl (−COOH) and methyl (−CH 3 ), were used as a simple model to study the effects of surface chemistry on NSC fate decisions. Contact angle measurement and x-ray photoelectron spectroscopy (XPS) examination implied that all types of alkanethiols self-assembled on gold into a close-packed phase structure with similar molecular densities. In this study, we evaluated NSC adhesion, migration and differentiation in response to different chemical functional groups cultured under serum-free conditions. Our studies showed that NSCs exhibited certain phenotypes with extreme sensitivity to surface chemical groups. Compared with other functional groups, the SAMs with hydroxyl end-groups provided the best micro-environment in promoting NSC migration and maintaining an undifferentiated or neuronal differentiation state.  −NH 2 surfaces directed neural stem cells into astrocytic lineages, while NSCs on  −COOH and  −CH 3 surfaces had a similar potency to differentiate into three nerve lineages. To further investigate the possible signaling pathway, the gene expression of integrin β1 and β4 were examined. The results indicated that a high expression of β1 integrin would probably have a tight correlation with the expression of nestin, which implied the stemness of NSCs, while β4 integrin seemed to correspond to the differentiated NSCs. The results presented here give useful information for the future design of biomaterials to regulate the preservation

  2. A comparative study of cross sections at few energy groups for thermal reactors fuel cells

    International Nuclear Information System (INIS)

    Claro, L.H.; Prati, A.

    1992-01-01

    A comparative study of nuclear constant calculated with LEOPARD and WIMSD-4 codes using a typical PWR cell was done. Few groups macroscopic cross section, spectral index burnup and power distribution were analyzed. (author)

  3. Necrotic enlargement of cone photoreceptor cells and the release of high-mobility group box-1 in retinitis pigmentosa

    Science.gov (United States)

    Murakami, Y; Ikeda, Y; Nakatake, S; Tachibana, T; Fujiwara, K; Yoshida, N; Notomi, S; Nakao, S; Hisatomi, T; Miller, J W; Vavvas, DG; Sonoda, KH; Ishibashi, T

    2015-01-01

    Retinitis pigmentosa (RP) refers to a group of inherited retinal degenerations resulting form rod and cone photoreceptor cell death. The rod cell death due to deleterious genetic mutations has been shown to occur mainly through apoptosis, whereas the mechanisms and features of the secondary cone cell death have not been fully elucidated. Our previous study showed that the cone cell death in rd10 mice, an animal model of RP, involves necrotic features and is partly mediated by the receptor interacting protein kinase. However, the relevancy of necrotic cone cell death in human RP patients remains unknown. In the present study, we showed that dying cone cells in rd10 mice exhibited cellular enlargement, along with necrotic changes such as cellular swelling and mitochondrial rupture. In human eyes, live imaging of cone cells by adaptive optics scanning laser ophthalmoscopy revealed significantly increased percentages of enlarged cone cells in the RP patients compared with the control subjects. The vitreous of the RP patients contained significantly higher levels of high-mobility group box-1, which is released extracellularly associated with necrotic cell death. These findings suggest that necrotic enlargement of cone cells is involved in the process of cone degeneration, and that necrosis may be a novel target to prevent or delay the loss of cone-mediated central vision in RP. PMID:27551484

  4. One-group transport theory calculation for three slabs cells

    International Nuclear Information System (INIS)

    Maia, C.R.M.

    1979-01-01

    As an idealized model of plate type fuel assemblies for nuclear reactors, three-slab cells are analysed numerically based on the exact solution of the transport equation in the one-group isotropic scattering model. From the equations describing the interface conditions, a set of regular integral equations for the coefficients of the singular eigenfunctions expansions is derived using the half-range orthogonality relations of the eigenfunctions and the recently developed method of regularization. Numerical solutions are obtained by solving this set of equations iteratively. The thermal utilization factor and thermal disadvantage factors as well as flux and current distributions are reported for the first time for various sets of parameters. The accuracy of the P sub(N) approximations is also analysed compared to the exact results. (Author) [pt

  5. Stomatal cell wall composition: distinctive structural patterns associated with different phylogenetic groups.

    Science.gov (United States)

    Shtein, Ilana; Shelef, Yaniv; Marom, Ziv; Zelinger, Einat; Schwartz, Amnon; Popper, Zoë A; Bar-On, Benny; Harpaz-Saad, Smadar

    2017-04-01

    Stomatal morphology and function have remained largely conserved throughout ∼400 million years of plant evolution. However, plant cell wall composition has evolved and changed. Here stomatal cell wall composition was investigated in different vascular plant groups in attempt to understand their possible effect on stomatal function. A renewed look at stomatal cell walls was attempted utilizing digitalized polar microscopy, confocal microscopy, histology and a numerical finite-elements simulation. The six species of vascular plants chosen for this study cover a broad structural, ecophysiological and evolutionary spectrum: ferns ( Asplenium nidus and Platycerium bifurcatum ) and angiosperms ( Arabidopsis thaliana and Commelina erecta ) with kidney-shaped stomata, and grasses (angiosperms, family Poaceae) with dumbbell-shaped stomata ( Sorghum bicolor and Triticum aestivum ). Three distinct patterns of cellulose crystallinity in stomatal cell walls were observed: Type I (kidney-shaped stomata, ferns), Type II (kidney-shaped stomata, angiosperms) and Type III (dumbbell-shaped stomata, grasses). The different stomatal cell wall attributes investigated (cellulose crystallinity, pectins, lignin, phenolics) exhibited taxon-specific patterns, with reciprocal substitution of structural elements in the end-walls of kidney-shaped stomata. According to a numerical bio-mechanical model, the end walls of kidney-shaped stomata develop the highest stresses during opening. The data presented demonstrate for the first time the existence of distinct spatial patterns of varying cellulose crystallinity in guard cell walls. It is also highly intriguing that in angiosperms crystalline cellulose appears to have replaced lignin that occurs in the stomatal end-walls of ferns serving a similar wall strengthening function. Such taxon-specific spatial patterns of cell wall components could imply different biomechanical functions, which in turn could be a consequence of differences in

  6. Reduction of the Nitro Group to Amine by Hydroiodic Acid to Synthesize o-Aminophenol Derivatives as Putative Degradative Markers of Neuromelanin

    OpenAIRE

    Wakamatsu, Kazumasa; Tanaka, Hitomi; Tabuchi, Keisuke; Ojika, Makoto; Zucca, Fabio; Zecca, Luigi; Ito, Shosuke

    2014-01-01

    Neuromelanin (NM) is produced in dopaminergic neurons of the substantia nigra (SN) and in noradrenergic neurons of the locus coeruleus (LC). The synthesis of NM in those neurons is a component of brain aging and there is the evidence that this pigment can be involved in the pathogenesis of neurodegenerative diseases such as Parkinson’s disease. NM is believed to derive from the oxidative polymerization of dopamine (DA) or norepinephrine (NE) with the participation of cysteine, dolichols and ...

  7. US DOE-EM On-Site Disposal Cell Working Group - Fostering Communication On Performance Assessment Challenges

    Energy Technology Data Exchange (ETDEWEB)

    Seitz, Roger R. [Savannah River Site (SRS), Aiken, SC (United States); Suttora, Linda C. [U.S. Department of Energy, Office of Site Restoration, Germantown, MD (United States); Phifer, Mark [Savannah River Site (SRS), Aiken, SC (United States)

    2014-03-01

    On-site disposal cells are in use and being considered at several U.S. Department of Energy (USDOE) sites as the final disposition for large amounts of waste associated with cleanup of contaminated areas and facilities. These facilities are typically developed with regulatory oversight from States and/or the US Environmental Protection Agency (USEPA) in addition to USDOE. The facilities are developed to meet design standards for disposal of hazardous waste as well as the USDOE performance based standards for disposal of radioactive waste. The involvement of multiple and different regulators for facilities across separate sites has resulted in some differences in expectations for performance assessments and risk assessments (PA/RA) that are developed for the disposal facilities. The USDOE-EM Office of Site Restoration formed a working group to foster improved communication and sharing of information for personnel associated with these Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) disposal cells and work towards more consistent assumptions, as appropriate, for technical and policy considerations related to performance and risk assessments in support of a Record of Decision and Disposal Authorization Statement. The working group holds teleconferences, as needed, focusing on specific topics of interest. The topics addressed to date include an assessment of the assumptions used for performance assessments and risk assessments (PA/RAs) for on-site disposal cells, requirements and assumptions related to assessment of inadvertent intrusion, DOE Manual 435.1-1 requirements, and approaches for consideration of the long-term performance of liners and covers in the context of PAs. The working group has improved communication among the staff and oversight personnel responsible for onsite disposal cells and has provided a forum to identify and resolve common concerns.

  8. Repair of damage by ultraviolet radiation in xeroderma pigmentosum cell strains of complementation groups E and F

    NARCIS (Netherlands)

    Zelle, B.; Berends, F.; Lohman, P.H.M.

    1980-01-01

    The xeroderma pignemtosum fibroblast strains XP2RO, complementation group E, and XP23OS, group F were compared with normal human primary fibroblasts UV. regard to repair of damage induced by 254-nn UV> In XP2RO cells, repair DNA synthesis, measured by autoradiography (unscheduled DNA synthesis =

  9. Noradrenergic signaling in the medial prefrontal cortex and amygdala differentially regulates vicarious trial-and-error in a spatial decision-making task.

    Science.gov (United States)

    Amemiya, Seiichiro; Kubota, Natsuko; Umeyama, Nao; Nishijima, Takeshi; Kita, Ichiro

    2016-01-15

    In uncertain choice situations, we deliberately search and evaluate possible options before taking an action. Once we form a preference regarding the current situation, we take an action more automatically and with less deliberation. In rats, the deliberation process can be seen in vicarious trial-and-error behavior (VTE), which is a head-orienting behavior toward options at a choice point. Recent neurophysiological findings suggest that VTE reflects the rat's thinking about future options as deliberation, expectation, and planning when rats feel conflict. VTE occurs depending on the demand: an increase occurs during initial learning, and a decrease occurs with progression in learning. However, the brain circuit underlying the regulation of VTE has not been thoroughly examined. In situations in which VTE often appears, the medial prefrontal cortex (mPFC) and the amygdala (AMY) are crucial for learning and decision making. Our previous study reported that noradrenaline regulates VTE. Here, to investigate whether the mPFC and AMY are involved in regulation of VTE, we examined the effects of local injection of clonidine, an alpha2 adrenergic autoreceptor agonist, into either region in rats during VTE and choice behavior during a T-maze choice task. Injection of clonidine into either region impaired selection of the advantageous choice in the task. Furthermore, clonidine injection into the mPFC suppressed occurrence of VTE in the early phase of the task, whereas injection into the AMY inhibited the decrease in VTE in the later phase and thus maintained a high level of VTE throughout the task. These results suggest that the mPFC and AMY play a role in the increase and decrease in VTE, respectively, and that noradrenergic mechanisms mediate the dynamic regulation of VTE over experiences. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Calculation of anisotropic few-group constants in asymptotic cells: the code ANICELL

    International Nuclear Information System (INIS)

    Devenyi, A.

    1985-10-01

    The theoretical background of the ANICELL computer program together with a user's manual is presented. ANICELL is a nuclear reactor neutron transport code which solves the traditional asymptotic and the so-called tilted flux transport problems in one-dimensional cylindrical geometry using linearly anisotropic scattering. The method of solution used is the first flight collision probability technique. Few-group constants including radial and axial diffusion coefficients for the cell are also prepared by the program. (author)

  11. 5-HT has contrasting effects in the frontal cortex, but not the hypothalamus, on changes in noradrenaline efflux induced by the monoamine releasing-agent, d-amphetamine, and the reuptake inhibitor, BTS 54 354.

    Science.gov (United States)

    Géranton, Sandrine M; Heal, David J; Stanford, S Clare

    2004-03-01

    There is extensive evidence for functional interactions between central noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used in freely-moving rats to compare the effects of 5-HT on noradrenergic transmission in the rat frontal cortex and hypothalamus. We studied the effects of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5-HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux of noradrenaline and on the noradrenergic responses to d-amphetamine, and the monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect spontaneous noradrenaline efflux in either brain region, whether or not alpha2-autoreceptors were inactivated by administration of the alpha2-antagonist, atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment augmented the amplitude of, and prolonged, the noradrenergic response to local infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50 microM). In the hypothalamus, pCPA did not affect the amplitude of the response to either of these agents but did prolong the effects of d-amphetamine on noradrenaline efflux. These findings suggest that serotonergic transmission has complex effects on the noradrenergic response to drugs that increase noradrenergic transmission in the frontal cortex, but has less influence in the hypothalamus.

  12. IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function.

    Science.gov (United States)

    Noval Rivas, Magali; Burton, Oliver T; Oettgen, Hans C; Chatila, Talal

    2016-09-01

    Food allergy is a major health issue, but its pathogenesis remains obscure. Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation. However their role in food allergy is largely unknown. We sought to investigate the role of ILC2s in food allergy. Food allergy-prone mice with a gain-of-function mutation in the IL-4 receptor α chain (Il4raF709) were orally sensitized with food allergens, and the ILC2 compartment was analyzed. The requirement for ILC2s in food allergy was investigated by using Il4raF709, IL-33 receptor-deficient (Il1rl1(-/-)), IL-13-deficient (Il13(-/-)), and IL-4-deficient (Il4(-/-)) mice and by adoptive transfer of in vitro-expanded ILC2s. Direct effects of ILC2s on regulatory T (Treg) cells and mast cells were analyzed in coculture experiments. Treg cell control of ILC2s was assessed in vitro and in vivo. Il4raF709 mice with food allergy exhibit increased numbers of ILC2s. IL-4 secretion by ILC2s contributes to the allergic response by reducing allergen-specific Treg cell and activating mast cell counts. IL-33 receptor deficiency in Il4raF709 Il1rl1(-/-) mice protects against allergen sensitization and anaphylaxis while reducing ILC2 induction. Adoptive transfer of wild-type and Il13(-/-) but not Il4(-/-) ILC2s restored sensitization in Il4raF709 Il1rl1(-/-) mice. Treg cells suppress ILC2s in vitro and in vivo. IL-4 production by IL-33-stimulated ILC2s blocks the generation of allergen-specific Treg cells and favors food allergy. Strategies to block ILC2 activation or the IL-33/IL-33 receptor pathway can lead to innovative therapies in the treatment of food allergy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. Protein replacement by receptor-mediated endocytosis corrects the sensitivity of Fanconi anemia group C cells to mitomycin C

    NARCIS (Netherlands)

    Youssoufian, H; Kruyt, FAE; Li, XT

    1999-01-01

    Current methods for direct gene transfer into hematopoietic cells are inefficient. Here we show that functional complementation of Fanconi anemia (FA) group C cells by protein replacement can be as efficacious as by transfection with wild-type FAC cDNA, We expressed a chimeric protein (called

  14. Tumor mutational load and immune parameters across metastatic Renal Cell Carcinoma (mRCC) risk groups

    Science.gov (United States)

    de Velasco, Guillermo; Miao, Diana; Voss, Martin H.; Hakimi, A. Ari; Hsieh, James J.; Tannir, Nizar M.; Tamboli, Pheroze; Appleman, Leonard J.; Rathmell, W. Kimryn; Van Allen, Eliezer M.; Choueiri, Toni K.

    2016-01-01

    Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared to patients with favorable or intermediate-risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole exome transcriptome data in RCC patients (n = 54) included in The Cancer Genome Atlas that ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Nonsynonymous mutational load did not differ significantly by MSKCC risk group, nor was the expression of cytolytic genes –granzyme A and perforin – or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis found that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. PMID:27538576

  15. CD1a presentation of endogenous antigens by group 2 innate lymphoid cells.

    Science.gov (United States)

    Hardman, Clare S; Chen, Yi-Ling; Salimi, Maryam; Jarrett, Rachael; Johnson, David; Järvinen, Valtteri J; Owens, Raymond J; Repapi, Emmanouela; Cousins, David J; Barlow, Jillian L; McKenzie, Andrew N J; Ogg, Graham

    2017-12-22

    Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells. CD1a expression is up-regulated by TSLP (thymic stromal lymphopoietin) at levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a previously unrecognized role for ILC2 in lipid surveillance and identify shared pathways of CD1a- and PLA2G4A-dependent ILC2 inflammation amenable to therapeutic intervention. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  16. The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall.

    Science.gov (United States)

    Lepiarczyk, E; Bossowska, A; Kaleczyc, J; Majewski, M

    2011-01-01

    Botulinum toxin (BTX) belongs to a family of neurotoxins which strongly influence the function of autonomic neurons supplying the urinary bladder. Accordingly, BTX has been used as an effective drug in experimental therapies of a range of neurogenic bladder disorders. However, there is no detailed information dealing with the influence of BTX on the morphological and chemical properties of nerve fibres supplying the urinary bladder wall. Therefore, the present study investigated, using double-labeling immunohistochemistry, the distribution, relative frequency and chemical coding of cholinergic and noradrenergic nerve fibers supplying the wall of the urinary bladder in normal female pigs (n = 6) and in the pigs (n = 6) after intravesical BTX injections. In the pigs injected with BTX, the number of adrenergic (DbetaH-positive) nerve fibers distributed in the bladder wall (urothelium, submucosa and muscle coat) was distinctly higher while the number of cholinergic (VAChT-positive) nerve terminals was lower than that found in the control animals. Moreover, the injections of BTX resulted in some changes dealing with the chemical coding of the adrenergic nerve fibers. In contrast to the normal pigs, in BTX injected animals the number of DbetaH/NPY- or DbetaH/CGRP-positive axons was higher in the muscle coat, and some fibres distributed in the urothelium and submucosa expressed immunoreactivity to CGRP. The results obtained suggest that the therapeutic effects of BTX on the urinary bladder might be dependent on changes in the distribution and chemical coding of nerve fibers supplying this organ.

  17. Comparative studies of upconversion luminescence characteristics and cell bioimaging based on one-step synthesized upconversion nanoparticles capped with different functional groups

    Energy Technology Data Exchange (ETDEWEB)

    Tsang, Ming-Kiu [Department of Applied Physics, The Hong Kong Polytechnic University, Hong Kong (China); Chan, Chi-Fai; Wong, Ka-Leung [Department of Chemistry, Hong Kong Baptist University (Hong Kong); Hao, Jianhua, E-mail: jh.hao@polyu.edu.hk [Department of Applied Physics, The Hong Kong Polytechnic University, Hong Kong (China)

    2015-01-15

    Herein, three types of upconverting NaGdF{sub 4}:Yb/Er nanoparticles (UCNPs) have been synthesized via one-step hydrothermal synthesis with polyethylene glycol (PEG), polyethylenimine (PEI) and 6-aminocapronic acid (6AA) functionalization. To evident the presence of these groups, FTIR spectra and ζ-potentials were measured to support the successful capping of PEG, PEI and 6AA on the UCNPs. The regular morphology and cubic phase of these functionalized UCNPs were attributed to the capping effect of the surfactants. Tunable upconversion luminescence (UCL) from red to green were observed under 980 nm laser excitation and the UCL tuning was attributed to the presence of various surface ligands. Moreover, surface group dependent UCL bioimaging was performed in HeLa cells. The enhanced UCL bioimaging demonstrated by PEI functionalized UCNPs evident high cell uptake. The significant cell uptake is explained by the electrostatic attraction between the amino groups (–NH{sub 2}) and the cell membrane. Moreover, the functionalized UCNPs demonstrated low cytotoxicity in MTT assay. Additional, paramagnetic property was presented by these UCNPs under magnetic field. - Highlights: • Tunable upconversion emission by capped functional groups under fixed composition. • Surface dependent upconversion luminescence bioimaging in HeLa cells. • Low cytotoxicity. • Additional paramagnetic property due to Gd{sup 3+} ions.

  18. Direct alcohol fuel cells: Increasing platinum performance by modification with sp-group metals

    Science.gov (United States)

    Figueiredo, Marta C.; Sorsa, Olli; Doan, Nguyet; Pohjalainen, Elina; Hildebrand, Helga; Schmuki, Patrik; Wilson, Benjamin P.; Kallio, Tanja

    2015-02-01

    By using sp group metals as modifiers, the catalytic properties of Pt can be improved toward alcohols oxidation. In this work we report the performance increase of direct alcohol fuel cells (DAFC) fuelled with ethanol or 2-propanol with platinum based anode electrodes modified with Bi and Sb adatoms. For example, by simply adding Sb to the Pt/C based anode ink during membrane electrode assembly fabrication of a direct ethanol fuel cell (DEFC) its performance is improved three-fold, with more than 100 mV increase in the open circuit potential. For the fuel cell fuelled with 2-propanol high power densities are obtained at very high potentials with these catalyst materials suggesting a great improvement for practical applications. Particularly in the case of Pt/C-Bi, the improvement is such that within 0.6 V (from 0.7 to 0.1 V) the power densities are between 7 and 9 mW/cm2. The results obtained with these catalysts are in the same range as those obtained with other bimetallic catalysts comprising of PtRu and PtSn, which are currently considered to be the best for these type of fuel cells and that are obtained by more complicated (and consequently more expensive) methods.

  19. CAUDAL MEDULLARY PATHWAYS TO LUMBOSACRAL MOTONEURONAL CELL GROUPS IN THE CAT - EVIDENCE FOR DIRECT PROJECTIONS POSSIBLY REPRESENTING THE FINAL COMMON PATHWAY FOR LORDOSIS

    NARCIS (Netherlands)

    VANDERHORST, VGJM; HOLSTEGE, G

    1995-01-01

    The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase

  20. Caudal Medullary Pathways To Lumbosacral Motoneuronal Cell Groups In The Cat; Evidence For Direct Projections Possibly Representing The Final Common Pathway For Lordosis.

    NARCIS (Netherlands)

    VanderHorst, Veronique G.J.M.; Holstege, Gert

    1995-01-01

    The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase

  1. Beta 1- and beta 2-adrenergic 125I-pindolol binding sites in the interpeduncular nucleus of the rat: Normal distribution and the effects of deafferentation

    International Nuclear Information System (INIS)

    Battisti, W.P.; Artymyshyn, R.P.; Murray, M.

    1989-01-01

    The plasticity of the beta 1- and beta 2-adrenergic receptor subtypes was examined in the interpeduncular nucleus (IPN) of the adult rat. The beta-adrenergic receptor antagonist 125I-pindolol (125I-PIN) was used in conjunction with the selective subtype antagonists ICI 118,551 and ICI 89,406 to determine the subnuclear distribution of beta 1- and beta 2-adrenergic receptors in this nucleus and to correlate the receptor distribution with the distribution of both noradrenergic afferents from the locus coeruleus (LC) and non-noradrenergic afferents from the fasiculus retroflexus (FR). The density of these binding sites was examined following lesions that decreased (LC lesions) or increased (FR lesions) the density of the noradrenergic projection in the IPN. Quantitative radioautography indicated that beta 1-labeled binding sites account for the larger percentage of binding sites in the IPN. The beta 1-binding sites are densest in those subnuclei that receive a noradrenergic projection from the LC: the central, rostral, and intermediate subnuclei. beta 1-binding sites are algo homogeneously distributed throughout the lateral subnuclei, where there is no detectable noradrenergic innervation. beta 2-binding sites have a more restricted distribution. They are concentrated in the ventral half of the lateral subnuclei, where they account for 70% of total 125I-PIN binding sites. beta 2-binding sites are also present along the ventral border of the IPN. Some of this labeling extends into the central and intermediate subnuclei. Bilateral lesions of the LC, which selectively remove noradrenergic innervation to the IPN, result in an increase in the beta 1-binding sites. Bilateral lesions of the FR, which remove the major cholinergic and peptidergic input from the IPN, elicit an increase in noradrenergic projections and a decrease in beta 1-binding sites

  2. Modeling Group B Streptococcus and Blood-Brain Barrier Interaction by Using Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells

    OpenAIRE

    Kim, Brandon J.; Bee, Olivia B.; McDonagh, Maura A.; Stebbins, Matthew J.; Palecek, Sean P.; Doran, Kelly S.; Shusta, Eric V.

    2017-01-01

    ABSTRACT Bacterial meningitis is a serious infection of the central nervous system (CNS) that occurs after bacteria interact with and penetrate the blood-brain barrier (BBB). The BBB is comprised of highly specialized brain microvascular endothelial cells (BMECs) that function to separate the circulation from the CNS and act as a formidable barrier for toxins and pathogens. Certain bacteria, such as Streptococcus agalactiae (group B Streptococcus [GBS]), possess the ability to interact with a...

  3. Role of the Group B antigen of Streptococcus agalactiae: a peptidoglycan-anchored polysaccharide involved in cell wall biogenesis.

    Directory of Open Access Journals (Sweden)

    Élise Caliot

    Full Text Available Streptococcus agalactiae (Group B streptococcus, GBS is a leading cause of infections in neonates and an emerging pathogen in adults. The Lancefield Group B carbohydrate (GBC is a peptidoglycan-anchored antigen that defines this species as a Group B Streptococcus. Despite earlier immunological and biochemical characterizations, the function of this abundant glycopolymer has never been addressed experimentally. Here, we inactivated the gene gbcO encoding a putative UDP-N-acetylglucosamine-1-phosphate:lipid phosphate transferase thought to catalyze the first step of GBC synthesis. Indeed, the gbcO mutant was unable to synthesize the GBC polymer, and displayed an important growth defect in vitro. Electron microscopy study of the GBC-depleted strain of S. agalactiae revealed a series of growth-related abnormalities: random placement of septa, defective cell division and separation processes, and aberrant cell morphology. Furthermore, vancomycin labeling and peptidoglycan structure analysis demonstrated that, in the absence of GBC, cells failed to initiate normal PG synthesis and cannot complete polymerization of the murein sacculus. Finally, the subcellular localization of the PG hydrolase PcsB, which has a critical role in cell division of streptococci, was altered in the gbcO mutant. Collectively, these findings show that GBC is an essential component of the cell wall of S. agalactiae whose function is reminiscent of that of conventional wall teichoic acids found in Staphylococcus aureus or Bacillus subtilis. Furthermore, our findings raise the possibility that GBC-like molecules play a major role in the growth of most if not all beta-hemolytic streptococci.

  4. The Importance of End Groups for Solution-Processed Small-Molecule Bulk-Heterojunction Photovoltaic Cells.

    Science.gov (United States)

    Duan, Ruomeng; Cui, Yong; Zhao, Yanfei; Li, Chen; Chen, Long; Hou, Jianhui; Wagner, Manfred; Baumgarten, Martin; He, Chang; Müllen, Klaus

    2016-05-10

    End groups in small-molecule photovoltaic materials are important owing to their strong influence on molecular stability, solubility, energy levels, and aggregation behaviors. In this work, a series of donor-acceptor pentads (D2 -A-D1 -A-D2 ) were designed and synthesized, aiming to investigate the effect of the end groups on the materials properties and photovoltaic device performance. These molecules share identical central A-D1 -A triads (with benzodithiophene as D1 and 6-carbonyl-thieno[3,4-b]thiophene as A), but with various D2 end groups composed of alkyl-substituted thiophene (T), thieno[3,2-b]thiophene (TT), and 2,2'-bithiophene (BT). The results indicate a relationship between conjugated segment/alkyl chain length of the end groups and the photovoltaic performance, which contributes to the evolving molecular design principles for high efficiency organic solar cells. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Sub-cell balanced nodal expansion methods using S4 eigenfunctions for multi-group SN transport problems in slab geometry

    International Nuclear Information System (INIS)

    Hong, Ser Gi; Lee, Deokjung

    2015-01-01

    A highly accurate S 4 eigenfunction-based nodal method has been developed to solve multi-group discrete ordinate neutral particle transport problems with a linearly anisotropic scattering in slab geometry. The new method solves the even-parity form of discrete ordinates transport equation with an arbitrary S N order angular quadrature using two sub-cell balance equations and the S 4 eigenfunctions of within-group transport equation. The four eigenfunctions from S 4 approximation have been chosen as basis functions for the spatial expansion of the angular flux in each mesh. The constant and cubic polynomial approximations are adopted for the scattering source terms from other energy groups and fission source. A nodal method using the conventional polynomial expansion and the sub-cell balances was also developed to be used for demonstrating the high accuracy of the new methods. Using the new methods, a multi-group eigenvalue problem has been solved as well as fixed source problems. The numerical test results of one-group problem show that the new method has third-order accuracy as mesh size is finely refined and it has much higher accuracies for large meshes than the diamond differencing method and the nodal method using sub-cell balances and polynomial expansion of angular flux. For multi-group problems including eigenvalue problem, it was demonstrated that the new method using the cubic polynomial approximation of the sources could produce very accurate solutions even with large mesh sizes. (author)

  6. Olanzapine and sibutramine have opposing effects on the motivation for palatable food

    NARCIS (Netherlands)

    van der Zwaal, Esther M.; Janhunen, Sanna K.; Luijendijk, Mieneke C. M.; Baclesanu, Roxana; Vanderschuren, Louk J. M. J.; Adan, Roger A. H.; la Fleur, Susanne E.

    2012-01-01

    Both olanzapine and sibutramine target serotonergic and noradrenergic neurotransmission and influence body weight, but in opposite ways. The second-generation antipsychotic olanzapine, an antagonist at serotonergic and noradrenergic receptors, frequently induces weight gain as a side-effect, whereas

  7. Group I mGlu receptor stimulation inhibits activation-induced cell death of human T lymphocytes

    Science.gov (United States)

    Chiocchetti, Annalisa; Miglio, Gianluca; Mesturini, Riccardo; Varsaldi, Federica; Mocellin, Marco; Orilieri, Elisabetta; Dianzani, Chiara; Fantozzi, Roberto; Dianzani, Umberto; Lombardi, Grazia

    2006-01-01

    The effects of L-glutamate on activation-induced cell death (AICD) of human activated (1 μg ml−1 phytohemagglutinin plus 2 U ml−1 interleukin-2; 8 days) T lymphocytes were studied by measuring anti-CD3 monoclonal antibody (10 μg ml−1; 18 h)-induced cell apoptosis (Annexin V and propidium iodide staining). L-Glutamate (1 × 10−8–1 × 10−4 M) significantly (P⩽0.01) inhibited AICD in a concentration-dependent manner (EC50=6.3 × 10−8 M; maximum inhibition 54.8±6.3% at 1 × 10−6 M). The L-glutamate inhibitory effect was pharmacologically characterized as mediated by group I mGlu receptors, since mGlu receptor agonists reproduced this effect. The EC50 values were: 3.2 × 10−7 M for (1S,3R)-ACPD; 4.5 × 10−8 M for quisqualate; 1.0 × 10−6 M for (S)-3,5-DHPG; 2.0 × 10−5 M for CHPG. Group I mGlu receptor antagonists inhibited the effects of quisqualate 1.0 × 10−6 M. The IC50 values calculated were: 8.7 × 10−5, 4.3 × 10−6 and 6.3 × 10−7 M for AIDA, LY 367385 and MPEP, respectively. L-Glutamate (1 × 10−6 M; 18 h) significantly (P⩽0.05) inhibited FasL expression (40.8±11.3%) (cytofluorimetric analysis), whereas it did not affect Fas signalling. Expression of both mGlu1 and mGlu5 receptor mRNA by T lymphocytes and T-cell lines, as demonstrated by reverse transcriptase–PCR analysis, suggests that L-glutamate-mediated inhibition of AICD was exerted on T cells. These data depict a novel role for L-glutamate in the regulation of the immune response through group I mGlu receptor-mediated mechanisms. PMID:16751798

  8. 杏仁核内去甲肾上腺素在应激激素调控记忆保持过程中的作用%Role of amygdala norepinephrine in mediating stress hormone regu-lation of memory storage

    Institute of Scientific and Technical Information of China (English)

    Barbara FERRY; James L McGAUGH

    2000-01-01

    There is extensive evidence indicating that the noradrenergic system of the amygdala, particularly the basolateral nucleus of the amygdala (BLA), is involved in memory consolidation. This article reviews the central hypothesis that stress hormones released during emotionally arousing experiences activate noradrenergic mechanisms in the BLA, resulting in enhanced memory for those events. Findings from expenments using rats have shown that the memory-modulatory effects of the adrenocortical stress hormones epinephrine and glucocorficoids involve activation of β-adrenoceptors in the BLA. In addition, both behavioral and microdialysis studies have shown that the noradrenergic system of the BLA also mediates the influences of other neuromodulatory systems such as opioid peptidergic and GABAergic systems on memory storage. Other findings indicate that this stress hormone-induced activation of noradrenergic mechanisms in the BLA regulates memory storage in other brain regions.

  9. Group A Streptococcus Prevents Mast Cell Degranulation to Promote Extracellular Trap Formation

    Directory of Open Access Journals (Sweden)

    Mary Clark

    2018-02-01

    Full Text Available The resurgence of Group A Streptococcus (GAS infections in the past two decades has been a rising major public health concern. Due to a large number of GAS infections occurring in the skin, mast cells (MCs, innate immune cells known to localize to the dermis, could play an important role in controlling infection. MCs can exert their antimicrobial activities either early during infection, by degranulation and release of antimicrobial proteases and the cathelicidin-derived antimicrobial peptide LL-37, or by forming antibacterial MC extracellular traps (MCETs in later stages of infection. We demonstrate that MCs do not directly degranulate in response to GAS, reducing their ability to control bacterial growth in early stages of infection. However, MC granule components are highly cytotoxic to GAS due to the pore-forming activity of LL-37, while MC granule proteases do not significantly affect GAS viability. We therefore confirmed the importance of MCETs by demonstrating their capacity to reduce GAS survival. The data therefore suggests that LL-37 from MC granules become embedded in MCETs, and are the primary effector molecule by which MCs control GAS infection. Our work underscores the importance of a non-traditional immune effector cell, utilizing a non-conventional mechanism, in the defense against an important human pathogen.

  10. Functional and phenotypic heterogeneity of group 3 innate lymphoid cells.

    Science.gov (United States)

    Melo-Gonzalez, Felipe; Hepworth, Matthew R

    2017-03-01

    Group 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid-related orphan receptor γt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR + ILC3 and LTi-like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation - with a focus on comparing and contrasting the relative contributions of ILC3 subsets. © 2016 The Authors. Immunology published by John Wiley & Sons Ltd.

  11. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System.

    Science.gov (United States)

    Withers, David R; Hepworth, Matthew R

    2017-01-01

    The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of "exogenous" signals, such as dietary metabolites and commensal microbes, and "endogenous" host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a "communications hub" in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell-cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.

  12. Effects of carboxyl and ester anchoring groups on solar conversion efficiencies of TiO2 dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Sepehrifard, A.; Stublla, A.; Haftchenary, S.; Chen, S.; Potvin, P.; Morin, S. [York Univ., Toronto, ON (Canada). Dept. of Chemistry

    2008-07-01

    This paper reported on a study in which 2 new Ruthenium (Ru(2)) dyes bearing different anchoring groups were applied to sensitize TiO2 for dye-sensitized solar cells (DSSCs). The solar conversion efficiencies were measured. Results for 2 of the dyes which carried ester and carboxyl anchoring groups were presented. The extent and nature of the surface binding was studied using electrochemical, UV-visible, fluorescence and FTIR measurements. Solar cell performance was discussed in terms of surface concentration of chemisorbed dyes, electronic properties of the photoanodes and electrochemical properties of adsorbed dyes. The study showed that carboxylic acid groups offer better dye adsorption than ester groups. However, sensitization with warm solutions improved the adsorption of the esterified dye, most likely through transesterification. It was concluded that this may be a useful means of improving solar conversion efficiencies of ester-bearing dyes. 6 refs., 1 tab., 2 figs.

  13. Effect of Content of Sulfate Groups in Seaweed Polysaccharides on Antioxidant Activity and Repair Effect of Subcellular Organelles in Injured HK-2 Cells

    Directory of Open Access Journals (Sweden)

    Xiao-Tao Ma

    2017-01-01

    Full Text Available This study aims to investigate the repair effect of subcellular structure injuries of the HK-2 cells of four degraded seaweed polysaccharides (DSPs, namely, the degraded Porphyra yezoensis, Gracilaria lemaneiformis, Sargassum fusiform, and Undaria pinnatifida polysaccharides. The four DSPs have similar molecular weight, but with different content of sulfate groups (i.e., 17.9%, 13.3%, 8.2%, and 5.5%, resp.. The damaged model was established using 2.8 mmol/L oxalate to injure HK-2 cells, and 60 μg/mL of various DSPs was used to repair the damaged cells. With the increase of sulfate group content in DSPs, the scavenging activity of radicals and their reducing power were all improved. Four kinds of DSPs have repair effect on the subcellular organelles of damaged HK-2 cells. After being repaired by DSPs, the release amount of lactate dehydrogenase was decreased, the integrity of cell membrane and lysosome increased, the Δψm increased, the cell of G1 phase arrest was inhibited, the proportion of S phase increased, and cell apoptotic and necrosis rates were significantly reduced. The greater the content of sulfate group is, the stronger is the repair ability of the polysaccharide. These DSPs, particularly the polysaccharide with higher sulfate group content, may be a potential drug for the prevention and cure of kidney stones.

  14. The Aromatic Head Group of Spider Toxin Polyamines Influences Toxicity to Cancer Cells.

    Science.gov (United States)

    Wilson, David; Boyle, Glen M; McIntyre, Lachlan; Nolan, Matthew J; Parsons, Peter G; Smith, Jennifer J; Tribolet, Leon; Loukas, Alex; Liddell, Michael J; Rash, Lachlan D; Daly, Norelle L

    2017-10-27

    Spider venoms constitute incredibly diverse libraries of compounds, many of which are involved in prey capture and defence. Polyamines are often prevalent in the venom and target ionotropic glutamate receptors. Here we show that a novel spider polyamine, PA 366 , containing a hydroxyphenyl-based structure is present in the venom of several species of tarantula, and has selective toxicity against MCF-7 breast cancer cells. By contrast, a polyamine from an Australian funnel-web spider venom, which contains an identical polyamine tail to PA 366 but an indole-based head-group, is only cytotoxic at high concentrations. Our results suggest that the ring structure plays a role in the cytotoxicity and that modification to the polyamine head group might lead to more potent and selective compounds with potential as novel cancer treatments.

  15. The Aromatic Head Group of Spider Toxin Polyamines Influences Toxicity to Cancer Cells

    Directory of Open Access Journals (Sweden)

    David Wilson

    2017-10-01

    Full Text Available Spider venoms constitute incredibly diverse libraries of compounds, many of which are involved in prey capture and defence. Polyamines are often prevalent in the venom and target ionotropic glutamate receptors. Here we show that a novel spider polyamine, PA366, containing a hydroxyphenyl-based structure is present in the venom of several species of tarantula, and has selective toxicity against MCF-7 breast cancer cells. By contrast, a polyamine from an Australian funnel-web spider venom, which contains an identical polyamine tail to PA366 but an indole-based head-group, is only cytotoxic at high concentrations. Our results suggest that the ring structure plays a role in the cytotoxicity and that modification to the polyamine head group might lead to more potent and selective compounds with potential as novel cancer treatments.

  16. Recognition Strategies of Group 3 Innate Lymphoid Cells

    OpenAIRE

    Killig, Monica; Glatzer, Timor; Romagnani, Chiara

    2014-01-01

    During the early phase of an inflammatory response, innate cells can use different strategies to sense environmental danger. These include the direct interaction of specific activating receptors (actR) with pathogen-encoded/danger molecules or the engagement of cytokine receptors by pro-inflammatory mediators produced by antigen presenting cells (APC) in the course of the infection. These general recognition strategies, which have been extensively described for innate myeloid cells, are share...

  17. Index of CD34+ Cells and Mononuclear Cells in the Bone Marrow of Spinal Cord Injury Patients of Different Age Groups: A Comparative Analysis

    Directory of Open Access Journals (Sweden)

    Vidyasagar Devaprasad Dedeepiya

    2012-01-01

    Full Text Available Introduction. Recent evidence of safety and efficacy of Bone Marrow Mononuclear Cells (BMMNC in spinal cord injury makes the Bone Marrow (BM CD34+ percentage and the BMMNC count gain significance. The indices of BM that change with body mass index and aging in general population have been reported but seldom in Spinal Cord Injury (SCI victims, whose parameters of relevance differ from general population. Herein, we report the indices of BMMNC in SCI victims. Materials and Methods. BMMNCs of 332 SCI patients were isolated under GMP protocols. Cell count by Trypan blue method and CD34+ cells by flow cytometry were documented and analysed across ages and gender. Results. The average BMMNC per ml in the age groups 0–20, 21–40, 41–60, and 61–80 years were 4.71, 4.03, 3.67, and 3.02 million and the CD34+ were 1.05%, 1.04%, 0.94%, and 0.93% respectively. The decline in CD34+ was sharp between 20–40 and 40–60 age groups. Females of reproductive age group had lesser CD34+. Conclusion. The BMMNC and CD34+ percentages decline with aging in SCI victims. Their lower values in females during reproductive age should be analysed for relevance to hormonal influence. This study offers reference values of BMMNC and CD34+ of SCI victims for successful clinical application.

  18. Increased mRNA expression of cytochrome oxidase in dorsal raphe nucleus of depressive suicide victims

    Directory of Open Access Journals (Sweden)

    A Sanchez-Bahillo

    2008-04-01

    Full Text Available A Sanchez-Bahillo1, V Bautista-Hernandez1, Carlos Barcia Gonzalez1, R Bañon2, A Luna2, EC Hirsch3, Maria-Trinidad Herrero11Clinical and Experimental Neuroscience, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED; 2Department of Legal Medicine, Department of Human Anatomy, School of Medicine, University of Murcia, Campus de Espinardo, Murcia 30100, Spain; 3INSERM U679 Hôpital de la Salpêtrière, Boulevard de l’Hôpital, Paris, FranceAbstract: Suicidal behavior is a problem with important social repercussions. Some groups of the population show a higher risk of suicide; for example, depression, alcoholism, psychosis or drug abuse frequently precedes suicidal behavior. However, the relationship between metabolic alterations in the brain and premorbid clinical symptoms of suicide remains uncertain. The serotonergic and noradrenergic systems have frequently been, implicated in suicidal behavior and the amount of serotonin in the brain and CSF of suicide victims has been found to be low compared with normal subjects. However, there are contradictory results regarding the role of noradrenergic neurons in the mediation of suicide attempts, possibly reflecting the heterogeneity of conditions that lead to a common outcome. In the present work we focus on the subgroup of suicide victims that share a common diagnosis of major depression. Based on post-mortem studies analyzing mRNA expression by in situ hybridization, serotonergic neurons from the dorsal raphe nucleus (DRN from depressive suicide victims are seen to over-express cytochrome oxidase mRNA. However, no corresponding changes were found in the expression of tyrosine hydroxylase (TH mRNA in the noradrenergic neurons of the Locus Coeruleus (LC. These results suggest that, despite of the low levels of serotonin described in suicide victims, the activity of DRN neurons could increase in the suicidally depressed, probably due to the over activation of

  19. One group neutron flux at a point in a cylindrical reactor cell calculated by Monte Carlo

    Energy Technology Data Exchange (ETDEWEB)

    Kocic, A [Institute of Nuclear Sciences Vinca, Beograd (Serbia and Montenegro)

    1974-01-15

    Mean values of the neutron flux over material regions and the neutron flux at space points in a cylindrical annular cell (one group model) have been calculated by Monte Carlo. The results are compared with those obtained by an improved collision probability method (author)

  20. Fucoidan cytotoxicity against human breast cancer T47D cell line increases with higher level of sulfate ester group

    Science.gov (United States)

    Saepudin, Endang; Alfita Qosthalani, Fildzah; Sinurat, Ellya

    2018-01-01

    The anticancer activity of different sulfate ester group content in different molecular weight was examined. The anticancer activity was achieved in vitro on human breast cancer T47D cell line. Fucoidan with lower molecular weight (5.79 kDa) tends to have lower sulfate ester group content (8.69%) and resulted in higher IC50 value (184.22 μg/mL). While fucoidan with higher molecular weight (785.12 kDa) tends to have higher sulfate level (18.63%) and achieved lower IC50 value (75.69 μg/mL). The result showed that in order to maintain fucoidan cytotoxic activity against human breast cancer T47D cell line, the sulfate content should be remain high. Keywords: fucoidan, sulfate ester group, human breast cancer

  1. Participation of locus coeruleus in breathing control in female rats.

    Science.gov (United States)

    de Carvalho, Débora; Patrone, Luis Gustavo A; Marques, Danuzia A; Vicente, Mariane C; Szawka, Raphael E; Anselmo-Franci, Janete A; Bícego, Kênia C; Gargaglioni, Luciane H

    2017-11-01

    Several evidences indicate that the locus coeruleus (LC) is involved in central chemoreception responding to CO 2 /pH and displaying a high percentage of chemosensitive neurons (>80%). However, there are no studies about the LC-mediated hypercapnic ventilation performed in females. Therefore, we assessed the role of noradrenergic LC neurons in non-ovariectomized (NOVX), ovariectomized (OVX) and estradiol (E2)-treated ovariectomized (OVX+E2) rats in respiratory response to hypercapnia, using a 6-hydroxydopamine (6-OHDA) - lesion model. A reduction in the number of tyrosine hydroxylase (TH) immunoreactive neurons (51-90% in 3 animals of NOVX group, 20-42% of lesion in 5 animals of NOVX females, 61.3% for OVX and 62.6% for OVX+E2 group) was observed seven days after microinjection of 6-OHDA in the LC. The chemical lesion of the LC resulted in decreased respiratory frequency under normocapnic conditions in OVX and OVX+E2 group. Hypercapnia increased ventilation in all groups as consequence of increases in respiratory frequency (fR) and tidal volume (V T ). Nevertheless, the hypercapnic ventilatory response was significantly decreased in 6-OHDA-NOVX>50% rats compared with SHAM-NOVX group and with females that had 20-42% of LC lesion. In OVX and OVX+E2 lesioned groups, no difference in CO 2 ventilatory response was observed when compared to SHAM-OVX and SHAM-OVX+E2 groups, respectively. Neither basal body temperature (Tb) nor Tb reduction in response to hypercapnia were affected by E2 treatment, ovariectomy or LC lesion. Thus, our data show that LC noradrenergic neurons seem to exert an excitatory role on the hypercapnic ventilatory response in female rats, as evidenced by the results in NOVX animals with LC lesioned more than 50%; however, this modulation is not observed in OVX and OVX+E2 rats. In addition, LC noradrenergic neurons of OVX females seem to provide a tonic excitatory drive to maintain breathing frequency in normocapnia, and this response may not to be

  2. Lineage specific expression of Polycomb Group Proteins in human embryonic stem cells in vitro.

    Science.gov (United States)

    Pethe, Prasad; Pursani, Varsha; Bhartiya, Deepa

    2015-05-01

    Human embryonic (hES) stem cells are an excellent model to study lineage specification and differentiation into various cell types. Differentiation necessitates repression of specific genes not required for a particular lineage. Polycomb Group (PcG) proteins are key histone modifiers, whose primary function is gene repression. PcG proteins form complexes called Polycomb Repressive Complexes (PRCs), which catalyze histone modifications such as H2AK119ub1, H3K27me3, and H3K9me3. PcG proteins play a crucial role during differentiation of stem cells. The expression of PcG transcripts during differentiation of hES cells into endoderm, mesoderm, and ectoderm lineage is yet to be shown. In-house derived hES cell line KIND1 was differentiated into endoderm, mesoderm, and ectoderm lineages; followed by characterization using RT-PCR for HNF4A, CDX2, MEF2C, TBX5, SOX1, and MAP2. qRT-PCR and western blotting was performed to compare expression of PcG transcripts and proteins across all the three lineages. We observed that cells differentiated into endoderm showed upregulation of RING1B, BMI1, EZH2, and EED transcripts. Mesoderm differentiation was characterized by significant downregulation of all PcG transcripts during later stages. BMI1 and RING1B were upregulated while EZH2, SUZ12, and EED remained low during ectoderm differentiation. Western blotting also showed distinct expression of BMI1 and EZH2 during differentiation into three germ layers. Our study shows that hES cells differentiating into endoderm, mesoderm, and ectoderm lineages show distinct PcG expression profile at transcript and protein level. © 2015 International Federation for Cell Biology.

  3. Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells.

    Science.gov (United States)

    Curto, Pedro; Simões, Isaura; Riley, Sean P; Martinez, Juan J

    2016-01-01

    Spotted fever group (SFG) rickettsiae are recognized as important agents of human tick-borne diseases worldwide, such as Mediterranean spotted fever (Rickettsia conorii) and Rocky Mountain spotted fever (Rickettsia rickettsii). Recent studies in several animal models have provided evidence of non-endothelial parasitism by pathogenic SFG Rickettsia species, suggesting that the interaction of rickettsiae with cells other than the endothelium may play an important role in pathogenesis of rickettsial diseases. These studies raise the hypothesis that the role of macrophages in rickettsial pathogenesis may have been underappreciated. Herein, we evaluated the ability of two SFG rickettsial species, R. conorii (a recognized human pathogen) and Rickettsia montanensis (a non-virulent member of SFG) to proliferate in THP-1 macrophage-like cells, or within non-phagocytic cell lines. Our results demonstrate that R. conorii was able to survive and proliferate in both phagocytic and epithelial cells in vitro. In contrast, R. montanensis was able to grow in non-phagocytic cells, but was drastically compromised in the ability to proliferate within both undifferentiated and PMA-differentiated THP-1 cells. Interestingly, association assays revealed that R. montanensis was defective in binding to THP-1-derived macrophages; however, the invasion of the bacteria that are able to adhere did not appear to be affected. We have also demonstrated that R. montanensis which entered into THP-1-derived macrophages were rapidly destroyed and partially co-localized with LAMP-2 and cathepsin D, two markers of lysosomal compartments. In contrast, R. conorii was present as intact bacteria and free in the cytoplasm in both cell types. These findings suggest that a phenotypic difference between a non-pathogenic and a pathogenic SFG member lies in their respective ability to proliferate in macrophage-like cells, and may provide an explanation as to why certain SFG rickettsial species are not associated

  4. Differences in intracellular fate of two spotted fever group Rickettsia in macrophage-like cells

    Directory of Open Access Journals (Sweden)

    Pedro Curto

    2016-07-01

    Full Text Available Spotted fever group (SFG rickettsiae are recognized as important agents of human tick-borne diseases worldwide, such as Mediterranean spotted fever (R. conorii and Rocky Mountain spotted fever (R. rickettsii. Recent studies in several animal models have provided evidence of non-endothelial parasitism by pathogenic SFG Rickettsia species, suggesting that the interaction of rickettsiae with cells other than the endothelium may play an important role in pathogenesis of rickettsial diseases. These studies raise the hypothesis that the role of macrophages in rickettsial pathogenesis may have been underappreciated. Herein, we evaluated the ability of two SFG rickettsial species, R. conorii (a recognized human pathogen and R. montanensis (a non-virulent member of SFG to proliferate in THP-1 macrophage-like cells, or within non-phagocytic cell lines. Our results demonstrate that R. conorii was able to survive and proliferate in both phagocytic and epithelial cells in vitro. In contrast, R. montanensis was able to grow in non-phagocytic cells, but was drastically compromised in the ability to proliferate within both undifferentiated and PMA-differentiated THP-1 cells. Interestingly, association assays revealed that R. montanensis was defective in binding to THP-1-derived macrophages; however, the invasion of the bacteria that are able to adhere did not appear to be affected. We have also demonstrated that R. montanensis which entered into THP-1-derived macrophages were rapidly destroyed and partially co-localized with LAMP-2 and cathepsin D, two markers of lysosomal compartments. In contrast, R. conorii was present as intact bacteria and free in the cytoplasm in both cell types. These findings suggest that a phenotypic difference between a non-pathogenic and a pathogenic SFG member lies in their respective ability to proliferate in macrophage-like cells, and may provide an explanation as to why certain SFG rickettsial species are not associated with

  5. Controlling the Morphology of BDTT-DPP-Based Small Molecules via End-Group Functionalization for Highly Efficient Single and Tandem Organic Photovoltaic Cells.

