Fingolimod modulates microglial activation to augment markers of remyelination

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Baker David

2011-07-01

Full Text Available Abstract Introduction Microglial activation in multiple sclerosis has been postulated to contribute to long-term neurodegeneration during disease. Fingolimod has been shown to impact on the relapsing remitting phase of disease by modulating autoreactive T-cell egress from lymph organs. In addition, it is brain penetrant and has been shown to exert multiple effects on nervous system cells. Methods In this study, the impact of fingolimod and other sphingosine-1-phosphate receptor active molecules following lysophosphotidyl choline-induced demyelination was examined in the rat telencephalon reaggregate, spheroid cell culture system. The lack of immune system components allowed elucidation of the direct effects of fingolimod on CNS cell types in an organotypic situation. Results Following demyelination, fingolimod significantly augmented expression of myelin basic protein in the remyelination phase. This increase was not associated with changes in neurofilament levels, indicating de novo myelin protein expression not associated with axonal branching. Myelin wrapping was confirmed morphologically using confocal and electron microscopy. Increased remyelination was associated with down-regulation of microglial ferritin, tumor necrosis factor alpha and interleukin 1 during demyelination when fingolimod was present. In addition, nitric oxide metabolites and apoptotic effectors caspase 3 and caspase 7 were reduced during demyelination in the presence of fingolimod. The sphingosine-1-phosphate receptor 1 and 5 agonist BAF312 also increased myelin basic protein levels, whereas the sphingosine-1-phosphate receptor 1 agonist AUY954 failed to replicate this effect on remyelination. Conclusions The results presented indicate that modulation of S1P receptors can ameliorate pathological effectors associated with microglial activation leading to a subsequent increase in protein and morphological markers of remyelination. In addition, sphingosine-1-phosphate

The effect of omega-3 fatty acids on central nervous system remyelination in fat-1 mice.

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Siegert, Elise; Paul, Friedemann; Rothe, Michael; Weylandt, Karsten H

2017-01-24

There is a large body of experimental evidence suggesting that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are capable of modulating immune function. Some studies have shown that these PUFAs might have a beneficial effect in patients suffering form multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system (CNS). This could be due to increased n-3 PUFA-derived anti-inflammatory lipid mediators. In the present study we tested the effect of an endogenously increased n-3 PUFA status on cuprizone-induced CNS demyelination and remyelination in fat-1 mice versus their wild-type (wt) littermates. Fat-1 mice express an n-3 desaturase, which allows them to convert n-6 PUFAs into n-3 PUFAs. CNS lipid profiles in fat-1 mice showed a significant increase of eicosapentaenoic acid (EPA) levels but similar docosahexaenoic acid levels compared to wt littermates. This was also reflected in significantly higher levels of monohydroxy EPA metabolites such as 18-hydroxyeicosapentaenoic acid (18-HEPE) in fat-1 brain tissue. Feeding fat-1 mice and wt littermates 0.2% cuprizone for 5 weeks caused a similar degree of CNS demyelination in both groups; remyelination was increased in the fat-1 group after a recovery period of 2 weeks. However, at p = 0.07 this difference missed statistical significance. These results indicate that n-3 PUFAs might have a role in promotion of remyelination after toxic injury to CNS oligodendrocytes. This might occur either via modulation of the immune system or via a direct effect on oligodendrocytes or neurons through EPA-derived lipid metabolites such as 18-HEPE.

The mechanism of Naringin-enhanced remyelination after spinal cord injury

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Wei Rong

2017-01-01

Full Text Available Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord. This study sought to reveal the mechanisms by which naringin improves oligodendrocyte precursor cell differentiation and maturation, and promotes remyelination. Spinal cord injury was induced in rats by the weight-drop method. Naringin was intragastrically administered daily (20, 40 mg/kg for 4 weeks after spinal cord injury induction. Behavioral assessment, histopathological staining, immunofluorescence spectroscopy, ultrastructural analysis and biochemical assays were employed. Naringin treatment remarkably mitigated demyelination in the white matter, increased the quality of myelinated nerve fibers and myelin sheath thickness, promoted oligodendrocyte precursor cell differentiation by upregulating the expression of NKx2.2 and 2′3′-cyclic nucleotide 3′-phosphodiesterase, and inhibited β-catenin expression and glycogen synthase kinase-3β (GSK-3β phosphorylation. These findings indicate that naringin treatment regulates oligodendrocyte precursor cell differentiation and promotes remyelination after spinal cord injury through the β-catenin/GSK-3β signaling pathway.

Experimental models of demyelination and remyelination.

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Torre-Fuentes, L; Moreno-Jiménez, L; Pytel, V; Matías-Guiu, J A; Gómez-Pinedo, U; Matías-Guiu, J

2017-08-29

Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary. We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models. Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Conceptual Understanding of Multiplicative Properties through Endogenous Digital Game Play

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Denham, Andre

2012-01-01

This study purposed to determine the effect of an endogenously designed instructional game on conceptual understanding of the associative and distributive properties of multiplication. Additional this study sought to investigate if performance on measures of conceptual understanding taken prior to and after game play could serve as predictors of…

Remyelination of the injured spinal cord

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Sasaki, Masanori; Li, Bingcang; Lankford, Karen L.; Radtke, Christine; Kocsis, Jeffery D.

2008-01-01

Contusive spinal cord injury (SCI) can result in necrosis of the spinal cord, but often long white matter tracts outside of the central necrotic core are demyelinated. One experimental strategy to improve functional outcome following SCI is to transplant myelin-forming cells to remyelinate these axons and improve conduction. This review focuses on transplantation studies using olfactory ensheathing cell (OEC) to improve functional outcome in experimental models of SCI and demyelination. The biology of the OEC, and recent experimental research and clinical studies using OECs as a potential cell therapy candidate are discussed. PMID:17618995

Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.

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Keirstead, Hans S; Nistor, Gabriel; Bernal, Giovanna; Totoiu, Minodora; Cloutier, Frank; Sharp, Kelly; Steward, Oswald

2005-05-11

Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

Delayed nerve stimulation promotes axon-protective neurofilament phosphorylation, accelerates immune cell clearance and enhances remyelination in vivo in focally demyelinated nerves.

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Nikki A McLean

Full Text Available Rapid and efficient axon remyelination aids in restoring strong electrochemical communication with end organs and in preventing axonal degeneration often observed in demyelinating neuropathies. The signals from axons that can trigger more effective remyelination in vivo are still being elucidated. Here we report the remarkable effect of delayed brief electrical nerve stimulation (ES; 1 hour @ 20 Hz 5 days post-demyelination on ensuing reparative events in a focally demyelinated adult rat peripheral nerve. ES impacted many parameters underlying successful remyelination. It effected increased neurofilament expression and phosphorylation, both implicated in axon protection. ES increased expression of myelin basic protein (MBP and promoted node of Ranvier re-organization, both of which coincided with the early reappearance of remyelinated axons, effects not observed at the same time points in non-stimulated demyelinated nerves. The improved ES-associated remyelination was accompanied by enhanced clearance of ED-1 positive macrophages and attenuation of glial fibrillary acidic protein expression in accompanying Schwann cells, suggesting a more rapid clearance of myelin debris and return of Schwann cells to a nonreactive myelinating state. These benefits of ES correlated with increased levels of brain derived neurotrophic factor (BDNF in the acute demyelination zone, a key molecule in the initiation of the myelination program. In conclusion, the tremendous impact of delayed brief nerve stimulation on enhancement of the innate capacity of a focally demyelinated nerve to successfully remyelinate identifies manipulation of this axis as a novel therapeutic target for demyelinating pathologies.

Delayed nerve stimulation promotes axon-protective neurofilament phosphorylation, accelerates immune cell clearance and enhances remyelination in vivo in focally demyelinated nerves.

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McLean, Nikki A; Popescu, Bogdan F; Gordon, Tessa; Zochodne, Douglas W; Verge, Valerie M K

2014-01-01

Rapid and efficient axon remyelination aids in restoring strong electrochemical communication with end organs and in preventing axonal degeneration often observed in demyelinating neuropathies. The signals from axons that can trigger more effective remyelination in vivo are still being elucidated. Here we report the remarkable effect of delayed brief electrical nerve stimulation (ES; 1 hour @ 20 Hz 5 days post-demyelination) on ensuing reparative events in a focally demyelinated adult rat peripheral nerve. ES impacted many parameters underlying successful remyelination. It effected increased neurofilament expression and phosphorylation, both implicated in axon protection. ES increased expression of myelin basic protein (MBP) and promoted node of Ranvier re-organization, both of which coincided with the early reappearance of remyelinated axons, effects not observed at the same time points in non-stimulated demyelinated nerves. The improved ES-associated remyelination was accompanied by enhanced clearance of ED-1 positive macrophages and attenuation of glial fibrillary acidic protein expression in accompanying Schwann cells, suggesting a more rapid clearance of myelin debris and return of Schwann cells to a nonreactive myelinating state. These benefits of ES correlated with increased levels of brain derived neurotrophic factor (BDNF) in the acute demyelination zone, a key molecule in the initiation of the myelination program. In conclusion, the tremendous impact of delayed brief nerve stimulation on enhancement of the innate capacity of a focally demyelinated nerve to successfully remyelinate identifies manipulation of this axis as a novel therapeutic target for demyelinating pathologies.

Resveratrol Promotes Remyelination in Cuprizone Model of Multiple Sclerosis: Biochemical and Histological Study.

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Ghaiad, Heba R; Nooh, Mohammed M; El-Sawalhi, Maha M; Shaheen, Amira A

2017-07-01

Multiple sclerosis (MS) is a demyelinating neurodegenerative disease, representing a major cause of neurological disability in young adults. Resveratrol is a stilbenoid polyphenol, known to pass blood brain barrier and exhibit antioxidant, anti-inflammatory, and neuroprotective effects in several brain injuries. Cuprizone model of MS is particularly beneficial in studying demyelination/remyelination. Our study examined the potential neuroprotective and pro-remyelination effects of resveratrol in cuprizone-intoxicated C57Bl/6 mice. Mice were fed with chow containing 0.7 % cuprizone for 7 days, followed by 3 weeks on 0.2 % cuprizone diet. Resveratrol (250 mg/kg/day, p.o.) was given for 3 weeks starting from the second week. At the end of the experiment, animals were tested on rotarod to evaluate changes in balance and motor coordination. Mice were then sacrificed to measure the brain content of glutathione, lipid peroxidation products, adenosine triphosphate, and phospho-inhibitory subunit of nuclear factor κB-α. The activities of cytochrome oxidase and superoxide dismutase were also assessed. The gene expression of myelin basic protein, 2',3'-cyclic nucleotide 3' phosphodiesterase, oligodendrocyte transcription factor-1 (Olig1), NF-κB p65 subunit, and tumor necrosis factor-α was also estimated. Luxol fast blue/periodic acid-Schiff stained brain sections were blindly scored to assess the myelin status. Resveratrol effectively enhanced motor coordination and balance, reversed cuprizone-induced demyelination, improved mitochondrial function, alleviated oxidative stress, and inhibited NF-κB signaling. Interestingly, resveratrol increased Olig1 expression that is positively correlated to active remyelination. The present study may be the first to indicate a pro-remyelinative effect for resveratrol which might represent a potential additive benefit in treating MS.

A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials

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Eleuteri, C.; Olla, S.; Veroni, C.; Umeton, R.; Mechelli, R.; Romano, S.; Buscarinu, Mc.; Ferrari, F.; Calò, G.; Ristori, G.; Salvetti, M.; Agresti, C.

2017-04-01

There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects. We then characterized the effects of these compounds on OPC proliferation and differentiation in mouse glial cultures, and on myelination and remyelination in organotypic cultures. Three molecules, edaravone, 5-methyl-7-methoxyisoflavone and lovastatin, gave positive results in all screening tiers. We validated the results by retesting independent stocks of the compounds, analyzing their purity, and performing dose-response curves. To identify the chemical features that may be modified to enhance the compounds’ activity, we tested chemical analogs and identified, for edaravone, the functional groups that may be essential for its activity. Among the selected remyelinating candidates, edaravone appears to be of strong interest, also considering that this drug has been approved as a neuroprotective agent for acute ischemic stroke and amyotrophic lateral sclerosis in Japan.

Progesterone Enhanced Remyelination in the Mouse Corpus Callosum After Cuprizone Induced Demyelination

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Iraj Ragerdi Kashani

2015-11-01

Full Text Available Background: Progesterone as a sex steroid hormone is thought to affect and prevent demyelination, but its role in promoting myelin repair is far less investigated. In this study, remyelinating potential of progesterone in corpus callosum was evaluated on an experimental model of MS. Methods: In this experimental study, adult male C57BL/6 mice were fed with 0.2% (w/w cuprizone in ground breeder chow ad libitum for 6 weeks. At day zero, after cuprizone removal, mice were divided randomly into two groups: (a placebo group, which received saline pellet implant, (b progesterone group, which received progesterone pellet implant. Some mice of the same age were fed with their normal diet to serve as the healthy control group. Two weeks after progesterone administration, Myelin content was assessed by Luxol-fast blue staining. The myelin basic protein (MBP and proteolipid protein (PLP expression were assessed using Western blot analysis and the changes in the number of oligodendrocytes and oligodendroglial progenitor cells were assessed by immunohistochemistry (IHC and flow cytometry. Results: Luxol-fast blue staining revealed enhanced remyelination in the progesterone group when compared with the placebo group. Densitometry measurements of immunoblots demonstrated that MBP and PLP proteins contents were significantly increased in the progesterone group compared with the placebo group. Flow cytometry and IHC analysis showed increases in Olig2 and O4 cells in the progesterone group compared with the placebo group. Conclusion: Overall, our results indicate that progesterone treatment can stimulate myelin production and that it may provide a feasible and practical way for remyelination in diseases such as multiple sclerosis.

Diosgenin promotes oligodendrocyte progenitor cell differentiation through estrogen receptor-mediated ERK1/2 activation to accelerate remyelination.

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Xiao, Lin; Guo, Dazhi; Hu, Chun; Shen, Weiran; Shan, Lei; Li, Cui; Liu, Xiuyun; Yang, Wenjing; Zhang, Weidong; He, Cheng

2012-07-01

Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is a prerequisite for remyelination after demyelination, and impairment of this process is suggested to be a major reason for remyelination failure. Diosgenin, a plant-derived steroid, has been implicated for therapeutic use in many diseases, but little is known about its effect on the central nervous system. In this study, using a purified rat OPC culture model, we show that diosgenin significantly and specifically promotes OPC differentiation without affecting the viability, proliferation, or migration of OPC. Interestingly, the effect of diosgenin can be blocked by estrogen receptor (ER) antagonist ICI 182780 but not by glucocorticoid and progesterone receptor antagonist RU38486, nor by mineralocorticoid receptor antagonist spirolactone. Moreover, it is revealed that both ER-alpha and ER-beta are expressed in OPC, and diosgenin can activate the extracellular signal-regulated kinase 1/2 (ERK1/2) in OPC via ER. The pro-differentiation effect of diosgenin can also be obstructed by the ERK inhibitor PD98059. Furthermore, in the cuprizone-induced demyelination model, it is demonstrated that diosgenin administration significantly accelerates/enhances remyelination as detected by Luxol fast blue stain, MBP immunohistochemistry and real time RT-PCR. Diosgenin also increases the number of mature oligodendrocytes in the corpus callosum while it does not affect the number of OPCs. Taking together, our results suggest that diosgenin promotes the differentiation of OPC into mature oligodendrocyte through an ER-mediated ERK1/2 activation pathway to accelerate remyelination, which implicates a novel therapeutic usage of this steroidal natural product in demyelinating diseases such as multiple sclerosis (MS). Copyright © 2012 Wiley Periodicals, Inc.

Survival and Functionality of Human Induced Pluripotent Stem Cell-Derived Oligodendrocytes in a Nonhuman Primate Model for Multiple Sclerosis

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Thiruvalluvan, Arun; Czepiel, Marcin; Kap, Yolanda A.; Mantingh-Otter, Ietje; Vainchtein, Ilia; Kuipers, Jeroen; Bijlard, Marjolein; Baron, Wia; Giepmans, Ben; Brueck, Wolfgang; 'T Hart, Bert A.; Boddeke, Erik; Copray, Sjef

2016-01-01

: Fast remyelination by endogenous oligodendrocyte precursor cells (OPCs) is essential to prevent axonal and subsequent retrograde neuronal degeneration in demyelinating lesions in multiple sclerosis (MS). In chronic lesions, however, the remyelination capacity of OPCs becomes insufficient. Cell

Demyelination versus remyelination in progressive multiple sclerosis

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Bramow, Stephan; Frischer, Josa M; Lassmann, Hans

2010-01-01

The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive...... multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination...... compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments...

Functional and Celluar Assessment of Limited Remyelination in the Cuprizone Model

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2012-01-01

finger  coordination.  These  motor  impairments   are  observed  in...remyelination  might  result  from  aberrations  in  one   or  more  these  cellular  properties  ( Millet  et  al.,  2009... Millet  et  al  2009,  Gallo  and  Armstrong  2008).                    Specific  manipulation

Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation.

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Kristel Kegler

Full Text Available Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas

Interactions Between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma on Neuroinflammation, Demyelination, and Remyelination in Multiple Sclerosis.

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Vallée, Alexandre; Vallée, Jean-Noël; Guillevin, Rémy; Lecarpentier, Yves

2018-05-01

Multiple sclerosis (MS) is marked by neuroinflammation and demyelination with loss of oligodendrocytes in the central nervous system. The immune response is regulated by WNT/beta-catenin pathway in MS. Activated NF-kappaB, a major effector of neuroinflammation, and upregulated canonical WNT/beta-catenin pathway positively regulate each other. Demyelinating events present an upregulation of WNT/beta-catenin pathway, whereas proper myelinating phases show a downregulation of WNT/beta-catenin pathway essential for the promotion of oligodendrocytes precursors cells proliferation and differentiation. The activation of WNT/beta-catenin pathway results in differentiation failure and impairment in remyelination. However, PI3K/Akt pathway and TCF7L2, two downstream targets of WNT/beta-catenin pathway, are upregulated and promote proper remyelination. The interactions of these signaling pathways remain unclear. PPAR gamma activation can inhibit NF-kappaB, and can also downregulate the WNT/beta-catenin pathway. PPAR gamma and canonical WNT/beta-catenin pathway act in an opposite manner. PPAR gamma agonists appear as a promising treatment for the inhibition of demyelination and the promotion of proper remyelination through the control of both NF-kappaB activity and canonical WNT/beta-catenin pathway.

Endogenous Learning and Consensual Understanding in Multilateral Negotiations: Arguing and Bargaining in the WTO

OpenAIRE

Wolfe, Robert

2010-01-01

People at home and trade negotiators in Geneva cannot bargain what they do not understand, and what they bargain must be based on consensual understanding among the relevant actors, whether or not they agree on what to do about it. Consensual understanding is endogenous, arising in an argumentative process of learning structured by constitutive principles of a regime. In a departure from both rationalist and constructivist approaches to negotiation analysis in political science, my goal in th...

Is There a Role for Endogenous 5-HT in Gastrointestinal Motility? How Recent Studies Have Changed Our Understanding.

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Spencer, Nick J; Keating, Damien J

2016-01-01

Over the past few years, there have been dramatic changes in our understanding of the role of endogenous 5-hydroxytryptamine (5-HT) in the generation of gastrointestinal (GI) motility patterns in the small and large intestine. The idea that endogenous 5-HT played a major role in the generation of peristalsis in the small intestine was first proposed in the mid 1950s, after it was discovered that endogenous 5-HT could be released from the mucosa at a similar time that peristalsis occurred; and that exogenous 5-HT could potently stimulate peristalsis. The fact that exogenous 5-HT stimulated peristalsis and that there was a similarity in timing between the release of 5-HT from the mucosa and the onset of peristalsis led investigators to propose that release of endogenous 5-HT from the mucosa was causally related to the generation of peristalsis. In further support of this, other studies showed that selective 5-HT antagonists could inhibit or block peristalsis, and other motor patterns, such as the migrating motor complex. Taken together, based on these findings, some laboratories believed that endogenous 5-HT (synthesized in the gut wall) was an important mediator, or initiator, of different propulsive motor patterns in the lower GI tract. This notion changed dramatically in the past few years, however, after it was discovered that removal of the mucosa abolished all cyclical release of endogenous 5-HT, but did not block peristalsis, nor the cyclical migrating complex. Furthermore, other laboratories revealed that genetic deletion of the gene tryptophan hydroxylase 1 (TPH-1) (that synthesizes endogenous 5-HT in the mucosa) actually had no inhibitory effect on transit of intestinal contents in live animals. Then, perhaps one of the most startling of all observations was the discovery that selective 5-HT receptor antagonists actually have the same inhibitory effects on peristalsis and the migrating complex in segments of intestine that had been depleted of all

17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

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Yan Chen

2016-01-01

Full Text Available Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2 on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation.

17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

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Chen, Yan; Guo, Wenjie; Li, Wenjuan; Cheng, Meng; Hu, Ying; Xu, Wenming

2016-01-01

Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2) on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP) expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation. PMID:27872858

The contribution of oligodendrocytes and oligodendrocyte progenitor cells to central nervous system repair in multiple sclerosis: perspectives for remyelination therapeutic strategies

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Adriana Octaviana Dulamea

2017-01-01

Full Text Available Oligodencrocytes (OLs are the main glial cells of the central nervous system involved in myelination of axons. In multiple sclerosis (MS, there is an imbalance between demyelination and remyelination processes, the last one performed by oligodendrocyte progenitor cells (OPCs and OLs, resulting into a permanent demyelination, axonal damage and neuronal loss. In MS lesions, astrocytes and microglias play an important part in permeabilization of blood-brain barrier and initiation of OPCs proliferation. Migration and differentiation of OPCs are influenced by various factors and the process is finalized by insufficient acummulation of OLs into the MS lesion. In relation to all these processes, the author will discuss the potential targets for remyelination strategies.

Discovery of endogenous opioid systems: what it has meant for the clinician's understanding of pain and its treatment.

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Ballantyne, Jane C; Sullivan, Mark D

2017-12-01

Before the discovery of the endogenous opioid system in the 1970s, opioids were understood only through the lens of opioid drug effects. Opium produced sleep, pain relief, and addiction. Once a variety of opioids had been extracted from opium, and still others synthesized chemically, it became clear that there must be endogenous receptors to explain differential drug effects. So, the search was on to identify the receptors, and subsequently their endogenous ligands. Even then, the consequential ways in which the endogenous opioid system influences the way we respond to the environment and survive took time to unravel. Today's understanding extends far beyond simply accepting pain relief and addiction as separate processes, to the realization that the endogenous opioid system achieves constant adjustments between punishment (pain) and reward in communicating areas of the brain previously thought to subserve separate functions. The system also plays a crucial role in socialization. Taken together, these 2 lines of research have led to new insights into why the endogenous opioid system is so important in terms of evolution, individual survival and day-to-day function, and how important it is to consider opioid medications within the context of these critical natural functions.

Postnatal Sonic hedgehog (Shh) responsive cells give rise to oligodendrocyte lineage cells during myelination and in adulthood contribute to remyelination.

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Sanchez, Maria A; Armstrong, Regina C

2018-01-01

Sonic hedgehog (Shh) regulates a wave of oligodendrocyte production for extensive myelination during postnatal development. During this postnatal period of oligodendrogenesis, we fate-labeled cells exhibiting active Shh signaling to examine their contribution to the regenerative response during remyelination. Bitransgenic mouse lines were generated for induced genetic fate-labeling of cells actively transcribing Shh or Gli1. Gli1 transcription is an effective readout for canonical Shh signaling. Shh CreERT2 mice and Gli1 CreERT2 mice were crossed to either R26 tdTomato mice to label cells with red fluorescence, or, R26 IAP mice to label membranes with alkaline phosphatase. When tamoxifen (TMX) was given on postnatal days 6-9 (P6-9), Shh ligand synthesis was prevalent in neurons of Shh CreERT2 ; R26 tdTomato mice and Shh CreERT2 ;R26 IAP mice. In Gli1 CreERT2 crosses, TMX from P6-9 detected Gli1 transcription in cells that populated the corpus callosum (CC) during postnatal myelination. Delaying TMX to P14-17, after the peak of oligodendrogenesis, significantly reduced labeling of Shh synthesizing neurons and Gli1 expressing cells in the CC. Importantly, Gli1 CreERT2 ;R26 tdTomato mice given TMX from P6-9 showed Gli1 fate-labeled cells in the adult (P56) CC, including cycling progenitor cells identified by EdU incorporation and NG2 immunolabeling. Furthermore, after cuprizone demyelination of the adult CC, Gli1 fate-labeled cells incorporated EdU and were immunolabeled by NG2 early during remyelination while forming myelin-like membranes after longer periods for remyelination to progress. These studies reveal a postnatal cell population with transient Shh signaling that contributes to oligodendrogenesis during CC myelination, and gives rise to cells that continue to proliferate in adulthood and contribute to CC remyelination. Published by Elsevier Inc.

Grey matter OPCs are less mature and less sensitive to IFN gamma than white matter OPCs : consequences for remyelination

NARCIS (Netherlands)

Lentferink, Dennis H; Jongsma, Jacomien M; Werkman, Inge; Baron, Wia

2018-01-01

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by the formation of demyelinated lesions in the central nervous system. At later stages of the disease repair in the form of remyelination often fails, which leads to axonal degeneration and neurological disability. For the

Bone Morphogenetic Protein Signaling and Olig1/2 Interact to Regulate the Differentiation and Maturation of Adult Oligodendrocyte Precursor Cells

OpenAIRE

Cheng, Xiaoxin; Wang, Yaping; He, Qian; Qiu, Mengsheng; Whittemore, Scott R.; Cao, Qilin

2007-01-01

Promotion of remyelination is an important therapeutic strategy for the treatment of the demyelinating neurological disorders. Adult oligodendrocyte precursor cells (OPCs), which normally reside quiescently in the adult central nervous system (CNS), become activated and proliferative after demyelinating lesions. However, the extent of endogenous remyelination is limited because of the failure of adult OPCs to mature into myelinating oligodendrocytes (OLs) in the demyelinated CNS. Understandin...

Opportunistic activation of TRP receptors by endogenous lipids: exploiting lipidomics to understand TRP receptor cellular communication.

Science.gov (United States)

Bradshaw, Heather B; Raboune, Siham; Hollis, Jennifer L

2013-03-19

Transient receptor potential channels (TRPs) form a large family of ubiquitous non-selective cation channels that function as cellular sensors and in many cases regulate intracellular calcium. Identification of the endogenous ligands that activate these TRP receptors is still under intense investigation with the majority of these channels still remaining "orphans." That these channels respond to a variety of external stimuli (e.g. plant-derived lipids, changes in temperature, and changes in pH) provides a framework for their abilities as cellular sensors, however, the mechanism of direct activation is still under much debate and research. In the cases where endogenous ligands (predominately lipids) have shown direct activation of a channel, multiple ligands have been shown to activate the same channel suggesting that these receptors are "promiscuous" in nature. Lipidomics of a growing class of endogenous lipids, N-acyl amides, the most famous of which is N-arachidonoyl ethanolamine (the endogenous cannabinoid, Anandamide) is providing a novel set of ligands that have been shown to activate some members of the TRP family and have the potential to deorphanize many more. Here it is argued that activation of TRPV receptors, a subset of the larger family of TRPs, by multiple endogenous lipids that are structurally analogous is a model system to drive our understanding that many TRP receptors are not promiscuous, but are more characteristically "opportunistic" in nature; exploiting the structural similarity and biosynthesis of a narrow range of analogous endogenous lipids. In addition, this manuscript will compare the activation properties of TRPC5 to the activity profile of an "orphan" lipid, N-palmitoyl glycine; further demonstrating that lipidomics aimed at expanding our knowledge of the family of N-acyl amides has the potential to provide novel avenues of research for TRP receptors. Copyright © 2012 Elsevier Inc. All rights reserved.

An Extract of Chinpi, the Dried Peel of the Citrus Fruit Unshiu, Enhances Axonal Remyelination via Promoting the Proliferation of Oligodendrocyte Progenitor Cells

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Hideaki Tokunaga

2016-01-01

Full Text Available The aging-induced decrease in axonal myelination/remyelination is due to impaired recruitment and differentiation of oligodendrocyte progenitor cells (OPCs. Our previous studies have shown that a monoclonal antibody to DEAD (Asp-Glu-Ala-Asp box polypeptide 54 (Ddx54, a member of the DEAD box family of RNA helicases, (1 specifically labels oligodendrocyte lineages, (2 binds to mRNA and protein isoforms of myelin basic proteins (MBP, and (3 regulates migration of OPCs from ventricular zone to corpus callosum in mice. It has also been demonstrated that specific loss of a 21.5 kDa MBP isoform (MBP21.5 reflects demyelination status, and oral administration of an extract of Chinpi, citrus unshiu peel, reversed the aging-induced demyelination. Here, we report that Chinpi treatment induced a specific increase in the MBP21.5, led to the reappearance of Ddx54-expressing cells in ventricular-subventricular zone and corpus callosum of aged mice, and promoted remyelination. Treatment of in vitro OPC cultures with Chinpi constituents, hesperidin plus narirutin, led to an increase in 5-bromo-2′-deoxyuridine incorporation in Ddx54-expressing OPCs, but not in NG2- or Olig2-expressing cell populations. The present study suggests that Ddx54 plays crucial role in remyelination. Furthermore, Chinpi and Chinpi-containing herbal medicines may be a therapeutic option for the aging-induced demyelination diseases.

Imaging outcomes for trials of remyelination in multiple sclerosis.

Science.gov (United States)

Mallik, Shahrukh; Samson, Rebecca S; Wheeler-Kingshott, Claudia A M; Miller, David H

2014-12-01

Trials of potential neuroreparative agents are becoming more important in the spectrum of multiple sclerosis research. Appropriate imaging outcomes are required that are feasible from a time and practicality point of view, as well as being sensitive and specific to myelin, while also being reproducible and clinically meaningful. Conventional MRI sequences have limited specificity for myelination. We evaluate the imaging modalities which are potentially more specific to myelin content in vivo, such as magnetisation transfer ratio (MTR), restricted proton fraction f (from quantitative magnetisation transfer measurements), myelin water fraction and diffusion tensor imaging (DTI) metrics, in addition to positron emission tomography (PET) imaging. Although most imaging applications to date have focused on the brain, we also consider measures with the potential to detect remyelination in the spinal cord and in the optic nerve. At present, MTR and DTI measures probably offer the most realistic and feasible outcome measures for such trials, especially in the brain. However, no one measure currently demonstrates sufficiently high sensitivity or specificity to myelin, or correlation with clinical features, and it should be useful to employ more than one outcome to maximise understanding and interpretation of findings with these sequences. PET may be less feasible for current and near-future trials, but is a promising technique because of its specificity. In the optic nerve, visual evoked potentials can indicate demyelination and should be correlated with an imaging outcome (such as optic nerve MTR), as well as clinical measures. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Prevalence, dynamics, and biochemical predictors of optic nerve remyelination after methanol-induced acute optic neuropathy: a 2-year prospective study in 54 patients

Czech Academy of Sciences Publication Activity Database

Nurieva, O.; Kotíková, K.; Urban, P.; Pelclová, D.; Petřík, V.; Navrátil, Tomáš; Zakharov, S.

2016-01-01

Roč. 147, č. 1 (2016), s. 239-249 ISSN 0026-9247 Institutional support: RVO:61388955 Keywords : methanol optic neuropathy * visual evoked potentials * remyelination Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.282, year: 2016

On the origins of endogenous thoughts.

Science.gov (United States)

Tillas, Alexandros

2017-05-01

Endogenous thoughts are thoughts that we activate in a top-down manner or in the absence of the appropriate stimuli. We use endogenous thoughts to plan or recall past events. In this sense, endogenous thinking is one of the hallmarks of our cognitive lives. In this paper, I investigate how it is that we come to possess endogenous control over our thoughts. Starting from the close relation between language and thinking, I look into speech production-a process motorically controlled by the inferior frontal gyrus (IFG). Interestingly, IFG is also closely related to silent talking, as well as volition. The connection between IFG and volition is important given that endogenous thoughts are or at least greatly resemble voluntary actions. Against this background, I argue that IFG is key to understanding the origins of conscious endogenous thoughts. Furthermore, I look into goal-directed thinking and show that IFG plays a key role also in unconscious endogenous thinking.

In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination

International Nuclear Information System (INIS)

Armstrong, R.; Friedrich, V.L. Jr.; Holmes, K.V.; Dubois-Dalcq, M.

1990-01-01

A demyelinating disease induced in C57B1/6N mice by intracranial injection of a coronavirus (murine hepatitis virus strain A59) is followed by functional recovery and efficient CNS myelin repair. To study the biological properties of the cells involved in this repair process, glial cells were isolated and cultured from spinal cords of these young adult mice during demyelination and remyelination. Using three-color immunofluorescence combined with [3H]thymidine autoradiography, we have analyzed the antigenic phenotype and mitotic potential of individual glial cells. We identified oligodendrocytes with an antibody to galactocerebroside, astrocytes with an antibody to glial fibrillary acidic protein, and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells with the O4 antibody. Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. This proliferation was not further enhanced by adding PDGF, basic fibroblast growth factor (bFGF), or insulin-like growth factor I (IGF-I) to the defined medium. However, bFGF and IGF-I seemed to influence the fate of O-2A lineage cells in cultures of demyelinated tissue. Basic FGF decreased the percentage of cells expressing galactocerebroside. In contrast, IGF-I increased the relative proportion of oligodendrocytes. Thus, O-2A lineage cells from adult mice display greater phenotypic plasticity and enhanced mitotic potential in response to an episode of demyelination. These properties may be linked to the efficient remyelination achieved in this demyelinating disease

Current Gaps in the Understanding of the Subcellular Distribution of Exogenous and Endogenous Protein TorsinA.

Science.gov (United States)

Harata, N Charles

2014-01-01

An in-frame deletion leading to the loss of a single glutamic acid residue in the protein torsinA (ΔE-torsinA) results in an inherited movement disorder, DYT1 dystonia. This autosomal dominant disease affects the function of the brain without causing neurodegeneration, by a mechanism that remains unknown. We evaluated the literature regarding the subcellular localization of torsinA. Efforts to elucidate the pathophysiological basis of DYT1 dystonia have relied partly on examining the subcellular distribution of the wild-type and mutated proteins. A typical approach is to introduce the human torsinA gene (TOR1A) into host cells and overexpress the protein therein. In both neurons and non-neuronal cells, exogenous wild-type torsinA introduced in this manner has been found to localize mainly to the endoplasmic reticulum, whereas exogenous ΔE-torsinA is predominantly in the nuclear envelope or cytoplasmic inclusions. Although these outcomes are relatively consistent, findings for the localization of endogenous torsinA have been variable, leaving its physiological distribution a matter of debate. As patients' cells do not overexpress torsinA proteins, it is important to understand why the reported distributions of the endogenous proteins are inconsistent. We propose that careful optimization of experimental methods will be critical in addressing the causes of the differences among the distributions of endogenous (non-overexpressed) vs. exogenously introduced (overexpressed) proteins.

Cytokines as endogenous pyrogens.

Science.gov (United States)

Dinarello, C A

1999-03-01

Cytokines are pleiotropic molecules mediating several pathologic processes. Long before the discovery of cytokines as immune system growth factors or as bone marrow stimulants, investigators learned a great deal about cytokines when they studied them as the endogenous mediators of fever. The terms "granulocytic" or "endogenous pyrogen" were used to describe substances with the biologic property of fever induction. Today, we recognize that pyrogenicity is a fundamental biologic property of several cytokines and hence the clinically recognizeable property of fever links host perturbations during disease with fundamental perturbations in cell biology. In this review, the discoveries made on endogenous pyrogens are revisited, with insights into the importance of the earlier work to the present-day understanding of cytokines in health and in disease.

Promoting peripheral myelin repair.

Science.gov (United States)

Zhou, Ye; Notterpek, Lucia

2016-09-01

Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

Endogenous Retroviruses in the Genomics Era.

Science.gov (United States)

Johnson, Welkin E

2015-11-01

Endogenous retroviruses comprise millions of discrete genetic loci distributed within the genomes of extant vertebrates. These sequences, which are clearly related to exogenous retroviruses, represent retroviral infections of the deep past, and their abundance suggests that retroviruses were a near-constant presence throughout the evolutionary history of modern vertebrates. Endogenous retroviruses contribute in myriad ways to the evolution of host genomes, as mutagens and as sources of genetic novelty (both coding and regulatory) to be acted upon by the twin engines of random genetic drift and natural selection. Importantly, the richness and complexity of endogenous retrovirus data can be used to understand how viruses spread and adapt on evolutionary timescales by combining population genetics and evolutionary theory with a detailed understanding of retrovirus biology (gleaned from the study of extant retroviruses). In addition to revealing the impact of viruses on organismal evolution, such studies can help us better understand, by looking back in time, how life-history traits, as well as ecological and geological events, influence the movement of viruses within and between populations.

Remyelination Is Correlated with Regulatory T Cell Induction Following Human Embryoid Body-Derived Neural Precursor Cell Transplantation in a Viral Model of Multiple Sclerosis.

Directory of Open Access Journals (Sweden)

Warren C Plaisted

Full Text Available We have recently described sustained clinical recovery associated with dampened neuroinflammation and remyelination following transplantation of neural precursor cells (NPCs derived from human embryonic stem cells (hESCs in a viral model of the human demyelinating disease multiple sclerosis. The hNPCs used in that study were derived by a novel direct differentiation method (direct differentiation, DD-NPCs that resulted in a unique gene expression pattern when compared to hNPCs derived by conventional methods. Since the therapeutic potential of human NPCs may differ greatly depending on the method of derivation and culture, we wanted to determine whether NPCs differentiated using conventional methods would be similarly effective in improving clinical outcome under neuroinflammatory demyelinating conditions. For the current study, we utilized hNPCs differentiated from a human induced pluripotent cell line via an embryoid body intermediate stage (EB-NPCs. Intraspinal transplantation of EB-NPCs into mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV resulted in decreased accumulation of CD4+ T cells in the central nervous system that was concomitant with reduced demyelination at the site of injection. Dampened neuroinflammation and remyelination was correlated with a transient increase in CD4+FOXP3+ regulatory T cells (Tregs concentrated within the peripheral lymphatics. However, compared to our earlier study, pathological improvements were modest and did not result in significant clinical recovery. We conclude that the genetic signature of NPCs is critical to their effectiveness in this model of viral-induced neurologic disease. These comparisons will be useful for understanding what factors are critical for the sustained clinical improvement.

Current Gaps in the Understanding of the Subcellular Distribution of Exogenous and Endogenous Protein TorsinA

Directory of Open Access Journals (Sweden)

N. Charles Harata

2014-09-01

Full Text Available Background: An in‐frame deletion leading to the loss of a single glutamic acid residue in the protein torsinA (ΔE‐torsinA results in an inherited movement disorder, DYT1 dystonia. This autosomal dominant disease affects the function of the brain without causing neurodegeneration, by a mechanism that remains unknown.Methods: We evaluated the literature regarding the subcellular localization of torsinA.Results: Efforts to elucidate the pathophysiological basis of DYT1 dystonia have relied partly on examining the subcellular distribution of the wild‐type and mutated proteins. A typical approach is to introduce the human torsinA gene (TOR1A into host cells and overexpress the protein therein. In both neurons and non‐neuronal cells, exogenous wild‐type torsinA introduced in this manner has been found to localize mainly to the endoplasmic reticulum, whereas exogenous ΔE‐torsinA is predominantly in the nuclear envelope or cytoplasmic inclusions. Although these outcomes are relatively consistent, findings for the localization of endogenous torsinA have been variable, leaving its physiological distribution a matter of debate.Discussion: As patients’ cells do not overexpress torsinA proteins, it is important to understand why the reported distributions of the endogenous proteins are inconsistent. We propose that careful optimization of experimental methods will be critical in addressing the causes of the differences among the distributions of endogenous (non‐overexpressed vs. exogenously introduced (overexpressed proteins.

Applying Endogenous Knowledge in the African Context ...

African Journals Online (AJOL)

The question presented in this article is how to improve the dispute resolution competence of practitioners in Africa. The response offered involves enhancing the endogenous knowledge of a dispute and how to resolve it. This requires not only an understanding of what endogenous knowledge is, but also an alignment of ...

Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses.

Science.gov (United States)

Arjan-Odedra, Shetal; Swanson, Chad M; Sherer, Nathan M; Wolinsky, Steven M; Malim, Michael H

2012-06-22

The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of host-pathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and non-LTR endogenous retroelements. Most significantly, RNAi-mediated silencing of endogenous MOV10 enhanced the replication of both LTR and non-LTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing. We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells.

Bone morphogenetic protein signaling and olig1/2 interact to regulate the differentiation and maturation of adult oligodendrocyte precursor cells.

Science.gov (United States)

Cheng, Xiaoxin; Wang, Yaping; He, Qian; Qiu, Mengsheng; Whittemore, Scott R; Cao, Qilin

2007-12-01

Promotion of remyelination is an important therapeutic strategy for the treatment of the demyelinating neurological disorders. Adult oligodendrocyte precursor cells (OPCs), which normally reside quiescently in the adult central nervous system (CNS), become activated and proliferative after demyelinating lesions. However, the extent of endogenous remyelination is limited because of the failure of adult OPCs to mature into myelinating oligodendrocytes (OLs) in the demyelinated CNS. Understanding the molecular mechanisms that regulate the differentiation of adult OPCs could lead to new therapeutic strategies to treat these disorders. In this study, we established a stable culture of adult spinal cord OPCs and developed a reliable in vitro protocol to induce their sequential differentiation. Adult OPCs expressed bone morphogenetic protein (BMP) type Ia, Ib, and II receptor subunits, which are required for BMP signal transduction. BMP2 and 4 promoted dose-dependent astrocyte differentiation of adult OPCs with concurrent suppression of OL differentiation. Treatment of OPCs with BMP2 and 4 increased ID4 expression and decreased the expression of olig1 and olig2. Overexpression of olig1 or olig2 blocked the astrocyte differentiation of adult OPCs induced by BMP2 and 4. Furthermore, overexpression of both olig1 and olig2, but not olig1 or olig2 alone, rescued OL differentiation from inhibition by BMP2 and 4. Our results demonstrated that downregulation of olig1 and olig2 is an important mechanism by which BMP2 and 4 inhibit OL differentiation of adult OPCs. These data suggest that blocking BMP signaling combined with olig1/2 overexpression could be a useful therapeutic strategy to enhance endogenous remyelination and facilitate functional recovery in CNS demyelinated disorders. Disclosure of potential conflicts of interest is found at the end of this article.

Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses

Science.gov (United States)

2012-01-01

Background The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of host-pathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. Results MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and non-LTR endogenous retroelements. Most significantly, RNAi-mediated silencing of endogenous MOV10 enhanced the replication of both LTR and non-LTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing. Conclusions We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells. PMID:22727223

MOESM1 of The effect of omega-3 fatty acids on central nervous system remyelination in fat-1 mice

OpenAIRE

Siegert, Elise; Paul, Friedemann; Rothe, Michael; Weylandt, Karsten

2017-01-01

Additional file 1: Figure S1. Experimental groups. In order to assess the impact of n-3 versus n-6 PUFAs on de- and remyelination, animals were divided into six experimental groups. Ten wt and twelve fat-1 animals were put on a 0.2 % cuprizone diet for five weeks, while four wt and four fat-1 animals were fed a normal diet instead. At the end of the five weeks both control groups and the five wt and six fat-1 animals that had been fed cuprizone were sacrificed. The remaining animals were allo...

Repetitive long-term hyperbaric oxygen treatment (HBOT administered after experimental traumatic brain injury in rats induces significant remyelination and a recovery of sensorimotor function.

Directory of Open Access Journals (Sweden)

Klaus Kraitsy

Full Text Available Cells in the central nervous system rely almost exclusively on aerobic metabolism. Oxygen deprivation, such as injury-associated ischemia, results in detrimental apoptotic and necrotic cell loss. There is evidence that repetitive hyperbaric oxygen therapy (HBOT improves outcomes in traumatic brain-injured patients. However, there are no experimental studies investigating the mechanism of repetitive long-term HBOT treatment-associated protective effects. We have therefore analysed the effect of long-term repetitive HBOT treatment on brain trauma-associated cerebral modulations using the lateral fluid percussion model for rats. Trauma-associated neurological impairment regressed significantly in the group of HBO-treated animals within three weeks post trauma. Evaluation of somatosensory-evoked potentials indicated a possible remyelination of neurons in the injured hemisphere following HBOT. This presumption was confirmed by a pronounced increase in myelin basic protein isoforms, PLP expression as well as an increase in myelin following three weeks of repetitive HBO treatment. Our results indicate that protective long-term HBOT effects following brain injury is mediated by a pronounced remyelination in the ipsilateral injured cortex as substantiated by the associated recovery of sensorimotor function.

Therapeutic targeting strategies using endogenous cells and proteins.

Science.gov (United States)

Parayath, Neha N; Amiji, Mansoor M

2017-07-28

Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems. Thus, use of endogenous targeting systems is increasingly gaining momentum. This review is focused on strategies for employing endogenous moieties, which could serve as safe and efficient carriers for targeted drug delivery. The first part of the review involves cells and cellular components as endogenous carriers for therapeutics in multiple disease states, while the second part discusses the use of endogenous plasma components as endogenous carriers. Further understanding of the biological tropism with cells and proteins and the newer generation of delivery strategies that exploits these endogenous approaches promises to provide better solutions for site-specific delivery and could further facilitate clinical translations. Copyright © 2017 Elsevier B.V. All rights reserved.

Fanconi anemia proteins and endogenous stresses

Energy Technology Data Exchange (ETDEWEB)

Pang Qishen [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States); Andreassen, Paul R., E-mail: Paul.Andreassen@cchmc.org [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States)

2009-07-31

Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.

Fanconi anemia proteins and endogenous stresses

International Nuclear Information System (INIS)

Pang Qishen; Andreassen, Paul R.

2009-01-01

Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.

Are endogenous feline leukemia viruses really endogenous?

Science.gov (United States)

Stewart, H; Jarrett, O; Hosie, M J; Willett, B J

2011-10-15

Full length endogenous feline leukemia virus (FeLV) proviruses exist within the genomes of many breeds of domestic cat raising the possibility that they may also exist in a transmissible exogenous form. Such viruses would share receptor usage with the recombinant FeLV-B subgroup, a viral subgroup that arises in vivo by recombination between exogenous subgroup A virus (FeLV-A) and endogenous FeLV. Accordingly, all isolates of FeLV-B made to date have contained a "helper" FeLV-A, consistent with their recombinatorial origin. In order to assess whether endogenous viruses are transmitted between cats, we examined primary isolates of FeLV for which the viral subgroup had been determined for the presence of a subgroup B virus that lacked an FeLV-A. Here we describe the identification of two primary field isolates of FeLV (2518 and 4314) that appeared to contain subgroup B virus only by classical interference assays, raising the possibility of between-host transmission of endogenous FeLV. Sequencing of the env gene and U3 region of the 3' long terminal repeat (LTR) confirmed that both viral genomes contained endogenous viral env genes. However the viral 3' LTRs appeared exogenous in origin with a putative 3' recombination breakpoint residing at the 3' end of the env gene. Further, the FeLV-2518 virions also co-packaged a truncated FeLV-A genome containing a defective env gene, termed FeLV-2518(A) whilst no helper subgroup A viral genome was detected in virions of FeLV-4314. The acquisition of an exogenous LTR by the endogenous FeLV in 4314 may have allowed a recombinant FeLV variant to outgrow an exogenous FeLV-A virus that was presumably present during first infection. Given time, a similar evolution may also occur within the 2518 isolate. The data suggest that endogenous FeLVs may be mobilised by acquisition of exogenous LTRs yielding novel viruses that type biologically as FeLV-B. Copyright © 2011 Elsevier B.V. All rights reserved.

Endogenous antipyretics.

Science.gov (United States)

Roth, Joachim

2006-09-01

The febrile increase of body temperature is regarded as a component of the complex host response to infection or inflammation that accompanies the activation of the immune system. Late phases of fever appear mediated by pro-inflammatory cytokines called endogenous pyrogens. The rise of body temperature is beneficial because it accelerates several components of the activated immune system. To prevent an excessive and dangerous rise of body temperature the febrile response is controlled, limited in strength and duration, and sometimes even prevented by the actions of endogenous antipyretic substances liberated systemically or within the brain during fever. In most cases the antipyretic effects are achieved by an inhibitory influence on the formation or action of endogenous pyrogens, or by effects on neuronal thermoregulatory circuits that are activated during fever. Endogenous antipyretic substances include steroid hormones, neuropeptides, cytokines and other molecules. It is the purpose of this review to consider the current state in the research on endogenous antipyretic systems.

PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [{sup 11}C]MeDAS, [{sup 11}C]CIC and [{sup 11}C]PIB

Energy Technology Data Exchange (ETDEWEB)

Paula Faria, Daniele de [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, Department of Neuroscience, Groningen (Netherlands); University of Sao Paulo Medical School, Center of Nuclear Medicine, Sao Paulo (Brazil); Copray, Sjef [University of Groningen, University Medical Center Groningen, Department of Neuroscience, Groningen (Netherlands); Sijbesma, Jurgen W.A.; Willemsen, Antoon T.M.; Dierckx, Rudi A.J.O.; Vries, Erik F.J. de [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Buchpiguel, Carlos A. [University of Sao Paulo Medical School, Center of Nuclear Medicine, Sao Paulo (Brazil)

2014-05-15

In this study, we compared the ability of [{sup 11}C]CIC, [{sup 11}C]MeDAS and [{sup 11}C]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake. Sprague-Dawley rats were stereotactically injected with either 1 % lysolecithin or saline into the corpus callosum and striatum of the right brain hemisphere. Dynamic PET imaging with simultaneous arterial blood sampling was performed 7 days after saline injection (control group), 7 days after lysolecithin injection (demyelination group) and 4 weeks after lysolecithin injection (remyelination group). The kinetics of [{sup 11}C]CIC, [{sup 11}C]MeDAS and [{sup 11}C]PIB was best fitted by Logan graphical analysis, suggesting that tracer binding is reversible. Compartment modelling revealed that all tracers were fitted best with the reversible two-tissue compartment model. Tracer uptake and distribution volume in lesions were in agreement with myelin status. However, the slow kinetics and homogeneous brain uptake of [{sup 11}C]CIC make this tracer less suitable for in vivo PET imaging. [{sup 11}C]PIB showed good uptake in the white matter in the cerebrum, but [{sup 11}C]PIB uptake in the cerebellum was low, despite high myelin density in this region. [{sup 11}C]MeDAS distribution correlated well with myelin density in different brain regions. This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible. Our comparison of three myelin tracers showed that [{sup 11}C]MeDAS has more favourable properties for quantitative PET imaging of demyelinated and remyelinated lesions throughout the CNS than [{sup 11}C]CIC and [{sup 11}C]PIB. (orig.)