    Science.gov (United States)

    Kim, Ji-Hoon; Park, Jong Baek; Yang, Hoichang; Jung, In Hwan; Yoon, Sung Cheol; Kim, Dongwook; Hwang, Do-Hoon

    2015-11-04

    A series of narrow-band gap, π-conjugated small molecules based on diketopyrrolopyrrole (DPP) electron acceptor units coupled with alkylthienyl-substituted-benzodithiophene (BDTT) electron donors were designed and synthesized for use as donor materials in solution-processed organic photovoltaic cells. In particular, by end-group functionalization of the small molecules with fluorine derivatives, the nanoscale morphologies of the photoactive layers of the photovoltaic cells were successfully controlled. The influences of different fluorine-based end-groups on the optoelectronic and morphological properties, carrier mobilities, and the photovoltaic performances of these materials were investigated. A high power conversion efficiency (PCE) of 6.00% under simulated solar light (AM 1.5G) illumination has been achieved for organic photovoltaic cells based on a small-molecule bulk heterojunction system consisting of a trifluoromethylbenzene (CF3) end-group-containing oligomer (BDTT-(DPP)2-CF3) as the donor and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) as the acceptor. As a result, the introduction of CF3 end-groups has been found to enhance both the short circuit current density (JSC) and fill factor (FF). A tandem photovoltaic device comprising an inverted BDTT-(DPP)2-CF3:PC71BM cell and a poly(3-hexylthiophene) (P3HT):indene-C60-bisadduct (IC60BA)-based cell as the top and bottom cell components, respectively, showed a maximum PCE of 8.30%. These results provide valuable guidelines for the rational design of conjugated small molecules for applications in high-performance organic photovoltaic cells. Furthermore, to the best of our knowledge, this is the first report on the design of fluorine-functionalized BDTT-DPP-based small molecules, which have been shown to be a viable candidate for use in inverted tandem cells.

  6. Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

    Science.gov (United States)

    Zhang, Xiaoling; Shang, Xun; Guo, Fukun; Murphy, Kim; Kirby, Michelle; Kelly, Patrick; Reeves, Lilith; Smith, Franklin O.; Williams, David A.

    2008-01-01

    Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by reexpression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway. PMID:18565850

  7. Group 3 innate lymphoid cells accumulate and exhibit disease-induced activation in the meninges in EAE.

    Science.gov (United States)

    Hatfield, Julianne K; Brown, Melissa A

    2015-10-01

    Innate lymphoid cells are immune cells that reside in tissues that interface with the external environment and contribute to the first line defense against pathogens. However, they also have roles in promoting chronic inflammation. Here we demonstrate that group 3 ILCs, (ILC3s - CD45+Lin-IL-7Rα+RORγt+), are normal residents of the meninges and exhibit disease-induced accumulation and activation in EAE. In addition to production of the pro-inflammatory cytokines IL-17 and GM-CSF, ILC3s constitutively express CD30L and OX40L, molecules required for memory T cell survival. We show that disease-induced trafficking of transferred wild type T cells to the meninges is impaired in ILC3-deficient Rorc-/- mice. Furthermore, lymphoid tissue inducer cells, a c-kit+ ILC3 subset that promotes ectopic lymphoid follicle development, a hallmark of many autoimmune diseases, are reduced in the meninges of EAE-resistant c-kit mutant Kit(W/Wv) mice. We propose that ILC3s sustain neuroinflammation by supporting T cell survival and reactivation in the meninges. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Integrating cell-free biosyntheses of heme prosthetic group and apoenzyme for the synthesis of functional P450 monooxygenase.

    Science.gov (United States)

    Kwon, Yong-Chan; Oh, In-Seok; Lee, Nahum; Lee, Kyung-Ho; Yoon, Yeo Joon; Lee, Eun Yeol; Kim, Byung-Gee; Kim, Dong-Myung

    2013-04-01

    Harnessing the isolated protein synthesis machinery, cell-free protein synthesis reproduces the cellular process of decoding genetic information in artificially controlled environments. More often than not, however, generation of functional proteins requires more than simple translation of genetic sequences. For instance, many of the industrially important enzymes require non-protein prosthetic groups for biological activity. Herein, we report the complete cell-free biogenesis of a heme prosthetic group and its integration with concurrent apoenzyme synthesis for the production of functional P450 monooxygenase. Step reactions required for the syntheses of apoenzyme and the prosthetic group have been designed so that these two separate pathways take place in the same reaction mixture, being insulated from each other. Combined pathways for the synthesis of functional P450 monooxygenase were then further integrated with in situ assay reactions to enable real-time measurement of enzymatic activity during its synthesis. Copyright © 2012 Wiley Periodicals, Inc.

  9. Microinjection of Micrococcus luteus UV-endonuclease restores UV-induced unscheduled DNA synthesis in cells of 9 xeroderma pigmentosum complementation groups.

    NARCIS (Netherlands)

    A.J.R. de Jonge; W. Vermeulen (Wim); W. Keijzer; J.H.J. Hoeijmakers (Jan); D. Bootsma (Dirk)

    1985-01-01

    textabstractThe UV-induced unscheduled DNA synthesis (UDS) in cultured cells of excision-deficient xeroderma pigmentosum (XP) complementation groups A through I was assayed after injection of Micrococcus luteus UV-endonuclease using glass microneedles. In all complementation groups a restoration of

  10. KCl stimulation increases norepinephrine transporter function in PC12 cells.

    Science.gov (United States)

    Mandela, Prashant; Ordway, Gregory A

    2006-09-01

    The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [3H]NE uptake via the NET and simultaneously increased [3H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca2+. Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [3H]NE uptake but did not block KCl-stimulated increases in [3H]NE uptake. In contrast, PMA increased [3H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca2+-activated signaling cascades with KN93 (a Ca2+ calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [3H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [3H]NE release. KCl-stimulated increases in [3H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca2+, different intracellular mechanisms mediate these two events.

  11. 40 CFR Appendix A to Part 76 - Phase I Affected Coal-Fired Utility Units With Group 1 or Cell Burner Boilers

    Science.gov (United States)

    2010-07-01

    ... Units With Group 1 or Cell Burner Boilers A Appendix A to Part 76 Protection of Environment... 1 or Cell Burner Boilers Table 1—Phase I Tangentially Fired Units State Plant Unit Operator ALABAMA... Vertically fired boiler. 2 Arch-fired boiler. Table 3—Phase I Cell Burner Technology Units State Plant Unit...

  12. β2-adrenergic receptor-mediated negative regulation of group 2 innate lymphoid cell responses.

    Science.gov (United States)

    Moriyama, Saya; Brestoff, Jonathan R; Flamar, Anne-Laure; Moeller, Jesper B; Klose, Christoph S N; Rankin, Lucille C; Yudanin, Naomi A; Monticelli, Laurel A; Putzel, Gregory Garbès; Rodewald, Hans-Reimer; Artis, David

    2018-03-02

    The type 2 inflammatory response is induced by various environmental and infectious stimuli. Although recent studies identified group 2 innate lymphoid cells (ILC2s) as potent sources of type 2 cytokines, the molecular pathways controlling ILC2 responses are incompletely defined. Here we demonstrate that murine ILC2s express the β 2 -adrenergic receptor (β 2 AR) and colocalize with adrenergic neurons in the intestine. β 2 AR deficiency resulted in exaggerated ILC2 responses and type 2 inflammation in intestinal and lung tissues. Conversely, β 2 AR agonist treatment was associated with impaired ILC2 responses and reduced inflammation in vivo. Mechanistically, we demonstrate that the β 2 AR pathway is a cell-intrinsic negative regulator of ILC2 responses through inhibition of cell proliferation and effector function. Collectively, these data provide the first evidence of a neuronal-derived regulatory circuit that limits ILC2-dependent type 2 inflammation. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  13. Radically altered T cell receptor signaling in glycopeptide-specific T cell hybridoma induced by antigen with minimal differences in the glycan group

    DEFF Research Database (Denmark)

    Jensen, T; Nielsen, M; Gad, Monika

    2001-01-01

    A T cell hybridoma raised against the synthetic glycopeptide T(72)(Tn) was used to study whether the initial TCR signaling events are markedly different when the hybridoma is stimulated with glycopeptides closely related to the cognate glycopeptide antigen. T(72)(Tn) has an alpha-D-GalNAc group O......)(alpha-D-GlcNAc), which differs from T(72)(Tn) solely by the orientation of a hydroxy group in the carbohydrate structure, completely failed to induce detectable tyrosine phosphorylation and IL-2 secretion. APC pulsed with S(72)(Tn), which differs from T(72)(Tn) by not having a methyl group in the serine......-linked to the central threonine in the decapeptide VITAFTEGLK, and the hybridoma is known to be highly specific for this carbohydrate group. T(72)(Tn)-pulsed APC induced tyrosine phosphorylation of the TCR-zeta 21- and 23-kDa proteins and the downstream p42/44 MAP kinase and strong IL-2 secretion. APC pulsed with T(72...

  14. Activity targets for nanostructured platinum-group-metal-free catalysts in hydroxide exchange membrane fuel cells

    Science.gov (United States)

    Setzler, Brian P.; Zhuang, Zhongbin; Wittkopf, Jarrid A.; Yan, Yushan

    2016-12-01

    Fuel cells are the zero-emission automotive power source that best preserves the advantages of gasoline automobiles: low upfront cost, long driving range and fast refuelling. To make fuel-cell cars a reality, the US Department of Energy has set a fuel cell system cost target of US$30 kW-1 in the long-term, which equates to US$2,400 per vehicle, excluding several major powertrain components (in comparison, a basic, but complete, internal combustion engine system costs approximately US$3,000). To date, most research for automotive applications has focused on proton exchange membrane fuel cells (PEMFCs), because these systems have demonstrated the highest power density. Recently, however, an alternative technology, hydroxide exchange membrane fuel cells (HEMFCs), has gained significant attention, because of the possibility to use stable platinum-group-metal-free catalysts, with inherent, long-term cost advantages. In this Perspective, we discuss the cost profile of PEMFCs and the advantages offered by HEMFCs. In particular, we discuss catalyst development needs for HEMFCs and set catalyst activity targets to achieve performance parity with state-of-the-art automotive PEMFCs. Meeting these targets requires careful optimization of nanostructures to pack high surface areas into a small volume, while maintaining high area-specific activity and favourable pore-transport properties.

  15. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II

    DEFF Research Database (Denmark)

    Krege, Susanne; Beyer, Jörg; Souchon, Rainer

    2007-01-01

    OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of ...

  16. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I

    DEFF Research Database (Denmark)

    Krege, Susanne; Beyer, Jörg; Souchon, Rainer

    2007-01-01

    OBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the A...

  17. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

    Directory of Open Access Journals (Sweden)

    David R. Withers

    2017-10-01

    Full Text Available The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3 are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.

  18. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

    Science.gov (United States)

    Withers, David R.; Hepworth, Matthew R.

    2017-01-01

    The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases. PMID:29085366

  19. Potentiation of NMDA receptor-dependent cell responses by extracellular high mobility group box 1 protein.

    Directory of Open Access Journals (Sweden)

    Marco Pedrazzi

    Full Text Available BACKGROUND: Extracellular high mobility group box 1 (HMGB1 protein can operate in a synergistic fashion with different signal molecules promoting an increase of cell Ca(2+ influx. However, the mechanisms responsible for this effect of HMGB1 are still unknown. PRINCIPAL FINDINGS: Here we demonstrate that, at concentrations of agonist per se ineffective, HMGB1 potentiates the activation of the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR in isolated hippocampal nerve terminals and in a neuroblastoma cell line. This effect was abolished by the NMDA channel blocker MK-801. The HMGB1-facilitated NMDAR opening was followed by activation of the Ca(2+-dependent enzymes calpain and nitric oxide synthase in neuroblastoma cells, resulting in an increased production of NO, a consequent enhanced cell motility, and onset of morphological differentiation. We have also identified NMDAR as the mediator of HMGB1-stimulated murine erythroleukemia cell differentiation, induced by hexamethylenebisacetamide. The potentiation of NMDAR activation involved a peptide of HMGB1 located in the B box at the amino acids 130-139. This HMGB1 fragment did not overlap with binding sites for other cell surface receptors of HMGB1, such as the advanced glycation end products or the Toll-like receptor 4. Moreover, in a competition assay, the HMGB1((130-139 peptide displaced the NMDAR/HMGB1 interaction, suggesting that it comprised the molecular and functional site of HMGB1 regulating the NMDA receptor complex. CONCLUSION: We propose that the multifunctional cytokine-like molecule HMGB1 released by activated, stressed, and damaged or necrotic cells can facilitate NMDAR-mediated cell responses, both in the central nervous system and in peripheral tissues, independently of other known cell surface receptors for HMGB1.

  20. AKR1B10 induces cell resistance to daunorubicin and idarubicin by reducing C13 ketonic group

    International Nuclear Information System (INIS)

    Zhong Linlin; Shen Honglin; Huang Chenfei; Jing, Hongwu; Cao Deliang

    2011-01-01

    Daunorubicin, idarubicin, doxorubicin and epirubicin are anthracyclines widely used for the treatment of lymphoma, leukemia, and breast, lung, and liver cancers, but tumor resistance limits their clinical success. Aldo-keto reductase family 1 B10 (AKR1B10) is an NADPH-dependent enzyme overexpressed in liver and lung carcinomas. This study was aimed to determine the role of AKR1B10 in tumor resistance to anthracyclines. AKR1B10 activity toward anthracyclines was measured using recombinant protein. Cell resistance to anthracycline was determined by ectopic expression of AKR1B10 or inhibition by epalrestat. Results showed that AKR1B10 reduces C13-ketonic group on side chain of daunorubicin and idarubicin to hydroxyl forms. In vitro, AKR1B10 converted daunorubicin to daunorubicinol at V max of 837.42 ± 81.39 nmol/mg/min, K m of 9.317 ± 2.25 mM and k cat /K m of 3.24. AKR1B10 showed better catalytic efficiency toward idarubicin with V max at 460.23 ± 28.12 nmol/mg/min, K m at 0.461 ± 0.09 mM and k cat /K m at 35.94. AKR1B10 was less active toward doxorubicin and epirubicin with a C14-hydroxyl group. In living cells, AKR1B10 efficiently catalyzed reduction of daunorubicin (50 nM) and idarubicin (30 nM) to corresponding alcohols. Within 24 h, approximately 20 ± 2.7% of daunorubicin (1 μM) or 23 ± 2.3% of idarubicin (1 μM) was converted to daunorubicinol or idarubicinol in AKR1B10 expression cells compared to 7 ± 0.9% and 5 ± 1.5% in vector control. AKR1B10 expression led to cell resistance to daunorubicin and idarubicin, but inhibitor epalrestat showed a synergistic role with these agents. Together our data suggest that AKR1B10 participates in cellular metabolism of daunorubicin and idarubicin, resulting in drug resistance. These data are informative for the clinical use of idarubicin and daunorubicin. - Highlights: → This study defines enzyme activity of AKR1B10 protein towards daunorubicin, idarubicin, doxorubicin, and epirubicin. → This study pinpoints

  1. Overexpression of xeroderma pigmentosum group C decreases the chemotherapeutic sensitivity of colorectal carcinoma cells to cisplatin.

    Science.gov (United States)

    Zhang, Yi; Cao, Jia; Meng, Yanni; Qu, Chunying; Shen, Feng; Xu, Leiming

    2018-05-01

    Xeroderma pigmentosum group C (XPC) is a DNA-damage-recognition gene active at the early stage of DNA repair. XPC also participates in regulation of cell-cycle checkpoint and DNA-damage-induced apoptosis. In the present study, the expression levels of genes involved in nucleotide excision repair (NER) were assessed in human colorectal cancer (CRC) tissue. This analysis revealed that expression of XPC mRNA significantly increased in colorectal carcinoma tissues compared with matched normal controls. Expression of XPC gradually increased along with the degree of progression of CRC. In vitro , an XTT assay demonstrated that small interfering RNA (siRNA) targeting XPC significantly increased the sensitivity of CRC SW480 cells to cisplatin, whereas cells transfected with a XPC-overexpression plasmid became more resistant to cisplatin. Furthermore, flow cytometry revealed that the proportion of apoptotic cells significantly increased in XPC-knockdown cells upon cisplatin treatment. However, the overexpression XPC significantly increased the resistance of cells to cisplatin. In vivo , tumor growth was significantly reduced in tumor-bearing mice when the XPC gene was knocked down. Upregulation of the expression of pro-apoptotic Bcl-associated X and downregulation of the anti-apoptotic B-cell lymphoma 2 proteins was observed in the implanted tumor tissue. In conclusion, XPC serves a key role in chemotherapeutic sensitivity of CRC to cisplatin, meaning that it may be a potential target for chemotherapy of CRC.

  2. Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Chia-I Ko

    2014-01-01

    Full Text Available The aryl hydrocarbon receptor (AHR is a transcription factor and environmental sensor that regulates expression of genes involved in drug-metabolism and cell cycle regulation. Chromatin immunoprecipitation analyses, Ahr ablation in mice and studies with orthologous genes in invertebrates suggest that AHR may also play a significant role in embryonic development. To address this hypothesis, we studied the regulation of Ahr expression in mouse embryonic stem cells and their differentiated progeny. In ES cells, interactions between OCT3/4, NANOG, SOX2 and Polycomb Group proteins at the Ahr promoter repress AHR expression, which can also be repressed by ectopic expression of reprogramming factors in hepatoma cells. In ES cells, unproductive RNA polymerase II binds at the Ahr transcription start site and drives the synthesis of short abortive transcripts. Activation of Ahr expression during differentiation follows from reversal of repressive marks in Ahr promoter chromatin, release of pluripotency factors and PcG proteins, binding of Sp factors, establishment of histone marks of open chromatin, and engagement of active RNAPII to drive full-length RNA transcript elongation. Our results suggest that reversible Ahr repression in ES cells holds the gene poised for expression and allows for a quick switch to activation during embryonic development.

  3. Group 2 Innate Lymphoid Cells Exhibit a Dynamic Phenotype in Allergic Airway Inflammation

    Science.gov (United States)

    Li, Bobby W. S.; Stadhouders, Ralph; de Bruijn, Marjolein J. W.; Lukkes, Melanie; Beerens, Dior M. J. M.; Brem, Maarten D.; KleinJan, Alex; Bergen, Ingrid; Vroman, Heleen; Kool, Mirjam; van IJcken, Wilfred F. J.; Rao, Tata Nageswara; Fehling, Hans Jörg; Hendriks, Rudi W.

    2017-01-01

    Group 2 innate lymphoid cells (ILC2) are implicated in allergic asthma as an early innate source of the type 2 cytokines IL-5 and IL-13. However, their induction in house dust mite (HDM)-mediated airway inflammation additionally requires T cell activation. It is currently unknown whether phenotypic differences exist between ILC2s that are activated in a T cell-dependent or T cell-independent fashion. Here, we compared ILC2s in IL-33- and HDM-driven airway inflammation. Using flow cytometry, we found that surface expression levels of various markers frequently used to identify ILC2s were dependent on their mode of activation, highly variable over time, and differed between tissue compartments, including bronchoalveolar lavage (BAL) fluid, lung, draining lymph nodes, and spleen. Whereas in vivo IL-33-activated BAL fluid ILC2s exhibited an almost uniform CD25+CD127+T1/ST2+ICOS+KLRG1+ phenotype, at a comparable time point after HDM exposure BAL fluid ILC2s had a very heterogeneous surface marker phenotype. A major fraction of HDM-activated ILC2s were CD25lowCD127+T1/ST2low ICOSlowKLRG1low, but nevertheless had the capacity to produce large amounts of type 2 cytokines. HDM-activated CD25low ILC2s in BAL fluid and lung rapidly reverted to CD25high ILC2s upon in vivo stimulation with IL-33. Genome-wide transcriptional profiling of BAL ILC2s revealed ~1,600 differentially expressed genes: HDM-stimulated ILC2s specifically expressed genes involved in the regulation of adaptive immunity through B and T cell interactions, whereas IL-33-stimulated ILC2s expressed high levels of proliferation-related and cytokine genes. In both airway inflammation models ILC2s were present in the lung submucosa close to epithelial cells, as identified by confocal microscopy. In chronic HDM-driven airway inflammation ILC2s were also found inside organized cellular infiltrates near T cells. Collectively, our findings show that ILC2s are phenotypically more heterogeneous than previously thought

  4. Group 2 Innate Lymphoid Cells Exhibit a Dynamic Phenotype in Allergic Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Bobby W. S. Li

    2017-12-01

    Full Text Available Group 2 innate lymphoid cells (ILC2 are implicated in allergic asthma as an early innate source of the type 2 cytokines IL-5 and IL-13. However, their induction in house dust mite (HDM-mediated airway inflammation additionally requires T cell activation. It is currently unknown whether phenotypic differences exist between ILC2s that are activated in a T cell-dependent or T cell-independent fashion. Here, we compared ILC2s in IL-33- and HDM-driven airway inflammation. Using flow cytometry, we found that surface expression levels of various markers frequently used to identify ILC2s were dependent on their mode of activation, highly variable over time, and differed between tissue compartments, including bronchoalveolar lavage (BAL fluid, lung, draining lymph nodes, and spleen. Whereas in vivo IL-33-activated BAL fluid ILC2s exhibited an almost uniform CD25+CD127+T1/ST2+ICOS+KLRG1+ phenotype, at a comparable time point after HDM exposure BAL fluid ILC2s had a very heterogeneous surface marker phenotype. A major fraction of HDM-activated ILC2s were CD25lowCD127+T1/ST2low ICOSlowKLRG1low, but nevertheless had the capacity to produce large amounts of type 2 cytokines. HDM-activated CD25low ILC2s in BAL fluid and lung rapidly reverted to CD25high ILC2s upon in vivo stimulation with IL-33. Genome-wide transcriptional profiling of BAL ILC2s revealed ~1,600 differentially expressed genes: HDM-stimulated ILC2s specifically expressed genes involved in the regulation of adaptive immunity through B and T cell interactions, whereas IL-33-stimulated ILC2s expressed high levels of proliferation-related and cytokine genes. In both airway inflammation models ILC2s were present in the lung submucosa close to epithelial cells, as identified by confocal microscopy. In chronic HDM-driven airway inflammation ILC2s were also found inside organized cellular infiltrates near T cells. Collectively, our findings show that ILC2s are phenotypically more heterogeneous than

  5. Group technology

    International Nuclear Information System (INIS)

    Rome, C.P.

    1976-01-01

    Group Technology has been conceptually applied to the manufacture of batch-lots of 554 machined electromechanical parts which now require 79 different types of metal-removal tools. The products have been grouped into 7 distinct families which require from 8 to 22 machines in each machine-cell. Throughput time can be significantly reduced and savings can be realized from tooling, direct-labor, and indirect-labor costs

  6. Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.

    Science.gov (United States)

    Becker, P S; Taylor, J A; Trobridge, G D; Zhao, X; Beard, B C; Chien, S; Adair, J; Kohn, D B; Wagner, J E; Shimamura, A; Kiem, H-P

    2010-10-01

    One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (Pgene-corrected cells in patients with FANCA.

  7. Expression and characterization of human group C rotavirus virus-like particles in insect cells

    International Nuclear Information System (INIS)

    Clark, Kristina B.; Lin, S.-C.; Humphrey, Charles; Foytich, Kimberly; Esona, Mathew; Wang Yuhuan; Liu, Merry; Jiang Baoming

    2009-01-01

    Group C rotavirus (GpC RV) is a causative agent of acute gastroenteritis in children and adults. We expressed the three major capsid proteins VP2, VP6 and VP7 of human GpC RV in baculovirus and demonstrated the self-assembly of VP2/6/7 or VP6/7 virus-like particles (VLPs) in insect cells. We examined a number of parameters, including the kinetics of protein synthesis in different cell lines and media, to optimize the most favorable conditions for the synthesis of recombinant viral proteins and the production of VLPs in Sf9 cells. Hyperimmune serum to VP2/6/7 and VP6/7 VLPs recognized individual recombinant proteins of human GpC RV by Western blot analysis. This serum also showed specific reactivities with the corresponding GpC VLPs but not GpA RV by using immune electron microscopy (IEM) and enzyme immunoassay (EIA). The ability to produce an unlimited amount of GpC RV antigen and the availability of high quality antibody will allow us to develop sensitive and specific diagnostic assays to better determine the epidemiology and disease burden of GpC RV in humans.

  8. Fibrin network pattern changes of platelet-rich fibrin in young versus old age group of individuals: A cell block cytology study

    OpenAIRE

    Shravanthi Raghav Yajamanya; Anirban Chatterjee; Chaitanya Nischay Babu; Deepika Karunanithi

    2016-01-01

    Background: To evaluate variations in fibrin network patterns of the platelet-rich fibrin (PRF) in different age groups. Materials and Methods: Ninety-five patients were divided into three age groups: Group 1: (20?39 years); Group 2: (40?59 years); and Group 3: (60 years and above). PRF was prepared from blood samples of all patients and were subjected to cell block cytology method of histological analysis and slides were prepared to histologically assess the age-related changes in (i) fibrin...

  9. Repair Effect of Seaweed Polysaccharides with Different Contents of Sulfate Group and Molecular Weights on Damaged HK-2 Cells

    Directory of Open Access Journals (Sweden)

    Poonam Bhadja

    2016-05-01

    Full Text Available The structure–activity relationships and repair mechanism of six low-molecular-weight seaweed polysaccharides (SPSs on oxalate-induced damaged human kidney proximal tubular epithelial cells (HK-2 were investigated. These SPSs included Laminaria japonica polysaccharide, degraded Porphyra yezoensis polysaccharide, degraded Gracilaria lemaneiformis polysaccharide, degraded Sargassum fusiforme polysaccharide, Eucheuma gelatinae polysaccharide, and degraded Undaria pinnatifida polysaccharide. These SPSs have a narrow difference of molecular weight (from 1968 to 4020 Da after degradation by controlling H2O2 concentration. The sulfate group (–SO3H content of the six SPSs was 21.7%, 17.9%, 13.3%, 8.2%, 7.0%, and 5.5%, respectively, and the –COOH contents varied between 1.0% to 1.7%. After degradation, no significant difference was observed in the contents of characteristic –SO3H and –COOH groups of polysaccharides. The repair effect of polysaccharides was determined using cell-viability test by CCK-8 assay and cell-morphology test by hematoxylin-eosin staining. The results revealed that these SPSs within 0.1–100 μg/mL did not express cytotoxicity in HK-2 cells, and each polysaccharide had a repair effect on oxalate-induced damaged HK-2 cells. Simultaneously, the content of polysaccharide –SO3H was positively correlated with repair ability. Furthermore, the low-molecular-weight degraded polysaccharides showed better repair activity on damaged HK-2 cells than their undegraded counterpart. Our results can provide reference for inhibiting the formation of kidney stones and for developing original anti-stone polysaccharide drugs.

  10. Reactivation, retrieval, replay and reconsolidation in and out of sleep: connecting the dots

    Directory of Open Access Journals (Sweden)

    Susan J Sara

    2010-12-01

    Full Text Available The neurobiology of memory has taken on a new look over the past decade. Re-discovery of cue-dependent amnesia, wide availability of functional imaging tools and increased dialogue among clinicians, cognitive psychologists, behavioral neuroscientists and neurobiologists have provided impetus for the search for new paradigms for the study of memory. Memory is increasingly viewed as an open-ended process, with retrieval being recognized as an intricate part of the encoding process. New memories are always made on the background of past experience, so that every consolidation is, in fact reconsolidation. serving to update and strengthen memories after retrieval. Spontaneous reactivation of memory circuits occurs during sleep and there is converging evidence from rodent and human studies that this is an important part of the extended off-line memory processing. The noradrenergic neuromodulatory system is engaged at retrieval, facilitating recall. The noradrenergic system is activated during sleep after learning and noradrenergic neurons fire in concert with cortical oscillations that are associated with reactivation of memory circuits. We suggest that the noradrenergic system and perhaps other neuromodulatory systems,[...

  11. Branched multifunctional polyether polyketals: variation of ketal group structure enables unprecedented control over polymer degradation in solution and within cells.

    Science.gov (United States)

    Shenoi, Rajesh A; Narayanannair, Jayaprakash K; Hamilton, Jasmine L; Lai, Benjamin F L; Horte, Sonja; Kainthan, Rajesh K; Varghese, Jos P; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Kizhakkedathu, Jayachandran N

    2012-09-12

    Multifunctional biocompatible and biodegradable nanomaterials incorporating specific degradable linkages that respond to various stimuli and with defined degradation profiles are critical to the advancement of targeted nanomedicine. Herein we report, for the first time, a new class of multifunctional dendritic polyether polyketals containing different ketal linkages in their backbone that exhibit unprecedented control over degradation in solution and within the cells. High-molecular-weight and highly compact poly(ketal hydroxyethers) (PKHEs) were synthesized from newly designed α-epoxy-ω-hydroxyl-functionalized AB(2)-type ketal monomers carrying structurally different ketal groups (both cyclic and acyclic) with good control over polymer properties by anionic ring-opening multibranching polymerization. Polymer functionalization with multiple azide and amine groups was achieved without degradation of the ketal group. The polymer degradation was controlled primarily by the differences in the structure and torsional strain of the substituted ketal groups in the main chain, while for polymers with linear (acyclic) ketal groups, the hydrophobicity of the polymer may play an additional role. This was supported by the log P values of the monomers and the hydrophobicity of the polymers determined by fluorescence spectroscopy using pyrene as the probe. A range of hydrolysis half-lives of the polymers at mild acidic pH values was achieved, from a few minutes to a few hundred days, directly correlating with the differences in ketal group structures. Confocal microscopy analyses demonstrated similar degradation profiles for PKHEs within live cells, as seen in solution and the delivery of fluorescent marker to the cytosol. The cell viability measured by MTS assay and blood compatibility determined by complement activation, platelet activation, and coagulation assays demonstrate that PKHEs and their degradation products are highly biocompatible. Taken together, these data

  12. USD Catalysis Group for Alternative Energy

    Energy Technology Data Exchange (ETDEWEB)

    Hoefelmeyer, James D.; Koodali, Ranjit; Sereda, Grigoriy; Engebretson, Dan; Fong, Hao; Puszynski, Jan; Shende, Rajesh; Ahrenkiel, Phil

    2012-03-13

    The South Dakota Catalysis Group (SDCG) is a collaborative project with mission to develop advanced catalysts for energy conversion with two primary goals: (1) develop photocatalytic systems in which polyfunctionalized TiO2 are the basis for hydrogen/oxygen synthesis from water and sunlight (solar fuels group), (2) develop new materials for hydrogen utilization in fuel cells (fuel cell group). In tandem, these technologies complete a closed chemical cycle with zero emissions.

  13. Effect of Prazosin and Naltrexone on Script Induced Alcohol Craving in Veterans with Alcohol Use Disorders with and without Co-occurring PTSD

    Science.gov (United States)

    2017-01-01

    and each is postulated to be mediated by different neurological substrates. The neural networks postulated to subserve reward and relief craving...noradrenergic system with craving-related brain systems, blocking α1 receptors with the noradrenergic antagonist, prazosin, theoretically has the...to evaluate whether specific individual characteristics, including PTSD status, moderate medication response. 15. SUBJECT TERMS Alcohol Drinking

  14. [Notochord cells enhance proliferation and phenotype-keeping of intervertebral disc chondroid cells].

    Science.gov (United States)

    Zhao, Xianfeng; Liu, Hao; Feng, Ganjun; Deng, Li; Li, Xiuqun; Liang, Tao

    2008-08-01

    To isolate and culture the chondroid cells and notochord cells from New Zealand rabbit immature nucleus pulposus (NP) in monolayer, and to evaluate the responsiveness of rabbit disc-derived chondroid cells to notochord cells with respect to cell proliferation and phenotype. The NP cells were released from the minced immature NP of 6 New Zealand rabbits (4-week-old) by 0.2% collagenase II digestion. The chondroid cells and notochord cells were purified by discontinuous gradient density centrifugation. The chondroid cells were cultured alone (group A) and co-cultured with notochord cells (group B) (1:1), and cell proliferation and phenotype including proteoglycan and collagen II were evaluated. The cells in both groups were observed by the inverted microscope, and the survival rates of the primary and passage cells were detected by toluidine blue staining. The growth curves of the second passage cells in both groups were determined by MTT. Besides, the expressions of proteoglycan and collagen II of the primary and passage cells were examined by toluidine blue and immunocytochemistry staining. The notochord cells and chondroid cells were isolated and purified. With the diameter of 10-15 microm, the notochord cell had abundant intracytoplasmic vesicles, while the chondroid cell, with the diameter of 4-6 microm, had no intracytoplasmic vesicle. The cell survival rate was 89.0%-95.3% in group A and 91.3%-96.3% in group B. There was no significant difference between the same passages in both groups (P > 0.05). The co-cultured cells (group B) increased in cell proliferation compared with the chondroid cells alone (group A) in repeated experiments. The cells in group A reached their logarithmic growth phase after 3-4 days of culture, while the cells in group B did after 2 days of culture. The cell proliferation in group B was more than that in group A after 4-day culture (P notochord cells are conducive for the proliferation and phenotype-keeping of the chondroid cells and

  15. Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups

    Science.gov (United States)

    Ekkapongpisit, Maneerat; Giovia, Antonino; Follo, Carlo; Caputo, Giuseppe; Isidoro, Ciro

    2012-01-01

    Background and methods Nanoparticles engineered to carry both a chemotherapeutic drug and a sensitive imaging probe are valid tools for early detection of cancer cells and to monitor the cytotoxic effects of anticancer treatment simultaneously. Here we report on the effect of size (10–30 nm versus 50 nm), type of material (mesoporous silica versus polystyrene), and surface charge functionalization (none, amine groups, or carboxyl groups) on biocompatibility, uptake, compartmentalization, and intracellular retention of fluorescently labeled nanoparticles in cultured human ovarian cancer cells. We also investigated the involvement of caveolae in the mechanism of uptake of nanoparticles. Results We found that mesoporous silica nanoparticles entered via caveolae-mediated endocytosis and reached the lysosomes; however, while the 50 nm nanoparticles permanently resided within these organelles, the 10 nm nanoparticles soon relocated in the cytoplasm. Naked 10 nm mesoporous silica nanoparticles showed the highest and 50 nm carboxyl-modified mesoporous silica nanoparticles the lowest uptake rates, respectively. Polystyrene nanoparticle uptake also occurred via a caveolae-independent pathway, and was negatively affected by serum. The 30 nm carboxyl-modified polystyrene nanoparticles did not localize in lysosomes and were not toxic, while the 50 nm amine-modified polystyrene nanoparticles accumulated within lysosomes and eventually caused cell death. Ovarian cancer cells expressing caveolin-1 were more likely to endocytose these nanoparticles. Conclusion These data highlight the importance of considering both the physicochemical characteristics (ie, material, size and surface charge on chemical groups) of nanoparticles and the biochemical composition of the cell membrane when choosing the most suitable nanotheranostics for targeting cancer cells. PMID:22904626

  16. The Fanconi anemia group A protein modulates homologous repair of DNA double-strand breaks in mammalian cells.

    Science.gov (United States)

    Yang, Yun-Gui; Herceg, Zdenko; Nakanishi, Koji; Demuth, Ilja; Piccoli, Colette; Michelon, Jocelyne; Hildebrand, Gabriele; Jasin, Maria; Digweed, Martin; Wang, Zhao-Qi

    2005-10-01

    Fanconi anemia (FA) cells exhibit hypersensitivity to DNA interstrand cross-links (ICLs) and high levels of chromosome instability. FA gene products have been shown to functionally or physically interact with BRCA1, RAD51 and the MRE11/RAD50/NBS1 complex, suggesting that the FA complex may be involved in the repair of DNA double-strand breaks (DSBs). Here, we have investigated specifically the function of the FA group A protein (FANCA) in the repair of DSBs in mammalian cells. We show that the targeted deletion of Fanca exons 37-39 generates a null for Fanca in mice and abolishes ubiquitination of Fancd2, the downstream effector of the FA complex. Cells lacking Fanca exhibit increased chromosomal aberrations and attenuated accumulation of Brca1 and Rad51 foci in response to DNA damage. The absence of Fanca greatly reduces gene-targeting efficiency in mouse embryonic stem (ES) cells and compromises the survival of fibroblast cells in response to ICL agent treatment. Fanca-null cells exhibit compromised homology-directed repair (HDR) of DSBs, particularly affecting the single-strand annealing pathway. These data identify the Fanca protein as an integral component in the early step of HDR of DSBs and thereby minimizing the genomic instability.

  17. Xeroderma pigmentosum complementation group C cells remove pyrimidine dimers selectively from the transcribed strand of active genes

    International Nuclear Information System (INIS)

    Venema, J.; van Hoffen, A.; Karcagi, V.; Natarajan, A.T.; van Zeeland, A.A.; Mullenders, L.H.

    1991-01-01

    The authors have measured the removal of UV-induced pyrimidine dimers from DNA fragments of the adenosine deaminase (ADA) and dihydrofolate reductase (DHFR) genes in primary normal human and xeroderma pigmentosum complementation group C (XP-C) cells. Using strand-specific probes, we show that in normal cells, preferential repair of the 5' part of the ADA gene is due to the rapid and efficient repair of the transcribed strand. Within 8 h after irradiation with UV at 10 J m-2, 70% of the pyrimidine dimers in this strand are removed. The nontranscribed strand is repaired at a much slower rate, with 30% dimers removed after 8 h. Repair of the transcribed strand in XP-C cells occurs at a rate indistinguishable from that in normal cells, but the nontranscribed strand is not repaired significantly in these cells. Similar results were obtained for the DHFR gene. In the 3' part of the ADA gene, however, both normal and XP-C cells perform fast and efficient repair of either strand, which is likely to be caused by the presence of transcription units on both strands. The factor defective in XP-C cells is apparently involved in the processing of DNA damage in inactive parts of the genome, including nontranscribed strands of active genes. These findings have important implications for the understanding of the mechanism of UV-induced excision repair and mutagenesis in mammalian cells

  18. [Blood groups - minuses and pluses. Do the blood group antigens protect us from infectious diseases?].

    Science.gov (United States)

    Czerwiński, Marcin

    2015-06-25

    Human blood can be divided into groups, which is a method of blood classification based on the presence or absence of inherited erythrocyte surface antigens that can elicit immune response. According to the International Society of Blood Transfusion, there are 341 blood group antigens collected in 35 blood group systems. These antigens can be proteins, glycoproteins or glycosphingolipids, and function as transmembrane transporters, ion channels, adhesion molecules or receptors for other proteins. The majority of blood group antigens is present also on another types of cells. Due to their localization on the surface of cells, blood group antigens can act as receptors for various pathogens or their toxins, such as protozoa (malaria parasites), bacteria (Helicobacter pylori, Vibrio cholerae and Shigella dysenteriae) and viruses (Noroviruses, Parvoviruses, HIV). If the presence of group antigen (or its variant which arised due to mutation) is beneficial for the host (e.g. because pathogens are not able to bind to the cells), the blood group may become a selection trait, leading to its dissemination in the population exposed to that pathogen. There are thirteen blood group systems that can be related to pathogen resistance, and it seems that the particular influence was elicit by malaria parasites. It is generally thought that the high incidence of blood groups such as O in the Amazon region, Fy(a-b-) in Africa and Ge(-) in Papua-New Guinea is the result of selective pressure from malaria parasite. This review summarizes the data about relationship between blood groups and resistance to pathogens.

  19. Proteomic analysis of human norepinephrine transporter complexes reveals associations with protein phosphatase 2A anchoring subunit and 14-3-3 proteins

    International Nuclear Information System (INIS)

    Sung, Uhna; Jennings, Jennifer L.; Link, Andrew J.; Blakely, Randy D.

    2005-01-01

    The norepinephrine transporter (NET) terminates noradrenergic signals by clearing released NE at synapses. NET regulation by receptors and intracellular signaling pathways is supported by a growing list of associated proteins including syntaxin1A, protein phosphatase 2A (PP2A) catalytic subunit (PP2A-C), PICK1, and Hic-5. In the present study, we sought evidence for additional partnerships by mass spectrometry-based analysis of proteins co-immunoprecipitated with human NET (hNET) stably expressed in a mouse noradrenergic neuroblastoma cell line. Our initial proteomic analyses reveal multiple peptides derived from hNET, peptides arising from the mouse PP2A anchoring subunit (PP2A-Ar) and peptides derived from 14-3-3 proteins. We verified physical association of NET with PP2A-Ar via co-immunoprecipitation studies using mouse vas deferens extracts and with 14-3-3 via a fusion pull-down approach, implicating specifically the hNET NH 2 -terminus for interactions. The transporter complexes described likely support mechanisms regulating transporter activity, localization, and trafficking

  20. Red cell antigen prevalence predicted by molecular testing in ethnic groups of South Texas blood donors.

    Science.gov (United States)

    Aranda, Lorena I; Smith, Linda A; Jones, Scott; Beddard, Rachel

    2015-01-01

    Alloimmunization to red blood cell antigens is seen in patients receiving chronic blood transfusion. Knowing the prevalence of blood group antigens of the different ethnicities of South Texas donors can provide better management of rare blood inventory for patients in this geographical area. A total of 4369 blood donors were tested and analyzed for various antigens in the following blood group systems: ABO, Rh, Kell, Duffy, Kidd, MNS, Lutheran, Dombrock, Landsteiner-Wiener, Diego, Colton, and Scianna. Donors tested to be group 0 or A were serologically tested for the Rh (C, E, c, e) antigens. Those that tested as presumably R1R1, R2R2, or Ror were then genotyped. Donors constituted three major ethnicities: black (18.3%), Hispanic (36.3%), and Caucasian (41.1%); ethnicities comprised of Asian, American Indian, multiracial, and other accounted for the remaining donors (4.3%). The most likely common Rh phenotype for each ethnicity is as follows: black -Ror (44.4%), Hispanic -R1R1 (59.0%), and Caucasian -R1R1 (38.9%). The prevalence of Kell, Duffy, and Kidd blood group system antigens in black and Caucasian donors is comparable with published reports for the entire U.S. The black South Texas donor population had an 8.8 percent increase in prevalence of the Fy(a+b-) phenotype as compared with these published reports; the Hispanic South Texas donor population had a prevalence of 36.1 percent of the Fy(a+b-) phenotype. Regarding the Diego blood group system, the Hispanic donor population in South Texas had a prevalence of 93.5 percent for the Di(a-b+) phenotype as compared with published reports for the entire U.S. (>99.9%). The Hispanic population had a prevalence of 7.9 percent of donors testing as M-N+S-s+ as compared with 20.2 percent and 15.6 percent for black and Caucasian donors, respectively. This study helped us determine the prevalence of each of the blood group antigens in the South Texas donor population to establish and maintain adequate rare inventory of

  1. Hindbrain A2 noradrenergic neuron adenosine 5'-monophosphate-activated protein kinase activation, upstream kinase/phosphorylase protein expression, and receptivity to hormone and fuel reporters of short-term food deprivation are regulated by estradiol.

    Science.gov (United States)

    Briski, Karen P; Alenazi, Fahaad S H; Shakya, Manita; Sylvester, Paul W

    2017-07-01

    Estradiol (E) mitigates acute and postacute adverse effects of 12 hr-food deprivation (FD) on energy balance. Hindbrain 5'-monophosphate-activated protein kinase (AMPK) regulates hyperphagic and hypothalamic metabolic neuropeptide and norepinephrine responses to FD in an E-dependent manner. Energy-state information from AMPK-expressing hindbrain A2 noradrenergic neurons shapes neural responses to metabolic imbalance. Here we investigate the hypothesis that FD causes divergent changes in A2 AMPK activity in E- vs. oil (O)-implanted ovariectomized female rats, alongside dissimilar adjustments in circulating metabolic fuel (glucose, free fatty acids [FFA]) and energy deficit-sensitive hormone (corticosterone, glucagon, leptin) levels. FD decreased blood glucose in oil (O)- but not E-implanted ovariectomized female rats and elevated and reduced glucagon levels in O and E, respectively. FD decreased circulating leptin in O and E, but increased corticosterone and FFA concentrations in E only. Western blot analysis of laser-microdissected A2 neurons showed that glucocorticoid receptor type II and very-long-chain acyl-CoA synthetase 3 protein profiles were amplified in FD/E vs. FD/O. A2 total AMPK protein was elevated without change in activity in FD/O, whereas FD/E exhibited increased AMPK activation along with decreased upstream phosphatase expression. The catecholamine biosynthetic enzyme dopamine-β-hydroxylase (DβH) was increased in FD/O but not FD/E A2 cells. The data show discordance between A2 AMPK activation and glycemic responses to FD; sensor activity was refractory to glucose decrements in FD/O but augmented in FD/E despite stabilized glucose and elevated FFA levels. E-dependent amplification of AMPK activity may reflect adaptive conversion to fatty acid oxidation and/or glucocorticoid stimulation. FD augmentation of A2 DβH protein profiles in FD/O but not FD/E animals suggests that FD may correspondingly regulate NE synthesis vs. metabolism/release in the

  2. Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development.

    Science.gov (United States)

    Sears, Catherine R; Zhou, Huaxin; Justice, Matthew J; Fisher, Amanda J; Saliba, Jacob; Lamb, Isaac; Wicker, Jessica; Schweitzer, Kelly S; Petrache, Irina

    2018-03-01

    Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema.

  3. Autoradiographic studies on the distribution of 14C-5,7-dihydroxytryptamine in the brain of new-born rat

    International Nuclear Information System (INIS)

    Lappe, U.

    1982-01-01

    The distribution of intracisternally injected 14 C-5,7-dihydroxy tryptamine (5,7-DHT) in the central nervous system of new-born rat is studied by means of autoradiography. The radio-active neurotoxin is incorporated into the neurones of all known serotonine nucleus groups. This labelling allows a detailed demonstration of the topography of the serotonine neurones in the brain stem of the new-born rat and to compare it with systems obtained by other methods. Serotonine neurones were mapped in 22 representative frontal sections through the brain stem. 14 C-5,7-DHT is incorporated into noradrenergic neurones, too. However, labelling is less marked than in serotonergic neurones. 14 C-5,7-DHT is incorporated at small quantities into the following extraneural elements: fibroblasts of the pia mater/arachnoidea, some endothelical cells of pial vessels, epithelial cells of the plexus choroideus, and subependymal macrophages. 6 h after injection of 25 μg 14 C-5,7-DHT, the vast majority of serotonergic neurones reveal strong degenerative changes which are irreversible. (orig./MG) [de

  4. Presence of corticotrophin-releasing factor and/or tyrosine hydroxylase in cells of a neural brain-testicular pathway that are labelled by a transganglionic tracer.

    Science.gov (United States)

    James, P; Rivier, C; Lee, S

    2008-02-01

    Our laboratory has shown that male testosterone levels are not solely controlled by the release of hypothalamic gonadotrophin-releasing hormone and pituitary luteinising hormone, but are also regulated by a multisynaptic pathway connecting the brain and the testis that interferes with the testosterone response to gonadotrophins. This pathway, which is independent of the pituitary gland, is activated by an i.c.v. injection of either the stress-related peptide corticotrophin-releasing factor (CRF) or of beta-adrenoceptor agonists, both of which alter androgen release and decrease levels of the peripheral-type benzodiazepine receptor and the steroidogenic acute regulatory protein within Leydig cells. Our original studies used the retrograde transganglionic tracer pseudorabies virus (PRV) to map progression of the virus from the testes to upper brain levels. The present study aimed to extend this work by identifying the regions where CRF and catecholamine neurones represented components of the stress-activated, brain-testicular pathway that prevents testosterone increases. To this end, anaesthetised adult male rats received an intra-testicular injection of PRV. Using immunofluorescence, we identified co-labelling of PRV and either CRF or tyrosine hydroxylase (TH), the enzyme responsible for biogenic amine synthesis. Co-labelling of PRV and CRF was found in the bed nucleus of the stria terminalis, the paraventricular nucleus of the hypothalamus (PVN) and the central amygdala. Co-labelling of PRV and TH was found in the PVN, substantia nigra, A7/Kölliker-Fuse area, area of A5, locus coeruleus, nucleus of solitary tract, area of C3, area of C2 and the area of C1/A1. These results indicate that most cell groups of the ventral noradrenergic pathway have neurones that are a part of the brain-testicular pathway. This suggests that the stress hormones CRF and catecholamines may act as neurotransmitters that signal the pathway to inhibit increases in plasma testosterone levels.

  5. Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in Subjects with Asthma.

    Science.gov (United States)

    Chen, Ruchong; Smith, Steven G; Salter, Brittany; El-Gammal, Amani; Oliveria, John Paul; Obminski, Caitlin; Watson, Rick; O'Byrne, Paul M; Gauvreau, Gail M; Sehmi, Roma

    2017-09-15

    Group 2 innate lymphoid cells (ILC2), a major source of type 2 cytokines, initiate eosinophilic inflammatory responses in murine models of asthma. To investigate the role of ILC2 in allergen-induced airway eosinophilic responses in subjects with atopy and asthma. Using a diluent-controlled allergen challenge crossover study, where all subjects (n = 10) developed allergen-induced early and late responses, airway eosinophilia, and increased methacholine airway responsiveness, bone marrow, blood, and sputum samples were collected before and after inhalation challenge. ILC2 (lin - FcεRI - CD45 + CD127 + ST2 + ) and CD4 + T lymphocytes were enumerated by flow cytometry, as well as intracellular IL-5 and IL-13 expression. Steroid sensitivity of ILC2 and CD4 + T cells was investigated in vitro. A significant increase in total, IL-5 + , IL-13 + , and CRTH2 + ILC2 was found in sputum, 24 hours after allergen, coincident with a significant decrease in blood ILC2. Total, IL-5 + , and IL-13 + , but not CRTH2 + , CD4 + T cells significantly increased at 24 and 48 hours after allergen in sputum. In blood and bone marrow, only CD4 + cells demonstrated increased activation after allergen. Airway eosinophilia correlated with IL-5 + ILC2 at all time points and allergen-induced changes in IL-5 + CD4 + cells at 48 hours after allergen. Dexamethasone significantly attenuated IL-2- and IL-33-stimulated IL-5 and IL-13 production by both cell types. Innate and adaptive immune cells are increased in the airways associated with allergic asthmatic responses. Total and type 2 cytokine-positive ILC2 are increased only within the airways, whereas CD4 + T lymphocytes demonstrated local and systemic increases. Steroid sensitivity of both cells may explain effectiveness of this therapy in those with mild asthma.

  6. Fibrin network pattern changes of platelet-rich fibrin in young versus old age group of individuals: A cell block cytology study

    Directory of Open Access Journals (Sweden)

    Shravanthi Raghav Yajamanya

    2016-01-01

    Full Text Available Background: To evaluate variations in fibrin network patterns of the platelet-rich fibrin (PRF in different age groups. Materials and Methods: Ninety-five patients were divided into three age groups: Group 1: (20–39 years; Group 2: (40–59 years; and Group 3: (60 years and above. PRF was prepared from blood samples of all patients and were subjected to cell block cytology method of histological analysis and slides were prepared to histologically assess the age-related changes in (i fibrin network patterns in terms of density and (ii entrapment of platelets and white blood cells (WBCs within fibrin meshwork. Results: Two types of fibrin network pattern arrangements noticed: Dense and loose types in three age groups. However, there was a noticeable decrease in the dense type of fibrin network with progressing age and increase in the loose type of fibrin arrangement. Furthermore, variation in a number of platelets and WBCs entrapped within fibrin network in relation to age was noticed. Conclusion: From the current study it can be concluded that age can be considered as one of the influencing factors on quality of PRF in terms of fibrin network patterns and hence, platelet and WBCs entrapment within these fibrin networks.