Axonal regeneration in zebrafish spinal cord

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Hui, Subhra Prakash

2018-01-01

Abstract In the present review we discuss two interrelated events—axonal damage and repair—known to occur after spinal cord injury (SCI) in the zebrafish. Adult zebrafish are capable of regenerating axonal tracts and can restore full functionality after SCI. Unlike fish, axon regeneration in the adult mammalian central nervous system is extremely limited. As a consequence of an injury there is very little repair of disengaged axons and therefore functional deficit persists after SCI in adult mammals. In contrast, peripheral nervous system axons readily regenerate following injury and hence allow functional recovery both in mammals and fish. A better mechanistic understanding of these three scenarios could provide a more comprehensive insight into the success or failure of axonal regeneration after SCI. This review summarizes the present understanding of the cellular and molecular basis of axonal regeneration, in both the peripheral nervous system and the central nervous system, and large scale gene expression analysis is used to focus on different events during regeneration. The discovery and identification of genes involved in zebrafish spinal cord regeneration and subsequent functional experimentation will provide more insight into the endogenous mechanism of myelination and remyelination. Furthermore, precise knowledge of the mechanism underlying the extraordinary axonal regeneration process in zebrafish will also allow us to unravel the potential therapeutic strategies to be implemented for enhancing regrowth and remyelination of axons in mammals. PMID:29721326

Combining Semi-Endogenous and Fully Endogenous Growth: a Generalization.

OpenAIRE

Cozzi, Guido

2017-01-01

This paper shows that combining the semi-endogenous and the fully endogenous growth mechanisms with a general CES aggregator, either growth process can prevail in the balanced growth path depending on their degree of complementarity/substitutability. Policy-induced long-run economic switches to the fully endogenous steady state as the R&D employment ratio surpasses a positive threshold are possible if the two growth engines are gross substitutes.

Primary Spinal OPC Culture System from Adult Zebrafish to Study Oligodendrocyte Differentiation In Vitro

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Volker Kroehne

2017-09-01

Full Text Available Endogenous oligodendrocyte progenitor cells (OPCs are a promising target to improve functional recovery after spinal cord injury (SCI by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neurons. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs. Therefore, researchers strive to control OPC responses, and utilize small molecule screening approaches in order to identify mechanisms of OPC activation, proliferation, migration and differentiation. In zebrafish, OPCs remyelinate axons of the optic tract after lysophosphatidylcholine (LPC-induced demyelination back to full thickness myelin sheaths. In contrast to zebrafish, mammalian OPCs are highly vulnerable to excitotoxic stress, a cause of secondary injury, and remyelination remains insufficient. Generally, injury induced remyelination leads to shorter internodes and thinner myelin sheaths in mammals. In this study, we show that myelin sheaths are lost early after a complete spinal transection injury, but are re-established within 14 days after lesion. We introduce a novel, easy-to-use, inexpensive and highly reproducible OPC culture system based on dormant spinal OPCs from adult zebrafish that enables in vitro analysis. Zebrafish OPCs are robust, can easily be purified with high viability and taken into cell culture. This method enables to examine why zebrafish OPCs remyelinate better than their mammalian counterparts, identify cell intrinsic responses, which could lead to pro-proliferating or pro-differentiating strategies, and to test small molecule approaches. In this methodology paper, we show efficient isolation of OPCs from adult zebrafish spinal cord and describe culture conditions that enable

Oligodendrogenesis and neurogenesis in remyelination in the cuprizone model of multiple sclerosis: correlation with the degree of lesion

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Pishchelko, A.; Khodanovich, M.; Pan, E.; Glazacheva, V.; Akulov, A.; Yarnykh, V.

2017-08-01

In this research, a cuprizone model of multiple sclerosis (MS) was used to study oligodendrogenesis and neurogenesis in remyelination. It has been shown that, with the administration of cuprizone, the amount of myelin in a number of structures of white and gray matter and the level of neurogenesis decrease, while the level of oligodendrogenesis increases. The withdrawal of cuprizone leads to the restoration of myelin content, the reduction of the excessive production of oligodendrocytes and to the restoration of the number of neurons to control values. The negative correlation between the number of oligodendrocyte precursors (OPCs) and the degree of demyelination of the corpus callosum indicates migration of OLG precursors from the subventricular zone (SVZ) to the structure during demyelination.

Demyelinating diseases and potential repair strategies

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Radtke, C.; Spies, M.; Sasaki, M.; Vogt, PM; Kocsis, J. D.

2009-01-01

Demyelination is associated with a number of neurological disorders including multiple sclerosis (MS), spinal cord injury and nerve compression. MS lesions often show axon loss and therefore reparative therapeutic goals include remyelination and neuroprotection of vulnerable axons. Experimental cellular transplantation has proven successful in a number of demyelination and injury models to remyelinate and improve functional outcome. Here we discuss the remyelination and neuroprotective potential of several myelin-forming cells types and their behavior in different demyelination and injury models. Better understanding of these models and current cell-based strategies for remyelination and neuroprotection offer exciting opportunities to develop strategies for clinical studies. PMID:17408905

Glucocorticoid-related bone changes from endogenous or exogenous glucocorticoids.

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Warriner, Amy H; Saag, Kenneth G

2013-12-01

Glucocorticoids have a negative impact on bone through direct effects on bone cells and indirect effects on calcium absorption. Here, recent findings regarding glucocorticoid-induced osteoporosis, bone changes in patients with endogenous glucocorticoid derangements, and treatment of steroid-induced bone disease are reviewed. Although the majority of our understanding arises from the outcomes of patients treated with exogenous steroids, endogenous overproduction appears to be similarly destructive to bone, but these effects are reversible with cure of the underlying disease process. Additionally, there are bone changes that occur in diseases that interrupt adrenal glucocorticoid production, both in response to our inability to perfectly match glucocorticoid replacement and also related to the underlying disease process. More investigation is required to understand which patients with endogenous overproduction or underproduction of glucocorticoid would benefit from osteoporosis treatment. Better understood is the benefit that can be achieved with currently approved treatments for glucocorticoid-induced osteoporosis from exogenous steroids. With growing concern of long-term use of bisphosphonates, however, further investigation into the duration of use and use in certain populations, such as children and premenopausal women, is essential. Glucocorticoid-induced osteoporosis is a complex disease that is becoming better understood through advances in the study of exogenous and endogenous glucocorticoid exposure. Further advancement of proper treatment and prevention is on the horizon.

Stimulating endogenous cardiac regeneration

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Amanda eFinan

2015-09-01

Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

Astrocytes from the contused spinal cord inhibit oligodendrocyte differentiation of adult oligodendrocyte precursor cells by increasing the expression of bone morphogenetic proteins.

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Wang, Yaping; Cheng, Xiaoxin; He, Qian; Zheng, Yiyan; Kim, Dong H; Whittemore, Scott R; Cao, Qilin L

2011-04-20

Promotion of remyelination is an important therapeutic strategy to facilitate functional recovery after traumatic spinal cord injury (SCI). Transplantation of neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) has been used to enhance remyelination after SCI. However, the microenvironment in the injured spinal cord is inhibitory for oligodendrocyte (OL) differentiation of NSCs or OPCs. Identifying the signaling pathways that inhibit OL differentiation in the injured spinal cord could lead to new therapeutic strategies to enhance remyelination and functional recovery after SCI. In the present study, we show that reactive astrocytes from the injured rat spinal cord or their conditioned media inhibit OL differentiation of adult OPCs with concurrent promotion of astrocyte differentiation. The expression of bone morphogenetic proteins (BMP) is dramatically increased in the reactive astrocytes and their conditioned media. Importantly, blocking BMP activity by BMP receptor antagonist, noggin, reverse the effects of active astrocytes on OPC differentiation by increasing the differentiation of OL from OPCs while decreasing the generation of astrocytes. These data indicate that the upregulated bone morphogenetic proteins in the reactive astrocytes are major factors to inhibit OL differentiation of OPCs and to promote its astrocyte differentiation. These data suggest that manipulation of BMP signaling in the endogenous or grafted NSCs or OPCs may be a useful therapeutic strategy to increase their OL differentiation and remyelination and enhance functional recovery after SCI.

Endogenous Receptor Agonists: Resolving Inflammation

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Gerhard Bannenberg

2007-01-01

Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS).

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KhorshidAhmad, Tina; Acosta, Crystal; Cortes, Claudia; Lakowski, Ted M; Gangadaran, Surendiran; Namaka, Michael

2016-03-01

Multiple sclerosis (MS) is a chronic progressive, neurological disease characterized by the targeted immune system-mediated destruction of central nervous system (CNS) myelin. Autoreactive CD4+ T helper cells have a key role in orchestrating MS-induced myelin damage. Once activated, circulating Th1-cells secrete a variety of inflammatory cytokines that foster the breakdown of blood-brain barrier (BBB) eventually infiltrating into the CNS. Inside the CNS, they become reactivated upon exposure to the myelin structural proteins and continue to produce inflammatory cytokines such as tumor necrosis factor α (TNFα) that leads to direct activation of antibodies and macrophages that are involved in the phagocytosis of myelin. Proliferating oligodendrocyte precursors (OPs) migrating to the lesion sites are capable of acute remyelination but unable to completely repair or restore the immune system-mediated myelin damage. This results in various permanent clinical neurological disabilities such as cognitive dysfunction, fatigue, bowel/bladder abnormalities, and neuropathic pain. At present, there is no cure for MS. Recent remyelination and/or myelin repair strategies have focused on the role of the neurotrophin brain-derived neurotrophic factor (BDNF) and its upstream transcriptional repressor methyl CpG binding protein (MeCP2). Research in the field of epigenetic therapeutics involving histone deacetylase (HDAC) inhibitors and lysine acetyl transferase (KAT) inhibitors is being explored to repress the detrimental effects of MeCP2. This review will address the role of MeCP2 and BDNF in remyelination and/or myelin repair and the potential of HDAC and KAT inhibitors as novel therapeutic interventions for MS.

Endogenous fertility and development traps with endogenous lifetime

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Fanti, Luciano; Gori, Luca

2010-01-01

We extend the literature on endogenous lifetime and economic growth by Chakraborty (2004) and Bunzel and Qiao (2005) to endogenous fertility. We show that development traps due to underinvestments in health cannot appear when fertility is an economic decision variable and the costs of children are represented by a constant fraction of the parents' income used for their upbringing.

Further comparisons of endogenous pyrogens and leukocytic endogenous mediators.

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Kampschmidt, R F; Upchurch, H F; Worthington, M L

1983-07-01

It was recently shown (Murphy et al., Infect. Immun. 34:177-183), that rabbit macrophages produce two biochemically and immunologically distinct endogenous pyrogens. One of these has or copurifies with substances having a molecular weight of 13,000 and a pI of 7.3. This protein was produced by blood monocytes or inflammatory cells elicited in 16-h rabbit peritoneal exudates. These acute peritoneal exudates were produced by the intraperitoneal injection of large volumes of saline containing shellfish glycogen. When the leukocytes in these exudates were washed and incubated at 37 degrees C in saline, they released an endogenous pyrogen. The injection of this pyrogen into rabbits, rats, or mice caused the biological manifestations which have been attributed to leukocytic endogenous mediator. These effects were increases in blood neutrophils, the lowering of plasma iron and zinc levels, and the increased synthesis of the acute-phase proteins. The other rabbit endogenous pyrogen seems to be a family of proteins with isoelectric points between 4.5 and 5.0. These proteins are produced by macrophages in the lung, liver, or in chronic peritoneal exudates. In these experiments, the lower-isoelectric-point endogenous pyrogens were produced by macrophages from the peritoneal cavity of rabbits that had been injected 4 days earlier with 50 ml of light mineral oil. These rabbit pyrogens were found to have leukocytic endogenous mediator activity in mice but to be completely inactive in rats. When injected into rabbits, these proteins produced fever, lowered plasma iron, increased blood neutrophils, but failed to elevate plasma fibrinogen.

Applying Endogenous Knowledge in the African Context ...

African Journals Online (AJOL)

This requires not only an understanding of what endogenous knowledge is, but also an alignment of personal values, innovative strategies and an attitude of activism. An integral part of an extensive skills set to implement specifi c dispute resolution strategies is the ability to facilitate the free sharing of information about all ...

Endogenous Cortical Oscillations Constrain Neuromodulation by Weak Electric Fields

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Schmidt, Stephen L.; Iyengar, Apoorva K.; Foulser, A. Alban; Boyle, Michael R.; Fröhlich, Flavio

2014-01-01

Background Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation modality that may modulate cognition by enhancing endogenous neocortical oscillations with the application of sine-wave electric fields. Yet, the role of endogenous network activity in enabling and shaping the effects of tACS has remained unclear. Objective We combined optogenetic stimulation and multichannel slice electrophysiology to elucidate how the effect of weak sine-wave electric field depends on the ongoing cortical oscillatory activity. We hypothesized that the structure of the response to stimulation depended on matching the stimulation frequency to the endogenous cortical oscillation. Methods We studied the effect of weak sine-wave electric fields on oscillatory activity in mouse neocortical slices. Optogenetic control of the network activity enabled the generation of in vivo like cortical oscillations for studying the temporal relationship between network activity and sine-wave electric field stimulation. Results Weak electric fields enhanced endogenous oscillations but failed to induce a frequency shift of the ongoing oscillation for stimulation frequencies that were not matched to the endogenous oscillation. This constraint on the effect of electric field stimulation imposed by endogenous network dynamics was limited to the case of weak electric fields targeting in vivo-like network dynamics. Together, these results suggest that the key mechanism of tACS may be enhancing but not overriding of intrinsic network dynamics. Conclusion Our results contribute to understanding the inconsistent tACS results from human studies and propose that stimulation precisely adjusted in frequency to the endogenous oscillations is key to rational design of non-invasive brain stimulation paradigms. PMID:25129402

Endogenous growth theory and regional development policy

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Cvetanović Slobodan

2015-01-01

Full Text Available The numerous versions of endogenous explanations of economic growth emphasize the importance of technological change driving forces, as well as the existence of appropriate institutional arrangements. Endogenous growth theory contributes to a better understanding of various experiences with long-term growth of countries and regions. It changes the key assumptions of the Neoclassical growth theory and participates in the modern regional development physiology explanation. Based on these conclusions, the paper: a explicates the most important theoretical postulates of the theory, b explains the most important factors of economic growth in the regions in light of the Endogenous growth theory messages and c emphasizes the key determinants of regional competitiveness which in our view is conceptually between the phenomena of micro- and macro-competitiveness and represents their necessary and unique connection. First of all, micro-competitiveness is transformed into a regional competitiveness; then regional competitiveness is transformed into a macro-competitiveness. In turn, macro - influences the microeconomic competitiveness, and the circle is closed. After that, the process starts over again.

Endogenous Lunar Volatiles

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McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Anand, M.; Boyce, J. W.; Burney, D.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Klima, R. L.; Magna, T.; Ni, P.; Steenstra, E.; Tartèse, R.; Vander Kaaden, K. E.

2018-04-01

This abstract discusses numerous outstanding questions on the topic of endogenous lunar volatiles that will need to be addressed in the coming years. Although substantial insights into endogenous lunar volatiles have been gained, more work remains.

Local delivery of thyroid hormone enhances oligodendrogenesis and myelination after spinal cord injury

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Shultz, Robert B.; Wang, Zhicheng; Nong, Jia; Zhang, Zhiling; Zhong, Yinghui

2017-06-01

Objective. Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplantation has demonstrated efficacy in promoting remyelination and functional recovery, the lack of ideal cell sources presents a major obstacle to clinical application. The adult spinal cord contains oligodendrocyte precursor cells and multipotent neural stem/progenitor cells that have the capacity to differentiate into mature, myelinating OLs. However, endogenous oligodendrogenesis and remyelination processes are limited by the upregulation of remyelination-inhibitory molecules in the post-injury microenvironment. Multiple growth factors/molecules have been shown to promote OL differentiation and myelination. Approach. In this study we screened these therapeutics and found that 3, 3‧, 5-triiodothyronine (T3) is the most effective in promoting oligodendrogenesis and OL maturation in vitro. However, systemic administration of T3 to achieve therapeutic doses in the injured spinal cord is likely to induce hyperthyroidism, resulting in serious side effects. Main results. In this study we developed a novel hydrogel-based drug delivery system for local delivery of T3 to the injury site without eliciting systemic toxicity. Significance. Using a clinically relevant cervical contusion injury model, we demonstrate that local delivery of T3 at doses comparable to safe human doses promoted new mature OL formation and myelination after SCI.

Differences between endogenous and exogenous emotion inhibition in the human brain.

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Kühn, Simone; Haggard, Patrick; Brass, Marcel

2014-05-01

The regulation of emotions is an integral part of our mental health. It has only recently been investigated using brain imaging techniques. In most studies, participants are instructed by a cue to inhibit a specific emotional reaction. The aim of the present study was to investigate the alternative situation where a person decides to inhibit an emotion as an act of endogenous self-control. Healthy participants viewed highly arousing pictures with negative valence. In the endogenous condition, participants could freely choose on each trial to inhibit or feel the emotions elicited by the picture. In an exogenous condition, a visual cue instructed them to either feel or inhibit the emotion elicited by the picture. Participants' subjective ratings of intensity of experienced emotion showed an interaction effect between source of control (endogenous/exogenous) and feel/inhibit based on a stronger modulation between feel and inhibition for the endogenous compared to the exogenous condition. Endogenous inhibition of emotions was associated with dorso-medial prefrontal cortex activation, whereas exogenous inhibition was found associated with lateral prefrontal cortex activation. Thus, the brain regions for both endogenous and exogenous inhibition of emotion are highly similar to those for inhibition of motor actions in Brass and Haggard (J Neurosci 27:9141-9145, 2007), Kühn et al. (Hum Brain Mapp 30:2834-2843, 2009). Functional connectivity analyses showed that dorsofrontomedial cortex exerts greater control onto pre-supplementary motor area during endogenous inhibition compared to endogenous feel. This functional dissociation between an endogenous, fronto-medial and an exogenous, fronto-lateral inhibition centre has important implications for our understanding of emotion regulation in health and psychopathology.

On the classification and evolution of endogenous retrovirus: human endogenous retroviruses may not be 'human' after all.

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Escalera-Zamudio, Marina; Greenwood, Alex D

2016-01-01

Retroviruses, as part of their replication cycle, become integrated into the genome of their host. When this occurs in the germline the integrated proviruses can become an endogenous retrovirus (ERV) which may eventually become fixed in the population. ERVs are present in the genomes of all vertebrates including humans, where more than 50 groups of human endogenous retrovirus (HERVs) have been described within the last 30 years. Despite state-of-the-art genomic tools available for retroviral discovery and the large number of retroviral sequences described to date, there are still gaps in understanding retroviral macroevolutionary patterns and host-retrovirus interactions and a lack of a coherent systematic classification particularly for HERVs. Here, we discuss the current knowledge on ERV (and HERV) classification, distribution and origins focusing on the role of cross-species transmission in retroviral diversity. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Electrical stimulation enhanced remyelination of injured sciatic nerves by increasing neurotrophins.

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Wan, L D; Xia, R; Ding, W L

2010-09-01

Previous studies have demonstrated that electrical stimulation (ES) enhances axonal regeneration following central and peripheral nerve injury. However, the effect of ES on peripheral remyelination after nerve damage has been investigated less, and the mechanism underlying its action remains unclear. In the present study, neuron/Schwann cell (SC) co-cultures in vitro and crush-injured sciatic nerves in rats were subjected to 1 h of continuous ES (20 Hz, 100 micros, 3 V). Electron microscopy and nerve morphometry were performed to investigate the extent of regenerated nerve myelination. The expression profiles of P0, Par-3 and brain-derived neurotrophic factor (BDNF) in vitro and in vivo were examined by western blotting. We reported that 20 Hz ES increased the number of regenerated and myelinated axons at 4 and 8 weeks after injury. P0 level in the ES-treated groups, as well as myelin sheath thickness, were enhanced compared with the controls. The earlier peak Par-3 in the ES-treated groups indicated earlier initiation of SC myelination. Moreover, the similar results were achieved in the cell co-culture. Additionally, brief ES significantly elevated BDNF expression in co-cultured cells and nerve tissues. In conclusion, ES of the site of nerve injury potentiates axonal regrowth and myelin maturation during peripheral nerve regeneration. Further, the therapeutic actions of ES on myelination that is mediated via enhanced BDNF signals, which driving the promyelination effect on SCs at the onset of myelination. Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Investigation of sequential growth factor delivery during cuprizone challenge in mice aimed to enhance oligodendrogliogenesis and myelin repair.

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Jennifer K Sabo

Full Text Available Repair in multiple sclerosis involves remyelination, a process in which axons are provided with a new myelin sheath by new oligodendrocytes. Bone morphogenic proteins (BMPs are a family of growth factors that have been shown to influence the response of oligodendrocyte progenitor cells (OPCs in vivo during demyelination and remyelination in the adult brain. We have previously shown that BMP4 infusion increases numbers of OPCs during cuprizone-induced demyelination, while infusion of Noggin, an endogenous antagonist of BMP4 increases numbers of mature oligodendrocytes and remyelinated axons following recovery. Additional studies have shown that insulin-like growth factor-1 (IGF-1 promotes the survival of OPCs during cuprizone-induced demyelination. Based on these data, we investigated whether myelin repair could be further enhanced by sequential infusion of these agents firstly, BMP4 to increase OPC numbers, followed by either Noggin or IGF-1 to increase the differentiation and survival of the newly generated OPCs. We identified that sequential delivery of BMP4 and IGF-1 during cuprizone challenge increased the number of mature oligodendrocytes and decreased astrocyte numbers following recovery compared with vehicle infused mice, but did not alter remyelination. However, sequential delivery of BMP4 and Noggin during cuprizone challenge did not alter numbers of oligodendrocytes or astrocytes in the corpus callosum compared with vehicle infused mice. Furthermore, electron microscopy analysis revealed no change in average myelin thickness in the corpus callosum between vehicle infused and BMP4-Noggin infused mice. Our results suggest that while single delivery of Noggin or IGF-1 increased the production of mature oligodendrocytes in vivo in the context of demyelination, only Noggin infusion promoted remyelination. Thus, sequential delivery of BMP4 and Noggin or IGF-1 does not further enhance myelin repair above what occurs with delivery of Noggin

The Endogenous Exposome

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Nakamura, Jun; Mutlu, Esra; Sharma, Vyom; Collins, Leonard; Bodnar, Wanda; Yu, Rui; Lai, Yongquan; Moeller, Benjamin; Lu, Kun; Swenberg, James

2014-01-01

The concept of the Exposome, is a compilation of diseases and one’s lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the Endogenous Exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions. PMID:24767943

Production of endogenous pyrogen.

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Dinarello, C A

1979-01-01

The production and release of endogenous pyrogen by the host is the first step in the pathogenesis of fever. Endogenous pyrogen is a low-molecular-weight protein released from phagocytic leukocytes in response to several substances of diverse nature. Some of these agents stimulate production of endogenous pyrogen because they are toxic; others act as antigens and interact with either antibody or sensitized lymphocytes in order to induce its production. Some tumors of macrophage origin produce the molecule spontaneously. Whatever the mechanism involved, endogenous pyrogen is synthesized following transcription of new DNA and translation of mRNA into new protein. Once synthesis is completed, the molecule is released without significant intracellular storage. Recent evidence suggests that following release, molecular aggregates form which are biologically active. In its monomer form, endogenous pyrogen is a potent fever-producing substance and mediates fever by its action on the thermoregulatory center.

Oligodendrogenesis after Cerebral Ischaemia and Traumatic Brain Injury

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Zheng Gang Zhang

2013-08-01

Full Text Available Stroke and traumatic brain injury (TBI damage white and grey matter. Loss of oligodendrocytes and their myelin, impairs axonal function. Remyelination involves oligodendrogenesis during which new myelinating oligodendrocytes are generated by differentiated oligodendrocyte progenitor cells (OPCs. This article briefly reviews the processes of oligodendrogenesis in adult rodent brains, and promising experimental therapies targeting the neurovascular unit that reduce oligodendrocyte damage and amplify endogenous oligodendrogenesis after stroke and TBI.

Endogenous Locus Reporter Assays.

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Liu, Yaping; Hermes, Jeffrey; Li, Jing; Tudor, Matthew

2018-01-01

Reporter gene assays are widely used in high-throughput screening (HTS) to identify compounds that modulate gene expression. Traditionally a reporter gene assay is built by cloning an endogenous promoter sequence or synthetic response elements in the regulatory region of a reporter gene to monitor transcriptional activity of a specific biological process (exogenous reporter assay). In contrast, an endogenous locus reporter has a reporter gene inserted in the endogenous gene locus that allows the reporter gene to be expressed under the control of the same regulatory elements as the endogenous gene, thus more accurately reflecting the changes seen in the regulation of the actual gene. In this chapter, we introduce some of the considerations behind building a reporter gene assay for high-throughput compound screening and describe the methods we have utilized to establish 1536-well format endogenous locus reporter and exogenous reporter assays for the screening of compounds that modulate Myc pathway activity.

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

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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.

Fungal mycelia show lag time before re-growth on endogenous carbon.

Science.gov (United States)

Pollack, Judith K; Li, Zheng Jian; Marten, Mark R

2008-06-15

Nutrient starvation is a common occurrence for filamentous fungi. To better understand the effects of starvation, we used a parallel plate flow chamber to study individual fungal mycelia when subjected to a step change in glucose concentration. We report the presence of a finite "lag time" in starved mycelia during which they ceased to grow/extend while switching from growth on exogenous carbon to re-growth on endogenous carbon. This lag time precedes other morphological or physiological changes such as change in growth rate (50-70% reduction), vacuolation (up to 16%), and decreased hyphal diameter (almost 50% reduction). Data suggests that during lag time, vacuolar degradation produces sufficient endogenous carbon to support survival and restart hyphal extension. Lag time is inversely related to the size of the mycelium at the time of starvation, which suggests a critical flow of endogenous carbon to the apical tip. We present a mathematical model consistent with our experimental observations that relate lag time, area, and flow of endogenous carbon. (c) 2008 Wiley Periodicals, Inc.

Endogenous time-varying risk aversion and asset returns.

Science.gov (United States)

Berardi, Michele

2016-01-01

Stylized facts about statistical properties for short horizon returns in financial markets have been identified in the literature, but a satisfactory understanding for their manifestation is yet to be achieved. In this work, we show that a simple asset pricing model with representative agent is able to generate time series of returns that replicate such stylized facts if the risk aversion coefficient is allowed to change endogenously over time in response to unexpected excess returns under evolutionary forces. The same model, under constant risk aversion, would instead generate returns that are essentially Gaussian. We conclude that an endogenous time-varying risk aversion represents a very parsimonious way to make the model match real data on key statistical properties, and therefore deserves careful consideration from economists and practitioners alike.

Endogenous Lunar Volatiles

Science.gov (United States)

McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Boyce, J. W.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Magna, T.; Ni, P.; Tartese, R.;

Biased Agonism of Endogenous Opioid Peptides at the μ-Opioid Receptor.

Science.gov (United States)

Thompson, Georgina L; Lane, J Robert; Coudrat, Thomas; Sexton, Patrick M; Christopoulos, Arthur; Canals, Meritxell

2015-08-01

Biased agonism is having a major impact on modern drug discovery, and describes the ability of distinct G protein-coupled receptor (GPCR) ligands to activate different cell signaling pathways, and to result in different physiologic outcomes. To date, most studies of biased agonism have focused on synthetic molecules targeting various GPCRs; however, many of these receptors have multiple endogenous ligands, suggesting that "natural" bias may be an unappreciated feature of these GPCRs. The μ-opioid receptor (MOP) is activated by numerous endogenous opioid peptides, remains an attractive therapeutic target for the treatment of pain, and exhibits biased agonism in response to synthetic opiates. The aim of this study was to rigorously assess the potential for biased agonism in the actions of endogenous opioids at the MOP in a common cellular background, and compare these to the effects of the agonist d-Ala2-N-MePhe4-Gly-ol enkephalin (DAMGO). We investigated activation of G proteins, inhibition of cAMP production, extracellular signal-regulated kinase 1 and 2 phosphorylation, β-arrestin 1/2 recruitment, and MOP trafficking, and applied a novel analytical method to quantify biased agonism. Although many endogenous opioids displayed signaling profiles similar to that of DAMGO, α-neoendorphin, Met-enkephalin-Arg-Phe, and the putatively endogenous peptide endomorphin-1 displayed particularly distinct bias profiles. These may represent examples of natural bias if it can be shown that they have different signaling properties and physiologic effects in vivo compared with other endogenous opioids. Understanding how endogenous opioids control physiologic processes through biased agonism can reveal vital information required to enable the design of biased opioids with improved pharmacological profiles and treat diseases involving dysfunction of the endogenous opioid system. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Endogenous Prospect Theory

OpenAIRE

Schmidt, Ulrich; Zank, Horst

2010-01-01

In previous models of (cumulative) prospect theory reference-dependence of preferences is imposed beforehand and the location of the reference point is exogenously determined. This paper provides an axiomatization of a new specification of cumulative prospect theory, termed endogenous prospect theory, where reference-dependence is derived from preference conditions and a unique reference point arises endogenously.

Immunohistochemical and transcriptome analyses indicate complex breakdown of axonal transport mechanisms in canine distemper leukoencephalitis.

Science.gov (United States)

Spitzbarth, Ingo; Lempp, Charlotte; Kegler, Kristel; Ulrich, Reiner; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang; Seehusen, Frauke

2016-07-01

CDV-DL (Canine distemper virus-induced demyelinating leukoencephalitis) represents a spontaneously occurring animal model for demyelinating disorders. Axonopathy represents a key pathomechanism in this disease; however, its underlying pathogenesis has not been addressed in detail so far. This study aimed at the characterization of axonal cytoskeletal, transport, and potential regenerative changes with a parallel focus upon Schwann cell remyelination. Immunohistochemistry of canine cerebellar tissue as well as a comparative analysis of genes from an independent microarray study were performed. Increased axonal immunoreactivity for nonphosphorylated neurofilament was followed by loss of cytoskeletal and motor proteins. Interestingly, a subset of genes encoding for neurofilament subunits and motor proteins was up-regulated in the chronic stage compared to dogs with subacute CDV-DL. However, immunohistochemically, hints for axonal regeneration were restricted to up-regulated axonal positivity of hypoxia-inducible factor 1 alpha, while growth-associated protein 43, erythropoietin and its receptor were not or even down-regulated. Periaxin-positive structures, indicative of Schwann cell remyelination, were only detected within few advanced lesions. The present findings demonstrate a complex sequence of axonal cytoskeletal breakdown mechanisms. Moreover, though sparse, this is the first report of Schwann cell remyelination in CDV-DL. Facilitation of these very limited endogenous regenerative responses represents an important topic for future research.

Habits, aspirations and endogenous fertility

OpenAIRE

Luciano Fanti

2012-01-01

Motivated by the increasing literature on endogenous preferences as well as on endogenous fertility, this paper investigates the implications of the interaction of the endogenous determination of the number of children with habit and aspiration formation in an OLG model. In contrast with the previous literature, we show that greater aspirations may lead to higher savings, and more interestingly, always increase the neoclassical economic growth.

Host-virus interactions of mammalian endogenous retroviruses

OpenAIRE

Farkašová, Helena

2017-01-01

Endogenous retroviruses (ERVs) originate by germline infection and subsequent mendelian inheritance of their exogenous counterparts. With notable exceptions, all mammalian ERVs are evolutionarily old and fixed in the population of its host species. Some groups of retroviruses were believed not to be able to form endogenous copies. We discovered an additional endogenous Lentivirus and a first endogenous Deltaretrovirus. Both of these groups were previously considered unable to form endogenous ...

Endogenous Monetary Policy Regime Change

OpenAIRE

Troy Davig; Eric M. Leeper

2006-01-01

This paper makes changes in monetary policy rules (or regimes) endogenous. Changes are triggered when certain endogenous variables cross specified thresholds. Rational expectations equilibria are examined in three models of threshold switching to illustrate that (i) expectations formation effects generated by the possibility of regime change can be quantitatively important; (ii) symmetric shocks can have asymmetric effects; (iii) endogenous switching is a natural way to formally model preempt...

ENDOGENEITY OF INDONESIAN MONEY SUPPLY

Directory of Open Access Journals (Sweden)

Meutia Safrina Rachma

2011-09-01

Full Text Available There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5-2010(6, the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not have control power on money supply. The bank is only able to maintain the stability and control the movement of broad money supply. Keywords: Endogenous variable, money supply, vector autoregressionJEL classification numbers: E51, E52, E58

REFERENCE MODELS OF ENDOGENOUS ECONOMIC GROWTH

OpenAIRE

GEAMĂNU MARINELA

2012-01-01

The new endogenous growth theories are a very important research area for shaping the most effective policies and long term sustainable development strategies. Endogenous growth theory has emerged as a reaction to the imperfections of neoclassical theory, by the fact that the economic growth is the endogenous product of an economical system.

ENDOGENEITY OF INDONESIAN MONEY SUPPLY

OpenAIRE

Rachma, Meutia Safrina

2011-01-01

There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5)-2010(6), the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not hav...

Endogeneity Of Indonesian Money Supply

OpenAIRE

Rachma, Meutia Safrina

2010-01-01

There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5)-2010(6), the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not hav...

The Endogenous Origins of Experience, Routines and Organizational Capabilities

DEFF Research Database (Denmark)

Foss, Nicolai Juul; Felin, Teppo

2011-01-01

In this paper we discuss the origins and emergence of organizational routines and capabilities. We first argue that there are theoretical and endogeneity-related concerns associated with the key antecedents and mechanisms specified by the extant routines and capabilities literature. Specifically,...... or rationalist, choice-based approach can provide a more fruitful (though preliminary) foundation for understanding organizational behavior and capabilities.......In this paper we discuss the origins and emergence of organizational routines and capabilities. We first argue that there are theoretical and endogeneity-related concerns associated with the key antecedents and mechanisms specified by the extant routines and capabilities literature. Specifically......, we explicate the behaviorist and empiricist foundations of the organizational routines and capabilities literature and the extant emphasis placed on experience, repetition, and observation as the key antecedents and mechanisms of routines and capabilities. Based on this discussion we highlight...

HYPERCORTISOLISM: CLASSIFICATION, PATHOGENESIS, CLINICAL MANIFESTATIONS. DIAGNOSIS OF ENDOGENOUS HYPERCORTISOLISM

Directory of Open Access Journals (Sweden)

Nikonova L. V.

2017-02-01

Full Text Available The relevance of the study of Cushing's syndrome with different etiology as well as the states of hypercorticism, which is not associated with endogenous hypercortisolism, is due to the difficulty of the diagnosis of this disease. Accurate knowledge of the classification criteria for the diagnosis of hypercorticism enables subsequently to establish the correct diagnosis and to administer the appropriate treatment. It was found that the cause of hypercorticism can be endogenous and exogenous factors. There is a particular group of patients requiring screening for hypercorticism using special diagnostic tests. Only a clear understanding of etiopathogenesis of hypercorticism and its clinical manifestations by the specialist, the correct interpretation of diagnostic results make it possible to establish the diagnosis, to administer the appropriate treatment and significantly reduce the morbidity and mortality of patients of this profile and improve their quality of life.

Running Performance, VO2max, and Running Economy: The Widespread Issue of Endogenous Selection Bias.

Science.gov (United States)

Borgen, Nicolai T

2018-05-01

Studies in sport and exercise medicine routinely use samples of highly trained individuals in order to understand what characterizes elite endurance performance, such as running economy and maximal oxygen uptake VO 2max . However, it is not well understood in the literature that using such samples most certainly leads to biased findings and accordingly potentially erroneous conclusions because of endogenous selection bias. In this paper, I review the current literature on running economy and VO 2max , and discuss the literature in light of endogenous selection bias. I demonstrate that the results in a large part of the literature may be misleading, and provide some practical suggestions as to how future studies may alleviate endogenous selection bias.

Quantifying the time scales over which exogenous and endogenous conditions affect soil respiration

Science.gov (United States)

Understanding how exogenous and endogenous factors and aboveground-belowground linkages modulate carbon dynamics is difficult because of influences of antecedent conditions. For example, there are variable lags between aboveground assimilation and belowground efflux, and the duration of antecedent p...

Endogenous growth and the environment

NARCIS (Netherlands)

Withagen, C.A.A.M.; Vellinga, N.

2001-01-01

This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

Endogenous growth and environmental policy

NARCIS (Netherlands)

Withagen, C.A.A.M.; Vellinga, N.

2001-01-01

This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

Endogenous retroviruses of sheep: a model system for understanding physiological adaptation to an evolving ruminant genome.

Science.gov (United States)

Spencer, Thomas E; Palmarini, Massimo

2012-01-01

Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. The sheep genome contains 27 endogenous betaretroviruses (enJSRVs) related to the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV), the causative agent of a transmissible lung cancer in sheep. The enJSRVs can protect their host against JSRV infection by blocking early and late steps of the JSRV replication cycle. In the female reproductive tract, enJSRVs are specifically expressed in the uterine luminal and glandular epithelia as well as in the conceptus (embryo and associated extraembryonic membranes) trophectoderm and in utero loss-of-function experiments found the enJSRVs envelope (env) to be essential for conceptus elongation and trophectoderm growth and development. Collectively, available evidence in sheep and other mammals indicate that ERVs coevolved with their hosts for millions of years and were positively selected for biological roles in genome plasticity and evolution, protection of the host against infection of related pathogenic and exogenous retroviruses, and placental development.

Endogenous pyrogen-like substance produced by reptiles.

Science.gov (United States)

Bernheim, H A; Kluger, M J

1977-06-01

1. Injection of lizards (Dipsosaurus dorsalis) with rabbit endogenous pyrogen led to a fever. Injections with denatured endogenous pyrogen did not affect body temperature. 2. Injection of lizards with lizard endogenous pyrogen led to a fever of short duration, while injection of denatured lizard endogenous pyrogen produced no change in body temperature. 3. These data support the hypothesis that the febrile mechanism observed in the higher vertebrates has its origins in some primitive vertebrate.

Rapid and reversible epigenome editing by endogenous chromatin regulators.

Science.gov (United States)

Braun, Simon M G; Kirkland, Jacob G; Chory, Emma J; Husmann, Dylan; Calarco, Joseph P; Crabtree, Gerald R

2017-09-15

Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells. Furthermore, Hp1/Suv39h1 heterochromatin complex recruitment to active promoters deposits H3K9me3 domains, resulting in gene silencing that can be reversed upon washout of the chemical dimerizer. This inducible recruitment strategy provides precise kinetic information to model epigenetic memory and plasticity. It is broadly applicable to mechanistic studies of chromatin in mammalian cells and is particularly suited to the analysis of endogenous multi-subunit chromatin regulator complexes.Understanding the link between epigenetic marks and gene regulation requires the development of new tools to directly manipulate chromatin. Here the authors demonstrate a Cas9-based system to recruit chromatin remodelers to loci of interest, allowing rapid, reversible manipulation of epigenetic states.

Central Nervous System Demyelination and Remyelination is Independent from Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.

Science.gov (United States)

Raddatz, Barbara B; Sun, Wenhui; Brogden, Graham; Sun, Yanyong; Kammeyer, Patricia; Kalkuhl, Arno; Colbatzky, Florian; Deschl, Ulrich; Naim, Hassan Y; Baumgärtner, Wolfgang; Ulrich, Reiner

2016-01-01

High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, microarrays and high-performance thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss of motor performance and demyelinating leukomyelitis. Gene expression associated with cholesterol biosynthesis was overall down-regulated in the spinal cord of TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin were reduced on day 196 post TMEV infection. Paigen diet induced serum hypercholesterolemia and hepatic lipidosis. However, high dietary fat and cholesterol intake led to no significant differences in clinical course, inflammatory response, astrocytosis, and the amount of demyelination and remyelination in the spinal cord of TMEV-infected animals. The results suggest that down-regulation of cholesterol biosynthesis is a transcriptional marker for demyelination, quantitative loss of myelin-specific lipids, but not cholesterol occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no significant effect on TMEV infection. © 2015 International Society of Neuropathology.

How Stock Markets Development Affect Endogenous Growth Theory

Directory of Open Access Journals (Sweden)

Najeb Masoud

2013-10-01

Full Text Available This paper can bedescribed as a significant exploratory study that will provide a significantcontribution to knowledge to consider crucial issues which need to be barriersto understanding or a temptation/ requirement to judge some practices as‘better’ than others for stock market development effective approach andimplement successful stock market performance and economic growth. Recentanalysis of the link between financial development and growth, gained frominsights acquired as a result of using the technique of endogenous growthmodels, has illustrated that growth without exogenous technical progress andthat growth rates could be related to technology, income distribution andinstitutional arrangements. This provides the theoretical background thatempirical studies have lacked; illustrating that financial intermediationaffects the level of economic growth. Resulting models have provided newimpetus to empirical research of the effects of financial development. Thebirth of the new endogenous growth theory has facilitated the development ofimproved growth models where the long-term rate could be affected by a numberof elements. These included technology, education and health policies in theprocess of economic development, capital accumulation, government policies andinstitutional activities in the role of financial development in economicgrowth.

Proteomics analysis of the endogenous, constitutive, leaf SUMOylome.

Science.gov (United States)

Colignon, Bertrand; Delaive, Edouard; Dieu, Marc; Demazy, Catherine; Muhovski, Yordan; Wallon, Cindy; Raes, Martine; Mauro, Sergio

2017-01-06

SUMOylation is a post-translational modification which regulates a number of critical biological processes in, for example mammals, yeast and plants. In order to fully understand the functional effects of SUMOylation an essential first step is the identification of endogenous targets for SUMOylation. Here we report the results of using a recently developed proteomic approach based on the use of 3D gels to identify the endogenous SUMO targets in leaves of Solanum tuberosum. By using 3D gels we avoid the problem of co-migration of proteins, which is a major limitation of 2D gels, and we enable the use of the highly sensitive CyDye DIGE fluor saturation dyes. Using this new method we have identified 39 individual proteins as probable SUMO targets in leaves of Solanum tuberosum. The advantages of this method compared with other approaches are discussed, and possible future developments are outlined. The authors have no conflicts of interest to declare. All authors have approved the manuscript and agree with submission to Journal of Proteomics. Copyright © 2016. Published by Elsevier B.V.

The Demand for Endogenous Money: A Lesson in Institutional Change

OpenAIRE

Peter Howells

2007-01-01

During a distinguished career, Basil Moore has made numerous important contributions to macroeconomics and monetary economics, and is renowned as the progenitor of the ‘horizontalist’ analysis of endogenous money. More recently, he has embraced complexity theory as part of an ongoing effort to understand macroeconomics as an evolving, path-dependent process. This book celebrates and explores Basil Moore’s interests in and contributions to monetary and macroeconomic theory.

Public Procurement of Innovation as Endogenous

DEFF Research Database (Denmark)

Rolfstam, Max

Public procurement used as an innovation policy instrument has attracted attention the last decade. It has been argued that public procurement can be used to stimulate innovation from the demand-side. This paper problematizes ‘demand’ understood as a problem defined by a public procurer given...... to potential suppliers to solve. By drawing on a cross-case analysis of two similar projects the paper attempts to explicate an understanding of the role of public procurement of innovation not primarily as a ‘demand-side innovation instrument’, as such thinking might run the risk of ignoring important...... underlying mechanisms critical for success. Instead the paper views public procurement of innovation as an instrument of endogenous- exogenous knowledge conversion....

Endogenous and exogenously-induced immunomodulation of tumour-host responsiveness

Directory of Open Access Journals (Sweden)

Richard J. Ablin

1987-01-01

Full Text Available In spite of the availability of multiple effector mechanisms of the immune system to combat tumour growth and metastases, their impairment frequently accompanies the appearance of cancer. Factors contributing to this impairment may be related to properties of the host and/or the tumour itself and may be with respect to their origin -endogenous or exogenour. Based on the unique biological behavior of prostate cancer (PCa, and its apparent escape from immune surveillance in the presence of tumour immuno genicity, continuing investigation of endogenous and exogenous factors thought to be relevant to its pathogenesis have been made. For this purpose further studies of the suggested role of human seminal plasma (SePl and the synthetic oestrogen, diethylstiboestrol (DES, as representative endogenous and exogenous immunomodulatory factors (IMF of tumour-host responsiveness, together with evaluation of human prostatic tissue extracts and leuprolide (the luteinizing-hormone-releasing-hormone proposed as an alternate to DES therapy have been made by evaluating their effect on the lytic activity of natural killer (NK cells. SePl and prostate extracts significantly suppressed NK cell lysis. Physicochemical studies suggest SePl and prostate IMF to be associated with high and low molecular weight macromolecules; and implicate the participation of transglutaminase and prostaglandins. Comparative study of therapeutic levels of DES vs. leuprolide on NK cell lysis demonstrated significant suppression by DES vs. a negligible effect of leuprolide. Metastases are highly prevalent in PCa, and contribute significantly to its morbidity and mortality. Further knowledge of the range of effects of endogenous and exogenous IMF on effector mechanisms of tumour-host responsiveness, to include suppression of NK cells, and elucidation of their nature, may contribute toward our understanding of the unique biological behavior of tumours of the prostate, in addition to

Quantifying the timescales over which exogenous and endogenous conditions affect soil respiration.

Science.gov (United States)

Barron-Gafford, Greg A; Cable, Jessica M; Bentley, Lisa Patrick; Scott, Russell L; Huxman, Travis E; Jenerette, G Darrel; Ogle, Kiona

2014-04-01

Understanding how exogenous and endogenous factors and above-ground-below-ground linkages modulate carbon dynamics is difficult because of the influences of antecedent conditions. For example, there are variable lags between above-ground assimilation and below-ground efflux, and the duration of antecedent periods are often arbitrarily assigned. Nonetheless, developing models linking above- and below-ground processes is crucial for estimating current and future carbon dynamics. We collected data on leaf-level photosynthesis (Asat ) and soil respiration (Rsoil ) in different microhabitats (under shrubs vs under bunchgrasses) in the Sonoran Desert. We evaluated timescales over which endogenous and exogenous factors control Rsoil by analyzing data in the context of a semimechanistic temperature-response model of Rsoil that incorporated effects of antecedent exogenous (soil water) and endogenous (Asat ) conditions. For both microhabitats, antecedent soil water and Asat significantly affected Rsoil , but Rsoil under shrubs was more sensitive to Asat than that under bunchgrasses. Photosynthetic rates 1 and 3 d before the Rsoil measurement were most important in determining current-day Rsoil under bunchgrasses and shrubs, respectively, indicating a significant lag effect. Endogenous and exogenous controls are critical drivers of Rsoil , but the relative importance and the timescale over which each factor affects Rsoil depends on above-ground vegetation and ecosystem structure characteristics. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Prion diseases and adult neurogenesis: how do prions counteract the brain's endogenous repair machinery?

Science.gov (United States)

Relaño-Ginés, Aroa; Lehmann, Sylvain; Crozet, Carole

2014-01-01

Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process, however it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies.

Ciliary neurotrophic factor is an endogenous pyrogen.

Science.gov (United States)

Shapiro, L; Zhang, X X; Rupp, R G; Wolff, S M; Dinarello, C A

1993-09-15

Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) following intravenous injection; CNTF fever was blocked by pretreatment with indomethacin. The fever induced by CNTF was not due to contaminating endotoxins. Increasing doses of CNTF resulted in prolongation of the fever, suggesting the subsequent induction of additional endogenous pyrogenic activity. After passive transfer of plasma obtained during CNTF-induced fever, endogenous pyrogen activity was not present in the circulation; CNTF also did not induce the endogenous pyrogens interleukin 1, tumor necrosis factor, or interleukin 6 in vitro. Nevertheless, a second endogenous pyrogen may originate within the central nervous system following the systemic injection of CNTF. Of the four endogenous pyrogens described to date (interleukin 1, tumor necrosis factor, interferon, and interleukin 6), CNTF, like interleukin 6, utilizes the cell-surface gp 130 signal-transduction apparatus.

Structural Analysis of Silicic Lavas Reveals the Importance of Endogenous Flow During Emplacement

Science.gov (United States)

Andrews, G. D.; Martens, A.; Isom, S.; Maxwell, A.; Brown, S. R.

2017-12-01

Recent observations of silicic lava flows in Chile strongly suggest sustained, endogeneous flow beneath an insulating carapace, where the flow advances through breakouts at the flow margin. New mapping of vertical exposures around the margin of Obsidian Dome, California, has identified discreet lobe structures in cross-section, suggesting that flow-front breakouts occured there during emplacement. The flow lobes are identified through structural measurements of flow-banding orientation and the stretching directions of vesicles. Newly acquired lidar of the Inyo Domes, including Obsidian Dome, is being analyzed to better understand the patterns of folding on the upper surface of the lavas, and to test for fold vergence patterns that may distinguish between endogenous and exogenous flow.

Remyelination in experimentally demyelinated connexin 32 KnockOut mice Remielinização em camundongos KnockOut para conexina 32 desmielinizados experimentalmente

Directory of Open Access Journals (Sweden)

Adriano Tony Ramos

2009-06-01

Full Text Available The aim of this study was to evaluate the role of connexin 32 (Cx 32 during remyelination of the peripheral nervous system, through a local injection of either 0,1% ethidium bromide solution or saline in the sciatic nerve of Cx 32 knockout mice. Euthanasia was performed ranging from 1, 2, 3, 7, 15, 21 to 30 days after injection. Histochemical, immunohistochemical, immunofluorescence and transmission electron microscopical techniques were used to analyze the development of the lesions. Within the sciatic nerves, Schwann cells initially showed signs of intoxication and rejected their sheaths; after seven days, some thin newly formed myelin sheaths with uneven compactness and redundant loops (tomacula were conspicuous. We concluded that the regeneration of lost myelin sheaths within the PNS followed the pattern already reported for this model in other laboratory species. Therefore, these results suggest that absence of Cx 32 did not interfere with the normal pattern of remyelination in this model in young mice.Este estudo visou avaliar o papel da conexina 32 (Cx 32 durante a remielinização no sistema nervoso periférico. Uma injeção local de 0,1% de solução de brometo de etídio foi realizada no nervo ciático de camundongos deletados para a Cx 32, com eutanásia dos animais aos 1, 2, 3, 7, 15, 21 e 30 dias pós-injeção. Avaliações histoquímicas, imunoistoquímicas, por imunofluorescência e por microscopia eletrônica de transmissão foram utilizadas na análise do desenvolvimento das lesões. Nos nervos ciáticos, células de Schwann mostraram inicialmente sinais de intoxicação e rejeitaram suas bainhas. Após sete dias, observaram-se finas bainhas neoformadas, com compactação desigual e alças redundantes (tomácula. Conclui-se que a regeneração de bainhas de mielina perdidas no SNP seguiu o padrão já relatado deste modelo em outras espécies de laboratório. Portanto, estes resultados sugerem que a ausência da Cx 32 n

Understanding the NG2 glial scar after spinal cord injury

Directory of Open Access Journals (Sweden)

Amber R Hackett

2016-11-01

Full Text Available NG2 cells, also known as oligodendrocyte progenitor cells, are located throughout the central nervous system and serve as a pool of progenitors to differentiate into oligodendrocytes. In response to spinal cord injury, NG2 cells increase their proliferation and differentiation into remyelinating oligodendrocytes. While astrocytes are typically associated with being the major cell type in the glial scar, many NG2 cells also accumulate within the glial scar but their function remains poorly understood. Similar to astrocytes, these cells hypertrophy, upregulate expression of chondroitin sulfate proteoglycans, inhibit axon regeneration, contribute to the glial-fibrotic scar border, and some even differentiate into astrocytes. Whether NG2 cells also have a role in other astrocyte functions, such as preventing the spread of infiltrating leukocytes and expression of inflammatory cytokines, is not yet known. Thus, NG2 cells are not only important for remyelination after spinal cord injury, but are also a major component of the glial scar with functions that overlap with astrocytes in this region. In this review, we describe the signaling pathways important for the proliferation and differentiation of NG2 cells, as well as the role of NG2 cells in scar formation and tissue repair.

Spider silk constructs enhance axonal regeneration and remyelination in long nerve defects in sheep.

Directory of Open Access Journals (Sweden)

Christine Radtke

Full Text Available BACKGROUND: Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. METHODOLOGY/PRINCIPAL FINDINGS: The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6 was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6 staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery.

Interaction between endogenous and exogenous orienting in crossmodal attention.

Science.gov (United States)

Chen, Xiaoxi; Chen, Qi; Gao, Dingguo; Yue, Zhenzhu

2012-08-01

Using a cue-target paradigm, we investigated the interaction between endogenous and exogenous orienting in cross-modal attention. A peripheral (exogenous) cue was presented after a central (endogenous) cue with a variable time interval. The endogenous and exogenous cues were presented in one sensory modality (auditory in Experiment 1 and visual in Experiment 2) whereas the target was presented in another modality. Both experiments showed a significant endogenous cuing effect (longer reaction times in the invalid condition than in the valid condition). However, exogenous cuing produced a facilitatory effect in both experiments in response to the target when endogenous cuing was valid, but it elicited a facilitatory effect in Experiment 1 and an inhibitory effect in Experiment 2 when endogenous cuing was invalid. These findings indicate that endogenous and exogenous cuing can co-operate in orienting attention to the crossmodal target. Moreover, the interaction between endogenous and exogenous orienting of attention is modulated by the modality between the cue and the target. © 2012 The Authors. Scandinavian Journal of Psychology © 2012 The Scandinavian Psychological Associations.

Are human endogenous retroviruses triggers of autoimmune diseases?

DEFF Research Database (Denmark)

Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

2016-01-01

factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...

Contagion risk in endogenous financial networks

International Nuclear Information System (INIS)

Li, Shouwei; Sui, Xin

2016-01-01

Highlights: • We propose an endogenous financial network model. • Endogenous networks include interbank networks, inter-firm networks and bank-firm networks. • We investigate contagion risk in endogenous financial networks. - Abstract: In this paper, we investigate contagion risk in an endogenous financial network, which is characterized by credit relationships connecting downstream and upstream firms, interbank credit relationships and credit relationships connecting firms and banks. The findings suggest that: increasing the number of potential lenders randomly selected can lead to an increase in the number of bank bankruptcies, while the number of firm bankruptcies presents a trend of increase after the decrease; after the intensity of choice parameter rises beyond a threshold, the number of bankruptcies in three sectors (downstream firms, upstream firms and banks) shows a relatively large margin of increase, and keeps at a relatively high level; there exists different trends for bankruptcies in different sectors with the change of the parameter of credits’ interest rates.

Endogenous price flexibility and optimal monetary policy

OpenAIRE

Ozge Senay; Alan Sutherland

2014-01-01

Much of the literature on optimal monetary policy uses models in which the degree of nominal price flexibility is exogenous. There are, however, good reasons to suppose that the degree of price flexibility adjusts endogenously to changes in monetary conditions. This article extends the standard new Keynesian model to incorporate an endogenous degree of price flexibility. The model shows that endogenizing the degree of price flexibility tends to shift optimal monetary policy towards complete i...

Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein.

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Christian Much

2016-06-01

Full Text Available Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse.

Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein.

Science.gov (United States)

Much, Christian; Auchynnikava, Tania; Pavlinic, Dinko; Buness, Andreas; Rappsilber, Juri; Benes, Vladimir; Allshire, Robin; O'Carroll, Dónal

2016-06-01

Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse.

Endogenous Pyrogen Physiology.

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Beisel, William R.

1980-01-01

Discusses the physiology of endogenous pyrogen (EP), the fever-producing factor of cellular origin. Included are: its hormone-like role, its molecular nature, bioassay procedures, cellular production and mechanisms of EP action. (SA)

Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition.

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Baglietto-Vargas, David; Kitazawa, Masashi; Le, Elaine J; Estrada-Hernandez, Tatiana; Rodriguez-Ortiz, Carlos J; Medeiros, Rodrigo; Green, Kim N; LaFerla, Frank M

2014-02-01

Recent studies on tauopathy animal models suggest that the concomitant expression of the endogenous murine tau delays the pathological accumulation of human tau, and interferes with the disease progression. To elucidate the role of endogenous murine tau in a model with both plaques and tangles, we developed a novel transgenic mouse model by crossing 3xTg-AD with mtauKO mice (referred to as 3xTg-AD/mtauKO mice). Therefore, this new model allows us to determine the pathological consequences of the murine tau. Here, we show that 3xTg-AD/mtauKO mice have lower tau loads in both soluble and insoluble fractions, and lower tau hyperphosphorylation level in the soluble fraction relative to 3xTg-AD mice. In the 3xTg-AD model endogenous mouse tau is hyperphosphorylated and significantly co-aggregates with human tau. Despite the deletion of the endogenous tau gene in 3xTg-AD/mtauKO mice, cognitive dysfunction was equivalent to 3xTg-AD mice, as there was no additional impairment on a spatial memory task, and thus despite increased tau phosphorylation, accumulation and NFTs in 3xTg-AD mice no further effects on cognition are seen. These findings provide better understanding about the role of endogenous tau to Alzheimer's disease (AD) pathology and for developing new AD models. © 2013.

Endogenous money: the evolutionary versus revolutionary views

OpenAIRE

Louis-Philippe Rochon; Sergio Rossi

2013-01-01

The purpose of this paper is to shed light on the endogenous nature of money. Contrary to the established post-Keynesian, or evolutionary, view, this paper argues that money has always been endogenous, irrespective of the historical period. Instead of the evolutionary theory of money and banking that can be traced back to Chick (1986), this paper puts forward a revolutionary definition of endogenous money consistent with many aspects of post-Keynesian economics as well as with the monetary ci...

Endogenous Peer Effects: Fact or Fiction?

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Yeung, Ryan; Nguyen-Hoang, Phuong

2016-01-01

The authors examine endogenous peer effects, which occur when a student's behavior or outcome is a function of the behavior or outcome of his or her peer group. Endogenous peer effects have important implications for educational policies such as busing, school choice and tracking. In this study, the authors quantitatively review the literature on…

OSP-Immunofluorescent remyelinating oligodendrocytes in the brainstem of toxically-demyelinated Wistar rats Oligodendrócitos remielinizantes positivos para OSP - proteína específica do oligodendrócito- no tronco encefálico de ratos Wistar desmielinizados toxicamente

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Eliza Simone Viégas Sallis

2006-06-01

Full Text Available Central nervous system (CNS remyelination following toxically-induced demyelination is a well known process. Oligodendrocytes constitute the bulk of the myelinating cells in the brain whereas Schwann cells overwhelm oligodendrocytes numbers in spinal cord remyelination. Despite the common knowledge of these facts, we still do not know completely the origin of both remyelinating cells. The present study investigated the participation of mature oligodendrocytes in remyelination after ethidium-bromide (EB induced demyelination in the brainstem of normal and cyclosporin A-immunosuppressed Wistar rats. Thirty adult female rats were divided into three experimental groups. In group 1 the rats received a single intracisternal injection of 10 muL of 0.1% ethidium bromide (EB in 0.9% saline (n=10; in group 2 the rats received the EB injection while immunosuppressed with cyclosporin A (n=10; in group 3 the rats received a single 10 muL injection of 0.9% saline while treated with cyclosporin A. The rats were killed at 15, 21 and 31 days after injection. Within the EB lesions, from 15 days onward many cells within the periphery of the lesions stained positive for OSP (oligodendrocyte specific protein a marker for mature oligodendrocytes and myelin. This cell marking signals that, at least, part of the process of repairing the myelin sheaths is carried out by mature cells of the oligodendrocyte lineage.A remielinização do sistema nervoso central após desmielinização tóxica é um processo bem conhecido. No encéfalo, os oligodendrócitos remielinizam uma área maior do que na medula espinhal, onde as células de Schwann são preponderantes. Embora esses fatos sejam bem conhecidos, ainda não se conhece com certeza a origem das células remielinizantes. Esta investigação foi desenhada para esclarecer a participação de oligodendrócitos maduros na reconstrução das bainhas perdidas após a desmielinização induzida por brometo de etídio (BE no

Silver resistance in Gram-negative bacteria: a dissection of endogenous and exogenous mechanisms.

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Randall, Christopher P; Gupta, Arya; Jackson, Nicole; Busse, David; O'Neill, Alex J

2015-04-01

To gain a more detailed understanding of endogenous (mutational) and exogenous (horizontally acquired) resistance to silver in Gram-negative pathogens, with an emphasis on clarifying the genetic bases for resistance. A suite of microbiological and molecular genetic techniques was employed to select and characterize endogenous and exogenous silver resistance in several Gram-negative species. In Escherichia coli, endogenous resistance arose after 6 days of exposure to silver, a consequence of two point mutations that were both necessary and sufficient for the phenotype. These mutations, in ompR and cusS, respectively conferred loss of the OmpC/F porins and derepression of the CusCFBA efflux transporter, both phenotypic changes previously linked to reduced intracellular accumulation of silver. Exogenous resistance involved derepression of the SilCFBA efflux transporter as a consequence of mutation in silS, but was additionally contingent on expression of the periplasmic silver-sequestration protein SilE. Silver resistance could be selected at high frequency (>10(-9)) from Enterobacteriaceae lacking OmpC/F porins or harbouring the sil operon and both endogenous and exogenous resistance were associated with modest fitness costs in vitro. Both endogenous and exogenous silver resistance are dependent on the derepressed expression of closely related efflux transporters and are therefore mechanistically similar phenotypes. The ease with which silver resistance can become selected in some bacterial pathogens in vitro suggests that there would be benefit in improved surveillance for silver-resistant isolates in the clinic, along with greater control over use of silver-containing products, in order to best preserve the clinical utility of silver. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

59 eyes with endogenous endophthalmitis

DEFF Research Database (Denmark)

Bjerrum, Søren Solborg; la Cour, Morten

2017-01-01

BACKGROUND: To study the epidemiology of patients with endogenous endophthalmitis in Denmark. MATERIAL AND METHODS: Retrospective and prospective case series of 59 eyes in patients with endogenous endophthalmitis in Denmark between 2000 and 2016. RESULTS: The age of the patients ranged from 28 to......, the visual outcome and the mortality of the patients. The epidemiology of the disease is very different in Scandinavia compared to Asia. The visual prognosis remains grave and the majority of the eyes lose useful vision....

Independent effects of endogenous and exogenous attention in touch.

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Jones, Alexander; Forster, Bettina

2013-12-01

Endogenous and exogenous attention in touch have typically been investigated separately. Here we use a double-cueing paradigm manipulating both types of orienting in each trial. Bilateral endogenous cues induced long-lasting facilitation of endogenous attention up to 2 s. However, the exogenous cue only elicited an effect at short intervals. Our results favour a supramodal account of attention and this study provides new insight into how endogenous and exogenous attention operates in the tactile modality.

Endogenous versus exogenous shocks in systems with memory

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Sornette, D.; Helmstetter, A.

2003-02-01

Systems with long-range persistence and memory are shown to exhibit different precursory as well as recovery patterns in response to shocks of exogenous versus endogenous origins. By endogenous, we envision either fluctuations resulting from an underlying chaotic dynamics or from a stochastic forcing origin which may be external or be an effective coarse-grained description of the microscopic fluctuations. In this scenario, endogenous shocks result from a kind of constructive interference of accumulated fluctuations whose impacts survive longer than the large shocks themselves. As a consequence, the recovery after an endogenous shock is in general slower at early times and can be at long times either slower or faster than after an exogenous perturbation. This offers the tantalizing possibility of distinguishing between an endogenous versus exogenous cause of a given shock, even when there is no “smoking gun”. This could help in investigating the exogenous versus self-organized origins in problems such as the causes of major biological extinctions, of change of weather regimes and of the climate, in tracing the source of social upheaval and wars, and so on. Sornette et al., Volatility fingerprints of large stocks: endogenous versus exogenous, cond-mat/0204626 has already shown how this concept can be applied concretely to differentiate the effects on financial markets of the 11 September 2001 attack or of the coup against Gorbachev on 19 August 1991 (exogenous) from financial crashes such as October 1987 (endogenous).

Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

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Rebollo, Rita; Mager, Dixie L

2016-01-01

Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR.

International Environmental Agreements with Endogenous or Exogenous Risk

OpenAIRE

Fuhai Hong; Larry Karp

2014-01-01

We examine the effect of endogenous and exogenous risk on the equilibrium (expected) membership of an International Environmental Agreement when countries are risk averse. Endogenous risk arises when countries use mixed rather than pure strategies at the participation game, and exogenous risk arises from the inherent uncertainty about the costs and benefits of increased abate- ment. Under endogenous risk, an increase in risk aversion increases expected participation. Under exogenous risk and ...

Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation.

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Gue, Ying X; Gorog, Diana A

2017-08-25

The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions.

Bilateral endogenous Fusarium solani endophthalmitis in a liver-transplanted patient

DEFF Research Database (Denmark)

Jørgensen, Jesper Skovlund; Prause, Jan Ulrik; Kiilgaard, Jens Folke

2014-01-01

Endogenous Fusarium endophthalmitis is a rare disease predominantly described in immunocompromised patients often due to leukemia. We report a case of bilateral endogenous Fusarium solani endophthalmitis in a liver-transplanted patient.......Endogenous Fusarium endophthalmitis is a rare disease predominantly described in immunocompromised patients often due to leukemia. We report a case of bilateral endogenous Fusarium solani endophthalmitis in a liver-transplanted patient....

Feeding Releases Endogenous Opioids in Humans.

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Tuulari, Jetro J; Tuominen, Lauri; de Boer, Femke E; Hirvonen, Jussi; Helin, Semi; Nuutila, Pirjo; Nummenmaa, Lauri

2017-08-23

The endogenous opioid system supports a multitude of functions related to appetitive behavior in humans and animals, and it has been proposed to govern hedonic aspects of feeding thus contributing to the development of obesity. Here we used positron emission tomography to investigate whether feeding results in hedonia-dependent endogenous opioid release in humans. Ten healthy males were recruited for the study. They were scanned with the μ-opioid-specific ligand [ 11 C]carfentanil three times, as follows: after a palatable meal, a nonpalatable meal, and after an overnight fast. Subjective mood, satiety, and circulating hormone levels were measured. Feeding induced significant endogenous opioid release throughout the brain. This response was more pronounced following a nonpalatable meal versus a palatable meal, and independent of the subjective hedonic responses to feeding. We conclude that feeding consistently triggers cerebral opioid release even in the absence of subjective pleasure associated with feeding, suggesting that metabolic and homeostatic rather than exclusively hedonic responses play a role in the feeding-triggered cerebral opioid release. SIGNIFICANCE STATEMENT The endogenous opioid system supports both hedonic and homeostatic functions. It has been proposed that overeating and concomitant opioid release could downregulate opioid receptors and promote the development of obesity. However, it remains unresolved whether feeding leads to endogenous opioid release in humans. We used in vivo positron emission tomography to test whether feeding triggers cerebral opioid release and whether this response is associated with pleasurable sensations. We scanned volunteers using the μ-opioid receptor-specific radioligand [ 11 C]carfentanil three times, as follows: after an overnight fast, after consuming a palatable meal, and after consuming a nonpalatable meal. Feeding led to significant endogenous opioid release, and this occurred also in the absence of feeding

The Endogenous-Exogenous Partition in Attribution Theory

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Kruglanski, Arie W.

1975-01-01

Within lay explanation of actions, several significant inferences are assumed to follow from the partition between endogenous and exogenous attributions. An endogenous action is judged to constitute an end in itself; an exogenous action is judged to serve as a means to some further end. (Editor/RK)

THE PROCESSES OF ENDOGENIZING IN THE ENDOGENOUS GROWTH: THE CASE OF TURKEY

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OSMAN DEMİR

2013-06-01

Full Text Available The aim of this study is to state how the main inputs of endogenous growth, i.e. knowledge, human capital and technological progress are made endogenous by education, R&D, university-industry cooperation, learning by doing and diffusion within the production process. Competitiveness of firms and countries would increase as educated people enter into workforce; as R&D produces new technologies which are used in the production process; as theoretical knowledge meets with practice by university-industry cooperation; and as workers have more experience by learning by doing. In empirical analysis for Turkey is made by using data of 1970-2001 term it was found that a positive relationship among labour and capital factors and GNP and a negative relationship among education expenditures and foreign trade volume and capital stock.

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage

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Yu, Rui; Lai, Yongquan; Hartwell, Hadley J.; Moeller, Benjamin C.; Doyle-Eisele, Melanie; Kracko, Dean; Bodnar, Wanda M.; Starr, Thomas B.; Swenberg, James A.

2015-01-01

Formaldehyde is not only a widely used chemical with well-known carcinogenicity but is also a normal metabolite of living cells. It thus poses unique challenges for understanding risks associated with exposure. N2-hydroxymethyl-dG (N2-HOMe-dG) is the main formaldehyde-induced DNA mono-adduct, which together with DNA-protein crosslinks (DPCs) and toxicity-induced cell proliferation, play important roles in a mutagenic mode of action for cancer. In this study, N2-HOMe-dG was shown to be an excellent biomarker for direct adduction of formaldehyde to DNA and the hydrolysis of DPCs. The use of inhaled [13CD2]-formaldehyde exposures of rats and primates coupled with ultrasensitive nano ultra performance liquid chromatography-tandem mass spectrometry permitted accurate determinations of endogenous and exogenous formaldehyde DNA damage. The results show that inhaled formaldehyde only reached rat and monkey noses, but not tissues distant to the site of initial contact. The amounts of exogenous adducts were remarkably lower than those of endogenous adducts in exposed nasal epithelium. Moreover, exogenous adducts accumulated in rat nasal epithelium over the 28-days exposure to reach steady-state concentrations, followed by elimination with a half-life (t1/2) of 7.1 days. Additionally, we examined artifact formation during DNA preparation to ensure the accuracy of nonlabeled N2-HOMe-dG measurements. These novel findings provide critical new data for understanding major issues identified by the National Research Council Review of the 2010 Environmental Protection Agency’s Draft Integrated Risk Information System Formaldehyde Risk Assessment. They support a data-driven need for reflection on whether risks have been overestimated for inhaled formaldehyde, whereas underappreciating endogenous formaldehyde as the primary source of exposure that results in bone marrow toxicity and leukemia in susceptible humans and rodents deficient in DNA repair. PMID:25904104

Endogenous Cartilage Repair by Recruitment of Stem Cells.

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Im, Gun-Il

2016-04-01

Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair.

The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts.

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Natalie Saini

2016-10-01

Full Text Available Accumulation of somatic changes, due to environmental and endogenous lesions, in the human genome is associated with aging and cancer. Understanding the impacts of these processes on mutagenesis is fundamental to understanding the etiology, and improving the prognosis and prevention of cancers and other genetic diseases. Previous methods relying on either the generation of induced pluripotent stem cells, or sequencing of single-cell genomes were inherently error-prone and did not allow independent validation of the mutations. In the current study we eliminated these potential sources of error by high coverage genome sequencing of single-cell derived clonal fibroblast lineages, obtained after minimal propagation in culture, prepared from skin biopsies of two healthy adult humans. We report here accurate measurement of genome-wide magnitude and spectra of mutations accrued in skin fibroblasts of healthy adult humans. We found that every cell contains at least one chromosomal rearrangement and 600–13,000 base substitutions. The spectra and correlation of base substitutions with epigenomic features resemble many cancers. Moreover, because biopsies were taken from body parts differing by sun exposure, we can delineate the precise contributions of environmental and endogenous factors to the accrual of genetic changes within the same individual. We show here that UV-induced and endogenous DNA damage can have a comparable impact on the somatic mutation loads in skin fibroblasts. Trial Registration: ClinicalTrials.gov NCT01087307.

Differential diagnosis algorithm of endogenous catatonia, catatonia-morphic and catatonia-mimicking states

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D. N. Safonov

2017-08-01

Full Text Available Subject relevance. The process of mental pathology pathomorphosis leads to the polymorphism of its clinical manifestations and, as a consequence – to difficulties in identification and differential diagnosis. The solution to this problem is in the adaption of diagnostic methodology to clinical realities by including into their structure instruments formed basing on pathomorphosis factors and trends. In this perspective, the most prominent example is endogenous catatonia, which in the academic tradition is conventionally affiliated with the form of schizophrenia with the same name. According to the classical understanding, endogenous catatonia, or, in the narrow sense – catatonic syndrome, is a group of intermittent motor disorders, arranged with polymorphic shell constellation of neuropsychiatric manifestations. The aim is to develop pathomorphosis adapted clinical algorithm of endogenous catatonia differential diagnostics. Materials and methods: 236 patients of Zaporizhzhia Regional Psychiatric Clinic were examined. Patients were divided into groups due to their mental disorders: – core group: patients with elements of endogenous catatonia in the structure of different clinical forms of schizophrenia (there were 144 patients in this group; – comparison group #1: 69 patients with late neurotropic effects of neuroleptic therapy (LNENT; – comparison group #2: 103 patients with catatonia-morphic dissociative disorders (CDD; – comparison group #3: 90 patients with organic catatonic disorder (OrCD; Results. Using Bush-Francis Catatonia Rating scale as an instrument of clinical analysis and statistical research of results with A. Wald’s sequential analysis (modificated by E. V. Gubler an algorithm of differential diagnostics of endogenus catatonia which includes 3 steps of Recognition Scale for Endogenous Catatonia is developed. Conclusion. Designed scales have a number of categorical differences from existing analogues, foremost by

Explaining Cigarette Smoking: An Endogenous-Exogenous Analysis.

Science.gov (United States)

McKillip, Jack

Kruglanski's endogenous-exogenous partition, when applied to reasons given by smokers for smoking cigarettes, distinguishes two types of actions: (1) endogenous reasons implying that the behavior of consuming the cigarette is the goal of the action and the actor is positive toward the behavior, and (2) exogenous reasons implying that the behavior…

Endogenous opiates and behavior: 2014.

Science.gov (United States)

Bodnar, Richard J

2016-01-01

This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular

The endogenous regenerative capacity of the damaged newborn brain: boosting neurogenesis with mesenchymal stem cell treatment.

Science.gov (United States)

Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; Kavelaars, Annemieke; Heijnen, Cobi J

2013-05-01

Neurogenesis continues throughout adulthood. The neurogenic capacity of the brain increases after injury by, e.g., hypoxia-ischemia. However, it is well known that in many cases brain damage does not resolve spontaneously, indicating that the endogenous regenerative capacity of the brain is insufficient. Neonatal encephalopathy leads to high mortality rates and long-term neurologic deficits in babies worldwide. Therefore, there is an urgent need to develop more efficient therapeutic strategies. The latest findings indicate that stem cells represent a novel therapeutic possibility to improve outcome in models of neonatal encephalopathy. Transplanted stem cells secrete factors that stimulate and maintain neurogenesis, thereby increasing cell proliferation, neuronal differentiation, and functional integration. Understanding the molecular and cellular mechanisms underlying neurogenesis after an insult is crucial for developing tools to enhance the neurogenic capacity of the brain. The aim of this review is to discuss the endogenous capacity of the neonatal brain to regenerate after a cerebral ischemic insult. We present an overview of the molecular and cellular mechanisms underlying endogenous regenerative processes during development as well as after a cerebral ischemic insult. Furthermore, we will consider the potential to use stem cell transplantation as a means to boost endogenous neurogenesis and restore brain function.

P-wave dispersion in endogenous and exogenous subclinical hyperthyroidism.

Science.gov (United States)

Gen, R; Akbay, E; Camsari, A; Ozcan, T

2010-02-01

The aim of this study was to measure maximum P wave duration (Pmax) and P wave dispersion (PWD), which can be indicators for the risk of paroxysmal atrial fibrillation when increased, and to reveal their relationship with thyroid hormone levels in patients with endogenous and exogenous subclinical hyperthyroidism. Seventy-one patients with sublinical thyrotoxicosis (34 endogenous, 37 exogenous) and 69 healthy individuals were enrolled in the study. Pmax and minimum P wave duration (Pmin) on electrocardiogram recordings were measured and PWD was calculated as Pmax-Pmin. Pmax (pendogenous subclinical hyperthyroidism compared with the control group. Pmax (pexogenous subclinical thyrotoxicosis compared with the control group. Pmax (p=0.710) and PWD (p=0.127) were not significantly different in patients with endogenous subclinical hyperthyroidism compared with exogenous subclinical hyperthyroid patients. Pmax and PWD negatively associated with TSH in endogenous and exogenous subclinical hyperthyroidism. In the present study, we observed that Pmax and PWD were longer in patients with endogenous and exogenous subclinical hyperthyroidism. Lack of a difference in Pmax and PWD between patients with endogenous and exogenous subclinical hyperthyroidism seems to support the idea that hormone levels rather than the etiology of thyrotoxicosis affect the heart.

Endogene CGRP

OpenAIRE

Höfer, Martina

2010-01-01

Hintergrund und Ziele Die vorliegende tierexperimentelle Arbeit beschäftigt sich mit der Frage, welche Rolle endogenes Calcitonin-gene related peptide (CGRP) in der Niere spielt. Hierbei untersuchten wir die renale CGRP Freisetzung aus renalen Afferenzen in vitro anhand von gesunden Tieren und einem pathologischen Modell der Glomerulonephritis. Man weiß bereits, dass sowohl sympathische als auch primär sensorische Neuronen die Entzündung und die Immunantwort in der Peripherie regulieren (68)....

[The endogenous opioid system and drug addiction].

Science.gov (United States)

Maldonado, R

2010-01-01

Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits. Several neurotransmitters, including the endogenous opioid system are involved in these changes. The opioid system plays a pivotal role in different aspects of addiction. Thus, opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within the reward circuits. Opioid receptors and peptides are selectively involved in several components of the addictive processes induced by opioids, cannabinoids, psychostimulants, alcohol and nicotine. This review is focused on the contribution of each component of the endogenous opioid system in the addictive properties of the different drugs of abuse. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Endogenous Money Supply and Money Demand

OpenAIRE

Woon Gyu Choi; Seonghwan Oh

2000-01-01

This paper explores the behavior of money demand by explicitly accounting for the money supply endogeneity arising from endogenous monetary policy and financial innovations. Our theoretical analysis indicates that money supply factors matter in the money demand function when the money supply partially responds to money demand. Our empirical results with U.S. data provide strong evidence for the relevance of the policy stance to the demand for MI under a regime in which monetary policy is subs...

Optimized endogenous post-stratification in forest inventories

Science.gov (United States)

Paul L. Patterson

2012-01-01

An example of endogenous post-stratification is the use of remote sensing data with a sample of ground data to build a logistic regression model to predict the probability that a plot is forested and using the predicted probabilities to form categories for post-stratification. An optimized endogenous post-stratified estimator of the proportion of forest has been...

Dynamic equilibrium of endogenous selenium nanoparticles in selenite-exposed cancer cells: a deep insight into the interaction between endogenous SeNPs and proteins.

Science.gov (United States)

Bao, Peng; Chen, Song-Can; Xiao, Ke-Qing

2015-12-01

Elemental selenium (Se) was recently found to exist as endogenous nanoparticles (i.e., SeNPs) in selenite-exposed cancer cells. By sequestrating critical intracellular proteins, SeNPs appear capable of giving rise to multiple cytotoxicity mechanisms including inhibition of glycolysis, glycolysis-dependent mitochondrial dysfunction, microtubule depolymerization and inhibition of autophagy. In this work, we reveal a dynamic equilibrium of endogenous SeNP assembly and disassembly in selenite-exposed H157 cells. Endogenous SeNPs are observed both in the cytoplasm and in organelles. There is an increase in endogenous SeNPs between 24 h and 36 h, and a decrease between 36 h and 72 h according to transmission electron microscopy results and UV-Vis measurements. These observations imply that elemental Se in SeNPs could be oxidized back into selenite by scavenging superoxide radicals and ultimately re-reduced into selenide; then the assembly and disassembly of SeNPs proceed simultaneously with the sequestration and release of SeNP high-affinity proteins. There is also a possibility that the reduction of elemental Se to selenide pathway may lie in selenite-exposed cancer cells, which results in the assembly and disassembly of endogenous SeNPs. Genome-wide expression analysis results show that endogenous SeNPs significantly altered the expression of 504 genes, compared to the control. The endogenous SeNPs induced mitochondrial impairment and decreasing of the annexin A2 level can lead to inhibition of cancer cell invasion and migration. This dynamic flux of endogenous SeNPs amplifies their cytotoxic potential in cancer cells, thus provide a starting point to design more efficient intracellular self-assembling systems for overcoming multidrug resistance.

Endogenous opioids regulate moment-to-moment neuronal communication and excitability

Science.gov (United States)

Winters, Bryony L.; Gregoriou, Gabrielle C.; Kissiwaa, Sarah A.; Wells, Oliver A.; Medagoda, Danashi I.; Hermes, Sam M.; Burford, Neil T.; Alt, Andrew; Aicher, Sue A.; Bagley, Elena E.

2017-01-01

Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability. Ultrastructural localization of endogenous ligands support these functional findings. This study demonstrates a new role for endogenously released opioids as neuromodulators engaged by synaptic activity to regulate moment-to-moment neuronal communication and excitability. These distinct actions through MOR and DOR may underlie the opposing effect of these receptor systems on anxiety and fear. PMID:28327612

Monocular channels have a functional role in endogenous orienting.

Science.gov (United States)

Saban, William; Sekely, Liora; Klein, Raymond M; Gabay, Shai

2018-03-01

The literature has long emphasized the role of higher cortical structures in endogenous orienting. Based on evolutionary explanation and previous data, we explored the possibility that lower monocular channels may also have a functional role in endogenous orienting of attention. Sensitive behavioral manipulation was used to probe the contribution of monocularly segregated regions in a simple cue - target detection task. A central spatially informative cue, and its ensuing target, were presented to the same or different eyes at varying cue-target intervals. Results indicated that the onset of endogenous orienting was apparent earlier when the cue and target were presented to the same eye. The data provides converging evidence for the notion that endogenous facilitation is modulated by monocular portions of the visual stream. This, in turn, suggests that higher cortical mechanisms are not exclusively responsible for endogenous orienting, and that a dynamic interaction between higher and lower neural levels, might be involved. Copyright © 2018 Elsevier Ltd. All rights reserved.

Endogenous retroviruses mobilized during friend murine leukemia virus infection.

Science.gov (United States)

Boi, Stefano; Rosenke, Kyle; Hansen, Ethan; Hendrick, Duncan; Malik, Frank; Evans, Leonard H

2016-12-01

We have demonstrated in a mouse model that infection with a retrovirus can lead not only to the generation of recombinants between exogenous and endogenous gammaretrovirus, but also to the mobilization of endogenous proviruses by pseudotyping entire polytropic proviral transcripts and facilitating their infectious spread to new cells. However, the frequency of this occurrence, the kinetics, and the identity of mobilized endogenous proviruses was unclear. Here we find that these mobilized transcripts are detected after only one day of infection. They predominate over recombinant polytropic viruses early in infection, persist throughout the course of disease and are comprised of multiple different polytropic proviruses. Other endogenous retroviral elements such as intracisternal A particles (IAPs) were not detected. The integration of the endogenous transcripts into new cells could result in loss of transcriptional control and elevated expression which may facilitate pathogenesis, perhaps by contributing to the generation of polytropic recombinant viruses. Published by Elsevier Inc.

Endogene opioider og deres terapeutiske anvendelse i smertebehandling

DEFF Research Database (Denmark)

Juul, A; Pedersen, A T

1990-01-01

Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients following epidural or intrathecal administration of endogenous opioids. Further investi...

Endogenous vs. exogenous regulations in the commons

DEFF Research Database (Denmark)

Abatayo, Anna Lou; Lynham, John

2016-01-01

It is widely believed that there is strong experimental evidence to support the idea that exogenously imposed regulations crowd out the intrinsic motivations of common pool resource (CPR) users to refrain from over-harvesting. We introduce a novel experimental design that attempts to disentangle...... potential confounds in previous experiments. A key feature of our experimental design is to have the exact same regulations chosen endogenously as those that are imposed exogenously. When we compare the same regulations chosen endogenously to those externally imposed, we observe no differences in extraction...... endogenous regulations with communication and exogenous regulations without communication. Our results suggest that externally imposed regulations do not crowd out intrinsic motivations in the lab and they confirm that communication facilitates cooperation to reduce extraction....

Exercise induced asthma and endogenous opioids.

Science.gov (United States)

Gaillard, R C; Bachman, M; Rochat, T; Egger, D; de Haller, R; Junod, A F

1986-01-01

Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma. PMID:2944240

Relationship between endogenous hydrogen sulfide and blood stasis syndrome based on the Qi-blood theory of Chinese medicine.

Science.gov (United States)

Li, Wei-wei; Guo, Hao; Wang, Xue-mei

2013-09-01

"Qi" and "blood" are two essential concepts in Chinese medicine (CM). As qi is intangible, the concept of qi is still controversial between CM and Western medicine. However, the endogenous hydrogen sulfide (H2S) and other gaseous signaling molecules provides a new approach for understanding the essence of qi in CM. Blood stasis syndrome is a common syndrome in CM. According to the CM theory, the incidence of blood stasis syndrome is closely correlated to the reckless movement of qi, as qi and blood are inseparable in regulating physiological functions. In recent years, more and more evidences suggest a close correlation between blood stasis syndrome and microcirculation dysfunction. In this paper, we discuss the relationship between endogenous H2S and blood stasis syndrome based on qi-blood theory of CM. We found that endogenous H2S maybe a material basis in concept of qi in CM, while dysfunctional microcirculation is the pathological basis of the blood stasis syndrome. As qi is closely associated with incidence and progression of blood stasis syndrome, endogenous H2S may play an important role in preventing and treating the blood stasis syndrome by improving the function of microcirculation.

Mobilization of endogenous retroviruses in mice after infection with an exogenous retrovirus.

Science.gov (United States)

Evans, Leonard H; Alamgir, A S M; Owens, Nick; Weber, Nick; Virtaneva, Kimmo; Barbian, Kent; Babar, Amenah; Malik, Frank; Rosenke, Kyle

2009-03-01

Mammalian genomes harbor a large number of retroviral elements acquired as germ line insertions during evolution. Although many of the endogenous retroviruses are defective, several contain one or more intact viral genes that are expressed under certain physiological or pathological conditions. This is true of the endogenous polytropic retroviruses that generate recombinant polytropic murine leukemia viruses (MuLVs). In these recombinants the env gene sequences of exogenous ecotropic MuLVs are replaced with env gene sequences from an endogenous polytropic retrovirus. Although replication-competent endogenous polytropic retroviruses have not been observed, the recombinant polytropic viruses are capable of replicating in numerous species. Recombination occurs during reverse transcription of a virion RNA heterodimer comprised of an RNA transcript from an endogenous polytropic virus and an RNA transcript from an exogenous ecotropic MuLV RNA. It is possible that homodimers corresponding to two full-length endogenous RNA genomes are also packaged. Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections.

After Nerve Injury, Lineage Tracing Shows That Myelin and Remak Schwann Cells Elongate Extensively and Branch to Form Repair Schwann Cells, Which Shorten Radically on Remyelination.

Science.gov (United States)

Gomez-Sanchez, Jose A; Pilch, Kjara S; van der Lans, Milou; Fazal, Shaline V; Benito, Cristina; Wagstaff, Laura J; Mirsky, Rhona; Jessen, Kristjan R

2017-09-13

generation of these repair-supportive Schwann cells involves an extensive cellular elongation and branching, often to form long, parallel processes. This generates a distinctive repair cell morphology that is favorable for the formation of the regeneration tracks that are essential for nerve repair. Remyelination, conversely, involves a striking cell shortening to form the typical short myelin cells of regenerated nerves. We also provide evidence for direct lineage relationships between: (1) repair cells and myelin and Remak cells of uninjured nerves and (2) remyelinating cells in regenerated nerves. Copyright © 2017 Gomez-Sanchez et al.

The theory of endogenous money and the LM schedule: prelude to a reconstruction of ISLM

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THOMAS I. PALLEY

Full Text Available ABSTRACT Money is at the center of macroeconomics, which makes understanding the money supply central for macroeconomic theory. This paper presents the Post Keynesian theory of endogenous money supply and shows how it is fundamentally different from the conventional money supply theory. The conventional approach relies on the money multiplier and bank lending is invisible. Post Keynesian theory discards the money multiplier and focuses on bank lending which drives money creation. The paper emphasizes the structuralist version of Post Keynesian theory which retains Keynes’ liquidity preference theory of long term interest rates and also recognizes banks are subject to financial constraints that limit their lending activities. The paper then shows how to derive the LM schedule in an endogenous money economy, which is a necessary prelude to reconstructing the ISLM model.

Tissue-specific tagging of endogenous loci in Drosophila melanogaster

Directory of Open Access Journals (Sweden)

Kate Koles

2016-01-01

Full Text Available Fluorescent protein tags have revolutionized cell and developmental biology, and in combination with binary expression systems they enable diverse tissue-specific studies of protein function. However these binary expression systems often do not recapitulate endogenous protein expression levels, localization, binding partners and/or developmental windows of gene expression. To address these limitations, we have developed a method called T-STEP (tissue-specific tagging of endogenous proteins that allows endogenous loci to be tagged in a tissue specific manner. T-STEP uses a combination of efficient CRISPR/Cas9-enhanced gene targeting and tissue-specific recombinase-mediated tag swapping to temporally and spatially label endogenous proteins. We have employed this method to GFP tag OCRL (a phosphoinositide-5-phosphatase in the endocytic pathway and Vps35 (a Parkinson's disease-implicated component of the endosomal retromer complex in diverse Drosophila tissues including neurons, glia, muscles and hemocytes. Selective tagging of endogenous proteins allows, for the first time, cell type-specific live imaging and proteomics in complex tissues.

Endogenous fields enhanced stochastic resonance in a randomly coupled neuronal network

International Nuclear Information System (INIS)

Deng, Bin; Wang, Lin; Wang, Jiang; Wei, Xi-le; Yu, Hai-tao

2014-01-01

Highlights: • We study effects of endogenous fields on stochastic resonance in a neural network. • Stochastic resonance can be notably enhanced by endogenous field feedback. • Endogenous field feedback delay plays a vital role in stochastic resonance. • The parameters of low-passed filter play a subtle role in SR. - Abstract: Endogenous field, evoked by structured neuronal network activity in vivo, is correlated with many vital neuronal processes. In this paper, the effects of endogenous fields on stochastic resonance (SR) in a randomly connected neuronal network are investigated. The network consists of excitatory and inhibitory neurons and the axonal conduction delays between neurons are also considered. Numerical results elucidate that endogenous field feedback results in more rhythmic macroscope activation of the network for proper time delay and feedback coefficient. The response of the network to the weak periodic stimulation can be notably enhanced by endogenous field feedback. Moreover, the endogenous field feedback delay plays a vital role in SR. We reveal that appropriately tuned delays of the feedback can either induce the enhancement of SR, appearing at every integer multiple of the weak input signal’s oscillation period, or the depression of SR, appearing at every integer multiple of half the weak input signal’s oscillation period for the same feedback coefficient. Interestingly, the parameters of low-passed filter which is used in obtaining the endogenous field feedback signal play a subtle role in SR

Endogenous Generalized Weights under DEA Control

DEFF Research Database (Denmark)

Agrell, Per J.; Bogetoft, Peter

Non-parametric efficiency analysis, such as Data Envelopment Analysis (DEA) relies so far on endogenous local or exogenous general weights, based on revealed preferences or market prices. However, as DEA is gaining popularity in regulation and normative budgeting, the strategic interest...... of the evaluated industry calls for attention. We offer endogenous general prices based on a reformulation of DEA where the units collectively propose the set of weights that maximize their efficiency. Thus, the sector-wide efficiency is then a result of compromising the scores of more specialized smaller units...

Endogenous Molecular-Cellular Network Cancer Theory: A Systems Biology Approach.

Science.gov (United States)

Wang, Gaowei; Yuan, Ruoshi; Zhu, Xiaomei; Ao, Ping

2018-01-01

In light of ever apparent limitation of the current dominant cancer mutation theory, a quantitative hypothesis for cancer genesis and progression, endogenous molecular-cellular network hypothesis has been proposed from the systems biology perspective, now for more than 10 years. It was intended to include both the genetic and epigenetic causes to understand cancer. Its development enters the stage of meaningful interaction with experimental and clinical data and the limitation of the traditional cancer mutation theory becomes more evident. Under this endogenous network hypothesis, we established a core working network of hepatocellular carcinoma (HCC) according to the hypothesis and quantified the working network by a nonlinear dynamical system. We showed that the two stable states of the working network reproduce the main known features of normal liver and HCC at both the modular and molecular levels. Using endogenous network hypothesis and validated working network, we explored genetic mutation pattern in cancer and potential strategies to cure or relieve HCC from a totally new perspective. Patterns of genetic mutations have been traditionally analyzed by posteriori statistical association approaches in light of traditional cancer mutation theory. One may wonder the possibility of a priori determination of any mutation regularity. Here, we found that based on the endogenous network theory the features of genetic mutations in cancers may be predicted without any prior knowledge of mutation propensities. Normal hepatocyte and cancerous hepatocyte stable states, specified by distinct patterns of expressions or activities of proteins in the network, provide means to directly identify a set of most probable genetic mutations and their effects in HCC. As the key proteins and main interactions in the network are conserved through cell types in an organism, similar mutational features may also be found in other cancers. This analysis yielded straightforward and testable

Integration of Higher Education and Endogenous Development in Staff, Students and Curricula Development Processes

Directory of Open Access Journals (Sweden)

A Mwadiwa

2013-01-01

Full Text Available Higher education in most developing countries, particularly on the African continent, suffers a major contradiction, where even though the populations in nearly all African countries are of mixed cultural backgrounds, the university curriculum content encompasses, predominantly, the modern western view. Accordingly efforts and experiences for staff, student and curriculum development incorporating research, teaching and learning capacities focus, primarily, on modern concepts, approaches and methodologies. Thus most development initiatives are consequently looking to modern western view to motivate individuals who have come to associate modern western schooling and school-type programmes with success and the non-modern western world views with failure (Rustemeyer 2011:15. Arguably, modern western view pervades nearly every aspect of daily lives of traditional societies dwelling in rural communities whilst being increasingly influenced by inevitable factors of universal marketplace economically. This article challenges the University of Technology to become more passionately initiative in supporting the essence of ‘endogenous development (ED meaning development originating from within through encouraging and promoting networking with rural Community-based Traditional Institutions. The international Comparing and Supporting Endogenous Development (COMPAS Network describes endogenous development as an empowering process of the community, in which cultural awakening, creation of unity and participatory action are essential elements (COMPAS 2006:9. The significant aspect of the endogenous development approach is the willingness of development experts to implant their work and effort in the worldviews of the Traditional Institutions even though the professionals may not fully understand or agree with the worldviews of the respective Traditional Institutions.

Invasive fungal infections in endogenous Cushing's syndrome

Science.gov (United States)

Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

2010-01-01

Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage.

Science.gov (United States)

Yu, Rui; Lai, Yongquan; Hartwell, Hadley J; Moeller, Benjamin C; Doyle-Eisele, Melanie; Kracko, Dean; Bodnar, Wanda M; Starr, Thomas B; Swenberg, James A

2015-07-01

Formaldehyde is not only a widely used chemical with well-known carcinogenicity but is also a normal metabolite of living cells. It thus poses unique challenges for understanding risks associated with exposure. N(2-)hydroxymethyl-dG (N(2)-HOMe-dG) is the main formaldehyde-induced DNA mono-adduct, which together with DNA-protein crosslinks (DPCs) and toxicity-induced cell proliferation, play important roles in a mutagenic mode of action for cancer. In this study, N(2)-HOMe-dG was shown to be an excellent biomarker for direct adduction of formaldehyde to DNA and the hydrolysis of DPCs. The use of inhaled [(13)CD2]-formaldehyde exposures of rats and primates coupled with ultrasensitive nano ultra performance liquid chromatography-tandem mass spectrometry permitted accurate determinations of endogenous and exogenous formaldehyde DNA damage. The results show that inhaled formaldehyde only reached rat and monkey noses, but not tissues distant to the site of initial contact. The amounts of exogenous adducts were remarkably lower than those of endogenous adducts in exposed nasal epithelium. Moreover, exogenous adducts accumulated in rat nasal epithelium over the 28-days exposure to reach steady-state concentrations, followed by elimination with a half-life (t1/2) of 7.1 days. Additionally, we examined artifact formation during DNA preparation to ensure the accuracy of nonlabeled N(2)-HOMe-dG measurements. These novel findings provide critical new data for understanding major issues identified by the National Research Council Review of the 2010 Environmental Protection Agency's Draft Integrated Risk Information System Formaldehyde Risk Assessment. They support a data-driven need for reflection on whether risks have been overestimated for inhaled formaldehyde, whereas underappreciating endogenous formaldehyde as the primary source of exposure that results in bone marrow toxicity and leukemia in susceptible humans and rodents deficient in DNA repair. © The Author 2015

MALDI Mass Spectrometry Imaging for Visualizing In Situ Metabolism of Endogenous Metabolites and Dietary Phytochemicals

Science.gov (United States)

Fujimura, Yoshinori; Miura, Daisuke

2014-01-01

Understanding the spatial distribution of bioactive small molecules is indispensable for elucidating their biological or pharmaceutical roles. Mass spectrometry imaging (MSI) enables determination of the distribution of ionizable molecules present in tissue sections of whole-body or single heterogeneous organ samples by direct ionization and detection. This emerging technique is now widely used for in situ label-free molecular imaging of endogenous or exogenous small molecules. MSI allows the simultaneous visualization of many types of molecules including a parent molecule and its metabolites. Thus, MSI has received much attention as a potential tool for pathological analysis, understanding pharmaceutical mechanisms, and biomarker discovery. On the other hand, several issues regarding the technical limitations of MSI are as of yet still unresolved. In this review, we describe the capabilities of the latest matrix-assisted laser desorption/ionization (MALDI)-MSI technology for visualizing in situ metabolism of endogenous metabolites or dietary phytochemicals (food factors), and also discuss the technical problems and new challenges, including MALDI matrix selection and metabolite identification, that need to be addressed for effective and widespread application of MSI in the diverse fields of biological, biomedical, and nutraceutical (food functionality) research. PMID:24957029

[Research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration].

Science.gov (United States)

Liang, Hang; Deng, Xiangyu; Shao, Zengwu

2017-10-01

To summarize the research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration and deduce the therapeutic potential of endogenous repair for intervertebral disc degeneration. The original articles about intervertebral disc endogenous stem cells for intervertebral disc regeneration were extensively reviewed; the reparative potential in vivo and the extraction and identification in vitro of intervertebral disc endogenous stem cells were analyzed; the prospect of endogenous stem cells for intervertebral disc regeneration was predicted. Stem cell niche present in the intervertebral discs, from which stem cells migrate to injured tissues and contribute to tissues regeneration under certain specific microenvironment. Moreover, the migration of stem cells is regulated by chemokines system. Tissue specific progenitor cells have been identified and successfully extracted and isolated. The findings provide the basis for biological therapy of intervertebral disc endogenous stem cells. Intervertebral disc endogenous stem cells play a crucial role in intervertebral disc regeneration. Therapeutic strategy of intervertebral disc endogenous stem cells is proven to be a promising biological approach for intervertebral disc regeneration.

Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34.

Directory of Open Access Journals (Sweden)

Yongxin Ren

Full Text Available Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH.Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/- mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/- mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/- mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/- mice compared to vehicle-treated wild-type and Pth(-/- mice.Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.

Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34).

Science.gov (United States)

Ren, Yongxin; Liu, Bo; Feng, Yuxu; Shu, Lei; Cao, Xiaojian; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

2011-01-01

Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH. Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/-)) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/-) mice compared to vehicle-treated wild-type and Pth(-/-) mice. Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.

Endogenous viral elements in animal genomes.

Directory of Open Access Journals (Sweden)

Aris Katzourakis

2010-11-01

Full Text Available Integration into the nuclear genome of germ line cells can lead to vertical inheritance of retroviral genes as host alleles. For other viruses, germ line integration has only rarely been documented. Nonetheless, we identified endogenous viral elements (EVEs derived from ten non-retroviral families by systematic in silico screening of animal genomes, including the first endogenous representatives of double-stranded RNA, reverse-transcribing DNA, and segmented RNA viruses, and the first endogenous DNA viruses in mammalian genomes. Phylogenetic and genomic analysis of EVEs across multiple host species revealed novel information about the origin and evolution of diverse virus groups. Furthermore, several of the elements identified here encode intact open reading frames or are expressed as mRNA. For one element in the primate lineage, we provide statistically robust evidence for exaptation. Our findings establish that genetic material derived from all known viral genome types and replication strategies can enter the animal germ line, greatly broadening the scope of paleovirological studies and indicating a more significant evolutionary role for gene flow from virus to animal genomes than has previously been recognized.

Exogenous and endogenous spatial attention effects on visuospatial working memory.

Science.gov (United States)

Botta, Fabiano; Santangelo, Valerio; Raffone, Antonino; Lupiáñez, Juan; Belardinelli, Marta Olivetti

2010-08-01

In this study, we investigate how exogenous and endogenous orienting of spatial attention affect visuospatial working memory (VSWM). Specifically, we focused on two attentional effects and their consequences on storage in VSWM, when exogenous (Experiment 1) or endogenous (Experiment 2) orienting cues were used. The first effect, known as the meridian effect, is given by a decrement in behavioural performance when spatial cues and targets are presented in locations separated by vertical and/or horizontal meridians. The second effect, known as the distance effect, is given by a decrement in the orienting effects as a function of the spatial distance between cues and targets. Our results revealed a dissociation between exogenous and endogenous orienting mechanisms in terms of both meridian and distance effects. We found that meridian crossing affects performance only when endogenous cues were used. Specifically, VSWM performance with endogenous cueing depended more on the number of meridian crossings than on distance between cue and target. By contrast, a U-shaped distance dependency was observed using exogenous cues. Our findings therefore suggest that exogenous and endogenous orienting mechanisms lead to different forms of attentional bias for storage in VSWM.

Sucessfull management of bilateral presumed Candida endogenous endophtalmitis following pancreatitis

Directory of Open Access Journals (Sweden)

Ricardo Evangelista Marrocos de Aragão

2016-06-01

Full Text Available ABSTRACT Endogenous endophthalmitis is a rare, and frequently devastating, ophthalmic disease. It occurs mostly in immunocompromised patients, or those with diabetes mellitus, cancer or intravenous drugs users. Candida infection is the most common cause of endogenous endophthalmitis. Ocular candidiasis develops within days to weeks of fungemia. The association of treatment for pancreatitis with endophthalmitis is unusual. Treatment with broad-spectrum antibiotics and total parenteral nutrition may explain endogenous endophthalmitis. We report the case of a patient with pancreatitis treated with broad-spectrum antibiotics and total parenteral nutrition who developed bilateral presumed Candida endogenous endophthalmitis that was successfully treated with vitrectomy and intravitreal amphotericin B.