  7. ABO blood groups and malaria related clinical outcome.

    Science.gov (United States)

    Deepa; Alwar, Vanamala A; Rameshkumar, Karuna; Ross, Cecil

    2011-03-01

    The study was undertaken to correlate the blood groups and clinical presentations in malaria patients and to understand the differential host susceptibility in malaria. From October 2007 to September 2008, malaria positive patients' samples were evaluated in this study. Hemoglobin, total leukocyte count, and platelet count of each patient were done on an automated cell counter. After determining the blood groups, malarial species and the severity of clinical course were correlated. A total of 100 patients were included in the study, of which 63 cases were positive for Plasmodium falciparum and 37 cases were positive for P. vivax infection and 11 patients had mixed infection. The results of the blood groups showed 22 - 'A' group, 42 - 'B' group, 35 - 'O' group and 1 was 'AB' group. When the clinical courses between different groups were compared using the following parameters for severe infection--a parasitic load of >10/1000 RBCs, severe anemia with hemoglobin 101°F and other organ involvement, it was observed that 'O' group had an advantage over other the groups. The difference in rosetting ability between red blood cells of different 'ABO' blood groups with a diminished rosetting potential in blood group 'O' red blood cells was due to the differential host susceptibility. 'O' group had an advantage over the other three blood groups. Based on literature and the results of this study, the diminished rosetting potential in blood group 'O' red blood cells is suggested as the basis for the differential host susceptibility.

  8. Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators

    Directory of Open Access Journals (Sweden)

    Arthur Dyer

    2017-03-01

    Full Text Available Enadenotucirev (EnAd is a chimeric group B adenovirus isolated by bioselection from a library of adenovirus serotypes. It replicates selectively in and kills a diverse range of carcinoma cells, shows effective anticancer activity in preclinical systems, and is currently undergoing phase I/II clinical trials. EnAd kills cells more quickly than type 5 adenovirus, and speed of cytotoxicity is dose dependent. The EnAd death pathway does not involve p53, is predominantly caspase independent, and appears to involve a rapid fall in cellular ATP. Infected cells show early loss of membrane integrity; increased exposure of calreticulin; extracellular release of ATP, HSP70, and HMGB1; and influx of calcium. The virus also causes an obvious single membrane blister reminiscent of ischemic cell death by oncosis. In human tumor biopsies maintained in ex vivo culture, EnAd mediated release of pro-inflammatory mediators such as TNF-α, IL-6, and HMGB1. In accordance with this, EnAd-infected tumor cells showed potent stimulation of dendritic cells and CD4+ T cells in a mixed tumor-leukocyte reaction in vitro. Whereas many viruses have evolved for efficient propagation with minimal inflammation, bioselection of EnAd for rapid killing has yielded a virus with a short life cycle that combines potent cytotoxicity with a proinflammatory mechanism of cell death.

  9. Extrinsic control of the release of galanin and VIP from intrinsic nerves of isolated, perfused, porcine ileum

    DEFF Research Database (Denmark)

    Messell, T; Harling, H; Poulsen, Steen Seier

    1992-01-01

    By immunohistochemistry galanin-like immunoreactivity and vasoactive intestinal polypeptide (VIP)-like immunoreactivity were found in nerve cell bodies mostly in the submucous plexus and in nerve fibres in the mucosa, submucosa and muscularis including the myenteric plexus of the porcine ileum an...... was not influenced by atropine. Our results suggest that the galanin- and VIP-producing intrinsic neurons receive inhibitory signals by noradrenergic nerve fibers and stimulatory signals mediated by cholinergic nerves, possibly via a cholinergic interneuron....

  10. Antimicrobial and anti-virulence activity of capsaicin against erythromycin-resistant, cell-invasive Group A streptococci

    Directory of Open Access Journals (Sweden)

    Emanuela eMarini

    2015-11-01

    Full Text Available Capsaicin (8-methyl-N-vanillyl-6-nonenamide is the active component of Capsicum plants (chilli peppers, which are grown as food and for medicinal purposes since ancient times, and is responsible for the pungency of their fruit. Besides its multiple pharmacological and physiological properties (pain relief, cancer prevention, and beneficial cardiovascular, and gastrointestinal effects capsaicin has recently attracted considerable attention because of its antimicrobial and anti-virulence activity. This is the first study of its in vitro antibacterial and anti-virulence activity against Streptococcus pyogenes [Group A streptococci (GAS], a major human pathogen. The test strains were previously characterized, erythromycin-susceptible (n=5 and erythromycin-resistant (n=27, cell-invasive pharyngeal isolates. The MICs of capsaicin were 64-128 μg/mL (the most common MIC was 128 µg/mL. The action of capsaicin was bactericidal, as suggested by MBC values that were equal or close to the MICs, and by early detection of dead cells in the live/dead assay. No capsaicin-resistant mutants were obtained in single-step resistance selection studies. Interestingly, growth in presence of sublethal capsaicin concentrations induced an increase in biofilm production (p ≤ 0.05 and in the number of bacteria adhering to A549 monolayers, and a reduction in cell-invasiveness and haemolytic activity (both p ≤ 0.05. Cell invasiveness fell so dramatically that a highly invasive strain became non-invasive. The dose-response relationship, characterized by opposite effects of low and high capsaicin doses, suggests a hormetic response. The present study documents that capsaicin has promising bactericidal activity against erythromycin-resistant, cell-invasive pharyngeal GAS isolates. The fact that sublethal concentrations inhibited cell invasion and reduced haemolytic activity, two important virulence traits of GAS, is also interesting, considering that cell

  11. Chemogenetic locus coeruleus activation restores reversal learning in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Rorabaugh, Jacki M; Chalermpalanupap, Termpanit; Botz-Zapp, Christian A; Fu, Vanessa M; Lembeck, Natalie A; Cohen, Robert M; Weinshenker, David

    2017-11-01

    See Grinberg and Heinsen (doi:10.1093/brain/awx261) for a scientific commentary on this article. Clinical evidence suggests that aberrant tau accumulation in the locus coeruleus and noradrenergic dysfunction may be a critical early step in Alzheimer’s disease progression. Yet, an accurate preclinical model of these phenotypes that includes early pretangle tau accrual in the locus coeruleus, loss of locus coeruleus innervation and deficits locus coeruleus/norepinephrine modulated behaviours, does not exist, hampering the identification of underlying mechanisms and the development of locus coeruleus-based therapies. Here, a transgenic rat (TgF344-AD) expressing disease-causing mutant amyloid precursor protein (APPsw) and presenilin-1 (PS1ΔE9) was characterized for histological and behavioural signs of locus coeruleus dysfunction reminiscent of mild cognitive impairment/early Alzheimer’s disease. In TgF344-AD rats, hyperphosphorylated tau was detected in the locus coeruleus prior to accrual in the medial entorhinal cortex or hippocampus, and tau pathology in the locus coeruleus was negatively correlated with noradrenergic innervation in the medial entorhinal cortex. Likewise, TgF344-AD rats displayed progressive loss of hippocampal norepinephrine levels and locus coeruleus fibres in the medial entorhinal cortex and dentate gyrus, with no frank noradrenergic cell body loss. Cultured mouse locus coeruleus neurons expressing hyperphosphorylation-prone mutant human tau had shorter neurites than control neurons, but similar cell viability, suggesting a causal link between pretangle tau accrual and altered locus coeruleus fibre morphology. TgF344-AD rats had impaired reversal learning in the Morris water maze compared to their wild-type littermates, which was rescued by chemogenetic locus coeruleus activation via designer receptors exclusively activated by designer drugs (DREADDs). Our results indicate that TgF344-AD rats uniquely meet several key criteria for a

  12. All polymer chip for amperometric studies of transmitter release from large groups of neuronal cells

    DEFF Research Database (Denmark)

    Larsen, Simon T.; Taboryski, Rafael

    2012-01-01

    We present an all polymer electrochemical chip for simple detection of transmitter release from large groups of cultured PC 12 cells. Conductive polymer PEDOT:tosylate microelectrodes were used together with constant potential amperometry to obtain easy-to-analyze oxidation signals from potassium......-induced release of transmitter molecules. The nature of the resulting current peaks is discussed, and the time for restoring transmitter reservoirs is studied. The relationship between released transmitters and potassium concentration was found to fit to a sigmoidal dose–response curve. Finally, we demonstrate...

  13. Group IVA Element (Si, Ge, Sn)-Based Alloying/Dealloying Anodes as Negative Electrodes for Full-Cell Lithium-Ion Batteries.

    Science.gov (United States)

    Liu, Dequan; Liu, Zheng Jiao; Li, Xiuwan; Xie, Wenhe; Wang, Qi; Liu, Qiming; Fu, Yujun; He, Deyan

    2017-12-01

    To satisfy the increasing energy demands of portable electronics, electric vehicles, and miniaturized energy storage devices, improvements to lithium-ion batteries (LIBs) are required to provide higher energy/power densities and longer cycle lives. Group IVA element (Si, Ge, Sn)-based alloying/dealloying anodes are promising candidates for use as electrodes in next-generation LIBs owing to their extremely high gravimetric and volumetric capacities, low working voltages, and natural abundances. However, due to the violent volume changes that occur during lithium-ion insertion/extraction and the formation of an unstable solid electrolyte interface, the use of Group IVA element-based anodes in commercial LIBs is still a great challenge. Evaluating the electrochemical performance of an anode in a full-cell configuration is a key step in investigating the possible application of the active material in LIBs. In this regard, the recent progress and important approaches to overcoming and alleviating the drawbacks of Group IVA element-based anode materials are reviewed, such as the severe volume variations during cycling and the relatively brittle electrode/electrolyte interface in full-cell LIBs. Finally, perspectives and future challenges in achieving the practical application of Group IVA element-based anodes in high-energy and high-power-density LIB systems are proposed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Angiotensinergic and noradrenergic neurons in the rat and human heart.

    Science.gov (United States)

    Patil, Jaspal; Stucki, Silvan; Nussberger, Juerg; Schaffner, Thomas; Gygax, Susanne; Bohlender, Juergen; Imboden, Hans

    2011-02-25

    Although the physiological and pharmacological evidences suggest a role for angiotensin II (Ang II) with the mammalian heart, the source and precise location of Ang II are unknown. To visualize and quantitate Ang II in atria, ventricular walls and interventricular septum of the rat and human heart and to explore the feasibility of local Ang II production and function, we investigated by different methods the expression of proteins involved in the generation and function of Ang II. We found mRNA of angiotensinogen (Ang-N), of angiotensin converting enzyme, of the angiotensin type receptors AT(1A) and AT₂ (AT(1B) not detected) as well as of cathepsin D in any part of the hearts. No renin mRNA was traceable. Ang-N mRNA was visualized by in situ hybridization in atrial ganglial neurons. Ang II and dopamine-β-hydroxylase (DβH) were either colocalized inside the same neuronal cell or the neurons were specialized for Ang II or DβH. Within these neurons, the vesicular acetylcholine transporter (VAChT) was neither colocalized with Ang II nor DβH, but VAChT-staining was found with synapses en passant encircle these neuronal cells. The fibers containing Ang II exhibited with blood vessels and with cardiomyocytes supposedly angiotensinergic synapses en passant. In rat heart, right atrial median Ang II concentration appeared higher than septal and ventricular Ang II. The distinct colocalization of neuronal Ang II with DβH in the heart may indicate that Ang II participates together with norepinephrine in the regulation of cardiac functions: produced as a cardiac neurotransmitter Ang II may have inotropic, chronotropic or dromotropic effects in atria and ventricles and contributes to blood pressure regulation. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. INCREASED VASOOCCLUSIVE CRISIS IN “O” BLOOD GROUP SICKLE CELL DISEASE PATIENTS: ASSOCIATION WITH UNDERLYING THROMBOSPONDIN LEVELS.

    Directory of Open Access Journals (Sweden)

    M. Al Huneini

    2017-04-01

    Full Text Available Abstract: Objectives: To explore the incidence of vaso-occlusive crisis (VOC in Blood Group “O” sickle cell disease (SCD patients, and correlate it with the blood group and thrombospondin (TSP levels. Methods: In 89 consecutive SCD patients, blood samples were obtained for vWF antigen, collagen binding activity, blood group typing, C-reactive protein, variant hemoglobin analysis (HPLC, Serum TSP 1 and TSP 2 levels, complete blood counts, liver function tests, LDH and renal function tests during VOC episodes and in steady state conditions. Results: In the steady state SCD patients (n=72, “O” blood group patients (n=37 showed significantly higher median serum TSP 1 and TSP 2 levels than the non “O” blood group patients [n=35] [p <0.05, Mann-Whitney test], with an inverse relation between VWF:Ag, Factor VIII:C and TSP levels. Furthermore, the serum TSP 1 and TSP 2 levels were significantly higher in patients presenting with acute VOC [n=17], and in those with repeated VOC’s (group 1, n=16 especially amongst those patients with blood group “O” [p, <0.05, Mann-Whitney test]. Conclusions: The study shows that there was an inverse relation between TSP and vWF levels, in blood group “O” SCD patients with an upregulation of the TSP levels. Expectedly, during active VOC crisis, the TSP 1 and TSP 2 levels were significantly elevated.    Key Words: VOC; SCD; TSP; vWD; Blood groups

  16. Hand-held cell phone use while driving legislation and observed driver behavior among population sub-groups in the United States

    OpenAIRE

    Rudisill, Toni M.; Zhu, Motao

    2017-01-01

    Abstract Background Cell phone use behaviors are known to vary across demographic sub-groups and geographic locations. This study examined whether universal hand-held calling while driving bans were associated with lower road-side observed hand-held cell phone conversations across drivers of different ages (16–24, 25–59, ≥60 years), sexes, races (White, African American, or other), ruralities (suburban, rural, or urban), and regions (Northeast, Midwest, South, and West). Methods Data from the...

  17. Comparative study of few energy group of cross sections for fuel cells of thermal reactors

    International Nuclear Information System (INIS)

    1991-08-01

    A comparative study of nuclear constants calculated with LEOPARD and WIMSD-4 codes using a typical PWR cell was done. Few groups macroscopic cross section, spectral index, burnup and power distribution were analyzed. (author) and safety concern with the transport of radioactive materials, looking for the control of eventual exposure of radiation to men, properties and environment, that is: specification of radioactive materials to be transported; choice of loaded materials; specification of requisites of loaded materials; general specification for any way of transport (earth, water and air), and responsibilities and administrative requisites. (author)

  18. Incorporation of ester groups into low band-gap diketopyrrolopyrrole containing polymers for solar cell applications

    DEFF Research Database (Denmark)

    Hu, Xiaolian; Zuo, Lijian; Fu, Weifei

    2012-01-01

    To increase the open circuit voltage (VOC) of polymer solar cells based on diketopyrrolopyrrole (DPP) containing polymers, the weakly electron-withdrawing thiophene-3,4-dicarboxylate unit was introduced into the polymer backbone. Two ester group functionalized DPP containing polymers, PCTDPP...... with a random structure and PDCTDPP with a regular structure, were designed and synthesized by the Stille coupling reaction. The resulting copolymers exhibit broad and strong absorption bands from 350 to 1000 nm with low optical band gaps below 1.40 eV. Through cyclic voltammetry measurements, it is found...

  19. Sex Differences in Stress and Group Housing Effects on the Number of Newly Proliferated Cells and Neuroblasts in Middle-Aged Dentate Gyrus.

    Science.gov (United States)

    Tzeng, Wen-Yu; Wu, Hsin-Hua; Wang, Ching-Yi; Chen, Jin-Chung; Yu, Lung; Cherng, Chianfang G

    2016-01-01

    Sex differences in stress and coping responses have been frequently documented in aged people, while whether such differences in aged people may appear at the middle age are unknown. This study was undertaken to study the impact of acute stress and social interaction on early neurogenesis in the dentate gyrus (DG) and hippocampus-related memory in two sexes of middle-aged mice. The number of newly proliferated cells, neuroblasts in DG, the object recognition and location memory in 9-month-old male and female C57BL/6N mice were assessed under baseline conditions as well as following an acute stressor regimen and group housing. Three conspecific companions, serving as "the housing group," were used to model the social interaction throughout the stressor regimen. Males had lower numbers of newly proliferated cells and neuroblasts under baseline conditions as compared to females. The stressor regimen caused rapid decreases in the number of newly proliferated cells and neuroblasts in female DG but no obvious changes were observed in male DG. Group housing, regardless of companions' age, prevented the stress-induced decreases in the number of newly proliferated cells and neuroblasts in female DG. In contrast, the presence of young or age-matched companions potentiated the stress effect in males by decreasing the number of newly proliferated cells and neuroblasts. Finally, neither the stressor regimen nor group housing affected mouse performances in the object recognition and location memory in either sex. These findings, taken together, provide evidence to support a notion that middle-aged females appear to demonstrate more stress susceptibility on early neurogenesis in DG as compared to middle-aged males, although the hippocampus-related memory performances are comparable and not affected by stress in these males and females. Experiencing stress, middle-aged females are more prone to benefit from social interaction as compared to middle-aged males in this regard. We

  20. Distribution of phytoplankton groups within the deep chlorophyll maximum

    KAUST Repository

    Latasa, Mikel

    2016-11-01

    The fine vertical distribution of phytoplankton groups within the deep chlorophyll maximum (DCM) was studied in the NE Atlantic during summer stratification. A simple but unconventional sampling strategy allowed examining the vertical structure with ca. 2 m resolution. The distribution of Prochlorococcus, Synechococcus, chlorophytes, pelagophytes, small prymnesiophytes, coccolithophores, diatoms, and dinoflagellates was investigated with a combination of pigment-markers, flow cytometry and optical and FISH microscopy. All groups presented minimum abundances at the surface and a maximum in the DCM layer. The cell distribution was not vertically symmetrical around the DCM peak and cells tended to accumulate in the upper part of the DCM layer. The more symmetrical distribution of chlorophyll than cells around the DCM peak was due to the increase of pigment per cell with depth. We found a vertical alignment of phytoplankton groups within the DCM layer indicating preferences for different ecological niches in a layer with strong gradients of light and nutrients. Prochlorococcus occupied the shallowest and diatoms the deepest layers. Dinoflagellates, Synechococcus and small prymnesiophytes preferred shallow DCM layers, and coccolithophores, chlorophytes and pelagophytes showed a preference for deep layers. Cell size within groups changed with depth in a pattern related to their mean size: the cell volume of the smallest group increased the most with depth while the cell volume of the largest group decreased the most. The vertical alignment of phytoplankton groups confirms that the DCM is not a homogeneous entity and indicates groups’ preferences for different ecological niches within this layer.

  1. I-L-C-2 it: type 2 immunity and group 2 innate lymphoid cells in homeostasis.

    Science.gov (United States)

    von Moltke, Jakob; Locksley, Richard M

    2014-12-01

    Innate type 2 immune cells are activated in response to helminths, allergens, and certain types of proteases and particulates. Recently, innate type 2 immune pathways have also been implicated in protective host responses to homeostatic perturbations, such as metabolic dysfunction, atherosclerosis, and tissue injury. In this context, innate type 2 cytokines stimulate local tissues, recruit eosinophils, and alternatively activate macrophages to restore homeostasis. As the major source of innate interleukin (IL)-5 and IL-13, group 2 innate lymphoid cells are positioned to initiate and maintain homeostatic type 2 responses. The absence of exogenous stimuli in these processes implicates endogenous pathways in the activation of type 2 immunity and suggests an alternative evolutionary trajectory for type 2 immunity, apart from its role in response to helminths and allergens. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. ICOS regulates the pool of group 2 innate lymphoid cells under homeostatic and inflammatory conditions in mice.

    Science.gov (United States)

    Paclik, Daniela; Stehle, Christina; Lahmann, Annette; Hutloff, Andreas; Romagnani, Chiara

    2015-10-01

    Group 2 innate lymphoid cells (ILC2s) are innate effectors playing an important role in the defense against helminthic infections and in the pathogenesis of allergic inflammation. Cytokines have been identified as the major stimuli driving ILC2 activation and expansion. Conversely, it is unclear whether costimulatory molecules contribute to regulation of ILC2 functions. ILC2s display high expression of inducible T-cell costimulator (ICOS), which belongs to the CD28 superfamily, and which has been shown to control late effector T-cell functions, and is of utmost importance for the humoral immune response. However, the biological function of ICOS expression on ILC2s is unknown. Here, we show that ICOS signaling in mice regulates ILC2 homeostasis independently of T cells and B cells, by promoting proliferation and accumulation of mature ILC2s in lung and intestine. In a model of IL-33-induced airway inflammation, ICOS controls ILC2 activation and eosinophil infiltration in the lung. Our data identify a role of ICOS in innate immunity and indicate that not only cytokines, but also costimulatory pathways such as those involving ICOS, can contribute to regulate the ILC2 pool. Thus, ICOS costimulation blockade, which is currently under clinical evaluation for inhibiting the humoral immune response, could also target innate inflammatory circuits. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Readthrough of stop codons by use of aminoglycosides in cells from xeroderma pigmentosum group C patients.

    Science.gov (United States)

    Kuschal, Christiane; Khan, Sikandar G; Enk, Benedikt; DiGiovanna, John J; Kraemer, Kenneth H

    2015-04-01

    Readthrough of premature termination (stop) codons (PTC) is a new approach to treatment of genetic diseases. We recently reported that readthrough of PTC in cells from some xeroderma pigmentosum complementation group C (XP-C) patients could be achieved with the aminoglycosides geneticin or gentamicin. We found that the response depended on several factors including the PTC sequence, its location within the gene and the aminoglycoside used. Here, we extended these studies to investigate the effects of other aminoglycosides that are already on the market. We reasoned that topical treatment could deliver much higher concentrations of drug to the skin, the therapeutic target, and thus increase the therapeutic effect while reducing renal or ototoxicity in comparison with systemic treatment. Our prior clinical studies indicated that only a few percent of normal XPC expression was associated with mild clinical disease. We found minimal cell toxicity in the XP-C cells with several aminoglycosides. We found increased XPC mRNA expression in PTC-containing XP-C cells with G418, paromomycin, neomycin and kanamycin and increased XPC protein expression with G418. We conclude that in selected patients with XP, topical PTC therapy can be investigated as a method of personalized medicine to alleviate their cutaneous symptoms. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  4. Organization of the sleep-related neural systems in the brain of the minke whale (Balaenoptera acutorostrata).

    Science.gov (United States)

    Dell, Leigh-Anne; Karlsson, Karl Ae; Patzke, Nina; Spocter, Muhammad A; Siegel, Jerome M; Manger, Paul R

    2016-07-01

    The current study analyzed the nuclear organization of the neural systems related to the control and regulation of sleep and wake in the basal forebrain, diencephalon, midbrain, and pons of the minke whale, a mysticete cetacean. While odontocete cetaceans sleep in an unusual manner, with unihemispheric slow wave sleep (USWS) and suppressed REM sleep, it is unclear whether the mysticete whales show a similar sleep pattern. Previously, we detailed a range of features in the odontocete brain that appear to be related to odontocete-type sleep, and here present our analysis of these features in the minke whale brain. All neural elements involved in sleep regulation and control found in bihemispheric sleeping mammals and the harbor porpoise were present in the minke whale, with no specific nuclei being absent, and no novel nuclei being present. This qualitative similarity relates to the cholinergic, noradrenergic, serotonergic and orexinergic systems, and the GABAergic elements of these nuclei. Quantitative analysis revealed that the numbers of pontine cholinergic (274,242) and noradrenergic (203,686) neurons, and hypothalamic orexinergic neurons (277,604), are markedly higher than other large-brained bihemispheric sleeping mammals. Small telencephalic commissures (anterior, corpus callosum, and hippocampal), an enlarged posterior commissure, supernumerary pontine cholinergic and noradrenergic cells, and an enlarged peripheral division of the dorsal raphe nuclear complex of the minke whale, all indicate that the suite of neural characteristics thought to be involved in the control of USWS and the suppression of REM in the odontocete cetaceans are present in the minke whale. J. Comp. Neurol. 524:2018-2035, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  5. Contributions of the Nucleus Accumbens Shell in Mediating the Enhancement in Memory Following Noradrenergic Activation of Either the Amygdala or Hippocampus

    Directory of Open Access Journals (Sweden)

    Erin C. Kerfoot

    2018-02-01

    Full Text Available The nucleus accumbens shell is a site of converging inputs during memory processing for emotional events. The accumbens receives input from the nucleus of the solitary tract (NTS regarding changes in peripheral autonomic functioning following emotional arousal. The shell also receives input from the amygdala and hippocampus regarding affective and contextual attributes of new learning experiences. The successful encoding of affect or context is facilitated by activating noradrenergic systems in either the amygdala or hippocampus. Recent findings indicate that memory enhancement produced by activating NTS neurons, is attenuated by suppressing accumbens functioning after learning. This finding illustrates the significance of the shell in integrating information from the periphery to modulate memory for arousing events. However, it is not known if the accumbens shell plays an equally important role in consolidating information that is initially processed in the amygdala and hippocampus. The present study determined if the convergence of inputs from these limbic regions within the nucleus accumbens contributes to successful encoding of emotional events into memory. Male Sprague-Dawley rats received bilateral cannula implants 2 mm above the accumbens shell and a second bilateral implant 2 mm above either the amygdala or hippocampus. The subjects were trained for 6 days to drink from a water spout. On day 7, a 0.35 mA footshock was initiated as the rat approached the spout and was terminated once the rat escaped into a white compartment. Subjects were then given intra-amygdala or hippocampal infusions of PBS or a dose of norepinephrine (0.2 μg previously shown to enhance memory. Later, all subjects were given intra-accumbens infusion of muscimol to functionally inactivate the shell. Muscimol inactivation of the accumbens shell was delayed to allow sufficient time for norepinephrine to activate intracellular cascades that lead to long-term synaptic

  6. Contributions of the Nucleus Accumbens Shell in Mediating the Enhancement in Memory Following Noradrenergic Activation of Either the Amygdala or Hippocampus.

    Science.gov (United States)

    Kerfoot, Erin C; Williams, Cedric L

    2018-01-01

    The nucleus accumbens shell is a site of converging inputs during memory processing for emotional events. The accumbens receives input from the nucleus of the solitary tract (NTS) regarding changes in peripheral autonomic functioning following emotional arousal. The shell also receives input from the amygdala and hippocampus regarding affective and contextual attributes of new learning experiences. The successful encoding of affect or context is facilitated by activating noradrenergic systems in either the amygdala or hippocampus. Recent findings indicate that memory enhancement produced by activating NTS neurons, is attenuated by suppressing accumbens functioning after learning. This finding illustrates the significance of the shell in integrating information from the periphery to modulate memory for arousing events. However, it is not known if the accumbens shell plays an equally important role in consolidating information that is initially processed in the amygdala and hippocampus. The present study determined if the convergence of inputs from these limbic regions within the nucleus accumbens contributes to successful encoding of emotional events into memory. Male Sprague-Dawley rats received bilateral cannula implants 2 mm above the accumbens shell and a second bilateral implant 2 mm above either the amygdala or hippocampus. The subjects were trained for 6 days to drink from a water spout. On day 7, a 0.35 mA footshock was initiated as the rat approached the spout and was terminated once the rat escaped into a white compartment. Subjects were then given intra-amygdala or hippocampal infusions of PBS or a dose of norepinephrine (0.2 μg) previously shown to enhance memory. Later, all subjects were given intra-accumbens infusion of muscimol to functionally inactivate the shell. Muscimol inactivation of the accumbens shell was delayed to allow sufficient time for norepinephrine to activate intracellular cascades that lead to long-term synaptic modifications

  7. Endothelial cell markers in vascular neoplasms: an immunohistochemical study comparing factor VIII-related antigen, blood group specific antigens, 6-keto-PGF1 alpha, and Ulex europaeus 1 lectin.

    Science.gov (United States)

    Little, D; Said, J W; Siegel, R J; Fealy, M; Fishbein, M C

    1986-06-01

    Markers for endothelial cells including Ulex europaeus 1 lectin, blood group A, B, and H, and the prostaglandin metabolite 6-keto-PGF1 alpha were evaluated in paraffin secretions from formalin-fixed benign and malignant vascular neoplasms using a variety of immunohistochemical techniques, and results compared with staining for factor VIII-related antigen. Staining for Ulex appeared more sensitive than factor VIII-related antigen in identifying poorly differentiated neoplasms including haemangiosarcomas and spindle cell proliferations in Kaposi's sarcoma. Staining for blood group related antigens correlated with blood group in all cases. Ulex europaeus 1 lectin was the only marker for endothelial cells in lymphangiomas.

  8. The neural cell adhesion molecule L1 is distinct from the N-CAM related group of surface antigens BSP-2 and D2

    DEFF Research Database (Denmark)

    Faissner, A; Kruse, J; Goridis, C

    1984-01-01

    The neural cell adhesion molecule L1 and the group of N-CAM related molecules, BSP-2 and D2 antigen, are immunochemically distinct molecular species. The two groups of surface molecules are also functionally distinct entities, since inhibition of Ca2+-independent adhesion among early post-natal m...

  9. A two-compartment description and kinetic procedure for measuring regional cerebral [11C]nomifensine uptake using positron emission tomography

    International Nuclear Information System (INIS)

    Salmon, E.; Brooks, D.J.; Leenders, K.L.; Turton, D.R.; Hume, S.P.; Cremer, J.E.; Jones, T.; Frackowiak, R.S.

    1990-01-01

    S-[11C]Nomifensine (S-[11C]NMF) is a positron-emitting tracer suitable for positron emission tomography, which binds to both dopaminergic and noradrenergic reuptake sites in the striatum and the thalamus. Modelling of the cerebral distribution of this drug has been hampered by the rapid appearance of glucuronide metabolites in the plasma, which do not cross the blood--brain barrier. To date, [11C]NMF uptake has simply been expressed as regional versus nonspecific cerebellar activity ratios. We have calculated a free NMF input curve from red cell activity curves, using the fact that the free drug rapidly equilibrates between red cells and plasma, while glucuronides do not enter red cells. With this free [11C]NMF input function, all regional cerebral uptake curves could be fitted to a conventional two-compartment model, defining tracer distribution in terms of [11C]NMF regional volume of distribution. Assuming that the cerebellar volume of distribution of [11C]NMF represents the nonspecific volume of distribution of the tracer in striatum and thalamus, we have calculated an equilibrium partition coefficient for [11C]NMF between freely exchanging specific and nonspecific compartments in these regions, representing its binding potential to dopaminergic or noradrenergic uptake sites (or complexes). This partition coefficient was lower in the striatum when the racemate rather than the active S-enantiomer of [11C]NMF was administered. In the striatum of patients suffering from Parkinson's disease and multiple-system atrophy, the specific compartmentation of S-[11C]NMF was significantly decreased compared with that of age-matched volunteers

  10. Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

    Science.gov (United States)

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-05-01

    Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

  11. Noradrenergic System and Memory

    KAUST Repository

    Zenger, Manuel; Burlet-Godinot, Sophie; Petit, Jean-Marie; Magistretti, Pierre J.

    2017-01-01

    There is ample evidence indicating that noradrenaline plays an important role in memory mechanisms. Noradrenaline is thought to modulate these procsses through activation of adrenergic receptors in neurons. Astrocytes that form essential partners for synaptic function, also express alpha- and beta-adrenergic receptors. In astrocytes, noradrenaline triggers metabolic actions such as the glycogenolysis leading to an increase in l-lactate formation and release. l-Lactate can be used by neurons as a sourc of energy during memory tasks and can also induc transcription of plasticity genes in neurons. Activation of β-adrenergic receptors can also trigger gliotransmitter release resulting of intracllular calcium waves. These gliotransmitters modulate the synaptic activity and thereby can modulate long-term potentiation mechanisms. In summary, recnt evidencs indicate that noradrenaline exerts its memory-promoting effects through different modes of action both on neurons and astrocytes.

  12. Noradrenergic System and Memory

    KAUST Repository

    Zenger, Manuel

    2017-07-22

    There is ample evidence indicating that noradrenaline plays an important role in memory mechanisms. Noradrenaline is thought to modulate these procsses through activation of adrenergic receptors in neurons. Astrocytes that form essential partners for synaptic function, also express alpha- and beta-adrenergic receptors. In astrocytes, noradrenaline triggers metabolic actions such as the glycogenolysis leading to an increase in l-lactate formation and release. l-Lactate can be used by neurons as a sourc of energy during memory tasks and can also induc transcription of plasticity genes in neurons. Activation of β-adrenergic receptors can also trigger gliotransmitter release resulting of intracllular calcium waves. These gliotransmitters modulate the synaptic activity and thereby can modulate long-term potentiation mechanisms. In summary, recnt evidencs indicate that noradrenaline exerts its memory-promoting effects through different modes of action both on neurons and astrocytes.

  13. Influence of VB group doped TiO2 on photovoltaic performance of dye-sensitized solar cells

    International Nuclear Information System (INIS)

    Liu, Jia; Duan, Yandong; Zhou, Xiaowen; Lin, Yuan

    2013-01-01

    Dye-sensitized solar cell with V B group (vanadium (V), niobium (Nb) and tantalum (Ta)) doped TiO 2 prepared by hydrothermal method shows a higher photovoltaic efficiency compared with the undoped TiO 2 . All the V B doping shift the flat band potential positively and increase the doping density which is investigated by Mott–Schottky plot. The positive shift of flat band potential improves the driving force of injecting electron from the LUMO of dye to the conduction band of TiO 2 and the photocurrent. On the other hand, the increase of doping density accelerates transfer rate of electrons in TiO 2 than the un-doped, which is confirmed by intensity-modulated photocurrent. V-, Nb-, Ta-doped TiO 2 exhibited photovoltaic performance with 7.80%, 8.33%, 8.18%, respectively, compared with that of the cells based on pure TiO 2 (7.42%).

  14. The effect of coniine on presynaptic nicotinic receptors.

    Science.gov (United States)

    Erkent, Ulkem; Iskit, Alper B; Onur, Rustu; Ilhan, Mustafa

    2016-01-01

    Toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), is manifested by characteristic nicotinic clinical signs including excitement, depression, hypermetria, seizures, opisthotonos via postsynaptic nicotinic receptors. There is limited knowledge about the role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine in the literature. The present study was undertaken to evaluate the possible role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine. For this purpose, the rat anococcygeus muscle and guinea-pig atria were used in vitro. Nicotine (100 μM) elicited a biphasic response composed of a relaxation followed by contraction through the activation of nitrergic and noradrenergic nerve terminals in the phenylephrine-contracted rat anococcygeus muscle. Coniine inhibited both the nitrergic and noradrenergic response in the muscle (-logIC(50) = 3.79 ± 0.11 and -logIC(50) = 4.57 ± 0.12 M, respectively). The effect of coniine on nicotinic receptor-mediated noradrenergic transmission was also evaluated in the guinea-pig atrium (-logIC(50) = 4.47 ± 0.12 M) and did not differ from the -logIC(50) value obtained in the rat anococcygeus muscle. This study demonstrated that coniine exerts inhibitory effects on nicotinic receptor-mediated nitrergic and noradrenergic transmitter response.

  15. Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups

    Directory of Open Access Journals (Sweden)

    Ekkapongpisit M

    2012-07-01

    Full Text Available Maneerat Ekkapongpisit,1 Antonino Giovia,1 Carlo Follo,1 Giuseppe Caputo,2,3 Ciro Isidoro11Laboratory of Molecular Pathology and Nanobioimaging, Department of Health Sciences, Università del Piemonte Orientale “A Avogadro”, Novara, 2Dipartimento di Chimica dell’Università di Torino, Torino, 3Cyanine Technology SpA, Torino, ItalyBackground and methods: Nanoparticles engineered to carry both a chemotherapeutic drug and a sensitive imaging probe are valid tools for early detection of cancer cells and to monitor the cytotoxic effects of anticancer treatment simultaneously. Here we report on the effect of size (10–30 nm versus 50 nm, type of material (mesoporous silica versus polystyrene, and surface charge functionalization (none, amine groups, or carboxyl groups on biocompatibility, uptake, compartmentalization, and intracellular retention of fluorescently labeled nanoparticles in cultured human ovarian cancer cells. We also investigated the involvement of caveolae in the mechanism of uptake of nanoparticles.Results: We found that mesoporous silica nanoparticles entered via caveolae-mediated endocytosis and reached the lysosomes; however, while the 50 nm nanoparticles permanently resided within these organelles, the 10 nm nanoparticles soon relocated in the cytoplasm. Naked 10 nm mesoporous silica nanoparticles showed the highest and 50 nm carboxyl-modified mesoporous silica nanoparticles the lowest uptake rates, respectively. Polystyrene nanoparticle uptake also occurred via a caveolae-independent pathway, and was negatively affected by serum. The 30 nm carboxyl-modified polystyrene nanoparticles did not localize in lysosomes and were not toxic, while the 50 nm amine-modified polystyrene nanoparticles accumulated within lysosomes and eventually caused cell death. Ovarian cancer cells expressing caveolin-1 were more likely to endocytose these nanoparticles.Conclusion: These data highlight the importance of considering both the

  16. Insulin resistance and beta-cell function in different ethnic groups in Kenya: the role of abdominal fat distribution

    DEFF Research Database (Denmark)

    Christensen, D.L.; Faurholt-Jepsen, D.; Faerch, K.

    2014-01-01

    Little is known about the pathophysiology of diabetes in Africans. Thus, we assessed whether insulin resistance and beta-cell function differed by ethnicity in Kenya and whether differences were modified by abdominal fat distribution. A cross-sectional study in 1,087 rural Luo (n = 361), Kamba (n...... to the Luo and Kamba, respectively. Adjustments of SAT (range 0.1–7.1 cm) and VAT (range 1.5–14.2 cm) largely explained these inter-group differences with the Maasai having the highest combined abdominal fat accumulation. The Maasai had the highest insulin resistance and secretion, but the lowest relative...... beta-cell function compared to the Luo and Kamba. These differences were primarily explained by abdominal fat distribution....

  17. Cell surface groups of two picocyanobacteria strains studied by zeta potential investigations, potentiometric titration, and infrared spectroscopy.

    Science.gov (United States)

    Dittrich, Maria; Sibler, Sabine

    2005-06-15

    In order to clarify the role of picocyanobacteria in aquatic biogeochemical processes (e.g., calcite precipitation), cell surface properties need to be investigated. An experimental study of the cell surface characteristics of two Synechococcus-type unicellular autotrophic picocyanobacterial strains was carried out. One strain was isolated from Lake Plon and contained phycocyanin, the other strain came from Lago Maggiore and was rich in phycoerythrin. Potentiometric titrations were conducted to determine the different types of sites present on the bacteria cell walls. Infrared spectroscopy allowed characterization of the various functional groups (RNH(2), RCOOH, ROH, RPO(2)) and investigations of zeta potential provided insight into the isoelectrical points of the strains. Titrations reveal three distinct sites on the bacterial surfaces of phycocyanin- and phycoerythrin-rich strains with pK values of 4.8+/-0.3/5.0+/-0.2, 6.6+/-0.2/6.7+/-0.4, and 8.8+/-0.1/8.7+/-0.2, corresponding to carboxyl, phosphate, and amine groups with surface densities of 2.6+/-0.4/7.4+/-1.6 x 10(-4), 1.9+/-0.5/4.4+/-0.8 x 10(-4), and 2.5+/-0.4/4.8+/-0.7 x 10(-4) mol/g of dry bacteria. The deprotonation constants are similar to those of bacterial strains and site densities are also within an order of magnitude of other strains. The phycoerythrin-rich strain had a higher number of binding sites than the phycocyanin-rich strain. The results showed that picocyanobacteria may adsorb either calcium cations or carbonate anions and therefore strongly influence the biogeochemical cycling of calcite in pelagic systems.

  18. Grouping annotations on the subcellular layered interactome demonstrates enhanced autophagy activity in a recurrent experimental autoimmune uveitis T cell line.

    Directory of Open Access Journals (Sweden)

    Xiuzhi Jia

    Full Text Available Human uveitis is a type of T cell-mediated autoimmune disease that often shows relapse-remitting courses affecting multiple biological processes. As a cytoplasmic process, autophagy has been seen as an adaptive response to cell death and survival, yet the link between autophagy and T cell-mediated autoimmunity is not certain. In this study, based on the differentially expressed genes (GSE19652 between the recurrent versus monophasic T cell lines, whose adoptive transfer to susceptible animals may result in respective recurrent or monophasic uveitis, we proposed grouping annotations on a subcellular layered interactome framework to analyze the specific bioprocesses that are linked to the recurrence of T cell autoimmunity. That is, the subcellular layered interactome was established by the Cytoscape and Cerebral plugin based on differential expression, global interactome, and subcellular localization information. Then, the layered interactomes were grouping annotated by the ClueGO plugin based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The analysis showed that significant bioprocesses with autophagy were orchestrated in the cytoplasmic layered interactome and that mTOR may have a regulatory role in it. Furthermore, by setting up recurrent and monophasic uveitis in Lewis rats, we confirmed by transmission electron microscopy that, in comparison to the monophasic disease, recurrent uveitis in vivo showed significantly increased autophagy activity and extended lymphocyte infiltration to the affected retina. In summary, our framework methodology is a useful tool to disclose specific bioprocesses and molecular targets that can be attributed to a certain disease. Our results indicated that targeted inhibition of autophagy pathways may perturb the recurrence of uveitis.

  19. Xeroderma Pigmentosum Group A Promotes Autophagy to Facilitate Cisplatin Resistance in Melanoma Cells through the Activation of PARP1.

    Science.gov (United States)

    Ge, Rui; Liu, Lin; Dai, Wei; Zhang, Weigang; Yang, Yuqi; Wang, Huina; Shi, Qiong; Guo, Sen; Yi, Xiuli; Wang, Gang; Gao, Tianwen; Luan, Qi; Li, Chunying

    2016-06-01

    Xeroderma pigmentosum group A (XPA), a key protein in the nucleotide excision repair pathway, has been shown to promote the resistance of tumor cells to chemotherapeutic drugs by facilitating the DNA repair process. However, the role of XPA in the resistance of melanoma to platinum-based drugs like cisplatin is largely unknown. In this study, we initially found that XPA was expressed at higher levels in cisplatin-resistant melanoma cells than in cisplatin-sensitive ones. Furthermore, the knockdown of XPA not only increased cellular apoptosis but also inhibited cisplatin-induced autophagy, which rendered the melanoma cells more sensitive to cisplatin. Moreover, we discovered that the increased XPA in resistant melanoma cells promoted poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) activation and that the inhibition of PARP1 could attenuate the cisplatin-induced autophagy. Finally, we proved that the inhibition of PARP1 and the autophagy process made resistant melanoma cells more susceptible to cisplatin treatment. Our study shows that XPA can promote cell-protective autophagy in a DNA repair-independent manner by enhancing the activation of PARP1 in melanoma cells resistant to cisplatin and that the XPA-PARP1-mediated autophagy process can be targeted to overcome cisplatin resistance in melanoma chemotherapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Novel polyfucosylated N-linked glycopeptides with blood group A, H, X and Y determinants from human small intestinal epithelial cells

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Finne, J.; Breimer, M.E.; Hansson, G.C.; Karlsson, K.-A.; Leffler, H.; Halbeek, H. van

    1989-01-01

    A novel type of N-linked glycopeptides representing a major part of the glycans in human small intestinal epithelial cells from blood group A and O individuals were isolated by gel filtrations and affinity chromatography on concanavalin A-Sepharose and Bandeiraea simplicifolia lectin I-Sepharose.

  1. Quality of life in Arab Muslim cancer survivors following hematopoietic stem cell transplantation: comparison with matched healthy group.

    Science.gov (United States)

    Alaloul, Fawwaz; Brockopp, Dorothy Y; Andrykowski, Michael A; Hall, Lynne A; Al Nusairat, Taghreed S

    2015-07-01

    The aims of this study were to determine if quality of life (QOL) among Arab Muslim hematopoietic stem cell transplantation (HSCT) survivors differs from that of a healthy matched comparison group and to examine the relationships of demographic and medical variables and perceived social support with post-HSCT QOL. HSCT survivors (n = 63) were recruited from the King Hussein Cancer Center outpatient clinic. A matched (age, gender, education), healthy comparison group (n = 63) was recruited through public advertisements. Participants completed the EORTC-30 QOL scale and the Medical Outcomes Study Social Support Survey. Differences were found between the Arab Muslim HSCT survivor and healthy comparison groups for physical functioning (p Western HSCT survivors in the social and emotional QOL domains. Given growing numbers of Arab and Muslim cancer survivors in the USA and other Western countries, future research is warranted.

  2. A Life-Cycle Model of Human Social Groups Produces a U-Shaped Distribution in Group Size.

    Directory of Open Access Journals (Sweden)

    Gul Deniz Salali

    Full Text Available One of the central puzzles in the study of sociocultural evolution is how and why transitions from small-scale human groups to large-scale, hierarchically more complex ones occurred. Here we develop a spatially explicit agent-based model as a first step towards understanding the ecological dynamics of small and large-scale human groups. By analogy with the interactions between single-celled and multicellular organisms, we build a theory of group lifecycles as an emergent property of single cell demographic and expansion behaviours. We find that once the transition from small-scale to large-scale groups occurs, a few large-scale groups continue expanding while small-scale groups gradually become scarcer, and large-scale groups become larger in size and fewer in number over time. Demographic and expansion behaviours of groups are largely influenced by the distribution and availability of resources. Our results conform to a pattern of human political change in which religions and nation states come to be represented by a few large units and many smaller ones. Future enhancements of the model should include decision-making rules and probabilities of fragmentation for large-scale societies. We suggest that the synthesis of population ecology and social evolution will generate increasingly plausible models of human group dynamics.

  3. Design and Synthesis of New Chacones Substituted with Azide/Triazole Groups and Analysis of Their Cytotoxicity Towards HeLa Cells

    Directory of Open Access Journals (Sweden)

    José A. F. P. Villar

    2012-08-01

    Full Text Available A series of new chalcones substituted with azide/triazole groups were designed and synthesized, and their cytotoxic activity was evaluated in vitro against the HeLa cell line. O-Alkylation, Claisen-Schmidt condensation and Cu(I-catalyzed cycloaddition of azides with terminal alkynes were applied in key steps. Fifteen compounds were tested against HeLa cells. Compound 8c was the most active molecule, with an IC50 value of 13.03 µM, similar to the value of cisplatin (7.37 µM.

  4. Genetic Basis for Developmental Homeostasis of Germline Stem Cell Niche Number: A Network of Tramtrack-Group Nuclear BTB Factors

    Science.gov (United States)

    Chalvet, Fabienne; Netter, Sophie; Dos Santos, Nicolas; Poisot, Emilie; Paces-Fessy, Mélanie; Cumenal, Delphine; Peronnet, Frédérique; Pret, Anne-Marie; Théodore, Laurent

    2012-01-01

    The potential to produce new cells during adult life depends on the number of stem cell niches and the capacity of stem cells to divide, and is therefore under the control of programs ensuring developmental homeostasis. However, it remains generally unknown how the number of stem cell niches is controlled. In the insect ovary, each germline stem cell (GSC) niche is embedded in a functional unit called an ovariole. The number of ovarioles, and thus the number of GSC niches, varies widely among species. In Drosophila, morphogenesis of ovarioles starts in larvae with the formation of terminal filaments (TFs), each made of 8–10 cells that pile up and sort in stacks. TFs constitute organizers of individual germline stem cell niches during larval and early pupal development. In the Drosophila melanogaster subgroup, the number of ovarioles varies interspecifically from 8 to 20. Here we show that pipsqueak, Trithorax-like, batman and the bric-à-brac (bab) locus, all encoding nuclear BTB/POZ factors of the Tramtrack Group, are involved in limiting the number of ovarioles in D. melanogaster. At least two different processes are differentially perturbed by reducing the function of these genes. We found that when the bab dose is reduced, sorting of TF cells into TFs was affected such that each TF contains fewer cells and more TFs are formed. In contrast, psq mutants exhibited a greater number of TF cells per ovary, with a normal number of cells per TF, thereby leading to formation of more TFs per ovary than in the wild type. Our results indicate that two parallel genetic pathways under the control of a network of nuclear BTB factors are combined in order to negatively control the number of germline stem cell niches. PMID:23185495

  5. Cell Biochips

    Science.gov (United States)

    Pioufle, B. Le; Picollet-D'Hahan, N.

    A cell biochip is a microsystem, equipped with electronic and microfluidic functions, designed to manipulate or analyse living cells. The first publications in this emerging area of research appeared toward the end of the 1980s. In 1989 Washizu described a biochip designed to fuse two cells by electropermeabilisation of the cytoplasmic membrane [1]. Research centers have devised a whole range of cell chip structures, for simultaneous or sequential analysis of single cells, cell groups, or cell tissues reconstituted on the chip. The cells are arranged in a square array on a parallel cell chip for parallel analysis, while they are examined and processed one by one in a microchannel in the case of a series cell chip. In contrast to these biochips for high-throughput analysis of a large number of cells, single-cell chips focus on the analysis of a single isolated cell. As in DNA microarrays, where a large number of oligonucleotides are ordered in a matrix array, parallel cell chips order living cells in a similar way. At each point of the array, the cells can be isolated, provided that the cell type allows this, e.g., blood cells, or cultivated in groups (most adhesion cells can only survive in groups). The aim is to allow massively parallel analysis or processing. Le Pioufle et al. describe a microdevice for the culture of single cells or small groups of cells in a micropit array [2]. Each pit is equipped to stimulate the cell or group of cells either electrically or fluidically. Among the applications envisaged are gene transfer, cell sorting, and screening in pharmacology. A complementary approach, combining the DNA microarray and cell biochip ideas, has been put forward by Bailey et al. [3]. Genes previously arrayed on the chip transfect the cultured cells on the substrate depending on their position in the array (see Fig. 19.1). This way of achieving differential lipofection on a chip was then taken up again by Yoshikawa et al. [4] with primary cells, more

  6. Anaphylaxis vulnerable groups

    African Journals Online (AJOL)

    Ehab

    Age groups vulnerable to serious attacks of anaphylaxis include infants, teenagers, pregnant women, and the elderly. Concomitant diseases, such as severe or uncontrolled asthma, cardiovascular disease, mastocytosis or clonal mast cell disorders and the concurrent use of some medications such as beta adrenergic ...

  7. MicroRNA-101 inhibits cell proliferation, promotes cell apoptosis and increases sensitivity of breast cancer MDA-MB-231 cells to paclitaxel

    Directory of Open Access Journals (Sweden)

    Qiu-Lin Ke

    2016-02-01

    Full Text Available Objective: To explore the effect that miR-101 inhibits breast cancer MDA-MB-231 cell proliferation and increases the chemosensitivity of paclitaxel to breast cancer MDA-MB-231 cells and its influence on protein expression level of target gene Bcl2. Methods: miR-101 was artificially synthesized, it used liposome 3000 to transfect MDA-MB-231 cells, and experiment was divided into three groups: blank control group, negative control group and miR-101 group. MTT assay was used to detect the effect of miR-101 on MDA-MB-231 cell proliferation and chemosensitivity of paclitaxel-mediated MDA-MB-231 cells; flow cytometer was used to detect cell apoptosis. Real-time PCR and Western bloting were used to detect the changes of mRNA and protein expression levels of Bcl2. Results: After miR-101 transfected MDA-MB- 231 cells, cell proliferation ability significantly decreased compared with negative control group, and differences had statistical significance (P<0.01; after paclitaxel was used to process cells, IC50 of miR-101-processing group decreased by 2.45 times compared with blank control group, differences had statistical significance (P<0.05 and differences between blank control group and negative control group had no statistical significance; detection results by flow cytometer showed that both early-stage and late-stage apoptosis rates of MDA-MB-231 cells of miR-101 group were significantly higher than those of negative control group (P<0.05, and early-stage apoptosis rate was more significant (P<0.01; after transfection of miR-101, mRNA and protein levels of Bcl2 of MDA-MB-231 cells significantly decreased, and differences had statistical significance (P<0.05. Conclusion: miR-101 can inhibit breast cancer MDAMB- 231 cell proliferation through targeting and downregulating Bcl2, thereby increasing the chemosensitivity of breast cancer cells to paclitaxel and promoting cell apoptosis.