Alpha Power Modulates Perception Independently of Endogenous Factors

Directory of Open Access Journals (Sweden)

Sasskia Brüers

2018-04-01

Full Text Available Oscillations are ubiquitous in the brain. Alpha oscillations in particular have been proposed to play an important role in sensory perception. Past studies have shown that the power of ongoing EEG oscillations in the alpha band is negatively correlated with visual outcome. Moreover, it also co-varies with other endogenous factors such as attention, vigilance, or alertness. In turn, these endogenous factors influence visual perception. Therefore, it remains unclear how much of the relation between alpha and perception is indirectly mediated by such endogenous factors, and how much reflects a direct causal influence of alpha rhythms on sensory neural processing. We propose to disentangle the direct from the indirect causal routes by introducing modulations of alpha power, independently of any fluctuations in endogenous factors. To this end, we use white-noise sequences to constrain the brain activity of 20 participants. The cross-correlation between the white-noise sequences and the concurrently recorded EEG reveals the impulse response function (IRF, a model of the systematic relationship between stimulation and brain response. These IRFs are then used to reconstruct rather than record the brain activity linked with new random sequences (by convolution. Interestingly, this reconstructed EEG only contains information about oscillations directly linked to the white-noise stimulation; fluctuations in attention and other endogenous factors may still modulate brain alpha rhythms during the task, but our reconstructed EEG is immune to these factors. We found that the detection of near-perceptual threshold targets embedded within these new white-noise sequences depended on the power of the ~10 Hz reconstructed EEG over parieto-occipital channels. Around the time of presentation, higher power led to poorer performance. Thus, fluctuations in alpha power, induced here by random luminance sequences, can directly influence perception: the relation between

Role of endogenous substances in enhancing radioresistance background

International Nuclear Information System (INIS)

Goncharenko, E.N.; Gorskaya, T.G.; Graevskaya, E.Eh.; Kozlova, M.A.

1979-01-01

Presumable sources of endogenous were studied amines in radiosensitive tissues under the effect of radioprotective agents were studied. The data obtained support the idea that mast cells of rats, having large deposits of biogenous amines, might be one of the reserves contributing to mobilization of endogeneous protective resources of the organism treated with radioprotective agents

An endogenous standard, radioisotopic ratio method in NAA

International Nuclear Information System (INIS)

Byrne, A.R.; Dermelj, M.

1997-01-01

A derivative form of NAA is proposed which is based on the use of an endogenous internal standard of already known concentration in the sample. If a comparator with a known ratio of the determinand and endogenous standard are co-irradiated with the sample, the determinand concentration is derived in terms of the endogenous standard concentration and the activity ratios of the two induced nuclides in the sample and comparator. As well as eliminating the sample mass and greatly reducing errors caused by pulse pile-up and geometrical differences, it was shown that in the radiochemical mode, if the endogenous standard is chosen so that the induced activity is radioisotopic with that from the determinand, the radiochemical yield is also eliminated and the risk non-achievement of isotopic exchange greatly reduced. The method is demonstrated with good results on reference materials for the determination of I, Mn and Ni. The advantages and disadvantages of this approach are discussed. It is suggested that it may be of application in quality control and in extending the range of certified elements in reference materials. (author)

Novel endogenous angiogenesis inhibitors and their therapeutic potential.

Science.gov (United States)

Rao, Nithya; Lee, Yu Fei; Ge, Ruowen

2015-10-01

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis. Endogenous angiogenesis inhibitors are proteins or protein fragments that are formed in the body and have the ability to limit angiogenesis. Many endogenous angiogenesis inhibitors have been discovered, and the list continues to grow. Endogenous protein/peptide inhibitors are relatively less toxic, better tolerated and have a lower risk of drug resistance, which makes them attractive as drug candidates. In this review, we highlight ten novel endogenous protein angiogenesis inhibitors discovered within the last five years, including ISM1, FKBPL, CHIP, ARHGAP18, MMRN2, SOCS3, TAp73, ZNF24, GPR56 and JWA. Although some of these proteins have been well characterized for other biological functions, we focus on their new and specific roles in angiogenesis inhibition and discuss their potential for therapeutic application.

Evolution of endogenous analgesia

NARCIS (Netherlands)

Niesters, Marieke

2014-01-01

Endogenous pain modulation is a complex phenomenon involved in the perception of pain. It consists of top-down inhibitory and facilitatory pathways that originate at higher sites within the central nervous system and converge at dorsal horn neurons in the spinal cord, to modulate incoming afferent

Demonstration of endogenous imipramine like material in rat brain

International Nuclear Information System (INIS)

Rehavi, M.; Ventura, I.; Sarne, Y.

1985-01-01

The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits [ 3 H] imipramine specific binding and mimics the inhibitory effect of imipramine on [ 3 H] serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits [ 3 H] imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum

Placebo analgesia: understanding the mechanisms

OpenAIRE

Medoff, Zev M; Colloca, Luana

2015-01-01

Expectations of pain relief drive placebo analgesia. Understanding how expectations of improvement trigger distinct biological systems to shape therapeutic analgesic outcomes has been the focus of recent pharmacologic and neuroimaging studies in the field of pain. Recent findings indicate that placebo effects can imitate the actions of real painkillers and promote the endogenous release of opioids and nonopioids in humans. Social support and observational learning also contribute to placebo a...

Horizontalists, verticalists, and structuralists: The theory of endogenous money reassessed

OpenAIRE

Palley, Thomas I.

2013-01-01

This paper uses the occasion of the twenty-fifth anniversary of Basil Moore’s book, Horizontalists and Verticalists, to reassess the theory of endogenous money. The paper distinguishes between horizontalists, verticalists, and structuralists. It argues Moore’s horizontalist representation of endogenous money was an over-simplification that discarded important enduring insights from monetary theory. The structuralist approach to endogenous money retains the basic insight that the money supply ...

ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

Science.gov (United States)

Taylor, Bradley K; Corder, Gregory

2015-01-01

Endogenous activation of μ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) that is masked by spinal MOR signaling for months, even after complete recovery from injury and re-establishment of normal pain thresholds. Disruption with MOR inverse agonists reinstates pain and precipitates cellular, somatic and aversive signs of physical withdrawal; this phenomenon requires N-methyl-D-aspartate receptor-mediated activation of calcium-sensitive adenylyl cyclase type 1 (AC1). In this review, we present a new conceptual model of the transition from acute to chronic pain, based on the delicate balance between LS and endogenous analgesia that develops after painful tissue injury. First, injury activates pain pathways. Second, the spinal cord establishes MOR constitutive activity (MORCA) as it attempts to control pain. Third, over time, the body becomes dependent on MORCA, which paradoxically sensitizes pain pathways. Stress or injury escalates opposing inhibitory and excitatory influences on nociceptive processing as a pathological consequence of increased endogenous opioid tone. Pain begets MORCA begets pain vulnerability in a vicious cycle. The final result is a silent insidious state characterized by the escalation of two opposing excitatory and inhibitory influences on pain transmission: LS mediated by AC1 (which maintains accelerator), and pain inhibition mediated by MORCA (which maintains the brake). This raises the prospect that opposing homeostatic interactions between MORCA analgesia and latent NMDAR–AC1-mediated pain sensitization create a lasting vulnerability to develop chronic pain. Thus, chronic pain syndromes may result from a failure in constitutive signaling of spinal MORs and a loss of endogenous analgesic control. An overarching long-term therapeutic goal of future research is to alleviate chronic pain by either: a) facilitating endogenous opioid

A taxonomy of endogenous and exogenous uncertainty in high-risk, high-impact contexts.

Science.gov (United States)

Alison, Laurence; Power, Nicola; van den Heuvel, Claudia; Waring, Sara

2015-07-01

By reference to a live hostage negotiation exercise, this study presents a taxonomy of uncertainty that can be usefully applied to assist in the categorization and application of findings from decision-making research conducted in naturalistic (specifically critical incident) settings. Uncertainty was measured via observational methods (during the exercise and by reference to video footage), decision logs, and postincident simulated recall interviews with trainee police officers. Transcripts were coded and analyzed thematically. Uncertainty was dichotomized as deriving from either endogenous sources (about the problem situation itself) or exogenous sources (about the operating system that is dealing with the incident). Overall, exogenous uncertainty (75%) was more prevalent than endogenous uncertainty (25%), specifically during discussions on plan formulation and execution. It was also qualitatively associated with poor role understanding and trust. Endogenous uncertainty was more prevalent during discussions on situation assessment and plan formulation. The taxonomy provides a useful way for organizational researchers to categorize uncertainty during the naturalistic observations of workplace interactions and decision making. It reduces the complexity associated with observational research to allow organizational psychologists to better tailor their recommendations for reducing uncertainty. Dealing with endogenous uncertainties would entail targeting decision making specific to the problem incident (e.g., introduce training or policy to reduce redundant fixation on rote-repetitive superordinate goals and focus on more short-term actionable goals during situation assessments). Dealing with exogenous uncertainties would entail improving decision making relating to management and team processes across critical incidents (e.g., training to clarify distributed roles in critical incident teams to aid plan formulation and execution). Organizational researchers interested

Exogenic and endogenic Europa minerals

Science.gov (United States)

Maynard-Casely, H. E.; Brand, H. E. A.; Wilson, S. A.

2016-12-01

The Galileo Near Infrared Mapping Spectrometer (NIMS) identified a significant `non-ice' component upon the surface of Jupiter's moon Europa. Current explanations invoke both endogenic and exogenic origins for this material. It has long been suggested that magnesium and sodium sulfate minerals could have leached from the rock below a putative ocean (endogenic) 1 and that sulfuric acid hydrate minerals could have been radiologically produced from ionised sulfur originally from Io's volcanoes (exogenic) 2. However, a more recent theory proposes that the `non-ice' component could be radiation damaged NaCl leached from Europa's speculative ocean 3. What if the minerals are actually from combination of both endogenic and exogenic sources? To investigate this possibility we have focused on discovering new minerals that might form in the combination of the latter two cases, that is a mixture of leached sulfates hydrates with radiologically produced sulfuric acid. To this end we have explored a number of solutions in the MgSO4-H2SO4-H2O and Na2SO4-H2SO4-H2O systems, between 80 and 280 K with synchrotron x-ray powder diffraction. We report a number of new materials formed in this these ternary systems. This suggests that it should be considered that the `non-ice' component of the Europa's surface could be a material derived from endogenic and exogenic components. 1 Kargel, J. S. Brine volcanism and the interior structures of asteroids and icy satellites. Icarus 94, 368-390 (1991). 2 Carlson, R. W., Anderson, M. S., Mehlman, R. & Johnson, R. E. Distribution of hydrate on Europa: Further evidence for sulfuric acid hydrate. Icarus 177, 461-471, doi:10.1016/j.icarus.2005.03.026 (2005). 3 Hand, K. P. & Carlson, R. W. Europa's surface color suggests an ocean rich with sodium chloride. Geophysical Research Letters, 2015GL063559, doi:10.1002/2015gl063559 (2015).

Endogenous Business Cycle Dynamics within Metzlers Inventory Model: Adding an Inventory Floor.

Science.gov (United States)

Sushko, Irina; Wegener, Michael; Westerhoff, Frank; Zaklan, Georg

2009-04-01

Metzlers inventory model may produce dampened fluctuations in economic activity, thus contributing to our understanding of business cycle dynamics. For some parameter combinations, however, the model generates oscillations with increasing amplitude, implying that the inventory stock of firms eventually turns negative. Taking this observation into account, we reformulate Metzlers model by simply putting a floor to the inventory level. Within the new piecewise linear model, endogenous business cycle dynamics may now be triggered via a center bifurcation, i.e. for certain parameter combinations production changes are (quasi-)periodic.

Unemployment and endogenous growth

NARCIS (Netherlands)

van Schaik, A.B.T.M.; de Groot, H.L.F.

1995-01-01

In this paper we develop a two-sector endogenous growth model with a dual labour market, based on efficiency wages. Growth is driven by intentional R&D performed in the high-tech and high-wage sector. It is examined how a change in rivalry among firms affects simultaneously growth and unemployment.

Endogenous scheduling preferences and congestion

DEFF Research Database (Denmark)

Fosgerau, Mogens; Small, Kenneth

2017-01-01

We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely and is i......We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely...... and is indistinguishable from that of a generalized version of the classical Vickrey bottleneck model, based on exogenous trip-timing preferences, but optimal policies differ: the Vickrey model will misstate the benefits of a capacity increase, it will underpredict the benefits of congestion pricing, and pricing may make...

Some observations about the endogenous money theory

OpenAIRE

Bertocco Giancarlo

2006-01-01

The endogenous money theory constitutes the core element of the post-keynesian monetary theory. The first formulation of this theory can be found in the works of Kaldor published in the 1970s. Taking these studies as a starting point, the post-keynesians elaborated two versions of the endogenous money theory which differ in their assumptions about the behaviour of the monetary authorities and the banking system, and hence offer different conclusions about the slope of the money supply curve. ...

CITROBACTER ENDOGENOUS ENDOPHTHALMITIS: A CASE REPORT AND REVIEW OF THE LITERATURE.

Science.gov (United States)

Wong, Daniel H T; Liu, Candice C H; Tong, Justin M K; Luk, Wei-Kwang; Li, Kenneth K W

2017-11-16

We present a case of endogenous endophthalmitis because of an unusual bacterium, Citrobacter koseri. A 57-year-old woman without previous history of eye surgery or trauma presented with diabetic ketoacidosis and a painful right eye with the reduction of vision. C. koseri was identified in blood culture; thus, a diagnosis of right eye endogenous endophthalmitis was made. Intravenous and intravitreal antibiotics were both started, and vitreous culture further confirmed C. koseri as the causative organism. Computed tomography of the abdomen and pelvis revealed a right C-shaped perinephric abscess, which was drained under ultrasound guidance. Because of rapid progression to corneal melting, evisceration was performed. Cases of endogenous endophthalmitis caused by Citrobacter are very limited, and a review of all published cases in the English literature and the present case revealed that endogenous Citrobacter endophthalmitis arose almost entirely from Citrobacter renal infection. Early recognition and drainage of renal abscess may lower the chance of uncontrolled infection and endogenous spread to the eyes. Despite prompt and intensive treatment, the clinical outcome of Citrobacter endogenous endophthalmitis seems to be poor.

Strategies for the photo-control of endogenous protein activity.

Science.gov (United States)

Brechun, Katherine E; Arndt, Katja M; Woolley, G Andrew

2017-08-01

Photo-controlled or 'optogenetic' effectors interfacing with endogenous protein machinery allow the roles of endogenous proteins to be probed. There are two main approaches being used to develop optogenetic effectors: (i) caging strategies using photo-controlled conformational changes, and (ii) protein relocalization strategies using photo-controlled protein-protein interactions. Numerous specific examples of these approaches have been reported and efforts to develop general methods for photo-control of endogenous proteins are a current focus. The development of improved screening and selection methods for photo-switchable proteins would advance the field. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endogenous lung regeneration: potential and limitations.

Science.gov (United States)

Rock, Jason; Königshoff, Melanie

2012-12-15

The exploration of the endogenous regenerative potential of the diseased adult human lung represents an innovative and exciting task. In this pulmonary perspective, we discuss three major components essential for endogenous lung repair and regeneration: epithelial progenitor populations, developmental signaling pathways that regulate their reparative and regenerative potential, and the surrounding extracellular matrix in the human diseased lung. Over the past years, several distinct epithelial progenitor populations have been discovered within the lung, all of which most likely respond to different injuries by varying degrees. It has become evident that several progenitor populations are mutually involved in maintenance and repair, which is highly regulated by developmental pathways, such as Wnt or Notch signaling. Third, endogenous progenitor cells and developmental signaling pathways act in close spatiotemporal synergy with the extracellular matrix. These three components define and refine the highly dynamic microenvironment of the lung, which is altered in a disease-specific fashion in several chronic lung diseases. The search for the right mixture to induce efficient and controlled repair and regeneration of the diseased lung is ongoing and will open completely novel avenues for the treatment of patients with chronic lung disease.

Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

Science.gov (United States)

Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

2014-01-01

Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

Staphylococcal endogenous endophthalmitis in association with pyogenic vertebral osteomyelitis.

Science.gov (United States)

Steeples, L R; Jones, N P

2016-01-01

PURPOSE To describe pyogenic vertebral osteomyelitis as a rare infection associated with endogenous endophthalmitis.METHODS A retrospective review of three patients with endogenous endophthalmitis and sepsis due to underlying Staphylococcal vertebral osteomyelitis presenting during a 21-month time period. The ophthalmic and systemic features and management and outcomes are presented.RESULTS One patient developed unilateral endophthalmitis with cervical spine osteomyelitis, Staphylococcus aureus being isolated from blood cultures. The second presented with bilateral endophthalmitis with disseminated Methicillin-resistant S. aureus (MRSA) infection, with thoracic and lumbar discitis and para-spinal abscesses. MRSA was cultured from vitreous, blood, and synovial fluid. Both patients received prolonged courses of intravenous antibiotics. Intravitreal antibiotic therapy was used in the second patient. Excellent visual and systemic outcomes were achieved in both cases with no ocular complications. The third patient developed lumbar osteomyelitis following spinal surgery and presented with disseminated S. aureus sepsis including unilateral endogenous endophthalmitis. Despite systemic antibiotics and intensive care the patient died.CONCLUSIONS Endogenous endophthalmitis should be suspected in septic patients developing eye symptoms. Endogenous endophthalmitis with staphylococcal bone infection is a rare but serious condition. Osteomyelitis should be considered as an infective source in any such patient reporting bone pain or reduced spinal mobility. Prompt investigation and treatment can achieve favourable visual and systemic outcomes.

The effect of triiodothyronine on maturation and differentiation of oligodendrocyte progenitor cells during remyelination following induced demyelination in male albino rat.

Science.gov (United States)

El-Tahry, H; Marei, H; Shams, A; El-Shahat, M; Abdelaziz, H; Abd El-Kader, M

2016-06-01

Demyelination was induced by two weeks cuprizone treatment. Rats of +ve control and triiodothyronine (T3) then received three subcutaneous injections of either saline or T3 day after day and sacrificed at the end of the third and fifth weeks. Animals in -ve control group received only standard rodent chow. After one week of cuprizone withdrawal the corpus callosum in +ve control and T3 treated rats was still demyelinated as revealed by MBP immunohistochemistry. The assay of PLP gene showed significant increase of T3 treated group compared to both the -ve control and +ve control groups. After three weeks, significant improvement in myelination was detected in T3-treated group compared to +ve control as detected by both MBP immunohistochemistry and electron microscopy. After one week of cuprizone withdrawal, PDGFRα positive cells and gene expression showed significant increase in +ve control and T3-treated groups as compared to -ve control with insignificant difference in between the former two groups. After three weeks of cuprizone withdrawal, PDGFRα positive cells in T3-treated and +ve control groups decreased to the control levels. These results suggest that T3 was effective in improving remyelination when administered during acute phase and might direct progenitor lineage toward oligodendrocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

The epigenetic alterations of endogenous retroelements in aging.

Science.gov (United States)

Cardelli, Maurizio

2018-02-16

Endogenous retroelements, transposons that mobilize through RNA intermediates, include some of the most abundant repetitive sequences of the human genome, such as Alu and LINE-1 sequences, and human endogenous retroviruses. Recent discoveries demonstrate that these mobile genetic elements not only act as intragenomic parasites, but also exert regulatory roles in living cells. The risk of genomic instability represented by endogenous retroelements is normally counteracted by a series of epigenetic control mechanisms which include, among the most important, CpG DNA methylation. Indeed, most of the genomic CpG sites subjected to DNA methylation in the nuclear DNA are carried by these repetitive elements. As other parts of the genome, endogenous retroelements and other transposable elements are subjected to deep epigenetic alterations during aging, repeatedly observed in the context of organismal and cellular senescence, in human and other species. This review summarizes the current status of knowledge about the epigenetic alterations occurring in this large, non-genic portion of the genome in aging and age-related conditions, with a focus on the causes and the possible functional consequences of these alterations. Copyright © 2018 Elsevier B.V. All rights reserved.

Expression and function of endogenous retroviruses in the placenta.

Science.gov (United States)

Denner, Joachim

2016-01-01

Although the expression of endogenous retroviruses in the placenta of numerous species was observed a long time ago, their physiological function during gestation was demonstrated only very recently. Expression of retroviral envelope proteins, also called syncytins, in the placenta allows generation of the multinuclear syncytiotrophoblast as an outer cellular layer of the placenta by fusion of the trophoblast cells. This fusion process is crucial for the development of the placenta and for successful pregnancy. It is still unclear whether the immunosuppressive properties of the transmembrane envelope protein of the endogenous retroviruses expressed in the placenta contribute to immunosuppression to prevent the rejection of the semiallotransplant embryo. The presence of placenta cells expressing retroviral envelope proteins surrounded by immune cells deep in the maternal tissue supports an immunosuppressive function. It is important to emphasize that during evolution different species utilized ('enslaved') different endogenous retroviruses and that two or more endogenous retroviruses are involved in placentogenesis in each species. © 2016 APMIS. Published by John Wiley & Sons Ltd.

School system evaluation by value added analysis under endogeneity.

Science.gov (United States)

Manzi, Jorge; San Martín, Ernesto; Van Bellegem, Sébastien

2014-01-01

Value added is a common tool in educational research on effectiveness. It is often modeled as a (prediction of a) random effect in a specific hierarchical linear model. This paper shows that this modeling strategy is not valid when endogeneity is present. Endogeneity stems, for instance, from a correlation between the random effect in the hierarchical model and some of its covariates. This paper shows that this phenomenon is far from exceptional and can even be a generic problem when the covariates contain the prior score attainments, a typical situation in value added modeling. Starting from a general, model-free definition of value added, the paper derives an explicit expression of the value added in an endogeneous hierarchical linear Gaussian model. Inference on value added is proposed using an instrumental variable approach. The impact of endogeneity on the value added and the estimated value added is calculated accurately. This is also illustrated on a large data set of individual scores of about 200,000 students in Chile.

Innate heart regeneration: endogenous cellular sources and exogenous therapeutic amplification.

Science.gov (United States)

Malliaras, Konstantinos; Vakrou, Styliani; Kapelios, Chris J; Nanas, John N

2016-11-01

The -once viewed as heretical- concept of the adult mammalian heart as a dynamic organ capable of endogenous regeneration has recently gained traction. However, estimated rates of myocyte turnover vary wildly and the underlying mechanisms of cardiac plasticity remain controversial. It is still unclear whether the adult mammalian heart gives birth to new myocytes through proliferation of resident myocytes, through cardiomyogenic differentiation of endogenous progenitors or through both mechanisms. In this review, the authors discuss the cellular origins of postnatal mammalian cardiomyogenesis and touch upon therapeutic strategies that could potentially amplify innate cardiac regeneration. The adult mammalian heart harbors a limited but detectable capacity for spontaneous endogenous regeneration. During normal aging, proliferation of pre-existing cardiomyocytes is the dominant mechanism for generation of new cardiomyocytes. Following myocardial injury, myocyte proliferation increases modestly, but differentiation of endogenous progenitor cells appears to also contribute to cardiomyogenesis (although agreement on the latter point is not universal). Since cardiomyocyte deficiency underlies almost all types of heart disease, development of therapeutic strategies that amplify endogenous regeneration to a clinically-meaningful degree is of utmost importance.

In situ tissue regeneration: chemoattractants for endogenous stem cell recruitment.

Science.gov (United States)

Vanden Berg-Foels, Wendy S

2014-02-01

Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration.

Social Laughter Triggers Endogenous Opioid Release in Humans.

Science.gov (United States)

Manninen, Sandra; Tuominen, Lauri; Dunbar, Robin I; Karjalainen, Tomi; Hirvonen, Jussi; Arponen, Eveliina; Hari, Riitta; Jääskeläinen, Iiro P; Sams, Mikko; Nummenmaa, Lauri

2017-06-21

The size of human social networks significantly exceeds the network that can be maintained by social grooming or touching in other primates. It has been proposed that endogenous opioid release after social laughter would provide a neurochemical pathway supporting long-term relationships in humans (Dunbar, 2012), yet this hypothesis currently lacks direct neurophysiological support. We used PET and the μ-opioid-receptor (MOR)-specific ligand [ 11 C]carfentanil to quantify laughter-induced endogenous opioid release in 12 healthy males. Before the social laughter scan, the subjects watched laughter-inducing comedy clips with their close friends for 30 min. Before the baseline scan, subjects spent 30 min alone in the testing room. Social laughter increased pleasurable sensations and triggered endogenous opioid release in thalamus, caudate nucleus, and anterior insula. In addition, baseline MOR availability in the cingulate and orbitofrontal cortices was associated with the rate of social laughter. In a behavioral control experiment, pain threshold-a proxy of endogenous opioidergic activation-was elevated significantly more in both male and female volunteers after watching laughter-inducing comedy versus non-laughter-inducing drama in groups. Modulation of the opioidergic activity by social laughter may be an important neurochemical pathway that supports the formation, reinforcement, and maintenance of human social bonds. SIGNIFICANCE STATEMENT Social contacts are vital to humans. The size of human social networks significantly exceeds the network that can be maintained by social grooming in other primates. Here, we used PET to show that endogenous opioid release after social laughter may provide a neurochemical mechanism supporting long-term relationships in humans. Participants were scanned twice: after a 30 min social laughter session and after spending 30 min alone in the testing room (baseline). Endogenous opioid release was stronger after laughter versus the

Endogenous induced technical change and the costs of Kyoto

International Nuclear Information System (INIS)

Buonanno, Paolo; Carraro, Carlo; Galeotti, M.

2001-09-01

Many predictions and conclusions in the climate change literature have been made and drawn on the basis of theoretical analyses and quantitative models that are either static or that allow for simple forms of changes in technology, often along exogenously given time paths. It is therefore not clear a priori whether those conclusions and policy recipes still hold in the more realistic case of endogenously evolving technologies. In this paper, a quantitative tool with the features of an endogenous growth model is presented, which also accounts for the possibility that technical change can be induced by environmental policy measures. Both the output production technology and the emission-output ratio depend upon the stock of knowledge, which accumulates through R and D activities. R and D is thus an additional policy variable that comes into play along with pollution abatement and capital investment. Two versions of this climate model are studied, one with endogenous technical change but exogenous environmental technical change (i.e. no induced technical change) and the other with both endogenous and induced technical change. Hence, in both models technical change evolves endogenously as far as the production technology is concerned, but endogenous environmental (or induced) technical change is only accounted for in the second version. Finally, a third version of the model also captures technological spillover effects. As an application, the three versions of the model are simulated allowing for trade of pollution permits as specified in the Kyoto Protocol and assessing the implications in terms of cost efficiency, economic growth and R and D efforts of the three different specifications of technical change

A panel Granger-causality test of endogenous vs. exogenous growth

OpenAIRE

Jochen Hartwig

2009-01-01

The paper proposes a new test of endogenous vs. exogenous growth theories based on the Granger-causality methodology and applies it to a panel of 20 OECD countries. The test yields divergent evidence with respect to physical and human capital. For physical capital, the test results favor Solow-type exogenous growth theory over AK-type endogenous growth models. On the other hand, the test results lend support to human capital oriented endogenous growth models - like the Uzawa-Lucas model - rat...

Alteration in the endogenous intestinal flora of swiss webster mice by experimental Angiostrongylus costaricensis infection

Directory of Open Access Journals (Sweden)

Vandack Nobre

2004-11-01

Full Text Available The association between worm infections and bacterial diseases has only recently been emphasized. This study examined the effect of experimental Angiostrongylus costaricensis infection on endogenous intestinal flora of Swiss Webster mice. Eight mice aging six weeks were selected for this experiment. Four were infected with A. costaricensis and the other four were used as controls. Twenty eight days after the worm infection, all mice in both groups were sacrificed and samples of the contents of the ileum and colon were obtained and cultured for aerobic and anaerobic bacteria. In the mice infected with A. costaricensis there was a significant increase in the number of bacteria of the endogenous intestinal flora, accompanied by a decrease in the number of Peptostreptococcus spp. This alteration in the intestinal flora of mice infected by the nematode may help to understand some bacterial infections described in humans.

Amplification and chromosomal dispersion of human endogenous retroviral sequences

International Nuclear Information System (INIS)

Steele, P.E.; Martin, M.A.; Rabson, A.B.; Bryan, T.; O'Brien, S.J.

1986-01-01

Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification and dispersion events may be linked

On the Endogeneity of the Mean-Variance Efficient Frontier.

Science.gov (United States)

Somerville, R. A.; O'Connell, Paul G. J.

2002-01-01

Explains that the endogeneity of the efficient frontier in the mean-variance model of portfolio selection is commonly obscured in portfolio selection literature and in widely used textbooks. Demonstrates endogeneity and discusses the impact of parameter changes on the mean-variance efficient frontier and on the beta coefficients of individual…

Biopsychosocial Factors Associated with Prurigo Nodularis in Endogenous Eczema.

Science.gov (United States)

Oh, Choon Chiat; Li, Huihua; Lee, Wellington; Tey, Hong Liang

2015-01-01

Prurigo nodularis is a dermatological manifestation secondary to chronic scratching or picking on focal areas of the skin. Its pathogenesis remains poorly understood, and limited data has indicated its association with psychological factors. To determine the biological, psychological and social factors associated with the occurrence of prurigo nodularis in patients with underlying endogenous eczema. A prospective case-control questionnaire -based study on patients with endogenous eczema, with and without prurigo nodules, was performed. The Impact of Skin Disease on Daily Life questionnaire was used to assess dimensions of physical functioning, including extent and severity of skin disease, itch, pain, fatigue and scratching, as well as dimensions of psychological and social functioning, including mood, illness cognition, disease-related impact, stigmatization and social support. Thirty-six cases and 47 controls were recruited. Patients with endogenous eczema and prurigo nodules indicated a higher itch score on the visual analog scale over the previous 4 weeks compared to those without prurigo nodules (p=0.0292). There were no significant differences between the 2 groups in the scores reflecting the other parameters of physical, psychological and social functioning. In patients with endogenous eczema, those with prurigo nodules experience a greater itch intensity compared to those without prurigo nodules. There were no other physical, psychological and social factors that were found to be associated with the occurrence of prurigo nodules in endogenous eczema.

Testing R&D-Based Endogenous Growth Models

DEFF Research Database (Denmark)

Kruse-Andersen, Peter Kjær

2017-01-01

R&D-based growth models are tested using US data for the period 1953-2014. A general growth model is developed which nests the model varieties of interest. The model implies a cointegrating relationship between multifactor productivity, research intensity, and employment. This relationship...... is estimated using cointegrated VAR models. The results provide evidence against the widely used fully endogenous variety and in favor of the semi-endogenous variety. Forecasts based on the empirical estimates suggest that the slowdown in US productivity growth will continue. Particularly, the annual long...

An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis

Science.gov (United States)

Quintana, Francisco J.; Murugaiyan, Gopal; Farez, Mauricio F.; Mitsdoerffer, Meike; Tukpah, Ann-Marcia; Burns, Evan J.; Weiner, Howard L.

2010-01-01

The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) participates in the differentiation of FoxP3+ Treg, Tr1 cells, and IL-17–producing T cells (Th17). Most of our understanding on the role of AHR on the FoxP3+ Treg compartment results from studies using the toxic synthetic chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin. Thus, the physiological relevance of AHR signaling on FoxP3+ Treg in vivo is unclear. We studied mice that carry a GFP reporter in the endogenous foxp3 locus and a mutated AHR protein with reduced affinity for its ligands, and found that AHR signaling participates in the differentiation of FoxP3+ Treg in vivo. Moreover, we found that treatment with the endogenous AHR ligand 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) given parenterally or orally induces FoxP3+ Treg that suppress experimental autoimmune encephalomyelitis. ITE acts not only on T cells, but also directly on dendritic cells to induce tolerogenic dendritic cells that support FoxP3+ Treg differentiation in a retinoic acid-dependent manner. Thus, our work demonstrates that the endogenous AHR ligand ITE promotes the induction of active immunologic tolerance by direct effects on dendritic and T cells, and identifies nontoxic endogenous AHR ligands as potential unique compounds for the treatment of autoimmune disorders. PMID:21068375

The theory of endogenous money and the LM schedule: prelude to a reconstruction of ISLM

OpenAIRE

PALLEY,THOMAS I.

2017-01-01

ABSTRACT Money is at the center of macroeconomics, which makes understanding the money supply central for macroeconomic theory. This paper presents the Post Keynesian theory of endogenous money supply and shows how it is fundamentally different from the conventional money supply theory. The conventional approach relies on the money multiplier and bank lending is invisible. Post Keynesian theory discards the money multiplier and focuses on bank lending which drives money creation. The paper em...

Endogenous change: on cooperation and water in ancient history

Science.gov (United States)

Pande, S.; Ertsen, M.

2013-04-01

We propose and test the theory of endogenous change based on historical reconstructions of two ancient civilizations, Indus and Hohokam, in two water scarce basins, the Indus basin in the Indian subcontinent and the Lower Colorado basin in Southwestern United States. The endogenous institutional change sees changes in institutions as a sequence of equilibria brought about by changes in "quasi-parameters" such as rainfall, population density, soil and land use induced water resource availability. In the historical reconstructions of ancient civilizations, institutions are proximated by the scale of cooperation be it in the form of the extent of trade, sophisticated irrigation network, a centrally planned state or a loosely held state with a common cultural identity. The "quasi-parameters" either change naturally or are changed by humans and the changes affect the stability of cooperative structures over time. However, human influenced changes in the quasi-parameters itself are conditioned on the scale of existing cooperative structures. We thus provide insights into the quantitative dimensions of water access by ancient populations and its co-evolution with the socioeconomic and sociopolitical organization of the human past. We however do not suggest that water manipulation was the single most significant factor in stimulating social development and complexity - clearly this has been shown as highly reductionist, even misleading. The paper cautiously contributes to proximate prediction of hydrological change by attempting to understand the complexity of coupled human-hydrological systems.

DMPD: Macrophage activation by endogenous danger signals. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18161744 Macrophage activation by endogenous danger signals. Zhang X, Mosser DM. J ...Pathol. 2008 Jan;214(2):161-78. (.png) (.svg) (.html) (.csml) Show Macrophage activation by endogenous dange...r signals. PubmedID 18161744 Title Macrophage activation by endogenous danger signals. Authors Zhang X, Moss

Spatial orienting around the fovea: exogenous and endogenous cueing effects.

Science.gov (United States)

Yang, Taoxi; Zhang, Jiyuan; Bao, Yan

2015-09-01

The effect of covert attention in perifoveal and peripheral locations has been studied extensively. However, it is less clear whether attention operates similarly in the foveal area itself. The present study aims to investigate whether the attentional orienting elicited by an exogenous or endogenous cue can operate within the foveal area and whether attentional orienting operates similarly between foveal and perifoveal regions. By manipulating exogenous orienting in Experiment 1 and endogenous orienting in Experiment 2, we observed both forms of cueing in the foveal area. Specifically, we observed a larger exogenous cue-induced inhibitory effect (i.e., inhibition of return effect) and a similar endogenous cue-elicited facilitatory effect for the perifoveal relative to the foveal targets. We conclude that exogenous and endogenous orienting subject to two independent attentional systems with distinct modulation patterns in the foveal area.

Avian endogenous provirus (ev-3) env gene sequencing: implication for pathogenic retrovirus origination.

Science.gov (United States)

Tikhonenko, A T; Lomovskaya, O L

1990-02-01

The avian endogenous env gene product blocks the surface receptor and, as a result, cells become immune to related exogenous retroviruses. On the other hand, the same sequence can be included in the pathogenic retrovirus genome, as shown by oligonucleotide mapping. However, since the complete env gene sequence was not known, the comparison of genomic nucleotide sequences was not possible. Therefore an avian endogenous provirus with an intact env gene was cloned from a chicken gene bank and the regions coding for the C terminus of the gp85 and gp37 proteins were sequenced. Comparison of this sequence with those of other retroviruses proved that one of the pathogenic viruses associated with osteopetrosis is a cross between avian endogenous virus and Rous sarcoma virus. Retroviruses and, especially, endogenous retroviruses are traditionally of the most developed models of viral carcinogenesis. Many endogenous retroviruses are implicated in neoplastic transformation of the cell. For instance, endogenous mouse mammary tumor virus of some inbred lines appears to be the only causative agent in these mammary cancers. Other even nonpathogenic murine endogenous retroviruses are involved in the origination of MCF-type recombinant acute leukosis viruses. Some endogenous retroviruses are implicated in the transduction or activation of cellular protooncogenes. Our interest in endogenous viruses is based on their ability to make cells resistant to exogenous retroviruses. Expression of their major envelope glycoprotein leads to cellular surface receptor blockage and imparts immunity to infection by the related leukemia retroviruses. This problem is quite elaborated for chicken endogenous virus RAV-O (7-9).(ABSTRACT TRUNCATED AT 250 WORDS)

Do Endogenous and Exogenous Action Control Compete for Perception?

Science.gov (United States)

Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

2012-01-01

Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the…

Endogenous Information, Risk Characterization, and the Predictability of Average Stock Returns

Directory of Open Access Journals (Sweden)

Pradosh Simlai

2012-09-01

Full Text Available In this paper we provide a new type of risk characterization of the predictability of two widely known abnormal patterns in average stock returns: momentum and reversal. The purpose is to illustrate the relative importance of common risk factors and endogenous information. Our results demonstrates that in the presence of zero-investment factors, spreads in average momentum and reversal returns correspond to spreads in the slopes of the endogenous information. The empirical findings support the view that various classes of firms react differently to volatility risk, and endogenous information harbor important sources of potential risk loadings. Taken together, our results suggest that returns are influenced by random endogenous information flow, which is asymmetric in nature, and can be used as a performance attribution factor. If one fails to incorporate the existing asymmetric endogenous information hidden in the historical behavior, any attempt to explore average stock return predictability will be subject to an unquantified specification bias.

Expression of endogenous proteins in maize hybrids in a multi-location field trial in India.

Science.gov (United States)

Gutha, Linga R; Purushottam, Divakar; Veeramachaneni, Aruna; Tigulla, Sarita; Kodappully, Vikas; Enjala, Chandana; Rajput, Hitendrasinh; Anderson, Jennifer; Hong, Bonnie; Schmidt, Jean; Bagga, Shveta

2018-05-17

Genetically modified (GM) crops undergo large scale multi-location field trials to characterize agronomics, composition, and the concentration of newly expressed protein(s) [herein referred to as transgenic protein(s)]. The concentration of transgenic proteins in different plant tissues and across the developmental stages of the plant is considered in the safety assessment of GM crops. Reference or housekeeping proteins are expected to maintain a relatively stable expression pattern in healthy plants given their role in cellular functions. Understanding the effects of genotype, growth stage and location on the concentration of endogenous housekeeping proteins may provide insight into the contribution these factors could have on transgenic protein concentrations in GM crops. The concentrations of three endogenous proteins (actin, elongation factor 1-alpha, and glyceraldehyde 3-phosphate dehydrogenase) were measured in several different maize hybrids grown across multiple field locations over 2 years. Leaf samples were collected from healthy plants at three developmental stages across the growing seasons, and protein concentrations were quantified by indirect enzyme-linked immunosorbent assay (ELISA) for each protein. In general, the concentrations of these three endogenous proteins were relatively consistent across hybrid backgrounds, when compared within one growth stage and location (2-26%CV), whereas the concentrations of proteins in the same hybrid and growth stage across different locations were more variable (12-64%CV). In general, the protein concentrations in 2013 and 2014 show similar trends in variability. Some degree of variability in protein concentrations should be expected for both transgenic and endogenous plant-expressed proteins. In the case of GM crops, the potential variation in protein concentrations due to location effects is captured in the current model of multi-location field testing.

Do endogenous and exogenous action control compete for perception?

Science.gov (United States)

Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

2012-04-01

Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the endogenous representation has to be deactivated first to give way to the exogenous system. Here we show that interference of endogenous and exogenous action control is not limited to motor-related aspects but also affects the perception of action-related stimuli. Participants associated two actions with contingent sensory effects in learning blocks. In subsequent test blocks, preparing one of these actions specifically impaired responding to the associated effect in an exogenous speeded detection task, yielding a blindness-like effect for arbitrary, learned action effects. In accordance with the theory of event coding, this finding suggests that action planning influences perception even in the absence of any physical similarities between action and to-be-perceived stimuli.

Endogenous opioid peptides as neurotransmitters in the rat hippocampus

International Nuclear Information System (INIS)

Neumaier, J.F.

1989-01-01

The role of endogenous opioid peptides as neurotransmitters in the rat hippocampus was investigated by using extracellular recording and radioligand binding techniques in the hippocampal slice preparation. Synaptic conductances from endogenously released opioid peptides have been difficult to detect. This problem was approach by designing a novel assay of opioid peptide release, in which release was detected by measuring binding competition between endogenous opioids and added radioligand. Membrane depolarization displaced [ 3 H]-diprenorphine binding in a transient, calcium-dependent, and peptidase-sensitive manner. Autoradiographic localization of the sites of [ 3 H]-diprenorphine binding displacement showed that significant opioid peptide release and receptor occupancy occurred in each major subregion of the hippocampal slices. This assay method can not be used to define optimal electrical stimulation conditions for releasing endogenous opioids. The binding displacement method was extended to the study of the sigma receptor. Depolarization of hippocampal slices was found to reduce the binding of the sigma-selective radioligand [ 3 H]-ditolylguanidine in a transient and calcium-dependent manner with no apparent direct effects on sigma receptor affinity

Stochastic Stability of Endogenous Growth: Theory and Applications

OpenAIRE

Boucekkine, Raouf; Pintus, Patrick; Zou, Benteng

2015-01-01

We examine the issue of stability of stochastic endogenous growth. First, stochastic stability concepts are introduced and applied to stochastic linear homogenous differen- tial equations to which several stochastic endogenous growth models reduce. Second, we apply the mathematical theory to two models, starting with the stochastic AK model. It’s shown that in this case exponential balanced paths, which characterize optimal trajectories in the absence of uncertainty, are not robust to uncerta...

Monopoly Insurance and Endogenous Information

DEFF Research Database (Denmark)

Lagerlöf, Johan N. M.; Schottmüller, Christoph

2018-01-01

We study a monopoly insurance model with endogenous information acquisi- tion. Through a continuous effort choice, consumers can determine the precision of a privately observed signal that is informative about their accident risk. The equilibrium effort is, depending on parameter values, either...

An endogenous Taylor condition in an endogenous growth monetary policy model

OpenAIRE

Le, Mai Vo; Gillman, Max; Minford, Patrick

2007-01-01

The paper derives a Taylor condition as part of the agent's equilibrium behavior in an endogenous growth monetary economy. It shows the assumptions necessary to make it almost identical to the original Taylor rule, and that it can interchangably take a money supply growth rate form. From the money supply form, simple policy experiments are conducted. A full central bank policy model is derived that includes the Taylor condition along with equations comparable to the standard aggregate-demand/...

Endogenous molecular network reveals two mechanisms of heterogeneity within gastric cancer

Science.gov (United States)

Li, Site; Zhu, Xiaomei; Liu, Bingya; Wang, Gaowei; Ao, Ping

2015-01-01

Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and research. Gastric cancer (GC) cells have generally been classified into two heterogeneous cellular phenotypes, the gastric and intestinal types, yet the mechanisms of maintaining two phenotypes and controlling phenotypic transition are largely unknown. A qualitative systematic framework, the endogenous molecular network hypothesis, has recently been proposed to understand cancer genesis and progression. Here, a minimal network corresponding to such framework was found for GC and was quantified via a stochastic nonlinear dynamical system. We then further extended the framework to address the important question of intratumor heterogeneity quantitatively. The working network characterized main known features of normal gastric epithelial and GC cell phenotypes. Our results demonstrated that four positive feedback loops in the network are critical for GC cell phenotypes. Moreover, two mechanisms that contribute to GC cell heterogeneity were identified: particular positive feedback loops are responsible for the maintenance of intestinal and gastric phenotypes; GC cell progression routes that were revealed by the dynamical behaviors of individual key components are heterogeneous. In this work, we constructed an endogenous molecular network of GC that can be expanded in the future and would broaden the known mechanisms of intratumor heterogeneity. PMID:25962957

Derivation of endogenous equivalent values to support risk assessment and risk management decisions for an endogenous carcinogen: Ethylene oxide.

Science.gov (United States)

Kirman, C R; Hays, S M

2017-12-01

An approach is presented for ethylene oxide (EO) to derive endogenous equivalent (EE) values, which are endogenous levels normally found within the body expressed in terms of exogenous exposures. EE values can be used to support risk assessment and risk management decisions for chemicals such as EO that have both endogenous and exogenous exposure pathways. EE values were derived using a meta-analysis of data from the published literature characterizing the distribution for an EO biomarker of exposure, hemoglobin N-(2-hydroxyethyl)-valine (HEV), in unexposed populations. These levels are compared to the those reported in exposed populations (smokers, workers). Correlation between the biomarker of exposure and external exposures of EO were applied to this distribution to determine corresponding EE values, which range from 0.13 to 6.9 ppb for EO in air. These values are orders of magnitude higher than risk-based concentration values derived for EO using default methods, and are provided as a pragmatic, data-driven alternative approach to managing the potential risks from exogenous exposures to EO. Copyright © 2017 Elsevier Inc. All rights reserved.

Endogenous versus exogenous growth factor regulation of articular chondrocytes.

Science.gov (United States)

Shi, Shuiliang; Chan, Albert G; Mercer, Scott; Eckert, George J; Trippel, Stephen B

2014-01-01

Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-β1 stimulated these reparative functions, while endogenous TGF-β1 had little effect. Endogenous TGF-β1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-β1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. This article is a U.S. Government work and is in the public domain in the USA.

Endogeneity in Strategy-Performance Analysis

DEFF Research Database (Denmark)

Rocha, Vera; Van Praag, Mirjam; B. Folta, Timothy

2018-01-01

, such as employees, strategic partners, customers, or investors, whose choices and preferences also affect the final decision. We discuss how endogeneity can plague the measurement of the performance effects of these two-sided strategic decisions—which are more complex, but more realistic, than prior representations...

Endogeneously arising network allocation rules

NARCIS (Netherlands)

Slikker, M.

2006-01-01

In this paper we study endogenously arising network allocation rules. We focus on three allocation rules: the Myerson value, the position value and the component-wise egalitarian solution. For any of these three rules we provide a characterization based on component efficiency and some balanced

DMPD: Endogenous ligands of Toll-like receptors. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 15178705 Endogenous ligands of Toll-like receptors. Tsan MF, Gao B. J Leukoc Biol. ...2004 Sep;76(3):514-9. Epub 2004 Jun 3. (.png) (.svg) (.html) (.csml) Show Endogenous ligands of Toll-like re...ceptors. PubmedID 15178705 Title Endogenous ligands of Toll-like receptors. Authors Tsan MF, Gao B. Publicat

An endogenous model of the credit network

Science.gov (United States)

He, Jianmin; Sui, Xin; Li, Shouwei

2016-01-01

In this paper, an endogenous credit network model of firm-bank agents is constructed. The model describes the endogenous formation of firm-firm, firm-bank and bank-bank credit relationships. By means of simulations, the model is capable of showing some obvious similarities with empirical evidence found by other scholars: the upper-tail of firm size distribution can be well fitted with a power-law; the bank size distribution can be lognormally distributed with a power-law tail; the bank in-degrees of the interbank credit network as well as the firm-bank credit network fall into two-power-law distributions.

Endogenous network of firms and systemic risk

Science.gov (United States)

Ma, Qianting; He, Jianmin; Li, Shouwei

2018-02-01

We construct an endogenous network characterized by commercial credit relationships connecting the upstream and downstream firms. Simulation results indicate that the endogenous network model displays a scale-free property which exists in real-world firm systems. In terms of the network structure, with the expansion of the scale of network nodes, the systemic risk increases significantly, while the heterogeneities of network nodes have no effect on systemic risk. As for firm micro-behaviors, including the selection range of trading partners, actual output, labor requirement, price of intermediate products and employee salaries, increase of all these parameters will lead to higher systemic risk.

[Mechanisms of leukocyte formation of endogenous pyrogen].

Science.gov (United States)

Rybakina, E G; Sorokin, A V

1982-06-01

A study was made of the kinetics of endogenous pyrogen production by rabbit blood and exudate leukocytes and possible role played by the products of activated leukocytes in autoregulation of the process. It was established that accumulation of endogenous pyrogen in the cell precedes its release by stimulated cells. Then the processes of active pyrogen formation and release gel interdependent: pyrogen formed releases from the cell; the lowering of pyrogen concentration in the cell is accompanied by the decrease of its content in the medium. No stimulating effect of the products activated during leukocyte inflammation on pyrogen formation by blood leukocytes was discovered.

Quantitative regularities of development of endogenous infection in irradiated organism

International Nuclear Information System (INIS)

Mal'tsev, V.N.

1979-01-01

A statistical analysis of data from the literature and the author's own experimental results are reviewed to show the functional relationships between the radiation dose and the development of endogenous infection in irradiated organisms. A direct linear dependence was found between the dose of radiation and the severity of endogenous infection at doses causing death from the ''bone marrow'' syndrome in acute radiation sickness. In case of death from the ''intestinal'' syndrome, an inverse linear dependence can be observed between the radiation dose and the culture yield of microbes from internal organs. In this case, the pathological effect on the organism is due to bacterial endotoxins formed during the disintegration of microbial cells in the organism. Endogenous infection and endotoxinaemia essentially aggravate the progress of acute radiation disease. The importance of endogenous infection for the death of the organism is minimized in irradiation at doses causing death ''under the ray''. (author)

Endogenous opioids encode relative taste preference.

Science.gov (United States)

Taha, Sharif A; Norsted, Ebba; Lee, Lillian S; Lang, Penelope D; Lee, Brian S; Woolley, Joshua D; Fields, Howard L

2006-08-01

Endogenous opioid signaling contributes to the neural control of food intake. Opioid signaling is thought to regulate palatability, the reward value of a food item as determined by orosensory cues such as taste and texture. The reward value of a food reflects not only these sensory properties but also the relative value of competing food choices. In the present experiment, we used a consummatory contrast paradigm to manipulate the relative value of a sucrose solution for two groups of rats. Systemic injection of the nonspecific opioid antagonist naltrexone suppressed sucrose intake; for both groups, however, this suppression was selective, occurring only for the relatively more valuable sucrose solution. Our results indicate that endogenous opioid signaling contributes to the encoding of relative reward value.

Invasive fungal infections in endogenous Cushing’s syndrome

Directory of Open Access Journals (Sweden)

Rafael Selbach Scheffel

2010-06-01

Full Text Available Cushing’s syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing’s original description of the disease. We describe here a patient with endo-genous Cushing’s syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease.

A General Outlook to the Endogenous Money Theory

OpenAIRE

ÖZGÜR, Gökçer

2008-01-01

The purpose of this study is to shed light on theorigins of the endogenous money theory and analyze the currentdebates on this topic. Endogenous money approach depends on a fundamental postulate: As banks meet the credit needs ofnon-financial businesses, new deposits emerge in the banking sector. Similarly,as the necessary reserves found for these new deposits the broad money expandsas well. Even though the central bank can intervene into this process it cannotfully control it. There...

EXOGENOUS OR ENDOGENOUS MONEY SUPPLY: EVIDENCE FROM AUSTRALIA

OpenAIRE

ZATUL E. BADARUDIN; AHMED M. KHALID; MOHAMED ARIFF

2012-01-01

This paper investigates the nature of money supply in Australia over two separate monetary policy regimes: monetary and inflation targeting. The post-Keynesian theory on endogenous money was tested with the aim of investigating whether endogenous money supply, if it did exist, followed the accomodationist, structuralist or liquidity preference viewpoints. Data used are quarterly series from 1977 to 2007 and we used vector error-correction model for long-run and short-run causality tests. We f...

Endogenizing Prospect Theory's Reference Point

OpenAIRE

Ulrich Schmidt; Horst Zank

2010-01-01

In previous models of (cumulative) prospect theory reference-dependence of preferences is imposed beforehand and the location of the reference point is exogenously determined. This note provides a foundation of prospect theory, where reference-dependence is derived from preference conditions and a unique reference point arises endogenously.

Increase in chemokine CXCL1 by ERβ ligand treatment is a key mediator in promoting axon myelination.

Science.gov (United States)

Karim, Hawra; Kim, Sung Hoon; Lapato, Andrew S; Yasui, Norio; Katzenellenbogen, John A; Tiwari-Woodruff, Seema K

2018-06-12

Estrogen receptor β (ERβ) ligands promote remyelination in mouse models of multiple sclerosis. Recent work using experimental autoimmune encephalomyelitis (EAE) has shown that ERβ ligands induce axon remyelination, but impact peripheral inflammation to varying degrees. To identify if ERβ ligands initiate a common immune mechanism in remyelination, central and peripheral immunity and pathology in mice given ERβ ligands at peak EAE were assessed. All ERβ ligands induced differential expression of cytokines and chemokines, but increased levels of CXCL1 in the periphery and in astrocytes. Oligodendrocyte CXCR2 binds CXCL1 and has been implicated in normal myelination. In addition, despite extensive immune cell accumulation in the CNS, all ERβ ligands promoted extensive remyelination in mice at peak EAE. This finding highlights a component of the mechanism by which ERβ ligands mediate remyelination. Hence, interplay between the immune system and central nervous system may be responsible for the remyelinating effects of ERβ ligands. Our findings of potential neuroprotective benefits arising from the presence of CXCL1 could have implications for improved therapies for multiple sclerosis. Copyright © 2018 the Author(s). Published by PNAS.

Dependence of PERT endpoint on endogenous lipase activity.

Science.gov (United States)

Gao, Wen-Yi; Mulberg, Andrew E

2014-11-01

To clarify and to understand the potential for misinterpretation of change in fecal fat quantitation during pancreatic enzyme replacement therapy (PERT) trials for treatment of exocrine pancreatic insufficiency. Analysis of clinical trials submitted to the U.S. Food and Drug Administration (FDA) for approval of PERT that enrolled 123 cystic fibrosis adult and pediatric patients treated with Creon, Pertzye, Ultresa, and Zenpep. The CFA% defines lipase activity as a percentage of converting substrate of "Total Daily Dietary Fat Intake." PERT trials performed to date have modified the definition to converting the "Shared Daily Fat Intake," generating "Partial CFA" for the exogenous lipase: the higher the activity of coexisting endogenous lipase, the lower the "Partial CFA" of exogenous measured. This review shows that "Partial CFA" is not CFA. Enrollment of patients with low HPLA during treatment may improve the interpretability of "Partial CFA" measured by PERT trials.

Cerebral systems in the pathogenesis of endogenous psychoses

Directory of Open Access Journals (Sweden)

Aníbal Silveira

1962-12-01

Full Text Available Mental processes imply a harmonious functioning of psychic systems, assembled into larger units, psychic spheres (Table I. Their neurophysiological representatives are brain systems of areas and pathways (Fig. 1-4. Under functional and/or organic disturbances these systems originate the leading mental symptoms (Table II characterizing the diverse endogenous psychoses: hence, the latter's distinctive patterns. Accordingly, understanding and classification of psychoses should rest on the pathogenic dynamisms, not on clinical description. This is why Kleist's and Leonhard's conceptions of the endogenous psychoses surpass any other to exist. Kleist stands among the founders of psychiatry, by describing the "degeneration psychoses" and many single psychoses, as well as redefining, isolating and clarifying the progressive ones, later on renamed as schizophrenias (Table III. Such pathogenic criterion may also be useful to define mental conditions other than psychoses, as hysteria, neuroses and psychopathic inferiority (Tables IV and V. One should consider here, besides the psychic systems and spheres involved, the way they were caught and the corresponding developmental phase. In Kleist's "degeneration psychoses" - cyclic or episodic (Table VI - the systems and spheres are disturbed by functional transient processes due to latent dispositions, while his and Leonhard's schizophrenias (Table VII show a rather progressive, deteriorating course. The nature of the disorder is itself genetically determined, as is either its confinement to one sphere or its spreading out. The spread out pattern, while exceptional in schizophrenia, represents a rule for the "degeneration psychoses", in discussant's mind. Both groups may have symptoms alike by involvement of the same sphere (Table VIII, but proper diagnosis is reached by taking pathogenesis into consideration.

The role of human endogenous retroviruses in brain development and function.

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Mortelmans, Kristien; Wang-Johanning, Feng; Johanning, Gary L

2016-01-01

Endogenous retroviral sequences are spread throughout the genome of all humans, and make up about 8% of the genome. Despite their prevalence, the function of human endogenous retroviruses (HERVs) in humans is largely unknown. In this review we focus on the brain, and evaluate studies in animal models that address mechanisms of endogenous retrovirus activation in the brain and central nervous system (CNS). One such study in mice found that TRIM28, a protein critical for mouse early development, regulates transcription and silencing of endogenous retroviruses in neural progenitor cells. Another intriguing finding in human brain cells and mouse models was that endogenous retrovirus HERV-K appears to be protective against neurotoxins. We also report on studies that associate HERVs with human diseases of the brain and CNS. There is little doubt of an association between HERVs and a number of CNS diseases. However, a cause and effect relationship between HERVs and these diseases has not yet been established. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Endogenous cueing attenuates object substitution masking.

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Germeys, Filip; Pomianowska, I; De Graef, P; Zaenen, P; Verfaillie, K

2010-07-01

Object substitution masking (OSM) is a form of visual masking in which a briefly presented target surrounded by four small dots is masked by the continuing presence of the four dots after target offset. A major parameter in the prediction of OSM is the time required for attention to be directed to the target following its onset. Object substitution theory (Di Lollo et al. in J Exp Psychol Gen 129:481-507, 2000) predicts that the sooner attention can be focused at the target's location, the less masking will ensue. However, recently Luiga and Bachmann (Psychol Res 71:634-640, 2007) presented evidence that precueing of attention to the target location prior to target-plus-mask onset by means of a central (endogenous) arrow cue does not reduce OSM. When attention was cued exogenously, OSM was attenuated. Based on these results, Luiga and Bachmann argued that object substitution theory should be adapted by differentiating the ways of directing attention to the target location. The goal of the present study was to further examine the dissociation between the effects of endogenous and exogenous precueing on OSM. Contrary to Luiga and Bachmann, our results show that prior shifts of attention to the target location initiated by both exogenous and endogenous cues reduce OSM as predicted by object substitution theory and its computational model CMOS.

The search for an endogenous activator.

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Gekowski, K. M.; Atkins, E.

1985-01-01

Certain febrile diseases are unaccompanied by infection or apparent hypersensitivity. In myocardial infarction or pulmonary embolism, for example, fever has been attributed to inflammation and/or tissue necrosis. Exogenous (microbial) pyrogens stimulate both human and animal monocytes/macrophages to produce endogenous pyrogen (EP) in vitro. To determine if plasma and cellular endogeneous mediators (EMs) of inflammation induced EP production, human mononuclear cells (M/L) were incubated for 18 hours with varying amounts of EM and the supernates assayed for EP in rabbits. Neutrophils (PMNs), which do not generate EP and yet are a feature of acute inflammation, were tested. Neither viable, phorbol myristic acetate-stimulated PMNs nor sonicated PMNs, red blood cells, or M/L stimulated human monocytes to produce EP. Human C3b and C5a, which mediate phagocytosis and chemotaxis, respectively, were also inactive. Despite its chemoattractant properties, the synthetic peptide FMLP failed to induce EP release. Since Poly I:Poly C (PIC: a synthetic, double-stranded RNA) is a potent pyrogen in rabbits, we investigated PIC, as well as a native, single-stranded RNA (from E. coli) and DNA (from calf thymus). None was active in vitro, and only PIC caused fever when given to rabbits intravenously. In summary, we have been unable to find an endogenous activator of EP from human monocytes to explain fevers associated with inflammation alone. PMID:3875936

Identification of endogenous flurophores in the layered retina

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Xu, Gaixia; Chen, Danni; Sun, Yiwen; Qu, Junle; Lin, Ziyang; Ding, Zhihua; Niu, Hanben

2007-05-01

In this paper, we measured and analyzed the characteristic of endogenous fluorophores in porcine layered retina by using advanced fluorescence spectroscopy and microscopy imaging technology. It was found that there were obvious contrasts corresponding to the different layers of retina, which may be important for fundus disease diagnosis. The retinal pigment epithelium cells exhibited strong autofluorescence with as emission peak of 600+/-10nm when excited with 860-nm light. The emission peak of photoreceptors was at 652+/-5nm, and the emission peak of retinal vessels layer was weak and at 640~700nm, when excited with 488-nm light. Autofluorescence images of three layers of retina were obtained using the same setup. We concluded that the main endogenous fluorophore in PRE was lipofuscin and that in retinal vessels was porphyrin. What's more, the FMHW (full width at half. maximum) of retinal fluorescence spectrum was broad, which suggested that there wasn't only one endogenous fluorophores of tissues excited.

Endogenous small RNAs and antibacterial immunity in plants.

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Jin, Hailing

2008-08-06

Small RNAs are non-coding regulatory RNA molecules that control gene expression by mediating mRNA degradation, translational inhibition, or chromatin modification. Virus-derived small RNAs induce silencing of viral RNAs and are essential for antiviral defense in both animal and plant systems. The role of host endogenous small RNAs on antibacterial immunity has only recently been recognized. Host disease resistance and defense responses are achieved by activation and repression of a large array of genes. Certain endogenous small RNAs in plants, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), are induced or repressed in response to pathogen attack and subsequently regulate the expression of genes involved in disease resistance and defense responses by mediating transcriptional or post-transcriptional gene silencing. Thus, these small RNAs play an important role in gene expression reprogramming in plant disease resistance and defense responses. This review focuses on the recent findings of plant endogenous small RNAs in antibacterial immunity.

Induced pluripotency with endogenous and inducible genes

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Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

2008-01-01

The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER TAM ) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols

Endogenous analgesic effect of pregabalin: A double-blind and randomized controlled trial.

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Sugimine, S; Saito, S; Araki, T; Yamamoto, K; Obata, H

2017-07-01

Conditioned pain modulation (CPM) is widely used to measure endogenous analgesia, and a recent study indicated that drugs that act on endogenous analgesia are more effective in individuals with lower CPM. Recent animal studies have indicated that pregabalin activates endogenous analgesia by stimulating the descending pain inhibitory system. The present study examined whether the analgesic effect of pregabalin is greater in individuals with lower original endogenous analgesia using CPM. Fifty-nine healthy subjects were randomly assigned to either a pregabalin group or a placebo group, and 50 of them completed the study. CPM was measured before and after pregabalin or placebo administration. The correlation of initial CPM to change in CPM was compared between the pregabalin and placebo groups. Initial CPM was significantly correlated with the change in CPM in the pregabalin group (r = -0.73, p CPM significantly affected the change in CPM in the pregabalin group but not in the placebo group (pregabalin group: adj R 2  = 0.51, p CPM) was stronger for subjects with lower original endogenous analgesia, suggesting that the mechanism of pregabalin involves the improvement of endogenous analgesia. © 2017 European Pain Federation - EFIC®.

Animal spirits, competitive markets, and endogenous growth

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Miyazaki, Kenji

2013-10-01

This paper uses a simple model with an endogenous discount rate and linear technology to investigate whether a competitive equilibrium has a higher balanced growth path (BGP) than the social planning solution and whether the BGP is determinate or indeterminate. The implications are as follows. To start with, people with an instinct to compare themselves with others possess an endogenous discount rate. In turn, this instinct affects the economic growth rate in a competitive market economy. The competitive market economy also sometimes achieves higher economic growth than a social planning economy. However, the outcomes of market economy occasionally fluctuate because of the presence of the self-fulfilling prophecy or animal spirits.

A comparative analysis of property of lychee polyphenoloxidase using endogenous and exogenous substrates.

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Sun, Jian; Shi, John; Zhao, Mouming; Xue, Sophia Jun; Ren, Jiaoyan; Jiang, Yueming

2008-06-01

Lychee polyphenoloxidase (PPO) was extracted and partially purified using ammonium sulphate precipitation and dialysis. The comparative analysis of PPO property was performed using its endogenous substrate (-)-epicatechin and exogenous substrate catechol. The pH optima for activity and activation temperature profiles of lychee PPO were very different when the enzyme reacted with endogenous and exogenous substrates. The addition of ethylenediaminetetraacetic acid disodium salt into the endogenous or exogenous substrate-enzyme system exhibited the same lowest inhibition of the PPO activity. However, l-cysteine was most effective in inhibiting enzymatic activity in the endogenous substrate-enzyme system while ascorbic acid was the best inhibitor in the exogenous substrate-enzyme system. Fe(2+) greatly accelerated the enzymatic reaction between endogenous substrate and PPO, but Cu(2+) exerted the same effect on the reaction between exogenous substrate and PPO. Based on the kinetic analysis, lychee PPO could strongly bind endogenous substrate but it possessed a higher catalytic efficiency to exogenous substrate. Copyright © 2007 Elsevier Ltd. All rights reserved.

Endogenous induced technical change and the costs of Kyoto

International Nuclear Information System (INIS)

Buonanno, Paolo; Carraro, Carlo; Galeotti, Marzio

2003-01-01

We present a model for climate change policy analysis which accounts for the possibility that technology evolves endogenously and that technical change can be induced by environmental policy measures. Both the output production technology and the emission-output ratio depend upon a stock of knowledge, which accumulates through R and D activities. Two versions of this model are studied, one with endogenous technical change but exogenous environmental technical change and the other with both endogenous and induced technical change. A third version also captures technological spillover effects. As an application, the model is simulated allowing for trade of pollution permits as specified in the Kyoto Protocol and assessing the implications in terms of cost efficiency, economic growth and R and D efforts of the three different specifications of technical change

Endogenous Money, Non-neutrality and Interest-sensitivity in the Theory of Long Period Unemployment

OpenAIRE

Peter Docherty

2006-01-01

This paper investigates the role played by endogenous money in models with interest-sensitive expenditures. In particular, it examines the impact of endogenous money on a baseline neoclassical model arguing against the frequently asserted claim that traditional neoclassical macroeconomics is compatible with endogenous money. It demonstrates firstly that endogenous money is a sufficient condition to render unstable a neoclassical model characterised by interest-sensitive expenditures, full emp...

Endogenous lentivirus in Malayan colugo (Galeopterus variegatus), a close relative of primates.

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Hron, Tomáš; Fábryová, Helena; Pačes, Jan; Elleder, Daniel

2014-10-04

A significant fraction of mammalian genomes is composed of endogenous retroviral (ERV) sequences that are formed by germline infiltration of various retroviruses. In contrast to other retroviral genera, lentiviruses only rarely form ERV copies. We performed a computational search aimed at identification of novel endogenous lentiviruses in vertebrate genomes. Using the in silico strategy, we have screened 104 publicly available vertebrate genomes for the presence of endogenous lentivirus sequences. In addition to the previously described cases, the search revealed the presence of endogenous lentivirus in the genome of Malayan colugo (Galeopterus variegatus). At least three complete copies of this virus, denoted ELVgv, were detected in the colugo genome, and approximately one hundred solo LTR sequences. The assembled consensus sequence of ELVgv had typical lentivirus genome organization including three predicted accessory genes. Phylogenetic analysis placed this virus as a distinct subgroup within the lentivirus genus. The time of insertion into the dermopteran lineage was estimated to be more than thirteen million years ago. We report the discovery of the first endogenous lentivirus in the mammalian order Dermoptera, which is a taxon close to the Primates. Lentiviruses have infiltrated the mammalian germline several times across millions of years. The colugo virus described here represents possibly the oldest documented endogenization event and its discovery can lead to new insights into lentivirus evolution. This is also the first report of an endogenous lentivirus in an Asian mammal, indicating a long-term presence of this retrovirus family in Asian continent.

Effect of endogenous carotenoids on “adaptive” mutation in Escherichia coli FC40

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Bridges, Bryn A.; Foster, Patricia L.; Timms, Andrew R.

2010-01-01

The appearance over many days of Lac+ frameshift mutations in Escherichia coli strain FC40 incubated on lactose selection plates is a classic example of apparent “adaptive” mutation in an episomal gene. We show that endogenously overproduced carotenoids reduce adaptive mutation under selective conditions by a factor of around two. Carotenoids are known to scavenge singlet oxygen suggesting that the accumulation of oxidative base damage may be an integral part of the adaptive mutation phenomenon. If so, the lesion cannot be 7,8-dihydro-8-oxoguanine since adaptive mutation in FC40 is unaffected by mutM and mutY mutations. If active oxygen species such as singlet oxygen are involved in adaptive mutation then they should also induce frameshift mutations in FC40 under non-selective conditions. We show that such mutations can be induced under non-selective conditions by protoporphyrin photosensitisation and that this photodynamic induction is reduced by a factor of just over two when endogenous carotenoids are present. We argue that the involvement of oxidative damage would in no way be inconsistent with current understanding of the mechanism of adaptive mutation and the role of DNA polymerases. PMID:11166030

Proteomics investigation of endogenous S-nitrosylation in Arabidopsis

International Nuclear Information System (INIS)

Fares, Abasse; Rossignol, Michel; Peltier, Jean-Benoît

2011-01-01

Highlights: ► Identification and quantification of nitrosothiols. ► A first dataset of endogenously nitrosylated cysteines in Arabidopsis cells. ► Nitrosothiols display apolar motifs not located in close vicinity of cysteines. ► Salt stress alters the endogenous nitrosylation of specific cysteines in Arabidopsis. -- Abstract: S-Nitrosylation emerges as an important protein modification in many processes. However, most data were obtained at the protein level after addition of a NO donor, particularly in plants where information about the cysteines nitrosylated in these proteins is scarce. An adapted work-flow, combining the classical biotin switch method and labeling with isotope-coded affinity tags (ICAT), is proposed. Without addition of NO donor, a total of 53 endogenous nitrosocysteines was identified in Arabidopsis cells, in proteins belonging to all cell territories, including membranes, and covering a large panel of functions. This first repertoire of nitrosothiols in plants enabled also preliminary structural description. Three apolar motifs, not located in close vicinity of cysteines and accounting for half the dataset, were detected and are proposed to complement nitrosylation prediction algorithms, poorly trained with plant data to date. Analysis of changes induced by a brief salt stress showed that NaCl modified the nitrosylation level of a small proportion of endogenously nitrosylated proteins and did not concern all nitrosothiols in these proteins. The possible role of some NO targets in the response to salt stress was discussed.

A generalized endogenous grid method for discrete-continuous choice

OpenAIRE

John Rust; Bertel Schjerning; Fedor Iskhakov

2012-01-01

This paper extends Carroll's endogenous grid method (2006 "The method of endogenous gridpoints for solving dynamic stochastic optimization problems", Economic Letters) for models with sequential discrete and continuous choice. Unlike existing generalizations, we propose solution algorithm that inherits both advantages of the original method, namely it avoids all root finding operations, and also efficiently deals with restrictions on the continuous decision variable. To further speed up the s...

Gut Microbial Glycerol Metabolism as an Endogenous Acrolein Source

OpenAIRE

Zhang, Jianbo; Sturla, Shana; Lacroix, Christophe; Schwab, Clarissa

2018-01-01

ABSTRACT Acrolein is a highly reactive electrophile causing toxic effects, such as DNA and protein adduction, oxidative stress, endoplasmic reticulum stress, immune dysfunction, and membrane damage. This Opinion/Hypothesis provides an overview of endogenous and exogenous acrolein sources, acrolein’s mode of action, and its metabolic fate. Recent reports underpin the finding that gut microbial glycerol metabolism leading to the formation of reuterin is an additional source of endogenous acrole...

Recruiting endogenous stem cells: a novel therapeutic approach for erectile dysfunction

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Zhong-Cheng Xin

2016-01-01

Full Text Available Transplanted stem cells (SCs, owing to their regenerative capacity, represent one of the most promising methods to restore erectile dysfunction (ED. However, insufficient source, invasive procedures, ethical and regulatory issues hamper their use in clinical applications. The endogenous SCs/progenitor cells resident in organ and tissues play critical roles for organogenesis during development and for tissue homeostasis in adulthood. Even without any therapeutic intervention, human body has a robust self-healing capability to repair the damaged tissues or organs. Therefore, SCs-for-ED therapy should not be limited to a supply-side approach. The resident endogenous SCs existing in patients could also be a potential target for ED therapy. The aim of this review was to summarize contemporary evidence regarding: (1 SC niche and SC biological features in vitro; (2 localization and mobilization of endogenous SCs; (3 existing evidence of penile endogenous SCs and their possible mode of mobilization. We performed a search on PubMed for articles related to these aspects in a wide range of basic studies. Together, numerous evidences hold the promise that endogenous SCs would be a novel therapeutic approach for the therapy of ED.

Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

DEFF Research Database (Denmark)

Paterson, Louise M; Tyacke, Robin J; Nutt, David J

2010-01-01

Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron......, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT(1A), 5-HT(2A), and 5-HT(4) receptors and the serotonin reuptake transporter...... have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made...

Endogenous compounds labeled with radionuclides of short half-life-some perspectives

DEFF Research Database (Denmark)

Roland Långström, Bengt; Karimi, F; Watanabe, Y

2013-01-01

In the article, the strategy and synthesis of some endogenous compounds labeled mainly with (11) C are presented. There are some examples illustrating how endogenous labeled compounds in connection with positron emission tomography have unique properties to describe various biological processes......, and a few examples of the use of tracers labeled with (13) N and (15) O are also discussed. Labeled endogenous compounds may be an important asset to describe the conditions and the status of biological systems and might therefore be a key for the future search of individualized medicine....

Co-factors necessary for PPAR mediated transactivation of endogenous target genes

DEFF Research Database (Denmark)

Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk

of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...

Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

DEFF Research Database (Denmark)

Paterson, Louise M; Tyacke, Robin J; Nutt, David J

2010-01-01

Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron ...

The issue of HPLC determination of endogenous lipoic acid in human plasma.

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Sechovcová, Soňa; Královcová, Pavla; Kanďár, Roman; Ventura, Karel

2018-05-01

Lipoic acid (LA) is used extensively as a therapeutic agent for the treatment of various diseases. Many methods have been reported for the determination of LA plasma levels and its metabolites after its supplementation, but available information concerning endogenous plasma levels is still scarce. Studies which directly focused on determining the endogenous plasma levels provided highly controversial results, endogenous plasma levels of LA: 2.4 and 4.9 nmol/L respectively. However, the levels of free LA in the plasma of nonsupplemented voluntary blood donors were not detectable in all cases. The presented results of our study show that endogenous concentrations of LA are <1.85 nmol/L. Copyright © 2017 John Wiley & Sons, Ltd.

Endogenous leukotriene formation during anaphylactic shock

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Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

1987-01-01

Leukotriene (LT)C 4 is a biologically active substance, presumed to play major roles as a mediator of allergic and anaphylactic reactions. It is formed e.g. by basophilic and eosinophilic leukocytes, monocytes, macrophages, and mast cells. In cells having IgE receptors, bridging of these by divalent anti-IgE-receptor antibodies or by interaction between receptor-bound IgE and anti-IgE will induce LTC 4 formation. Leukotriene formation has also been demonstrated in other in vitro models of immediate hypersensivity. The biological actions of LTC 4 , comprise induction of airway obstruction, constriction of coronary arteries, hypotension, and plasma extravasation. Leukotriene formation in vivo may mediate anaphylactic shock symptoms and cause the death of an animal. In order to prove the presumed mediator role of this substance in anaphylactic reactions, it is necessary to demonstrate its endogenous formation during shock. Studies on the metabolism of LTC 4 have revealed rapid catabolism by various transformations of the peptide substituent. Recently, three metabolites were demonstrated to be excreted as end-products in man (LTE 4 ,) and the rat (N-acetyl LTE 4 and N-acetyl 11-trans LTE 4 ). By monitoring biliary N-acetyl LTE 4 levels, endogenous leukotriene formation in the rat was demonstrated in vivo after tissue trauma and endotoxin shock. We now wish to report evidence for endogenous leukotriene C 4 production during anaphylactic shock in guinea pigs. 37 refs. (author)

Treatment of skeletal impairment in patients with endogenous hypercortisolism: when and how?

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Scillitani, A; Mazziotti, G; Di Somma, C; Moretti, S; Stigliano, A; Pivonello, R; Giustina, A; Colao, A

2014-02-01

Guidelines for the management of osteoporosis induced by endogenous hypercortisolism are not available. Both the American College of Rheumatology and the International Osteoporosis Foundation recommend to modulate the treatment of exogenous glucocorticoid-induced osteoporosis (GIO) based on the individual fracture risk profile (calculated by FRAX) and dose of glucocorticoid used, but it is difficult to translate corticosteroid dosages to different degrees of endogenous hypercortisolism, and there are no data on validation of FRAX stratification method in patients with endogenous hypercortisolism. Consequently, it is unclear whether such recommendations may be adapted to patients with endogenous hypercortisolism. Moreover, patients with exogenous GIO take glucocorticoids since suffering a disease that commonly affects bone. On the other hand, the correction of coexistent risk factors, which may contribute to increase the fracture risk in patients exposed to glucocorticoid excess, and the removal of the cause of endogenous hypercortisolism, may lead to the recovery of bone health. Although the correction of hypercortisolism and of possible coexistent risk factors is necessary to favor the normalization of bone turnover with recovery of bone mass; in some patients, the fracture risk could not be normalized and specific anti-osteoporotic drugs should be given. Who, when, and how the patient with endogenous hypercortisolism should be treated with bone-active therapy is discussed.

[Endogenous Endophthalmitis: Epidemiology, Clinic, Therapy and Visual Outcome].

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Mayer, Christian; Loos, Daria; Feucht, Nikolaus; Zapp, Daniel; Prahs, Philipp Maximilian; Tandogan, Tamer; Khoramnia, Ramin

2018-04-11

Endogenous endophthalmitis is a rare and severe inflammation of the eye in the context of a systemic infectious disease, which can lead to the loss of the affected eye in the worst case. In a 5-year period, 20 eyes were treated for endogenous endophthalmitis and evaluated retrospectively. Evaluation parameters were epidemiological data, causes, concomitant diseases, assessment of the pathogen spectrum, therapy and visual acuity. 13.2% (n = 20/152; 20 eyes of 17 patients) of all endophthalmitis cases were of endogenous origin. In 15% (n = 3/20) of the cases, bilateral endogenous endophthalmitis was present. The cause for the endophthalmitis was generalised sepsis in 9 of 17 cases, an infection of the urogenital tract in 2 of 17 cases and endocarditis and liver abscess in 1 of 17 cases, respectively. In 4 of 17 cases, no primary foci were detected. Eight of 17 patients suffered from diabetes mellitus, 6 of 17 from renal insufficiency and 2 of 17 from malignancies, pneumonia or rheumatism. Two of 17 patients had had an organ transplantation, 15 of 17 suffered from cardiovascular diseases, 3 of 17 were immunosuppressed and 2 of 17 reported drug abuse. Four of 17 infections were caused by streptococci, 3 of 17 by Candida, 2 of 17 by herpes viruses and 1 of 17 by Staphylococcus aureus and Bacillus cereus. No pathogen could be found in 5 cases. The time interval between the onset of symptoms and diagnosis and the beginning of the therapy was 4 days (min.: 1 day; max.: 39 days). This was significantly longer in comparison with other causes of endophthalmitis (p Endogenous endophthalmitis is often misdiagnosed due to a severe underlying non-ophthalmological disease. Delayed presentation with consequent late initiation of therapy is an unresolved problem, because colleagues from other fields are often unexperienced in diagnosing the ocular infection. This is also a cause of the already poor visual prognosis. Ophthalmologists can usually only influence the choice

Inhibition of endogenous lactate turnover with lactate infusion in humans

International Nuclear Information System (INIS)

Searle, G.L.; Feingold, K.R.; Hsu, F.S.; Clark, O.H.; Gertz, E.W.; Stanley, W.C.

1989-01-01

The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U- 14 C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production

Quantitative live imaging of endogenous DNA replication in mammalian cells.

Directory of Open Access Journals (Sweden)

Andrew Burgess

Full Text Available Historically, the analysis of DNA replication in mammalian tissue culture cells has been limited to static time points, and the use of nucleoside analogues to pulse-label replicating DNA. Here we characterize for the first time a novel Chromobody cell line that specifically labels endogenous PCNA. By combining this with high-resolution confocal time-lapse microscopy, and with a simplified analysis workflow, we were able to produce highly detailed, reproducible, quantitative 4D data on endogenous DNA replication. The increased resolution allowed accurate classification and segregation of S phase into early-, mid-, and late-stages based on the unique subcellular localization of endogenous PCNA. Surprisingly, this localization was slightly but significantly different from previous studies, which utilized over-expressed GFP tagged forms of PCNA. Finally, low dose exposure to Hydroxyurea caused the loss of mid- and late-S phase localization patterns of endogenous PCNA, despite cells eventually completing S phase. Taken together, these results indicate that this simplified method can be used to accurately identify and quantify DNA replication under multiple and various experimental conditions.

Gastrointestinal Endogenous Proteins as a Source of Bioactive Peptides - An In Silico Study

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Dave, Lakshmi A.; Montoya, Carlos A.; Rutherfurd, Shane M.; Moughan, Paul J.

2014-01-01

Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein. PMID:24901416

Gastrointestinal endogenous proteins as a source of bioactive peptides--an in silico study.

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Dave, Lakshmi A; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

2014-01-01

Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein.

Endogenous hydrogen peroxide production in the epithelium of the developing embryonic lens.

Science.gov (United States)

Basu, Subhasree; Rajakaruna, Suren; Dickinson, Bryan C; Chang, Christopher J; Menko, A Sue

2014-01-01

Hydrogen peroxide (H2O2) is an endogenously produced reactive oxygen species (ROS) present in a variety of mammalian systems. This particular ROS can play dichotomous roles, being beneficial in some cases and deleterious in others, which reflects the level and location of H2O2 production. While much is known about the redox regulation of ROS by antioxidant and repair systems in the lens, little is known about the endogenous production of H2O2 in embryonic lens tissue or the physiologic relevance of endogenous H2O2 to lens development. This gap in knowledge exists primarily from a lack of reagents that can specifically detect endogenous H2O2 in the intact lens. Here, using a recently developed chemoselective fluorescent boronate probe, peroxyfluor-6 acetoxymethyl ester (PF6-AM), which selectively detects H2O2 over related ROS, we examined the endogenous H2O2 signals in the embryonic lens. Embryonic day 10 chick whole lenses in ex vivo organ culture and lens epithelial cells in primary culture were loaded with the H2O2 probe PF6-AM. To determine the relationship between localization of mitochondria with active membrane potential and the region of H2O2 production in the lens, cells were exposed to the mitochondrial probe MitoTracker Red CMXRos together with PF6-AM. Diphenyleneiodonium (DPI), a flavin inhibitor that blocks generation of intracellular ROS production, was used to confirm that the signal from PF6-AM was due to endogenous ROS production. All imaging was performed by live confocal microscopy. PF6-AM detected endogenous H2O2 in lens epithelial cells in whole lenses in ex vivo culture and in lens epithelial cells grown in primary culture. No endogenous H2O2 signal could be detected in differentiating lens fiber cells with this probe. Treatment with DPI markedly attenuated the fluorescence signal from the peroxide-specific probe PF6-AM in the lens epithelium, suggesting that basal generation of ROS occurs in this region. The lens epithelial cells producing an

DMPD: Regulation of endogenous apolipoprotein E secretion by macrophages. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18388328 Regulation of endogenous apolipoprotein E secretion by macrophages. Kockx ...svg) (.html) (.csml) Show Regulation of endogenous apolipoprotein E secretion by macrophages. PubmedID 18388...328 Title Regulation of endogenous apolipoprotein E secretion by macrophages. Aut

Endogenous Natural Complement Inhibitor Regulates Cardiac Development

DEFF Research Database (Denmark)

Mortensen, Simon A; Skov, Louise L; Kjaer-Sorensen, Kasper

2017-01-01

mechanisms during fetal development and adult homeostasis. In this article, we describe the function of an endogenous complement inhibitor, mannan-binding lectin (MBL)-associated protein (MAp)44, in regulating the composition of a serine protease-pattern recognition receptor complex, MBL-associated serine...... of MAp44 caused impaired cardiogenesis, lowered heart rate, and decreased cardiac output. These defects were associated with aberrant neural crest cell behavior. We found that MAp44 competed with MASP-3 for pattern recognition molecule interaction, and knockdown of endogenous MAp44 expression could...... be rescued by overexpression of wild-type MAp44. Our observations provide evidence that immune molecules are centrally involved in the orchestration of cardiac tissue development....

A Reformulation of Normative Economics for Models with Endogenous

OpenAIRE

Bhatt, Vipul; Ogaki, Masao; Yaguchi, Yuichi

2015-01-01

This paper proposes a framework to balance considerations of welfarism and virtue ethics in the normative analysis of economic models with endogenous preferences. We introduce the moral evaluation function (MEF), which ranks alternatives based purely on virtue ethics, and define the social objective function (SOF), which combines the Social Welfare Function (SWF) and the MEF. In a model of intergenerational altruism with endogenous time preference, using numerical simulations we show that max...

Glacial cycles:exogenous orbital changes vs. endogenous climate dynamics

OpenAIRE

Kaufmann, R. K.; Juselius, Katarina

2010-01-01

We use a statistical model, the cointegrated vector autoregressive model, to assess the degree to which variations in Earth's orbit and endogenous climate dynamics can be used to simulate glacial cycles during the late Quaternary (390 kyr-present). To do so, we estimate models of varying complexity and compare the accuracy of their in-sample simulations. Results indicate that strong statistical associations between endogenous climate variables are not enough for statistical models to reproduc...

Label-Free Proteomic Identification of Endogenous, Insulin-Stimulated Interaction Partners of Insulin Receptor Substrate-1

Science.gov (United States)

Geetha, Thangiah; Langlais, Paul; Luo, Moulun; Mapes, Rebekka; Lefort, Natalie; Chen, Shu-Chuan; Mandarino, Lawrence J.; Yi, Zhengping

2011-03-01

Protein-protein interactions are key to most cellular processes. Tandem mass spectrometry (MS/MS)-based proteomics combined with co-immunoprecipitation (CO-IP) has emerged as a powerful approach for studying protein complexes. However, a majority of systematic proteomics studies on protein-protein interactions involve the use of protein overexpression and/or epitope-tagged bait proteins, which might affect binding stoichiometry and lead to higher false positives. Here, we report an application of a straightforward, label-free CO-IP-MS/MS method, without the use of protein overexpression or protein tags, to the investigation of changes in the abundance of endogenous proteins associated with a bait protein, which is in this case insulin receptor substrate-1 (IRS-1), under basal and insulin stimulated conditions. IRS-1 plays a central role in the insulin signaling cascade. Defects in the protein-protein interactions involving IRS-1 may lead to the development of insulin resistance and type 2 diabetes. HPLC-ESI-MS/MS analyses identified eleven novel endogenous insulin-stimulated IRS-1 interaction partners in L6 myotubes reproducibly, including proteins play an important role in protein dephosphorylation [protein phosphatase 1 regulatory subunit 12A, (PPP1R12A)], muscle contraction and actin cytoskeleton rearrangement, endoplasmic reticulum stress, and protein folding, as well as protein synthesis. This novel application of label-free CO-IP-MS/MS quantification to assess endogenous interaction partners of a specific protein will prove useful for understanding how various cell stimuli regulate insulin signal transduction.

Endogenous Opiates and Behavior: 2006

Science.gov (United States)

Bodnar, Richard J.

2009-01-01

This paper is the twenty-ninth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning thirty years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:17949854

Endogenous opiates and behavior: 2012.

Science.gov (United States)

Bodnar, Richard J

2013-12-01

This paper is the thirty-fifth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2012 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). Copyright © 2013 Elsevier Inc. All rights reserved.

High Yield of Adult Oligodendrocyte Lineage Cells Obtained from Meningeal Biopsy

Directory of Open Access Journals (Sweden)

Sissi Dolci

2017-10-01

Full Text Available Oligodendrocyte loss can lead to cognitive and motor deficits. Current remyelinating therapeutic strategies imply either modulation of endogenous oligodendrocyte precursors or transplantation of in vitro expanded oligodendrocytes. Cell therapy, however, still lacks identification of an adequate source of oligodendrocyte present in adulthood and able to efficiently produce transplantable cells. Recently, a neural stem cell-like population has been identified in meninges. We developed a protocol to obtain high yield of oligodendrocyte lineage cells from one single biopsy of adult rat meningeal tissue. From 1 cm2 of adult rat spinal cord meninges, we efficiently expanded a homogenous culture of 10 millions of meningeal-derived oligodendrocyte lineage cells in a short period of time (approximately 4 weeks. Meningeal-derived oligodendrocyte lineage cells show typical mature oligodendrocyte morphology and express specific oligodendrocyte markers, such as galactosylceramidase and myelin basic protein. Moreover, when transplanted in a chemically demyelinated spinal cord model, meningeal-derived oligodendrocyte lineage cells display in vivo-remyelinating potential. This oligodendrocyte lineage cell population derives from an accessible and adult source, being therefore a promising candidate for autologous cell therapy of demyelinating diseases. In addition, the described method to differentiate meningeal-derived neural stem cells into oligodendrocyte lineage cells may represent a valid in vitro model to dissect oligodendrocyte differentiation and to screen for drugs capable to promote oligodendrocyte regeneration.

Neural correlates of endogenous attention, exogenous attention and inhibition of return in touch.

Science.gov (United States)

Jones, Alexander; Forster, Bettina

2014-07-01

Selective attention helps process the myriad of information constantly touching our body. Both endogenous and exogenous mechanisms are relied upon to effectively process this information; however, it is unclear how they relate in the sense of touch. In three tasks we contrasted endogenous and exogenous event-related potential (ERP) and behavioural effects. Unilateral tactile cues were followed by a tactile target at the same or opposite hand. Clear behavioural effects showed facilitation of expected targets both when the cue predicted targets at the same (endogenous predictive task) and opposite hand (endogenous counter-predictive task), and these effects also correlated with ERP effects of endogenous attention. In an exogenous task, where the cue was non-informative, inhibition of return (IOR) was observed. The electrophysiological results demonstrated early effects of exogenous attention followed by later endogenous attention modulations. These effects were independent in both the endogenous predictive and exogenous tasks. However, voluntarily directing attention away from a cued body part influenced the early exogenous marker (N80). This suggests that the two mechanisms are interdependent, at least when the task requires more demanding shifts of attention. The early marker of exogenous tactile attention, the N80, was not directly related to IOR, which may suggest that exogenous attention and IOR are not necessarily two sides of the same coin. This study adds valuable new insight into how we process and select information presented to our body, showing both independent and interdependent effects of endogenous and exogenous attention in touch. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period.

Science.gov (United States)

Pappa, Theodora; Alevizaki, Maria

2012-08-01

Cardio- and cerebro-vascular diseases are two leading causes of death and long-term disability in postmenopausal women. The acute fall of estrogen in menopause is associated with increased cardiovascular risk. The relative contribution of androgen to this risk is also being recognized. The use of more sensitive assays for estradiol measurement and the study of receptor and carrier protein gene polymorphisms have provided some new information on the clinical relevance of endogenous sex steroids. We provide an update on the role of endogenous sex steroids on cardio- and cerebro-vascular disease in the postmenopausal period. We performed a PubMed search using the terms 'endogenous estrogen', 'androgen', 'cardiovascular disease', 'cerebro-vascular disease', 'stroke', 'carotid artery disease', and 'subclinical atherosclerosis'. The majority of studies show a beneficial effect of endogenous estrogen on the vasculature; however, there are a few studies reporting the contrary. A significant body of literature has reported associations of endogenous estrogen and androgen with early markers of atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex steroids in heart disease and stroke are inconclusive. Most studies support a beneficial role of endogenous estrogens and, probably, an adverse effect of androgens in the vasculature in postmenopausal women. However, the described associations may not always be considered as causal. It is possible that circulating estrogen might represent a marker of general health status or alternatively reflect the sum of endogenous androgens aromatized in the periphery. Elucidating the role of sex steroids in cardio- and cerebro-vascular disease remains an interesting field of future research.

Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.

Science.gov (United States)

Sarkies, Peter; Ashe, Alyson; Le Pen, Jérémie; McKie, Mikel A; Miska, Eric A

2013-08-01

Positive-strand RNA viruses encompass more than one-third of known virus genera and include many medically and agriculturally relevant human, animal, and plant pathogens. The nematode Caenorhabditis elegans and its natural pathogen, the positive-strand RNA virus Orsay, have recently emerged as a new animal model to understand the mechanisms and evolution of innate immune responses. In particular, the RNA interference (RNAi) pathway is required for C. elegans resistance to viral infection. Here we report the first genome-wide analyses of gene expression upon viral infection in C. elegans. Using the laboratory strain N2, we identify a novel C. elegans innate immune response specific to viral infection. A subset of these changes is driven by the RNAi response to the virus, which redirects the Argonaute protein RDE-1 from its endogenous small RNA cofactors, leading to loss of repression of endogenous RDE-1 targets. Additionally, we show that a C. elegans wild isolate, JU1580, has a distinct gene expression signature in response to viral infection. This is associated with a reduction in microRNA (miRNA) levels and an up-regulation of their target genes. Intriguingly, alterations in miRNA levels upon JU1580 infection are associated with a transformation of the antiviral transcriptional response into an antibacterial-like response. Together our data support a model whereby antiviral RNAi competes with endogenous small RNA pathways, causing widespread transcriptional changes. This provides an elegant mechanism for C. elegans to orchestrate its antiviral response, which may have significance for the relationship between small RNA pathways and immune regulation in other organisms.

Erbium-doped yttrium aluminium garnet ablative laser treatment for endogenous ochronosis.

Science.gov (United States)

Chaptini, Cassandra; Huilgol, Shyamala C

2015-08-01

Ochronosis is a rare disease characterised clinically by bluish-grey skin discolouration and histologically by yellow-brown pigment deposits in the dermis. It occurs in endogenous and exogenous forms. Endogenous ochronosis, also known as alkaptonuria, is an autosomal recessive disease of tyrosine metabolism, resulting in the accumulation and deposition of homogentisic acid in connective tissue. We report a case of facial endogenous ochronosis and coexistent photodamage, which was successfully treated with erbium-doped yttrium aluminium garnet laser resurfacing and deep focal point treatment to remove areas of residual deep pigment. © 2014 The Australasian College of Dermatologists.

The Influence of Endogenous and Exogenous Spatial Attention on Decision Confidence.

Science.gov (United States)

Kurtz, Phillipp; Shapcott, Katharine A; Kaiser, Jochen; Schmiedt, Joscha T; Schmid, Michael C

2017-07-25

Spatial attention allows us to make more accurate decisions about events in our environment. Decision confidence is thought to be intimately linked to the decision making process as confidence ratings are tightly coupled to decision accuracy. While both spatial attention and decision confidence have been subjected to extensive research, surprisingly little is known about the interaction between these two processes. Since attention increases performance it might be expected that confidence would also increase. However, two studies investigating the effects of endogenous attention on decision confidence found contradictory results. Here we investigated the effects of two distinct forms of spatial attention on decision confidence; endogenous attention and exogenous attention. We used an orientation-matching task, comparing the two attention conditions (endogenous and exogenous) to a control condition without directed attention. Participants performed better under both attention conditions than in the control condition. Higher confidence ratings than the control condition were found under endogenous attention but not under exogenous attention. This finding suggests that while attention can increase confidence ratings, it must be voluntarily deployed for this increase to take place. We discuss possible implications of this relative overconfidence found only during endogenous attention with respect to the theoretical background of decision confidence.

Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

Science.gov (United States)

Paterson, Louise M; Tyacke, Robin J; Nutt, David J; Knudsen, Gitte M

2010-01-01

Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron emission tomography, but has not yet been adequately extended to other neurotransmitter systems. This review focuses on how the technique has been applied to the study of the 5-hydroxytryptamine (5-HT) system. The principles behind visualising fluctuations in neurotransmitters are introduced, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT1A, 5-HT2A, and 5-HT4 receptors and the serotonin reuptake transporter have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made as to how the selection of targets, radiotracers, challenge paradigms, and experimental design might be optimised to improve our chances of successfully imaging endogenous neurotransmitters in the future. PMID:20664611

Microbial endogenous response to acute inhibitory impact of antibiotics.

Science.gov (United States)

Pala-Ozkok, I; Kor-Bicakci, G; Çokgör, E U; Jonas, D; Orhon, D

2017-06-13

Enhanced endogenous respiration was observed as the significant/main response of the aerobic microbial culture under pulse exposure to antibiotics: sulfamethoxazole, tetracycline and erythromycin. Peptone mixture and acetate were selected as organic substrates to compare the effect of complex and simple substrates. Experiments were conducted with microbial cultures acclimated to different sludge ages of 10 and 2 days, to visualize the effect of culture history. Evaluation relied on modeling of oxygen uptake rate profiles, reflecting the effect of all biochemical reactions associated with substrate utilization. Model calibration exhibited significant increase in values of endogenous respiration rate coefficient with all antibiotic doses. Enhancement of endogenous respiration was different with antibiotic type and initial dose. Results showed that both peptone mixture and acetate cultures harbored resistance genes against the tested antibiotics, which suggests that biomass spends cellular maintenance energy for activating the required antibiotic resistance mechanisms to survive, supporting higher endogenous decay rates. [Formula: see text]: maximum growth rate for X H (day -1 ); K S : half saturation constant for growth of X H (mg COD/L); b H : endogenous decay rate for X H (day -1 ); k h : maximum hydrolysis rate for S H1 (day -1 ); K X : hydrolysis half saturation constant for S H1 (mg COD/L); k hx : maximum hydrolysis rate for X S1 (day -1 ); K XX : hydrolysis half saturation constant for X S1 (mg COD/L); k STO : maximum storage rate of PHA by X H (day -1 ); [Formula: see text]: maximum growth rate on PHA for X H (day -1 ); K STO : half saturation constant for storage of PHA by X H (mg COD/L); X H1 : initial active biomass (mg COD/L).

Endogenous phosphorus excretion by sheep fed hydrolyzed sugarcane bagasse, lucerne hay and citrus pulp

International Nuclear Information System (INIS)

Dias, R.S.; Roque, A.P.; Vitti, D.M.S.S.

2006-01-01

The objective of this study was to determine endogenous phosphorus excretion in sheep fed with different diets. Sixteen male growing sheep, received a basic diet with: 42% hydrolyzed sugarcane bagasse (HSB), 45% lucerne hay (LH) plus 14% hydrolyzed sugarcane bagasse, and 30% citrus pulp (CTP) plus 40% hydrolyzed sugarcane bagasse. A dose of 7.7 MBq 32 P was injected into the left jugular vein of each animal. The P endogenous fecal losses were: 1.69, 2.50, 2.33 and 1.45 g/animal for treatments HSB, LH, and CTP respectively (P>0.05). The type of diet influenced slight endogenous P excretion but altered excretion of P in urine. Endogenous P excreted in feces (P F ) comes mainly from saliva and represents an important loss of P. The estimation of net requirements of phosphorus (P) for ruminants includes endogenous losses, which is also essential for calculating true absorption of this mineral. Physical structure of the feed may influence endogenous losses, altering the metabolism of P and also the demand of this mineral, therefore being important to know how different feeds affect endogenous P losses. (author)

Multi-spectral endogenous fluorescence imaging for bacterial differentiation

Science.gov (United States)

Chernomyrdin, Nikita V.; Babayants, Margarita V.; Korotkov, Oleg V.; Kudrin, Konstantin G.; Rimskaya, Elena N.; Shikunova, Irina A.; Kurlov, Vladimir N.; Cherkasova, Olga P.; Komandin, Gennady A.; Reshetov, Igor V.; Zaytsev, Kirill I.

2017-07-01

In this paper, the multi-spectral endogenous fluorescence imaging was implemented for bacterial differentiation. The fluorescence imaging was performed using a digital camera equipped with a set of visual bandpass filters. Narrowband 365 nm ultraviolet radiation passed through a beam homogenizer was used to excite the sample fluorescence. In order to increase a signal-to-noise ratio and suppress a non-fluorescence background in images, the intensity of the UV excitation was modulated using a mechanical chopper. The principal components were introduced for differentiating the samples of bacteria based on the multi-spectral endogenous fluorescence images.

Exogenous vs. Endogenous Separation

OpenAIRE

Ramey, Garey

2008-01-01

This paper assesses how various approaches to modelling the separation margin a¤ect the ability of the Mortensen-Pissarides job matching model to explain key facts about the aggregate labor market. Allowing for realistic time variation in the separation rate, whether exogenous or endogenous, greatly in- creases the unemployment variability generated by the model. Speci…cations with exogenous separation rates, whether constant or time-varying, fail to pro- duce realistic volatility and prod...

Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling.

Science.gov (United States)

Delvendahl, Igor; Jablonski, Lukasz; Baade, Carolin; Matveev, Victor; Neher, Erwin; Hallermann, Stefan

2015-06-09

Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca(2+) signals, which are confined in their spatiotemporal extent by endogenous Ca(2+) buffers. However, it remains elusive how rapid and reliable Ca(2+) signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca(2+) imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca(2+)-binding ratio (∼ 15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca(2+) from the active zone during repetitive firing. Measuring Ca(2+) signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca(2+) buffering enables fast active zone Ca(2+) signaling, suggesting that the strength of endogenous Ca(2+) buffering limits the rate of synchronous synaptic transmission.

Endogenous α-crystallin inhibits expression of caspase-3 induced by hypoxia in retinal neurons.

Science.gov (United States)

Ying, Xi; Peng, Yanli; Zhang, Jiaping; Wang, Xingli; Wu, Nan; Zeng, Yuxiao; Wang, Yi

2014-08-28

To investigate the expression of endogenous, hypoxic stress-induced α-crystallin and caspase-3 in rat retinal neurons in vitro. Retinal neurons were cultured from Long-Evans rats. The expression of endogenous α-crystallin was analyzed by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Furthermore, hypoxic exposure was performed in cultured cells, and the expression of endogenous α-crystallin and caspase-3 was assayed by Western blotting. Positive α-crystallin staining was observed in cultured retinal neurons, and expression of endogenous α-crystallin mRNA peaked 3-5d after inoculation (Pendogenous, hypoxic stress-induced α-crystallin expression increased gradually, peaking 6h after hypoxia. The expression was more abundant compared to the control (Pendogenous α-crystallin in retinal neurons, especially over-expression induced by hypoxic stress, results in the down regulation of caspase-3. The data suggest that endogenous α-crystallin may act as an endogenous neuroprotective factor in retinal neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

Cinnamaldehyde promotes root branching by regulating endogenous hydrogen sulfide.

Science.gov (United States)

Xue, Yan-Feng; Zhang, Meng; Qi, Zhong-Qiang; Li, You-Qin; Shi, Zhiqi; Chen, Jian

2016-02-01

Cinnamaldehyde (CA) has been widely applied in medicine and food preservation. However, whether and how CA regulates plant physiology is largely unknown. To address these gaps, the present study investigated the beneficial effect of CA on root branching and its possible biochemical mechanism. The lateral root (LR) formation of pepper seedlings could be markedly induced by CA at specific concentrations without any inhibitory effect on primary root (PR) growth. CA could induce the generation of endogenous hydrogen sulfide (H2S) by increasing the activity of L-cysteine desulfhydrase in roots. By fluorescently tracking endogenous H2S in situ, it could be clearly observed that H2S accumulated in the outer layer cells of the PR where LRs emerge. Sodium hydrosulfide (H2S donor) treatment induced LR formation, while hypotaurine (H2S scavenger) showed an adverse effect. The addition of hypotaurine mitigated the CA-induced increase in endogenous H2S level, which in turn counteracted the inducible effect of CA on LR formation. CA showed great potential in promoting LR formation, which was mediated by endogenous H2S. These results not only shed new light on the application of CA in agriculture but also extend the knowledge of H2S signaling in the regulation of root branching. © 2015 Society of Chemical Industry.