  8. Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors

    DEFF Research Database (Denmark)

    Arendrup, M; Hansen, J E; Clausen, H

    1991-01-01

    Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility...... for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did...... not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can...

  9. Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors

    DEFF Research Database (Denmark)

    Arendrup, M; Hansen, J E; Clausen, H

    1991-01-01

    Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility...... not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can...... for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did...

  10. The Number of Positive Pelvic Lymph Nodes and Multiple Groups of Pelvic Lymph Node Metastasis Influence Prognosis in Stage IA-IIB Cervical Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2015-01-01

    Full Text Available Background: Pelvic lymph node metastasis (LNM is an important prognostic factor in cervical cancer. Cervical squamous cell carcinoma accounts for approximately 75-80% of all cervical cancers. Analyses of the effects of the number of positive lymph nodes (LNs, unilateral versus bilateral pelvic LNM and a single group versus multiple groups of pelvic LNM on survival and recurrence of cervical squamous cell carcinoma are still lacking. The study aimed to analyze the effects of the number of positive pelvic LNs and a single group versus multiple groups of pelvic LNM on survival and recurrence. Methods: We performed a retrospective review of 296 patients diagnosed with Stage IA-IIB cervical squamous cell carcinoma who received extensive/sub-extensive hysterectomy with pelvic lymphadenectomy/pelvic LN sampling at Peking University People′s Hospital from November 2004 to July 2013. Ten clinicopathological variables were evaluated as risk factors for pelvic LNM: Age at diagnosis, gravidity, clinical stage, histological grade, tumor diameter, lymph-vascular space involvement (LVSI, depth of cervical stromal invasion, uterine invasion, parametrial invasion, and neoadjuvant chemotherapy. Results: The incidence of pelvic LNM was 20.27% (60/296 cases. Pelvic LNM (P = 0.00 was significantly correlated with recurrence. Pelvic LNM (P = 0.00, the number of positive pelvic LNs (P = 0.04 and a single group versus multiple groups of pelvic LNM (P = 0.03 had a significant influence on survival. Multivariate analysis revealed that LVSI (P = 0.00, depth of cervical stromal invasion (P = 0.00 and parametrial invasion (P = 0.03 were independently associated with pelvic LNM. Conclusions: Patients with pelvic LNM had a higher recurrence rate and poor survival outcomes. Furthermore, more than 2 positive pelvic LNs and multiple groups of pelvic LNM appeared to identify patients with worse survival outcomes in node-positive IA-IIB cervical squamous cell carcinoma. LVSI

  11. A Novel Physiology-Based Mathematical Model to Estimate Red Blood Cell Lifespan in Different Human Age Groups.

    Science.gov (United States)

    An, Guohua; Widness, John A; Mock, Donald M; Veng-Pedersen, Peter

    2016-09-01

    Direct measurement of red blood cell (RBC) survival in humans has improved from the original accurate but limited differential agglutination technique to the current reliable, safe, and accurate biotin method. Despite this, all of these methods are time consuming and require blood sampling over several months to determine the RBC lifespan. For situations in which RBC survival information must be obtained quickly, these methods are not suitable. With the exception of adults and infants, RBC survival has not been extensively investigated in other age groups. To address this need, we developed a novel, physiology-based mathematical model that quickly estimates RBC lifespan in healthy individuals at any age. The model is based on the assumption that the total number of RBC recirculations during the lifespan of each RBC (denoted by N max) is relatively constant for all age groups. The model was initially validated using the data from our prior infant and adult biotin-labeled red blood cell studies and then extended to the other age groups. The model generated the following estimated RBC lifespans in 2-year-old, 5-year-old, 8-year-old, and 10-year-old children: 62, 74, 82, and 86 days, respectively. We speculate that this model has useful clinical applications. For example, HbA1c testing is not reliable in identifying children with diabetes because HbA1c is directly affected by RBC lifespan. Because our model can estimate RBC lifespan in children at any age, corrections to HbA1c values based on the model-generated RBC lifespan could improve diabetes diagnosis as well as therapy in children.

  12. Relationship between secretion of the Anton blood group antigen in saliva and adherence of Haemophilus influenzae to oropharynx epithelial cells

    NARCIS (Netherlands)

    van Alphen, L.; van Ham, M.; Geelen-van den Broek, L.; Pieters, T.

    1989-01-01

    Inhibition of adherence of bacteria to epithelial cells contributes to a reduction of infections by these bacteria. We have shown that the Anton blood group antigen, the erythrocyte receptor for Haemophilus influenzae (van Alphen et al. 1986, FEMS Microbiol. Lett. 37, 69-71), occurs in saliva, that

  13. Effect of carboxyl anchoring groups in asymmetric zinc phthalocyanine with large steric hindrance on the dye-sensitized solar cell performance

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Wenye; Peng, Bosi; Lin, Li; Li, Renjie; Zhang, Jing, E-mail: jzhang03@whu.edu.cn; Peng, Tianyou, E-mail: typeng@whu.edu.cn

    2015-08-01

    Asymmetric zinc phthalocyanines containing tribenzonaphtho-condensed porphyrazine with six bulky diphenylphenoxy and one or two carboxyl groups are used as sensitizers for dye-sensitized solar cells (DSSCs). It is found that Zn-tri-PcNc-4 having two carboxyl groups shows a slight redshift in the Q-band absorption but a significantly decreased absorbance as compared with Zn-tri-PcNc-8 having one carboxyl group, and Zn-tri-PcNc-4 can be more stably and perpendicularly grafted onto the TiO{sub 2} surface than Zn-tri-PcNc-8, which further leads to the differences in the interfacial charge transfer dynamics and dye-loaded amount. Zn-tri-PcNc-4 with two carboxyl groups grafted onto the TiO{sub 2} electrode surface of DSSC results in a photovoltaic conversion efficiency of 3.22%, higher than that (3.01%) of the analog with one carboxyl group (Zn-tri-PcNc-8), which exhibits a lower short-circuit current but much higher open-circuit voltage. The additional carboxyl group in Zn-tri-PcNc-4 leads to the enhanced dye-loaded amount and the molecular orbital energy level shift toward positive direction, causing more efficient electron injection and higher short-circuit current than Zn-tri-PcNc-8; while the two carboxyl groups of Zn-tri-PcNc-4 would cause more protonation of TiO{sub 2} surface, which possibly leads to the downward shift of TiO{sub 2} conduction band edge, and then to the decreased open-circuit voltage. The present results demonstrate the molecular engineering aspect of ZnPc dyes in which the fine tuning of the energy levels and molecular structures is crucial for high conversion efficiency of DSSCs. - Highlights: • ZnPcs with six diphenylphenoxy and one/two carboxyl groups are used as dyes for DSSCs. • Effect of carboxyl group number on the ZnPc-sensitized cell property are scrutinized. • Grafting two carboxyl groups on ZnPc leads to the enhanced photocurrent and efficiency. • ZnPc with one COOH has a higher open-circuit voltage than its analog with two

  14. Basal cell carcinoma in farmers: an occupation group at high risk.

    Science.gov (United States)

    Szewczyk, Mateusz; Pazdrowski, Jakub; Golusiński, Paweł; Dańczak-Pazdrowska, Aleksandra; Łuczewski, Łukasz; Marszałek, Sławomir; Majchrzak, Ewa; Golusiński, Wojciech

    2016-04-01

    Skin cancer is the most commonly diagnosed cancer type worldwide, and 80 % of skin cancers are basal cell carcinoma (BCC). The main risk factor for developing BCC is exposure to ultraviolet radiation (UVR), particularly high-dose exposure at a young age. Outdoor workers, particularly farmers, are at high risk of developing BCC. However, studies of BCC in this population are scant. To comprehensively evaluate all cases of BCC of the head and neck region treated during the years 2007-2013 at our hospital in Poland, and to compare the tumour characteristics in farmers to non-farmers. Retrospective analysis of 312 patients treated for head and neck BCC during the study period (2007-2013). Most patients (198 cases; 63 %) were males, with 114 females (37 %). Median age was 73 years (range 32-96 years). The most common tumour location was the nose and cheek (114 pts; 37 %) followed by the auricle (82 pts; 26 %), lips (54 pts; 18 %), scalp (26 pts; 8 %), and eye (36 pts; 12 %). The most common disease stage on presentation was stage T2 (104 pts, 33 %), followed by stage T1 (79 pts; 25 %), stage T3 (89 pts; 28 %), and stage T4 (40 pts; 14 %). By occupation, farmers accounted for 33 % of all patients (102 of 312 pts). The most common tumour localisations in the farmer subgroup were the nose and cheek (50 pts; 49 %; p farmer group were significantly younger than non-farmers (62 vs. 73 years; p Farmers were significantly more likely to present disease recurrence (27 vs. 12 % of cases; p farmers. It is therefore necessary to consider enhancing educational programmes and other preventative measures in this occupational group and to evaluate the effectiveness of such programmes.

  15. Stem Cell Gene Therapy for Fanconi Anemia: Report from the 1st International Fanconi Anemia Gene Therapy Working Group Meeting

    Science.gov (United States)

    Tolar, Jakub; Adair, Jennifer E; Antoniou, Michael; Bartholomae, Cynthia C; Becker, Pamela S; Blazar, Bruce R; Bueren, Juan; Carroll, Thomas; Cavazzana-Calvo, Marina; Clapp, D Wade; Dalgleish, Robert; Galy, Anne; Gaspar, H Bobby; Hanenberg, Helmut; Von Kalle, Christof; Kiem, Hans-Peter; Lindeman, Dirk; Naldini, Luigi; Navarro, Susana; Renella, Raffaele; Rio, Paula; Sevilla, Julián; Schmidt, Manfred; Verhoeyen, Els; Wagner, John E; Williams, David A; Thrasher, Adrian J

    2011-01-01

    Survival rates after allogeneic hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) have increased dramatically since 2000. However, the use of autologous stem cell gene therapy, whereby the patient's own blood stem cells are modified to express the wild-type gene product, could potentially avoid the early and late complications of allogeneic HCT. Over the last decades, gene therapy has experienced a high degree of optimism interrupted by periods of diminished expectation. Optimism stems from recent examples of successful gene correction in several congenital immunodeficiencies, whereas diminished expectations come from the realization that gene therapy will not be free of side effects. The goal of the 1st International Fanconi Anemia Gene Therapy Working Group Meeting was to determine the optimal strategy for moving stem cell gene therapy into clinical trials for individuals with FA. To this end, key investigators examined vector design, transduction method, criteria for large-scale clinical-grade vector manufacture, hematopoietic cell preparation, and eligibility criteria for FA patients most likely to benefit. The report summarizes the roadmap for the development of gene therapy for FA. PMID:21540837

  16. Blood group genotyping: from patient to high-throughput donor screening

    NARCIS (Netherlands)

    Veldhuisen, B.; van der Schoot, C. E.; de Haas, M.

    2009-01-01

    Blood group antigens, present on the cell membrane of red blood cells and platelets, can be defined either serologically or predicted based on the genotypes of genes encoding for blood group antigens. At present, the molecular basis of many antigens of the 30 blood group systems and 17 human

  17. [gammadelta T cells stimulated by zoledronate kill osteosarcoma cells].

    Science.gov (United States)

    Jiang, Hui; Xu, Qiang; Yang, Chao; Cao, Zhen-Guo; Li, Zhao-Xu; Ye, Zhao-Ming

    2010-12-01

    To investigate the cytotoxicity of human γδT cells from PBMCs stimulated by zoledronate against osteosarcoma cell line HOS in vitro and in vivo and evaluate the relavent pathways. The peripheral blood mononuclear cells (PBMCs)of healthy donors were stimulated by single dose zoledronate and cultured in the present of IL-2 for two weeks, analysising the percentage of γδT cells on a FACSCalibur cytometer.Study the cytotoxicity of γδT cells against the osteosarcoma line HOS using LDH release assay kit. Pre-treatment of γδT cells with anti-human γδTCR antibody, anti-human NKG2D antibody and concanamycin A to bolck the relavent pathways for evaluating the mechenisms of its cytotoxicity. In vivo, BALB/c mice were inoculated subcutaneously osteosarcoma cell HOS for developing hypodermal tumors. And they were randomized into two groups: unteated group, γδT cell therapy group. Tumor volume and weight of the two groups were compared. After two weeks of culture, γδT cells from zoledronate-stimulated PBMCs could reach (95±3)%. When the E:T as 6:1, 12:1, 25:1, 50:1, the percentage of osteosarcoma cell HOS killed by γδT cells was 26.8%, 31.5%, 37.8%, 40.9%, respectively.When anti-huma γδTCR antibody, anti-human NKG2D antibody and concanamycin A blocked the relavent pathways, the percentage was 32.3%, 4.7%, 16.7% ( E:T as 25:1), respectively. In vivo, the tumor inhibition rate of the group of γδT cell therapy was 42.78%. γδT cells derived from PBMCs stimulated by zoledronate can acquired pure γδT cells. And they show strong cytoxicity against osteosarcoma cell line HOS in vitro and in vivo.

  18. Intracellular high mobility group B1 protein (HMGB1) represses HIV-1 LTR-directed transcription in a promoter- and cell-specific manner

    International Nuclear Information System (INIS)

    Naghavi, Mojgan H.; Nowak, Piotr; Andersson, Jan; Soennerborg, Anders; Yang Huan; Tracey, Kevin J.; Vahlne, Anders

    2003-01-01

    We investigated whether the high mobility group B 1 (HMGB1), an abundant nuclear protein in all mammalian cells, affects HIV-1 transcription. Intracellular expression of human HMGB1 repressed HIV-1 gene expression in epithelial cells. This inhibitory effect of HMGB1 was caused by repression of long terminal repeat (LTR)-mediated transcription. Other viral promoters/enhancers, including simian virus 40 or cytomegalovirus, were not inhibited by HMGB1. In addition, HMGB1 inhibition of HIV-1 subtype C expression was dependent on the number of NFκB sites in the LTR region. The inhibitory effect of HMGB1 on viral gene expression observed in HeLa cells was confirmed by an upregulation of viral replication in the presence of antisense HMGB1 in monocytic cells. In contrast to what was found in HeLa cells and monocytic cells, endogenous HMGB1 expression did not affect HIV-1 replication in unstimulated Jurkat cells. Thus, intracellular HMGB1 affects HIV-1 LTR-directed transcription in a promoter- and cell-specific manner

  19. Diabetes-Induced Oxidative Stress in Endothelial Progenitor Cells May Be Sustained by a Positive Feedback Loop Involving High Mobility Group Box-1

    Directory of Open Access Journals (Sweden)

    Han Wu

    2016-01-01

    Full Text Available Oxidative stress is considered to be a critical factor in diabetes-induced endothelial progenitor cell (EPC dysfunction, although the underlying mechanisms are not fully understood. In this study, we investigated the role of high mobility group box-1 (HMGB-1 in diabetes-induced oxidative stress. HMGB-1 was upregulated in both serum and bone marrow-derived monocytes from diabetic mice compared with control mice. In vitro, advanced glycation end productions (AGEs induced, expression of HMGB-1 in EPCs and in cell culture supernatants in a dose-dependent manner. However, inhibition of oxidative stress with N-acetylcysteine (NAC partially inhibited the induction of HMGB-1 induced by AGEs. Furthermore, p66shc expression in EPCs induced by AGEs was abrogated by incubation with glycyrrhizin (Gly, while increased superoxide dismutase (SOD activity in cell culture supernatants was observed in the Gly treated group. Thus, HMGB-1 may play an important role in diabetes-induced oxidative stress in EPCs via a positive feedback loop involving the AGE/reactive oxygen species/HMGB-1 pathway.

  20. Physical forces shape group identity of swimming Pseudomonas putida cells

    Directory of Open Access Journals (Sweden)

    David Rodriguez-Espeso

    2016-09-01

    Full Text Available The often striking macroscopic patterns developed by motile bacterial populations on agar plates are a consequence of the environmental conditions where the cells grow and spread. Parameters such as medium stiffness and nutrient concentration have been reported to alter cell swimming behavior, while mutual interactions among populations shape collective patterns. One commonly observed occurrence is the mutual inhibition of clonal bacteria when moving towards each other, which results in a distinct halt at a finite distance on the agar matrix before having direct contact. The dynamics behind this phenomenon (i.e. intolerance to mix in time and space with otherwise identical others has been traditionally explained in terms of cell-to-cell competition/cooperation regarding nutrient availability. In this work, the same scenario has been revisited from an alternative perspective: the effect of the physical mechanics that frame the process, in particular the consequences of collisions between moving bacteria and the semi-solid matrix of the swimming medium. To this end we set up a simple experimental system in which the swimming patterns of Pseudomonas putida were tested with different geometries and agar concentrations. A computational analysis framework that highlights cell-to-medium interactions was developed to fit experimental observations. Simulated outputs suggested that the medium is compressed in the direction of the bacterial front motion. This phenomenon generates what was termed a compression wave that goes through the medium preceding the swimming population and that determines the visible high-level pattern. Taken together, the data suggested that the mechanical effects of the bacteria moving through the medium created a factual barrier that impedes to merge with neighboring cells swimming from a different site. The resulting divide between otherwise clonal bacteria is thus brought about by physical forces –not genetic or metabolic

  1. Exploiting natural killer group 2D receptors for CAR T-cell therapy.

    Science.gov (United States)

    Demoulin, Benjamin; Cook, W James; Murad, Joana; Graber, David J; Sentman, Marie-Louise; Lonez, Caroline; Gilham, David E; Sentman, Charles L; Agaugue, Sophie

    2017-08-01

    Chimeric antigen receptors (CARs) are genetically engineered proteins that combine an extracellular antigen-specific recognition domain with one or several intracellular T-cell signaling domains. When expressed in T cells, these CARs specifically trigger T-cell activation upon antigen recognition. While the clinical proof of principle of CAR T-cell therapy has been established in hematological cancers, CAR T cells are only at the early stages of being explored to tackle solid cancers. This special report discusses the concept of exploiting natural killer cell receptors as an approach that could broaden the specificity of CAR T cells and potentially enhance the efficacy of this therapy against solid tumors. New data demonstrating feasibility of this approach in humans and supporting the ongoing clinical trial are also presented.

  2. Pro-cognitive drug effects modulate functional brain network organization

    Science.gov (United States)

    Giessing, Carsten; Thiel, Christiane M.

    2012-01-01

    Previous studies document that cholinergic and noradrenergic drugs improve attention, memory and cognitive control in healthy subjects and patients with neuropsychiatric disorders. In humans neural mechanisms of cholinergic and noradrenergic modulation have mainly been analyzed by investigating drug-induced changes of task-related neural activity measured with functional magnetic resonance imaging (fMRI). Endogenous neural activity has often been neglected. Further, although drugs affect the coupling between neurons, only a few human studies have explicitly addressed how drugs modulate the functional connectome, i.e., the functional neural interactions within the brain. These studies have mainly focused on synchronization or correlation of brain activations. Recently, there are some drug studies using graph theory and other new mathematical approaches to model the brain as a complex network of interconnected processing nodes. Using such measures it is possible to detect not only focal, but also subtle, widely distributed drug effects on functional network topology. Most important, graph theoretical measures also quantify whether drug-induced changes in topology or network organization facilitate or hinder information processing. Several studies could show that functional brain integration is highly correlated with behavioral performance suggesting that cholinergic and noradrenergic drugs which improve measures of cognitive performance should increase functional network integration. The purpose of this paper is to show that graph theory provides a mathematical tool to develop theory-driven biomarkers of pro-cognitive drug effects, and also to discuss how these approaches can contribute to the understanding of the role of cholinergic and noradrenergic modulation in the human brain. Finally we discuss the “global workspace” theory as a theoretical framework of pro-cognitive drug effects and argue that pro-cognitive effects of cholinergic and noradrenergic drugs

  3. Transient correction of excision repair defects in fibroblasts of 9 xeroderma pigmentosum complementation groups by microinjection of crude human cell extract.

    NARCIS (Netherlands)

    W. Vermeulen (Wim); P. Osseweijer; A.J.R. de Jonge; J.H.J. Hoeijmakers (Jan)

    1986-01-01

    textabstractCrude extracts from human cells were microinjected into the cytoplasm of cultured fibroblasts from 9 excision-deficient xeroderma pigmentosum (XP) complementation groups. The level of UV-induced unscheduled DNA synthesis (UDS) was measured to determine the effect of the extract on the

  4. Expression of blood group I and i active carbohydrate sequences on cultured human and animal cell lines assessed by radioimmunoassays with monoclonal cold agglutinins

    International Nuclear Information System (INIS)

    Childs, R.A.; Kapadia, A.; Feizi, T.

    1980-01-01

    Human monoclonal anti-I and anti-i, reactive with known carbohydrate sequences, have been used as reagents to quantitate (by radioimmunoassay) and visualize (by immunofluorescence) the expression of the various blood group I and i antigenic determinants in a variety of cultured cell lines commonly used in laboratory investigations. It has been shown that the antigens they recognize are widely distributed on the surface of human and animal cell lines, expressed in varying amounts in different cell lines and on individual cells within a given cell line. In two cell lines, a transformation-associated increase in the expression of I antigen was observed. Because of their precise specificity for defined carbohydrate chain domains, these autoantibodies have become valuable reagents in biological chemistry. (orig.) [de

  5. Infrared multiple photon dissociation spectroscopy of group I and group II metal complexes with Boc-hydroxylamine

    NARCIS (Netherlands)

    Dain, R.P.; Gresham, G.; Groenewold, G.S.; Steill, J.D.; Oomens, J.; van Stipdonk, M.J.

    2013-01-01

    RATIONALE: Hydroxamates are essential growth factors for some microbes, acting primarily as siderophores that solubilize iron for transport into a cell. Here we determined the intrinsic structure of 1:1 complexes between Boc-protected hydroxylamine and group I ([M(L)](+)) and group II ([M(L-H)](+))

  6. Group I Metabotropic Glutamate Receptors

    DEFF Research Database (Denmark)

    Erichsen, Julie Ladeby; Blaabjerg, Morten; Bogetofte Thomasen, Helle

    2015-01-01

    differentiated an immortalized, forebrain-derived stem cell line in the presence or absence of glutamate and with addition of either the group I mGluR agonist DHPG or the selective antagonists; MPEP (mGluR5) and LY367385 (mGluR1). Characterization of differentiated cells revealed that both mGluR1 and mGluR5 were...

  7. Impact of sickle cell trait on the thrombotic risk associated with non-O blood groups in northern Nigeria.

    Science.gov (United States)

    Ahmed, Sagir G; Kagu, Modu B; Ibrahim, Umma A; Bukar, Audu A

    2015-10-01

    The non-O blood group is an established risk factor for deep vein thrombosis (DVT), while controversy surrounds the role of sickle cell trait (SCT) as a risk factor for DVT. We hypothesised that if SCT is a risk factor for DVT, individuals with non-O blood groups and SCT (Hb AS) would have a higher risk of DVT than their counterparts with non-O blood groups and normal haemoglobin phenotype (Hb AA). We retrospectively analysed the prevalence of SCT and non-O blood groups among 148 DVT patients with control subjects in order to determine the role of SCT as a risk factor for DVT and its impact on the risk of DVT among patients with non-O blood groups. In comparison with control subjects, DVT patients had significantly higher prevalences of SCT (35.1% vs 27.7%, p=0.04) and non-O blood groups (68.9% vs 45.9%, p=0.02). The odds ratios for DVT due to SCT, non-O blood groups with normal Hb phenotype (Hb AA) and non-O blood groups with SCT (Hb AS) were 1.3, 2.4 and 3.5, respectively. These results suggest that SCT by itself is a weak risk factor for DVT but it has the potential of escalating the DVT risk among patients with non-O blood groups. The combined effects of elevated clotting factors (non-O group effect) and increased clotting factor activation (SCT effect) were responsible for the escalated DVT risk among patients with co-inheritance of non-O blood groups and SCT. Co-inheritance of SCT and non-O blood group is, therefore, an important mixed risk factor for DVT. This should be taken into account when assessing DVT risk profiles of patients in Africa and other parts of the world where the SCT is prevalent.

  8. Characterization of noradrenaline release in the locus coeruleus of freely moving awake rats by in vivo microdialysis.

    Science.gov (United States)

    Fernández-Pastor, Begoña; Mateo, Yolanda; Gómez-Urquijo, Sonia; Javier Meana, J

    2005-07-01

    The origin and regulation of noradrenaline (NA) in the locus coeruleus (LC) is unknown. The neurochemical features of NA overflow (nerve impulse dependence, neurotransmitter synthesis, vesicle storage, reuptake, alpha2-adrenoceptor-mediated regulation) were characterized in the LC. Brain microdialysis was performed in awake rats. Dialysates were analyzed for NA. NA in the LC decreased via local infusion of Ca2+-free medium (-42+/-5%) or the sodium channel blocker tetrodotoxine (TTX) (-47+/-8%) but increased (333+/-40%) via KCl-induced depolarization. The tyrosine hydroxylase (TH) inhibitor alpha-methyl-p-tyrosine (250 mg kg(-1), i.p.) and the vesicle depletory drug reserpine (5 mg kg(-1), i.p.) decreased NA. Therefore, extracellular NA in the LC satisfies the criteria for an impulse flow-dependent vesicular exocytosis of neuronal origin. Local perfusion of the alpha2-adrenoceptor agonist clonidine (0.1-100 microM) decreased NA (E(max)=-79+/-5%) in the LC, whereas the opposite effect (E(max)=268+/-53%) was observed with the alpha2A-adrenoceptor antagonist BRL44408 (0.1-100 microM). This suggests a tonic modulation of NA release through local alpha2A-adrenoceptors. The selective NA reuptake inhibitor desipramine (DMI) (0.1-100 microM) administered into the LC increased NA in the LC (E(max)=223+/-40%) and simultaneously decreased NA in the cingulate cortex, confirming the modulation exerted by NA in the LC on firing activity of noradrenergic cells and on the subsequent NA release in noradrenergic terminals. Synaptic processes underlying NA release in the LC are similar to those in noradrenergic terminal areas. NA in the LC could represent local somatodendritic release, but also the presence of neurotransmitter release from collateral axon terminals.

  9. Diazo groups endure metabolism and enable chemoselectivity in cellulo.

    Science.gov (United States)

    Andersen, Kristen A; Aronoff, Matthew R; McGrath, Nicholas A; Raines, Ronald T

    2015-02-25

    We introduce a stabilized diazo group as a reporter for chemical biology. ManDiaz, which is a diazo derivative of N-acetylmannosamine, is found to endure cellular metabolism and label the surface of a mammalian cell. There its diazo group can undergo a 1,3-dipolar cycloaddition with a strained alkyne, providing a signal comparable to that from the azido congener, ManNAz. The chemoselectivity of diazo and alkynyl groups enables dual labeling of cells that is not possible with azido and alkynyl groups. Thus, the diazo group, which is approximately half the size of an azido group, provides unique opportunities for orthogonal labeling of cellular components.

  10. Derivation of corneal endothelial cell-like cells from rat neural crest cells in vitro.

    Directory of Open Access Journals (Sweden)

    Chengqun Ju

    Full Text Available The aim of this study was to investigate the feasibility of inducing rat neural crest cells (NCC to differentiate to functional corneal endothelial cell (CEC-like cells in vitro. Rat NCC were induced with adult CEC-derived conditioned medium. Immunofluorescence, flow cytometry and real time RT-PCR assay were used to detect expression of the corneal endothelium differentiation marker N-cadherin and transcription factors FoxC1 and Pitx2. CFDA SE-labeled CEC-like cells were transplanted to the corneal endothelium of a rat corneal endothelium deficiency model, and an eye-down position was maintained for 24 hours to allow cell attachment. The animals were observed for as long as 2 months after surgery and underwent clinical and histological examination. Spindle-like NCC turned to polygonal CEC-like after induction and expressed N-cadherin, FoxC1, Pitx2, zonula occludens-1 and sodium-potassium pump Na(+/K(+ ATPase. The corneas of the experimental group were much clearer than those of the control group and the mean corneal thickness in the experimental group was significantly less than in the control group7, 14, 21 and 28 days after surgery. Confocal microscopy through focusing and histological analysis confirmed that green fluorescence-positive CEC-like cells formed a monolayer covering the Descemet's membrane in the experimental group. In conclusion, CEC-like cells derived from NCCs displayed characters of native CEC, and the induction protocol provides guidance for future human CEC induction from NCC.

  11. Disentangling the roles of arousal and amygdala activation in emotional declarative memory.

    Science.gov (United States)

    de Voogd, Lycia D; Fernández, Guillén; Hermans, Erno J

    2016-09-01

    A large body of evidence in animals and humans implicates the amygdala in promoting memory for arousing experiences. Although the amygdala can trigger threat-related noradrenergic-sympathetic arousal, in humans amygdala activation and noradrenergic-sympathetic arousal do not always concur. This raises the question how these two processes play a role in enhancing emotional declarative memory. This study was designed to disentangle these processes in a combined subsequent-memory/fear-conditioning paradigm with neutral items belonging to two conceptual categories as conditioned stimuli. Functional MRI, skin conductance (index of sympathetic activity), and pupil dilation (indirect index of central noradrenergic activity) were acquired throughout procedures. Recognition memory for individual items was tested 24 h later. We found that pupil dilation and skin conductance responses were higher on CS+ (associated with a shock) compared with CS- trials, irrespective of later memory for those items. By contrast, amygdala activity was only higher for CS+ items that were later confidently remembered compared with CS+ items that were later forgotten. Thus, amygdala activity and not noradrenergic-sympathetic arousal, predicted enhanced declarative item memory. This dissociation is in line with animal models stating that the amygdala integrates arousal-related neuromodulatory changes to alter mnemonic processes elsewhere in the brain. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  12. Electrophysiological and neurochemical changes in the rat hippocampus after in vitro and in vivo treatments with cocaine

    International Nuclear Information System (INIS)

    Yasuda, R.P.

    1986-01-01

    The in vitro and in vivo effects of cocaine in the noradrenergic pathway in the rat hippocampus were examined. Although the blockade of [ 3 H]-norepinephrine-uptake by cocaine has been well-characterized in both the central and peripheral nervous systems, investigations characterizing the electrophysiological effects of cocaine in the central nervous system have been limited. The first part of this thesis examines the relationship between the ability of cocaine to potentiate the electrophysiological response to norepinephrine (NE) and the ability of cocaine to block noradrenergic high affinity uptake in rat hippocampal slices. The second part of this thesis examines the effects of the repeated administration of cocaine on noradrenergic pre- and postsynaptic function and receptors of the rat hippocampus. These studies demonstrate that after repeated administration of cocaine (10 mg/kg/day) for 8 and 14 days there is a 50% decrease in NE high affinity uptake in the rat hippocampus. This was accompanied by a 40% increase in a binding site for NE uptake inhibitors at 14 days. In contrast to these effects, there was no effect on β-adrenergic receptor number or the isoproterenol induced electrophysiological responsiveness in the rat hippocampus. The conclusion of these studies is that the repeated administration of cocaine has a greater effect on presynaptic targets in the noradrenergic system than on postsynaptic neurons

  13. Grafted functional groups on expanded tetrafluoroethylene (ePTFE) support for fuel cell and water transport membranes

    Science.gov (United States)

    Fuller, Timothy J.; Jiang, Ruichun

    2017-01-24

    A method for forming a modified solid polymer includes a step of contacting a solid fluorinated polymer with a sodium sodium-naphthalenide solution to form a treated fluorinated solid polymer. The treated fluorinated solid polymer is contacted with carbon dioxide, sulfur dioxide, or sulfur trioxide to form a solid grafted fluorinated polymer. Characteristically, the grafted fluorinated polymer includes appended CO.sub.2H or SO.sub.2H or SO.sub.3H groups. The solid grafted fluorinated polymer is advantageously incorporated into a fuel cell as part of the ion-conducting membrane or a water transport membrane in a humidifier.

  14. Evaluation of the secretion and release of vascular endothelial growth factor from two-dimensional culture and three-dimensional cell spheroids formed with stem cells and osteoprecursor cells.

    Science.gov (United States)

    Lee, Hyunjin; Lee, Sung-Il; Ko, Youngkyung; Park, Jun-Beom

    2018-05-18

    Co-culture has been applied in cell therapy, including stem cells, and has been reported to give enhanced functionality. In this study, stem-cell spheroids were formed in concave micromolds at different ratios of stem cells to osteoprecursor cells, and the amount of secretion of vascular endothelial growth factor (VEGF) was evaluated. Gingiva-derived stem cells and osteoprecursor cells in the amount of 6 × 105 were seeded on a 24-well culture plate or concave micromolds. The ratios of stem cells to osteoprecursor cells included: 0:4 (group 1), 1:3 (group 2), 2:2 (group 3), 3:1 (group 4), and 4:0 (group 5). The morphology of cells in a 2-dimensional culture (groups 1-5) showed a fibroblast-like appearance. The secretion of VEGF increased with the increase in stem cells, and a statistically significant increase was noted in groups 3, 4 and 5 when compared with the media-only group (p cells formed spheroids in concave microwells, and no noticeable change in the morphology was noted with the increase in stem cells. Spheroids containing stem cells were positive for the stem-cell markers SSEA-4. The secretion of VEGF from cell spheroids increased with the increase in stem cells. This study showed that cell spheroids formed with stem cells and osteoprecursor cells with different ratios, using microwells, had paracrine effects on the stem cells. The secretion of VEGF increased with the increase in stem cells. This stem-cell spheroid may be applied for tissue-engineering purposes.

  15. Cell-Free DNA, High-Mobility Group Box-1, and Procalcitonin Concentrations in Dogs With Gastric Dilatation–Volvulus Syndrome

    OpenAIRE

    Roberta Troia; Massimo Giunti; Stefano Calipa; Robert Goggs

    2018-01-01

    Canine gastric dilatation–volvulus (GDV) is a life-threatening disease characterized by extensive tissue ischemia, tissue hypoperfusion, and systemic inflammation. Biomarkers that better reflect the severity of gastric necrosis and systemic inflammation would aid clinicians in the management of these patients. This study aimed to investigate the prognostic significance of cell-free DNA (cfDNA), high-mobility group box-1 (HMGB1), and procalcitonin (PCT) in dogs with GDV. Concentrations of cfDN...

  16. Endogenous salivary α-amylase does not interact with skin conductance response during fear extinction in posttraumatic stress disorder.

    Science.gov (United States)

    Zuj, Daniel V; Palmer, Matthew A; Malhi, Gin S; Bryant, Richard A; Felmingham, Kim L

    2018-04-01

    Posttraumatic Stress Disorder (PTSD) is associated with elevated noradrenergic signaling, which has an impact on emotional learning and memory. Fear extinction is thought to underlie the processes of exposure therapy, however the relationship between noradrenaline and extinction in PTSD is unclear. Participants with PTSD (n = 21), trauma-exposure without PTSD (TC; n = 36), and non-trauma-exposed controls (NTC; n = 27) completed a fear conditioning and extinction paradigm, and conditioned fear was indexed by skin conductance response (SCR). Salivary α-amylase (sAA) collected at baseline and immediately post-fear acquisition was used as an index of noradrenaline, and we examined whether sAA in response to fear acquisition was a moderator between fear extinction and PTSD symptoms. While there was a significant increase in sAA from baseline to post-fear acquisition, this was not modulated by group. Compared to TC and NTC, the PTSD group displayed a slower decline in SCRs during early extinction, which generalized across stimulus type, and was not moderated by sAA. These findings suggest that the relationship between fear extinction and PTSD symptoms does not change as a function of sAA levels; however previous research suggests other processes of fear learning may be associated with noradrenergic activity in PTSD. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  17. The reciprocal interaction of sympathetic nervous system and cAMP-PKA-NF-kB pathway in immune suppression after experimental stroke.

    Science.gov (United States)

    Zuo, Lei; Shi, Luhang; Yan, Fuling

    2016-08-03

    Sympathetic nervous system(SNS) is involved in the mechanism of immune suppression after stroke. Furthermore, as the pro-inflammatory effect of nuclear factor kappa B(NF-kB) is inhibited after stroke, which is regulated by cyclic adenosine monophosphate(cAMP) and proteinkinase A(PKA). The cAMP-PKA-NF-kB pathway might play an important role in noradrenergic-mediated immune dysfunction. The purpose of our research is to analyze how SNS interfere with the immune system after acute stroke and the underlying mechanism of cAMP-PKA-NF-kB pathway in regulating the inflammation. 32 healthy male Sprague-Dawley rats were divided into 4 groups equally and randomly (1) Sham operation group; (2) middle cerebral artery occlusion; (MCAO) control group; (3) propranolol MCAO group; (4) isopropylarterenol sham group. 72h later after MCAO or sham operation, tumor necrosis factor-α(TNF-α)and interleukine-10(IL-10) in serum as well as cAMP, PKA and NF-kB in spleen cells were tested. TNF-α decreased while IL-10 increased in serum after acute ischemia stroke (pkB was inhibited (pkB is down-regulated. Since the pro-inflammatory effect of NF-kB slacked, the immune system may be inhibited after stroke. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. An ABO blood grouping discrepancy: Probable B(A) phenotype.

    Science.gov (United States)

    Jain, Ashish; Gupta, Anubhav; Malhotra, Sheetal; Marwaha, Neelam; Sharma, Ratti Ram

    2017-06-01

    In B(A) phenotype, an autosomal dominant phenotype, there is a weak A expression on group B RBCs. We herein report a case of a probable B(A) phenotype in a first time 20-year old male donor. The cell and serum grouping were done using tube technique and also with blood grouping gel card (Diaclone, ABD cards for donors, BioRad, Switzerland). The antisera used were commercial monoclonal IgM type. To check for the weak subgroup of A, cold adsorption and heat elution was performed. The cell grouping was A weak B RhD positive while the serum grouping was B. There was no agglutination with O cells and the autologous control was also negative. It was a group II ABO discrepancy with or without group IV discrepancy. Results for both the eluate and last wash were negative. Hence, the possibility of weak subgroup of A was unlikely. Blood grouping gel card also showed a negative reaction in the anti-A column. One lot of anti-A was showing 'weak +' agglutination while the other lot was showing 'negative' reaction with the donor RBCs by tube technique. There was no agglutination observed with anti-A1 lectin. Our case highlights the serological characteristics of a B(A) phenotype. This case emphasizes the vital role of cell and serum grouping in detecting such discrepancies especially in donors which can lead to mislabeling of the blood unit and may be a potential risk for the transfusion recipient if not resolved appropriately. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Monoamine Oxidase A Gene Methylation and Its Role in Posttraumatic Stress Disorder: First Evidence from the South Eastern Europe (SEE)-PTSD Study.

    Science.gov (United States)

    Ziegler, Christiane; Wolf, Christiane; Schiele, Miriam A; Feric Bojic, Elma; Kucukalic, Sabina; Sabic Dzananovic, Emina; Goci Uka, Aferdita; Hoxha, Blerina; Haxhibeqiri, Valdete; Haxhibeqiri, Shpend; Kravic, Nermina; Muminovic Umihanic, Mirnesa; Cima Franc, Ana; Jaksic, Nenad; Babic, Romana; Pavlovic, Marko; Warrings, Bodo; Bravo Mehmedbasic, Alma; Rudan, Dusko; Aukst-Margetic, Branka; Kucukalic, Abdulah; Marjanovic, Damir; Babic, Dragan; Bozina, Nada; Jakovljevic, Miro; Sinanovic, Osman; Avdibegovic, Esmina; Agani, Ferid; Dzubur-Kulenovic, Alma; Deckert, Jürgen; Domschke, Katharina

    2018-05-01

    Posttraumatic stress disorder is characterized by an overactive noradrenergic system conferring core posttraumatic stress disorder symptoms such as hyperarousal and reexperiencing. Monoamine oxidase A is one of the key enzymes mediating the turnover of noradrenaline. Here, DNA methylation of the monoamine oxidase A gene exonI/intronI region was investigated for the first time regarding its role in posttraumatic stress disorder risk and severity. Monoamine oxidase A methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells in a total sample of N=652 (441 male) patients with current posttraumatic stress disorder, patients with remitted posttraumatic stress disorder, and healthy probands (comparison group) recruited at 5 centers in Bosnia-Herzegovina, Croatia, and the Republic of Kosovo. Posttraumatic stress disorder severity was measured by means of the Clinician-Administered Posttraumatic Stress Disorder Scale and its respective subscores representing distinct symptom clusters. In the male, but not the female sample, patients with current posttraumatic stress disorder displayed hypermethylation of 3 CpGs (CpG3=43656362; CpG12=43656514; CpG13=43656553, GRCh38.p2 Assembly) as compared with remitted Posttraumatic Stress Disorder patients and healthy probands. Symptom severity (Clinician-Administered Posttraumatic Stress Disorder Scale scores) in male patients with current posttraumatic stress disorder significantly correlated with monoamine oxidase A methylation. This applied particularly to symptom clusters related to reexperiencing of trauma (cluster B) and hyperarousal (cluster D). The present findings suggest monoamine oxidase A gene hypermethylation, potentially resulting in enhanced noradrenergic signalling, as a disease status and severity marker of current posttraumatic stress disorder in males. If replicated, monoamine oxidase A hypermethylation might serve as a surrogate marker of a hyperadrenergic subtype of

  20. A Red Blood Cell Membrane-Camouflaged Nanoparticle Counteracts Streptolysin O-Mediated Virulence Phenotypes of Invasive Group A Streptococcus

    Directory of Open Access Journals (Sweden)

    Tamara Escajadillo

    2017-07-01

    Full Text Available Group A Streptococcus (GAS, an important human-specific Gram-positive bacterial pathogen, is associated with a broad spectrum of disease, ranging from mild superficial infections such as pharyngitis and impetigo, to serious invasive infections including necrotizing fasciitis and streptococcal toxic shock syndrome. The GAS pore-forming streptolysin O (SLO is a well characterized virulence factor produced by nearly all GAS clinical isolates. High level expression of SLO is epidemiologically linked to intercontinental dissemination of hypervirulent clonotypes and poor clinical outcomes. SLO can trigger macrophage and neutrophil cell death and/or the inactivation of immune cell functions, and promotes tissue injury and bacterial survival in animal models of infection. In the present work, we describe how the pharmacological presentation of red blood cell (RBC derived biomimetic nanoparticles (“nanosponges” can sequester SLO and block the ability of GAS to damage host cells, thereby preserving innate immune function and increasing bacterial clearance in vitro and in vivo. Nanosponge administration protected human neutrophils, macrophages, and keratinocytes against SLO-mediated cytotoxicity. This therapeutic intervention prevented SLO-induced macrophage apoptosis and increased neutrophil extracellular trap formation, allowing increased GAS killing by the respective phagocytic cell types. In a murine model of GAS necrotizing skin infection, local administration of the biomimetic nanosponges was associated with decreased lesion size and reduced bacterial colony-forming unit recovery. Utilization of a toxin decoy and capture platform that inactivates the secreted SLO before it contacts the host cell membrane, presents a novel virulence factor targeted strategy that could be a powerful adjunctive therapy in severe GAS infections where morbidity and mortality are high despite antibiotic treatment.

  1. High mobility group box-1 is phosphorylated by protein kinase C zeta and secreted in colon cancer cells

    International Nuclear Information System (INIS)

    Lee, Hanna; Park, Minhee; Shin, Nara; Kim, Gamin; Kim, Yun Gi; Shin, Jeon-Soo; Kim, Hoguen

    2012-01-01

    Highlights: ► Specific enzyme for HMGB1 phosphorylation and its secretion is proposed. ► Inhibition of PKC-ζ leads to significant reduction of the secreted HMGB1. ► Phosphorylation of specific site of HMGB1 redirects its secretion in cancer cells. ► Activation of PKC-ζ in cancers explains the enhanced HMGB1 secretion. -- Abstract: High mobility group box-1 (HMGB1), a nuclear protein, is overexpressed and secreted in cancer cells. Phosphorylation on two different nuclear localization signal regions are known to be important for the nuclear-to-cytoplasmic transport and secretion of HMGB1. However, little is known about the biochemical mechanism of HMGB1 modifications and its subsequent secretion from cancer cells. To identify the specific enzyme and important sites for HMGB1 phosphorylation, we screened the protein kinase C (PKC) family in a colon cancer cell line (HCT116) for HMGB1 binding by pull-down experiments using a 3XFLAG-HMGB1 construct. Strong interactions between atypical PKCs (PKC-ζ, λ, and ι) and cytoplasmic HMGB1 were observed in HCT116 cells. We further identified the most critical PKC isotype that regulates HMGB1 secretion is PKC-ζ by using PKC inhibitors and siRNA experiments. The serine residues at S39, S53 and S181 of HMGB1 were related to enhancing HMGB1 secretion. We also demonstrated overexpression and activation of PKC-ζ in colon cancer tissues. Our findings suggest that PKC-ζ is involved in the phosphorylation of HMGB1, and the phosphorylation of specific serine residues in the nuclear localization signal regions is related to enhanced HMGB1 secretion in colon cancer cells.

  2. Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells

    Science.gov (United States)

    Sato, Hiromi

    2017-01-01

    Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways

  3. Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells.

    Science.gov (United States)

    Sato, Hiromi; Coburn, Jenifer

    2017-07-01

    Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways

  4. Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells.

    Directory of Open Access Journals (Sweden)

    Hiromi Sato

    2017-07-01

    Full Text Available Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1 extracellular matrix, 2 intercellular adhesion molecules and cell surface receptors, 3 intracellular proteins, 4 cell-cell junction proteins, and 5 a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or

  5. Testicular Sertoli cells influence the proliferation and immunogenicity of co-cultured endothelial cells

    International Nuclear Information System (INIS)

    Fan, Ping; He, Lan; Pu, Dan; Lv, Xiaohong; Zhou, Wenxu; Sun, Yining; Hu, Nan

    2011-01-01

    Research highlights: → The proliferation of dramatic increased by co-cultured with Sertoli cells. → VEGF receptor-2 expression of ECs was up-regulated by co-cultured with Sertoli cells. → The MHC expression of ECs induced by INF-γ and IL-6, IL-8 and sICAM induced by TNF-α decreased respectively after co-cultured with Sertoli cells. → ECs co-cultured with Sertoli cells also didn't increase the stimulation index of spleen lymphocytes. -- Abstract: The major problem of the application of endothelial cells (ECs) in transplantation is the lack of proliferation and their immunogenicity. In this study, we co-cultured ECs with Sertoli cells to monitor whether Sertoli cells can influence the proliferation and immunogenicity of co-cultured ECs. Sertoli cells were isolated from adult testicular tissue. ECs were divided into the control group and the experimental group, which included three sub-groups co-cultured with 1 x 10 3 , 1 x 10 4 or 1 x 10 5 cell/ml of Sertoli cells. The growth and proliferation of ECs were observed microscopically, and the expression of vascular endothelial growth factor (VEGF) receptor-2 (KDR) was examined by Western blotting. In another experiment, ECs were divided into the control group, the single culture group and the co-culture group with the optimal concentration of Sertoli cells. After INF-γ and TNF-α were added to the culture medium, MHC II antigen expression was detected by immunofluorescence staining and western blotting; interleukin (IL)-6, IL-8 and soluble intercellular adhesion molecule (sICAM) were measured in the culture medium by ELISA. We demonstrated that 1 x 10 4 cell/ml Sertoli cells promoted the proliferation of co-cultured ECs more dramatically than that in other groups (P 4 cell/ml of the Sertoli cells was most effective in the up-regulation of KDR expression in the co-cultured ECs (P < 0.05). Sertoli cells can effectively suppress INF-γ-induced MHC II antigen expression in co-cultured ECs compared with single

  6. Pheochromocytoma-paraganglioma: Biochemical and genetic diagnosis.

    Science.gov (United States)

    Cano Megías, Marta; Rodriguez Puyol, Diego; Fernández Rodríguez, Loreto; Sención Martinez, Gloria Lisette; Martínez Miguel, Patricia

    Pheochromocytomas and paragangliomas are tumours derived from neural crest cells, which can be diagnosed by biochemical measurement of metanephrine and methoxytyramine. Advances in genetic research have identified many genes involved in the pathogenesis of these tumours, suggesting that up to 35-45% may have an underlying germline mutation. These genes have a singular transcriptional signature and can be grouped into 2 clusters (or groups): cluster 1 (VHL and SHDx), involved in angiogenesis and hypoxia pathways; and cluster 2 (MEN2 and NF1), linked to the kinase signalling pathway. In turn, these genes are associated with a characteristic biochemical phenotype (noradrenergic and adrenergic), and clinical features (location, biological behaviour, age of presentation, etc.) in a large number of cases. Early diagnosis of these tumours, accompanied by a correct genetic diagnosis, should eventually become a priority to enable better treatment, early detection of complications, proper screening of family members and related tumours, as well as an improvement in the overall prognosis of these patients. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Emergency Department Sickle Cell Assessment of Needs and Strengths (ED-SCANS), a Focus Group and Decision Support Tool Development Project

    Science.gov (United States)

    Tanabe, Paula; Reddin, Christopher; Thornton, Victoria L.; Todd, Knox H.; Wun, Ted; Lyons, John S.

    2010-01-01

    Objectives A decision support tool may guide emergency clinicians in recognizing assessment, analgesic and overall management, and health service delivery needs for patients with sickle cell disease (SCD) in the emergency department (ED). We aimed to identify data and process elements important in making decisions regarding evaluation and management of adult patients in the ED with painful episodes of sickle cell disease. Methods Qualitative methods using a series of focus groups and grounded theory were used. Eligible participants included adult clients with SCD, and emergency physicians and nurses with a minimum of one year of experience providing care to patients with SCD in the ED. Patients were recruited in conjunction with annual SCD meetings, and providers included clinicians who were and were not affiliated with sickle cell centers. Groups were conducted until saturation was reached, and included a total of two patient groups, three physician groups, and two nurse groups. Focus groups were held in New York, Durham, Chicago, New Orleans, and Denver. Clinician participants were asked the following three questions to guide the discussion: 1) what information would be important to know about patients with SCD in the ED setting to effectively care for them and help you identify patient analgesic, treatment, and referral needs? 2) what treatment decisions would you make with this information? and 3) what characteristics would a decision support tool need to have to make it meaningful and useful? Client participants were asked the same questions with re-wording to reflect what they believed providers should know to provide the best care, and what they should do with the information. All focus groups were audio taped and transcribed. The constant comparative method was used to analyze the data. Two coders independently coded participant responses and identified focal themes based on the key questions. An investigator and assistant independently reviewed the

  8. Structure activity correlations in the inhibition of brain synaptosomal 3H-norepinephrine uptake by phenethylamine analogs. The role of α-alkyl side chain and methoxyl ring substitutions

    International Nuclear Information System (INIS)

    Makriyannis, A.; Bowerman, D.; Sze, P.Y.; Fournier, D.; Jong, A.P. de

    1982-01-01

    α-Ethylphenethylamine proved to be a weaker inhibitor of rat brain synaptosomal [ 3 H]norepinephrine ([ 3 H]NE) uptake than amphetamine, while 2-amino-tetralin and 2-amino-1,2-dihydronaphtalene, compounds in which the α-side chain ethyl group is tied to the aromatic ring have a similar inhibiting potency as amphetamine. Hallucinogenic polymethoxy substituted phenethylamine analogs have very low inhibitory potencies indicating that inhibition of NE-reuptake in brain noradrenergic neurons is not associated with the drug-induced hallucinogenic syndrome. (Auth.)