Endogenous mitigation of H2S inside of the landfills.

Science.gov (United States)

Fang, Yuan; Zhong, Zhong; Shen, Dongsheng; Du, Yao; Xu, Jing; Long, Yuyang

2016-02-01

Vast quantities of hydrogen sulfide (H2S) emitted from landfill sites require urgent disposal. The current study focused on source control and examined the migration and conversion behavior of sulfur compounds in two lab-scale simulated landfills with different operation modes. It aimed to explore the possible strategies and mechanisms for H2S endogenous mitigation inside of landfills during decomposition. It was found that the strength of H2S emissions from the landfill sites was dependent on the municipal solid waste (MSW) degradation speed and vertical distribution of sulfide. Leachate recirculation can shorten both the H2S influence period and pollution risk to the surrounding environment. H2S endogenous mitigation may be achieved by chemical oxidation, biological oxidation, adsorption, and/or precipitation in different stages. Migration and conversion mainly affected H2S release behavior during the initial stabilization phase in the landfill. Microbial activities related to sulfur, nitrogen, and iron can further promote H2S endogenous mitigation during the high reducing phase. Thus, H2S endogenous mitigation can be effectively enhanced via control of the aforementioned processes.

Endogenous Quality Effects of Trade Policy

NARCIS (Netherlands)

J.L. Moraga-Gonzalez (José Luis); J.M.A. Viaene (Jean-Marie)

1999-01-01

textabstractWe study the optimal trade policy against a foreign oligopoly with endogenous quality. We show that, under the Most Favoured Nation (MFN) clause, a uniform tariff policy is always welfare improving over the free trade equilibrium. However, a nonuniform tariff policy is always desirable

Conditions for Effective Application of Analysis of Symmetrically-Predicted Endogenous Subgroups

Science.gov (United States)

Peck, Laura R.

2015-01-01

Several analytic strategies exist for opening up the "black box" to reveal more about what drives policy and program impacts. This article focuses on one of these strategies: the Analysis of Symmetrically-Predicted Endogenous Subgroups (ASPES). ASPES uses exogenous baseline data to identify endogenously-defined subgroups, keeping the…

Human-Specific Endogenous Retroviruses

Directory of Open Access Journals (Sweden)

Anton Buzdin

2007-01-01

Full Text Available This review focuses on a small family of human-specific genomic repetitive elements, presented by 134 members that shaped ~330 kb of the human DNA. Although modest in terms of its copy number, this group appeared to modify the human genome activity by endogenizing ~50 functional copies of viral genes that may have important implications in the immune response, cancer progression, and antiretroviral host defense. A total of 134 potential promoters and enhancers have been added to the human DNA, about 50% of them in the close gene vicinity and 22% in gene introns. For 60 such human-specific promoters, their activity was confirmed by in vivo assays, with the transcriptional level varying ~1000-fold from hardly detectable to as high as ~3% of β-actin transcript level. New polyadenylation signals have been provided to four human RNAs, and a number of potential antisense regulators of known human genes appeared due to human-specific retroviral insertional activity. This information is given here in the context of other major genomic changes underlining differences between human and chimpanzee DNAs. Finally, a comprehensive database, is available for download, of human-specific and polymorphic endogenous retroviruses is presented, which encompasses the data on their genomic localization, primary structure, encoded viral genes, human gene neighborhood, transcriptional activity, and methylation status.

Endogenous Money, Output and Prices in India

OpenAIRE

Das, Rituparna

2009-01-01

This paper proposes to quantify the macroeconometric relationships among the variables broad money, lending by banks, price, and output in India using simultaneous equations system keeping in view the issue of endogeneity.

Does liver-intestine significantly degrade circulating endogenous substance P in man?

DEFF Research Database (Denmark)

Henriksen, Jens Henrik Sahl; Schaffalitzky de Muckadell, O B; Bülow, J B

1986-01-01

Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P was determi......Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P....... The results indicate that degradation of circulating endogenous substance P in man is not confined to liver-intestine or kidney but may take place in many tissues....

Measurement of endogenous allergens in genetically modified soybeans--short communication.

Science.gov (United States)

Ladics, Gregory S; Budziszewski, Gregory J; Herman, Rod A; Herouet-Guicheney, Corinne; Joshi, Saurabh; Lipscomb, Elizabeth A; McClain, Scott; Ward, Jason M

2014-10-01

The measurement of endogenous allergens is required by the European Commission (EC) as part of the compositional analysis for GM products from host plants that are common causes of food allergy, such as soybean (EC Implementing Regulation No. 503/2013). In each case, the EC Implementing Regulation indicates that analysis be conducted on identified allergens as specified in the Organization of Economic Cooperation and Development (OECD) consensus documents on compositional considerations for new plant varieties. This communication discusses the methods available to measure endogenous allergens as well as the endogenous soybean allergens that should be analyzed. It is suggested herein that in conjunction with the 2012 OECD consensus document on soybean, any list of soybean allergens should be based on clinically relevant data among publicly available allergen databases and peer-reviewed scientific publications, and the ability to measure the identified allergen. Based on a detailed analysis of the scientific literature, the following key points are recommended: (1) the acceptance of serum-free, quantitative analytical method data as an alternative to traditional IgE reactivity qualitative or semi-quantitative data for evaluation of endogenous soybean allergen content; (2) eight of the 15 potential allergens listed in the OECD soybean consensus document (Gly m 3, Gly m 4, Gly m Bd28K, Gly m Bd30K, Gly m 5, Gly m 6, Gly m 8, and Kunitz trypsin inhibitor) have both appropriate supporting clinical data and sufficient sequence information to be evaluated in comparative endogenous soybean allergen studies; and (3) the remaining seven proteins (Gly m 1, Gly m 2, unknown 50kDa protein, unknown 39kDa protein, P-22-25, lipoxygenase and lectin) lack sufficient data for clear classification as confirmed allergens and/or available sequence information and should not be currently included in the measurement of endogenous soybean allergens in the compositional analysis for the EU

Endogenous subclinical hyperthyroidism and cardiovascular system: time to reconsider?

Science.gov (United States)

Patanè, Salvatore; Marte, Filippo; Sturiale, Mauro

2011-05-19

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. Exogenous sublinical hyperthyroidism is a thyroid metabolic state caused by L-thyroxine administration. Endogenous subclinical hyperthyroidism is a thyroid metabolic state in patients with autonomously functioning thyroid nodule or multinodular goiter, various forms of thyroiditis, in areas with endemic goiter and particularly in elderly subjects. Endogenous subclinical hyperthyroidism is currently the subject of numerous studies and it yet remains controversial particularly as it relates to its treatment and to cardiovascular impact nevertheless established effects have been demonstrated. Recently, acute myocardial infarction without significant coronary stenoses and recurrent acute pulmonary embolism have been reported associated with subclinical hyperthyroidism without L-thyroxine administration. So, it is very important to recognize and to treat promptly also endogenous subclinical hyperthyroidism. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

The Deacetylase HDAC6 Mediates Endogenous Neuritic Tau Pathology

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Jui-Heng Tseng

2017-08-01

Full Text Available The initiating events that promote tau mislocalization and pathology in Alzheimer’s disease (AD are not well defined, partly because of the lack of endogenous models that recapitulate tau dysfunction. We exposed wild-type neurons to a neuroinflammatory trigger and examined the effect on endogenous tau. We found that tau re-localized and accumulated within pathological neuritic foci, or beads, comprised of mostly hypo-phosphorylated, acetylated, and oligomeric tau. These structures were detected in aged wild-type mice and were enhanced in response to neuroinflammation in vivo, highlighting a previously undescribed endogenous age-related tau pathology. Strikingly, deletion or inhibition of the cytoplasmic shuttling factor HDAC6 suppressed neuritic tau bead formation in neurons and mice. Using mass spectrometry-based profiling, we identified a single neuroinflammatory factor, the metalloproteinase MMP-9, as a mediator of neuritic tau beading. Thus, our study uncovers a link between neuroinflammation and neuritic tau beading as a potential early-stage pathogenic mechanism in AD.

Endogenous Circadian Regulation of Pro-inflammatory Cytokines and Chemokines in the Presence of Bacterial Lipopolysaccharide in Humans

Science.gov (United States)

Rahman, Shadab A.; Castanon-Cervantes, Oscar; Scheer, Frank A.J.L.; Shea, Steven A.; Czeisler, Charles A.; Davidson, Alec J.; Lockley, Steven W.

2015-01-01

Various aspects of immune response exhibit 24-hour variations suggesting that infection susceptibility and treatment efficacy may vary by time of day. Whether these 24-hour variations are endogenous or evoked by changes in environmental or behavioral conditions is not known. We assessed the endogenous circadian control and environmental and behavioral influences on ex-vivo lipopolysaccharide stimulation of whole blood in thirteen healthy participants under 48 hours of baseline conditions with standard sleep-wake schedules and 40–50 hours of constant environmental and behavioral (constant routine; CR) conditions. Significant 24-hour rhythms were observed under baseline conditions in Monocyte Chemotactic Protein, Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin 8 but not Tumor Necrosis Factor alpha whereas significant 24-hour rhythms were observed in all four immune factors under CR conditions. The rhythm amplitudes, expressed as a percentage of mean, were comparable between immune factors and across conditions. In contrast, the acrophase time (time of the fitted peak) was different between immune factors, and included daytime and nighttime peaks and changes across behavioral conditions. These results suggest that the endogenous circadian system underpins the temporal organization of immune responses in humans with additional effects of external environmental and behavioral cycles. These findings have implications for understanding the adverse effects of recurrent circadian disruption and sleep curtailment on immune function. PMID:25452149

Hume and Endogenous Money

OpenAIRE

Maria Pia Paganelli

2006-01-01

David Hume’s monetary theory has three standard yet inconsistent readings. As a forefather of the quantity theory of money, Hume sees money as neutral. As an inflationist, Hume sees an active positive role for monetary policy. As a monetarist, Hume sees an active positive role for monetary policy only in the short run. This paper reads Hume consistently instead by showing that for Hume money is endogenous and demand-driven. Hume would read the money equation in terms of reverse causation and ...

[Protective effects of endogenous carbon monoxide against myocardial ischemia-reperfusion injury in rats].

Science.gov (United States)

Zhou, Zhen; Ma, Shuang; Liu, Jie; Ji, Qiao-Rong; Cao, Cheng-Zhu; Li, Xiao-Na; Tang, Feng; Zhang, Wei

2018-04-25

The present study is aimed to explore the effects of endogenous carbon monoxide on the ischemia-reperfusion in rats. Wistar rats were intraperitoneally injected with protoporphyrin cobalt chloride (CoPP, an endogenous carbon monoxide agonist, 5 mg/kg), zinc protoporphyrin (ZnPP, an endogenous carbon monoxide inhibitor, 5 mg/kg) or saline. Twenty-four hours after injection, the myocardial ischemia-reperfusion model was made by Langendorff isolated cardiac perfusion system, and cardiac function parameters were collected. Myocardial cGMP content was measured by ELISA, and the endogenous carbon monoxide in plasma and myocardial enzymes in perfusate at 10 min after reperfusion were measured by colorimetry. The results showed that before ischemia the cardiac functions of CoPP, ZnPP and control groups were stable, and there were no significant differences. After reperfusion, cardiac functions had significant differences among the three groups (P endogenous carbon monoxide can maintain cardiac function, shorten the time of cardiac function recovery, and play a protective role in cardiac ischemia-reperfusion.

Pathophysiological Features of Endogenous Intoxication in Pregnant Women with Arterial Hypertension

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N. V. Kabanova

2008-01-01

Full Text Available Objective: to determine the nature and specific features of development of endogenous intoxication in pregnant women with arterial hypertension. Subjects and materials. Humoral extracellular fluid volume regulation, partial renal functions, placental hormonal function, membranous lipid peroxidation activity, antiradical defense, the parameters of central hemodynamics, endogenous intoxication, and a biochemical coagulogram were studied and differential blood count with the leukocytic ratio indices was estimated in 172 pregnant females with arterial hypertension and 54 healthy pregnant ones in the third trimester. The statistical package «Stadia» was applied. Results. Arterial hypertension caused by pregnancy was ascertained to involve pathogenetically different types: low-, normal-, and high-renin ones. In pregnant women with arterial hypertension, the general pathogenetic homeostatic changes were placental hormonal imbalance, activated membranous lipid peroxidation, impaired lymph outflow, sodium and water retention, hepatic and renal failure, and endogenous intoxication. Conclusion. Placental ischemia appearing as placental hormonal imbalance (extrarenal pressor system was accompanied by a compensatory humoral response: arterial hypertension and metabolic disturbances. Changes in medium-weight molecule 280, leukocytic intoxication index, erythrocytic sorption capacity, and Paramecium test, by confirming the presence of endogenous intoxication in pregnant females with arterial hypertension, were caused by a type of arterial hypertension (by the hemodynamic profile and the type of impaired partial renal functions. Key words: pregnancy, arterial hypertension, endogenous intoxication.

Viral and cellular requirements for the budding of Feline Endogenous Retrovirus RD-114

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Fukuma Aiko

2011-12-01

Full Text Available Abstract Background RD-114 virus is a feline endogenous retrovirus and produced as infectious viruses in some feline cell lines. Recently, we reported the contamination of an infectious RD-114 virus in a proportion of live attenuated vaccines for dogs and cats. It is very difficult to completely knock out the RD-114 proviruses from cells, as endogenous retroviruses are usually integrated multiply into the host genome. However, it may be possible to reduce the risk of contamination of RD-114 virus by regulating the viral release from cells. Results In this study, to understand the molecular mechanism of RD-114 virus budding, we attempted to identify the viral and cellular requirements for RD-114 virus budding. Analyses of RD-114 L-domain mutants showed that the PPPY sequence in the pp15 region of Gag plays a critical role in RD-114 virus release as viral L-domain. Furthermore, we investigated the cellular factors required for RD-114 virus budding. We demonstrated that RD-114 virus release was inhibited by overexpression of dominant negative mutants of Vps4A, Vps4B, and WWP2. Conclusions These results strongly suggest that RD-114 budding utilizes the cellular multivesicular body sorting pathway similar to many other retroviruses.

INVESTMENT EFFECTS OF ENDOGENOUS AND EXOGENOUS DEPRECIATION: IMPROVED PASTURES IN URUGUAY

OpenAIRE

Ekboir, Javier M.; Jarvis, Lovell S.; Rey, Carlos

1998-01-01

The depreciation rate for capital assets may have endogenous and exogenous components. Change in the exogenous component depends on technological change and/or environmental factors, shifts the production function, and independently affects profitability and investment. Change in the endogenous component does not. These hypotheses are tested using data on Uruguayan grass-legume pastures.

THE ROLE OF ENTEROSORBENTS IN TREATMENT OF ENDOGENOUS INTOXICATION SYNDROME

OpenAIRE

N. I. Ursova

2012-01-01

Usage of enterosorbents in treatment of almost all types of acute and chronic disorders accompanied with endogenous intoxication syndrome takes on special significance. The critical point of endogenous intoxication pathogenesis is dysfunction of microbiocenosis and intestinal barrier. The necessity of enterosorbents usage is very high due to their efficacy, safety and wide availability. Smectite dioctaedric (diosmectite), which has been successfully used in clinical practice for a long period...

Influence of endogenous pyrogen on the cerebral prostaglandin-synthetase system.

Science.gov (United States)

Ziel, R; Krupp, P

1976-11-15

The biotransformation of arachidonic acid to prostaglandins in vitro is specifically augmented by endogenous pyrogen to a degree depending on the concentration applied, providing that the microsomal fraction of the cerebral cortex is used as prostaglandin-synthetase system. This effect is inhibited by non-steroidal anti-inflammatory agents. These findings are compatible with the hypothesis that prostaglandins might act as mediators of the febrile reaction induced by endogenous pyrogen.

Endogenous Magnetic Reconnection in Solar Coronal Loops

Science.gov (United States)

Asgari-Targhi, M.; Coppi, B.; Basu, B.; Fletcher, A.; Golub, L.

2017-12-01

We propose that a magneto-thermal reconnection process occurring in coronal loops be the source of the heating of the Solar Corona [1]. In the adopted model, magnetic reconnection is associated with electron temperature gradients, anisotropic electron temperature fluctuations and plasma current density gradients [2]. The input parameters for our theoretical model are derived from the most recent observations of the Solar Corona. In addition, the relevant (endogenous) collective modes can produce high energy particle populations. An endogenous reconnection process is defined as being driven by factors internal to the region where reconnection takes place. *Sponsored in part by the U.S. D.O.E. and the Kavli Foundation* [1] Beafume, P., Coppi, B. and Golub, L., (1992) Ap. J. 393, 396. [2] Coppi, B. and Basu, B. (2017) MIT-LNS Report HEP 17/01.

Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea

International Nuclear Information System (INIS)

Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A.

1990-01-01

Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients

Vitamin D receptor–retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation

Science.gov (United States)

de la Fuente, Alerie Guzman; Errea, Oihana; van Wijngaarden, Peter; Gonzalez, Ginez A.; Kerninon, Christophe; Jarjour, Andrew A.; Lewis, Hilary J.; Jones, Clare A.; Nait-Oumesmar, Brahim; Zhao, Chao; Huang, Jeffrey K.; ffrench-Constant, Charles

2015-01-01

The mechanisms regulating differentiation of oligodendrocyte (OLG) progenitor cells (OPCs) into mature OLGs are key to understanding myelination and remyelination. Signaling via the retinoid X receptor γ (RXR-γ) has been shown to be a positive regulator of OPC differentiation. However, the nuclear receptor (NR) binding partner of RXR-γ has not been established. In this study we show that RXR-γ binds to several NRs in OPCs and OLGs, one of which is vitamin D receptor (VDR). Using pharmacological and knockdown approaches we show that RXR–VDR signaling induces OPC differentiation and that VDR agonist vitamin D enhances OPC differentiation. We also show expression of VDR in OLG lineage cells in multiple sclerosis. Our data reveal a role for vitamin D in the regenerative component of demyelinating disease and identify a new target for remyelination medicines. PMID:26644513

Evidence for endogenous opioid release in the amygdala during positive emotion.

Science.gov (United States)

Koepp, M J; Hammers, A; Lawrence, A D; Asselin, M C; Grasby, P M; Bench, C J

2009-01-01

Endogenous opioid release has been linked to relief from aversive emotional memories, thereby promoting a euphoric state and subsequent interactions towards social stimuli resulting in the formation of social preferences. However, this theory remains controversial. Using positron emission tomography and [(11)C]diprenorphine (DPN) in healthy volunteers, we found significantly reduced DPN binding to opioid receptor in the hippocampus during positive mood induction compared to neutral mood. Furthermore, the magnitude of positive mood change correlated negatively with DPN binding in the amygdala bilaterally. Our finding of reduced DPN binding is consistent with increased release of endogenous opioids, providing direct evidence that localised release of endogenous opioids is involved in the regulation of positive emotion in humans.

[Exploration of the Essence of "Endogenous Turbidity" in Chinese Medicine].

Science.gov (United States)

Fan, Xin-rong; Tang, Nong; Ji, Yun-xi; Zhang, Yao-zhong; Jiang, Li; Huang, Gui-hua; Xie, Sheng; Li, Liu-mei; Song, Chun-hui; Ling, Jiang-hong

2015-08-01

The essence of endogenous turbidity in Chinese medicine (CM) is different from cream, fat, phlegm, retention, damp, toxicity, and stasis. Along with the development of modern scientific technologies and biology, researches on the essence of endogenous turbidity should keep pace with the time. Its material bases should be defined and new connotation endowed at the microscopic level. The essence of turbidity lies in abnormal functions of zang-fu organs. Sugar, fat, protein, and other nutrient substances cannot be properly decomposed, but into semi-finished products or intermediate metabolites. They are inactive and cannot participate in normal material syntheses and decomposition. They cannot be transformed to energy metabolism, but also cannot be synthesized as executive functioning of active proteins. If they cannot be degraded by autophagy-lysosome or ubiquitin-prosome into glucose, fatty acids, amino acids, and other basic nutrients to be used again, they will accumulate inside the human body and become endogenous turbidity. Therefore, endogenous turbidity is different from final metabolites such as urea, carbon dioxide, etc., which can transform vital qi. How to improve the function of zang-fu organs, enhance its degradation by autophagy-lysosome or ubiquitin-prosome is of great significance in normal operating of zang-fu organs and preventing the emergence and progress of related diseases.

Neuronal Rat Brain Damage Caused by Endogenous and Exogenous Hyperthermia

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Mustafa Aydın

2012-03-01

Full Text Available OBJECTIVE: Hyperthermia may induce pathologic alterations within body systems and organs including brain. In this study, neuronal effects of endogenous and exogenous hyperthermia (41°C were studied in rats. METHODS: The endogenous hyperthermia (41°C was induced by lipopolysaccharide and the exogenous by an (electric heater. Possible neuronal damage was evaluated by examining healthy, apoptotic and necrotic cells, and heat shock proteins (HSP 27, HSP 70 in the cerebral cortex, cerebellum and hypothalamus RESULTS: At cellular level, when all neuronal tissues are taken into account; (i a significant increase in the necrotic cells was observed in the both groups (p0.05. CONCLUSION: The neural tissue of brain can show different degree of response to hyperthermia. But we can conclude that endogenous hyperthermia is more harmful to central nervous system than exogenous hyperthermia

Recent advances in matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) for in situ analysis of endogenous molecules in plants.

Science.gov (United States)

Qin, Liang; Zhang, Yawen; Liu, Yaqin; He, Huixin; Han, Manman; Li, Yanyan; Zeng, Maomao; Wang, Xiaodong

2018-04-17

Mass spectrometry imaging (MSI) as a label-free and powerful imaging technique enables in situ evaluation of a tissue metabolome and/or proteome, becoming increasingly popular in the detection of plant endogenous molecules. The characterization of structure and spatial information of endogenous molecules in plants are both very important aspects to better understand the physiological mechanism of plant organism. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a commonly-used tissue imaging technique, which requires matrix to assist in situ detection of a variety of molecules on the surface of a tissue section. In previous studies, MALDI-MSI was mostly used for the detection of molecules from animal tissue sections, compared to plant samples due to cell structural limitations, such as plant cuticles, epicuticular waxes, and cell walls. Despite the enormous progress that has been made in tissue imaging, there is still a challenge for MALDI-MSI suitable for the imaging of endogenous compounds in plants. This review summarises the recent advances in MALDI-MSI, focusing on the application of in situ detection of endogenous molecules in different plant organs, i.e. root, stem, leaf, flower, fruit, and seed. Further improvements on instrumentation sensitivity, matrix selection, image processing and sample preparation will expand the application of MALDI-MSI in plant research. Copyright © 2018 John Wiley & Sons, Ltd.

Immigration, Endogenous Technology Adoption and Wages

NARCIS (Netherlands)

Ray Chaudhuri, A.; Pandey, Manish

2015-01-01

We document that immigration to U.S. states has increased the mass of workers at the lower range of the skill distribution. We use this change in skill distribution of workers to analyze the effect of immigration on wages. Our model allows firms to endogenously respond to the immigration-induced

MODELS OF AN-TYPE INNOVATIVE ENDOGENOUS GROWTH AND THEIR SUBSTANTIATION

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Askar A. Akaev

2015-01-01

Full Text Available The article presents an analysis of some classical models of economic growth of exogenous and endogenous type, based on the calculation of the motion of physical capital. It is shown that the simplest AN-type model, based on the calculation of population dynamics and endogenous technological progress, is more adequate for the description of the current economic development and provides a more accurate long-term forecast of economic dynamics.

A Reformulation of Normative Economics for Models with Endogenous Preferences

OpenAIRE

Vipul Bhatt; Masao Ogaki; Yuichi Yaguchi

2014-01-01

This paper proposes a framework to balance considerations of welfarism and virtue ethics in the normative analysis of economic models with endogenous preferences. We introduce the moral evaluation function (MEF), which ranks alternatives based purely on virtue ethics, and define the social objective function (SOF), which combines the Social Welfare Function (SWF) and the MEF. In a model of intergenerational altruism with endogenous time preference, using numerical simulations we show that max...

Endogenously and exogenously driven selective sustained attention: Contributions to learning in kindergarten children.

Science.gov (United States)

Erickson, Lucy C; Thiessen, Erik D; Godwin, Karrie E; Dickerson, John P; Fisher, Anna V

2015-10-01

Selective sustained attention is vital for higher order cognition. Although endogenous and exogenous factors influence selective sustained attention, assessment of the degree to which these factors influence performance and learning is often challenging. We report findings from the Track-It task, a paradigm that aims to assess the contribution of endogenous and exogenous factors to selective sustained attention within the same task. Behavioral accuracy and eye-tracking data on the Track-It task were correlated with performance on an explicit learning task. Behavioral accuracy and fixations to distractors during the Track-It task did not predict learning when exogenous factors supported selective sustained attention. In contrast, when endogenous factors supported selective sustained attention, fixations to distractors were negatively correlated with learning. Similarly, when endogenous factors supported selective sustained attention, higher behavioral accuracy was correlated with greater learning. These findings suggest that endogenously and exogenously driven selective sustained attention, as measured through different conditions of the Track-It task, may support different kinds of learning. Copyright © 2015 Elsevier Inc. All rights reserved.

DMPD: Endogenous anti-inflammatory substances, inter-alpha-inhibitor and bikunin. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17132099 Endogenous anti-inflammatory substances, inter-alpha-inhibitor and bikunin.... Kobayashi H. Biol Chem. 2006 Dec;387(12):1545-9. (.png) (.svg) (.html) (.csml) Show Endogenous anti-inflam...matory substances, inter-alpha-inhibitor and bikunin. PubmedID 17132099 Title Endogenous anti-inflammatory s

Structural classification of endogenous regulatory oligopeptides.

Science.gov (United States)

Zamyatnin, A A

1991-07-01

Based on the criteria of 50% identity in the amino acid sequence, a new method for grouping endogenous regulatory oligopeptides into structural families is presented. Data from the EROP-Moscow data bank on 579 oligopeptides fitting a preset spectrum of functional activities revealed 73 structural oligopeptide groups, 36 of which were called families.

The Endogenous Feedback Network

DEFF Research Database (Denmark)

Augustenborg, Claudia Carrara

2010-01-01

proposals, it will first be considered the extents of their reciprocal compatibility, tentatively shaping an integrated, theoretical profile of consciousness. A new theory, the Endogenous Feedback Network (EFN) will consequently be introduced which, beside being able to accommodate the main tenets...... of the reviewed theories, appears able to compensate for the explanatory gaps they leave behind. The EFN proposes consciousness as the phenomenon emerging from a distinct network of neural paths broadcasting the neural changes associated to any mental process. It additionally argues for the need to include a 5th...

Endogenous neurogenesis in the human brain following cerebral infarction.

Science.gov (United States)

Minger, Stephen L; Ekonomou, Antigoni; Carta, Eloisa M; Chinoy, Amish; Perry, Robert H; Ballard, Clive G

2007-01-01

Increased endogenous neurogenesis has a significant regenerative role in many experimental models of cerebrovascular diseases, but there have been very few studies in humans. We therefore examined whether there was evidence of altered endogenous neurogenesis in an 84-year-old patient who suffered a cerebrovascular accident 1 week prior to death. Using antibodies that specifically label neural stem/neural progenitor cells, we examined the presence of immunopositive cells around and distant from the infarcted area, and compared this with a control, age-matched individual. Interestingly, a large number of neural stem cells, vascular endothelial growth factor-immunopositive cells and new blood vessels were observed only around the region of infarction, and none in the corresponding brain areas of the healthy control. In addition, an increased number of neural stem cells was observed in the neurogenic region of the lateral ventricle wall. Our results suggest increased endogenous neurogenesis associated with neovascularization and migration of newly-formed cells towards a region of cerebrovascular damage in the adult human brain and highlight possible mechanisms underlying this process.

Endogenous technological and demographic change under increasing water scarcity

Science.gov (United States)

Pande, Saket; Ertsen, Maurits; Sivapalan, Murugesu

2014-05-01

The ancient civilization in the Indus Valley civilization dispersed under extreme dry conditions; there are indications that the same holds for many other ancient societies. Even contemporary societies, such as the one in Murrumbidgee river basin in Australia, have started to witness a decline in overall population under increasing water scarcity. Hydroclimatic change may not be the sole predictor of the fate of contemporary societies in water scarce regions and many critics of such (perceived) hydroclimatic determinism have suggested that technological change may ameliorate the effects of increasing water scarcity and as such counter the effects of hydroclimatic changes. To study the role of technological change on the dynamics of coupled human-water systems, we develop a simple overlapping-generations model of endogenous technological and demographic change. We model technological change as an endogenous process that depends on factors such as the investments that are (endogenously) made in a society, the (endogenous) diversification of a society into skilled and unskilled workers, a society's patience in terms of its present consumption vs. future consumption, production technology and the (endogenous) interaction of all of these factors. In the model the population growth rate is programmed to decline once consumption per capita crosses a "survival" threshold. This means we do not treat technology as an exogenous random sequence of events, but instead assume that it results (endogenously) from societal actions. The model demonstrates that technological change may indeed ameliorate the effects of increasing water scarcity but typically it does so only to a certain extent. It is possible that technological change may allow a society to escape the effect of increasing water scarcity, leading to a (super)-exponential rise in technology and population. However, such cases require the rate of success of investment in technological advancement to be high. In other

Endogenous technological and population change under increasing water scarcity

Science.gov (United States)

Pande, S.; Ertsen, M.; Sivapalan, M.

2013-11-01

The ancient civilization in the Indus Valley civilization dispersed under extreme dry conditions; there are indications that the same holds for many other ancient societies. Even contemporary societies, such as the one in Murrumbidgee river basin in Australia, have started to witness a decline in overall population under increasing water scarcity. Hydroclimatic change may not be the sole predictor of the fate of contemporary societies in water scarce regions and many critics of such (perceived) hydroclimatic determinism have suggested that technological change may ameliorate the effects of increasing water scarcity and as such counter the effects of hydroclimatic changes. To study the role of technological change on the dynamics of coupled human-water systems, we develop a simple overlapping-generations model of endogenous technological and demographic change. We model technological change as an endogenous process that depends on factors such as the investments that are (endogenously) made in a society, the (endogenous) diversification of a society into skilled and unskilled workers, a society's patience in terms of its present consumption vs. future consumption, production technology and the (endogenous) interaction of all of these factors. In the model the population growth rate is programmed to decline once consumption per capita crosses a "survival" threshold. This means we do not treat technology as an exogenous random sequence of events, but instead assume that it results (endogenously) from societal actions. The model demonstrates that technological change may indeed ameliorate the effects of increasing water scarcity but typically it does so only to a certain extent. It is possible that technological change may allow a society to escape the effect of increasing water scarcity, leading to a (super)-exponential rise in technology and population. However, such cases require the rate of success of investment in technological advancement to be high. In other

The Different Effects Of Endogenous And Exogenous Sex Hormones On Cerebrovascular Diseases

Directory of Open Access Journals (Sweden)

Mehdi Shafiee Sabet

2017-02-01

infarct volume in acyclic females, which could be due to decreased availability of IGF-1, a neuroprotectant which decreases with advancing age and is down-regulated by estrogen treatment. A wealth of experimental evidence supports the neuroprotective properties of progesterone, and associated metabolites, following various types of central nervous system injury. In particular, for ischemic stroke, studies have also begun to reveal possible mechanisms of such neuroprotection. Conclusion: In conclusion, sex hormones have major roles in sex dimorphism in ischemic stroke. As the debate on the effects of sex hormones continues, understanding the minutie of the implication of them becomes increasingly important. An understanding of the effects of endogenous and exogenous estrogens on cerebral hemodynamics could guide research into explaining how sex hormones have paradoxical outcomes in ischemic events in men and women.

Role of endogenous serotonin in the mechanism of action of radioprotective substances

International Nuclear Information System (INIS)

Konstantinova, M.M.; Nekrasova, I.V.; Gusareva, Eh.V.; Dontsova, G.V.

1978-01-01

A study is made of a correlation between radiomodifying activity of noradrenaline (NA), N-ethylmaleimide (NEM) and a combination of these agents and their effect on the content of endogenous serotonin in cells of Ehrlich's ascites tumor and E. coli B. There is no uniformity in the response of different cells and uniform direction of the changes in their radioresistance and endogenous serotonin content both under the effect of the substances (NA and NEM) given separately and under a combined effect of the protector and the agent, which removes the protective effect or prevents realization of the latter (NEM). This enables us to arrive at a conclusion that endogenous serotonin is not the only factor responsible for the radioprotective effect of the protective substances. At the same time, it is not excluded that endogenous serotonin is involved in the chain of reactions which are necessary for the radioprotective effect to come into play

Endogenous and recombinant type I interferons and disease activity in multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, Finn; Krakauer, Martin; Limborg, Signe

2012-01-01

the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion......Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-ß lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship...... with endogenous type I IFN-like activity, the effect of IFN-ß therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells...

Endogen endoftalmitis som første kliniske manifestation af aortaklapendokarditis

DEFF Research Database (Denmark)

Rudbæk, Torsten; Haastrup, Peter; Frydkjær-Olsen, Ulrik

2012-01-01

Infectious endocarditis is considered one of the most severe infections in the Western world. Complications include septic embolism, for example to the brain or the eye. Endogeneous endophthalmitis is a rare but severe eye disease. It is important to remember that clinical signs from the eye can...... be the first manifestation of systemic disease. We present a case report of an 81-year-old woman with endogenous endophthalmitis as the first clinical manifestation of infectious endocarditis....

Breastfeeding and the risk of childhood asthma: A two-stage instrumental variable analysis to address endogeneity.

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Sharma, Nivita D

2017-09-01

Several explanations for the inconsistent results on the effects of breastfeeding on childhood asthma have been suggested. The purpose of this study was to investigate one unexplored explanation, which is the presence of a potential endogenous relationship between breastfeeding and childhood asthma. Endogeneity exists when an explanatory variable is correlated with the error term for reasons such as selection bias, reverse causality, and unmeasured confounders. Unadjusted endogeneity will bias the effect of breastfeeding on childhood asthma. To investigate potential endogeneity, a cross-sectional study of breastfeeding practices and incidence of childhood asthma in 87 pediatric patients in Georgia, the USA, was conducted using generalized linear modeling and a two-stage instrumental variable analysis. First, the relationship between breastfeeding and childhood asthma was analyzed without considering endogeneity. Second, tests for presence of endogeneity were performed and having detected endogeneity between breastfeeding and childhood asthma, a two-stage instrumental variable analysis was performed. The first stage of this analysis estimated the duration of breastfeeding and the second-stage estimated the risk of childhood asthma. When endogeneity was not taken into account, duration of breastfeeding was found to significantly increase the risk of childhood asthma (relative risk ratio [RR]=2.020, 95% confidence interval [CI]: [1.143-3.570]). After adjusting for endogeneity, duration of breastfeeding significantly reduced the risk of childhood asthma (RR=0.003, 95% CI: [0.000-0.240]). The findings suggest that researchers should consider evaluating how the presence of endogeneity could affect the relationship between duration of breastfeeding and the risk of childhood asthma. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Regulatory effect of triiodothyronine on brain myelination and astrogliosis after cuprizone-induced demyelination in mice.

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Zendedel, Adib; Kashani, Iraj Ragerdi; Azimzadeh, Maryam; Pasbakhsh, Parichehr; Omidi, Negar; Golestani, Abolfazl; Beyer, Cordian; Clarner, Tim

2016-04-01

Chronic demyelination and plaque formation in multiple sclerosis is accompanied by persisting astrogliosis, negatively influencing central nervous system recovery and remyelination. Triiodothyronin (T3) is thought to enhance remyelination in the adult brain by the induction of oligodendrocyte maturation. We investigated additional astrocyte-mediated mechanisms by which T3 might promote remyelination in chronically demyelinated lesions using the cuprizone mouse model. C57BL/6 mice were fed cuprizone for 12 weeks to induce lesions with an impaired remyelination capacity. While the expression of oligodenrocyte progenitor markers, i.e., platelet derived growth factor-α receptor was not affected by T3 administration, myelination status, myelin protein expression as well as total and adult oligodendrocyte numbers were markedly increased compared to cuprizone treated controls. In addition to these effects on oligodendrocyte numbers and function, astrogliosis but not microgliosis was ameliorated by T3 administration. Intermediate filament proteins vimentin and nestin as well as the extracellular matrix component tenascin C were significantly reduced after T3 exposure, indicating additional effects of T3 on astrocytes and astrogliosis. Our data clearly indicate that T3 promotes remyelination in chronic lesions by both enhancing oligodendrocyte maturation and attenuating astrogliosis.

Clinical breath analysis: Discriminating between human endogenous compounds and exogenous (environmental) chemical confounders

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Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous ...

A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells

Science.gov (United States)

Nüske, Stefan; Scholz, Armin M.; Bogner, Jacqueline; Ruf, Benjamin; Zolghadr, Kourosh; Drexler, Sophie E.; Drexler, Guido A.; Girst, Stefanie; Greubel, Christoph; Reindl, Judith; Siebenwirth, Christian; Romer, Tina; Friedl, Anna A.; Rothbauer, Ulrich

2016-01-01

Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa), termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair. PMID:26950694

A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells.

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Andrea Buchfellner

Full Text Available Poly(ADP-ribose polymerase 1 (PARP1 is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa, termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair.

A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells.

Science.gov (United States)

Buchfellner, Andrea; Yurlova, Larisa; Nüske, Stefan; Scholz, Armin M; Bogner, Jacqueline; Ruf, Benjamin; Zolghadr, Kourosh; Drexler, Sophie E; Drexler, Guido A; Girst, Stefanie; Greubel, Christoph; Reindl, Judith; Siebenwirth, Christian; Romer, Tina; Friedl, Anna A; Rothbauer, Ulrich

2016-01-01

Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa), termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair.

Endogenous pyrogen production by Hodgkin's disease and human histiocytic lymphoma cell lines in vitro.

Science.gov (United States)

Bodel, P; Ralph, P; Wenc, K; Long, J C

1980-02-01

Fever not explained by infection may occur in patients with malignant lymphoma presumably caused by a release of endogenous pyrogen. Although pyrogen has been found in some tumors with a mixed cell population, production of endogenous pyrogen by the neoplastic cells has not been demonstrated. This report documents the apparently spontaneous synthesis and release of such pyrogen by two human tumor cell lines derived from patients with Hodgkin's disease and histiocytic lymphoma. The endogenous pyrogen from the two cell lines was similar and closely resembled that produced by normal human monocytes in antigenic properties as well as heat and pronase sensitivity. The Hodgkin's disease and histiocytic lymphoma cell lines do not require specific stimulation for the production of endogenous pyrogen suggesting that the mechanism of pyrogen release by neoplastic macrophage-related cells differs from that of normal phagocytic cells. The tumor-associated fever in some patients with malignant lymphoma may be caused by a release of endogenous pyrogen by proliferating neoplastic cells.

Sensitive and rapid detection of endogenous hydrogen sulfide distributing in different mouse viscera via a two-photon fluorescent probe

International Nuclear Information System (INIS)

Chen, Qian; Yang, Jinfeng; Li, Yinhui; Zheng, Jing; Yang, Ronghua

2015-01-01

Development of efficient methods for detection of endogenous H 2 S in living cells and tissues is of considerable significance for better understanding the biological and pathological functions of H 2 S. Two-photon (TP) fluorescent probes are favorable as powerful molecular tools for studying physiological process due to its non-invasiveness, high spatiotemporal resolution and deep-tissues imaging. Up to date, several TP probes for intracellular H 2 S imaging have been designed, but real-time imaging of endogenous H 2 S-related biological processes in tissues is hampered due to low sensitivity, long response time and interference from other biothiols. To address this issue, we herein report a novel two-photon fluorescent probe (TPP-H 2 S) for highly sensitive and fast monitoring and imaging H 2 S levels in living cells and tissues. In the presence of H 2 S, it exhibits obviously improved sensitivity (LOD: 0.12 μM) and fast response time (about 2 min) compared with the reported two-photon H 2 S probes. With two-photon excitation, TPP-H 2 S displays high signal-to-noise ratio and sensitivity even no interference in cell growth media. As further application, TPP-H 2 S is applied for fast imaging of H 2 S in living cells and different fresh tissues by two-photon confocal microscope. Most importantly we first measured the endogenous H 2 S level in different viscera by vivisection and found that the distribution of endogenous H 2 S mostly in brain, liver and lung. The excellent sensing properties of TPP-H 2 S make it a practically useful tool for further studying biological roles of H 2 S. - Highlights: • This two-photon probe exhibits an improved sensitivity and response time to H 2 S. • This probe shows excellent membrane permeability and fast visualization of H 2 S in living cells and tissues. • This probe is successfully applied to measure the endogenously produced H 2 S levels in different viscera of mouse.

Endogenous Opioid Function and Responses to Morphine: The Moderating Effects of Anger Expressiveness.

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Burns, John W; Bruehl, Stephen; France, Christopher R; Schuster, Erik; Orlowska, Daria; Chont, Melissa; Gupta, Rajnish K; Buvanendran, Asokumar

2017-08-01

Long-term use of opioid analgesics may be ineffective or associated with significant negative side effects for some people. At present, there is no sound method of identifying optimal opioid candidates. Individuals with chronic low back pain (n = 89) and healthy control individuals (n = 102) underwent ischemic pain induction with placebo, opioid blockade (naloxone), and morphine in counterbalanced order. They completed the Spielberger Anger-Out subscale. Endogenous opioid function × Anger-out × Pain status (chronic pain, healthy control) interactions were tested for morphine responses to ischemic threshold, tolerance, and pain intensity (McGill Sensory and Affective subscales) and side effects. For individuals with chronic pain and healthy control participants, those with low endogenous opioid function and low anger-out scores exhibited the largest morphine analgesic responses, whereas those with high anger-out and low endogenous opioid function showed relatively weaker morphine analgesic responses. Further, individuals with chronic pain with low endogenous opioid function and low anger-out scores also reported the fewest negative effects to morphine, whereas those with low endogenous opioid function and high anger-out reported the most. Findings point toward individuals with chronic pain who may strike a favorable balance of good analgesia with few side effects, as well as those who have an unfavorable balance of poor analgesia and many side effects. We sought to identify optimal candidates for opioid pain management. Low back pain patients who express anger and also have deficient endogenous opioid function may be poor candidates for opioid therapy. In contrast, low back patients who tend not to express anger and who also have deficient endogenous opioid function may make optimal candidates for opioid therapy. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Endogenous field feedback promotes the detectability for exogenous electric signal in the hybrid coupled population

Energy Technology Data Exchange (ETDEWEB)

Wei, Xile; Zhang, Danhong; Wang, Jiang; Yu, Haitao, E-mail: htyu@tju.edu.cn [Tianjin Key Laboratory of Process Measurement and Control, School of Electrical Engineering and Automation, Tianjin University, Tianjin 300072 (China); Lu, Meili [School of Informational Technology and Engineering, Tianjin University of Technology and Education, Tianjin 300222 (China); Che, Yanqiu [School of Automation and Electrical Engineering, Tianjin University of Technology and Education, Tianjin 300222 (China)

2015-01-15

This paper presents the endogenous electric field in chemical or electrical synaptic coupled networks, aiming to study the role of endogenous field feedback in the signal propagation in neural systems. It shows that the feedback of endogenous fields to network activities can reduce the required energy of the noise and enhance the transmission of input signals in hybrid coupled populations. As a common and important nonsynaptic interactive method among neurons, particularly, the endogenous filed feedback can not only promote the detectability of exogenous weak signal in hybrid coupled neural population but also enhance the robustness of the detectability against noise. Furthermore, with the increasing of field coupling strengths, the endogenous field feedback is conductive to the stochastic resonance by facilitating the transition of cluster activities from the no spiking to spiking regions. Distinct from synaptic coupling, the endogenous field feedback can play a role as internal driving force to boost the population activities, which is similar to the noise. Thus, it can help to transmit exogenous weak signals within the network in the absence of noise drive via the stochastic-like resonance.

Discrepancy of neural response between exogenous and endogenous task switching: an event-related potentials study.

Science.gov (United States)

Miyajima, Maki; Toyomaki, Atsuhito; Hashimoto, Naoki; Kusumi, Ichiro; Murohashi, Harumitsu; Koyama, Tsukasa

2012-08-01

Task switching is a well-known cognitive paradigm to explore task-set reconfiguration processes such as rule shifting. In particular, endogenous task switching is thought to differ qualitatively from stimulus-triggered exogenous task switching. However, no previous study has examined the neural substrate of endogenous task switching. The purpose of the present study is to explore the differences between event-related potential responses to exogenous and endogenous rule switching at cue stimulus. We modified two patterns of cued switching tasks: exogenous (bottom-up) rule switching and endogenous (top-down) rule switching. In each task cue stimulus was configured to induce switching or maintaining rule. In exogenous switching tasks, late positive deflection was larger in the switch rule condition than in the maintain rule condition. However, in endogenous switching tasks late positive deflection was unexpectedly larger in the maintain-rule condition than in the switch-rule condition. These results indicate that exogenous rule switching is explicit stimulus-driven processes, whereas endogenous rule switching is implicitly parallel processes independent of external stimulus.

Endogenous field feedback promotes the detectability for exogenous electric signal in the hybrid coupled population.

Science.gov (United States)

Wei, Xile; Zhang, Danhong; Lu, Meili; Wang, Jiang; Yu, Haitao; Che, Yanqiu

2015-01-01

This paper presents the endogenous electric field in chemical or electrical synaptic coupled networks, aiming to study the role of endogenous field feedback in the signal propagation in neural systems. It shows that the feedback of endogenous fields to network activities can reduce the required energy of the noise and enhance the transmission of input signals in hybrid coupled populations. As a common and important nonsynaptic interactive method among neurons, particularly, the endogenous filed feedback can not only promote the detectability of exogenous weak signal in hybrid coupled neural population but also enhance the robustness of the detectability against noise. Furthermore, with the increasing of field coupling strengths, the endogenous field feedback is conductive to the stochastic resonance by facilitating the transition of cluster activities from the no spiking to spiking regions. Distinct from synaptic coupling, the endogenous field feedback can play a role as internal driving force to boost the population activities, which is similar to the noise. Thus, it can help to transmit exogenous weak signals within the network in the absence of noise drive via the stochastic-like resonance.

Endogenous field feedback promotes the detectability for exogenous electric signal in the hybrid coupled population

International Nuclear Information System (INIS)

Wei, Xile; Zhang, Danhong; Wang, Jiang; Yu, Haitao; Lu, Meili; Che, Yanqiu

2015-01-01

This paper presents the endogenous electric field in chemical or electrical synaptic coupled networks, aiming to study the role of endogenous field feedback in the signal propagation in neural systems. It shows that the feedback of endogenous fields to network activities can reduce the required energy of the noise and enhance the transmission of input signals in hybrid coupled populations. As a common and important nonsynaptic interactive method among neurons, particularly, the endogenous filed feedback can not only promote the detectability of exogenous weak signal in hybrid coupled neural population but also enhance the robustness of the detectability against noise. Furthermore, with the increasing of field coupling strengths, the endogenous field feedback is conductive to the stochastic resonance by facilitating the transition of cluster activities from the no spiking to spiking regions. Distinct from synaptic coupling, the endogenous field feedback can play a role as internal driving force to boost the population activities, which is similar to the noise. Thus, it can help to transmit exogenous weak signals within the network in the absence of noise drive via the stochastic-like resonance

Endogenous thrombin potential in polycystic ovary syndrome

DEFF Research Database (Denmark)

Aziz, Mubeena; Sidelmann, Johannes Jakobsen; Wissing, Marie Louise Muff

2015-01-01

OBJECTIVES: The objective of this study is to investigate plasma endogenous thrombin generation in four different phenotypes of polycystic ovary syndrome (PCOS) defined by Body Mass Index (BMI) and insulin resistance (IR). PCOS is diagnosed according to the Rotterdam criteria. DESIGN: Multicenter...

Excitatory Modulation of the preBötzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide

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Glauber S. F. da Silva

2017-06-01

Full Text Available Hydrogen Sulfide (H2S is one of three gasotransmitters that modulate excitability in the CNS. Global application of H2S donors or inhibitors of H2S synthesis to the respiratory network has suggested that inspiratory rhythm is modulated by exogenous and endogenous H2S. However, effects have been variable, which may reflect that the RTN/pFRG (retrotrapezoid nucleus, parafacial respiratory group and the preBötzinger Complex (preBötC, critical for inspiratory rhythm generation are differentially modulated by exogenous H2S. Importantly, site-specific modulation of respiratory nuclei by H2S means that targeted, rather than global, manipulation of respiratory nuclei is required to understand the role of H2S signaling in respiratory control. Thus, our aim was to test whether endogenous H2S, which is produced by cystathionine-β-synthase (CBS in the CNS, acts specifically within the preBötC to modulate inspiratory activity under basal (in vitro/in vivo and hypoxic conditions (in vivo. Inhibition of endogenous H2S production by bath application of the CBS inhibitor, aminooxyacetic acid (AOAA, 0.1–1.0 mM to rhythmic brainstem spinal cord (BSSC and medullary slice preparations from newborn rats, or local application of AOAA into the preBötC (slices only caused a dose-dependent decrease in burst frequency. Unilateral injection of AOAA into the preBötC of anesthetized, paralyzed adult rats decreased basal inspiratory burst frequency, amplitude and ventilatory output. AOAA in vivo did not affect the initial hypoxia-induced (10% O2, 5 min increase in ventilatory output, but enhanced the secondary hypoxic respiratory depression. These data suggest that the preBötC inspiratory network receives tonic excitatory modulation from the CBS-H2S system, and that endogenous H2S attenuates the secondary hypoxic respiratory depression.

Proliferation of murine midbrain neural stem cells depends upon an endogenous sonic hedgehog (Shh) source.

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Martínez, Constanza; Cornejo, Víctor Hugo; Lois, Pablo; Ellis, Tammy; Solis, Natalia P; Wainwright, Brandon J; Palma, Verónica

2013-01-01

The Sonic Hedgehog (Shh) pathway is responsible for critical patterning events early in development and for regulating the delicate balance between proliferation and differentiation in the developing and adult vertebrate brain. Currently, our knowledge of the potential role of Shh in regulating neural stem cells (NSC) is largely derived from analyses of the mammalian forebrain, but for dorsal midbrain development it is mostly unknown. For a detailed understanding of the role of Shh pathway for midbrain development in vivo, we took advantage of mouse embryos with cell autonomously activated Hedgehog (Hh) signaling in a conditional Patched 1 (Ptc1) mutant mouse model. This animal model shows an extensive embryonic tectal hypertrophy as a result of Hh pathway activation. In order to reveal the cellular and molecular origin of this in vivo phenotype, we established a novel culture system to evaluate neurospheres (nsps) viability, proliferation and differentiation. By recreating the three-dimensional (3-D) microenvironment we highlight the pivotal role of endogenous Shh in maintaining the stem cell potential of tectal radial glial cells (RGC) and progenitors by modulating their Ptc1 expression. We demonstrate that during late embryogenesis Shh enhances proliferation of NSC, whereas blockage of endogenous Shh signaling using cyclopamine, a potent Hh pathway inhibitor, produces the opposite effect. We propose that canonical Shh signaling plays a central role in the control of NSC behavior in the developing dorsal midbrain by acting as a niche factor by partially mediating the response of NSC to epidermal growth factor (EGF) and fibroblast growth factor (FGF) signaling. We conclude that endogenous Shh signaling is a critical mechanism regulating the proliferation of stem cell lineages in the embryonic dorsal tissue.