  9. Effects of 3-AB on PARP expression of Hela cells and apoptosis and cell cycle progression of Hela cells after X-rays irradiation

    International Nuclear Information System (INIS)

    Du Xiang; Zhao Hongguang; Guo Wei; Gong Shouliang; Wang Wen

    2007-01-01

    Objective: To study the changes of apoptosis and cell cycle progression of Hela cells after the poly (ADP- ribose) polymerase (PARP) was inhibited by its inhibitor 3-aminobenzamid (3-AB) and the mechanisms of PARP interaction with Hela cells damaged by irradiation. Methods: Hela cell line was used. Flow cytometry (FCM) was used to examine the PARP expression of control and 3 AB groups at 0, 2, 4, 8, 12 h alter administration with 5 mmol·L -1 3-AB. The percentage of apoptotic cells and cell cycle progression ol control, irradiation, 3-AB plus irradiation groups were measured with FCM at 2, 8, 12, 24 h after exposure to 2 Gy irradiation following administration with 5 mmol·L -1 3-AB. Results: The percentage of Hela cells with positive expression of PARP protein decreased after administration with 3-AB and there was significant difference between 3-AB plus irradiation group and control group (P 2 cells in the 3-AB plus irradiation group were lower than those in the irradiation group (P 2 arrest induced by irradiation. (authors)

  10. Antitumor Cell-Complex Vaccines Employing Genetically Modified Tumor Cells and Fibroblasts

    Directory of Open Access Journals (Sweden)

    Antonio Miguel

    2014-02-01

    Full Text Available The present study evaluates the immune response mediated by vaccination with cell complexes composed of irradiated B16 tumor cells and mouse fibroblasts genetically modified to produce GM-CSF. The animals were vaccinated with free B16 cells or cell complexes. We employed two gene plasmid constructions: one high producer (pMok and a low producer (p2F. Tumor transplant was performed by injection of B16 tumor cells. Plasma levels of total IgG and its subtypes were measured by ELISA. Tumor volumes were measured and survival curves were obtained. The study resulted in a cell complex vaccine able to stimulate the immune system to produce specific anti-tumor membrane proteins (TMP IgG. In the groups vaccinated with cells transfected with the low producer plasmid, IgG production was higher when we used free B16 cell rather than cell complexes. Nonspecific autoimmune response caused by cell complex was not greater than that induced by the tumor cells alone. Groups vaccinated with B16 transfected with low producer plasmid reached a tumor growth delay of 92% (p ≤ 0.01. When vaccinated with cell complex, the best group was that transfected with high producer plasmid, reaching a tumor growth inhibition of 56% (p ≤ 0.05. Significant survival (40% was only observed in the groups vaccinated with free transfected B16 cells.

  11. Group 2 innate lymphoid cell production of IL-5 is regulated by NKT cells during influenza virus infection.

    Directory of Open Access Journals (Sweden)

    Stacey Ann Gorski

    2013-09-01

    Full Text Available Respiratory virus infections, such as influenza, typically induce a robust type I (pro-inflammatory cytokine immune response, however, the production of type 2 cytokines has been observed. Type 2 cytokine production during respiratory virus infection is linked to asthma exacerbation; however, type 2 cytokines may also be tissue protective. Interleukin (IL-5 is a prototypical type 2 cytokine that is essential for eosinophil maturation and egress out of the bone marrow. However, little is known about the cellular source and underlying cellular and molecular basis for the regulation of IL-5 production during respiratory virus infection. Using a mouse model of influenza virus infection, we found a robust transient release of IL-5 into infected airways along with a significant and progressive accumulation of eosinophils into the lungs, particularly during the recovery phase of infection, i.e. following virus clearance. The cellular source of the IL-5 was group 2 innate lymphoid cells (ILC2 infiltrating the infected lungs. Interestingly, the progressive accumulation of eosinophils following virus clearance is reflected in the rapid expansion of c-kit⁺ IL-5 producing ILC2. We further demonstrate that the enhanced capacity for IL-5 production by ILC2 during recovery is concomitant with the enhanced expression of the IL-33 receptor subunit, ST2, by ILC2. Lastly, we show that NKT cells, as well as alveolar macrophages (AM, are endogenous sources of IL-33 that enhance IL-5 production from ILC2. Collectively, these results reveal that c-kit⁺ ILC2 interaction with IL-33 producing NKT and AM leads to abundant production of IL-5 by ILC2 and accounts for the accumulation of eosinophils observed during the recovery phase of influenza infection.

  12. Risk-group definition by recursive partitioning analysis of patients with squamous cell head and neck carcinoma treated with surgery and postoperative radiotherapy

    NARCIS (Netherlands)

    Langendijk, JA; Slotman, BJ; van der Waal, [No Value; Doornaert, P; Berkof, J; Leemans, CR

    2005-01-01

    BACKGROUND. The objective of this study was to define different prognostic groups with regard to locoregional control (LRC) derived from recursive partitioning analysis (RPA). METHODS. Eight hundred one patients with squamous cell head and neck carcinoma underwent with primary surgery and received

  13. Working group 'Reglementat'hy'on'; Groupe de travail reglementat'hy'on

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    HyPac is a french platform on the hydrogen and fuel cells applications, created in 2008. This working group deals with the french regulation concerning the hydrogen fuels. It presents the problems of the existing regulation, the objectives and the actions planing of the group. (A.L.B.)

  14. Contribution of the RgfD Quorum Sensing Peptide to rgf Regulation and Host Cell Association in Group B Streptococcus

    Directory of Open Access Journals (Sweden)

    Robert E. Parker

    2017-01-01

    Full Text Available Streptococcus agalactiae (group B Streptococcus; GBS is a common inhabitant of the genitourinary and/or gastrointestinal tract in up to 40% of healthy adults; however, this opportunistic pathogen is able to breach restrictive host barriers to cause disease and persist in harsh and changing conditions. This study sought to identify a role for quorum sensing, a form of cell to cell communication, in the regulation of the fibrinogen-binding (rgfBDAC two-component system and the ability to associate with decidualized endometrial cells in vitro. To do this, we created a deletion in rgfD, which encodes the putative autoinducing peptide, in a GBS strain belonging to multilocus sequence type (ST-17 and made comparisons to the wild type. Sequence variation in the rgf operon was detected in 40 clinical strains and a non-synonymous single nucleotide polymorphism was detected in rgfD in all of the ST-17 genomes that resulted in a truncation. Using qPCR, expression of rgf operon genes was significantly decreased in the ST-17 ΔrgfD mutant during exponential growth with the biggest difference (3.3-fold occurring at higher cell densities. Association with decidualized endometrial cells was decreased 1.3-fold in the mutant relative to the wild type and rgfC expression was reduced 22-fold in ΔrgfD following exposure to the endometrial cells. Collectively, these data suggest that this putative quorum sensing molecule is important for attachment to human tissues and demonstrate a role for RgfD in GBS pathogenesis through regulation of rgfC.

  15. High mobility group box-1 is phosphorylated by protein kinase C zeta and secreted in colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hanna; Park, Minhee; Shin, Nara; Kim, Gamin [Department of Pathology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Kim, Yun Gi [Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of); Shin, Jeon-Soo [Department of Microbiology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Kim, Hoguen, E-mail: hkyonsei@yuhs.ac [Department of Pathology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of)

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer Specific enzyme for HMGB1 phosphorylation and its secretion is proposed. Black-Right-Pointing-Pointer Inhibition of PKC-{zeta} leads to significant reduction of the secreted HMGB1. Black-Right-Pointing-Pointer Phosphorylation of specific site of HMGB1 redirects its secretion in cancer cells. Black-Right-Pointing-Pointer Activation of PKC-{zeta} in cancers explains the enhanced HMGB1 secretion. -- Abstract: High mobility group box-1 (HMGB1), a nuclear protein, is overexpressed and secreted in cancer cells. Phosphorylation on two different nuclear localization signal regions are known to be important for the nuclear-to-cytoplasmic transport and secretion of HMGB1. However, little is known about the biochemical mechanism of HMGB1 modifications and its subsequent secretion from cancer cells. To identify the specific enzyme and important sites for HMGB1 phosphorylation, we screened the protein kinase C (PKC) family in a colon cancer cell line (HCT116) for HMGB1 binding by pull-down experiments using a 3XFLAG-HMGB1 construct. Strong interactions between atypical PKCs (PKC-{zeta}, {lambda}, and {iota}) and cytoplasmic HMGB1 were observed in HCT116 cells. We further identified the most critical PKC isotype that regulates HMGB1 secretion is PKC-{zeta} by using PKC inhibitors and siRNA experiments. The serine residues at S39, S53 and S181 of HMGB1 were related to enhancing HMGB1 secretion. We also demonstrated overexpression and activation of PKC-{zeta} in colon cancer tissues. Our findings suggest that PKC-{zeta} is involved in the phosphorylation of HMGB1, and the phosphorylation of specific serine residues in the nuclear localization signal regions is related to enhanced HMGB1 secretion in colon cancer cells.

  16. A Zinc Porphyrin Sensitizer Modified with Donor and Acceptor Groups for Dye-ensitized Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, See Woo; Sarker, K. Ashis; Hong, Jong Dal [Incheon National University, Incheon (Korea, Republic of)

    2014-09-15

    In this article, we have designed and synthesized a novel donor-π-acceptor (D-π-A) type porphyrin-based sensitizer (denoted UI-5), in which a carboxyl anchoring group and a 9,9-dimethyl fluorene were introduced at the meso-positions of porphyrin ring via phenylethynyl and ethynyl bridging units, respectively. Long alkoxy chains in ortho-positions of the phenyls were supposed to reduce the degree of dye aggregation, which tends to affect electron injection yield in a photovoltaic cell. The cyclic voltammetry was employed to determine the band gap of UI-5 to be 1.41 eV based on the HOMO and LUMO energy levels, which were estimated by the onset oxidation and reduction potentials. The incident monochromatic photon-to-current conversion efficiency of the UI-5 DSSC assembled with double-layer (20 nm-sized TiO{sub 2}/400 nm-sized TiO{sub 2}) film electrodes appeared lower upon overall ranges of the excitation wavelengths, but exhibited a higher value over the NIR ranges (λ = 650-700 nm) compared to the common reference sensitizer N719. The UI-5-sensitized cell yielded a relatively poor device performance with an overall conversion efficiency of 0.74% with a short circuit photocurrent density of 3.05 mA/cm2, an open circuit voltage of 0.54 mV and a fill factor of 0.44 under the standard global air mass (AM 1.5) solar conditions. However, our report about the synthesis and the photovoltaic characteristics of a porphyrin-based sensitizer in a D-π-A structure demonstrated a significant complex relationship between the sensitizer structure and the cell performance.

  17. Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates.

    Science.gov (United States)

    Shikhagaie, Medya Mara; Björklund, Åsa K; Mjösberg, Jenny; Erjefält, Jonas S; Cornelissen, Anne S; Ros, Xavier Romero; Bal, Suzanne M; Koning, Jasper J; Mebius, Reina E; Mori, Michiko; Bruchard, Melanie; Blom, Bianca; Spits, Hergen

    2017-02-14

    Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1 + group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1 + ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1 + ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1 - cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1 + ILC3s. NRP1 + ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. The Hydroxyl at Position C1 of Genipin Is the Active Inhibitory Group that Affects Mitochondrial Uncoupling Protein 2 in Panc-1 Cells.

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available Genipin (GNP effectively inhibits uncoupling protein 2 (UCP2, which regulates the leakage of protons across the inner mitochondrial membrane. UCP2 inhibition may induce pancreatic adenocarcinoma cell death by increasing reactive oxygen species (ROS levels. In this study, the hydroxyls at positions C10 (10-OH and C1 (1-OH of GNP were hypothesized to be the active groups that cause these inhibitory effects. Four GNP derivatives in which the hydroxyl at position C10 or C1 was replaced with other chemical groups were synthesized and isolated. Differences in the inhibitory effects of GNP and its four derivatives on pancreatic carcinoma cell (Panc-1 proliferation were assessed. The effects of GNP and its derivatives on apoptosis, UCP2 inhibition and ROS production were also studied to explore the relationship between GNP's activity and its structure. The derivatives with 1-OH substitutions, geniposide (1-GNP1 and 1-ethyl-genipin (1-GNP2 lacked cytotoxic effects, while the other derivatives that retained 1-OH, 10-piv-genipin (10-GNP1 and 10-acetic acid-genipin (10-GNP2 exerted biological effects similar to those of GNP, even in the absence of 10-OH. Thus, 1-OH is the key functional group in the structure of GNP that is responsible for GNP's apoptotic effects. These cytotoxic effects involve the induction of Panc-1 cell apoptosis through UCP2 inhibition and subsequent ROS production.

  19. The Hydroxyl at Position C1 of Genipin Is the Active Inhibitory Group that Affects Mitochondrial Uncoupling Protein 2 in Panc-1 Cells.

    Science.gov (United States)

    Yang, Yang; Yang, Yifu; Hou, Jianwei; Ding, Yue; Zhang, Tong; Zhang, Yong; Wang, Jianying; Shi, Chenchen; Fu, Wenwei; Cai, Zhenzhen

    2016-01-01

    Genipin (GNP) effectively inhibits uncoupling protein 2 (UCP2), which regulates the leakage of protons across the inner mitochondrial membrane. UCP2 inhibition may induce pancreatic adenocarcinoma cell death by increasing reactive oxygen species (ROS) levels. In this study, the hydroxyls at positions C10 (10-OH) and C1 (1-OH) of GNP were hypothesized to be the active groups that cause these inhibitory effects. Four GNP derivatives in which the hydroxyl at position C10 or C1 was replaced with other chemical groups were synthesized and isolated. Differences in the inhibitory effects of GNP and its four derivatives on pancreatic carcinoma cell (Panc-1) proliferation were assessed. The effects of GNP and its derivatives on apoptosis, UCP2 inhibition and ROS production were also studied to explore the relationship between GNP's activity and its structure. The derivatives with 1-OH substitutions, geniposide (1-GNP1) and 1-ethyl-genipin (1-GNP2) lacked cytotoxic effects, while the other derivatives that retained 1-OH, 10-piv-genipin (10-GNP1) and 10-acetic acid-genipin (10-GNP2) exerted biological effects similar to those of GNP, even in the absence of 10-OH. Thus, 1-OH is the key functional group in the structure of GNP that is responsible for GNP's apoptotic effects. These cytotoxic effects involve the induction of Panc-1 cell apoptosis through UCP2 inhibition and subsequent ROS production.

  20. [EXPERIMENTAL RESEARCH OF DIFFERENTIATION OF HUMAN AMNIOTIC MESENCHYMAL STEM CELLS INTO LIGAMENT CELLS IN VITRO].

    Science.gov (United States)

    Jin, Ying; Li, Yuwan; Zhang, Chenghao; Wu, Shuhong; Cheng, Daixiong; Liu, Yi

    2016-02-01

    To discuss whether human amniotic mesenchymal stem cells (hAMSCs) possesses the characteristic of mesenchymal stem cells, and could differentiate into ligament cells in vitro after induction. The hAMSCs were separated through enzyme digestion, and the phenotypic characteristics of hAMSCs were tested through flow cytometry. The cells at passage 3 were cultured with L-DMEM/F12 medium containing transforming growth factor beta1 (TGF-beta1) + basic fibroblast growth factor (bFGF) (group A), containing hyaluronic acid (HA) (group B), containing TGF-beta1+bFGF+HA (group C), and simple L-DMEM/F12 medium (group D) as control group. The morphology changes of cells in each group were observed by inverted phase contrast microscope at 21 days after induction; the cellular activities and proliferation were examined by sulforhodamine (SRB) colorimetric method; and specific mRNA and protein expressions of ligament including collagen type I, collagen type III, and tenascin C (TNC) were measured by real-time fluorescence quantitative PCR and immunohistochemical staining. The flow cytometry result indicated that hAMSCs expressed mesenchymal stem cell phenotype. After 21 days of induction, the cells in groups A, B, and C grew like spindle-shaped fibroblasts under inverted phase contrast microscope, and cells showed single shape, obvious directivity, and compact arrangement in group C. The SRB result indicated that the cells in each group reached the peak of growth curve at 6 days; the cellular activities of groups A, B, and C were significantly higher than that of group D at 6 days after induction. Also, the immunohistochemical staining results showed that no expressions of TNC were detected in 4 groups at 7 days; expressions of collagen type I in groups A, B, and C were significantly higher than that in group D at 7, 14, and 21 days (Pligament specific genes can be up-regulated and the synthesis of ligament specific proteins can be also strengthened. As a result, it can be used as

  1. Temozolomide in patients with advanced non-small cell lung cancer with and without brain metastases. a phase II study of the EORTC Lung Cancer Group (08965).

    NARCIS (Netherlands)

    Dziadziuszko, R; Ardizzoni, A.; Postmus, P.E.; Smit, E.F.; Price, A; Debruyne, C.; Legrand, C; Giaccone, G.

    2003-01-01

    This study was performed to evaluate the activity of single-agent temozolomide in two groups of chemotherapy-naive non-small cell lung cancer (NSCLC) patients, with (12 patients) and without (13 patients) brain metastases (BM). Patients in both groups were treated with temozolomide 200 mg/m(2)/day,

  2. Pharmacological and therapeutic directions in ADHD: Specificity in the PFC

    Directory of Open Access Journals (Sweden)

    Levy Florence

    2008-02-01

    Full Text Available Abstract Background Recent directions in the treatment of ADHD have involved both a broadening of pharmacological perspectives to include nor-adrenergic as well as dopaminergic agents. A review of animal and human studies of pharmacological and therapeutic directions in ADHD suggests that the D1 receptor is a specific site for dopaminergic regulation of the PFC, but optimal levels of dopamine (DA are required for beneficial effects on working memory. Animal and human studies indicate that the alpha-2A receptor is also important for prefrontal regulation, leaving open the question of the relative importance of these receptor sites. The therapeutic effects of ADHD medications in the prefrontal cortex have focused attention on the development of working memory capacity in ADHD. Hypothesis The actions of dopaminergic vs noradrenergic agents, currently available for the treatment of ADHD have overlapping, but different actions in the prefrontal cortex (PFC and subcortical centers. While stimulants act on D1 receptors in the dorsolateral prefrontal cortex, they also have effects on D2 receptors in the corpus striatum and may also have serotonergic effects at orbitofrontal areas. At therapeutic levels, dopamine (DA stimulation (through DAT transporter inhibition decreases noise level acting on subcortical D2 receptors, while NE stimulation (through alpha-2A agonists increases signal by acting preferentially in the PFC possibly on DAD1 receptors. On the other hand, alpha-2A noradrenergic transmission is more limited to the prefrontal cortex (PFC, and thus less likely to have motor or stereotypic side effects, while alpha-2B and alpha-2C agonists may have wider cortical effects. The data suggest a possible hierarchy of specificity in the current medications used in the treatment of ADHD, with guanfacine likely to be most specific for the treatment of prefrontal attentional and working memory deficits. Stimulants may have broader effects on both vigilance

  3. Correlation between E-cadherin-regulated cell adhesion and human osteosarcoma MG-63 cell anoikis.

    Science.gov (United States)

    Lin, Ding-Sheng; Cai, Le-Yi; Ding, Jian; Gao, Wei-Yang

    2014-01-01

    The aim of this study was to investigate the relationship between cell adhesion and anoikis evasion among human osteosarcoma cells (MG-63), and to further study the molecular mechanisms. Human osteosarcoma cells (MG-63) were assessed for apoptosis, and caspase-3, E-cadherin and β-catenin expression in EDTA and control non-EDTA groups. MG-63 cells were predominantly aggregated when in suspension, and the suspended cells were more dispersed in the EDTA group. Following culture in suspension for 24 h, 48 h, or 72 h, the rates of apoptosis were 34.88%±3.64%, 59.3%±7.22% and 78.5%±5.21% in the experimental group and 7.34%±2.13%, 14.7%±3.69%, and 21.4%±3.60% in the control group, respectively. Caspase-3 expression progressively increased and E-cadherin and β-catenin were decreased in the experimental group, whereas there was no change in the control group. MG-63 cells could avoid anoikis through cell adhesion, and E-cadherin might play a role in this process.

  4. Polycomb Group Protein PHF1 Regulates p53-dependent Cell Growth Arrest and Apoptosis*

    Science.gov (United States)

    Yang, Yang; Wang, Chenji; Zhang, Pingzhao; Gao, Kun; Wang, Dejie; Yu, Hongxiu; Zhang, Ting; Jiang, Sirui; Hexige, Saiyin; Hong, Zehui; Yasui, Akira; Liu, Jun O.; Huang, Haojie; Yu, Long

    2013-01-01

    Polycomb group protein PHF1 is well known as a component of a novel EED-EZH2·Polycomb repressive complex 2 complex and plays important roles in H3K27 methylation and Hox gene silencing. PHF1 is also involved in the response to DNA double-strand breaks in human cells, promotes nonhomologous end-joining processes through interaction with Ku70/Ku80. Here, we identified another function of PHF1 as a potential p53 pathway activator in a pathway screen using luminescence reporter assay. Subsequent studies showed PHF1 directly interacts with p53 proteins both in vivo and in vitro and co-localized in nucleus. PHF1 binds to the C-terminal regulatory domain of p53. Overexpression of PHF1 elevated p53 protein level and prolonged its turnover. Knockdown of PHF1 reduced p53 protein level and its target gene expression both in normal state and DNA damage response. Mechanically, PHF1 protects p53 proteins from MDM2-mediated ubiquitination and degradation. Furthermore, we showed that PHF1 regulates cell growth arrest and etoposide-induced apoptosis in a p53-dependent manner. Finally, PHF1 expression was significantly down-regulated in human breast cancer samples. Taken together, we establish PHF1 as a novel positive regulator of the p53 pathway. These data shed light on the potential roles of PHF1 in tumorigenesis and/or tumor progression. PMID:23150668

  5. High mobility group box associated with cell proliferation appears to play an important role in hepatocellular carcinogenesis in rats and humans.

    Science.gov (United States)

    Suzuki, Shugo; Takeshita, Kentaro; Asamoto, Makoto; Takahashi, Satoru; Kandori, Hitoshi; Tsujimura, Kazunari; Saito, Fumiyo; Masuko, Kazuo; Shirai, Tomoyuki

    2009-01-31

    To identify genes important in hepatocellular carcinogenesis, especially processes involved in malignant transformation, we focused on differences in gene expression between adenomas and carcinomas by DNA microarray. Eighty-one genes for which expression was specific in carcinomas were analyzed using Ingenuity Pathway Analysis software and Gene Ontology, and found to be associated with TP53 and regulators of cell proliferation. In the genes associated with TP53, we selected high mobility group box (HMGB) for detailed analysis. Immunohistochemistry revealed expression of HMGBs in carcinomas to be significantly higher than in other lesions among both human and rat liver, and a positive correlation between HMGBs and TP53 was detected in rat carcinomas. Knock-down of HMGB 2 expression in a rat hepatocellular carcinoma cell line by RNAi resulted in inhibition of cell growth, although no effects on invasion were evident in vitro. These results suggest that acquisition of malignant potential in the liver requires specific signaling pathways related to high cell proliferation associated with TP53. In particular, HMGBs appear to have an important role for progression and cell proliferation associated with loss of TP53 function in rat and in human hepatocarcinogenesis.

  6. High mobility group box associated with cell proliferation appears to play an important role in hepatocellular carcinogenesis in rats and humans

    International Nuclear Information System (INIS)

    Suzuki, Shugo; Takeshita, Kentaro; Asamoto, Makoto; Takahashi, Satoru; Kandori, Hitoshi; Tsujimura, Kazunari; Saito, Fumiyo; Masuko, Kazuo; Shirai, Tomoyuki

    2009-01-01

    To identify genes important in hepatocellular carcinogenesis, especially processes involved in malignant transformation, we focused on differences in gene expression between adenomas and carcinomas by DNA microarray. Eighty-one genes for which expression was specific in carcinomas were analyzed using Ingenuity Pathway Analysis software and Gene Ontology, and found to be associated with TP53 and regulators of cell proliferation. In the genes associated with TP53, we selected high mobility group box (HMGB) for detailed analysis. Immunohistochemistry revealed expression of HMGBs in carcinomas to be significantly higher than in other lesions among both human and rat liver, and a positive correlation between HMGBs and TP53 was detected in rat carcinomas. Knock-down of HMGB 2 expression in a rat hepatocellular carcinoma cell line by RNAi resulted in inhibition of cell growth, although no effects on invasion were evident in vitro. These results suggest that acquisition of malignant potential in the liver requires specific signaling pathways related to high cell proliferation associated with TP53. In particular, HMGBs appear to have an important role for progression and cell proliferation associated with loss of TP53 function in rat and in human hepatocarcinogenesis

  7. Anti-dopamine beta-hydroxylase immunotoxin-induced sympathectomy in adult rats

    Science.gov (United States)

    Picklo, M. J.; Wiley, R. G.; Lonce, S.; Lappi, D. A.; Robertson, D.

    1995-01-01

    Anti-dopamine beta-hydroxylase immunotoxin (DHIT) is an antibody-targeted noradrenergic lesioning tool comprised of a monoclonal antibody against the noradrenergic enzyme, dopamine beta-hydroxylase, conjugated to saporin, a ribosome-inactivating protein. Noradrenergic-neuron specificity and completeness and functionality of sympathectomy were assessed. Adult, male Sprague-Dawley rats were given 28.5, 85.7, 142 or 285 micrograms/kg DHIT i.v. Three days after injection, a 6% to 73% decrease in the neurons was found in the superior cervical ganglia of the animals. No loss of sensory, nodose and dorsal root ganglia, neurons was observed at the highest dose of DHIT. In contrast, the immunotoxin, 192-saporin (142 micrograms/kg), lesioned all three ganglia. To assess the sympathectomy, 2 wk after treatment (285 micrograms/kg), rats were anesthetized with urethane (1 g/kg) and cannulated in the femoral artery and vein. DHIT-treated animals' basal systolic blood pressure and heart rate were significantly lower than controls. Basal plasma norepinephrine levels were 41% lower in DHIT-treated animals than controls. Tyramine-stimulated release of norepinephrine in DHIT-treated rats was 27% of controls. Plasma epinephrine levels of DHIT animals were not reduced. DHIT-treated animals exhibited a 2-fold hypersensitivity to the alpha-adrenergic agonist phenylephrine. We conclude that DHIT selectively delivered saporin to noradrenergic neurons resulting in destruction of these neurons. Anti-dopamine beta-hydroxylase immunotoxin administration produces a rapid, irreversible sympathectomy.

  8. Cortisol boosts risky decision-making behavior in men but not in women.

    Science.gov (United States)

    Kluen, Lisa Marieke; Agorastos, Agorastos; Wiedemann, Klaus; Schwabe, Lars

    2017-10-01

    Acute stress may escalate risky decision-making in men, while there is no such effect in women. Although first evidence links these gender-specific effects of stress to stress-induced changes in cortisol, whether elevated cortisol is indeed sufficient to boost risk-taking, whether a potential cortisol effect depends on simultaneous noradrenergic activation, and whether cortisol and noradrenergic activation exert distinct effects on risk-taking in men and women is unknown. In this experiment, we therefore set out to elucidate the impact of cortisol and noradrenergic stimulation on risky decision-making in men and women. In a fully-crossed, placebo-controlled, double-blind design, male and female participants received orally either a placebo, hydrocortisone, yohimbine, an alpha-2-adrenoceptor-antagonist leading to increased noradrenergic stimulation, or both drugs before completing the balloon analogue risk task, a validated measure of risk-taking. Overall, participants' choice was risk-sensitive as reflected in reduced responding in high- compared to moderate- and low-risk conditions. Cortisol, however, led to a striking increase in risk-taking in men, whereas it had no effect on risk-taking behavior in women. Yohimbine had no such effect and the gender-specific effect of cortisol was not modulated by yohimbine. Our data show that cortisol boosts risk-taking behavior in men but not in women. This differential effect of cortisol on risk-taking may drive gender differences in risky decision-making under stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Bioprocessing automation in cell therapy manufacturing: Outcomes of special interest group automation workshop.

    Science.gov (United States)

    Ball, Oliver; Robinson, Sarah; Bure, Kim; Brindley, David A; Mccall, David

    2018-04-01

    Phacilitate held a Special Interest Group workshop event in Edinburgh, UK, in May 2017. The event brought together leading stakeholders in the cell therapy bioprocessing field to identify present and future challenges and propose potential solutions to automation in cell therapy bioprocessing. Here, we review and summarize discussions from the event. Deep biological understanding of a product, its mechanism of action and indication pathogenesis underpin many factors relating to bioprocessing and automation. To fully exploit the opportunities of bioprocess automation, therapeutics developers must closely consider whether an automation strategy is applicable, how to design an 'automatable' bioprocess and how to implement process modifications with minimal disruption. Major decisions around bioprocess automation strategy should involve all relevant stakeholders; communication between technical and business strategy decision-makers is of particular importance. Developers should leverage automation to implement in-process testing, in turn applicable to process optimization, quality assurance (QA)/ quality control (QC), batch failure control, adaptive manufacturing and regulatory demands, but a lack of precedent and technical opportunities can complicate such efforts. Sparse standardization across product characterization, hardware components and software platforms is perceived to complicate efforts to implement automation. The use of advanced algorithmic approaches such as machine learning may have application to bioprocess and supply chain optimization. Automation can substantially de-risk the wider supply chain, including tracking and traceability, cryopreservation and thawing and logistics. The regulatory implications of automation are currently unclear because few hardware options exist and novel solutions require case-by-case validation, but automation can present attractive regulatory incentives. Copyright © 2018 International Society for Cellular Therapy

  10. Responses of human normal osteoblast cells and osteoblast-like cell line, MG-63 cells, to pulse electromagnetic field (PEMF

    Directory of Open Access Journals (Sweden)

    Suttatip Kamolmatyakul

    2008-01-01

    Full Text Available The objective of this in vitro study is to investigate the effect of pulsed electromagnetic field (PEMF on cellular proliferation and osteocalcin production of osteoblast-like cell line, MG-63 cells, and human normal osteoblast cells (NHOC obtained from surgical bone specimens. The cells were placed in 24-well culture plates in the amount of 3x104 cell/wells with 2 ml αMEM media supplemented with 10% FBS. The experimental plates were placed between a pair of Helmoltz coils powered by a pulse generator (PEMF, 50 Hz, 1.5 mV/cm in the upper compartment of a dual incubator (Forma. The control plates were placed in the lower compartment of the incubator without Helmotz coils. After three days, the cell proliferation was measured by the method modified from Mossman (J. Immunol Methods 1983; 65: 55-63. Other sets of plates were used for osteocalcin production assessment. Media from these sets were collected after 6 days and assessed for osteocalcin production using ELISA kits. The data were analyzed using a one-way analysis of variance (ANOVA. The results showed that MG-63 cells from the experimental group proliferated significantly more than those from the control group (20% increase, p<0.05. No significant difference in osteocalcin production was detected between the two groups. On the other hand, NHOC from the experimental group produced larger amount of osteocalcin (25% increase, p<0.05 and proliferated significantly more than those from the control group (100% increase, p<0.05. In conclusion, PEMF effect on osteoblasts might depend on their cell type of origin. For osteoblast-like cell line, MG-63 cells, PEMF increased proliferation rate but not osteocalcin production of the cells. However, PEMF stimulation effect on human normal osteoblast cells was most likely associated with enhancement of both osteocalcin production and cell proliferation.

  11. Comparative Evaluation of the Mast Cells between Oral and Cutaneous Squamous Cell Carcinoma

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    E Mohammadnia Sarvi

    2017-04-01

    Full Text Available BACKGROUND AND OBJECTIVE: It has been mentioned that mast cells may help to tumor invasion. According to different aggressive behavior of oral squamous cell carcinoma (OSCC compared to cutaneous SCC (CSCC, the aim of this study was to compare mast cells count between OSCC and CSCC to understand the role of them in different biologic behavior of these two tumors. METHODS: This cross-sectional study consisted of 90 samples including 30 cases of OSCC, 30 cases of CSCC, 15 cases of normal skin and 15 cases of normal oral mucosa (as control groups. Number of mast cells was counted under light microscope in 10 successive fields in invasive front of OSCCs and CSCCs at 400X magnification and mean mast cells count/mm2 were calculated and compared between studied groups using one way ANOVA statistical test. FINDINGS: Mean mast cells count in CSCC, OSCC, normal skin and normal oral mucosa groups were 20.31±14.67, 10.41±8.01, 5.10±8.67 and 4.87±2.68, respectively. There were significant differences in mast cell count between CSCC and normal skin groups (p<0.001 and between CSCC and OSCC groups (p=0.002. This difference wasn’t significant between OSCC and normal oral mucosa groups (p=0.337. CONCLUSION: Lower level of mast cells in OSCCs may reflect less need for activation of mast cells in order to increase angiogenesis in OSCCs .Increase in mast cell density in CSCCs suggests a possible role for mast cell in tumor progression of CSCCs.

  12. The cellular prion protein interacts with the tissue non-specific alkaline phosphatase in membrane microdomains of bioaminergic neuronal cells.

    Directory of Open Access Journals (Sweden)

    Myriam Ermonval

    Full Text Available BACKGROUND: The cellular prion protein, PrP(C, is GPI anchored and abundant in lipid rafts. The absolute requirement of PrP(C in neurodegeneration associated to prion diseases is well established. However, the function of this ubiquitous protein is still puzzling. Our previous work using the 1C11 neuronal model, provided evidence that PrP(C acts as a cell surface receptor. Besides a ubiquitous signaling function of PrP(C, we have described a neuronal specificity pointing to a role of PrP(C in neuronal homeostasis. 1C11 cells, upon appropriate induction, engage into neuronal differentiation programs, giving rise either to serotonergic (1C11(5-HT or noradrenergic (1C11(NE derivatives. METHODOLOGY/PRINCIPAL FINDINGS: The neuronal specificity of PrP(C signaling prompted us to search for PrP(C partners in 1C11-derived bioaminergic neuronal cells. We show here by immunoprecipitation an association of PrP(C with an 80 kDa protein identified by mass spectrometry as the tissue non-specific alkaline phosphatase (TNAP. This interaction occurs in lipid rafts and is restricted to 1C11-derived neuronal progenies. Our data indicate that TNAP is implemented during the differentiation programs of 1C11(5-HT and 1C11(NE cells and is active at their cell surface. Noteworthy, TNAP may contribute to the regulation of serotonin or catecholamine synthesis in 1C11(5-HT and 1C11(NE bioaminergic cells by controlling pyridoxal phosphate levels. Finally, TNAP activity is shown to modulate the phosphorylation status of laminin and thereby its interaction with PrP. CONCLUSION/SIGNIFICANCE: The identification of a novel PrP(C partner in lipid rafts of neuronal cells favors the idea of a role of PrP in multiple functions. Because PrP(C and laminin functionally interact to support neuronal differentiation and memory consolidation, our findings introduce TNAP as a functional protagonist in the PrP(C-laminin interplay. The partnership between TNAP and PrP(C in neuronal cells may

  13. Connecting single cell to collective cell behavior in a unified theoretical framework

    Science.gov (United States)

    George, Mishel; Bullo, Francesco; Campàs, Otger

    Collective cell behavior is an essential part of tissue and organ morphogenesis during embryonic development, as well as of various disease processes, such as cancer. In contrast to many in vitro studies of collective cell migration, most cases of in vivo collective cell migration involve rather small groups of cells, with large sheets of migrating cells being less common. The vast majority of theoretical descriptions of collective cell behavior focus on large numbers of cells, but fail to accurately capture the dynamics of small groups of cells. Here we introduce a low-dimensional theoretical description that successfully captures single cell migration, cell collisions, collective dynamics in small groups of cells, and force propagation during sheet expansion, all within a common theoretical framework. Our description is derived from first principles and also includes key phenomenological aspects of cell migration that control the dynamics of traction forces. Among other results, we explain the counter-intuitive observations that pairs of cells repel each other upon collision while they behave in a coordinated manner within larger clusters.

  14. An international investigation into O red blood cell unit administration in hospitals: the GRoup O Utilization Patterns (GROUP) study.

    Science.gov (United States)

    Zeller, Michelle P; Barty, Rebecca; Aandahl, Astrid; Apelseth, Torunn O; Callum, Jeannie; Dunbar, Nancy M; Elahie, Allahna; Garritsen, Henk; Hancock, Helen; Kutner, José Mauro; Manukian, Belinda; Mizuta, Shuichi; Okuda, Makoto; Pagano, Monica B; Pogłód, Ryszard; Rushford, Kylie; Selleng, Kathleen; Sørensen, Claess Henning; Sprogøe, Ulrik; Staves, Julie; Weiland, Thorsten; Wendel, Silvano; Wood, Erica M; van de Watering, Leo; van Wordragen-Vlaswinkel, Maria; Ziman, Alyssa; Jan Zwaginga, Jaap; Murphy, Michael F; Heddle, Nancy M; Yazer, Mark H

    2017-10-01

    Transfusion of group O blood to non-O recipients, or transfusion of D- blood to D+ recipients, can result in shortages of group O or D- blood, respectively. This study investigated RBC utilization patterns at hospitals around the world and explored the context and policies that guide ABO blood group and D type selection practices. This was a retrospective study on transfusion data from the 2013 calendar year. This study included a survey component that asked about hospital RBC selection and transfusion practices and a data collection component where participants submitted information on RBC unit disposition including blood group and D type of unit and recipient. Units administered to recipients of unknown ABO or D group were excluded. Thirty-eight hospitals in 11 countries responded to the survey, 30 of which provided specific RBC unit disposition data. Overall, 11.1% (21,235/191,397) of group O units were transfused to non-O recipients; 22.6% (8777/38,911) of group O D- RBC units were transfused to O D+ recipients, and 43.2% (16,800/38,911) of group O D- RBC units were transfused to recipients that were not group O D-. Disposition of units and hospital transfusion policy varied within and across hospitals of different sizes, with transfusion of group O D- units to non-group O D- patients ranging from 0% to 33%. A significant proportion of group O and D- RBC units were transfused to compatible, nonidentical recipients, although the frequency of this practice varied across sites. © 2017 AABB.

  15. Analysis of point mutations in an ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F

    International Nuclear Information System (INIS)

    Yagi, T.; Tatsumi-Miyajima, J.; Sato, M.; Kraemer, K.H.; Takebe, H.

    1991-01-01

    To assess the contribution to mutagenesis by human DNA repair defects, a UV-treated shuttle vector plasmid, pZ189, was passed through fibroblasts derived from Japanese xeroderma pigmentosum (XP) patients in two different DNA repair complementation groups (A and F). Patients with XP have clinical and cellular UV hypersensitivity, increased frequency of skin cancer, and defects in DNA repair. The XP DNA repair defects represented by complementation groups A (XP-A) and F (XP-F) are more common in Japan than in Europe or the United States. In comparison to results with DNA repair-proficient human cells (W138-VA13), UV-treated pZ189 passed through the XP-A [XP2OS(SV)] or XP-F [XP2YO(SV)] cells showed fewer surviving plasmids (XP-A less than XP-F) and a higher frequency of mutated plasmids (XP-A greater than XP-F). Base sequence analysis of more than 200 mutated plasmids showed the major type of base substitution mutation to be the G:C----A:T transition with all three cell lines. The XP-A and XP-F cells revealed a higher frequency of G:C----A:T transitions and a lower frequency of transversions among plasmids with single or tandem mutations and a lower frequency of plasmids with multiple point mutations compared to the normal line. The spectrum of mutations in pZ189 with the XP-A cells was similar to that with the XP-F cells. Seventy-six to 91% of the single base substitution mutations occurred at G:C base pairs in which the 5'-neighboring base of the cytosine was thymine or cytosine. These studies indicate that the DNA repair defects in Japanese XP patients in complementation groups A and F result in different frequencies of plasmid survival and mutagenesis but in similar types of mutagenic abnormalities despite marked differences in clinical features

  16. Neuroprotective effects of metabotropic glutamate receptor group II and III activators against MPP(+)-induced cell death in human neuroblastoma SH-SY5Y cells: the impact of cell differentiation state.

    Science.gov (United States)

    Jantas, D; Greda, A; Golda, S; Korostynski, M; Grygier, B; Roman, A; Pilc, A; Lason, W

    2014-08-01

    Recent studies have documented that metabotropic glutamate receptors from group II and III (mGluR II/III) are a potential target in the symptomatic treatment of Parkinson's disease (PD), however, the neuroprotective effects of particular mGluR II/III subtypes in relation to PD pathology are recognized only partially. In the present study, we investigated the effect of various mGluR II/III activators in the in vitro model of PD using human neuroblastoma SH-SY5Y cell line and mitochondrial neurotoxin MPP(+). We demonstrated that all tested mGluR ligands: mGluR II agonist - LY354740, mGluR III agonist - ACPT-I, mGluR4 PAM - VU0361737, mGluR8 agonist - (S)-3,4-DCPG, mGluR8 PAM - AZ12216052 and mGluR7 allosteric agonist - AMN082 were protective against MPP(+)-evoked cell damage in undifferentiated (UN-) SH-SY5Y cells with the highest neuroprotection mediated by mGluR8-specific agents. However, in retinoic acid- differentiated (RA-) SH-SY5Y cells we found protection mediated only by mGluR8 activators. We also demonstrated the cell proliferation stimulating effect for mGluR4 and mGluR8 PAMs. Next, we showed that the protection mediated by mGluR II/III activators in UN-SH-SY5Y was not accompanied by the modulation of caspase-3 activity, however, a decrease in the number of apoptotic nuclei was found. Finally, we showed that the inhibitor of necroptosis, necrostatin-1 blocked the mGluR III-mediated protection. Altogether our comparative in vitro data add a further proof to neuroprotective effects of mGluR agonists or PAMs and point to mGluR8 as a promising target for neuroprotective interventions in PD. The results also suggest the participation of necroptosis-related molecular pathways in neuroprotective effects of mGluR III activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. On the chromospheric network structure around deVeloped groups of sunspots

    International Nuclear Information System (INIS)

    Kartashova, L.G.

    1980-01-01

    The chromospheric network structure around several developed groups of sunspots were studied on the basis of the observations in the Hsub(α) line. The resolution on the filtergrams was of 2. The following was found: 1) in the neighbourhood of the groups of sunspots 70% (from 870) of network cells stretch along fibrils direction (with accuracy 30 deg), and 15% of cells stretch approximately across that (at angles 70-90 deg); 2) out of the boundary of the main radial fibrils structure the groups of sunspots is often rounded by the system of network cells stretched approximately perpendicular to radial direction

  18. Effects of ionizing radiation on differentiation of murine bone marrow cells into mast cells

    International Nuclear Information System (INIS)

    Murakami, Sho; Yoshino, Hironori; Ishikawa, Junya; Yamaguchi, Masaru; Tsujiguchi, Takakiyo; Nishiyama, Ayaka; Yokoyama, Kouki; Kashiwakura, Ikuo

    2015-01-01

    Mast cells, immune effector cells produced from bone marrow cells, play a major role in immunoglobulin E–mediated allergic responses. Ionizing radiation affects the functions of mast cells, which are involved in radiation-induced tissue damage. However, whether ionizing radiation affects the differential induction of mast cells is unknown. Here we investigated whether bone marrow cells of X-irradiated mice differentiated into mast cells. To induce mast cells, bone marrow cells from X-irradiated and unirradiated mice were cultured in the presence of cytokines required for mast cell induction. Although irradiation at 0.5 Gy and 2 Gy decreased the number of bone marrow cells 1 day post-irradiation, the cultured bone marrow cells of X-irradiated and unirradiated mice both expressed mast cell–related cell-surface antigens. However, the percentage of mast cells in the irradiated group was lower than in the unirradiated group. Similar decreases in the percentage of mast cells induced in the presence of X-irradiation were observed 10 days post irradiation, although the number of bone marrow cells in irradiated mice had recovered by this time. Analysis of mast cell function showed that degranulation of mast cells after immunoglobulin E–mediated allergen recognition was significantly higher in the X-irradiated group compared with in the unirradiated group. In conclusion, bone marrow cells of X-irradiated mice differentiated into mast cells, but ionizing radiation affected the differentiation efficiency and function of mast cells. (author)

  19. Epidemiology and treatment of mood disorders in a day hospital setting from 1996 to 2007: an Italian study

    Directory of Open Access Journals (Sweden)

    Luca M

    2013-02-01

    Full Text Available Maria Luca,1 Giuseppa Prossimo,1 Vincenzo Messina,1 Antonina Luca,2 Salvatore Romeo,1 Carmela Calandra11Department of Medical and Surgery Specialties, Psychiatry Unit, 2Department of Neuroscience, University Hospital Policlinico-Vittorio Emanuele, Catania, Sicily, ItalyBackground: The present study aimed: to assess prescribing patterns in the treatment of major depression, bipolar disorder type I, cyclothymia, and dysthymia from 1996 to 2007 in a day hospital setting; to evaluate the prevalence of the above-mentioned mood disorders and gender distribution; and to relate familiality, comorbidity, and marital status to each diagnosis.Methods: Medical records for 777 day hospital patients with a diagnosis of major depression, bipolar disorder type I, cyclothymia, or dysthymia were grouped into two 6-year periods so as to compare the prescribing patterns of tricyclic antidepressants, selective serotonin reuptake inhibitors, noradrenergic reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, noradrenergic and specific serotonergic antidepressants, first-generation antipsychotics, second-generation antipsychotics, and mood stabilizers. Gender, prevalence, familiality, comorbidity, and marital status were related to each diagnosis.Results: The most common mood disorder, with a female preponderance, was major depression, regardless of marital status. High percentages of familiality and comorbidity were found for major depression, while a reduction was found in the utilization of tricyclic antidepressants. There was no statistically significant difference in rates of prescription of selective serotonin reuptake inhibitors and noradrenergic reuptake inhibitors, but some irregularities were found upon evaluating each diagnosis (eg, increased utilization of these agents in dysthymia and major depression, respectively. There was an increase in prescriptions for serotonin and norepinephrine reuptake inhibitors, but no marked differences in

  20. The role of prophylactic cranial irradiation in regionally advanced non-small cell lung cancer. A Southwest Oncology Group Study

    Energy Technology Data Exchange (ETDEWEB)

    Rusch, V.W.; Griffin, B.R.; Livingston, R.B. (Univ. of Washington, Seattle (USA))

    1989-10-01

    Lung cancer is the most common malignant disease in the United States. Only the few tumors detected very early are curable, but there has been some progress in the management of more advanced non-small cell lung cancer, particularly in regionally inoperable disease. Prevention of central nervous system relapse is an important issue in this group of patients because brain metastases ultimately develop in 20% to 25% of them. Seventy-three patients with regionally advanced non-small cell lung cancer were entered into a Phase II trial of neutron chest radiotherapy sandwiched between four cycles of chemotherapy including cisplatin, vinblastine, and mitomycin C. Prophylactic cranial irradiation was administered concurrently with chest radiotherapy (3000 cGy in 10 fractions in 15 patients; 3600 cGy in 18 fractions in the remaining 50 patients). Patients underwent computed tomographic scan of the brain before treatment and every 3 months after treatment. The initial overall response rate was 79%, but 65 of the 73 patients have subsequently died of recurrent disease. Median follow-up is 9 months for all 73 patients and 26 months for eight long-term survivors. No patient who completed the prophylactic cranial irradiation program had clinical or radiologic brain metastases. Toxic reactions to prophylactic cranial irradiation included reversible alopecia in all patients, progressive dementia in one patient, and possible optic neuritis in one patient. Both of these patients received 300 cGy per fraction of irradiation. The use of prophylactic cranial irradiation has been controversial, but its safety and efficacy in this trial supports its application in a group of patients at high risk for central nervous system relapse. Further evaluation of prophylactic cranial irradiation in clinical trials for regionally advanced non-small cell lung cancer is warranted.

  1. Low-frequency electrical stimulation induces the proliferation and differentiation of peripheral blood stem cells into Schwann cells.

    Science.gov (United States)

    Gu, Xudong; Fu, Jianming; Bai, Jing; Zhang, Chengwen; Wang, Jing; Pan, Wenping

    2015-02-01

    Functional recovery after peripheral nerve injury remains a tough problem at present. Specifically, a type of glial cell exists in peripheral nerves that promotes axonal growth and myelin formation and secretes various active substances, such as neurotrophic factors, extracellular matrix and adherence factors. These substances have important significance for the survival, growth and regeneration of nerve fibers. Numerous recent studies have shown that electrical stimulation can increase the number of myelinated nerve fibers. However, whether electrical stimulation acts on neurons or Schwann cells has not been verified in vivo. This study investigates low-frequency electrical stimulation-induced proliferation and differentiation of peripheral blood stem cells into Schwann cells and explores possible mechanisms. Peripheral blood stem cells from Sprague-Dawley rats were primarily cultured. Cells in passage 3 were divided into 4 groups: a low-frequency electrical stimulation group (20 Hz, 100 μs, 3 V), a low-frequency electrical stimulation+PD98059 (blocking the extracellular signal-regulated kinase [ERK] signaling pathway) group, a PD98059 group and a control group (no treatment). After induction, the cells were characterized. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide assay was employed to measure the absorbance values at 570 nm in the 4 groups. A Western blot assay was used to detect the expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) in each group. No significant difference in cell viability was detected before induction. Peripheral blood stem cells from the 4 groups differentiated into Schwann cells. Phosphorylated ERK 1/2, cyclin D1 and CDK4 protein levels were highest in the low-frequency electrical stimulation group and lowest in the ERK blockage group. Phosphorylated ERK 1/2, cyclin D1 and CDK4 protein levels in the low-frequency electrical stimulation+ERK blockage group were lower than those in the low-frequency electrical

  2. Caudal fourth ventricular administration of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside regulates glucose and counterregulatory hormone profiles, dorsal vagal complex metabolosensory neuron function, and hypothalamic Fos expression.

    Science.gov (United States)

    Ibrahim, Baher A; Tamrakar, Pratistha; Gujar, Amit D; Cherian, Ajeesh Koshy; Briski, Karen P

    2013-09-01

    This study investigated the hypothesis that estrogen controls hindbrain AMP-activated protein kinase (AMPK) activity and regulation of blood glucose, counterregulatory hormone secretion, and hypothalamic nerve cell transcriptional status. Dorsal vagal complex A2 noradrenergic neurons were laser microdissected from estradiol benzoate (E)- or oil (O)-implanted ovariectomized female rats after caudal fourth ventricular (CV4) delivery of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR), for Western blot analysis. E advanced AICAR-induced increases in A2 phospho-AMPK (pAMPK) expression and in blood glucose levels and was required for augmentation of Fos, estrogen receptor-α (ERα), monocarboxylate transporter-2, and glucose transporter-3 protein in A2 neurons and enhancement of corticosterone secretion by this treatment paradigm. CV4 AICAR also resulted in site-specific modifications in Fos immunolabeling of hypothalamic metabolic structures, including the paraventricular, ventromedial, and arcuate nuclei. The current studies demonstrate that estrogen regulates AMPK activation in caudal hindbrain A2 noradrenergic neurons during pharmacological replication of energy shortage in this area of the brain, and that this sensor is involved in neural regulation of glucostasis, in part, through control of corticosterone secretion. The data provide unique evidence that A2 neurons express both ERα and -β proteins and that AMPK upregulates cellular sensitivity to ERα-mediated signaling during simulated energy insufficiency. The results also imply that estrogen promotes glucose and lactate uptake by these cells under those conditions. Evidence for correlation between hindbrain AMPK and hypothalamic nerve cell genomic activation provides novel proof for functional connectivity between this hindbrain sensor and higher order metabolic brain loci while demonstrating a modulatory role for estrogen in this interaction. Copyright © 2013 Wiley Periodicals, Inc.