Controlling for endogeneity in attributable costs of vancomycin-resistant enterococci from a Canadian hospital.

Science.gov (United States)

Lloyd-Smith, Patrick

2017-12-01

Decisions regarding the optimal provision of infection prevention and control resources depend on accurate estimates of the attributable costs of health care-associated infections. This is challenging given the skewed nature of health care cost data and the endogeneity of health care-associated infections. The objective of this study is to determine the hospital costs attributable to vancomycin-resistant enterococci (VRE) while accounting for endogeneity. This study builds on an attributable cost model conducted by a retrospective cohort study including 1,292 patients admitted to an urban hospital in Vancouver, Canada. Attributable hospital costs were estimated with multivariate generalized linear models (GLMs). To account for endogeneity, a control function approach was used. The analysis sample included 217 patients with health care-associated VRE. In the standard GLM, the costs attributable to VRE are $17,949 (SEM, $2,993). However, accounting for endogeneity, the attributable costs were estimated to range from $14,706 (SEM, $7,612) to $42,101 (SEM, $15,533). Across all model specifications, attributable costs are 76% higher on average when controlling for endogeneity. VRE was independently associated with increased hospital costs, and controlling for endogeneity lead to higher attributable cost estimates. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Endogenous Retrovirus 3 – History, Physiology, and Pathology

Science.gov (United States)

Bustamante Rivera, Yomara Y.; Brütting, Christine; Schmidt, Caroline; Volkmer, Ines; Staege, Martin S.

2018-01-01

Endogenous viral elements (EVE) seem to be present in all eukaryotic genomes. The composition of EVE varies between different species. The endogenous retrovirus 3 (ERV3) is one of these elements that is present only in humans and other Catarrhini. Conservation of ERV3 in most of the investigated Catarrhini and the expression pattern in normal tissues suggest a putative physiological role of ERV3. On the other hand, ERV3 has been implicated in the pathogenesis of auto-immunity and cancer. In the present review we summarize knowledge about this interesting EVE. We propose the model that expression of ERV3 (and probably other EVE loci) under pathological conditions might be part of a metazoan SOS response. PMID:29379485

Endogenous Retrovirus 3 – History, Physiology, and Pathology

Directory of Open Access Journals (Sweden)

Yomara Y. Bustamante Rivera

2018-01-01

Full Text Available Endogenous viral elements (EVE seem to be present in all eukaryotic genomes. The composition of EVE varies between different species. The endogenous retrovirus 3 (ERV3 is one of these elements that is present only in humans and other Catarrhini. Conservation of ERV3 in most of the investigated Catarrhini and the expression pattern in normal tissues suggest a putative physiological role of ERV3. On the other hand, ERV3 has been implicated in the pathogenesis of auto-immunity and cancer. In the present review we summarize knowledge about this interesting EVE. We propose the model that expression of ERV3 (and probably other EVE loci under pathological conditions might be part of a metazoan SOS response.

Quantitative tissue-specific dynamics of in vivo GILZ mRNA expression and regulation by endogenous and exogenous glucocorticoids.

Science.gov (United States)

Ayyar, Vivaswath S; Almon, Richard R; Jusko, William J; DuBois, Debra C

2015-06-01

Glucocorticoids (GC) are steroid hormones, which regulate metabolism and immune function. Synthetic GCs, or corticosteroids (CS), have appreciable clinical utility via their ability to suppress inflammation in immune-mediated diseases like asthma and rheumatoid arthritis. Recent work has provided insight to novel GC-induced genes that mediate their anti-inflammatory effects, including glucocorticoid-induced leucine zipper (GILZ). Since GILZ comprises an important part of GC action, its regulation by both drug and hormone will influence CS therapy. In addition, GILZ expression is often employed as a biomarker of GC action, which requires judicious selection of sampling time. Understanding the in vivo regulation of GILZ mRNA expression over time will provide insight into both the physiological regulation of GILZ by endogenous GC and the dynamics of its enhancement by CS. A highly quantitative qRT-PCR assay was developed for measuring GILZ mRNA expression in tissues obtained from normal and CS-treated rats. This assay was applied to measure GILZ mRNA expression in eight tissues; to determine its endogenous regulation over time; and to characterize its dynamics in adipose tissue, muscle, and liver following treatment with CS. We demonstrate that GILZ mRNA is expressed in several tissues. GILZ mRNA expression in adipose tissue displayed a robust circadian rhythm that was entrained with the circadian oscillation of endogenous corticosterone; and is strongly enhanced by acute and chronic dosing. Single dosing also enhanced GILZ mRNA in muscle and liver, but the dynamics varied. In conclusion, GILZ is widely expressed in the rat and highly regulated by endogenous and exogenous GCs. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Chemical Atherogenesis: Role of Endogenous and Exogenous Poisons in Disease Development

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Matthew K. Ross

2014-01-01

Full Text Available Chemical atherogenesis is an emerging field that describes how environmental pollutants and endogenous toxins perturb critical pathways that regulate lipid metabolism and inflammation, thus injuring cells found within the vessel wall. Despite growing awareness of the role of environmental pollutants in the development of cardiovascular disease, the field of chemical atherogenesis can broadly include both exogenous and endogenous poisons and the study of molecular, biochemical, and cellular pathways that become dysregulated during atherosclerosis. This integrated approach is logical because exogenous and endogenous toxins often share the same mechanism of toxicity. Chemical atherogenesis is a truly integrative discipline because it incorporates concepts from several different fields, including biochemistry, chemical biology, pharmacology, and toxicology. This review will provide an overview of this emerging research area, focusing on cellular and animal models of disease.

Chemical Atherogenesis: Role of Endogenous and Exogenous Poisons in Disease Development.

Science.gov (United States)

Ross, Matthew K; Matthews, Anberitha T; Mangum, Lee C

Chemical atherogenesis is an emerging field that describes how environmental pollutants and endogenous toxins perturb critical pathways that regulate lipid metabolism and inflammation, thus injuring cells found within the vessel wall. Despite growing awareness of the role of environmental pollutants in the development of cardiovascular disease, the field of chemical atherogenesis can broadly include both exogenous and endogenous poisons and the study of molecular, biochemical, and cellular pathways that become dysregulated during atherosclerosis. This integrated approach is logical because exogenous and endogenous toxins often share the same mechanism of toxicity. Chemical atherogenesis is a truly integrative discipline because it incorporates concepts from several different fields, including biochemistry, chemical biology, pharmacology, and toxicology. This review will provide an overview of this emerging research area, focusing on cellular and animal models of disease.

The interactions of multisensory integration with endogenous and exogenous attention

Science.gov (United States)

Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

2016-01-01

Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. PMID:26546734

Methemoglobin Is an Endogenous Toll-Like Receptor 4 Ligand—Relevance to Subarachnoid Hemorrhage

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Min Seong Kwon

2015-03-01

Full Text Available Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage (SAH, and may be responsible for important complications of SAH. Signaling by Toll-like receptor 4 (TLR4-mediated nuclear factor κB (NFκB in microglia plays a critical role in neuronal damage after SAH. Three molecules derived from erythrocyte breakdown have been postulated to be endogenous TLR4 ligands: methemoglobin (metHgb, heme and hemin. However, poor water solubility of heme and hemin, and lipopolysaccharide (LPS contamination have confounded our understanding of these molecules as endogenous TLR4 ligands. We used a 5-step process to obtain highly purified LPS-free metHgb, as confirmed by Fourier Transform Ion Cyclotron Resonance mass spectrometry and by the Limulus amebocyte lysate assay. Using this preparation, we show that metHgb is a TLR4 ligand at physiologically relevant concentrations. metHgb caused time- and dose-dependent secretion of the proinflammatory cytokine, tumor necrosis factor α (TNFα, from microglial and macrophage cell lines, with secretion inhibited by siRNA directed against TLR4, by the TLR4-specific inhibitors, Rs-LPS and TAK-242, and by anti-CD14 antibodies. Injection of purified LPS-free metHgb into the rat subarachnoid space induced microglial activation and TNFα upregulation. Together, our findings support the hypothesis that, following SAH, metHgb in the subarachnoid space can promote widespread TLR4-mediated neuroinflammation.

Endogenous pyrogen production by Hodgkin's disease and human histiocytic lymphoma cell lines in vitro.

OpenAIRE

Bodel, P; Ralph, P; Wenc, K; Long, J C

1980-01-01

Fever not explained by infection may occur in patients with malignant lymphoma presumably caused by a release of endogenous pyrogen. Although pyrogen has been found in some tumors with a mixed cell population, production of endogenous pyrogen by the neoplastic cells has not been demonstrated. This report documents the apparently spontaneous synthesis and release of such pyrogen by two human tumor cell lines derived from patients with Hodgkin's disease and histiocytic lymphoma. The endogenous ...

Targeted detection of in vivo endogenous DNA base damage reveals preferential base excision repair in the transcribed strand.

Science.gov (United States)

Reis, António M C; Mills, Wilbur K; Ramachandran, Ilangovan; Friedberg, Errol C; Thompson, David; Queimado, Lurdes

2012-01-01

Endogenous DNA damage is removed mainly via base excision repair (BER), however, whether there is preferential strand repair of endogenous DNA damage is still under intense debate. We developed a highly sensitive primer-anchored DNA damage detection assay (PADDA) to map and quantify in vivo endogenous DNA damage. Using PADDA, we documented significantly higher levels of endogenous damage in Saccharomyces cerevisiae cells in stationary phase than in exponential phase. We also documented that yeast BER-defective cells have significantly higher levels of endogenous DNA damage than isogenic wild-type cells at any phase of growth. PADDA provided detailed fingerprint analysis at the single-nucleotide level, documenting for the first time that persistent endogenous nucleotide damage in CAN1 co-localizes with previously reported spontaneous CAN1 mutations. To quickly and reliably quantify endogenous strand-specific DNA damage in the constitutively expressed CAN1 gene, we used PADDA on a real-time PCR setting. We demonstrate that wild-type cells repair endogenous damage preferentially on the CAN1 transcribed strand. In contrast, yeast BER-defective cells accumulate endogenous damage preferentially on the CAN1 transcribed strand. These data provide the first direct evidence for preferential strand repair of endogenous DNA damage and documents the major role of BER in this process.

Investigations into the differential reactivity of endogenous and exogenous mercury species in coastal sediments.

Science.gov (United States)

Bouchet, S; Rodriguez-Gonzalez, P; Bridou, R; Monperrus, M; Tessier, E; Anschutz, P; Guyoneaud, R; Amouroux, D

2013-03-01

Stable isotopic tracer methodologies now allow the evaluation of the reactivity of the endogenous (ambient) and exogenous (added) Hg to further predict the potential effect of Hg inputs in ecosystems. The differential reactivity of endogenous and exogenous Hg was compared in superficial sediments collected in a coastal lagoon (Arcachon Bay) and in an estuary (Adour River) from the Bay of Biscay (SW France). All Hg species (gaseous, aqueous, and solid fraction) and ancillary data were measured during time course slurry experiments under variable redox conditions. The average endogenous methylation yield was higher in the estuarine (1.2 %) than in the lagoonal sediment (0.5 %), although both methylation and demethylation rates were higher in the lagoonal sediment in relation with a higher sulfate-reducing activity. Demethylation was overall more consistent than methylation in both sediments. The endogenous and exogenous Hg behaviors were always correlated but the exogenous inorganic Hg (IHg) partitioning into water was 2.0-4.3 times higher than the endogenous one. Its methylation was just slightly higher (1.4) in the estuarine sediment while the difference in the lagoonal sediment was much larger (3.6). The relative endogenous and exogenous methylation yields were not correlated to IHg partitioning, demonstrating that the bioavailable species distributions were different for the two IHg pools. In both sediments, the exogenous IHg partitioning equaled the endogenous one within a week, while its higher methylation lasted for months. Such results provide an original assessment approach to compare coastal sediment response to Hg inputs.

Alkyl caffeates as antioxidants in O/W emulsions: Impact of emulsifier type and endogenous tocopherols

DEFF Research Database (Denmark)

Sørensen, Ann-Dorit Moltke; Villeneuve, Pierre; Jacobsen, Charlotte

2017-01-01

, the aim was to evaluate the impact of emulsifiers (Citrem and Tween80) and presence of endogenous tocopherols on the efficacies of caffeic acid and caffeates (C1–C20) as antioxidants in emulsions. Lipid oxidation was evaluated during storage and partitioning of caffeic acid and caffeates was estimated...... by measuring their concentrations in the aqueous phase. Partitioning of caffeic acid and caffeates was influenced by emulsifier type and the presence of endogenous tocopherols. Caffeic acid was the most efficient antioxidant in Citrem and Tween stabilized emulsions in the presence of endogenous tocopherol....... In contrast, for Tween stabilized emulsions, caffeic acid acted as a prooxidant and the evaluated caffeates acted as strong antioxidants in the absence of endogenous tocopherol. Thus, when endogenous tocopherol was present lipophilization of caffeic acid did not increase its efficacy as an antioxidant...

Optimal income taxation with endogenous human capital

NARCIS (Netherlands)

Jacobs, B.

2005-01-01

This paper augments the theory of optimal linear income taxation by taking into account human capital accumulation as a dimension of labor supply. The distribution of earning potentials is endogenous because agents differ in the ability to learn. Taxation affects utilization rates of human capital

Managing spillovers: an endogenous sunk cost approach

Czech Academy of Sciences Publication Activity Database

Senyuta, Olena; Žigić, Krešimir

2016-01-01

Roč. 35, June (2016), s. 45-64 ISSN 0167-6245 R&D Projects: GA ČR(CZ) GAP402/12/0961 Institutional support: PRVOUK-P23 Keywords : endogenous sunk costs * innovations * knowledge spillovers Subject RIV: AH - Economics Impact factor: 0.739, year: 2016

Endogenous retrovirus sequences expressed in male mammalian ...

African Journals Online (AJOL)

Objectives: To review the research findings on the expression of endogenous retroviruses and retroviral-related particles in male mammalian reproductive tissues, and to discuss their possible role in normal cellular events and association with disease conditions in male reproductive tissues. Data sources: Published ...

Money, banks and endogenous volatility

OpenAIRE

Pere Gomis-Porqueras

2000-01-01

In this paper I consider a monetary growth model in which banks provide liquidity, and the government fixes a constant rate of money creation. There are two underlying assets in the economy, money and capital. Money is dominated in rate of return. In contrast to other papers with a larger set of government liabilities, I find a unique equilibrium when agents' risk aversion is moderate. However, indeterminacies and endogenous volatility can be observed when agents are relatively risk averse.

Endogenous and Exogenous Natural Adjuvants for Vaccine Development.

Science.gov (United States)

Bolhassani, Azam; Talebi, Somayeh; Anvar, Ali

2017-01-01

Objective & Background: Various adjuvants are usually co-injected with an antigen for stimulation of effective immune responses. Adjuvants are able to elicit innate immune responses at the injection site. Depending on the activated type of innate responses, adjuvants can modify the quality and quantity of adaptive immune responses. Their mechanisms of action in vaccine development include: a) enhancement of the total antibody titers; b) reduction of the antigen dose; c) induction of potent cell-mediated immunity; d) increase in the speed and duration of the protective response; e) stimulation of mucosal immunity; and f) cross-protection. Up to now, different exogenous adjuvants have been identified to boost immune responses including inorganic compounds, mineral oil, bacterial products, non-bacterial organics, detergents or Quil A, plant saponins, Freund's complete or incomplete adjuvants, and delivery systems. However, some immune responses can be generated in the absence of the exogenous adjuvants. Indeed, endogenous adjuvants released from the cells were known as the danger signals and immunogenic compounds. Several main endogenous adjuvants contain cytokines, chemokines, alarmins, dendritic cells (DCs), toll like receptor (TLR) ligands or agonists, and antibodies. In this review, the immune activities of the natural adjuvants especially endogenous adjuvants and their mechanisms of action are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Exogenous or endogenous Toll-like receptor ligands: which is the MVP in tumorigenesis?

Science.gov (United States)

Yu, Li; Wang, Liantang; Chen, Shangwu

2012-03-01

Toll-like receptors (TLRs) are a class of pattern recognition receptors sensing microbial components and triggering an immune response against pathogens. In addition to their role in anti-infection immunity, increasing evidence indicates that engagement of TLRs can promote cancer cell survival and proliferation, induce tumor immune evasion, and enhance tumor metastasis and chemoresistance. Recent studies have demonstrated that endogenous molecules or damage-associated molecular patterns released from damaged/necrotic tissues are capable of activating TLRs and that the endogenous ligands-mediated TLR signaling is implicated in the tumor development and affects the therapeutic efficacy of tumors. Since both exogenous and endogenous TLR ligands can initiate TLR signaling, which is the most valuable player in tumor development becomes an interesting question. Here, we summarize the effect of TLR signaling on the development and progression of tumors, and discuss the role of exogenous and endogenous TLR ligands in the tumorigenesis.

Quantitative regularities of development of endogenous infection in irradiated organism. (Survey of literature)

Energy Technology Data Exchange (ETDEWEB)

Mal' tsev, V N [Institut Biofiziki, Moscow (USSR)

1979-01-01

A statistical analysis of data from the literature and the author's own experimental results are reviewed to show the functional relationships between the radiation dose and the development of endogenous infection in irradiated organisms. A direct linear dependence was found between the dose of radiation and the severity of endogenous infection at doses causing death from the ''bone marrow'' syndrome in acute radiation sickness. In case of death from the ''intestinal'' syndrome, an inverse linear dependence can be observed between the radiation dose and the culture yield of microbes from internal organs. In this case, the pathological effect on the organism is due to bacterial endotoxins formed during the disintegration of microbial cells in the organism. Endogenous infection and endotoxinaemia essentially aggravate the progress of acute radiation disease. The importance of endogenous infection for the death of the organism is minimized in irradiation at doses causing death ''under the ray''.

Differential effects of exogenous and endogenous attention on second-order texture contrast sensitivity

Science.gov (United States)

Barbot, Antoine; Landy, Michael S.; Carrasco, Marisa

2012-01-01

The visual system can use a rich variety of contours to segment visual scenes into distinct perceptually coherent regions. However, successfully segmenting an image is a computationally expensive process. Previously we have shown that exogenous attention—the more automatic, stimulus-driven component of spatial attention—helps extract contours by enhancing contrast sensitivity for second-order, texture-defined patterns at the attended location, while reducing sensitivity at unattended locations, relative to a neutral condition. Interestingly, the effects of exogenous attention depended on the second-order spatial frequency of the stimulus. At parafoveal locations, attention enhanced second-order contrast sensitivity to relatively high, but not to low second-order spatial frequencies. In the present study we investigated whether endogenous attention—the more voluntary, conceptually-driven component of spatial attention—affects second-order contrast sensitivity, and if so, whether its effects are similar to those of exogenous attention. To that end, we compared the effects of exogenous and endogenous attention on the sensitivity to second-order, orientation-defined, texture patterns of either high or low second-order spatial frequencies. The results show that, like exogenous attention, endogenous attention enhances second-order contrast sensitivity at the attended location and reduces it at unattended locations. However, whereas the effects of exogenous attention are a function of the second-order spatial frequency content, endogenous attention affected second-order contrast sensitivity independent of the second-order spatial frequency content. This finding supports the notion that both exogenous and endogenous attention can affect second-order contrast sensitivity, but that endogenous attention is more flexible, benefitting performance under different conditions. PMID:22895879

Differential effects of exogenous and endogenous attention on second-order texture contrast sensitivity.

Science.gov (United States)

Barbot, Antoine; Landy, Michael S; Carrasco, Marisa

2012-08-15

The visual system can use a rich variety of contours to segment visual scenes into distinct perceptually coherent regions. However, successfully segmenting an image is a computationally expensive process. Previously we have shown that exogenous attention--the more automatic, stimulus-driven component of spatial attention--helps extract contours by enhancing contrast sensitivity for second-order, texture-defined patterns at the attended location, while reducing sensitivity at unattended locations, relative to a neutral condition. Interestingly, the effects of exogenous attention depended on the second-order spatial frequency of the stimulus. At parafoveal locations, attention enhanced second-order contrast sensitivity to relatively high, but not to low second-order spatial frequencies. In the present study we investigated whether endogenous attention-the more voluntary, conceptually-driven component of spatial attention--affects second-order contrast sensitivity, and if so, whether its effects are similar to those of exogenous attention. To that end, we compared the effects of exogenous and endogenous attention on the sensitivity to second-order, orientation-defined, texture patterns of either high or low second-order spatial frequencies. The results show that, like exogenous attention, endogenous attention enhances second-order contrast sensitivity at the attended location and reduces it at unattended locations. However, whereas the effects of exogenous attention are a function of the second-order spatial frequency content, endogenous attention affected second-order contrast sensitivity independent of the second-order spatial frequency content. This finding supports the notion that both exogenous and endogenous attention can affect second-order contrast sensitivity, but that endogenous attention is more flexible, benefitting performance under different conditions.

Comparison of febrile responsiveness of rats and rabbits to endogenous pyrogen.

Science.gov (United States)

Stitt, J T; Shimada, S G; Bernheim, H A

1985-12-01

The fever responses of rats and rabbits were compared in detail using a single common source of semipurified endogenous pyrogen prepared from human monocytes. The characteristics and dynamics of the fever-response curves for each species were examined and their dose-response curves were determined and compared. The fevers displayed by rats were qualitatively similar to those of rabbits, but, typically, they developed and terminated more rapidly than those of rabbits. Rabbits were much more sensitive to the endogenous pyrogen than rats. The threshold dose of pyrogen required to elicit a fever was 5 times lower in the rabbit, and the slope of the rabbit's dose-response curve was 1.5 times steeper than that of the rat. The maximum fevers attainable in rabbits were approximately twice those attainable in rats. It was also shown that the more rapid febrile responses of the rat were not due to the 10-fold smaller mass of the rat; instead, we proposed that this difference was more likely due to a closer diffusional proximity of the pyrogen receptor sites to the circulation in rats. The lower sensitivity of the rat to endogenous pyrogen was attributed to a relative insensitivity of the pyrogen receptor sites in rats in the translation of the endogenous pyrogen stimulus into fever.

HERVd: the Human Endogenous Retrovirus Database: update

Czech Academy of Sciences Publication Activity Database

Pačes, Jan; Pavlíček, A.; Zíka, Radek; Jurka, J.; Pačes, Václav

2004-01-01

Roč. 32, č. 1 (2004), s. 50-50 ISSN 0305-1048 R&D Projects: GA MŠk LN00A079 Institutional research plan: CEZ:AV0Z5052915 Keywords : human * endogenous retrovirus * database Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.260, year: 2004

Endogenous technological change with leisure-dependent utility.

NARCIS (Netherlands)

Hek, de P.A.

1999-01-01

This paper investigates the effect of introducing leisure-dependent utility into two models of endogenous technological change. Due to the flexibility in the labour supply the dynamics of the models change significantly. It is shown that if agents attach enough value to leisure in comparison to

Place branding, embeddedness and endogenous rural development

NARCIS (Netherlands)

Donner, Mechthild; Horlings, Lummina; Fort, Fatiha; Vellema, Sietze

2017-01-01

This article deals with place branding on the regional scale, in the rural context of food and tourism networks in Europe. Place branding is linked to the concepts of endogenous rural development, territory and embeddedness, by analysing how the valorisation of specific rural assets takes shape.

Climate changes and farmers' endogenous adaptation strategies ...

African Journals Online (AJOL)

It has been claimed that climate changes impact studies often assume certain adaptations and little explicit examination of how, when, why, and under what conditions they occur. This research aims at analysing the endogenous strategies developed by farmers in agricultural land and crop management. With random ...

The Limit of Public Policy : Endogenous Preferences

NARCIS (Netherlands)

Bar-Gill, O.; Fershtman, C.

2000-01-01

In designing public policy it is not enough to consider the possible reaction of individuals to the chosen policy.Public policy may also affect the formation of preferences and norms in a society.The endogenous evolution of preferences, in addition to introducing a conceptual difficulty in

Optimized Formation of Benzyl Isothiocyanate by Endogenous ...

African Journals Online (AJOL)

Purpose: To use endogenous myrosinase in Carica papaya seed to convert benzyl glucosinolate (BG) to benzyl isothiocyanate (BITC) and then extract it for further studies. Methods: Process variables including seed powder particle size, sample-to-solvent ratio, pH of buffer solution, enzymolysis temperature, enzymolysis ...

Endogenous egg immune defenses in the yellow mealworm beetle (Tenebrio molitor).

Science.gov (United States)

Jacobs, Chris G C; Gallagher, Joe D; Evison, Sophie E F; Heckel, David G; Vilcinskas, Andreas; Vogel, Heiko

2017-05-01

In order to survive microbe encounters, insects rely on both physical barriers as well as local and systemic immune responses. Most research focusses on adult or larval defenses however, whereas insect eggs are also in need of protection. Lately, the defense of eggs against microbes has received an increasing amount of attention, be it through endogenous egg defenses, trans-generational immune priming (TGIP) or parental investment. Here we studied the endogenous immune response in eggs and adults of Tenebrio molitor. We show that many immune genes are induced in both adults and eggs. Furthermore, we show that eggs reach comparable levels of immune gene expression as adults. These findings show that the eggs of Tenebrio are capable of an impressive endogenous immune response, and indicate that such inducible egg defenses are likely common in insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endogeneity of Money Supply: Evidence From Turkey

Directory of Open Access Journals (Sweden)

Oguzhan Cepni

2017-02-01

Full Text Available There is a long discussion among academics and central bankers about the theories of money supply. According to the exogenous view, central banks have the full control over money supply via policy actions including the adjustments of interest rates and reserve ratios, both of which alter commercial banks’ lending decisions. However, the theory of endogenous money supply emphasizes the role of demand for bank loans in money creation. More specifically, banks create money by meeting the demand of economic agents. In this study, we investigate which of the money supply theories holds in Turkish economy for the period 2006-2015 by employing cointegration and causality tests. Our findings show that the causality runs from bank loans to money supply both in the short and long terms, which supports the endogenous view in a sense that central bank and the banks fully meet the total demand for money in Turkish economy.

Endogenous-cue prospective memory involving incremental updating of working memory: an fMRI study.

Science.gov (United States)

Halahalli, Harsha N; John, John P; Lukose, Ammu; Jain, Sanjeev; Kutty, Bindu M

2015-11-01

Prospective memory paradigms are conventionally classified on the basis of event-, time-, or activity-based intention retrieval. In the vast majority of such paradigms, intention retrieval is provoked by some kind of external event. However, prospective memory retrieval cues that prompt intention retrieval in everyday life are commonly endogenous, i.e., linked to a specific imagined retrieval context. We describe herein a novel prospective memory paradigm wherein the endogenous cue is generated by incremental updating of working memory, and investigated the hemodynamic correlates of this task. Eighteen healthy adult volunteers underwent functional magnetic resonance imaging while they performed a prospective memory task where the delayed intention was triggered by an endogenous cue generated by incremental updating of working memory. Working memory and ongoing task control conditions were also administered. The 'endogenous-cue prospective memory condition' with incremental working memory updating was associated with maximum activations in the right rostral prefrontal cortex, and additional activations in the brain regions that constitute the bilateral fronto-parietal network, central and dorsal salience networks as well as cerebellum. In the working memory control condition, maximal activations were noted in the left dorsal anterior insula. Activation of the bilateral dorsal anterior insula, a component of the central salience network, was found to be unique to this 'endogenous-cue prospective memory task' in comparison to previously reported exogenous- and endogenous-cue prospective memory tasks without incremental working memory updating. Thus, the findings of the present study highlight the important role played by the dorsal anterior insula in incremental working memory updating that is integral to our endogenous-cue prospective memory task.

Endogenous Technology Adoption and Medical Costs.

Science.gov (United States)

Lamiraud, Karine; Lhuillery, Stephane

2016-09-01

Despite the claim that technology has been one of the most important drivers of healthcare spending growth over the past decades, technology variables are rarely introduced explicitly in cost equations. Furthermore, technology is often considered exogenous. Using 1996-2007 panel data on Swiss geographical areas, we assessed the impact of technology availability on per capita healthcare spending covered by basic health insurance whilst controlling for the endogeneity of health technology availability variables. Our results suggest that medical research, patent intensity and the density of employees working in the medical device industry are influential factors for the adoption of technology and can be used as instruments for technology availability variables in the cost equation. These results are similar to previous findings: CT and PET scanner adoption is associated with increased healthcare spending, whilst increased availability of percutaneous transluminal coronary angioplasty facilities is associated with reductions in per capita spending. However, our results suggest that the magnitude of these relationships is much greater in absolute value than that suggested by previous studies that did not control for the possible endogeneity of the availability of technologies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Endogenous money, circuits and financialization

OpenAIRE

Malcolm Sawyer

2013-01-01

This paper locates the endogenous money approach in a circuitist framework. It argues for the significance of the credit creation process for the evolution of the economy and the absence of any notion of ‘neutrality of money’. Clearing banks are distinguished from other financial institutions as the providers of initial finance in a circuit whereas other financial institutions operate in a final finance circuit. Financialization is here viewed in terms of the growth of financial assets an...

Endogenous retroviruses in fish genomes: from relics of past infections to evolutionary innovations?

Directory of Open Access Journals (Sweden)

Magali Naville

2016-08-01

Full Text Available The increasing availability of fish genome sequences has allowed to gain new insights into the diversity and host distribution of retroviruses in fish and other vertebrates. This distribution can be assessed through the identification and analysis of endogenous retroviruses, which are proviral remnants of past infections integrated in genomes. Retroviral sequences are probably important for evolution through their ability to induce rearrangements and to contribute regulatory and coding sequences; they may also protect their host against new infections. We argue that the current mass of genome sequences will soon strongly improve our understanding of retrovirus diversity and evolution in aquatic animals, with the identification of new/re-emerging elements and host resistance genes that restrict their infectivity.

Bullet trains and steam engines: exogenous attention zips but endogenous attention chugs along.

Science.gov (United States)

Chakravarthi, Ramakrishna; VanRullen, Rufin

2011-04-20

Analyzing a scene requires shifting attention from object to object. Although several studies have attempted to determine the speed of these attentional shifts, there are large discrepancies in their estimates. Here, we adapt a method pioneered by T. A. Carlson, H. Hogendoorn, and F. A. J. Verstraten (2006) that directly measures pure attentional shift times. We also test if attentional shifts can be handled in parallel by the independent resources available in the two cortical hemispheres. We present 10 "clocks," with single revolving hands, in a ring around fixation. Observers are asked to report the hand position on one of the clocks at the onset of a transient cue. The delay between the reported time and the veridical time at cue onset can be used to infer processing and attentional shift times. With this setup, we use a novel subtraction method that utilizes different combinations of exogenous and endogenous cues to determine shift times for both types of attention. In one experiment, subjects shift attention to an exogenously cued clock (baseline condition) in one block, and in other blocks, subjects perform one further endogenous shift to a nearby clock (test condition). In another experiment, attention is endogenously cued to one clock (baseline condition), and on other trials, an exogenous cue further shifts attention to a nearby clock (test condition). Subtracting report delays in the baseline condition from those obtained in the test condition allows us to isolate genuine attentional shift times. In agreement with previous studies, our results reveal that endogenous attention is much slower than exogenous attention (endogenous: 250 ms; exogenous: 100 ms). Surprisingly, the dependence of shift time on distance is minimal for exogenous attention, whereas it is steep for endogenous attention. In the final experiment, we find that endogenous shifts are faster across hemifields than within a hemifield suggesting that the two hemispheres can simultaneously

A novel endogenous betaretrovirus group characterized from polar bears (Ursus maritimus) and giant pandas (Ailuropoda melanoleuca)

DEFF Research Database (Denmark)

Mayer, Jens; Tsangaras, Kyriakos; Heeger, Felix

2013-01-01

. Molecular dating indicates the group originated before the divergence of bears from a common ancestor but is not present in all carnivores. Closely related sequences were identified in the giant panda (Ailuropoda melanoleuca) and characterized from its genome. We have designated the polar bear and giant...... panda sequences U. maritimus endogenous retrovirus (UmaERV) and A. melanoleuca endogenous retrovirus (AmeERV), respectively. Phylogenetic analysis demonstrated that the bear virus group is nested within the HERV-K supergroup among bovine and bat endogenous retroviruses suggesting a complex evolutionary......Transcriptome analysis of polar bears (Ursus maritimus) yielded sequences with highest similarity to the human endogenous retrovirus group HERV-K(HML-2). Further analysis of the polar bear draft genome identified an endogenous betaretrovirus group comprising 26 proviral copies and 231 solo LTRs...

The interactions of multisensory integration with endogenous and exogenous attention.

Science.gov (United States)

Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

2016-02-01

Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

Packaging of human endogenous retrovirus sequences is undetectable in porcine endogenous retrovirus particles produced from human cells

International Nuclear Information System (INIS)

Suling, Kristen; Quinn, Gary; Wood, James; Patience, Clive

2003-01-01

The chronic shortage of human donor organs and tissues for allotransplantation could be relieved if clinical xenotransplantation were to become a viable clinical therapy. Balanced against the benefits of xenotransplantation are the possible consequences of zoonotic infections, and in particular, infection by porcine endogenous retrovirus (PERV). An often-proclaimed risk of PERV infection is the possible recombination of PERV with human endogenous retroviruses (HERV) . To address this issue, we examined the potential for HERV sequences to be cross-packaged into PERV particles produced from infected human 293 cells. Although HERV-K, W, E, R, and ERV-9 RNA transcripts are expressed in 293 cells, we did not detect cross-packaging of any of these HERV groups. Quantitative analysis indicated that less than approximately 1 in 10 4 -10 7 PERV particles might contain HERV sequences. In comparison, we found that murine leukemia virus (MLV)-based vector transcripts were cross-packaged at a rate of approximately one copy in 10 4 PERV particles. Our results indicate that the potential for recombination of PERV and HERV sequences is low and that novel viruses generated by this mechanism are unlikely to represent a significant risk for xenotransplantation

Two cognitive and neural systems for endogenous and exogenous spatial attention.

Science.gov (United States)

Chica, Ana B; Bartolomeo, Paolo; Lupiáñez, Juan

2013-01-15

Orienting of spatial attention is a family of phylogenetically old mechanisms developed to select information for further processing. Information can be selected via top-down or endogenous mechanisms, depending on the goals of the observers or on the task at hand. Moreover, salient and potentially dangerous events also attract spatial attention via bottom-up or exogenous mechanisms, allowing a rapid and efficient reaction to unexpected but important events. Fronto-parietal brain networks have been demonstrated to play an important role in supporting spatial attentional orienting, although there is no consensus on whether there is a single attentional system supporting both endogenous and exogenous attention, or two anatomical and functionally different attentional systems. In the present paper we review behavioral evidence emphasizing the differential characteristics of both systems, as well as their possible interactions for the control of the final orienting response. Behavioral studies reporting qualitative differences between the effects of both systems as well as double dissociations of the effects of endogenous and exogenous attention on information processing, suggest that they constitute two independent attentional systems, rather than a single one. Recent models of attentional orienting in humans have put forward the hypothesis of a dorsal fronto-parietal network for orienting spatial attention, and a more ventral fronto-parietal network for detecting unexpected but behaviorally relevant events. Non-invasive neurostimulation techniques, as well as neuropsychological data, suggest that endogenous and exogenous attention are implemented in overlapping, although partially segregated, brain circuits. Although more research is needed in order to refine our anatomical and functional knowledge of the brain circuits underlying spatial attention, we conclude that endogenous and exogenous spatial orienting constitute two independent attentional systems, with

Endogenous network states predict gain or loss of functions for genetic mutations in hepatocellular carcinoma.

Science.gov (United States)

Wang, Gaowei; Su, Hang; Yu, Helin; Yuan, Ruoshi; Zhu, Xiaomei; Ao, Ping

2016-02-01

Cancers have been typically characterized by genetic mutations. Patterns of such mutations have traditionally been analysed by posteriori statistical association approaches. One may ponder the possibility of a priori determination of any mutation regularity. Here by exploring biological processes implied in a mechanistic theory recently developed (the endogenous molecular-cellular network theory), we found that the features of genetic mutations in cancers may be predicted without any prior knowledge of mutation propensities. With hepatocellular carcinoma (HCC) as an example, we found that the normal hepatocyte and cancerous hepatocyte can be represented by robust stable states of one single endogenous network. These stable states, specified by distinct patterns of expressions or activities of proteins in the network, provide means to directly identify a set of most probable genetic mutations and their effects in HCC. As the key proteins and main interactions in the network are conserved through cell types in an organism, similar mutational features may also be found in other cancers. This analysis yielded straightforward and testable predictions on accumulated and preferred mutation spectra in normal tissue. The validation of predicted cancer state mutation patterns demonstrates the usefulness and potential of a causal dynamical framework to understand and predict genetic mutations in cancer. © 2016 The Author(s).

Glacial cycles: exogenous orbital changes vs. endogenous climate dynamics

Science.gov (United States)

Kaufmann, R. K.; Juselius, K.

2010-04-01

We use a statistical model, the cointegrated vector autoregressive model, to assess the degree to which variations in Earth's orbit and endogenous climate dynamics can be used to simulate glacial cycles during the late Quaternary (390 kyr-present). To do so, we estimate models of varying complexity and compare the accuracy of their in-sample simulations. Results indicate that strong statistical associations between endogenous climate variables are not enough for statistical models to reproduce glacial cycles. Rather, changes in solar insolation associated with changes in Earth's orbit are needed to simulate glacial cycles accurately. Also, results suggest that non-linear dynamics, threshold effects, and/or free oscillations may not play an overriding role in glacial cycles.

Essays on Policy Evaluation with Endogenous Adoption

Science.gov (United States)

Gentile, Elisabetta

2011-01-01

Over the last decade, experimental and quasi-experimental methods have been favored by researchers in empirical economics, as they provide unbiased causal estimates. However, when implementing a program, it is often not possible to randomly assign subjects to treatment, leading to a possible endogeneity bias. This dissertation consists of two…

Endogenous retrovirus sequences expressed in male mammalian ...

African Journals Online (AJOL)

In humans, one ERV family, human endogenous retrovirus- K (HERV-K) is abundantly expressed, and is associated with germ cell tumours, while ERV3 env is expressed in normal human testis. Conclusion: The expression of ERVs in male reproductive tissues suggests a possible role in normal and disease conditions ...

Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses.

Science.gov (United States)

Byrd-Leotis, Lauren; Liu, Renpeng; Bradley, Konrad C; Lasanajak, Yi; Cummings, Sandra F; Song, Xuezheng; Heimburg-Molinaro, Jamie; Galloway, Summer E; Culhane, Marie R; Smith, David F; Steinhauer, David A; Cummings, Richard D

2014-06-03

Influenza viruses bind to host cell surface glycans containing terminal sialic acids, but as studies on influenza binding become more sophisticated, it is becoming evident that although sialic acid may be necessary, it is not sufficient for productive binding. To better define endogenous glycans that serve as viral receptors, we have explored glycan recognition in the pig lung, because influenza is broadly disseminated in swine, and swine have been postulated as an intermediary host for the emergence of pandemic strains. For these studies, we used the technology of "shotgun glycomics" to identify natural receptor glycans. The total released N- and O-glycans from pig lung glycoproteins and glycolipid-derived glycans were fluorescently tagged and separated by multidimensional HPLC, and individual glycans were covalently printed to generate pig lung shotgun glycan microarrays. All viruses tested interacted with one or more sialylated N-glycans but not O-glycans or glycolipid-derived glycans, and each virus demonstrated novel and unexpected differences in endogenous N-glycan recognition. The results illustrate the repertoire of specific, endogenous N-glycans of pig lung glycoproteins for virus recognition and offer a new direction for studying endogenous glycan functions in viral pathogenesis.

Synthetic mRNA devices that detect endogenous proteins and distinguish mammalian cells.

Science.gov (United States)

Kawasaki, Shunsuke; Fujita, Yoshihiko; Nagaike, Takashi; Tomita, Kozo; Saito, Hirohide

2017-07-07

Synthetic biology has great potential for future therapeutic applications including autonomous cell programming through the detection of protein signals and the production of desired outputs. Synthetic RNA devices are promising for this purpose. However, the number of available devices is limited due to the difficulty in the detection of endogenous proteins within a cell. Here, we show a strategy to construct synthetic mRNA devices that detect endogenous proteins in living cells, control translation and distinguish cell types. We engineered protein-binding aptamers that have increased stability in the secondary structures of their active conformation. The designed devices can efficiently respond to target proteins including human LIN28A and U1A proteins, while the original aptamers failed to do so. Moreover, mRNA delivery of an LIN28A-responsive device into human induced pluripotent stem cells (hiPSCs) revealed that we can distinguish living hiPSCs and differentiated cells by quantifying endogenous LIN28A protein expression level. Thus, our endogenous protein-driven RNA devices determine live-cell states and program mammalian cells based on intracellular protein information. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Post-stimulus endogenous and exogenous oscillations are differentially modulated by task difficulty.

Science.gov (United States)

Li, Yun; Lou, Bin; Gao, Xiaorong; Sajda, Paul

2013-01-01

We investigate the modulation of post-stimulus endogenous and exogenous oscillations when a visual discrimination is made more difficult. We use exogenous frequency tagging to induce steady-state visually evoked potentials (SSVEP) while subjects perform a face-car discrimination task, the difficulty of which varies on a trial-to-trial basis by varying the noise (phase coherence) in the image. We simultaneously analyze amplitude modulations of the SSVEP and endogenous alpha activity as a function of task difficulty. SSVEP modulation can be viewed as a neural marker of attention toward/away from the primary task, while modulation of post-stimulus alpha is closely related to cortical information processing. We find that as the task becomes more difficult, the amplitude of SSVEP decreases significantly, approximately 250-450 ms post-stimulus. Significant changes in endogenous alpha amplitude follow SSVEP modulation, occurring at approximately 400-700 ms post-stimulus and, unlike the SSVEP, the alpha amplitude is increasingly suppressed as the task becomes less difficult. Our results demonstrate simultaneous measurement of endogenous and exogenous oscillations that are modulated by task difficulty, and that the specific timing of these modulations likely reflects underlying information processing flow during perceptual decision-making.

Managing the endogeneity problem of the market structure: a study on banking competition

Directory of Open Access Journals (Sweden)

Tri Mulyaningsih

2015-10-01

Full Text Available Recent literature suggests that the market structure is an endogenous variable that is determined by a firm’s behaviour and the competitive environment of the industry. This study examines the relation between the market structure and the banks’ behaviour in Indonesian banking by considering the endogeneity problem of them as variables. The estimations using the Vector-Error-Correction approach suggest that the structural approach provides a valid prediction of the relationship between market structure and bank behaviour by recognizing the endogeneity issue between those two variables. The banking industry would be more competitive if the market was less concentrated.

Immunoadjuvants enhance the febrile responses of rats to endogenous pyrogen.

Science.gov (United States)

Stitt, J T; Shimada, S G

1989-11-01

The febrile responses of male Sprague-Dawley rats to a semipurified endogenous pyrogen produced from human monocytes were characterized by establishing fever dose-response curves. The animals were then injected intravenously with a number of substances that possessed the common properties of stimulating the phagocytic activity of the cells of the reticuloendothelial system and of acting as immunoadjuvants. The substances used were zymosan, lipopolysaccharide endotoxin, and muramyl dipeptide. Three days after any of these immunoadjuvants were injected, the fever sensitivity of the rats was remeasured. In each case, the slope of the fever dose-response curve tripled, and in some instances the response threshold for fever response was reduced by factors of three to eight. Furthermore, the maximum increase in body temperature produced by the endogenous pyrogen was more than doubled after immunoadjuvant treatment. By contrast latex beads, which are also phagocytized by the cells of the reticuloendothelial system but do not subsequently increase their phagocytic index nor do they enhance immune responses, had no effect on the fever sensitivity of rats in response to endogenous pyrogen. In the light of these findings, it is suggested that the febrile responses of rats to endogenous pyrogen are mediated in some manner by cells that possess some of the properties of reticuloendothelial cells. The location of these putative cells must be close to the circulation, because the immunoadjuvants used in this study were, for the most part, large molecular weight molecules that could not cross the blood-brain barrier easily.

Differentiation of endogenous and exogenous steroids by gas chromatography-combustion-mass spectrometry isotope ratio

International Nuclear Information System (INIS)

Montes de Oca Porto, Rodny; Rosado Perez, Aristides; Correa Vidal, Margarita Teresa

2007-01-01

Urinary steroids profiles are used to control the misuse of endogenous steroids such as testosterone and dihydrotestosterone. The testosterone/epistestosterone ratio, measured by Gas Chromatography-Mass Spectrometry, is used to control testosterone administration. When T/E ratio is higher than 4, consumption of testosterone or its precursors is suspected. Recent researches have demonstrated the effectiveness of Carbon Isotope Ratio Mass Spectrometry to detect and confirm endogenous steroids administration. The ratio of the two stable carbon isotopes 1 3 C and 1 2 C allows the differentiation of natural and synthetic steroids because synthetic steroids have lower 1 3 C abundance. In fact, the carbon isotope ratios can be used to determine endogenous steroids administration even when testosterone/epistestosterone ratio is at its normal value. In the current work, some of the most important aspects related to differentiation of endogenous and exogenous steroids by means of Gas Chromatography-Combustion-Isotope Ratio Mass Spectrometry are discussed. Also, this article provides a review about the purification and sample preparation previous to the analysis, and diet effects on carbon isotope ratio of endogenous anabolics steroids is presented too

Biology and evolution of the endogenous koala retrovirus.

Science.gov (United States)

Tarlinton, R; Meers, J; Young, P

2008-11-01

Although endogenous retroviruses are ubiquitous features of all mammalian genomes, the process of initial germ line invasion and subsequent inactivation from a pathogenic element has not yet been observed in a wild species. Koala retrovirus (KoRV) provides a unique opportunity to study this process of endogenisation in action as it still appears to be spreading through the koala population. Ongoing expression of the endogenous sequence and consequent high levels of viraemia have been linked to neoplasia and immunosuppression in koalas. This apparently recent invader of the koala genome shares a remarkably close sequence relationship with the pathogenic exogenous Gibbon ape leukaemia virus (GALV), and comparative analyses of KoRV and GALVare helping to shed light on how retroviruses in general adapt to a relatively benign or at least less pathogenic existence within a new host genome. (Part of a multi-author review).

Endogenous MMTV proviruses induce susceptibility to both viral and bacterial pathogens.

Directory of Open Access Journals (Sweden)

Sanchita Bhadra

2006-12-01

Full Text Available Most inbred mice carry germline proviruses of the retrovirus, mouse mammary tumor virus (MMTV (called Mtvs, which have multiple replication defects. A BALB/c congenic mouse strain lacking all endogenous Mtvs (Mtv-null was resistant to MMTV oral and intraperitoneal infection and tumorigenesis compared to wild-type BALB/c mice. Infection of Mtv-null mice with an MMTV-related retrovirus, type B leukemogenic virus, also resulted in severely reduced viral loads and failure to induce T-cell lymphomas, indicating that resistance is not dependent on expression of a superantigen (Sag encoded by exogenous MMTV. Resistance to MMTV in Mtv-null animals was not due to neutralizing antibodies. Further, Mtv-null mice were resistant to rapid mortality induced by intragastric inoculation of the Gram-negative bacterium, Vibrio cholerae, but susceptibility to Salmonella typhimurium was not significantly different from BALB/c mice. Susceptibility to both MMTV and V. cholerae was reconstituted by the presence of any one of three endogenous Mtvs located on different chromosomes and was associated with increased pathogen load. One of these endogenous proviruses is known to encode only Sag. Therefore, Mtv-encoded Sag appears to provide a unique genetic susceptibility to specific viruses and bacteria. Since human endogenous retroviruses also encode Sags, these studies have broad implications for pathogen-induced responses in mice and humans.

Studies on the pathogenesis of fever. IX. Characteristics of endogenous serum pyrogen and mechanisms governing its release.

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PETERSDORF, R G; KEENE, W R; BENNETT, I L

1957-12-01

The "endogenous serum pyrogen" that appears in the circulating blood after a single intravenous injection of endotoxin does not produce leukopenia in normal animals, fails to provoke the local Shwartzman reaction, and elicits no "tolerance" when injected daily. Suppression of the febrile response to endotoxin by prednisone does not prevent the appearance of pyrogen in the blood. Animals given large amounts of endotoxin daily continue to respond with high fevers despite failure of endogenous serum pyrogen to appear in detectable amounts after the first two or three injections. Analysis of the response to daily injections shows clearly that the fever during the first 2 hours after administration of endotoxin is unrelated to levels of endogenous serum pyrogen; in contrast, the magnitude of the fever after the 2nd hour correlates well with endogenous pyrogen in some instances. The leukopenic response to endotoxin could not be correlated with the appearance of endogenous serum pyrogen. The differences between endotoxin and endogenous pyrogen and the similarities between leukocyte extracts (sterile exudates) and endogenous pyrogen are summarized and discussed. Dissociation of the febrile response to bacterial endotoxin and levels of endogenous serum pyrogen are discussed and it is concluded that a mechanism involving both direct and indirect action of endotoxins offers the best explanation for the pyrogenic action of these bacterial products.

Endogenous lycopene improves ethanol production under acetic acid stress in Saccharomyces cerevisiae.

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Pan, Shuo; Jia, Bin; Liu, Hong; Wang, Zhen; Chai, Meng-Zhe; Ding, Ming-Zhu; Zhou, Xiao; Li, Xia; Li, Chun; Li, Bing-Zhi; Yuan, Ying-Jin

2018-01-01

Acetic acid, generated from the pretreatment of lignocellulosic biomass, is a significant obstacle for lignocellulosic ethanol production. Reactive oxidative species (ROS)-mediated cell damage is one of important issues caused by acetic acid. It has been reported that decreasing ROS level can improve the acetic acid tolerance of Saccharomyces cerevisiae . Lycopene is known as an antioxidant. In the study, we investigated effects of endogenous lycopene on cell growth and ethanol production of S. cerevisiae in acetic acid media. By accumulating endogenous lycopene during the aerobic fermentation of the seed stage, the intracellular ROS level of strain decreased to 1.4% of that of the control strain during ethanol fermentation. In the ethanol fermentation system containing 100 g/L glucose and 5.5 g/L acetic acid, the lag phase of strain was 24 h shorter than that of control strain. Glucose consumption rate and ethanol titer of yPS002 got to 2.08 g/L/h and 44.25 g/L, respectively, which were 2.6- and 1.3-fold of the control strain. Transcriptional changes of INO1 gene and CTT1 gene confirmed that endogenous lycopene can decrease oxidative stress and improve intracellular environment. Biosynthesis of endogenous lycopene is first associated with enhancing tolerance to acetic acid in S. cerevisiae . We demonstrate that endogenous lycopene can decrease intracellular ROS level caused by acetic acid, thus increasing cell growth and ethanol production. This work innovatively   puts forward a new strategy for second generation bioethanol production during lignocellulosic fermentation.