  3. Effects of catecholamine agonists and antagonists on alcohol uptake in rats with different stages of experimental alcoholism

    Energy Technology Data Exchange (ETDEWEB)

    Burov, Yu V; Varov, A I

    1985-02-01

    The effects of various catecholamine agonists and antagonists on 15% ethanol ingestion by outbred albino rats were studied in relation to the stage of experimental alcoholism. In animals with stage I and II alcoholism, alcohol intake was most profoundly inhibited by administration of alpha-adrenoblockers (AA), klofelin, and alpha-methyl-DOPA (AMD), while L-DOPA and cocaine stimulated a significant increase in ethanol ingestion. In stage III alcoholism, both AA and L-DOPA depressed alcohol intake, while AMD and haloperidol had a stimulatory effect. It appears, therefore, that different neurochemical mechanisms are involved in alcohol dependence in different stages of experimental alcoholism in the rat. Furthermore, it seems evident that alpha-adrenergic receptors have a key function in maintaining alcohol dependence. In well-established physical dependence, the importance of the noradrenergic system seems to diminish and dopaminergic mechanisms appear to become predominant. Consequently, in the initial stages of alcoholism, agents which depress the noradrenergic system seem indicated, while at the stage of physical dependence agents which normalize noradrenergic mechanisms and depress dopaminergic mechanisms should be considered. 13 references.

  4. Selective noradrenaline depletion impairs working memory and hippocampal neurogenesis.

    Science.gov (United States)

    Coradazzi, Marino; Gulino, Rosario; Fieramosca, Francesco; Falzacappa, Lucia Verga; Riggi, Margherita; Leanza, Giampiero

    2016-12-01

    Noradrenergic neurons in the locus coeruleus play a role in learning and memory, and their loss is an early event in Alzheimer's disease pathogenesis. Moreover, noradrenaline may sustain hippocampal neurogenesis; however, whether are these events related is still unknown. Four to five weeks following the selective immunotoxic ablation of locus coeruleus neurons, young adult rats underwent reference and working memory tests, followed by postmortem quantitative morphological analyses to assess the extent of the lesion, as well as the effects on proliferation and/or survival of neural progenitors in the hippocampus. When tested in the Water Maze task, lesioned animals exhibited no reference memory deficit, whereas working memory abilities were seen significantly impaired, as compared with intact or sham-lesioned controls. Stereological analyses confirmed a dramatic noradrenergic neuron loss associated to reduced proliferation, but not survival or differentiation, of 5-bromo-2'deoxyuridine-positive progenitors in the dentate gyrus. Thus, ascending noradrenergic afferents may be involved in more complex aspects of cognitive performance (i.e., working memory) possibly via newly generated progenitors in the hippocampus. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Killing effect of peripheral blood mononuclear cells irradiated by γ ray on human gastric cancer MKN-28 cell

    International Nuclear Information System (INIS)

    Wu Daocheng; Zhang Xianqing; Mu Shijie; Liu Zhongxiang; Xia Aijun; Huang Xiaofeng; An Qunxing

    2007-01-01

    Objective: To observe the killing effect of peripheral blood mononuclear cells (PBMCs) irradiated by γ ray on cultured human gastric cancer cell line MKN-28. Methods: The experiment were divided into MKN-28 tumor cell control group, PBMCs groups and MKN-28 cells with irradiated or non-irradiated PBMCs co-culture groups. Radidation dosage were from 0.5 to 3 Gy, acridine orange/ethidium bromide (AO/EB) staining were used to observe the kill effect of PBMCs on tumor cells in different period. Results: After culture for 144h, the dead cells of several dosage irradiated PBMCs are much more than those of non-irradiated PBMCs group. At 240 hours of culture, the alive PBMCs deareses in number in both irradiated and non-irradiared groups, but decreases in radiated groups are more obvious. After culture for 72 h in the co-cultured groups, the difference is not evident among all radiation dosage groups. After 96-240 h of co-culture, the killing effect of 0.5-2Gy irradiated PBMCs on tumor cells is very strong, especially in 1Gy group, but the killing effect of PBMCs irradiated by 2.5-3Gy on tumor cells were weaker than that of 0.5-2Gy irradiated groups. At 240 hours co-cultured groups irradiated by 2.5-3Gy, tumor cells still survive and proliferate. Conclusion: Gamma ray irradiation have killing effect to some PBMCs. The cytocidal effect of PBMCs irradiated by 0.5-2Gy on tumor cells were increased. Chemotaxis and cytocidal effect of tumor cells to postirradiated PBMCs were also found. The killing effect of PBMCs irradiated by 2.5 and 3 Gy on tumor cells were restrained. (authors)

  6. Integrating the health and mental health needs of the chronically ill: a group for individuals with depression and sickle cell disease.

    Science.gov (United States)

    Comer, Edna W

    2004-01-01

    Concerns about high rates of depression among persons with sickle cell disease and no effective interventions for treatment of this condition were the impetuses for the study described in this paper. A groupwork service using cognitive-behavioral and self-management techniques were integrated into health care services at a Comprehensive Sickle Cell Center to treat depression in a small group of patients. An interdisciplinary team that included health care and mental health providers from the Center and a social work researcher guided the endeavor. Principles of Intervention Research were applied in the development of the service and to evaluate its effectiveness. Among the findings were that study participants realized a decrease in depressive symptoms.

  7. Effect of VEGF-C siRNA and endostatin on ring formation and proliferation of esophageal squamous cell carcinoma lymphatic endothelial cells

    Directory of Open Access Journals (Sweden)

    Zheng YP

    2016-10-01

    Full Text Available Yuping Zheng,1–3,* Miaomiao Sun,4,* Jinyan Chen,1,2 Lulu He,1,2 Na Zhao,1,2 Kuisheng Chen1,2 1Pathology Department, The First Affiliated Hospital of Zhengzhou University, 2Henan Key Laboratory of Tumor Pathology, 3Pathology Department, The Second Hospital of Shandong University, Jinan, 4Pathology Department, Henan Tumor Hospital, Zhengzhou, People’s Republic of China *These authors contributed equally to this work Objective: To study the effects of vascular endothelial growth factor C small interfering RNA and endostatin on esophageal squamous cell carcinoma-related ring formation in vitro and proliferation of lymphatic endothelial cells.Materials and methods: KYSE150 cells were subjected to analysis of cell transfection and endostatin operation. The groups were as follows: negative group, blank group, negative plus endostatin group, endostatin group, SG1 group, SG2 group, SG1 plus endostatin group, and SG2 plus endostatin group. The esophageal cancer-related microlymphatic endothelial cells were three-dimensionally cultured. Cell Counting Kit-8 (CCK-8 assay was employed to detect cell proliferation.Results: The negative group’s three-dimensional culture result was the highest, followed by the blank group, negative plus endostatin group, endostatin group, SG2 group, SG1 group, SG1 plus endostatin group, and SG2 plus endostatin group. The quantity of living cells in the blank group was the highest, followed by the negative control, endostatin, SG2, SG1, negative plus endostatin, SG1 plus endostatin, and SG2 plus endostatin groups. Conclusion: Both vascular endothelial growth factor C small interfering RNA and endostatin could inhibit ring formation in esophageal squamous cell carcinoma and proliferation of lymphatic endothelial cells. Keywords: esophageal squamous carcinoma cells, esophageal cancer-associated lymphatic endothelial cells, VEGF-C, ring formation, proliferation

  8. The polycomb group protein Suz12 is required for embryonic stem cell differentiation

    DEFF Research Database (Denmark)

    Pasini, Diego; Bracken, Adrian P; Hansen, Jacob Bo Højberg

    2007-01-01

    results in early lethality of mouse embryos. Here, we demonstrate that Suz12(-/-) mouse embryonic stem (ES) cells can be established and expanded in tissue culture. The Suz12(-/-) ES cells are characterized by global loss of H3K27 trimethylation (H3K27me3) and higher expression levels of differentiation......-specific genes. Moreover, Suz12(-/-) ES cells are impaired in proper differentiation, resulting in a lack of repression of ES cell markers as well as activation of differentiation-specific genes. Finally, we demonstrate that the PcGs are actively recruited to several genes during ES cell differentiation, which...... despite an increase in H3K27me3 levels is not always sufficient to prevent transcriptional activation. In summary, we demonstrate that Suz12 is required for the establishment of specific expression programs required for ES cell differentiation. Furthermore, we provide evidence that PcGs have different...

  9. Identification of novel rabbit hemorrhagic disease virus B-cell epitopes and their interaction with host histo-blood group antigens.

    Science.gov (United States)

    Song, Yanhua; Wang, Fang; Fan, Zhiyu; Hu, Bo; Liu, Xing; Wei, Houjun; Xue, Jiabin; Xu, Weizhong; Qiu, Rulong

    2016-02-01

    Rabbit haemorrhagic disease, caused by rabbit hemorrhagic disease virus (RHDV), results in the death of millions of adult rabbits worldwide, with a mortality rate that exceeds 90%. The sole capsid protein, VP60, is divided into shell (S) and protruding (P) domains, and the more exposed P domain likely contains determinants for cell attachment and antigenic diversity. Nine mAbs against VP60 were screened and identified. To map antigenic epitopes, a set of partially overlapping and consecutive truncated proteins spanning VP60 were expressed. The minimal determinants of the linear B-cell epitopes of VP60 in the P domain, N(326)PISQV(331), D(338)MSFV(342) and K(562)STLVFNL(569), were recognized by one (5H3), four (1B8, 3D11, 4C2 and 4G2) and four mAbs (1D4, 3F7, 5G2 and 6B2), respectively. Sequence alignment showed epitope D(338)MSFV(342) was conserved among all RHDV isolates. Epitopes N(326)PISQV(331) and K(562)STLVFNL(569) were highly conserved among RHDV G1-G6 and variable in RHDV2 strains. Previous studies demonstrated that native viral particles and virus-like particles (VLPs) of RHDV specifically bound to synthetic blood group H type 2 oligosaccharides. We established an oligosaccharide-based assay to analyse the binding of VP60 and epitopes to histo-blood group antigens (HBGAs). Results showed VP60 and its epitopes (aa 326-331 and 338-342) in the P2 subdomain could significantly bind to blood group H type 2. Furthermore, mAbs 1B8 and 5H3 could block RHDV VLP binding to synthetic H type 2. Collectively, these two epitopes might play a key role in the antigenic structure of VP60 and interaction of RHDV and HBGA.

  10. The PD-1/B7-H1 pathway modulates the natural killer cells versus mouse glioma stem cells.

    Directory of Open Access Journals (Sweden)

    Bo Yuan Huang

    Full Text Available Glioblastoma multiforme (GBM is the most malignant primary type of brain tumor in adults. There has been increased focus on the immunotherapies to treat GBM patients, the therapeutic value of natural killer (NK cells is still unknown. Programmed death-1 (PD-1 is a major immunological checkpoint that can negatively regulate the T-cell-mediated immune response. We tested the combination of the inhibiting the PD-1/B7H1 pathway with a NK-cell mediated immune response in an orthotopic mouse model of GBM.Mouse glioma stem cells (GL261GSCs and mouse NK cells were isolated and identified. A lactate dehydrogenase (LDH assay was perfomed to detect the cytotoxicity of NK cells against GL261GSCs. GL261GSCs were intracranially implanted into mice, and the mice were stratified into 3 treatment groups: 1 control, 2 NK cells treatment, and 3 PD-1 inhibited NK cells treatment group. Overall survival was quantified, and animal magnetic resonance imaging (MRI was performed to determine tumor growth. The brains were harvested after the mice were euthanized, and immunohistochemistry against CD45 and PCNA was performed.The mouse NK cells were identified as 90% CD3- NK1.1+CD335+ by flow cytometric analysis. In the LDH assay, the ratios of the damaged GL261GSCs, with the E:T ratios of 2.5:1, 5:1, and 10:1, were as follows: 1 non-inhibited group: 7.42%, 11.31%, and 15.1%, 2 B7H1 inhibited group: 14.75%, 18.25% and 29.1%, 3 PD-1 inhibited group: 15.53%, 19.21% and 29.93%, 4 double inhibited group: 33.24%, 42.86% and 54.91%. In the in vivo experiments, the mice in the PD-1 inhibited NK cells treatment group and IL-2-stimulated-NK cells treatment group displayed a slowest tumor growth (F = 308.5, P<0.01 and a slower tumor growth compared with control group (F = 118.9, P<0.01, respectively. The median survival of the mice in the three groups were as follows: 1 conrol group: 29 days, 2 NK cells treatment group: 35 days (P = 0.0012, 3 PD-1 inhibited NK cells treatment group

  11. STUDIES ON HUMAN FALLOPIAN TUBAL EPITHELIUM IN DIFFERENT AGE GROUPS

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    Jayasri

    2016-02-01

    Full Text Available BACKGROUND AND AIMS The “fallopian tubes” (oviducts or uterine tubes are long paired flexuous reproductive organ which transports ova, spermatozoa, zygotes, the pre-implantation morulae and blastocyst. It has major role during reproductive period, but it remains as if vestigial organ before puberty and after menopause. Due to increasing rate of tubal block and infertility, oviducts and their structures gaining importance and have become a subject of research in present days particularly epithelium. The aim of the study is to ascertain any histological difference of tubal epithelium in different age groups and the research work could be utilized for investigation and management of infertility. MATERIALS AND METHODS Seven samples of each group i.e., prereproductive, reproductive & postmenopausal were collected from fresh unembalmed human cadavers received in the department of Anatomy, FAA Medical College, Barpeta, Assam. The slides were prepared using the standard laboratory procedure. Under low and high power objectives the type of cells were observed and epithelial height was measured in the different segments. Stress was given for any significant difference of epithelial height between the different age groups. RESULTS Study revealed that among the groups within the same segment, epithelial height was recorded highest (33.57µm in reproductive group as against the lowest (22.91µm in post-menopausal group. Epithelial structures of the prereproductive and reproductive groups were significantly differed (p<0.01 from the postmenopausal group. CONCLUSIONS From the findings of the present study it can be concluded that: 1. In all the groups fallopian tubal epithelium is of simple columnar type and contains three types of cells. Cells are ciliated, secretory & peg (intercalary cells. 2. In all the groups same type of increasing trend of epithelial height from intramural segment to ampullary segment was recorded. 3. In intergroup comparison of

  12. Dissociation of immediate and delayed effects of emotional arousal on episodic memory.

    Science.gov (United States)

    Schümann, Dirk; Bayer, Janine; Talmi, Deborah; Sommer, Tobias

    2018-02-01

    Emotionally arousing events are usually better remembered than neutral ones. This phenomenon is in humans mostly studied by presenting mixed lists of neutral and emotional items. An emotional enhancement of memory is observed in these studies often already immediately after encoding and increases with longer delays and consolidation. A large body of animal research showed that the more efficient consolidation of emotionally arousing events is based on an activation of the central noradrenergic system and the amygdala (Modulation Hypothesis; Roozendaal & McGaugh, 2011). The immediately superior recognition of emotional items is attributed primarily to their attraction of attention during encoding which is also thought to be based on the amygdala and the central noradrenergic system. To investigate whether the amygdala and noradrenergic system support memory encoding and consolidation via shared neural substrates and processes a large sample of participants (n = 690) encoded neutral and arousing pictures. Their memory was tested immediately and after a consolidation delay. In addition, they were genotyped in two relevant polymorphisms (α 2B -adrenergic receptor and serotonin transporter). Memory for negative and positive emotional pictures was enhanced at both time points where these enhancements were correlated (immediate r = 0.60 and delayed test r = 0.46). Critically, the effects of emotional arousal on encoding and consolidation correlated only very low (negative r = 0.14 and positive r = 0.03 pictures) suggesting partly distinct underlying processes consistent with a functional heterogeneity of the central noradrenergic system. No effect of genotype on either effect was observed. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. [Effects of three Wenyang Jianpi Tang on cell proliferation and apoptosis of nonalcoholic fatty liver cells].

    Science.gov (United States)

    Yang, Jia-Yao; Tao, Dong-Qing; Liu, Song; Zhang, Shu; Ma, Wei; Shi, Zhao-Hong

    2017-04-01

    To investigate the effects of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang on the cell proliferation and apoptosis of nonalcoholic fatty liver cells through the nonalcoholic fatty liver cell model established by inducing L02 cells with oleic acid. Different concentrations of oleic acid were added into L02 cells to induce the nonalcoholic fatty liver cell model. Oil red O staining was used to observe fatty droplets of fatty liver cells. Automatic biochemical analyzer was used to detect the levels of aspartic transaminase(AST), alanine aminotransferase(ALT), total cholesterol(TC), and triglyceride(TG) in the cell supernatants. There were five groups, namely normal group, model group, model and Sijunzi Tang group, model and Lizhong Tang group, and model and Fuzi Lizhong Tang group. The cell proliferation and apoptosis of the five groups were detected by MTT colorimetry test and flow cytometer. The expressions of PCNA, cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax and Bcl-2 proteins of the five groups were detected by Western blot. The oil red O staining results showed that the optimum concentration of oleic acid that was used to induce nonalcoholic fatty liver cell models was 80 mg•L-1. The levels of AST, ALT, TC and TG in the nonalcoholic fatty liver cell supernatants were higher than that in normal liver cell supernatants(PTang, Lizhong Tang and Fuzi Lizhong Tang could effectively promote the cell proliferation, and inhibit the cellular apoptosis of nonalcoholic fatty liver cells(PTang showed the best effect. Western blot results showed that Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could down-regulate the expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9 and Bax proteins, and up-regulate the expressions of PCNA and Bcl-2 proteins of nonalcoholic fatty liver cells. And Fuzi Lizhong Tang showed the best effect. In conclusion, all of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could effectively promote the cell

  14. [Astragalus polysaccharide may increase sensitivity of cervical cancer HeLa cells to cisplatin by regulating cell autophagy].

    Science.gov (United States)

    Zhai, Qiu-Li; Hu, Xiang-Dan; Xiao, Jing; Yu, Dong-Qing

    2018-02-01

    This study aimed to investigate the possible sensitivity of Astragalus polysaccharides, in order to improve the chemosensitivity of cervical cancer HeLa cells to cisplatin by regulating the cell autophagy, and explore its possible mechanism. In this study, HeLa cells were divided into control group, cisplatin group, Astragalus polysaccharide group, and Astragalus polysaccharide combined with cisplatin group. MTT assay was used to detect the proliferation of cervical cancer HeLa cells. Flow cytometry was used to detect the apoptosis and cycle of HeLa cells in each experimental group. RT-PCR was used to detect the mRNA expression of autophagy-related proteins beclin1, LC3Ⅱ and p62. The expression levels of autophagy-related proteins beclin1, LC3Ⅱ, LC3Ⅰ and p62 were detected by WB method. MTT results showed that compared with the control group, the proliferation of HeLa cells was significantly inhibited in each administration group( P HeLa cells was significantly increased( P HeLa cells to cisplatin by regulating the cell autophagy. Its possible mechanism of action is correlated with the up-regulation of autophagy-related proteins beclin1, the promote the conversion from LC3Ⅰ to LC3Ⅱ, the down-regulation of labeled protein p62, and the enhancement of HeLa cell autophagic activity, thereby increasing the sensitivity of HeLa cells to cisplatin chemotherapy. Copyright© by the Chinese Pharmaceutical Association.

  15. Effect of low dose radiation on cell cycle and expression of its related proteins of HCT-8 cells

    International Nuclear Information System (INIS)

    Xu Ying; Ma Kewei; Li Wei; Wang Guanjun

    2009-01-01

    Objective: To study the effects of low dose radiation (LDR) on cell cycle and the expression of its related proteins of HCT-8 cells and provide theoretical basis for clinical application of LDR. Methods: Human colon carcinoma cells (HCT-8) cultivated in vitro were divided into seven groups: sham radiation group (0 mGy), LDR groups (25, 50, 75, 100 and 200 mGy) and high dose radiation group (1000 mGy). The proliferation rate was detected with the method of cell count and MTT, the ratios of G 0 /G 1 , S, G 2 /M in cell cycle were determined with flow cytometry after LDR, The cell cycle and expressions of related signal proteins were analyzed with protein assay system. Results: The results of cell count and MTT showed that there were no significant differences of proliferation rate of HCT-8 cells between 25, 50, 75, 100, 200 mGy LDR groups and sham radiation group (P>0.05); compared with high dose radiation group, there were significant differences (P 0 /G 1 phase of HCT-8 cells increased (P>0.05), the ratio of S phase decreased significantly (P 2 /M phase increased obviously (P 0 /G 1 , S, and G 2 /M phases of HCT-8 cells 48 h after radiation compared with sham radiation group (P>0.05). The protein assay result indicated that the expressions of AKt, PCNA, p27, CDK2, cyclin E, EGFR, ERK1/2, p-ERK, p-GSK-32/β in HCT-8 cells after LDR decreased compared with sham radiation group. Conclusion: LDR has no stimulating effect on HCT-8 cells. However, to some extent LDR suppress the expressions of some proteins related to proliferation and cell cycle. (authors)

  16. High-mobility group box 1 released by autophagic cancer-associated fibroblasts maintains the stemness of luminal breast cancer cells.

    Science.gov (United States)

    Zhao, Xi-Long; Lin, Yong; Jiang, Jun; Tang, Zhuo; Yang, Shuai; Lu, Lu; Liang, Yan; Liu, Xue; Tan, Jiao; Hu, Xu-Gang; Niu, Qin; Fu, Wen-Juan; Yan, Ze-Xuan; Guo, De-Yu; Ping, Yi-Fang; Wang, Ji Ming; Zhang, Xia; Kung, Hsiang-Fu; Bian, Xiu-Wu; Yao, Xiao-Hong

    2017-11-01

    Cancer stem cells/cancer-initiating cells (CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer-associated fibroblasts (CAFs) are major components of the niche of breast cancer-initiating cells (BCICs), and their interactions may profoundly affect breast cancer progression. Autophagy has been considered to be a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance has not been determined. In this study, we found that the presence of CAFs containing high levels of microtubule-associated protein 1 light chain 3 (LC3II), a marker of autophagosomes, was associated with more aggressive luminal human breast cancer. CAFs in human luminal breast cancer tissues with high autophagy activity enriched BCICs with increased tumourigenicity. Mechanistically, autophagic CAFs released high-mobility group box 1 (HMGB1), which activated its receptor, Toll-like receptor (TLR) 4, expressed by luminal breast cancer cells, to enhance their stemness and tumourigenicity. Furthermore, immunohistochemistry of 180 luminal breast cancers revealed that high LC3II/TLR4 levels predicted an increased relapse rate and a poorer prognosis. Our findings demonstrate that autophagic CAFs play a critical role in promoting the progression of luminal breast cancer through an HMGB1-TLR4 axis, and that both autophagy in CAFs and TLR4 on breast cancer cells constitute potential therapeutic targets. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  17. Innate Lymphoid Cell Biology: Lessons Learnt from Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Yuhao Jiao

    2016-10-01

    Full Text Available Group 1 innate lymphoid cells (ILC comprise the natural killer (NK cells and ILC1 which reside within peripheral tissues. Several different ILC1 subsets have recently been characterised, however no unique markers to define these subsets have been identified. Whether ILC1 and NK cells are in fact distinct lineages, or alternately exhibit transitional molecular programs, that allow them to adapt to different tissue niches remains an open question. NK cells are the prototypic member of the Group 1 ILC and have been historically assigned the functions of what now appears to be a multi-subset family that are distributed throughout the body. This raises the question of whether each of these populations mediate distinct functions during infection and tumour immunosurveillance. Here, we review the diversity in the Group 1 ILC subsets with regards to their transcriptional regulation, localization, mobility and receptor expression and highlight the challenges in unraveling the individual functions of these different populations of cells.

  18. Comparison of closed-cell and hybrid-cell stent designs in carotid artery stenting: clinical and procedural outcomes

    Directory of Open Access Journals (Sweden)

    Ersan TatlI

    2017-05-01

    Full Text Available Introduction: Carotid artery stenting (CAS is a promising alternative to surgery in high-risk patients. However, the impact of stent cell design on outcomes in CAS is a matter of continued debate. Aim : To compare the periprocedural and clinical outcomes of different stent designs for CAS with distal protection devices. Material and methods : All CAS procedures with both closed- and hybrid-cell stents performed at our institution between February 2010 and December 2015 were analyzed retrospectively. Adverse events were defined as death, major stroke, minor stroke, transient ischemic attack and myocardial infarction. Periprocedural and 30-day adverse events and internal carotid artery (ICA vasospasm rates were compared between the closed-cell and hybrid-cell stent groups. Results : The study included 234 patients comprising 146 patients with a closed-cell stent (Xact stent, Abbott Vascular (mean age: 68.5 ±8.6; 67.1% male and 88 patients with a hybrid-cell stent (Cristallo Ideale, Medtronic (mean age: 67.2 ±12.8; 68.2% male. There was no significant difference between the groups with respect to periprocedural or 30-day adverse event rates. While there was no difference in terms of tortuosity index between the groups, there was a higher procedural ICA vasospasm rate in the closed-cell stent group (35 patients, 23% compared with the hybrid-cell stent group (10 patients, 11% (p = 0.017. Conclusions : The results of this study showed no significant difference in the clinical adverse event rates after CAS between the closed-cell stent group and the hybrid-cell stent group. However, procedural ICA vasospasm was more common in the closed-cell stent group.

  19. Radiosensitization of C225 on human non-small cell lung cancer cell line H-520

    International Nuclear Information System (INIS)

    Zhang Yingdong; Wang Junjie; Liu Feng; Zhao Yong

    2008-01-01

    Objective: To investigate the efficacy of C225 (cetuximab), a chimeric human-mouse anti-epithelial growth factor receptor monoclonal antibody, combined with 60 Co gamma irradiation against human non-small cell lung cancer cell line H-520. Methods: H-520 cells were treated either with different dose of 60 Co irradiation (1,2,4,6,8 and 10 Gy)alone or together with C225 (100 nmol/L). Colony forming capacity was determined to create the survival curve 10 days after the treatment. Cells in different groups were harvested 72 hours after irradiation for apoptosis analysis or 48 hours after irradiation for cell cycle analysis by flow cytometry assay. Results: The clone number in combinational treatment group was less than that in irradiation only group, which suggested that the cell survival rate in the combinational treatment group was significantly decreased comparing with irradiation only group (F=6.36, P O + G 1 phases for C225 treatment, in G 2 + M phases for 60 Co irradiation, and in both G 0 + G 1 and G 2 + M phases for C225 in combination with 60 Co irradiation. Conclusions: C225 has radiosensitizing effects on H-520 cells, which may through the enhancement of 60 Co irradiation-induced cell death and cell cycle arrest. This study provides a supportive evidence for clinical treatment in non-small cell lung cancer. (authors)

  20. With the Radiobiology Group

    CERN Multimedia

    CERN PhotoLab

    1980-01-01

    The Radiobiology Group carries out experiments to study the effect of radiation on living cells. The photo shows the apparatus for growing broad beans which have been irradiated by 250 GeV protons. The roots are immersed in a tank of running water (CERN Weekly Bulletin 26 January 1981 and Annual Report 1980 p. 160). Karen Panman, Marilena Streit-Bianchi, Roger Paris.

  1. The Effects of β-Adrenergic Blockade on the Degrading Effects of Eye Movements on Negative Autobiographical Memories.

    Science.gov (United States)

    Littel, Marianne; Kenemans, J Leon; Baas, Johanna M P; Logemann, H N Alexander; Rijken, Nellie; Remijn, Malou; Hassink, Rutger J; Engelhard, Iris M; van den Hout, Marcel A

    2017-10-15

    Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. During EMDR, patients make horizontal eye movements (EMs) while simultaneously recalling a traumatic memory, which renders the memory less vivid and emotional when it is later recalled again. Recalling highly emotional autobiographical memories enhances noradrenergic neurotransmission. Noradrenaline (NA) strengthens memory (re)consolidation. However, memories become less vivid after recall+EMs. Therefore, NA might either play no significant role or serve to strengthen memories that are degraded by EMs. The present study was designed to test the latter hypothesis. We predicted that blocking NA would abolish the memory degrading effects of EMs. Fifty-six healthy participants selected three negative autobiographical memories. One was then recalled while making EMs, one was recalled without EMs, and one was not recalled. Vividness and emotionality of the memories as well as heart rate and skin conductance level during memory retrieval were measured before, directly after, and 24 hours after the EM task. Before the task, participants received a placebo or the noradrenergic β-receptor blocker propranolol (40 mg). There were no effects of EMs on memory emotionality or psychophysiological measures in the propranolol and placebo groups. However, in the placebo group, but not in the propranolol group, memory vividness significantly decreased from pretest to posttest and follow-up after recall+EMs relative to the control conditions. Blocking NA abolished the effects of EMs on the vividness of emotional memories, indicating that NA is crucial for EMDR effectiveness and possibly strengthens the reconsolidation of the degraded memory. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Molecular genotyping of ABO blood groups in some population groups from India.

    Science.gov (United States)

    Ray, Sabita; Gorakshakar, Ajit C; Vasantha, K; Nadkarni, Anita; Italia, Yazdi; Ghosh, Kanjaksha

    2014-01-01

    Indian population is characterized by the presence of various castes and tribal groups. Various genetic polymorphisms have been used to differentiate among these groups. Amongst these, the ABO blood group system has been extensively studied. There is no information on molecular genotyping of ABO blood groups from India. Therefore, the main objective of this study was to characterize the common A, B and O alleles by molecular analysis in some Indian population groups. One hundred samples from the mixed population from Mumbai, 101 samples from the Dhodia tribe and 100 samples from the Parsi community were included in this study. Initially, the samples were phenotyped by standard serologic techniques. PCR followed by single strand conformational polymorphsim (SSCP) was used for molecular ABO genotyping. Samples showing atypical SSCP patterns were further analysed by DNA sequencing to characterize rare alleles. Seven common ABO alleles with 19 different genotypes were found in the mixed population. The Dhodias showed 12 different ABO genotypes and the Parsis revealed 15 different ABO genotypes with six common ABO alleles identified in each of them. Two rare alleles were also identified. This study reports the distribution of molecular genotypes of ABO alleles among some population groups from India. Considering the extremely heterogeneous nature of the Indian population, in terms of various genotype markers like blood groups, red cell enzymes, etc., many more ABO alleles are likely to be encountered.

  3. DNA-cell conjugates

    Science.gov (United States)

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2016-05-03

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  4. DNA-cell conjugates

    Science.gov (United States)

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2018-05-15

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  5. Blood group genotyping: from patient to high-throughput donor screening.

    Science.gov (United States)

    Veldhuisen, B; van der Schoot, C E; de Haas, M

    2009-10-01

    Blood group antigens, present on the cell membrane of red blood cells and platelets, can be defined either serologically or predicted based on the genotypes of genes encoding for blood group antigens. At present, the molecular basis of many antigens of the 30 blood group systems and 17 human platelet antigens is known. In many laboratories, blood group genotyping assays are routinely used for diagnostics in cases where patient red cells cannot be used for serological typing due to the presence of auto-antibodies or after recent transfusions. In addition, DNA genotyping is used to support (un)-expected serological findings. Fetal genotyping is routinely performed when there is a risk of alloimmune-mediated red cell or platelet destruction. In case of patient blood group antigen typing, it is important that a genotyping result is quickly available to support the selection of donor blood, and high-throughput of the genotyping method is not a prerequisite. In addition, genotyping of blood donors will be extremely useful to obtain donor blood with rare phenotypes, for example lacking a high-frequency antigen, and to obtain a fully typed donor database to be used for a better matching between recipient and donor to prevent adverse transfusion reactions. Serological typing of large cohorts of donors is a labour-intensive and expensive exercise and hampered by the lack of sufficient amounts of approved typing reagents for all blood group systems of interest. Currently, high-throughput genotyping based on DNA micro-arrays is a very feasible method to obtain a large pool of well-typed blood donors. Several systems for high-throughput blood group genotyping are developed and will be discussed in this review.

  6. A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells

    DEFF Research Database (Denmark)

    Claessens, Antoine; Adams, Yvonne; Ghumra, Ashfaq

    2012-01-01

    Cerebral malaria is the most deadly manifestation of infection with Plasmodium falciparum. The pathology of cerebral malaria is characterized by the accumulation of infected erythrocytes (IEs) in the microvasculature of the brain caused by parasite adhesins on the surface of IEs binding to human...... receptors on microvascular endothelial cells. The parasite and host molecules involved in this interaction are unknown. We selected three P. falciparum strains (HB3, 3D7, and IT/FCR3) for binding to a human brain endothelial cell line (HBEC-5i). The whole transcriptome of isogenic pairs of selected.......029) but not by antibodies from controls with uncomplicated malaria (Mann-Whitney test, P = 0.58). This work describes a binding phenotype for virulence-associated group A P. falciparum erythrocyte membrane protein 1 variants and identifies targets for interventions to treat or prevent cerebral malaria....

  7. The roles of Sertoli cells in fate determinations of spermatogonial stem cells

    Directory of Open Access Journals (Sweden)

    Maryam Khanehzad

    2016-03-01

    Full Text Available Background: Spermatogenesis is a complex and highly organized process of proliferation and differentiation of spermatogonial stem cells. Spermatogonial stem cells (SSCs as a unique stem cell have the potential to self-renewal, differentiation and transmit genetic information to the next generation and play a vital role in maintaining fertility. Sertoli cells as the only somatic cells within the seminiferous epithelium play central roles in the formation of niche and balance between self-renewal and differentiation by secrete many growth factors. Given the importance and widespread use of SSCs, particularly in the treatment of infertility, the aim of this study was to create an optimal environment for the proliferation of SSCs. So we decided to study of undifferentiated (ID4 and differentiated (c-Kit gene expression in SSCs followed by co-culture with Sertoli cells for a one-month. Methods: This experimental study was conducted from November 2013 to December 2014 in Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, on immature NMRI mouse (6-3 days old. Initially, Sertoli cells and SSCs were isolated from neonates mouse testes during the two-step enzymatic digestion characteristics Sertoli cells with vimentin marker and SSCs with promyelocytic leukemia zinc-finger (PLZF marker were confirmed. Then SSCs were cultured in two groups: co-culture with Sertoli and without co-culture (control. Undifferentiated (ID4 and differentiation (c-Kit gene expression were evaluated by Real-time PCR technique. Results: Spermatogonial stem cells purity was obtained 66.91% by flow cytometry. The relative expression levels of gene ID4 in co-culture group at the end of each week, compared to the control group showed a significant increase (P<0.05. While the expression of this gene significantly decreased in each group over time (P<0.05. The results of the comparison of the relative expression of c-Kit gene in co-culture group are

  8. Comparison of Mast Cells and Inflammatory Cells within Periapical Lesions and Comparison of Degranulated Mast Cells Between Fibrous and Inflamed Area in Radicular Cysts: An Immunohistochemical Study.

    Science.gov (United States)

    Shiromany, Aseem; Sood, Rahul; Akifuddin, Syed; Sidhu, Gagandeep Kaur; Khan, Nadia; Singla, Kapil

    2014-12-01

    The role of mast cells as the key effector of allergic inflammation, anaphylactic inflammatory reactions and in the pathogenesis of chronic inflammation, is well-known. The present study is adopted to compare mast cells and inflammatory cells within periapical granuloma and cysts and localize the mast cells and quantify their number in the periapical cysts so as to propose a role of mast cells in the pathogenesis of this lesion. Biopsy specimens of 30 periapical lesions were stained with hematoxylin-eosin, and immunohistochemical Mast Cell Tryptase from Bio SB (IHC detection system kit) antibody. The tryptase positive mast cells and mononuclear inflammatory cells were counted in 10 consecutive high power fields (100X) using the binocular microscope from Motic attached to a computer with Motic Advanced Images 3.2 software. Comparative microscopic analysis indicated that periapical cyst shows more percentage of mast cells and less percentage of inflammatory cell than periapical granuloma (comparison of mean and standard deviation of total number of mast cells and inflammatory cells, mast cells 3.15±1.39 in the granuloma group and 4.43±1.91in the cyst group, inflammatory cells, 67.11±1.2 in the granuloma group and 52.66±0.8 in the cyst group). Numerous degranulated mast cells were observed in the fibrous wall than the inflammatory infiltrate of the periapical cysts. The mean and standard deviation of degranulated mast cells between the inflammatory and fibrous zone within the cyst group, being 0.95±1.10 and1.68±1.34 respectively. The values varied significantly between the two zones. The number of inflammatory cells in the cyst group is less than periapical granuloma and total number of mast cells in the cyst group is more as compared to periapical granuloma. The degranulated cells were quantified and they were higher in the fibrous area of the cysts than the inflammatory zone. This study could support the fact that the various mediators released on

  9. Serotonin noradrenaline reuptake inhibitors: New hope for the treatment of chronic pain.

    Science.gov (United States)

    Delgado, Pedro L

    2006-01-01

    Depression and painful symptoms occur frequently together. Over 75% of depressed patients report painful symptoms such as headache, stomach pain, neck and back pain as well as non-specific generalized pain. In addition, World Health Organization data have shown that primary care patients with chronic pain have a four fold greater risk of becoming depressed than pain-free patients. Increasingly, pain is considered as an integral symptom of depression and there evidence to suggest that pain and depression may arise from a common neurobiological dysfunction. Serotonergic cell bodies, in the raphe nucleus, and noradrenergic cell bodies in the locus coeruleus send projections to various parts of the brain, where they are involved in the control of mood, movement, cognitive functioning and emotions. In addition both serotonergic and noradrenergic neurons project to the spinal cord. These descending pathways serve to inhibit input from the intestines, skeletal muscles and other sensory inputs. Usually, these inhibitory effects are modest, but in times of stress, in the interest of the survival of the individual, they can completely inhibit the input from painful stimuli. A dysfunction of the serotonergic and noradrenergic neurons can thus affect both the ascending and descending pathways resulting in the psychological symptoms of depression and somatic pain symptoms such as chronic pain, fibromyalgia, non-cardiac chest pain, or irritable bowel syndrome. In view of this, it is not surprising that tricyclic antidepressants have been a standard treatment of chronic pain for many years. In contrast and in spite of their improved tolerance, selective serotonin reuptake inhibitors do not appear to be particularly effective in the treatment of pain. Recently, a number of open and controlled trials with selective serotonin and noradrenaline reuptake inhibitors such as venlafaxine, milnacipran and duloxetine, suggest that these compounds may be more effective in relieving pain

  10. Neuromelanin marks the spot: identifying a locus coeruleus biomarker of cognitive reserve in healthy aging.

    Science.gov (United States)

    Clewett, David V; Lee, Tae-Ho; Greening, Steven; Ponzio, Allison; Margalit, Eshed; Mather, Mara

    2016-01-01

    Leading a mentally stimulating life may build up a reserve of neural and mental resources that preserve cognitive abilities in late life. Recent autopsy evidence links neuronal density in the locus coeruleus (LC), the brain's main source of norepinephrine, to slower cognitive decline before death, inspiring the idea that the noradrenergic system is a key component of reserve (Robertson, I. H. 2013. A noradrenergic theory of cognitive reserve: implications for Alzheimer's disease. Neurobiol. Aging. 34, 298-308). Here, we tested this hypothesis using neuromelanin-sensitive magnetic resonance imaging to visualize and measure LC signal intensity in healthy younger and older adults. Established proxies of reserve, including education, occupational attainment, and verbal intelligence, were linearly correlated with LC signal intensity in both age groups. Results indicated that LC signal intensity was significantly higher in older than younger adults and significantly lower in women than in men. Consistent with the LC-reserve hypothesis, both verbal intelligence and a composite reserve score were positively associated with LC signal intensity in older adults. LC signal intensity was also more strongly associated with attentional shifting ability in older adults with lower cognitive reserve. Together these findings link in vivo estimates of LC neuromelanin signal intensity to cognitive reserve in normal aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Effect of growth at low pH on the cell surface properties of a typical strain of Lactobacillus casei group.

    Science.gov (United States)

    Hossein Nezhad, M; Stenzel, Dj; Britz, Ml

    2010-09-01

    Although members of the Lactobacillus casei group are known to survive under acidic conditions, the underlying mechanisms of growth at acidic condition and the impact of low pH on the relative level of protein expression at the cell surface remain poorly studied. After confirming the taxonomy of L. casei strain GCRL 12 which was originally isolated from cheese and confirmed by 16S rRNA sequence analysis, the impact of acidic pH on growth rate was determined. Late log-phase cells cultured at pH 4.0 showed obvious changes in Gram staining properties while transmission electron microscopy analysis revealed evidence of structural distortions of the cell surface relative to the controls cultured at pH 6.5. When comparing cytosolic or whole cell preparations on SDS-PAGE, few changes in protein profiles were observed under the two growth conditions. However, analysis of surface protein extracted by 5M LiCl demonstrated changes in the proportions of proteins present in the molecular weight range of 10 to 80 kDa, with some proteins more dominant at pH 6.5 and other at pH 4. These data suggest that surface proteins of this strain are associated with growth and survival at low pH. The function of these proteins is subject to further investigation.

  12. ABO blood groups and oral premalignancies: A clinical study in selected Indian population.

    Science.gov (United States)

    Bhateja, S; Arora, G

    2014-01-01

    Background: The ABO blood group antigens are present on the surface of red blood cells and various epithelial cells. As the majority of human cancers are derived from epithelial cells, changes in blood group antigens constitute an important aspect of human cancers. The aim of the study was to establish clinical usefulness of ABO blood group as a predisposing factor in early diagnosis and management of patients with oral precancerous lesions/conditions. Materials and Methods: The study sample consisted of 50 control and 50 oral precancer (25 leukoplakia and 25 Oral Submucous Fibrosis) confirmed by histopathologic examination. All samples were subjected to blood group testing and their prevalence was compared by Z-test using STATA version 8. Results: The "A" blood group was prevalent among the precancerous group. Significant differences on prevalences of blood groups were found (P blood group. Conclusion: Blood group type should be considered along with other risk factors to understand the individual patient's risk and further studies in larger samples with inclusion of Rh factor is needed to elucidate the relationship with ABO blood group types.

  13. Evaluating the Role of Immunological Cells (Tissue Eosinophils and Mast Cells) in Progression of Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Saxena, S; Singh, A; Singh, P; Sundaragiri, K S; Sankhla, B; Bhargava, A

    2018-04-01

    Mast cells and eosinophils are increased in oral squamous cell carcinoma. The significance of such an association has been variably thought to be either a potential diagnostic tool for stromal invasion or as a prognostic indicator. The aim of the study was to study the mast cells and eosinophils between normal oral mucosa, leukoplakia and oral squamous cell carcinoma and to study the significance of mast cells in the progression of the lesion. A retrospective study was done on archival tissue received from January 2015 to December 2015, in the Department of Oral Pathology, RUHS College of Dental Sciences, Jaipur, Rajasthan, India. Seventy (70) cases were studied (30 cases each of leukoplakia and carcinoma and 10 cases of control group), sections were stained with toluidine blue solution to reveal mast cells. Eosinophils were studied in Haematoxylin & Eosin stained sections. Mast cell density significantly increased from: normal mucosa to oral leukoplakia to carcinoma, suggesting a role of the mast cells in the development of these lesions. The higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion. The assessment of these could become, in the future, useful for therapeutic approaches in this subset of the patient.

  14. Protein covalent immobilization via its scarce thiol versus abundant amine groups: Effect on orientation, cell binding domain exposure and conformational lability.

    Science.gov (United States)

    Ba, O M; Hindie, M; Marmey, P; Gallet, O; Anselme, K; Ponche, A; Duncan, A C

    2015-10-01

    Quantity, orientation, conformation and covalent linkage of naturally cell adhesive proteins adsorbed or covalently linked to a surface, are known to influence the preservation of their subsequent long term cell adhesion properties and bioactivity. In the present work, we explore two different strategies for the covalent linking of plasma fibronectin (pFN) - used as a cell adhesive model protein, onto a polystyrene (PS) surface. One is aimed at tethering the protein to the surface in a semi-oriented fashion (via one of the 4 free thiol reactive groups on the protein) with a heterofunctional coupling agent (SSMPB method). The other aims to immobilize the protein in a more random fashion by reaction between the abundant pendant primary amine bearing amino acids of the pFN and activated carboxylic surface functions obtained after glutaric anhydride surface treatment (GA method). The overall goal will be to verify the hypothesis of a correlation between covalent immobilization of a model cell adhesive protein to a PS surface in a semi-oriented configuration (versus randomly oriented) with promotion of enhanced exposure of the protein's cell binding domain. This in turn would lead to enhanced cell adhesion. Ideally the goal is to elaborate substrates exhibiting a long term stable protein monolayer with preserved cell adhesive properties and bioactivity for biomaterial and/or cell adhesion commercial plate applications. However, the initial restrictive objective of this paper is to first quantitatively and qualitatively investigate the reversibly (merely adsorbed) versus covalently irreversibly bound protein to the surface after the immobilization procedure. Although immobilized surface amounts were similar (close to the monolayer range) for all immobilization approaches, covalent grafting showed improved retention and stronger "tethering" of the pFN protein to the surface (roughly 40%) after SDS rinsing compared to that for mere adsorption (0%) suggesting an added value

  15. Catechol Groups Enable Reactive Oxygen Species Scavenging-Mediated Suppression of PKD-NFkappaB-IL-8 Signaling Pathway by Chlorogenic and Caffeic Acids in Human Intestinal Cells

    Directory of Open Access Journals (Sweden)

    Hee Soon Shin

    2017-02-01

    Full Text Available Chlorogenic acid (CHA and caffeic acid (CA are phenolic compounds found in coffee, which inhibit oxidative stress-induced interleukin (IL-8 production in intestinal epithelial cells, thereby suppressing serious cellular injury and inflammatory intestinal diseases. Therefore, we investigated the anti-inflammatory mechanism of CHA and CA, both of which inhibited hydrogen peroxide (H2O2-induced IL-8 transcriptional activity. They also significantly suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB transcriptional activity, nuclear translocation of the p65 subunit, and phosphorylation of IκB kinase (IKK. Additionally, upstream of IKK, protein kinase D (PKD was also suppressed. Finally, we found that they scavenged H2O2-induced reactive oxygen species (ROS and the functional moiety responsible for the anti-inflammatory effects of CHA and CA was the catechol group. Therefore, we conclude that the presence of catechol groups in CHA and CA allows scavenging of intracellular ROS, thereby inhibiting H2O2-induced IL-8 production via suppression of PKD-NF-κB signaling in human intestinal epithelial cells.

  16. Impact of a Low CD34+ Cell Dose on Allogeneic Peripheral Blood Stem Cell Transplantation.

    Science.gov (United States)

    Yamamoto, Chihiro; Ogawa, Hiroyasu; Fukuda, Takahiro; Igarashi, Aiko; Okumura, Hirokazu; Uchida, Naoyuki; Hidaka, Michihiro; Nakamae, Hirohisa; Matsuoka, Ken-Ichi; Eto, Tetsuya; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu

    2018-04-01

    Although the CD34 + cell dose in allogeneic peripheral blood stem cell transplantation (PBSCT) is considered to be associated with transplantation outcomes, a lower acceptable threshold has not been defined. We retrospectively analyzed 2919 adult patients with hematologic malignancies who underwent related PBSCT in Japan between 2001 and 2014. According to the number of CD34 + cells in the graft, we categorized 2494 patients in the standard group (2 to 5 × 10 6 cells/kg), 377 patient in the low group (1 to 2 × 10 6 cells/kg), and 48 patients in the very low group (<1 × 10 6 cells/kg). Compared with the standard group, the low and very low groups showed delayed neutrophil recovery (93.8%, 89.5%, and 78.3%, respectively at day +28; P < .001) and platelet recovery (69.3%, 53.0%, and 45.5%, respectively at day +28; P < .001). The 2-year overall survival (OS) in the 3 groups was 45.5%, 45.3%, and 29.8%, respectively, with inferior survival in the very low group. However, a higher percentage of high-risk patients may account for the inferior survival in the very low group, and no significant difference in OS was found in a multivariate analysis. There were no differences in relapse, nonrelapse mortality, or the development of graft-versus-host disease among the 3 groups. In conclusion, allogeneic PBSCT with low CD34 + cell doses of 1 to 2 × 10 6 cells/kg gives acceptable results, whereas further investigations are needed to evaluate the effects of lower doses of <1 × 10 6 cells/kg owing to the smaller number and the higher percentage of patients with adverse prognostic factors in this cohort. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  17. Cockayne syndrome group B (Csb) and group a (Csa) deficiencies predispose to hearing loss and cochlear hair cell degeneration in mice.

    Science.gov (United States)

    Nagtegaal, A Paul; Rainey, Robert N; van der Pluijm, Ingrid; Brandt, Renata M C; van der Horst, Gijsbertus T J; Borst, J Gerard G; Segil, Neil

    2015-03-11

    Sensory hair cells in the cochlea, like most neuronal populations that are postmitotic, terminally differentiated, and non-regenerating, depend on robust mechanisms of self-renewal for lifelong survival. We report that hair cell homeostasis requires a specific sub-branch of the DNA damage nucleotide excision repair pathway, termed transcription-coupled repair (TCR). Cockayne syndrome (CS), caused by defects in TCR, is a rare DNA repair disorder with a broad clinical spectrum that includes sensorineural hearing loss. We tested hearing and analyzed the cellular integrity of the organ of Corti in two mouse models of this disease with mutations in the Csb gene (CSB(m/m) mice) and Csa gene (Csa(-/-) mice), respectively. Csb(m/m) and Csa(-/-) mice manifested progressive hearing loss, as measured by an increase in auditory brainstem response thresholds. In contrast to wild-type mice, mutant mice showed reduced or absent otoacoustic emissions, suggesting cochlear outer hair cell impairment. Hearing loss in Csb(m/m) and Csa(-/-) mice correlated with progressive hair cell loss in the base of the organ of Corti, starting between 6 and 13 weeks of age, which increased by 16 weeks of age in a basal-to-apical gradient, with outer hair cells more severely affected than inner hair cells. Our data indicate that the hearing loss observed in CS patients is reproduced in mouse models of this disease. We hypothesize that accumulating DNA damage, secondary to the loss of TCR, contributes to susceptibility to hearing loss. Copyright © 2015 the authors 0270-6474/15/354280-07$15.00/0.

  18. Retinol-induced changes in the phosphorylation levels of histones and high mobility group proteins from Sertoli cells

    Directory of Open Access Journals (Sweden)

    Moreira J.C.F.

    2000-01-01

    Full Text Available Chromatin proteins play a role in the organization and functions of DNA. Covalent modifications of nuclear proteins modulate their interactions with DNA sequences and are probably one of the multiple factors involved in the process of switch on/off transcriptionally active regions of DNA. Histones and high mobility group proteins (HMG are subject to many covalent modifications that may modulate their capacity to bind to DNA. We investigated the changes induced in the phosphorylation pattern of cultured Wistar rat Sertoli cell histones and high mobility group protein subfamilies exposed to 7 µM retinol for up to 48 h. In each experiment, 6 h before the end of the retinol treatment each culture flask received 370 KBq/ml [32P]-phosphate. The histone and HMGs were isolated as previously described [Moreira et al. Medical Science Research (1994 22: 783-784]. The total protein obtained by either method was quantified and electrophoresed as described by Spiker [Analytical Biochemistry (1980 108: 263-265]. The gels were stained with Coomassie brilliant blue R-250 and the stained bands were cut and dissolved in 0.5 ml 30% H2O2 at 60oC for 12 h. The vials were chilled and 5.0 ml scintillation liquid was added. The radioactivity in each vial was determined with a liquid scintillation counter. Retinol treatment significantly changed the pattern of each subfamily of histone and high mobility group proteins.

  19. Card9-dependent IL-1β regulates IL-22 production from group 3 innate lymphoid cells and promotes colitis-associated cancer.

    Science.gov (United States)

    Bergmann, Hanna; Roth, Susanne; Pechloff, Konstanze; Kiss, Elina A; Kuhn, Sabine; Heikenwälder, Mathias; Diefenbach, Andreas; Greten, Florian R; Ruland, Jürgen

    2017-08-01

    Inflammatory bowel diseases (IBD) are key risk factors for the development of colorectal cancer, but the mechanisms that link intestinal inflammation with carcinogenesis are insufficiently understood. Card9 is a myeloid cell-specific signaling protein that regulates inflammatory responses downstream of various pattern recognition receptors and which cooperates with the inflammasomes for IL-1β production. Because polymorphisms in Card9 were recurrently associated with human IBD, we investigated the function of Card9 in a colitis-associated cancer (CAC) model. Card9 -/- mice develop smaller, less proliferative and less dysplastic tumors compared to their littermates and in the regenerating mucosa we detected dramatically impaired IL-1β generation and defective IL-1β controlled IL-22 production from group 3 innate lymphoid cells. Consistent with the key role of immune-derived IL-22 in activating STAT3 signaling during normal and pathological intestinal epithelial cell (IEC) proliferation, Card9 -/- mice also exhibit impaired tumor cell intrinsic STAT3 activation. Our results imply a Card9-controlled, ILC3-mediated mechanism regulating healthy and malignant IEC proliferation and demonstrates a role of Card9-mediated innate immunity in inflammation-associated carcinogenesis. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Effect of cotransplantation of hematopoietic stem cells and embryonic AGM stromal cells on hematopoietic reconstitution in mice after bone marrow transplantation

    International Nuclear Information System (INIS)

    Tao Si; Sun Hanying; Liu Wenli

    2007-01-01

    Objective: To explore the effects of cotransplantation of hematopoietic stem cells and stromal cells derived from aorta-gonad-mesonephros (AGM) region on hematopoietic reconstitution in mice after bone marrow transplantation (BMT). Methods: The typical mice model of syngeneic BMT was established and the mice were randomly divided into 4 groups: the control group, the BMT group, the group of cotransplantation of HSC with AGM stromal cells (the cotransplantation group) and the ligustrazine group (the LT group). On days 3, 7, 10, 14, 21 and 28 after BMT, the peripheral blood cells and bone marrow mononuclear cells (BMMNC) were counted, and histology changes of bone marrow were detected. Results: The levels of peripheral WBC, RBC, platelet, and BMMNC in the contransplantation group were significantly higher than those in the single BMT group and the LT group (P<0.05). Conclusions: Cotransplantation with AGM stromal cells could significantly promote hematopoietic reconstruction in mice after BMT. (authors)

  1. Preparation and characterization of micro-cell membrane chromatographic column with N-hydroxysuccinimide group-modified silica-based porous layer open tubular capillary.

    Science.gov (United States)

    Xu, Liang; Xu, Bei; Zhao, Zhi-Yu; Yang, Hui-Ping; Tang, Cheng; Dong, Lin-Yi; Liu, Kun; Fu, Li; Wang, Xian-Hua

    2017-09-22

    Cell membrane chromatography (CMC) is an effective tool in screening active compounds from natural products and studying membrane protein interactions. Nevertheless, it always consumes a large amount of cells (e.g. 10 7 -10 8 ) for column preparation. To overcome this, micro-CMC (mCMC), that employs a silica capillary as membrane carrier, was developed. However, both CMC and mCMC suffer from short column life span (e.g. 3days), mainly due to the falling-off of cellular membranes (CMs). This has greatly limited further application of CMC and mCMC, especially when the cells are hard to obtain. To solve this, N-hydroxysuccinimide (NHS)-modified silica-based porous layer open tubular capillary was first prepared for mCMC. The NHS groups can easily react with amino groups on CMs to form a stable covalent bond under a mild condition. So, CMs immobilized on the NHS-modified capillary are less likely to fall off. To verify this, SKBR3/mCMC (Her2 positive) and BALL1/mCMC (CD20 positive) columns were prepared. Two monoclonal antibody drugs, trastuzumab (anti-Her2) and rituximab (anti-CD20), were selected as analytes to characterize the columns. As a result, NHS-modified column for mCMC can afford higher chromatographic retention than non-modified column. Besides, the column life span was significantly improved to more than 16days for SKBR3/mCMC and 14days for BALL1/mCMC, while the compared column showed a sharp decline in retention factor in first 3days. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Evaluation of Hematopoietic Stem Cell Mobilization Rates with Early Plerixafor Administration for Adult Stem Cell Transplantation.

    Science.gov (United States)

    Stover, Jessica T; Shaw, J Ryan; Kuchibhatla, Maragatha; Horwitz, Mitchell E; Engemann, Ashley M

    2017-08-01

    The addition of plerixafor to high-dose colony-stimulating growth factor has been shown to improve stem cell mobilization rates in autologous transplant patients with multiple myeloma and non-Hodgkin lymphoma. This study evaluates the change in administration time of plerixafor to determine if cell mobilization rates are similar between the US Food and Drug Administration-approved administration time of 11 hours before apheresis and an earlier administration time of 16 hours before apheresis. Medical records of patients age ≥ 18 years undergoing autologous stem cell transplantation requiring the use of plerixafor after at least 4 days of granulocyte colony-stimulating factor therapy to complete stem cell mobilization from January 1, 2010 through September 30, 2014 were retrospectively reviewed. The primary outcome was CD34 + cell mobilization success rates when plerixafor was administered 11 ± 2 hours (standard administration group) compared with 16 ± 2 hours before cell apheresis (early administration group), as defined as collection of  ≥2 × 10 6 CD34 + cells/kg. Secondary outcomes included the number of plerixafor therapy days required to collect a total of ≥2 × 10 6 CD34 + cells/kg, the number of apheresis cycles required to achieve ≥2 × 10 6 CD34 + cells/kg, the median CD34 + cells/kg collected in each apheresis session, and the rates of reported adverse events that occurred in the standard administration time group compared with the early administration time group. Of the 197 patients included, 114 patients received plerixafor 11 ± 2 hours before apheresis and 83 patients received plerixafor 16 hours ± 2 hours before apheresis. Ninety-four percent of patients in the early administration group achieved successful stem cell mobilization compared with 81.6% in the standard administration group (P = .0111). The median number of plerixafor days to reach the collection goal of  ≥2 × 10 6 CD34 + cells/kg was 1 day for

  3. Identification of risk groups in patients with completely resected N1 non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Sawyer, T.E.; Bonner, J.A.; Gould, P.J.; Foote, R.L.; Deschamps, C.; Trastek, V.F.; Pairolero, P.C.; Allen, M.S.; Lange, C. M.; Li, H.

    1997-01-01

    Purpose: Although the potential benefits of radiation therapy and chemotherapy in the management of completely resected AJCC N1 non-small cell lung cancer are unknown, the majority of studies have failed to demonstrate a survival benefit with any neoadjuvant or adjuvant therapy. While it is possible that radiation therapy and chemotherapy are ineffective adjunctive therapies in this disease, it is also possible that previous studies have been diluted by the inclusion of patients at low risk for local recurrence and/or distant metastasis and therefore, this study was undertaken to assess these risks. Methods: From 1987 through 1990, 107 patients underwent complete resection of AJCC N1 non-small cell lung carcinoma and received no other treatment. These patients were the subject of a retrospective review to separate patients into high-, medium-, and low-risk groups with respect to freedom from local recurrence (FFLR), freedom from distant metastasis (FFDM), and overall survival (OS) utilizing a regression analysis of Cox and a regression tree analysis (Breiman LI et al, Wadsworth International Group, Belmont, CA 1984). Results: The 5-year rates of FFLR, FFDM, and OS were 62%, 53%, and 32% respectively. The following factors were assessed for potential relationships with FFLR, FFDM, and OS: status of the pre-operative bronchoscopy, type of surgery performed (segmentectomy/wedge resection vs. lobectomy vs. bilobectomy/pneumonectomy), number of involved N1 nodes, number of involved N1 stations, number of N1 nodes removed, number of N2 nodes removed, number of lung lobes involved, tumor grade, tumor histology (squamous vs non-squamous), AJCC T-stage, pathologic tumor size, and pathologic margin status. Regression analyses revealed that the factors independently associated with an improved outcome included a positive bronchoscopy (FFLR, p=.005), a greater number of N1 nodes dissected (FFDM, p=.02), and a lesser T-stage (OS, p=.01). Regression tree analyses were then

  4. C-cells in colloid goiter

    Directory of Open Access Journals (Sweden)

    Lima Marcus A.

    2003-01-01

    Full Text Available PURPOSE: The aim of this investigation was to quantitatively evaluate C-cells in colloid goiters, analyzing 36 thyroids that were obtained through thyroidectomy from 24 patients with goiter and 12 normal glands from adult patients without thyroid disease, which were used as the control group. MATERIAL AND METHODS: On average, 6 different thyroid areas were sampled and labeled by immunohistochemistry with a monoclonal anticalcitonin antibody, utilizing the avidin-biotin-peroxidase complex. C-cells were counted in fields measuring 1 square centimeter, and the mean number of cells per field was then calculated. Data were statistically analyzed using the Mann-Whitney test. RESULTS: In the colloid goiter group, the number of C-cells ranged from 0 to 23 per field, while in normal controls they ranged from 20 to 148 per field. CONCLUSIONS: These results demonstrate a significant decrease of C-cell number in the colloid goiter group compared with control group, indicating that the hyperplastic process is restricted to follicular cells, to the detriment of C-cells, which probably cease to receive trophic stimuli.

  5. Paper-based device for rapid typing of secondary human blood groups.

    Science.gov (United States)

    Li, Miaosi; Then, Whui Lyn; Li, Lizi; Shen, Wei

    2014-01-01

    We report the use of bioactive paper for typing of secondary human blood groups. Our recent work on using bioactive paper for human blood typing has led to the discovery of a new method for identifying haemagglutination of red blood cells. The primary human blood groups, i.e., ABO and RhD groups, have been successfully typed with this method. Clinically, however, many secondary blood groups can also cause fatal blood transfusion accidents, despite the fact that the haemagglutination reactions of secondary blood groups are generally weaker than those of the primary blood groups. We describe the design of a user-friendly sensor for rapid typing of secondary blood groups using bioactive paper. We also present mechanistic insights into interactions between secondary blood group antibodies and red blood cells obtained using confocal microscopy. Haemagglutination patterns under different conditions are revealed for optimization of the assay conditions.

  6. Polycomb group proteins in hematopoietic stem cell aging and malignancies

    NARCIS (Netherlands)

    Klauke, Karin; de Haan, Gerald

    Protection of the transcriptional "stemness" network is important to maintain a healthy hematopoietic stem cells (HSCs) compartment during the lifetime of the organism. Recent evidence shows that fundamental changes in the epigenetic status of HSCs might be one of the driving forces behind many

  7. Optical and Photovoltaic Properties of Thieno[3,2-b]thiophene-Based Push-Pull Organic Dyes with Different Anchoring Groups for Dye-Sensitized Solar Cells.

    Science.gov (United States)

    Fernandes, Sara S M; Castro, M Cidália R; Pereira, Ana Isabel; Mendes, Adélio; Serpa, Carlos; Pina, João; Justino, Licínia L G; Burrows, Hugh D; Raposo, M Manuela M

    2017-12-31

    The effect of anchoring groups on the optical and electrochemical properties of triphenylamine-thienothiophenes, and on the photovoltaic performance of DSSCs photosensitized with the prepared dyes, was studied using newly synthesized compounds with cyanoacetic acid or rhodanine-3-acetic acid groups. Precursor aldehydes were synthesized through Suzuki cross-coupling, whereas Knoevenagel condensation of these with 2-cyanoacetic acid or rhodanine-3-acetic acid afforded the final push-pull dyes. A comprehensive photophysical study was performed in solution and in the solid state. The femtosecond time-resolved transient absorption spectra for the synthesized dyes were obtained following photoexcitation in solution and for the dyes adsorbed to TiO 2 mesoporous films. Information on conformation, electronic structure, and electron distribution was obtained by density functional theory (DFT) and time-dependent DFT calculations. Triphenylamine-thienothiophene functionalized with a cyanoacetic acid anchoring group displayed the highest conversion efficiency (3.68%) as the dye sensitizer in nanocrystalline TiO 2 solar cells. Coadsorption studies were performed for this dye with the ruthenium-based N719 dye, and they showed dye power conversion efficiencies enhanced by 20-64%. The best cell performance obtained with the coadsorbed N719 and cyanoacetic dye showed an efficiency of 6.05%.

  8. Optical and Photovoltaic Properties of Thieno[3,2-b]thiophene-Based Push–Pull Organic Dyes with Different Anchoring Groups for Dye-Sensitized Solar Cells

    Science.gov (United States)

    2017-01-01

    The effect of anchoring groups on the optical and electrochemical properties of triphenylamine-thienothiophenes, and on the photovoltaic performance of DSSCs photosensitized with the prepared dyes, was studied using newly synthesized compounds with cyanoacetic acid or rhodanine-3-acetic acid groups. Precursor aldehydes were synthesized through Suzuki cross-coupling, whereas Knoevenagel condensation of these with 2-cyanoacetic acid or rhodanine-3-acetic acid afforded the final push–pull dyes. A comprehensive photophysical study was performed in solution and in the solid state. The femtosecond time-resolved transient absorption spectra for the synthesized dyes were obtained following photoexcitation in solution and for the dyes adsorbed to TiO2 mesoporous films. Information on conformation, electronic structure, and electron distribution was obtained by density functional theory (DFT) and time-dependent DFT calculations. Triphenylamine–thienothiophene functionalized with a cyanoacetic acid anchoring group displayed the highest conversion efficiency (3.68%) as the dye sensitizer in nanocrystalline TiO2 solar cells. Coadsorption studies were performed for this dye with the ruthenium-based N719 dye, and they showed dye power conversion efficiencies enhanced by 20–64%. The best cell performance obtained with the coadsorbed N719 and cyanoacetic dye showed an efficiency of 6.05%. PMID:29302638

  9. Distribution of phytoplankton groups within the deep chlorophyll maximum

    KAUST Repository

    Latasa, Mikel; Cabello, Ana Marí a; Moran, Xose Anxelu G.; Massana, Ramon; Scharek, Renate

    2016-01-01

    and optical and FISH microscopy. All groups presented minimum abundances at the surface and a maximum in the DCM layer. The cell distribution was not vertically symmetrical around the DCM peak and cells tended to accumulate in the upper part of the DCM layer

  10. Evaluation of royal jelly as an alternative to fetal bovine serum in cell culture using cell proliferation assays and live cell imaging.

    Science.gov (United States)

    Musa, Marahaini; Nasir, Nurul Fatihah Mohamad; Thirumulu, Kannan Ponnuraj

    2014-01-01

    Royal jelly is a nutritious substance produced by the young nurse bees and contains significant amounts of proteins which are important for cell growth and proliferation. The aim of this study was to evaluate the effect of royal jelly as an alternative to fetal bovine serum (FBS) in cell culture using cell proliferation assays and live cell imaging. MRC-5 cells were treated with various concentrations of royal jelly extract in MTT assay. The control groups were comprised of Alpha-Minimal Essential Medium (α-MEM) alone and α-MEM with 10% FBS. Subsequently, the cell proliferation was studied for 10 days using Alamar Blue assay and live cell imaging from 48 to 72 h. The population doubling time (PDT) was determined using trypan blue assay after live cell imaging. In MTT assay, 0.156 and 0.078 mg/ml of royal jelly produced higher cell viability compared to positive control group but were not significantly different (P > 0.05). In the Alamar Blue assay, 0.156 and 0.078 mg/ml of royal jelly produced greater percentage of reduction at day 3 even though no significant difference was found (P > 0.05). Based on live cell imaging, the PDT for positive, negative, 0.156 and 0.078 mg/ml of royal jelly groups were 29.09, 62.50, 41.67 and 41.67 h respectively. No significant difference was found in the PDT between all the groups (P > 0.05). Royal jelly does not exhibit similar ability like FBS to facilitate cell growth under the present test conditions.

  11. Identification of the Fanconi Anemia Complementation Group I Gene, FANCI

    Directory of Open Access Journals (Sweden)

    Josephine C. Dorsman

    2007-01-01

    Full Text Available To identify the gene underlying Fanconi anemia (FA complementation group I we studied informative FA-I families by a genome-wide linkage analysis, which resulted in 4 candidate regions together encompassing 351 genes. Candidates were selected via bioinformatics and data mining on the basis of their resemblance to other FA genes/proteins acting in the FA pathway, such as: degree of evolutionary conservation, presence of nuclear localization signals and pattern of tissue-dependent expression. We found a candidate, KIAA1794 on chromosome 15q25-26, to be mutated in 8 affected individuals previously assigned to complementation group I. Western blots of endogenous FANCI indicated that functionally active KIAA1794 protein is lacking in FA-I individuals. Knock-down of KIAA1794 expression by siRNA in HeLa cells caused excessive chromosomal breakage induced by mitomycin C, a hallmark of FA cells. Furthermore, phenotypic reversion of a patient-derived cell line was associated with a secondary genetic alteration at the KIAA1794 locus. These data add up to two conclusions. First, KIAA1794 is a FA gene. Second, this gene is identical to FANCI, since the patient cell lines found mutated in this study included the reference cell line for group I, EUFA592.

  12. Differential Internalization Rates and Postendocytic Sorting of the Norepinephrine and Dopamine Transporters Are Controlled by Structural Elements in the N Termini*

    Science.gov (United States)

    Vuorenpää, Anne; Jørgensen, Trine N.; Newman, Amy H.; Madsen, Kenneth L.; Scheinin, Mika

    2016-01-01

    The norepinephrine transporter (NET) mediates reuptake of synaptically released norepinephrine in central and peripheral noradrenergic neurons. The molecular processes governing availability of NET in the plasma membrane are poorly understood. Here we use the fluorescent cocaine analogue JHC 1-64, as well as several other approaches, to investigate the trafficking itinerary of NET in live noradrenergic neurons. Confocal imaging revealed extensive constitutive internalization of JHC 1-64-labeled NET in the neuronal somata, proximal extensions and presynaptic boutons. Phorbol 12-myristate 13-acetate increased intracellular accumulation of JHC 1-64-labeled NET and caused a parallel reduction in uptake capacity. Internalized NET strongly colocalized with the “long loop” recycling marker Rab11, whereas less overlap was seen with the “short loop” recycling marker Rab4 and the late endosomal marker Rab7. Moreover, mitigating Rab11 function by overexpression of dominant negative Rab11 impaired NET function. Sorting of NET to the Rab11 recycling compartment was further supported by confocal imaging and reversible biotinylation experiments in transfected differentiated CATH.a cells. In contrast to NET, the dopamine transporter displayed markedly less constitutive internalization and limited sorting to the Rab11 recycling compartment in the differentiated CATH.a cells. Exchange of domains between the two homologous transporters revealed that this difference was determined by non-conserved structural elements in the intracellular N terminus. We conclude that NET displays a distinct trafficking itinerary characterized by continuous shuffling between the plasma membrane and the Rab11 recycling compartment and that the functional integrity of the Rab11 compartment is critical for maintaining proper presynaptic NET function. PMID:26786096

  13. Preferential repair of nuclear matrix associated DNA in xeroderma pigmentosum complementation group C

    International Nuclear Information System (INIS)

    Mullenders, L.H.F.; Kesteren, A.C. van; Bussmann, C.J.M.; Zeeland, A.A. van; Natarajan, A.T.

    1984-01-01

    The distribution of ultraviolet-induced DNA repair patches in the genome of xeroderma pigmentosum cells of complementation group C was investigated by determining the molecular weight distribution of repair labeled DNA and prelabeled DNA in alkaline sucrose gradients after treatment with the dimer-specific endonuclease V of bacteriophage T 4 . The results suggest that DNA-repair synthesis in xeroderma pigmentosum cells of complementation group C occurs in localized regions of the genome. Analysis of the spatial distribution of ultraviolet-induced repair patches in DNA loops attached to the nuclear matrix revealed that in xeroderma pigmentosum cells of complementation group C repair patches are preferentially situated near the attachment sites of DNA loops at the nuclear matrix. In normal human fibroblasts the authors observed no enrichment of repair-labeled DNA at the nuclear matrix and repair patches appeared to be distributed randomly along the DNA loops. The enrichment of repair-labeled DNA at the nuclear matrix in xeroderma pigmentosum cells of complementation group C may indicate that the residual DNA-repair synthesis in these cells occurs preferentially in regions of the genome. (Auth.)

  14. Influence of platinum group metal-free catalyst synthesis on microbial fuel cell performance

    Science.gov (United States)

    Santoro, Carlo; Rojas-Carbonell, Santiago; Awais, Roxanne; Gokhale, Rohan; Kodali, Mounika; Serov, Alexey; Artyushkova, Kateryna; Atanassov, Plamen

    2018-01-01

    Platinum group metal-free (PGM-free) ORR catalysts from the Fe-N-C family were synthesized using sacrificial support method (SSM) technique. Six experimental steps were used during the synthesis: 1) mixing the precursor, the metal salt, and the silica template; 2) first pyrolysis in hydrogen rich atmosphere; 3) ball milling; 4) etching the silica template using harsh acids environment; 5) the second pyrolysis in ammonia rich atmosphere; 6) final ball milling. Three independent batches were fabricated following the same procedure. The effect of each synthetic parameters on the surface chemistry and the electrocatalytic performance in neutral media was studied. Rotating ring disk electrode (RRDE) experiment showed an increase in half wave potential and limiting current after the pyrolysis steps. The additional improvement was observed after etching and performing the second pyrolysis. A similar trend was seen in microbial fuel cells (MFCs), in which the power output increased from 167 ± 2 μW cm-2 to 214 ± 5 μW cm-2. X-ray Photoelectron Spectroscopy (XPS) was used to evaluate surface chemistry of catalysts obtained after each synthetic step. The changes in chemical composition were directly correlated with the improvements in performance. We report outstanding reproducibility in both composition and performance among the three different batches.

  15. Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: An International Lymphoma Radiation Oncology Group Multi-institutional Experience

    Energy Technology Data Exchange (ETDEWEB)

    Million, Lynn, E-mail: lmillion@stanford.edu [Stanford Cancer Institute, Stanford, California (United States); Yi, Esther J.; Wu, Frank; Von Eyben, Rie [Stanford Cancer Institute, Stanford, California (United States); Campbell, Belinda A. [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Dabaja, Bouthaina [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tsang, Richard W. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Ng, Andrea [Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Wilson, Lynn D. [Department of Therapeutic Radiology/Radiation Oncology, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut (United States); Ricardi, Umberto [Department of Oncology, University of Turin, Turin (Italy); Kirova, Youlia [Institut Curie, Paris (France); Hoppe, Richard T. [Stanford Cancer Institute, Stanford, California (United States)

    2016-08-01

    Purpose: To collect response rates of primary cutaneous anaplastic large cell lymphoma, a rare cutaneous T-cell lymphoma, to radiation therapy (RT), and to determine potential prognostic factors predictive of outcome. Methods and Materials: The study was a retrospective analysis of patients with primary cutaneous anaplastic large cell lymphoma who received RT as primary therapy or after surgical excision. Data collected include initial stage of disease, RT modality (electron/photon), total dose, fractionation, response to treatment, and local recurrence. Radiation therapy was delivered at 8 participating International Lymphoma Radiation Oncology Group institutions worldwide. Results: Fifty-six patients met the eligibility criteria, and 63 tumors were treated: head and neck (27%), trunk (14%), upper extremities (27%), and lower extremities (32%). Median tumor size was 2.25 cm (range, 0.6-12 cm). T classification included T1, 40 patients (71%); T2, 12 patients (21%); and T3, 4 patients (7%). The median radiation dose was 35 Gy (range, 6-45 Gy). Complete clinical response (CCR) was achieved in 60 of 63 tumors (95%) and partial response in 3 tumors (5%). After CCR, 1 tumor recurred locally (1.7%) after 36 Gy and 7 months after RT. This was the only patient to die of disease. Conclusions: Primary cutaneous anaplastic large cell lymphoma is a rare, indolent cutaneous lymphoma with a low death rate. This analysis, which was restricted to patients selected for treatment with radiation, indicates that achieving CCR was independent of radiation dose. Because there were too few failures (<2%) for statistical analysis on dose response, 30 Gy seems to be adequate for local control, and even lower doses may suffice.

  16. Embryonic cell-cell adhesion: a key player in collective neural crest migration.

    Science.gov (United States)

    Barriga, Elias H; Mayor, Roberto

    2015-01-01

    Cell migration is essential for morphogenesis, adult tissue remodeling, wound healing, and cancer cell migration. Cells can migrate as individuals or groups. When cells migrate in groups, cell-cell interactions are crucial in order to promote the coordinated behavior, essential for collective migration. Interestingly, recent evidence has shown that cell-cell interactions are also important for establishing and maintaining the directionality of these migratory events. We focus on neural crest cells, as they possess extraordinary migratory capabilities that allow them to migrate and colonize tissues all over the embryo. Neural crest cells undergo an epithelial-to-mesenchymal transition at the same time than perform directional collective migration. Cell-cell adhesion has been shown to be an important source of planar cell polarity and cell coordination during collective movement. We also review molecular mechanisms underlying cadherin turnover, showing how the modulation and dynamics of cell-cell adhesions are crucial in order to maintain tissue integrity and collective migration in vivo. We conclude that cell-cell adhesion during embryo development cannot be considered as simple passive resistance to force, but rather participates in signaling events that determine important cell behaviors required for cell migration. © 2015 Elsevier Inc. All rights reserved.

  17. Noradrenergic and hormonal responses to physical exercise in adolescents. Relationship to anxiety and tolerance to frustration.

    Science.gov (United States)

    Gerra, G; Caccavari, R; Reali, N; Bonvicini, P; Marcato, A; Fertonani, G; Delsignore, R; Passeri, M; Brambilla, F

    1993-01-01

    Seventy physically healthy 14-year-old adolescents, 40 boys and 30 girls, were evaluated psychologically and endocrinologically. After the psychological tests (Anxiety Score Test for Adolescents, Rosenzweig, Pictures Frustration Test for Children), subjects were divided into group A, with low anxiety/sense of guilt and high self-esteem/tolerance to frustration and group B with the opposite. In both groups, we measured basal plasma levels of noradrenaline (NE), growth hormone (GH), prolactin (PRL), melatonin (MT) and luteinizing hormone (LH) and their response to physical exercise (the Harvard step test). Basal levels of the hormones and of NE were not different in the two groups. After the physical stimulus, NE levels rose significantly more in B girls than in A and significantly less in B than in A boys. GH and PRL levels increased only in A girls and MT in B boys, while LH levels decreased in A boys and girls but not in B subjects.

  18. Comparative genome analysis of Bacillus cereus group genomes withBacillus subtilis

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Iain; Sorokin, Alexei; Kapatral, Vinayak; Reznik, Gary; Bhattacharya, Anamitra; Mikhailova, Natalia; Burd, Henry; Joukov, Victor; Kaznadzey, Denis; Walunas, Theresa; D' Souza, Mark; Larsen, Niels; Pusch,Gordon; Liolios, Konstantinos; Grechkin, Yuri; Lapidus, Alla; Goltsman,Eugene; Chu, Lien; Fonstein, Michael; Ehrlich, S. Dusko; Overbeek, Ross; Kyrpides, Nikos; Ivanova, Natalia

    2005-09-14

    Genome features of the Bacillus cereus group genomes (representative strains of Bacillus cereus, Bacillus anthracis and Bacillus thuringiensis sub spp israelensis) were analyzed and compared with the Bacillus subtilis genome. A core set of 1,381 protein families among the four Bacillus genomes, with an additional set of 933 families common to the B. cereus group, was identified. Differences in signal transduction pathways, membrane transporters, cell surface structures, cell wall, and S-layer proteins suggesting differences in their phenotype were identified. The B. cereus group has signal transduction systems including a tyrosine kinase related to two-component system histidine kinases from B. subtilis. A model for regulation of the stress responsive sigma factor sigmaB in the B. cereus group different from the well studied regulation in B. subtilis has been proposed. Despite a high degree of chromosomal synteny among these genomes, significant differences in cell wall and spore coat proteins that contribute to the survival and adaptation in specific hosts has been identified.

  19. The PD-1/B7-H1 pathway modulates the natural killer cells versus mouse glioma stem cells.

    Science.gov (United States)

    Huang, Bo Yuan; Zhan, Yi Ping; Zong, Wen Jing; Yu, Chun Jiang; Li, Jun Fa; Qu, Yan Ming; Han, Song

    2015-01-01

    Glioblastoma multiforme (GBM) is the most malignant primary type of brain tumor in adults. There has been increased focus on the immunotherapies to treat GBM patients, the therapeutic value of natural killer (NK) cells is still unknown. Programmed death-1 (PD-1) is a major immunological checkpoint that can negatively regulate the T-cell-mediated immune response. We tested the combination of the inhibiting the PD-1/B7H1 pathway with a NK-cell mediated immune response in an orthotopic mouse model of GBM. Mouse glioma stem cells (GL261GSCs) and mouse NK cells were isolated and identified. A lactate dehydrogenase (LDH) assay was perfomed to detect the cytotoxicity of NK cells against GL261GSCs. GL261GSCs were intracranially implanted into mice, and the mice were stratified into 3 treatment groups: 1) control, 2) NK cells treatment, and 3) PD-1 inhibited NK cells treatment group. Overall survival was quantified, and animal magnetic resonance imaging (MRI) was performed to determine tumor growth. The brains were harvested after the mice were euthanized, and immunohistochemistry against CD45 and PCNA was performed. The mouse NK cells were identified as 90% CD3- NK1.1+CD335+ by flow cytometric analysis. In the LDH assay, the ratios of the damaged GL261GSCs, with the E:T ratios of 2.5:1, 5:1, and 10:1, were as follows: 1) non-inhibited group: 7.42%, 11.31%, and 15.1%, 2) B7H1 inhibited group: 14.75%, 18.25% and 29.1%, 3) PD-1 inhibited group: 15.53%, 19.21% and 29.93%, 4) double inhibited group: 33.24%, 42.86% and 54.91%. In the in vivo experiments, the mice in the PD-1 inhibited NK cells treatment group and IL-2-stimulated-NK cells treatment group displayed a slowest tumor growth (F = 308.5, Pmouse NK cells to kill the GL261GSCs, and the PD-1-inhibited NK cells could be a feasible immune therapeutic approach against GBM.

  20. FDG uptake in cold and heat treated MCF-7 cells, comparison with cell viability, apoptosis, and tumor marker changes

    International Nuclear Information System (INIS)

    Zhang, C.; Sun, X.; Huang, G.; Liu, J.

    2007-01-01

    Full text: Objectives-To investigate the FDG uptake changes in cold and hyperthermia therapy and its correlation with cell viability, apoptosis and tumor marker changes. Methods: An in vitro cultured breast adenocarcinoma cell line, MCF- 7, was divided into 5 groups. Hyperthermia group: cell was treated in 43 degree centigrade 30 min. Hypothermia group: cell was treated in 0 degree centigrade 30 min. Hypo- and hyperthermia group: cell was treated in 0 degree centigrade 30 min and 43 degree centigrade 30 min. chemotherapy group: cell was treated with 21 microgram Cisplatin for 6 hours. And Control group: cell was untreated. The levels 18F-labelled FDG uptake, a 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyltetrazoliumbromide viability assay, flow cytometry assay and tumor markers (CA153, CA125) were detected at 24 hour and 48 hour. Results: The change of 18F- FDG uptake (which came out at the 24h) is early than tumor marker (which came out at the 48h) under our study conditions. In treated MCF-7 cells, the levels of 18F-labelled FDG uptake were significantly lower than control group. The levels of 18F-FDG uptake depression were well correlated with cell viability and apoptosis data. Conclusion: FDG uptake is sensitive and well correlated with cell viability and apoptosis assay, and can be used for early response monitoring in hypo- and hyperthermia therapy. (author)

  1. Curcumin Induces Autophagy, Apoptosis, and Cell Cycle Arrest in Human Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yaping Zhu

    2017-01-01

    Full Text Available Objective. Curcumin is an active extract from turmeric. The aim of this study was to identify the underlying mechanism of curcumin on PCa cells and the role of autophagy in this process. Methods. The inhibitory effect of curcumin on the growth of PANC1 and BxPC3 cell lines was detected by CCK-8 assay. Cell cycle distribution and apoptosis were tested by flow cytometry. Autophagosomes were tested by cell immunofluorescence assay. The protein expression was detected by Western blot. The correlation between LC3II/Bax and cell viability was analyzed. Results. Curcumin inhibited the cell proliferation in a dose- and time-dependent manner. Curcumin could induce cell cycle arrest at G2/M phase and apoptosis of PCa cells. The autophagosomes were detected in the dosing groups. Protein expression of Bax and LC3II was upregulated, while Bcl2 was downregulated in the high dosing groups of curcumin. There was a significant negative correlation between LC3II/Bax and cell viability. Conclusions. Autophagy could be triggered by curcumin in the treatment of PCa. Apoptosis and cell cycle arrest also participated in this process. These findings imply that curcumin is a multitargeted agent for PCa cells. In addition, autophagic cell death may predominate in the high concentration groups of curcumin.

  2. Protein-energy malnutrition halts hemopoietic progenitor cells in the G0/G1 cell cycle stage, thereby altering cell production rates

    Directory of Open Access Journals (Sweden)

    P. Borelli

    2009-06-01

    Full Text Available Protein energy malnutrition (PEM is a syndrome that often results in immunodeficiency coupled with pancytopenia. Hemopoietic tissue requires a high nutrient supply and the proliferation, differentiation and maturation of cells occur in a constant and balanced manner, sensitive to the demands of specific cell lineages and dependent on the stem cell population. In the present study, we evaluated the effect of PEM on some aspects of hemopoiesis, analyzing the cell cycle of bone marrow cells and the percentage of progenitor cells in the bone marrow. Two-month-old male Swiss mice (N = 7-9 per group were submitted to PEM with a low-protein diet (4% or were fed a control diet (20% protein ad libitum. When the experimental group had lost about 20% of their original body weight after 14 days, we collected blood and bone marrow cells to determine the percentage of progenitor cells and the number of cells in each phase of the cell cycle. Animals of both groups were stimulated with 5-fluorouracil. Blood analysis, bone marrow cell composition and cell cycle evaluation was performed after 10 days. Malnourished animals presented anemia, reticulocytopenia and leukopenia. Their bone marrow was hypocellular and depleted of progenitor cells. Malnourished animals also presented more cells than normal in phases G0 and G1 of the cell cycle. Thus, we conclude that PEM leads to the depletion of progenitor hemopoietic populations and changes in cellular development. We suggest that these changes are some of the primary causes of pancytopenia in cases of PEM.

  3. High Throughput Single-cell and Multiple-cell Micro-encapsulation

    OpenAIRE

    Lagus, Todd P.; Edd, Jon F.

    2012-01-01

    Microfluidic encapsulation methods have been previously utilized to capture cells in picoliter-scale aqueous, monodisperse drops, providing confinement from a bulk fluid environment with applications in high throughput screening, cytometry, and mass spectrometry. We describe a method to not only encapsulate single cells, but to repeatedly capture a set number of cells (here we demonstrate one- and two-cell encapsulation) to study both isolation and the interactions between cells in groups of ...

  4. A human repair gene ERCC5 is involved in group G xeroderma pigmentosum

    International Nuclear Information System (INIS)

    Shiomi, Tadahiro

    1994-01-01

    In E. coli, ultraviolet-induced DNA damage is removed by the coordinated action of UVR A, B, C, and D proteins (1). In Saccharomyces cerevisiae, more than ten genes have been reported to be involved in excision repair (2). The nucleotide excision repair pathway has been extensively studied in these organisms. To facilitate studying nucleotide excision repair in mammalian cells. Ultraviolet-sensitive rodent cell mutants have been isolated and classified into 11 complementation groups (9,10). The human nucleotide excision repair genes which complement the defects of the mutants have been designated as the ERCC (excision repair cross-complementing) genes; a number is added to refer to the particular rodent complementation group that is corrected by the gene. Recently, several human DNA repair genes have been cloned using rodent cell lines sensitive to ultraviolet. These include ERCC2 (3), ERCC3 (4), and ERCC6 (5), which correspond to the defective genes in the ultraviolet-sensitive human disorders xeroderma pigmentosum (XP) group D (6) and group B (4), and Cockayne's syndrome (CS) group B (7), respectively. The human excision repair gene ERCC5 was cloned after DNA-mediated gene transfer of human HeLa cell genomic DNA into the ultraviolet-sensitive mouse mutant XL216, a member of rodent complementation group 5 (11,12) and the gene was mapped on human chromosome 13q32.3-q33.1 by the replication R-banding fluorescence in situ hybridization method (13). The ERCC5 cDNA encodes a predicted 133 kDa nuclear protein that shares some homology with product of the yeast DNA repair gene RAD 2. Transfection with mouse ERCC5 cDNA restored normal levels of ultraviolet-resistance to XL216 cells. Microinjection of ERCC5 cDNA specifically restored the defect of XP group G cells (XP-G) as measured by unscheduled DNA synthesis (UDS), and XP-G cells stably transformed with ERCC5 cDNA showed nearly normal ultraviolet resistance. (J.P.N.)

  5. Effect of bionic electrical stimulation on the differentiation of embryonic stem cells into cardiomyocytes in the presence myocardial cells in vitro

    Directory of Open Access Journals (Sweden)

    Li-na ZHENG

    2011-08-01

    Full Text Available Objective To investigate the effects of electrical stimulation on the differentiation of embryonic stem cells(ESCs into cardiomyocytes in the presence of myocardial cells in vitro.Methods ESCs and neonate rat cardiomyocytes were isolated and cultured.These cells of primary culture were divided into 5 groups according to whether or not electric stimulation was given and the presence of cardiomyocytes: control group,stimulation group,cardiomyocytes group,stimulation+ cardiomyocyte conditioned medium group,and stimulation+cardiomyocytes group.Expression of troponin T(cTnT in the differentiated cells from ESCs was examined by immunofluoresence on the 5th,7th and 14th day.Results In the group co-cultured with myocardial cell and electrical stimulation,the differentiating ratio of cardiomyocytes derived from ESCs and expressing cTnT was 40.00%±2.39%,and it was higher than that in control group(2.00%±1.60%,stimulation group(3.00%±2.00%,cardiomyocytes group(28.70%±4.06%,stimulation+cardiomyocyte conditioned medium group(17.10%±2.23%,P < 0.05.Conclusion Bionic electric stimulation promotes the differentiation of ESCs into cardiomyocyte in a microenvironment consisting of myocardial cells.

  6. Transcriptional regulation by Polycomb group proteins

    DEFF Research Database (Denmark)

    Di Croce, Luciano; Helin, Kristian

    2013-01-01

    Polycomb group (PcG) proteins are epigenetic regulators of transcription that have key roles in stem-cell identity, differentiation and disease. Mechanistically, they function within multiprotein complexes, called Polycomb repressive complexes (PRCs), which modify histones (and other proteins......) and silence target genes. The dynamics of PRC1 and PRC2 components has been the focus of recent research. Here we discuss our current knowledge of the PRC complexes, how they are targeted to chromatin and how the high diversity of the PcG proteins allows these complexes to influence cell identity....

  7. Changes of Langerhans cells during skin ageing

    Directory of Open Access Journals (Sweden)

    Barbara Zegarska

    2017-05-01

    Full Text Available Introduction : During the process of skin ageing, changes occur in all skin layers and all cells, including the Langerhans cells. Aim: To assess whether any quantitative difference in the number of CD1a+ LC cells/mm 2 and HLA-DR+ LC cells/mm 2 as well as in their morphological features can be observed during the course of different types of skin ageing. Material and methods: The study was conducted in a group of 60 women, which was divided into three independent groups: group I with symptoms of menopausal skin ageing, group II with symptoms of photoageing, group III with symptoms of chronological ageing. Skin biopsy samples were taken from the pre-auricular region from all of the participants. The number of CD1a+ LC cells/mm 2 and HLA-DR+ LC cells/mm 2 as well as their morphological features were evaluated. Results : The frequency of CD1a+ LC and HLA-DR+ LC in all the studied groups was diverse. In groups I and III, the LC with large cell bodies and long, multi-branched processes were the majority. In group II, the LC had small cell bodies and their processes were mainly short and unbranched. Conclusions : The obtained results indicate the presence of quantitative and morphological changes of the CD1a+ LC and HLA-DR+ LC during the course of different types of skin ageing.

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

    Directory of Open Access Journals (Sweden)

    William R Henderson

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

  9. Tissue distribution of histo-blood group antigens

    DEFF Research Database (Denmark)

    Ravn, V; Dabelsteen, Erik

    2000-01-01

    carrier carbohydrate chains. Histo-blood group antigens are found in most epithelial tissues. Meanwhile, several factors influence the type, the amount, and the histological distribution of histoblood group antigens, i.e. the ABO, Lewis, and saliva-secretor type of the individual, and the cell- and tissue......The introduction of immunohistochemical techniques and monoclonal antibodies to specific carbohydrate epitopes has made it possible to study in detail the tissue distribution of histo-blood group antigens and related carbohydrate structures. The present paper summarizes the available data...... concerning the histological distribution of histo-blood group antigens and their precursor structures in normal human tissues. Studies performed have concentrated on carbohydrate antigens related to the ABO, Lewis, and TTn blood group systems, i.e. histo-blood group antigens carried by type 1, 2, and 3 chain...

  10. 21 CFR 864.9175 - Automated blood grouping and antibody test system.

    Science.gov (United States)

    2010-04-01

    ...) Identification. An automated blood grouping and antibody test system is a device used to group erythrocytes (red blood cells) and to detect antibodies to blood group antigens. (b) Classification. Class II (performance... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated blood grouping and antibody test system...

  11. Relationships between High-mobility Group Protein B1 and Triggering Receptor Expressed on Myeloid Cells Concentrations in Gingival Crevicular Fluid and Chronic Periodontitis.

    Science.gov (United States)

    Paknejad, Mojgan; Sattari, Mandana; Roozbahani, Zohreh; Ershadi, Morteza; Mehrfard, Ali

    2016-10-01

    One of the inflammatory mediators which is secreted by inflammatory cells is high-mobility group protein B1 (HMGB1). Interaction of HMGB1 and toll-like receptors (TLRs) leads to increased production of inflammatory cytokines. On the other hand, it was shown that triggering receptor expressed on myeloid cells (TREM-1) also can be activated by TLRs, and its soluble form (sTREM-1) can be formed by cleaving of membrane-bound form of TREM-1 proteinases. Since there is not enough knowledge about the precise role of HMGB1 and sTREM-1 in periodontal diseases, the aim of this study was to evaluate the concentration of HMGB1 and sTREM-1 in gingival crevicular fluid (GCF) samples of patients with chronic periodontitis. Gingival crevicular fluid (GCF) samples were obtained from a total of 24 individuals with clinically healthy gingiva and 24 patients with moderate to severe chronic periodontitis. For collecting GCF samples, periopapers were placed at the entrance of the crevice and left in position for 30 seconds. Then, they were stored at -80°C. Enzyme-linked immunosorbent assay (ELISA) was used for measuring the concentration of HMGB1 and sTREM-1 in GCF samples. The concentration of HMGB1 (pchronic periodontitis group. In addition, there was a significant positive correlation between HMGB1 and sTREM-1 concentration in chronic periodontitis group (pperiodontal tissues and they can promote inflammatory process, which leads to tissue destruction.

  12. Cell differentiation: therapeutical challenges in diabetes.

    Science.gov (United States)

    Roche, Enrique; Vicente-Salar, Nestor; Arribas, Maribel; Paredes, Beatriz

    2012-01-01

    Stem cells, derived from either embryonic or adult tissues, are considered to be potential sources of insulin-secreting cells to be transplanted into type 1 and advanced stages of type 2 diabetic patients. Many laboratories have considered this possibility, resulting in a large amount of published protocols, with a wide degree of complexity among them. Our group was the first to report that it was possible to obtain insulin-secreting cells from mouse embryonic stem cells, proving the feasibility of this new challenge. The same observation was immediately reported using human embryonic stem cells. However, the resulting cell product was not properly characterised, affecting the reproducibility of the protocol by other groups. A more elaborated protocol was developed by Lumelsky and co-workers, demonstrating that neuroectodermal cells could be an alternative source for insulin-producing cells. However, the resulting cells of this protocol produced low amounts of the hormone. This aimed other groups to perform key changes in order to improve the insulin content of the resulting cells. Recently, Baetge's group has published a new protocol based on the knowledge accumulated in pancreatic development. In this protocol, human embryonic stem cells were differentiated into islet-like structures through a five step protocol, emulating the key steps during embryonic development of the endocrine pancreas. The final cell product, however, seemed to be in an immature state, thus further improvement is required. Despite this drawback, the protocol represents the culmination of work performed by different groups and offers new research challenges for the investigators in this exciting field. Concerning adult stem cells, the possibility of identifying pancreatic precursors or of reprogramming extrapancreatic derived cells are key possibilities that may circumvent the problems that appear when using embryonic stem cells, such as immune rejection and tumour formation.

  13. Effect of radiation dosage changes on the cell viability and the apoptosis induction on normal and tumorigenic cells

    International Nuclear Information System (INIS)

    Park, In Woo; Choi, Soon Chul; Lee, Sam Sun; Heo, Min Suk

    1999-01-01

    The study was aimed to detect the differences in the cell viability and the apoptosis induction after irradiation on normal and tumorigenic cells. The study, that was generated for two human normal cells (RHEK, HGF-1) and two human tumor cells (KB, HT-1080), was tested using MTT assay at 1 day and 3 day after irradiation and TUNEL assay under confocal laser scanning microscope at 1 day after irradiation. Single irradiation of 0.5, 1, 2, 4, and 8 Gy were applied to the cells. The two fractions of 1, 2, 4, and 8 Gy were separated with a 4 hour time interval. The irradiation was done with 5.38 Gy/min dose rate using Cs-137 irradiator at room temperature. 1. In 3-day group, the cell viability of HGF-1 cell was significantly decreased at 2, 4 and 8 Gy irradiation, the cell viability of KB cell was significantly decreased at 8 Gy irradiation and the cell viability of HT-1080 cell was significantly decreased at 4 and 8 Gy irradiation. 2. There was significant difference between RHEK and KB cell line in the cell viability of 3-day group at 8 Gy irradiation. There was significant difference between RHEK and HGF-1 cell line in the cell viability of 3-day group at 4 and 8 Gy irradiation. 3. There was a significantly decreased cell viability in 3-day group than those in 1-day group at 2, 4 and 8 Gy on HGF-1 cell, at 4 and 8 Gy on HT-1080 cell, at 8 Gy on KB cell.4. We could detect DNA fragmented cells only on KB cell. Number of apoptotic cells of KB cell was significantly increased at 4 and 8 Gy irradiation. However, there was no correlation between cell viability and apoptosis.5. On all 4 cell lines, there were no differences between single and split irradiation method in cell viability and apoptosis.

  14. Immunocapture of CD133-positive cells from human cancer cell lines by using monodisperse magnetic poly(glycidyl methacrylate) microspheres containing amino groups

    Energy Technology Data Exchange (ETDEWEB)

    Kuan, Wei-Chih [Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhisung 621, Taiwan (China); Horák, Daniel, E-mail: horak@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6 (Czech Republic); Plichta, Zdeněk [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6 (Czech Republic); Lee, Wen-Chien [Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhisung 621, Taiwan (China)

    2014-01-01

    Magnetic poly(glycidyl methacrylate)-based macroporous microspheres with an average particle size of 4.2 μm were prepared using a modified multi-step swelling polymerization method and by introducing amino functionality on their surfaces. Antibody molecules were oxidized on their carbohydrate moieties and bound to the amino-containing magnetic microspheres via a site-directed procedure. CD133-positive cells could be effectively captured from human cancer cell lines (HepG2, HCT116, MCF7, and IMR-32) by using magnetic microspheres conjugated to an anti-human CD133 antibody. After further culture, the immunocaptured CD133-expressing cells from IMR-32 proliferated and gradually detached from the magnetic microspheres. Flow-cytometric analysis confirmed the enrichment of CD133-expressing cells by using the antibody-bound magnetic microspheres. Such microspheres suitable for immunocapture are very promising for cancer diagnosis because the CD133-expressing cells in cancer cell lines have been suggested to be cancer stem cells. - Highlights: • Multi-step swelling polymerization produced poly(glycidyl methacrylate) microspheres. • Anti-human CD133 antibodies were bound to the amino-containing magnetic microspheres. • CD133-positive cells were effectively captured from human cancer cell lines. • Immunocaptured CD133-expressing cells proliferated and were detached from microspheres. • Enrichment of CD133-expressing cells was confirmed by flow-cytometric analysis.

  15. MAGIC user's group software

    International Nuclear Information System (INIS)

    Warren, G.; Ludeking, L.; McDonald, J.; Nguyen, K.; Goplen, B.

    1990-01-01

    The MAGIC User's Group has been established to facilitate the use of electromagnetic particle-in-cell software by universities, government agencies, and industrial firms. The software consists of a series of independent executables that are capable of inter-communication. MAGIC, SOS, μ SOS are used to perform electromagnetic simulations while POSTER is used to provide post-processing capabilities. Each is described in the paper. Use of the codes for Klystrode simulation is discussed

  16. HPV Infection and Prognostic Factors of Tongue Squamous Cell Carcinoma in Different Ethnic Groups from Geographically Closed Cohort in Xinjiang, China

    Directory of Open Access Journals (Sweden)

    Hua Zhang

    2016-01-01

    Full Text Available Background. The effect of HPV infection status and ethnic differences on the prognosis of tongue squamous cell carcinoma in Xinjiang presents an interesting set of conditions that has yet to be studied. Methods. A comprehensive analysis of clinical data was undertaken for a cohort consisting of 63 patients with tongue squamous cell carcinoma recruited from three ethnic groups in Xinjiang. PCR was used for the detection of HPV16 and HPV18 infections. Kaplan-Meier survival analysis was used for analyzing survival outcome in addition to the assessment of other prognostic factors. Results. The overall infection rate for HPV was 28.6% (18/63; the 5-year survival rate among the HPV-positive patients was 47.8% and 30.3% for HPV-negative patients. The survival rate for HPV-positive patients who received radiotherapy and chemotherapy was better than for those who did not receive radiotherapy and chemotherapy. N staging and HPV infection were found to be two independent and significant prognostic factors. Conclusion. HPV-positive patients with tongue squamous cell carcinoma are more sensitive to chemotherapy. Higher N staging indicates poor prognosis.

  17. Nitrogen-rich functional groups carbon nanoparticles based fluorescent pH sensor with broad-range responding for environmental and live cells applications.

    Science.gov (United States)

    Shi, Bingfang; Su, Yubin; Zhang, Liangliang; Liu, Rongjun; Huang, Mengjiao; Zhao, Shulin

    2016-08-15

    A nitrogen-rich functional groups carbon nanoparticles (N-CNs) based fluorescent pH sensor with a broad-range responding was prepared by one-pot hydrothermal treatment of melamine and triethanolamine. The as-prepared N-CNs exhibited excellent photoluminesence properties with an absolute quantum yield (QY) of 11.0%. Furthermore, the N-CNs possessed a broad-range pH response. The linear pH response range was 3.0 to 12.0, which is much wider than that of previously reported fluorescent pH sensors. The possible mechanism for the pH-sensitive response of the N-CNs was ascribed to photoinduced electron transfer (PET). Cell toxicity experiment showed that the as-prepared N-CNs exhibited low cytotoxicity and excellent biocompatibility with the cell viabilities of more than 87%. The proposed N-CNs-based pH sensor was used for pH monitoring of environmental water samples, and pH fluorescence imaging of live T24 cells. The N-CNs is promising as a convenient and general fluorescent pH sensor for environmental monitoring and bioimaging applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Hyperthermia enhances radiosensitivity of colorectal cancer cells through ROS inducing autophagic cell death.

    Science.gov (United States)

    Ba, Ming-Chen; Long, Hui; Wang, Shuai; Wu, Yin-Bing; Zhang, Bo-Huo; Yan, Zhao-Fei; Yu, Fei-Hong; Cui, Shu-Zhong

    2018-04-01

    Hyperthermia (HT) enhances the anti-cancer effects of radiotherapy (RT), but the precise biochemical mechanisms involved are unclear. This study was aim to investigate if mild HT sensitizes colorectal cancer cells to RT through reactive oxygen species (ROS)-inducing autophagic cell death in a mice model of HCT116 human colorectal cancer. HCT116 mice model were randomly divided into five groups: mock group, hyperthermia group (HT), radiotherapy group (RT), HT + RT group, and HT + RT +N-acetyl L-cysteine (NAC) group (HT + CT + NAC). After four weeks of treatment, cancer growth inhibition, rate and mitochondrial membrane potential were measured with MTT and JC-1 assays, respectively, while ROS were estimated fluorimetrically. The relationship of these parameters to expressions of autophagy-related genes Beclin1, LC3B, and mTOR was analyzed. Gene expression was measured by Real-Time polymerase chain reaction (RT-PCR). There were significant increases in ROS levels and mitochondrial membrane potential in the HT + RT group. ROS levels in the HT + RT group increased more significantly than in any other group. In contrast, ROS levels in the HT + RT + NAC group were significantly decreased relative to the HT + RT group. The number of autophagic bodies in HT + RT group was higher than that of mock group. There were significant increases in the expression of Beclin1 and LC3B genes, while mTOR expression was significantly decreased in the HT + CT group. Treatment with NAC reversed the pattern of these changes. These results indicate that HT enhances the radiosensitivity of colorectal cancer cells to RT through ROS inducing autophagic cell death. © 2017 Wiley Periodicals, Inc.

  19. Effect of bcl-2 antisense oligodexynucleotides on chemotherapy efficacy of Vp-16 on human small cell lung cancer cell line NCI-H69

    International Nuclear Information System (INIS)

    He Wenqian; Liu Zhonghua

    2007-01-01

    Objective: To study the effect of bcl-2 antisense oligodexynucleotides on chemotherapy efficacy of Vp-16 on human small cell lung cancer cell line NCI-H69. Methods: Cultured NCI-H69 cells were derided into 4 groups: bcl-2 antisense oligodexynucleotides (ASODN) added, sense oligodexynucleotides (SODN) added, nonsense oligodexynucleotides (NSODN) added and control (no nucleotides added), the oligodexynucleotides were transfected into the cultured cells with oligofectamine. The cellular expression of Bcl-2 protein 72h later was examined with Western-Blot. The four different groups of cultured tumor cells were treated with etopside(Vp-16) at different concentrations (0, 0.25, 0.5, 1.0, 2.0 and 4.0 μg/ml) for 48hr then the cell survival fraction was assessed with MTY test. Results: The apoptotic rate of cells in the ASODN group was significantly higher than that of the control group, also, the survival fraction of cells in ASODN group was significantly lower than that of the control group. The Bcl-2 protein expression in ASODN group was significantly lower than that in the control group, but no inhibition was observed in SODN and NSODN groups. Conclusion: The bcl-2 ASODN could enhance the sensitivity to chemotherapy with Vp-16 in small cell lung cancer cell line NCI-H69 by effectively blocking bcl-2 gene expression. (authors)

  20. WIMSCORE, 2-Group Constant from WIMS-D/4 for Programs TDB, TRITON, CITATION

    International Nuclear Information System (INIS)

    Bartal, Yair

    1991-01-01

    1 - Description of program or function: The code processes the WIMS-D/4 binary output files for producing two-group microscopic Cross sections and macroscopic lattice cell constants (zone and cell macroscopic Cross sections, D, M, and K-infinity) in a more flexible Format needed for reactor burnup codes like CITATION, for reactor dynamics codes like NADYP-W and for other reactor codes. The purpose of the WIMSCORE-ENEA code is to facilitate the automation of data transfer between the cell calculation code WIMS and the diffusion-burnup codes. 2 - Method of solution: The code spatially homogenizes and group collapses the various Cross sections into two-group homogenized microscopic Cross sections using the flux per mesh for each energy group for WIMS multigroup lattice calculations. 3 - Restrictions on the complexity of the problem: None

  1. [Relationship between sensitivity of tumor cells to chemotherapeutic agent in vivo and in vitro: experiment with mouse lymphoma cells].

    Science.gov (United States)

    Li, Chuan-gang; Li, Mo-lin; Shu, Xiao-hong; Jia, Yu-jie; Liu, Yong-ji; Li, Ming

    2007-06-12

    To study the relationship of the sensitivity of tumor cells to chemotherapeutic agent between in vivo and in vitro. Mouse lymphoma cells of the line E14 were cultured and melphalan resistant EL4 cell line (EL4/melphalan) was established by culturing EL4 cells with continuous low-concentration and intermittent gradually-increasing-concentration of melphalan in vitro. MTT assay was used to evaluate the drug sensitivity and the resistance index of the EL4/melphalan cells to melphalan was calculated. EL4/melphalan and EL4 cells of the concentration of 5 x 10(8)/L were inoculated separately into 20 C57BL/6 mice subcutaneously. 12 days later, the EL4 and EL4/melphalan tumor-bearing mice were randomly divided into 2 groups respectively, 5 mice in each group. Treatment groups were given 7.5 mg/kg melphalan intraperitoneally, and control groups were given the same volume of normal saline. The tumor size was observed every other day. Compared with the EL4 cells, the EL4/melphalan cells had no obvious changes morphologically. They could grow in RPMI 1640 medium containing 5 mg/ml melphalan. The resistance index was 2.87 against melphalan. After the treatment of melphalan of the dose 7.5 mg/kg, the tumor sizes of the treatment groups and control groups inoculated with both EL4 cells and the EL4/melphalan cells gradually decreased at the similar speed, and about one week later all tumors disappeared. However, the tumors of the control groups grew progressively and all the mice died at last. The chemotherapeutic effects of tumors in vivo have nothing to do with the effects of the chemotherapeutic agents on tumor cells in vitro. The tumor cells resistant to melphalan in vitro remain sensitive to the drug in vivo.

  2. An Effective Approach for Immunotherapy Using Irradiated Tumor Cells

    International Nuclear Information System (INIS)

    Mostafa, D.M.B.

    2011-01-01

    This study has been aimed to investigate the effect of injection of Irradiated Ehrlich tumor cells alone or concurrent with immunomodulator in mice before and after challenge with viable Ehrlich tumor cells for enhancement of immune system. This study includes the estimation of survival, tumor size, lymphocyte count, LDH, MTT, granzyme B, and DNA fragmentation. In order to fulfill the target of this study, a total of 120 female swiss albino mice were used. They were divided into two classes vaccinated (injection of vaccine before challenge) and therapeutic class (injection of vaccine after challenge). Each class was divided into four groups, group (1) mice injected with viable Ehrlich tumor cells (G1), group (2) mice injected with irradiated tumor cells (G2), group (3) mice injected with immunomodulator (G3), and group (4) mice injected with irradiated tumor cells + immunomodulator (G4). Results obtained from this study demonstrated that, the lymphocyte count and granzyme B activity were increased in both the vaccinated and therapeutic classes compared with control group. LDH activity was decreased in all groups of vaccinated class and also in G2 and G4 groups of therapeutic class compared with control group. There was a significant increase in percent apoptosis of tumor cells cultured with spleenocytes of the groups of vaccinated class as compared with control group. Cellular DNA from Ehrlich tumor cell line cultured with spleenocytes of immunized groups was fragmented into discrete bands of approximate multiples of 200 bp. Revealing significant apoptosis in tumor cells due to vaccination. It is concluded that, vaccination with irradiated tumor cells is an effective approach in stimulation of immune system against viable tumor cells.

  3. A cyclopalladated complex interacts with mitochondrial membrane thiol-groups and induces the apoptotic intrinsic pathway in murine and cisplatin-resistant human tumor cells

    International Nuclear Information System (INIS)

    Serrano, Fabiana A; Machado, Joel Jr; Santos, Edson L; Pesquero, João B; Martins, Rafael M; Travassos, Luiz R; Caires, Antonio CF; Rodrigues, Elaine G; Matsuo, Alisson L; Monteforte, Priscila T; Bechara, Alexandre; Smaili, Soraya S; Santana, Débora P; Rodrigues, Tiago; Pereira, Felipe V; Silva, Luis S

    2011-01-01

    Systemic therapy for cancer metastatic lesions is difficult and generally renders a poor clinical response. Structural analogs of cisplatin, the most widely used synthetic metal complexes, show toxic side-effects and tumor cell resistance. Recently, palladium complexes with increased stability are being investigated to circumvent these limitations, and a biphosphinic cyclopalladated complex {Pd 2 [S (-) C 2 , N-dmpa] 2 (μ-dppe)Cl 2 } named C7a efficiently controls the subcutaneous development of B16F10-Nex2 murine melanoma in syngeneic mice. Presently, we investigated the melanoma cell killing mechanism induced by C7a, and extended preclinical studies. B16F10-Nex2 cells were treated in vitro with C7a in the presence/absence of DTT, and several parameters related to apoptosis induction were evaluated. Preclinical studies were performed, and mice were endovenously inoculated with B16F10-Nex2 cells, intraperitoneally treated with C7a, and lung metastatic nodules were counted. The cytotoxic effects and the respiratory metabolism were also determined in human tumor cell lines treated in vitro with C7a. Cyclopalladated complex interacts with thiol groups on the mitochondrial membrane proteins, causes dissipation of the mitochondrial membrane potential, and induces Bax translocation from the cytosol to mitochondria, colocalizing with a mitochondrial tracker. C7a also induced an increase in cytosolic calcium concentration, mainly from intracellular compartments, and a significant decrease in the ATP levels. Activation of effector caspases, chromatin condensation and DNA degradation, suggested that C7a activates the apoptotic intrinsic pathway in murine melanoma cells. In the preclinical studies, the C7a complex protected against murine metastatic melanoma and induced death in several human tumor cell lineages in vitro, including cisplatin-resistant ones. The mitochondria-dependent cell death was also induced by C7a in human tumor cells. The cyclopalladated C7a complex is

  4. Ability of Group IVB metallocene polyethers containing dienestrol to arrest the growth of selected cancer cell lines

    International Nuclear Information System (INIS)

    Roner, Michael R; Carraher, Charles E Jr; Shahi, Kimberly; Ashida, Yuki; Barot, Girish

    2009-01-01

    Monomeric Group IVB (Ti, Zr and Hf) metallocenes represent a new class of antitumor compounds. There is literature on the general biological activities of some organotin compounds. Unfortunately, there is little information with respect to the molecular level activity of these organotin compounds. We recently started focusing on the anti-cancer activity of organotin polymers that we had made for other purposes and as part of our platinum anti-cancer effort. For this study, we synthesized a new series of metallocene-containing compounds coupling the metallocene unit with dienestrol, a synthetic, nonsteroidal estrogen. This is part of our effort to couple known moieties that offer antitumor activity with biologically active units hoping to increase the biological activity of the combination. The materials were confirmed to be polymeric using light scattering photometry and the structural repeat unit was verified employing matrix assisted laser desorption ionization mass spectrometry and infrared spectroscopy results. The polymers demonstrated the ability to suppress the growth of a series of tumor cell lines originating from breast, colon, prostrate, and lung cancers at concentrations generally lower than those required for inhibition of cell growth by the commonly used antitumor drug cisplatin. These drugs show great promise in vitro against a number of cancer cell lines and due to their polymeric nature will most likely be less toxic than currently used metal-containing drugs such as cisplatin. These drugs also offer several addition positive aspects. First, the reactants are commercially available so that additional synthetic steps are not needed. Second, synthesis of the polymer is rapid, occurring within about 15 seconds. Third, the interfacial synthetic system is already industrially employed in the synthesis of aromatic nylons and polycarbonates. Thus, the ability to synthesize large amounts of the drugs is straight forward

  5. Ability of Group IVB metallocene polyethers containing dienestrol to arrest the growth of selected cancer cell lines

    Directory of Open Access Journals (Sweden)

    Ashida Yuki

    2009-10-01

    Full Text Available Abstract Background Monomeric Group IVB (Ti, Zr and Hf metallocenes represent a new class of antitumor compounds. There is literature on the general biological activities of some organotin compounds. Unfortunately, there is little information with respect to the molecular level activity of these organotin compounds. We recently started focusing on the anti-cancer activity of organotin polymers that we had made for other purposes and as part of our platinum anti-cancer effort. Methods For this study, we synthesized a new series of metallocene-containing compounds coupling the metallocene unit with dienestrol, a synthetic, nonsteroidal estrogen. This is part of our effort to couple known moieties that offer antitumor activity with biologically active units hoping to increase the biological activity of the combination. The materials were confirmed to be polymeric using light scattering photometry and the structural repeat unit was verified employing matrix assisted laser desorption ionization mass spectrometry and infrared spectroscopy results. Results The polymers demonstrated the ability to suppress the growth of a series of tumor cell lines originating from breast, colon, prostrate, and lung cancers at concentrations generally lower than those required for inhibition of cell growth by the commonly used antitumor drug cisplatin. Conclusion These drugs show great promise in vitro against a number of cancer cell lines and due to their polymeric nature will most likely be less toxic than currently used metal-containing drugs such as cisplatin. These drugs also offer several addition positive aspects. First, the reactants are commercially available so that additional synthetic steps are not needed. Second, synthesis of the polymer is rapid, occurring within about 15 seconds. Third, the interfacial synthetic system is already industrially employed in the synthesis of aromatic nylons and polycarbonates. Thus, the ability to synthesize large amounts of

  6. Lack of any association between blood groups and lung cancer, independent of histology.

    Science.gov (United States)

    Oguz, Arzu; Unal, Dilek; Tasdemir, Arzu; Karahan, Samet; Aykas, Fatma; Mutlu, Hasan; Cihan, Yasemin Benderli; Kanbay, Mehmet

    2013-01-01

    Lung cancer, the leading cause of cancer deaths, is divided into 2 main classes based on its biology, therapy and prognosis: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Many cases are at an advanced stage at diagnosis, which is a major obstacle to improving outcomes. It is important to define the high risk group patients for early diagnosis and chance of cure. Blood group antigens are chemical components on erythrocyte membranes but they are also expressed on a variety of epithelial cells. Links between ABO blood groups with benign or malignant diseases, such as gastric and pancreas cancers, have been observed for a long time. In this study, we aimed to investigate any possible relationship between lung cancer histological subtypes and ABO-Rh blood groups. The files of 307 pathologically confirmed lung cancer patients were were reviewed retrospectively. Cases with a serologically determined blood group and Rh factor were included and those with a history of another primary cancer were excluded, leaving a total of 221. The distribution of blood groups of the lung cancer patients were compared with the distribution of blood groups of healthy donors admitted to the Turkish Red Crescent Blood Service in our city in the year 2012. There was no significant difference between patients with lung cancer of either type and the control group in terms of distribution of ABO blood groups and Rh factor (p: 0.073). There was also no relationship with non small cell cancer histological subtypes. In this study, we found no relationship between the ABO-Rhesus blood groups and NSCLC and SCLC groups. To our knowledge this is the first analysis of ABO blood groups in SCLC patients.

  7. Metastatic non-small cell lung cancer Current treatment based on evidence (ONCOL Group)

    International Nuclear Information System (INIS)

    Castro, Carlos; Cardona, Andres Felipe; Reveiz, Ludovic; Serrano, Silvia Juliana; Carranza, Hernan; Vargas, Carlos Alberto; Reguart, Noemi; Campo, Felipe; Ospina, Edgar Guillermo; Sanchez, Oswaldo; Torres, Diana; Otero, Jorge Miguel

    2010-01-01

    to perform a review of evidence about the treatment of non-small cell lung cancer (NSCLC). Source of data: the information was obtained from searches conducted in Medline, CCTR, Biosis, Embase, Lilacs and CINHAL. We also collected the most representative references presented during the last five years at Asco, ESMO and IASLC. Data extraction: data were extracted by associate members to the ONCOL Group. The collection of information did not follow a uniform strategy. Results of data synthesis: therapy for NSCLC can prolong survival and improve quality of life, but the majority of advanced stage patients dies due to disease progression within 2 years, meaning that there is room for improvement. The standard chemotherapy for NSCLC involves one of a number of platinum-based doublets that have been shown to improve survival when compared with single agents or best supportive care. These doublets are generally comparable in terms of efficacy, differing primarily in their toxicity profiles. However, encouraging new options may be approaching, including therapies targeted to specific patient subpopulations, and the use of combinations of current and new drugs to produce synergistic effects. This review present a detailed analysis of current evidence regarding the treatment of NSCLC based on a representative case series. This review didn't conduct a systematic evaluation of the evidence. Conclusion: medical therapy for NSCLC produces positive changes in main outcomes, including quality of life

  8. Frequency distribution 0f ABO, RH blood groups and blood ...

    African Journals Online (AJOL)

    One hundred and fifty students (150) were randomly selected from the Department of Cell Biology and Genetics of University of Lagos, Akoka, Nigeria for ABO, RH blood groups and 6 haemoglobin genotypes studies. Blood group O was the highest with the percentage frequency of 55.3%, followed by blood group A (25.3%) ...

  9. Molecular blood grouping of donors.

    Science.gov (United States)

    St-Louis, Maryse

    2014-04-01

    For many decades, hemagglutination has been the sole means to type blood donors. Since the first blood group gene cloning in the early 1990s, knowledge on the molecular basis of most red blood cell, platelet and neutrophil antigens brought the possibility of using nucleotide-based techniques to predict phenotype. This review will summarized methodologies available to genotype blood groups from laboratory developed assays to commercially available platforms, and how proficiency assays become more present. The author will also share her vision of the transfusion medicine future. The field is presently at the crossroads, bringing new perspectives to a century old practice. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. One-group constant libraries for nuclear equilibrium state

    Energy Technology Data Exchange (ETDEWEB)

    Mizutani, Akihiko; Sekimoto, Hiroshi [Tokyo Inst. of Tech. (Japan). Research Lab. for Nuclear Reactors

    1997-03-01

    One-group constant libraries for the nuclear equilibrium state were generated for both liquid sodium cooled MOX fuel type fast reactor and PWR type thermal reactor with Equilibrium Cell Iterative Calculation System (ECICS) using JENDL-3.2, -3, -2 and ENDF/B-VI nuclear data libraries. ECICS produced one-group constant sets for 129 heavy metal nuclides and 1238 fission products. (author)

  11. Promotion of cooperation by selective group extinction

    Science.gov (United States)

    Böttcher, Marvin A.; Nagler, Jan

    2016-06-01

    Multilevel selection is an important organizing principle that crucially underlies evolutionary processes from the emergence of cells to eusociality and the economics of nations. Previous studies on multilevel selection assumed that the effective higher-level selection emerges from lower-level reproduction. This leads to selection among groups, although only individuals reproduce. We introduce selective group extinction, where groups die with a probability inversely proportional to their group fitness. When accounting for this the critical benefit-to-cost ratio is substantially lowered. Because in game theory and evolutionary dynamics the degree of cooperation crucially depends on this ratio above which cooperation emerges, previous studies may have substantially underestimated the establishment and maintenance of cooperation.

  12. A Group Counseling Approach for Persons Who Work With Sickle Cell Anemia Clients.

    Science.gov (United States)

    Calvin, Richmond

    Although many workshops on sickle cell anemia have been held, it is still difficult to implement a comprehensive training program for sickle cell anemia clients in many communities. Research data on the topic are somewhat nebulous and insufficient political and social pressure have been exerted to change attitudes and take action towards the…

  13. Organization of the sleep-related neural systems in the brain of the harbour porpoise (Phocoena phocoena).

    Science.gov (United States)

    Dell, Leigh-Anne; Patzke, Nina; Spocter, Muhammad A; Siegel, Jerome M; Manger, Paul R

    2016-07-01

    The present study provides the first systematic immunohistochemical neuroanatomical investigation of the systems involved in the control and regulation of sleep in an odontocete cetacean, the harbor porpoise (Phocoena phocoena). The odontocete cetaceans show an unusual form of mammalian sleep, with unihemispheric slow waves, suppressed REM sleep, and continuous bodily movement. All the neural elements involved in sleep regulation and control found in bihemispheric sleeping mammals were present in the harbor porpoise, with no specific nuclei being absent, and no novel nuclei being present. This qualitative similarity of nuclear organization relates to the cholinergic, noradrenergic, serotonergic, and orexinergic systems and is extended to the γ-aminobutyric acid (GABA)ergic elements involved with these nuclei. Quantitative analysis of the cholinergic and noradrenergic nuclei of the pontine region revealed that in comparison with other mammals, the numbers of pontine cholinergic (126,776) and noradrenergic (122,878) neurons are markedly higher than in other large-brained bihemispheric sleeping mammals. The diminutive telencephalic commissures (anterior commissure, corpus callosum, and hippocampal commissure) along with an enlarged posterior commissure and supernumerary pontine cholinergic and noradrenergic neurons indicate that the control of unihemispheric slow-wave sleep is likely to be a function of interpontine competition, facilitated through the posterior commissure, in response to unilateral telencephalic input related to the drive for sleep. In addition, an expanded peripheral division of the dorsal raphe nuclear complex appears likely to play a role in the suppression of REM sleep in odontocete cetaceans. Thus, the current study provides several clues to the understanding of the neural control of the unusual sleep phenomenology present in odontocete cetaceans. J. Comp. Neurol. 524:1999-2017, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals

  14. [Effect of Evn-50 on cell growth and apoptosis in tamoxifen-resistance human breast cancer cell line MCF-7/TAM-R].

    Science.gov (United States)

    Hu, Hui-yong; Zhou, Jun; Wan, Fang; Dong, Li-feng; Zhang, Feng; Wang, Yi-ke; Chen, Fang-fang; Chen, Yi-ding

    2012-09-01

    To investigate the effect of Evn-50 extracted from Vitex negundo on human breast cancer cell line MCF-7 and MCF-7/TAM-R cells in vitro. MCF-7 and tamoxifen-resistant MCF-7/TAM-R cells were treated with Evn-50,tamoxifen or combination of Evn-50 and tamoxifen. Cell proliferation inhibition rates were determined by MTT assay. The apoptosis rate and the change of cell cycle were detected by PI staining flow cytometry. Protein expression of phospho-MAPK 44/42 (Thr202/Tyr204),MAPK P44/42, phospho-AKT (Ser473) and AKT were detected with Western blotting. The viability of MCF-7 cells was decreased in combination group [(28.65 ±11.43)%] and Evn-50 group [(53.02 ±15.14)%] compared with TAM group (PTAM-R in combination group [(42.11 ±14.30)%] was significantly lower than that in TAM group [(92.18 ±13.16)%] (PTAM-R cells,the expression of phosphorylation of AKT and MAPK44/42 protein was not changed in Evn-50 or TAM alone group,but significantly inhibited in the combination group at 72 h. Evn-50 can inhibit cell growth and induce apoptosis in MCF-7 and MCF-7/TAM-R cells,it can reverse tamoxifen-resistance of MCF-7/TAM-R cells.The mechanisms may be related to the down-regulation of phosphorylated ERK1/2 in MAPK signal pathway and phosphorylated AKT in AKT signal pathway.

  15. Culturing bone marrow cells with dexamethasone and ascorbic acid improves osteogenic cell sheet structure.

    Science.gov (United States)

    Akahane, M; Shimizu, T; Kira, T; Onishi, T; Uchihara, Y; Imamura, T; Tanaka, Y

    2016-11-01

    To assess the structure and extracellular matrix molecule expression of osteogenic cell sheets created via culture in medium with both dexamethasone (Dex) and ascorbic acid phosphate (AscP) compared either Dex or AscP alone. Osteogenic cell sheets were prepared by culturing rat bone marrow stromal cells in a minimal essential medium (MEM), MEM with AscP, MEM with Dex, and MEM with Dex and AscP (Dex/AscP). The cell number and messenger (m)RNA expression were assessed in vitro, and the appearance of the cell sheets was observed after mechanical retrieval using a scraper. β-tricalcium phosphate (β-TCP) was then wrapped with the cell sheets from the four different groups and subcutaneously implanted into rats. After mechanical retrieval, the osteogenic cell sheets from the MEM, MEM with AscP, and MEM with Dex groups appeared to be fragmented or incomplete structures. The cell sheets cultured with Dex/AscP remained intact after mechanical retrieval, without any identifiable tears. Culture with Dex/AscP increased the mRNA and protein expression of extracellular matrix proteins and cell number compared with those of the other three groups. More bridging bone formation was observed after transplantation of the β-TCP scaffold wrapped with cell sheets cultured with Dex/AscP, than in the other groups. These results suggest that culture with Dex/AscP improves the mechanical integrity of the osteogenic cell sheets, allowing retrieval of the confluent cells in a single cell sheet structure. This method may be beneficial when applied in cases of difficult tissue reconstruction, such as nonunion, bone defects, and osteonecrosis.Cite this article: M. Akahane, T. Shimizu, T. Kira, T. Onishi, Y. Uchihara, T. Imamura, Y. Tanaka. Culturing bone marrow cells with dexamethasone and ascorbic acid improves osteogenic cell sheet structure. Bone Joint Res 2016;5:569-576. DOI: 10.1302/2046-3758.511.BJR-2016-0013.R1. © 2016 Akahane et al.

  16. New patient with both xeroderma pigmentosum and Cockayne syndrome establishes the new xeroderma pigmentosum complementation group H

    International Nuclear Information System (INIS)

    Moshell, A.N.; Ganges, M.B.; Lutzner, M.A.; Coon, H.G.; Barrett, S.F.; Dupuy, J.M.; Robbins, J.H.

    1983-01-01

    A second patient, XP-CS-2, has been discovered with both xeroderma pigmentosum and Cockayne syndrome. His fibroblasts have 30% of the normal rate of uv-induced unscheduled DNA synthesis. His fibroblasts were fused with those from each of the xeroderma pigmentosum groups A through G. His cells complemented every cell line, since in each case there were obtained multinucleate cells which had a normal amount of uv-induced unscheduled DNA synthesis. Since the XP-CS-2 cells complement all the currently established xeroderma pigmentosum complementation groups, this new XP-CS patient is in a new group which we designate group H. 10 references, 1 figure

  17. Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Aires, M.B. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Santos, J.R.A. [Departamento de Enfermagem, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Souza, K.S.; Farias, P.S. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Santos, A.C.V. [Departamento de Enfermagem, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Fioretto, E.T. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Maria, D.A. [Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, SP (Brazil)

    2015-07-10

    The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers.

  18. Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

    International Nuclear Information System (INIS)

    Aires, M.B.; Santos, J.R.A.; Souza, K.S.; Farias, P.S.; Santos, A.C.V.; Fioretto, E.T.; Maria, D.A.

    2015-01-01

    The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers

  19. Increased Fos expression among midbrain dopaminergic cell groups during birdsong tutoring.

    Science.gov (United States)

    Nordeen, E J; Holtzman, D A; Nordeen, K W

    2009-08-01

    During avian vocal learning, birds memorize conspecific song patterns and then use auditory feedback to match their vocal output to this acquired template. Some models of song learning posit that during tutoring, conspecific visual, social and/or auditory cues activate neuromodulatory systems that encourage acquisition of the tutor's song and attach incentive value to that specific acoustic pattern. This hypothesis predicts that stimuli experienced during social tutoring activate cell populations capable of signaling reward. Using immunocytochemistry for the protein product of the immediate early gene c-Fos, we found that brief exposure of juvenile male zebra finches to a live familiar male tutor increased the density of Fos+ cells within two brain regions implicated in reward processing: the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). This activation of Fos appears to involve both dopaminergic and non-dopaminergic VTA/SNc neurons. Intriguingly, a familiar tutor was more effective than a novel tutor in stimulating Fos expression within these regions. In the periaqueductal gray, a dopamine-enriched cell population that has been implicated in emotional processing, Fos labeling also was increased after tutoring, with a familiar tutor again being more effective than a novel conspecific. As several neural regions implicated in song acquisition receive strong dopaminergic projections from these midbrain nuclei, their activation in conjunction with hearing the tutor's song could help to establish sensory representations that later guide motor sequence learning.

  20. Cytokines, hepatic cell profiling and cell interactions during bone marrow cell therapy for liver fibrosis in cholestatic mice.

    Directory of Open Access Journals (Sweden)

    Daphne Pinheiro

    Full Text Available Bone marrow cells (BMC migrate to the injured liver after transplantation, contributing to regeneration through multiple pathways, but mechanisms involved are unclear. This work aimed to study BMC migration, characterize cytokine profile, cell populations and proliferation in mice with liver fibrosis transplanted with GFP+ BMC. Confocal microscopy analysis showed GFP+ BMC near regions expressing HGF and SDF-1 in the fibrotic liver. Impaired liver cell proliferation in fibrotic groups was restored after BMC transplantation. Regarding total cell populations, there was a significant reduction in CD68+ cells and increased Ly6G+ cells in transplanted fibrotic group. BMC contributed to the total populations of CD144, CD11b and Ly6G cells in the fibrotic liver, related to an increment of anti-fibrotic cytokines (IL-10, IL-13, IFN-γ and HGF and reduction of pro-inflammatory cytokines (IL-17A and IL-6. Therefore, HGF and SDF-1 may represent important chemoattractants for transplanted BMC in the injured liver, where these cells can give rise to populations of extrahepatic macrophages, neutrophils and endothelial progenitor cells that can interact synergistically with other liver cells towards the modulation of an anti-fibrotic cytokine profile promoting the onset of liver regeneration.

  1. Adrenal stress hormones, amygdala activation, and memory for emotionally arousing experiences.

    Science.gov (United States)

    Roozendaal, Benno; Barsegyan, Areg; Lee, Sangkwan

    2008-01-01

    Extensive evidence indicates that stress hormones released from the adrenal glands are critically involved in memory consolidation of emotionally arousing experiences. Epinephrine or glucocorticoids administered after exposure to emotionally arousing experiences enhance the consolidation of long-term memories of these experiences. Our findings indicate that adrenal stress hormones influence memory consolidation via interactions with arousal-induced activation of noradrenergic mechanisms within the amygdala. In turn, the amygdala regulates memory consolidation via its efferent projections to many other brain regions. In contrast to the enhancing effects on consolidation, high circulating levels of stress hormones impair memory retrieval and working memory. Such effects also require noradrenergic activation of the amygdala and interactions with other brain regions.

  2. Distribution of ABO and Rh-Hr blood group antigens, alleles and ...

    African Journals Online (AJOL)

    ABO and Rh-Hr blood group antigens represent a genetically stably determined trait with many-sided biological and clinical significance. The indigenous Ajarian population (105 subjects) was investigated for ABO Rh-Hr red cell blood group antigens. Using immunoserologic methods, seven blood group antigens (A, B, C, c, ...

  3. Influence of cell printing on biological characters of chondrocytes.

    Science.gov (United States)

    Qu, Miao; Gao, Xiaoyan; Hou, Yikang; Shen, Congcong; Xu, Yourong; Zhu, Ming; Wang, Hengjian; Xu, Haisong; Chai, Gang; Zhang, Yan

    2015-01-01

    To establish a two-dimensional biological printing technique of chondrocytes and compare the difference of related biological characters between printed chondrocytes and unprinted cells so as to control the cell transfer process and keep cell viability after printing. Primary chondrocytes were obtained from human mature and fetal cartilage tissues and then were regularly sub-cultured to harvest cells at passage 2 (P2), which were adjusted to the single cell suspension at a density of 1×10(6)/mL. The experiment was divided into 2 groups: experimental group P2 chondrocytes were transferred by rapid prototype biological printer (driving voltage value 50 V, interval in x-axis 300 μm, interval in y-axis 1500 μm). Afterwards Live/Dead viability Kit and flow cytometry were respectively adopted to detect cell viability; CCK-8 Kit was adopted to detect cell proliferation viability; immunocytochemistry, immunofluorescence and RT-PCR was employed to identify related markers of chondrocytes; control group steps were the same as the printing group except that cell suspension received no printing. Fluorescence microscopy and flow cytometry analyses showed that there was no significant difference between experimental group and control group in terms of cell viability. After 7-day in vitro culture, control group exhibited higher O.D values than experimental group from 2nd day to 7th day but there was no distinct difference between these two groups (P>0.05). Inverted microscope observation demonstrated that the morphology of these two groups had no significant difference either. Similarly, Immunocytochemistry, immunofluorescence and RT-PCR assays also showed that there was no significant difference in the protein and gene expression of type II collagen and aggrecan between these two groups (P>0.05). Conclusion Cell printing has no distinctly negative effect on cell vitality, proliferation and phenotype of chondrocytes. Biological printing technique may provide a novel approach

  4. Significance of neo-angiogenesis and immuno-surveillance cells in squamous cell carcinoma of the tongue

    Directory of Open Access Journals (Sweden)

    Juma O. Alkhabuli

    2007-02-01

    Full Text Available Background: Neo-angiogenesis is an essential process in physiological and pathological conditions. However, it is a complex process. Several studies demonstrated that intra-tumoural microvessel number is a significant predictor of metastasis and clinical outcome in many tumours, including oral malignancies. The immuno-surveillance cells, mast cells and eosinophils are implicated in the biological behaviour of tumours. Nevertheless, their function in tissues is uncertain. Mast cells are involved in homeostatic regulation of blood vessels as well as host defence. In some malignancies, high mast cell density has been found to correlate with favourable prognosis. However, others reported unfavourable associations. Tumour associated tissue eosinophilia is a well-known phenomena. It has been associated with good and poor prognosis. However, the role of eosinophils in tumours remains controversial. Therefore, this study was designed to investigate the prognostic value of microvessel, mast cell and eosinophil densities in the context of clinico-pathological parameters and survival in squamous cell carcinoma of the tongue.Materials and Methods: Anti-CD105 and anti-tryptase monoclonal antibodies were utilized to highlight and count microvessels and mast cells respectively in 81 cases of tongue squamous cell carcinoma. Eosinophils were demonstrated using carbol chromotrope histochemical stain. The densities were counted per mm2 and correlated with patients’ outcome and other clinico-pathological parameters using non-parametric tests and student’s t-test. Clinically, the cases were divided into 4 main groups depending on survival time, lymph-node or distant metastasis.Results: The 5 year survival was significantly lower in patients with a low mast cell density than those with a high density (p=0.006, Kruskal-Wallis test. The survival group-A demonstrated significantly higher mast cell and microvessel numbers than group-D (p=0.007, student’s t

  5. Interim report of the LASL nondestructive testing group

    International Nuclear Information System (INIS)

    Morris, R.A.; Bryant, L.

    1979-01-01

    Topics discussed include: high-pressure diamond cell work; x-ray fluorescence analysis; shroud of turin; laser fusion target inspection; and scanning electron microscope. Organization charts for the M-1 group are included

  6. Amide group anchored glucose oxidase based anodic catalysts for high performance enzymatic biofuel cell

    Science.gov (United States)

    Chung, Yongjin; Ahn, Yeonjoo; Kim, Do-Heyoung; Kwon, Yongchai

    2017-01-01

    A new enzyme catalyst is formed by fabricating gold nano particle (GNP)-glucose oxidase (GOx) clusters that are then attached to polyethyleneimine (PEI) and carbon nanotube (CNT) with cross-linkable terephthalaldehyde (TPA) (TPA/[CNT/PEI/GOx-GNP]). Especially, amide bonds belonging to TPA play an anchor role for incorporating rigid bonding among GNP, GOx and CNT/PEI, while middle size GNP is well bonded with thiol group of GOx to form strong GNP-GOx cluster. Those bonds are identified by chemical and electrochemical characterizations like XPS and cyclic voltammogram. The anchording effect of amide bonds induces fast electron transfer and strong chemical bonding, resulting in enhancements in (i) catalytic activity, (ii) amount of immobilized GOx and (ii) performance of enzymatic biofuel cell (EBC) including the catalyst. Regarding the catalytic activity, the TPA/[CNT/PEI/GOx-GNP] produces high electron transfer rate constant (6 s-1), high glucose sensitivity (68 μA mM-1 cm-2), high maximum current density (113 μA cm-2), low charge transfer resistance (17.0 Ω cm2) and long-lasting durability while its chemical structure is characterized by XPS confirming large portion of amide bond. In EBC measurement, it has high maximum power density (0.94 mW cm-2) compatible with catalytic acitivity measurements.

  7. Huperzine A protects neural stem cells against Aβ-induced apoptosis in a neural stem cells and microglia co-culture system

    Science.gov (United States)

    Zhu, Ning; Lin, Jizong; Wang, Kewan; Wei, Meidan; Chen, Qingzhuang; Wang, Yong

    2015-01-01

    Objectives: This study aims to explore whether Huperzine A (HupA) could protect neural stem cells against amyloid beta-peptide Aβ induced apoptosis in a neural stem cells (NSCs) and microglia co-culture system. Methods: Rat NSCs and microglial cells were isolated, cultured and identified with immunofluorescence Assays (IFA). Co-culture systems of NSCs and microglial cells were employed using Transwell Permeable Supports. The effects of Aβ1-42 on NSCs were studied in 4 groups using co-culture systems: NSCs, Aβ+NSCs, co-culture and Aβ+co-culture groups. Bromodeoxyuridine (BrdU) incorporation and flow cytometry were utilized to assess the differences of proliferation, differentiation and apoptosis of NSCs between the groups. LQ test was performed to assess the amounts of IL-6, TNF-α and MIP-α secreted, and flow cytometry and Western blotting were used to assess apoptosis of NSCs and the expressions of Bcl-2 and Bax in each group. Results: IFA results showed that isolated rat NSCs were nestin-positive and microglial cells were CD11b/c-positive. Among all the groups, the Aβ+co-culture group has the lowest BrdU expression level, the lowest MAP2-positive, ChAT-positive cell counts and the highest NSC apoptosis rate. Smaller amounts of IL-6, TNF-α and MIP-α were being secreted by microglial cells in the HupA+Aβ+co-culture group compared with those in the Aβ+ co-culture group. Also the Bcl-2: Bax ratio was much higher in the HupA+Aβ+co-culture group than in the Aβ+co-culture group. Conclusions: HupA inhibits cell apoptosis through restraining microglia’s inflammatory response induced by Aβ1-42. PMID:26261518

  8. Neutronic calculation of reactor cells

    International Nuclear Information System (INIS)

    Jaliff, J.O.

    1981-01-01

    Multigroup calculations of cylindrical pin cells were programmed, in Fortran IV, upon the basis of collision probabilities in each energy group. A rational approximation to the fuel-to-fuel collision probability in resonance groups was used. Together with the intermediate resonance theory, cross sections corrected for heterogeneity and absorber interactions were found. For the optimization of the program, the cell of a BWR reactor was taken as reference. Data for such a cell and the reactor's operating conditions are presented. PINCEL is a fast and flexible program, with checked results, around a 69-group library. (M.E.L.) [es

  9. Increased opioid dependence in a mouse model of panic disorder

    Directory of Open Access Journals (Sweden)

    Xavier Gallego

    2010-02-01

    Full Text Available Panic disorder is a highly prevalent neuropsychiatric disorder that shows co-occurrence with substance abuse. Here, we demonstrate that TrkC, the high affinity receptor for neurotrophin-3, is a key molecule involved in panic disorder and opiate dependence, using a transgenic mouse model (TgNTRK3. Constitutive TrkC overexpression in TgNTRK3 mice dramatically alters spontaneous firing rates of locus coeruleus neurons and the response of the noradrenergic system to chronic opiate exposure, possibly related to the altered regulation of neurotrophic peptides observed. Notably, TgNTRK3 locus coeruleus neurons showed an increased firing rate in saline-treated conditions and profound abnormalities in their response to met5-enkephalin. Behaviorally, chronic morphine administration induced a significantly increased withdrawal syndrome in TgNTRK3 mice. In conclusion, we show here that the NT-3/TrkC system is an important regulator of neuronal firing in locus coeruleus and could contribute to the adaptations of the noradrenergic system in response to chronic opiate exposure. Moreover, our results indicate that TrkC is involved in the molecular and cellular changes in noradrenergic neurons underlying both panic attacks and opiate dependence and support a functional endogenous opioid deficit in panic disorder patients.

  10. Coenzyme Q10 protects hair cells against aminoglycoside.

    Directory of Open Access Journals (Sweden)

    Kazuma Sugahara

    Full Text Available It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10 is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group. In the neomycin group, utricles were cultured with neomycin (1 mM to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30-0.3 µM. Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.

  11. Effects on proliferation and cell cycle of irradiated KG-1 cells stimulated by CM-CSF

    International Nuclear Information System (INIS)

    Guo Dehuang; Dong Bo; Wen Gengyun; Luo Qingliang; Mao Bingzhi

    2000-01-01

    In order to explore the variety of cell proliferation and cell cycle after exposure to ionizing radiation, the responses of irradiated KG-1 cells of the human myeloid leukemia stimulated by GM-CSF, the most common used cytokine in clinic, were investigated. The results showed that GM-CSF enhance KG-1 cells proliferation, reduce G0/G1 block, increase S phase and G2/M phase. The stimulation effects of the GM-CSF are more effective in irradiated group than in control group

  12. CD28-Negative CD4+ and CD8+ T Cells in Antiretroviral Therapy–Naive HIV-Infected Adults Enrolled in Adult Clinical Trials Group Studies

    Science.gov (United States)

    Tassiopoulos, Katherine; Landay, Alan; Collier, Ann C.; Connick, Elizabeth; Deeks, Steven G.; Hunt, Peter; Lewis, Dorothy E.; Wilson, Cara; Bosch, Ronald

    2012-01-01

    Background Individuals infected with human immunodeficiency virus (HIV) have higher risk than HIV-negative individuals for diseases associated with aging. T-cell senescence, characterized by expansion of cells lacking the costimulatory molecule CD28, has been hypothesized to mediate these risks. Methods We measured the percentage of CD28−CD4+ and CD8+ T cells from HIV-infected treatment-naive adults from 5 Adult Clinical Trials Group (ACTG) antiretroviral therapy (ART) studies and the ALLRT (ACTG Longitudinal Linked Randomized Trials) cohort, and from 48 HIV-negative adults. Pretreatment and 96-week posttreatment %CD28− cells were assessed using linear regression for associations with age, sex, race/ethnicity, CD4 count, HIV RNA, ART regimen, and hepatitis C virus (HCV) infection. Results In total, 1291 chronically HIV-infected adults were studied. Pretreatment, lower CD4 count was associated with higher %CD28−CD4+ and %CD28−CD8+ cells. For CD8+ cells, younger age and HCV infection were associated with a lower %CD28−. ART reduced %CD28− levels at week 96 among virally suppressed individuals. Older age was strongly predictive of higher %CD28−CD8+. Compared to HIV-uninfected individuals, HIV-infected individuals maintained significantly higher %CD28−. Conclusions Effective ART reduced the proportion of CD28− T cells. However, levels remained abnormally high and closer to levels in older HIV-uninfected individuals. This finding may inform future research of increased rates of age-associated disease in HIV-infected adults. PMID:22448010

  13. HUG - the Hydrogen Utility Group

    International Nuclear Information System (INIS)

    Tinkler, M.

    2006-01-01

    The Hydrogen Utility Group (HUG) was formally established in October 2005 by a group of leading electric utilities with a common interest in sharing hydrogen experiences and lessons learned. HUG's Mission Statement is: 'To accelerate utility integration of promising hydrogen energy related business applications through the coordinated efforts and actions of its members in collaboration with key stakeholders, including government agencies and utility support organizations.' In February 2006, HUG members presented a briefing to the US Senate Hydrogen and Fuel Cell Caucus in Washington, DC, outlining the significant role that the power industry should play in an emerging hydrogen economy. This presentation provides an overview of that briefing, summarizing the HUG's ongoing interests and activities

  14. Molecular cloning of a mouse DNA repair gene that complements the defect of group-A xeroderma pigmentosum

    International Nuclear Information System (INIS)

    Tanaka, K.; Satokata, I.; Ogita, Z.; Uchida, T.; Okada, Y.

    1989-01-01

    For isolation of the gene responsible for xeroderma pigmentosum (XP) complementation group A, plasmid pSV2gpt and genomic DNA from a mouse embryo were cotransfected into XP2OSSV cells, a group-A XP cell line. Two primary UV-resistant XP transfectants were isolated from about 1.6 X 10(5) pSV2gpt-transformed XP colonies. pSV2gpt and genomic DNA from the primary transfectants were again cotransfected into XP2OSSV cells and a secondary UV-resistant XP transfectant was obtained by screening about 4.8 X 10(5) pSV2gpt-transformed XP colonies. The secondary transfectant retained fewer mouse repetitive sequences. A mouse gene that complements the defect of XP2OSSV cells was cloned into an EMBL3 vector from the genome of a secondary transfectant. Transfections of the cloned DNA also conferred UV resistance on another group-A XP cell line but not on XP cell lines of group C, D, F, or G. Northern blot analysis of poly(A)+ RNA with a subfragment of cloned mouse DNA repair gene as the probe revealed that an approximately 1.0 kilobase mRNA was transcribed in the donor mouse embryo and secondary transfectant, and approximately 1.0- and approximately 1.3-kilobase mRNAs were transcribed in normal human cells, but none of these mRNAs was detected in three strains of group-A XP cells. These results suggest that the cloned DNA repair gene is specific for group-A XP and may be the mouse homologue of the group-A XP human gene

  15. All-trans retinoic acid inhibits craniopharyngioma cell growth: study on an explant cell model.

    Science.gov (United States)

    Li, Qiang; You, Chao; Zhou, Liangxue; Sima, Xiutian; Liu, Zhiyong; Liu, Hao; Xu, Jianguo

    2013-05-01

    The ratio between FABP5 and CRABPII determines cellular response to physiological level of retinoic acid; tumor cells undergo proliferation with high level of FABP5 and apoptosis with high level of CRABPII. We intended to study FABP5 and CRABPII expression in craniopharyngiomas, to establish craniopharyngioma cell model using explants method, and to study the effect of pharmacological dose of retinoic acid on craniopharyngioma cells. Expression of FABP5 and CRABPII in craniopharyngioma tissue from 20 patients was studied using immunohistochemistry. Primary craniopharyngioma cell cultures were established using tissue explants method. Craniopharyngioma cells were treated using various concentrations of all-trans retinoic acid, and cell growth curve, apoptosis, expression of FABP5, CRABPII and NF-κB were assayed in different groups. FABP5/CRABPII ratio was significantly higher in adamatinomatous group than that in papillary group. Cell cultures were established in 19 cases (95 %). Pharmacological level retinoic acid inhibited cell growth and induced cellular apoptosis in dose dependent manner, and apoptosis rate cells treated with 30 μM retinoic acid for 24 h was 43 %. Also, retinoic acid increased CRABPII, and decreased FABP5 and NF-κB expression in craniopharyngioma cells. High FABP5/CRABPII ratio is observed in adamatinomatous craniopharyngioma. Retinoic acid at pharmacological level induced craniopharyngioma cell apoptosis via increasing FABP5/CRABPII ratio and inhibiting NF-κB signaling pathway. Our study demonstrated that all-trans retinoic acid might be a candidate for craniopharyngioma adjuvant chemotherapy in future.

  16. Endocrine cells in the denervated intestine

    Science.gov (United States)

    Santos, Gilda C; Zucoloto, Sérgio; Garcia, Sérgio B

    2000-01-01

    This study deals with the effects of myenteric denervation of the proximal jejunum on endocrine cell population of the crypt-villus unit, 5 months after treatment with benzalkonium chloride (BAC). Male Wistar albino rats weighing on average 100 g were allocated to two groups: the BAC group − the proximal jejunal serosa was treated with 2 mm BAC for 30 min, and the control group − treated with saline solution (0,9% NaCl). There was a significant reduction in neurone number in the jejunal myenteric plexus of the BAC group and the endocrine cell population (serotoninergic and argyrophilic cells) was significantly increased in this intestine segment. In conclusion, the present findings provide further evidence that the myenteric denervation induced by BAC may lead to the development of a local imbalance of the neurotransmitters, with a consequent induction of enteroendocrine cell (argyrophilic and serotoninergic cells) hyperplasia in the crypt and villus. PMID:10971748

  17. MURALB - a programme for calculating neutron fluxes in many groups

    International Nuclear Information System (INIS)

    MacDougall, J.

    1977-09-01

    The program MURALB solves the multi-group transport equation (with no upscatter) in many equal lethargy groups to produce neutron fluxes in these groups. The code has been made very flexible by confining the spatial flux solution to a single subroutine which takes as input the cross section data and source for a single group and calculates the flux for that group. In this way by supplying different versions of this routine different geometries and methods of solution of the transport equation may be treated. At present plane, cylindrical and spherical diffusion theory and collision probability solutions are available, together with a two region collision probability solution for a rod in a square cell. There is no basic restriction to one dimension but the practical size of problem tends to be limited to about 30 spatial regions by core storage requirements. In addition to the flux solution, the code calculates neutron balance, reaction rates and few groups cross sections for each mesh region, together with the values averaged over the system (cell or reactor). The program is available both as a stand-alone code and integrated into the COSMOS system. (author)

  18. In vitro secretion of TNF-α from bone marrow mononuclear cells incubated on amino group modified TiO2 nano-composite under ultrasound irradiation

    International Nuclear Information System (INIS)

    Furuzono, T.; Masuda, M.; Nitta, N.; Kaya, A.; Yamane, T.; Okada, M.

    2010-01-01

    It is recently known that titanium dioxide (TiO 2 ) can be excited by ultrasound and release of OH radicals on the surface. In this study, secretion of an indirect angiogenic factor, tumor necrosis factor-α (TNF-α), from bone marrow mononuclear cells (BM-MNC) incubated on amino group modified TiO 2 nano-particles covalently coated on polyester fabric (TiO 2 /PET) under ultrasonic irradiation was examined in vitro. The cell viability and TNF-α secretion were measured under ultrasound irradiation condition with 255 mW/cm 2 of intensity, which is below the highest output (1 W/cm 2 ) specified in the safety standard for a medical ultrasonic diagnostic apparatus. The living cell number on the TiO 2 /PET and original PET with/without continuous ultrasound irradiation was unchanged statistically by ANOVA test. TNF-α secretion level from BM-MNC remarkably increased on the TiO 2 /PET under ultrasonic irradiation without cell damage. It was, therefore, thought that the high level of TNF-α secretion on the TiO 2 nano-composite by ultrasound irradiation was due to oxidative stress induced from OH radicals on TiO 2 .

  19. Isolation of Human Innate Lymphoid Cells.

    Science.gov (United States)

    Krabbendam, Lisette; Nagasawa, Maho; Spits, Hergen; Bal, Suzanne M

    2018-06-29

    Innate lymphoid cells (ILCs) are innate immune cells of lymphoid origin that have important effector and regulatory functions in the first line of defense against pathogens, but also regulate tissue homeostasis, remodeling, and repair. Their function mirrors T helper cells and cytotoxic CD8 + T lymphocytes, but they lack expression of rearranged antigen-specific receptors. Distinct ILC subsets are classified in group 1 ILCs (ILC1s), group 2 ILCs (ILC2s), and group 3 ILCs (ILC3s and lymphoid tissue-inducer cells), based on the expression of transcription factors and the cytokines they produce. As the frequency of ILCs is low, their isolation requires extensive depletion of other cell types. The lack of unique cell surface antigens further complicates the identification of these cells. Here, methods for ILC isolation and characterization from human peripheral blood and different tissues are described. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

  20. Effect of individual and group housing of mice on the level of radioresistance

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    Dorozhkina O.V.

    2015-12-01

    Full Text Available Aim: to examine the effect of individual and group housing of mice on radioresistance. Material and methods. Effects of individual and group housing of mice on immunity and blood systems were studied on ICR (CD-1 and C57BI6 male mice before and after proton irradiation. Results. Group housing of intact animals resulted in a decline in the number of nucleated cells in the femur bone marrow and thymus mass. The irradiation with proton with energy of 171 MeV at a dose of 1 Gy causes a statistically significant greater reduction of the number of nucleated cells in the femur bone marrow in group-housed mice. A trend toward greater safety of the number of leukocytes in the peripheral blood and higher proliferative activity of bone marrow cells, as well as lower level of aberrant mitoses have been noted in individually-housed mice. Reduction processes in the recovery period of radiation sickness take place at a greater rate in group-housed mice. Conclusion. Group housing of male mice causes increased sensitivity of the blood and immunity systems to the effects of radiation and at the same time accelerates processes of radiation recovery.