Endogenous repair mechanisms enhanced in Parkinson's disease following stem cell therapy

Directory of Open Access Journals (Sweden)

Eleonora Napoli

2017-01-01

Full Text Available This mini-review highlights the innovative observation that transplanted human neural stem cells can bring about endogenous brain repair through the stimulation of multiple regenerative processes in the neurogenic area (i.e., subventricular zone [SVZ] in an animal model of Parkinson's disease (PD. In addition, we convey that identifying anti-inflammatory cytokines, therapeutic proteomes, and neurotrophic factors within the SVZ may be essential to induce brain repair and behavioral recovery. This work opens up a new area of research for further understanding the pathology and treatment of PD. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

Persistent Inflammation Alters the Function of the Endogenous Brain Stem Cell Compartment

OpenAIRE

Pluchino, Stefano; Muzio, Luca; Alfaro-Cervello, Clara; Salani, Giuliana; Porcheri, Cristina; Brambilla, Elena; Cavasinni, Francesca; Bergamaschi, Andrea; Garcia-Verdugo, Jose Manuel; Comi, Giancarlo; Martino, Gianvito; Imitola, Jaime; Deleidi, Michela; Khoury, Samia Joseph

2008-01-01

Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain in...

Endogenous hallucinogens as ligands of the trace amine receptors: a possible role in sensory perception.

Science.gov (United States)

Wallach, J V

2009-01-01

While the endogenous hallucinogens, N,N-dimethyltryptamine, 5-hydroxy-N,N-dimethyl-tryptamine and 5-methoxy-N,N-dimethyltryptamine, have been acknowledged as naturally occurring components of the mammalian body for decades, their biological function remains as elusive now as it was at the time of their discovery. The recent discovery of the trace amine associated receptors and the activity of DMT and other hallucinogenic compounds at these receptor sites leads to the hypothesis that the endogenous hallucinogens act as neurotransmitters of a subclass of these trace amine receptors. Additionally, while activity at the serotonin 5-HT2A receptor has been proposed as being responsible for the hallucinogenic affects of administered hallucinogens, in their natural setting the 5-HT2A receptor may not interact with the endogenous hallucinogens at all. Additionally 5-HT2A agonist activity is unable to account for the visual altering effects of many of the administered hallucinogens; these effects may be mediated by one of the endogenous hallucinogen trace amine receptors rather than the serotonin 5-HT2A receptor. Therefore, activity at the trace amine receptors, in addition to serotonin receptors, may play a large role in the sensory altering effects of administered hallucinogens and the trace amine receptors along with their endogenous hallucinogen ligands may serve an endogenous role in mediating sensory perception in the mammalian central nervous system. Thus the theory proposed states that these compounds act as true endogenous hallucinogenic transmitters acting in regions of the central nervous system involved in sensory perception.

Dietary cholesterol promotes repair of demyelinated lesions in the adult brain.

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Berghoff, Stefan A; Gerndt, Nina; Winchenbach, Jan; Stumpf, Sina K; Hosang, Leon; Odoardi, Francesca; Ruhwedel, Torben; Böhler, Carolin; Barrette, Benoit; Stassart, Ruth; Liebetanz, David; Dibaj, Payam; Möbius, Wiebke; Edgar, Julia M; Saher, Gesine

2017-01-24

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes.

An active role for endogenous beta-1,3-glucanase genes in transgene-mediated co-suppression in tobacco.

Science.gov (United States)

Sanders, Matthew; Maddelein, Wendy; Depicker, Anna; Van Montagu, Marc; Cornelissen, Marc; Jacobs, John

2002-11-01

Post-transcriptional gene silencing (PTGS) is characterized by the accumulation of short interfering RNAs that are proposed to mediate sequence-specific degradation of cognate and secondary target mRNAs. In plants, it is unclear to what extent endogenous genes contribute to this process. Here, we address the role of the endogenous target genes in transgene-mediated PTGS of beta-1,3-glucanases in tobacco. We found that mRNA sequences of the endogenous glucanase glb gene with varying degrees of homology to the Nicotiana plumbaginifolia gn1 transgene are targeted by the silencing machinery, although less efficiently than corresponding transgene regions. Importantly, we show that endogene-specific nucleotides in the glb sequence provide specificity to the silencing process. Consistent with this finding, small sense and antisense 21- to 23-nucleotide RNAs homologous to the endogenous glb gene were detected. Combined, these data demonstrate that a co-suppressed endogenous glucan ase gene is involved in signal amplification and selection of homologous targets, and show that endogenous genes can actively participate in PTGS in plants. The findings are introduced as a further sophistication of the post-transciptional silencing model.

Indicators for the total duration of premenopausal endogenous estrogen exposure in relation to BMD

NARCIS (Netherlands)

Hagemans, M.L.C.; Schouw, van der Y.T.; Kleijn, de M.J.J.; Staveren, van W.A.; Pop, V.J.M.; Leusink, G.L.; Grobbee, D.E.

2004-01-01

BACKGROUND: Previous studies have shown that age at menopause is an important indicator of duration of endogenous estrogen exposure. The present study investigates whether combining more information on reproductive factors is useful in estimating individual total duration of exposure to endogenous

Acute myocardial infarction without significant coronary stenoses associated with endogenous subclinical hyperthyroidism.

Science.gov (United States)

Patanè, Salvatore; Marte, Filippo; Sturiale, Mauro

2012-04-05

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. Nowadays, there is growing interest regarding endogenous sublinical hyperthyroidism and the cardiovascular system. We present a case of acute myocardial infarction without significant coronary stenoses in a 75-year-old Italian woman with endogenous subclinical hyperthyroidism. Also this case focuses attention on the importance of a correct evaluation of endogenous subclinical hyperthyroidism. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Isolating Exogenous and Endogenous Modes of Temporal Attention

Science.gov (United States)

Lawrence, Michael A.; Klein, Raymond M.

2013-01-01

The differential allocation of information processing resources over time, here termed "temporal attention," may be achieved by relatively automatic "exogenous" or controlled "endogenous" mechanisms. Over 100 years of research has confounded these theoretically distinct dimensions of temporal attention. The current…

Endogenous heparin levels in the controlled asthmatic patient ...

African Journals Online (AJOL)

Background. Since heparin possesses anti-inflammatory properties, it is hypothesised that asthmatic patients have decreased levels of circulating heparin compared with healthy individuals. Design. We compared endogenous heparin levels in controlled asthmatic patients (53 adults) from the Asthma Clinic at ...

Ageing, human capital and demographic dividends with endogenous growth, labour supply and foreign capital

NARCIS (Netherlands)

Edle von Gaessler, Anne; Ziesemer, Thomas

2017-01-01

We modify a Lucas-type endogenous growth model to contain endogenous labour supply, imperfect international capital movements, and estimated interest and education time functions. Solutions based on realistic calibrations show that (i) the rate of human capital depreciation through ageing has a much

Endogenous Endophthalmitis in Patients with MRSA Septicemia: A Case Series and Review of Literature.

Science.gov (United States)

Shenoy, Shailaja Bhat; Thotakura, Meena; Kamath, Yogish; Bekur, Ragini

2016-10-01

To report the presentation, predisposing factors, clinical features and outcome in 6 eyes of 3 patients with endogenous endophthalmitis secondary to methicillin resistant staphylococcus aureus (MRSA) septicaemia. Retrospective review of case records of 3 patients who were treated for endogenous endophthalmitis secondary to MRSA septicaemia in a tertiary referral institution. All three patients had systemic predisposition to endogenous endophthalmitis (diabetes, urosepsis). Two patients presented within 1 week of onset of visual symptoms and the third after 3 months. Blood culture was positive for MRSA in all patients. Visual and anatomical improvement was noted in two patients who presented early. The third patient's visual outcome despite early treatment with intravitreal antibiotics and vitrectomy was not satisfactory. Endogenous endophthalmitis by MRSA is a rare but serious condition. Early and specific therapy based on reliable detection of the underlying microorganism is needed for good anatomical and functional outcome.

Endogenous and exogenous control of ecosystem function: N cycling in headwater streams

OpenAIRE

Valett, H. M.; Thomas, S. A.; Mulholland, P. J.; Webster, J. R.; Dahm, C. N.; Fellows, C. S.; Crenshaw, C. L.; Peterson, C. G.

2008-01-01

Allochthonous inputs act as resource subsidies to many ecosystems, where they exert strong influences on metabolism and material cycling. At the same time, metabolic theory proposes endogenous thermal control independent of resource supply. To address the relative importance of exogenous and endogenous influences, we quantified spatial and temporal variation in ecosystem metabolism and nitrogen (N) uptake using seasonal releases of (15)N as nitrate in six streams differing in riparian-stream ...

Endogenous scheduling preferences and congestion

DEFF Research Database (Denmark)

Fosgerau, Mogens; Small, Kenneth

2010-01-01

and leisure, but agglomeration economies at home and at work lead to scheduling preferences forming endogenously. Using bottleneck congestion technology, we obtain an equilibrium queuing pattern consistent with a general version of the Vickrey bottleneck model. However, the policy implications are different....... Compared to the predictions of an analyst observing untolled equilibrium and taking scheduling preferences as exogenous, we find that both the optimal capacity and the marginal external cost of congestion have changed. The benefits of tolling are greater, and the optimal time varying toll is different....

Estimation of endogenous faecal calcium in buffalo (BOS bubalis) by isotope dilution technique

International Nuclear Information System (INIS)

Singh, S.; Sareen, V.K.; Marwaha, S.R.; Sekhon, B.; Bhatia, I.S.

1973-01-01

Detailed investigations on the isotope-dilution technique for the estimation of endogenous faecal calcium were conducted with buffalo calves fed on growing ration. The ration consisted of wheat straw, green lucerne and concentrate mix. The endogenous faecal calcium was 3.71 g/day, which is 17.8 percent of the total faecal calcium. The apparent and true digestibilities of Ca were calculated as 51 and 60 percent respectively. The endogenous faecal calcium can be estimated in buffalo calves by giving single subcutaneous injection of Ca 45 and collecting blood samples on 12th and 21st days only, and representative sample from the faeces collected from 13th through 22nd day after the injection. (author)

Parvovirus-derived endogenous viral elements in two South American rodent genomes.

Science.gov (United States)

Arriagada, Gloria; Gifford, Robert J

2014-10-01

We describe endogenous viral elements (EVEs) derived from parvoviruses (family Parvoviridae) in the genomes of the long-tailed chinchilla (Chinchilla lanigera) and the degu (Octodon degus). The novel EVEs include dependovirus-related elements and representatives of a clearly distinct parvovirus lineage that also has endogenous representatives in marsupial genomes. In the degu, one dependovirus-derived EVE was found to carry an intact reading frame and was differentially expressed in vivo, with increased expression in the liver. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Lethal doses of ionizing radiation versus endogenous level of superoxide dismutase

Energy Technology Data Exchange (ETDEWEB)

Lipecka, K; Domanski, T; Dniaszewska, K; Grabowska, B; Pietrowicz, D; Lindner, P; Cisowska, B; Gorski, H [Military Medical Academy, Lodz (Poland). Inst. of Occupational Medicine

1982-06-22

The stability of superoxide dismutase (SOD) as well as its activity distribution in a human population were investigated. The SOD activity level of the erythrocytes proved to be an index for the endogenous SOD activity in the whole body. In a rat population, having similar SOD frequency distribution as a human population, the mortality due to acute irradiation depended on the SOD level; after a single acute dose approximating the lethal dose (LD/sub 50/30/) the survival depended distinctly on the endogenous SOD activity level.

Endogenous opioid systems: physiological role in the self-limitation of seizures.

Science.gov (United States)

Tortella, F C; Long, J B; Holaday, J W

1985-04-15

Immediately following a seizure, the severity of subsequent seizures is significantly reduced. The involvement of endogenous opioid systems as a physiological regulator of this postseizure inhibition was studied in rats using repeated maximal electroshock (MES) seizures. Both the opiate antagonist (-)-naloxone and morphine tolerance abolished the progressive seizure protection associated with repeated MES. We propose that endogenous opioids, activated by a prior seizure, provide a central homeostatic inhibitory mechanism which may be responsible for the initiation of a postictal refractory state in the epileptic.

Inflation Targeting and Liquidity Traps under Endogenous Credibility

NARCIS (Netherlands)

Hommes, C.; Lustenhouwer, J.

2015-01-01

We derive policy implications for an inflation targeting central bank, who's credibility is endogenous and depends on its past ability to achieve its targets. We do this in a New Keynesian framework with heterogeneous agents and boundely rational expectations. Our assumptions about expectation

Endogenous and Exogenous Attention Shifts are Mediated by the Same Large-Scale Neural Network.

NARCIS (Netherlands)

Peelen, M.V.; Heslenfeld, D.J.; Theeuwes, J.

2004-01-01

Event-related fMRI was used to examine the neural basis of endogenous (top-down) and exogenous (bottom-up) spatial orienting. Shifts of attention were induced by central (endogenous) or peripheral (exogenous) cues. Reaction times on subsequently presented targets showed the expected pattern of

Development of an enrichment method for endogenous phosphopeptide characterization in human serum.

Science.gov (United States)

La Barbera, Giorgia; Capriotti, Anna Laura; Cavaliere, Chiara; Ferraris, Francesca; Laus, Michele; Piovesana, Susy; Sparnacci, Katia; Laganà, Aldo

2018-01-01

The work describes the development of an enrichment method for the analysis of endogenous phosphopeptides in serum. Endogenous peptides can play significant biological roles, and some of them could be exploited as future biomarkers. In this context, blood is one of the most useful biofluids for screening, but a systematic investigation of the endogenous peptides, especially phosphorylated ones, is still lacking, mainly due to the lack of suitable analytical methods. Thus, in this paper, different phosphopeptide enrichment strategies were pursued, based either on metal oxide affinity chromatography (MOAC, in the form of commercial TiO 2 spin columns or magnetic graphitized carbon black-TiO 2 composite), or on immobilized metal ion affinity chromatography (IMAC, in the form of Ti 4+ -IMAC magnetic material or commercial Fe 3+ -IMAC spin columns). While MOAC strategies proved completely unsuccessful, probably due to interfering phospholipids displacing phosphopeptides, the IMAC materials performed very well. Different sample preparation strategies were tested, comprising direct dilution with the loading buffer, organic solvent precipitation, and lipid removal from the matrix, as well as the addition of phosphatase inhibitors during sample handling for maximized endogenous phosphopeptide enrichment. All data were acquired by a shotgun peptidomics approach, in which peptide samples were separated by reversed-phase nanoHPLC hyphenated with high-resolution tandem mass spectrometry. The devised method allowed the identification of 176 endogenous phosphopeptides in fresh serum added with inhibitors by the direct dilution protocol and the Ti 4+ -IMAC magnetic material enrichment, but good results could also be obtained from the commercial Fe 3+ -IMAC spin column adapted to the batch enrichment protocol.

Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions

Directory of Open Access Journals (Sweden)

R.A. Johnson

1999-01-01

Full Text Available Carbon monoxide (CO is a pollutant commonly recognized for its toxicological attributes, including CNS and cardiovascular effects. But CO is also formed endogenously in mammalian tissues. Endogenously formed CO normally arises from heme degradation in a reaction catalyzed by heme oxygenase. While inhibitors of endogenous CO production can raise arterial pressure, heme loading can enhance CO production and lead to vasodepression. Both central and peripheral tissues possess heme oxygenases and generate CO from heme, but the inability of heme substrate to cross the blood brain barrier suggests the CNS heme-heme oxygenase-CO system may be independent of the periphery. In the CNS, CO apparently acts in the nucleus tractus solitarii (NTS promoting changes in glutamatergic neurotransmission and lowering blood pressure. At the periphery, the heme-heme oxygenase-CO system can affect cardiovascular functions in a two-fold manner; specifically: 1 heme-derived CO generated within vascular smooth muscle (VSM can promote vasodilation, but 2 its actions on the endothelium apparently can promote vasoconstriction. Thus, it seems reasonable that the CNS-, VSM- and endothelial-dependent actions of the heme-heme oxygenase-CO system may all affect cardiac output and vascular resistance, and subsequently blood pressure.

Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

Energy Technology Data Exchange (ETDEWEB)

Marion, Tracy L., E-mail: tracylmarion@qualyst.com [Curriculum in Toxicology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7270 (United States); Perry, Cassandra H., E-mail: cassandraperry@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); St Claire, Robert L., E-mail: bobstclaire@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); Brouwer, Kim L.R., E-mail: kbrouwer@unc.edu [Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, CB 7569 Kerr Hall, Chapel Hill, NC 27599-7569 (United States)

2012-05-15

Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR{sup ®} technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na{sup +}-taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA

Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

International Nuclear Information System (INIS)

Marion, Tracy L.; Perry, Cassandra H.; St Claire, Robert L.; Brouwer, Kim L.R.

2012-01-01

Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR ® technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na + -taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA concentrations

A comparative assessment of endogenous water institutional change

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Pande, Saket; Ersten, Maurits

2013-04-01

This paper builds the theory of endogenous institutional change, first proposed by Greif and Laitin (2004), for water scarce regions in context of water institutions. The current emphasis on environmental change, including hydrological change, largely ignores the adaptation of human societies to change. Humans have mostly been considered as boundary conditions or parameters of the dynamics of hydrological change and are not considered as conduits of feedbacks. Nonetheless, the dynamical representation of hydrological change with feedbacks between various components of a system is assuring since it is reminiscent of processual ecological anthropology(Orlove, 1980), except that individual decision making is absent. This paper proposes to consider selected dryland basins of the world, to conceptualize proxies of water relevant socio-economic organisation, such as spatial scales of upstream-downstream cooperation in water use, synthesized over time and then proposes a comparative assessment to test regularities predicted by an extension of river game theory (Ambec and Ehlers, 2008; van der Brink et al, 2012) to endogenous institutional change. References: Orlove, B. S. (1980). Ecological Anthropology. Annual Review of Anthropology, Vol. 9 (1980), pp. 235-273. Greif. A. and D. D. Laitin (2004). A Theory of Endogenous Institutional Change. American Political Science Review, Vol. 98, No. 4 November 2004. Ambec, S. and L. Ehlers (2008). Sharing a river amongst satiable agents. Games and Economic Behavior, 64, 35-50. Van der Brink, G. van der Laan and N. Moes (2012). Fair agreements for sharing international rivers with multiple springs and externalities. Journal of Environmental Economics and Management, 63, 388-403.

THE ROLE OF ENTEROSORBENTS IN TREATMENT OF ENDOGENOUS INTOXICATION SYNDROME

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N. I. Ursova

2012-01-01

Full Text Available Usage of enterosorbents in treatment of almost all types of acute and chronic disorders accompanied with endogenous intoxication syndrome takes on special significance. The critical point of endogenous intoxication pathogenesis is dysfunction of microbiocenosis and intestinal barrier. The necessity of enterosorbents usage is very high due to their efficacy, safety and wide availability. Smectite dioctaedric (diosmectite, which has been successfully used in clinical practice for a long period of time, is of an increased interest among the natural enterosorbents. The main quality of diosmectite is its restoration effect on the microbiocenisis and intestinal barrier function, and with a high degree of evidence-based efficacy and safety.

A novel endogenous betaretrovirus group characterized from polar bears (Ursus maritimus) and giant pandas (Ailuropoda melanoleuca).

Science.gov (United States)

Mayer, Jens; Tsangaras, Kyriakos; Heeger, Felix; Avila-Arcos, María; Stenglein, Mark D; Chen, Wei; Sun, Wei; Mazzoni, Camila J; Osterrieder, Nikolaus; Greenwood, Alex D

2013-08-15

Transcriptome analysis of polar bears (Ursus maritimus) yielded sequences with highest similarity to the human endogenous retrovirus group HERV-K(HML-2). Further analysis of the polar bear draft genome identified an endogenous betaretrovirus group comprising 26 proviral copies and 231 solo LTRs. Molecular dating indicates the group originated before the divergence of bears from a common ancestor but is not present in all carnivores. Closely related sequences were identified in the giant panda (Ailuropoda melanoleuca) and characterized from its genome. We have designated the polar bear and giant panda sequences U. maritimus endogenous retrovirus (UmaERV) and A. melanoleuca endogenous retrovirus (AmeERV), respectively. Phylogenetic analysis demonstrated that the bear virus group is nested within the HERV-K supergroup among bovine and bat endogenous retroviruses suggesting a complex evolutionary history within the HERV-K group. All individual remnants of proviral sequences contain numerous frameshifts and stop codons and thus, the virus is likely non-infectious. Copyright © 2013 Elsevier Inc. All rights reserved.

Peptic ulcer disease in endogenous hypercortisolism: myth or reality?

Science.gov (United States)

Hatipoglu, Esra; Caglar, Asli Sezgin; Caglar, Erkan; Ugurlu, Serdal; Tuncer, Murat; Kadioglu, Pinar

2015-11-01

Many clinicians believe hypercortisolism is ulcerogenic. However, data from clinical studies show that prophylaxis for peptic ulcer disease is no longer recommended in patients receiving corticosteroid treatment. This has not yet been verified in endogenous hypercortisolism by controlled clinical studies. The purpose of the current study was to evaluate the relationship between endogenous Cushing's syndrome (CS) and peptic ulcer disease and Helicobacter pylori infection. The study group contained 20 cases with CS resulting from ACTH-dependent endogenous hypercortisolism. The control groups consisted of 14 age- and gender-matched cases receiving exogenous corticosteroid therapy and 100 cases of dyspepsia with non-cushingoid features. Upper gastrointestinal endoscopy was performed on all cases. Biopsies were taken from five different points: two samples from the antrum, two samples from the corpus, and one sample from the fundus. A histological diagnosis of Helicobacter pylori infection was also obtained from evaluation of biopsy specimens. The frequency of stomach and duodenal ulcers did not vary between the groups (p = 0.5 and p = 0.7). Antral gastritis was less frequent and pangastritis was more common in cases with CS compared to the healthy controls (p = 0.001 and p peptic ulcer or Helicobacter pylori infection. Prophylactic use of proton pump inhibitors is not compulsory for hypercortisolism of any type.

A revised nomenclature for transcribed human endogenous retroviral loci

Science.gov (United States)

2011-01-01

Background Endogenous retroviruses (ERVs) and ERV-like sequences comprise 8% of the human genome. A hitherto unknown proportion of ERV loci are transcribed and thus contribute to the human transcriptome. A small proportion of these loci encode functional proteins. As the role of ERVs in normal and diseased biological processes is not yet established, transcribed ERV loci are of particular interest. As more transcribed ERV loci are likely to be identified in the near future, the development of a systematic nomenclature is important to ensure that all information on each locus can be easily retrieved. Results Here we present a revised nomenclature of transcribed human endogenous retroviral loci that sorts loci into groups based on Repbase classifications. Each symbol is of the format ERV + group symbol + unique number. Group symbols are based on a mixture of Repbase designations and well-supported symbols used in the literature. The presented guidelines will allow newly identified loci to be easily incorporated into the scheme. Conclusions The naming system will be employed by the HUGO Gene Nomenclature Committee for naming transcribed human ERV loci. We hope that the system will contribute to clarifying a certain aspect of a sometimes confusing nomenclature for human endogenous retroviruses. The presented system may also be employed for naming transcribed loci of human non-ERV repeat loci. PMID:21542922

When endogenous spatial attention improves conscious perception: effects of alerting and bottom-up activation.

Science.gov (United States)

Botta, Fabiano; Lupiáñez, Juan; Chica, Ana B

2014-01-01

Recent studies have consistently demonstrated that conscious perception interacts with exogenous attentional orienting, but it can be dissociated from endogenous attentional orienting (Chica Lasaponara, et al., 2011; Wyart & Tallon-Baudry, 2008). It has been hypothesized that enhanced conscious processing at exogenously attended locations results from a synergistic action of spatial orienting, bottom-up activation, and phasic alerting induced by the abrupt onset of the exogenous cue (Chica, Lasaponara, et al., 2011). Instead, as endogenous cues need more time to be interpreted, the phasic alerting they produce may have dissipated when the target appears. Furthermore, endogenous cues presumably elicit a weak bottom-up activation at the cued location. Consistent with these hypotheses, we observed that endogenous attention modulated conscious perception, but only when phasic alerting or bottom-up activation was increased. Results are discussed in the context of recent theoretical models of consciousness (Dehaene, Changeux, Naccache, Sackur, & Sergent, 2006). Copyright © 2013 Elsevier Inc. All rights reserved.

Role of endogenous opioid peptides in the pathogenesis of motion sickness

International Nuclear Information System (INIS)

Yasnetsov, V.V.; Il'ina, S.L.; Karsanova, S.K.; Medvedev, O.S.; Mokrousova, A.V.; Sabaev, V.V.; Shashkov, V.A.; Tigranyan, R.A.; Vakulina, O.P

1986-01-01

This paper examines the pathogenesis of motion sickness and the role of the various neurochemical systems of the body in the genesis of the condition. It has been shown that the endogenous opioid system participates in the genesis of several pathological processes; this was the motivation for the study. The plasma beta-endorphin level was determined in samples from 19 clinically healthy males. Considering the positive prophylactic and therapeutic effect of naloxone against motion sickness it can be postulated that endogenous opioid peptides participate in the genesis of the vestibulo-autonomic disorders in motion sickness

Role of endogenous opioid peptides in the pathogenesis of motion sickness

Energy Technology Data Exchange (ETDEWEB)

Yasnetsov, V.V.; Il' ina, S.L.; Karsanova, S.K.; Medvedev, O.S.; Mokrousova, A.V.; Sabaev, V.V.; Shashkov, V.A.; Tigranyan, R.A.; Vakulina, O.P

1986-01-01

This paper examines the pathogenesis of motion sickness and the role of the various neurochemical systems of the body in the genesis of the condition. It has been shown that the endogenous opioid system participates in the genesis of several pathological processes; this was the motivation for the study. The plasma beta-endorphin level was determined in samples from 19 clinically healthy males. Considering the positive prophylactic and therapeutic effect of naloxone against motion sickness it can be postulated that endogenous opioid peptides participate in the genesis of the vestibulo-autonomic disorders in motion sickness.

Decreased Endogenous Hydrogen Sulfide Generation in Penile Tissues of Diabetic Rats with Erectile Dysfunction.

Science.gov (United States)

Zhang, Yan; Yang, Jun; Wang, Tao; Wang, Shao-Gang; Liu, Ji-Hong; Yin, Chun-Ping; Ye, Zhang-Qun

2016-03-01

Hydrogen sulfide (H2S) is an endogenous gasotransmitter. The levels of H2S-generating enzyme expression and endogenous H2S production in diabetic rats with erectile dysfunction (ED) remain unknown. The aim of this study was to investigate the expression of the H2S-generating enzymes and endogenous production of H2S in penile tissues of diabetic ED rats. Experimental rats were randomly divided into normal control group, apomorphine (APO)-positive group and APO-negative group. Primary rat corpus cavernosum smooth muscle cells (CCSMCs) and aortic endothelial cells (AECs) were isolated and cultured in vitro under 3 different conditions: normal glucose (NG) condition, high glucose (HG) condition, and osmotic control (OC) condition. Erectile function; H2S concentrations in plasma or penile tissues; expression of H2S-generating enzymes and endogenous H2S production in penile tissues, CCSMCs, and AECs. Erectile function was significantly decreasedin the APO-negative group. In addition to significantly decreased expression of cysteine aminotransferase (CAT), d-amino acid oxidase (DAO), and 3-mercaptopyruvate sulfurtransferase (3-MST), the H2S concentrations in plasma and penile tissues and endogenous H2S production were significantly decreased in the APO-negative group. Endogenous H2S production by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) decreased to the same levels in the APO-negative and APO-positive groups as that in the normal control group. However, CBS and CSE expression remained unchanged in the 3 groups. Under HG conditions, H2S-generating enzyme expression in AECs did not change, while CAT, DAO, and 3-MST expression in CCSMCs was significantly decreased. In both cell types, H2S production by these enzymes was decreased in the HG group. Endogenous H2S production was significantly decreased in the diabetic ED rats' penile tissues due to downregulated expression of the CAT/3-MST and DAO/3-MST pathways and low activities of CBS and CSE

Novel MeCP2 isoform-specific antibody reveals the endogenous MeCP2E1 expression in murine brain, primary neurons and astrocytes.

Directory of Open Access Journals (Sweden)

Robby M Zachariah

Full Text Available Rett Syndrome (RTT is a severe neurological disorder in young females, and is caused by mutations in the X-linked MECP2 gene. MECP2/Mecp2 gene encodes for two protein isoforms; MeCP2E1 and MeCP2E2 that are identical except for the N-terminus region of the protein. In brain, MECP2E1 transcripts are 10X higher, and MeCP2E1 is suggested to be the relevant isoform for RTT. However, due to the unavailability of MeCP2 isoform-specific antibodies, the endogenous expression pattern of MeCP2E1 is unknown. To gain insight into the expression of MeCP2E1 in brain, we have developed an anti-MeCP2E1 antibody and validated its specificity in cells exogenously expressing individual MeCP2 isoforms. This antibody does not show any cross-reactivity with MeCP2E2 and detects endogenous MeCP2E1 in mice brain, with no signal in Mecp2(tm1.1Bird y/- null mice. Additionally, we show the endogenous MeCP2E1 expression throughout different brain regions in adult mice, and demonstrate its highest expression in the brain cortex. Our results also indicate that MeCP2E1 is highly expressed in primary neurons, as compared to primary astrocytes. This is the first report of the endogenous MeCP2E1 expression at the protein levels, providing novel avenues for understanding different aspects of MeCP2 function.

Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors.

Science.gov (United States)

Montgomery, David C; Sorum, Alexander W; Guasch, Laura; Nicklaus, Marc C; Meier, Jordan L

2015-08-20

The finding that chromatin modifications are sensitive to changes in cellular cofactor levels potentially links altered tumor cell metabolism and gene expression. However, the specific enzymes and metabolites that connect these two processes remain obscure. Characterizing these metabolic-epigenetic axes is critical to understanding how metabolism supports signaling in cancer, and developing therapeutic strategies to disrupt this process. Here, we describe a chemical approach to define the metabolic regulation of lysine acetyltransferase (KAT) enzymes. Using a novel chemoproteomic probe, we identify a previously unreported interaction between palmitoyl coenzyme A (palmitoyl-CoA) and KAT enzymes. Further analysis reveals that palmitoyl-CoA is a potent inhibitor of KAT activity and that fatty acyl-CoA precursors reduce cellular histone acetylation levels. These studies implicate fatty acyl-CoAs as endogenous regulators of histone acetylation, and suggest novel strategies for the investigation and metabolic modulation of epigenetic signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantitative metabolic imaging using endogenous fluorescence to detect stem cell differentiation

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Quinn, Kyle P.; Sridharan, Gautham V.; Hayden, Rebecca S.; Kaplan, David L.; Lee, Kyongbum; Georgakoudi, Irene

2013-12-01

The non-invasive high-resolution spatial mapping of cell metabolism within tissues could provide substantial advancements in assessing the efficacy of stem cell therapy and understanding tissue development. Here, using two-photon excited fluorescence microscopy, we elucidate the relationships among endogenous cell fluorescence, cell redox state, and the differentiation of human mesenchymal stem cells into adipogenic and osteoblastic lineages. Using liquid chromatography/mass spectrometry and quantitative PCR, we evaluate the sensitivity of an optical redox ratio of FAD/(NADH + FAD) to metabolic changes associated with stem cell differentiation. Furthermore, we probe the underlying physiological mechanisms, which relate a decrease in the redox ratio to the onset of differentiation. Because traditional assessments of stem cells and engineered tissues are destructive, time consuming, and logistically intensive, the development and validation of a non-invasive, label-free approach to defining the spatiotemporal patterns of cell differentiation can offer a powerful tool for rapid, high-content characterization of cell and tissue cultures.

The Impact of Credit Constraints on Housing Demand: Assessed with Endogenous Price and Expenditure

OpenAIRE

Li, Yarui; Leatham, David J.

2013-01-01

This article assesses the impact of credit constraints on housing demand with price and expenditure treated as endogenous variables. Using AIDS model, we find the model without controlling for endogeneities tends to underestimate the impact of credit constraint on the budget shares and the estimates are less significant.

Endogenous allergens and compositional analysis in the allergenicity assessment of genetically modified plants.

Science.gov (United States)

Fernandez, A; Mills, E N C; Lovik, M; Spoek, A; Germini, A; Mikalsen, A; Wal, J M

2013-12-01

Allergenicity assessment of genetically modified (GM) plants is one of the key pillars in the safety assessment process of these products. As part of this evaluation, one of the concerns is to assess that unintended effects (e.g. over-expression of endogenous allergens) relevant for the food safety have not occurred due to the genetic modification. Novel technologies are now available and could be used as complementary and/or alternative methods to those based on human sera for the assessment of endogenous allergenicity. In view of these developments and as a step forward in the allergenicity assessment of GM plants, it is recommended that known endogenous allergens are included in the compositional analysis as additional parameters to be measured. Copyright © 2013 Elsevier Ltd. All rights reserved.

Heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylated variants of a single polypeptide chain.

Science.gov (United States)

Murphy, P A; Cebula, T A; Windle, B E

1981-10-01

Rabbit endogenous pyrogens were of about the same molecular size, but showed considerable heterogeneity of their isoelectric points. We attempted to show that this heterogeneity was attributable to variable glycosylation of a single polypeptide chain. When peritoneal exudate cells were stimulated to make pyrogens in the presence of 2-deoxy-D-glucose, there was a relatively trivial suppression of pyrogen release, and analysis by isoelectric focusing showed parallel inhibition of secretion of all the forms of endogenous pyrogen. When cells were stimulated in the presence of 3H-labeled amino acids and 14C-labeled glucosamine or glucose, the purified pyrogens were labeled with 3H but not with 14C. Macrophage membrane preparations were made which contained glycosyl transferases and could transfer sugar residues from sugar nucleotides to deglycosylated fetuin. These macrophage membrane preparations did not transfer sugars to the pI 7.3 endogenous pyrogen. Treatment of endogenous pyrogens with neuraminidase or with periodate produced no evidence suggesting that the pyrogens were glycosylated. Last, endogenous pyrogens did not bind to any of four lectins with different carbohydrate specificities. This evidence suggests that the heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylation and must have some other cause.

Molecular genetic characterization of the RD-114 gene family of endogenous feline retroviral sequences.

Science.gov (United States)

Reeves, R H; O'Brien, S J

1984-01-01

RD-114 is a replication-competent, xenotropic retrovirus which is homologous to a family of moderately repetitive DNA sequences present at ca. 20 copies in the normal cellular genome of domestic cats. To examine the extent and character of genomic divergence of the RD-114 gene family as well as to assess their positional association within the cat genome, we have prepared a series of molecular clones of endogenous RD-114 DNA segments from a genomic library of cat cellular DNA. Their restriction endonuclease maps were compared with each other as well as to that of the prototype-inducible RD-114 which was molecularly cloned from a chronically infected human cell line. The endogenous sequences analyzed were similar to each other in that they were colinear with RD-114 proviral DNA, were bounded by long terminal redundancies, and conserved many restriction sites in the gag and pol regions. However, the env regions of many of the sequences examined were substantially deleted. Several of the endogenous RD-114 genomes contained a novel envelope sequence which was unrelated to the env gene of the prototype RD-114 env gene but which, like RD-114 and endogenous feline leukemia virus provirus, was found only in species of the genus Felis, and not in other closely related Felidae genera. The endogenous RD-114 sequences each had a distinct cellular flank which indicates that these sequences are not tandem but dispersed nonspecifically throughout the genome. Southern analysis of cat cellular DNA confirmed the conclusions about conserved restriction sites in endogenous sequences and indicated that a single locus may be responsible for the production of the major inducible form of RD-114. Images PMID:6090693

Proliferation of Endogenous Retroviruses in the Early Stages of a Host Germ Line Invasion

Science.gov (United States)

Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D.; Roca, Alfred L.

2015-01-01

Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire–dam–progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5′- and 3′-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5′-LTR sequence was identical to the 3′-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200–49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. PMID:25261407

BILATERAL ENDOGENOUS BACTERIAL ENDOPHTHALMITIS SECONDARY TO PNEUMONIA IN AN AIDS PATIENT : A CASE REPORT

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Rajendra Ku.

2015-08-01

Full Text Available INTRODUCTI ON: Endogenous or metastatic endophthalmitis is a very rare sever form of ocular disease which is uncommon now - a - days. Prevalence of endogenous bacterial endophthalmitis is 2 - 8% of all cases of endophthalmitis 1 . Mostly it is associated with chronic disease like diabetes mellitus, renal failure, liver abscesses, prolong placement of catheter, IV line or central venous line, drug abusers and immunocompromise d patients. Gram +bacteria are the most common causative organism of the endogenous bacterial endophthalmitis . 1 A few cases of endogenous bacterial endophthalmitis due to klebsiella pneumonias, a gram - ve organism have been documented and majority of them were in Taiwan . 2, 3,4,5,6, 7 K. pneumonia endophthalmitis is associated with diabetes mellitus and hepatic abscesses can be bilateral and resulted into poor visual outcome . 2,3,4,5,6, 7 K. pneumonia pneumonia has been reported most frequently from patients with alcoholic liver diseases and one of the common cause of acute osteomyelitis and septic arthritis . 8,9 In this scenario we report the case of a Malawian in African Continent who developed bilateral endogenous bacterial endophthalmitis after suffering from pneumonia in immunocompromise state. PURPOSE : to report a case bilateral endogenous endophthalmitis secondary to pneumonia in an AIDS patient . DESIGN : Observational case report . METHODS : A patient with bilateral pain full red eye with diminution of vision was seen in c onsultation by ophthalmology. RESULT : with clinical characteristic and laboratory diagnosis of sputum and blood conf i rmed the causative agent for pneumonia and endophthalmitis is K.pneumonia. CONCLUSION : it is unusual disease, required early detection and prompt treatment.

Endogenous retinoic acid activity in principal cells and intercalated cells of mouse collecting duct system.

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Yuen Fei Wong

2011-02-01

Full Text Available Retinoic acid is the bioactive derivative of vitamin A, which plays an indispensible role in kidney development by activating retinoic acid receptors. Although the location, concentration and roles of endogenous retinoic acid in post-natal kidneys are poorly defined, there is accumulating evidence linking post-natal vitamin A deficiency to impaired renal concentrating and acidifying capacity associated with increased susceptibility to urolithiasis, renal inflammation and scarring. The aim of this study is to examine the presence and the detailed localization of endogenous retinoic acid activity in neonatal, young and adult mouse kidneys, to establish a fundamental ground for further research into potential target genes, as well as physiological and pathophysiological roles of endogenous retinoic acid in the post-natal kidneys.RARE-hsp68-lacZ transgenic mice were employed as a reporter for endogenous retinoic acid activity that was determined by X-gal assay and immunostaining of the reporter gene product, β-galactosidase. Double immunostaining was performed for β-galactosidase and markers of kidney tubules to localize retinoic acid activity. Distinct pattern of retinoic acid activity was observed in kidneys, which is higher in neonatal and 1- to 3-week-old mice than that in 5- and 8-week-old mice. The activity was present specifically in the principal cells and the intercalated cells of the collecting duct system in all age groups, but was absent from the glomeruli, proximal tubules, thin limbs of Henle's loop and distal tubules.Endogenous retinoic acid activity exists in principal cells and intercalated cells of the mouse collecting duct system after birth and persists into adulthood. This observation provides novel insights into potential roles for endogenous retinoic acid beyond nephrogenesis and warrants further studies to investigate target genes and functions of endogenous retinoic acid in the kidney after birth, particularly in the

A comparison of exogenous and endogenous CEST MRI methods for evaluating in vivo pH.

Science.gov (United States)

Lindeman, Leila R; Randtke, Edward A; High, Rachel A; Jones, Kyle M; Howison, Christine M; Pagel, Mark D

2018-05-01

Extracellular pH (pHe) is an important biomarker for cancer cell metabolism. Acido-chemical exchange saturation transfer (CEST) MRI uses the contrast agent iopamidol to create spatial maps of pHe. Measurements of amide proton transfer exchange rates (k ex ) from endogenous CEST MRI were compared to pHe measurements by exogenous acido-CEST MRI to determine whether endogenous k ex could be used as a proxy for pHe measurements. Spatial maps of pHe and k ex were obtained using exogenous acidoCEST MRI and an endogenous CEST MRI analyzed with the omega plot method, respectively, to evaluate mouse kidney, a flank tumor model, and a spontaneous lung tumor model. The pHe and k ex results were evaluated using pixelwise comparisons. The k ex values obtained from endogenous CEST measurements did not correlate with the pHe results from exogenous CEST measurements. The k ex measurements were limited to fewer pixels and had a limited dynamic range relative to pHe measurements. Measurements of k ex with endogenous CEST MRI cannot substitute for pHe measurements with acidoCEST MRI. Whereas endogenous CEST MRI may still have good utility for evaluating some specific pathologies, exogenous acido-CEST MRI is more appropriate when evaluating pathologies based on pHe values. Magn Reson Med 79:2766-2772, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Gut Microbial Glycerol Metabolism as an Endogenous Acrolein Source

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Jianbo Zhang

2018-01-01

Full Text Available Acrolein is a highly reactive electrophile causing toxic effects, such as DNA and protein adduction, oxidative stress, endoplasmic reticulum stress, immune dysfunction, and membrane damage. This Opinion/Hypothesis provides an overview of endogenous and exogenous acrolein sources, acrolein’s mode of action, and its metabolic fate. Recent reports underpin the finding that gut microbial glycerol metabolism leading to the formation of reuterin is an additional source of endogenous acrolein. Reuterin is an antimicrobial multicomponent system consisting of 3-hydroxypropionaldehyde, its dimer and hydrate, and also acrolein. The major conclusion is that gut microbes can metabolize glycerol to reuterin and that this transformation occurs in vivo. Given the known toxicity of acrolein, the observation that acrolein is formed in the gut necessitates further investigations on functional relevance for gut microbiota and the host.

Endogenous Losses of Nitrogen and Protein Requirement for ...

African Journals Online (AJOL)

Four fistulated and four intact West African dwarf wether sheep, maintained on hay and concentrate supplements were used for a study of metabolic faecal nitrogen (MEN) and endogenous urinary nitrogen (EUN). The composition of the faecal losses was examined. The values obtained enabled calculation of nitrogen ...

MDR1 P-glycoprotein transports endogenous opioid peptides

NARCIS (Netherlands)

Oude Elferink, R. P.; Zadina, J.

2001-01-01

MDR1 P-glycoprotein is generally regarded as an efflux pump for amphipathic toxic compounds. The question remains, however, whether certain endogenous compounds are also substrates for this transporter. Certain peptides have been shown to interact with MDR1 Pgp as well and we have therefore

Occupational Choice and the Endogenous Supply of Ability

DEFF Research Database (Denmark)

Klynge, Alice Heegaard

I develop a selection model in which the individual’s supply of ability is endogenous and subject to selection along with occupation. Additionally, I identify and estimate the returns to creative and innovative ability, communication ability, and reading and math ability for white-collar and blue...

Endogenous attention modulates attentional and motor interference from distractors: Evidence from behavioral and electrophysiological results.

Directory of Open Access Journals (Sweden)

Elisa eMartín-Arévalo

2015-02-01

Full Text Available Selective visual attention enhances the processing of relevant stimuli and filters out irrelevant stimuli and/or distractors. However, irrelevant information is sometimes processed, as demonstrated by the Simon effect (Simon & Rudell, 1967. We examined whether fully irrelevant distractors (task and target-irrelevant produce interference (measured as the Simon effect, and whether endogenous orienting modulated this interference. Despite being fully irrelevant, distractors were attentionally coded (as reflected by the distractor-related N2pc component, and interfered with the processing of the target response (as reflected by the target-related LRP component. Distractor’s attentional capture depended on endogenous attention, and their interference with target responses was modulated by both endogenous attention and distractor location repetition. These results demonstrate both endogenous attentional and motor modulations over the Simon effect produced by fully irrelevant distractors.

Endogenous ghrelin-O-acyltransferase (GOAT) acylates local ghrelin in the hippocampus.

Science.gov (United States)

Murtuza, Mohammad I; Isokawa, Masako

2018-01-01

Ghrelin is an appetite-stimulating peptide. Serine 3 on ghrelin must be acylated by octanoate via the enzyme ghrelin-O-acyltransferase (GOAT) for the peptide to bind and activate the cognate receptor, growth hormone secretagogue receptor type 1a (GHSR1a). Interest in GHSR1a increased dramatically when GHSR1a mRNA was demonstrated to be widespread in the brain, including the cortex and hippocampus, indicating that it has multifaceted functions beyond the regulation of metabolism. However, the source of octanoylated ghrelin for GHSR1a in the brain, outside of the hypothalamus, is not well understood. Here, we report the presence of GOAT and its ability to acylate non-octanoylated ghrelin in the hippocampus. GOAT immunoreactivity is aggregated at the base of the dentate granule cell layer in the rat and wild-type mouse. This immunoreactivity was not affected by the pharmacological inhibition of GHSR1a or the metabolic state-dependent fluctuation of systemic ghrelin levels. However, it was absent in the GHSR1a knockout mouse hippocampus, pointing the possibility that the expression of GHSR1a may be a prerequisite for the production of GOAT. Application of fluorescein isothiocyanate (FITC)-conjugated non-octanoylated ghrelin in live hippocampal slice culture (but not in fixed culture or in the presence of GOAT inhibitors) mimicked the binding profile of FITC-conjugated octanoylated ghrelin, suggesting that extracellularly applied non-octanoylated ghrelin was acylated by endogenous GOAT in the live hippocampus while GOAT being mobilized out of neurons. Our results will advance the understanding for the role of endogenous GOAT in the hippocampus and facilitate the search for the source of ghrelin that is intrinsic to the brain. © 2017 International Society for Neurochemistry.

Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy.

Science.gov (United States)

Järnum, Sofia; Runström, Anna; Bockermann, Robert; Winstedt, Lena; Crispin, Max; Kjellman, Christian

2017-09-01

Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Here, we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors. We show that therapeutic antibodies against breast cancer (trastuzumab), colon cancer (cetuximab), and lymphomas (rituximab and alemtuzumab) can be potentiated when endogenous IgG is removed. Overall, IdeS is shown to be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells and thereby create an armada of dedicated tumor-seeking immune cells. Mol Cancer Ther; 16(9); 1887-97. ©2017 AACR . ©2017 American Association for Cancer Research.

Endogenous pyrogen production by human blood monocytes stimulated by staphylococcal cell wall components.

Science.gov (United States)

Oken, M M; Peterson, P K; Wilkinson, B J

1981-01-01

To determine the properties of Staphylococcus aureus contributing to its pyrogenicity, we compared, in human monocytes, endogenous pyrogen production stimulated by heat-killed S. aureus with that stimulated by purified S. aureus cell walls or by particulate peptidoglycan prepared from the same strain. Peptidoglycan, but not the purified cell wall preparation, was found comparable to S. aureus as an endogenous pyrogen stimulus. This finding was associated with a more effective monocyte phagocytosis of S. aureus and peptidoglycan as compared with that of purified cell walls. Lysostaphin digestion of peptidoglycan markedly reduced its pyrogenicity. To test whether the chemical composition of the ingested particles is important, latex particles were tested as possible stimuli for monocyte endogenous pyrogen release. Although 40 to 68% of monocytes ingested latex particles during the first hour, there was no evidence of endogenous pyrogen activity in the supernatant even when supernatants equivalent to 5.2 X 10(6) monocytes were tested. This study demonstrates that the pyrogenic moiety of the S. aureus cell wall resides in the peptidoglycan component. Phagocytosis is not in itself a pyrogenic stimulus, but rather serves as an effective mechanism to bring about contact between the chemical stimulus and the monocyte.

Rhodotorula Endogenous Endophthalmitis: A Novel Harbinger of the Injection Drug Epidemic in the United States

Directory of Open Access Journals (Sweden)

Preston M. Luong

2017-01-01

Full Text Available Endogenous endophthalmitis is a rare but feared infectious ocular complication of injection drug use (IDU. The recent opioid epidemic in the United States threatens to increase the incidence of this disease. We report the first case of endogenous endophthalmitis in the United States caused by the emerging fungal pathogen Rhodotorula in an injection drug user which led to no light perception vision (NLP. Worldwide experience with Rhodotorula endogenous endophthalmitis is limited, but existing cases suggest infection by this particular fungal genus has a grim prognosis.

Two-stage residual inclusion estimation: addressing endogeneity in health econometric modeling.

Science.gov (United States)

Terza, Joseph V; Basu, Anirban; Rathouz, Paul J

2008-05-01

The paper focuses on two estimation methods that have been widely used to address endogeneity in empirical research in health economics and health services research-two-stage predictor substitution (2SPS) and two-stage residual inclusion (2SRI). 2SPS is the rote extension (to nonlinear models) of the popular linear two-stage least squares estimator. The 2SRI estimator is similar except that in the second-stage regression, the endogenous variables are not replaced by first-stage predictors. Instead, first-stage residuals are included as additional regressors. In a generic parametric framework, we show that 2SRI is consistent and 2SPS is not. Results from a simulation study and an illustrative example also recommend against 2SPS and favor 2SRI. Our findings are important given that there are many prominent examples of the application of inconsistent 2SPS in the recent literature. This study can be used as a guide by future researchers in health economics who are confronted with endogeneity in their empirical work.

SwePep, a database designed for endogenous peptides and mass spectrometry.

Science.gov (United States)

Fälth, Maria; Sköld, Karl; Norrman, Mathias; Svensson, Marcus; Fenyö, David; Andren, Per E

2006-06-01

A new database, SwePep, specifically designed for endogenous peptides, has been constructed to significantly speed up the identification process from complex tissue samples utilizing mass spectrometry. In the identification process the experimental peptide masses are compared with the peptide masses stored in the database both with and without possible post-translational modifications. This intermediate identification step is fast and singles out peptides that are potential endogenous peptides and can later be confirmed with tandem mass spectrometry data. Successful applications of this methodology are presented. The SwePep database is a relational database developed using MySql and Java. The database contains 4180 annotated endogenous peptides from different tissues originating from 394 different species as well as 50 novel peptides from brain tissue identified in our laboratory. Information about the peptides, including mass, isoelectric point, sequence, and precursor protein, is also stored in the database. This new approach holds great potential for removing the bottleneck that occurs during the identification process in the field of peptidomics. The SwePep database is available to the public.

A new unextracted-sample radioimmunoassay method for hepatic endogenous nuclear L-tri-iodothyronine content

International Nuclear Information System (INIS)

Yagura, T.; Walfish, P.G.

1982-01-01

Endogenous L-tri-iodothyronine content in an hepatic nuclear extract was measured by a new unextracted-sample radioimmunoassay method using 8-anilinonaphthalene-1-sulphonic acid to inhibit the L-[ 125 I]tri-iodothyronine binding to the nuclear L-tri-iodothyronine receptor within the extract. The amount of endogenous L-tri-iodothyronine was 10-40 pg/0.2 ml of hepatic nuclear extract from euthyroid rats, compared with less than 3.125 pg/0.2ml from thyroidectomized rats. The results obtained were compared with a Sephadex G-25 column extracted-sample radioimmunoassay method and showed a good agreement. The values for the endogenous L-tri-iodothyronine content were utilized to correct for the L-tri-iodothyronine concentration within the binding assay mixture in order to accurately determine by Scatchard analysis the binding characteristics of the nuclear L-tri-iodothyronine receptor. The validity of the correction for endogenous L-tri-iodothyronine was demonstrated by using a nuclear extract from a thyroidectomized rat which was preincubated with a small known amount of L-tri-iodothyronine before determining the nuclear L-tri-iodothyronine receptor binding characteristics. It is concluded that the necessity and validity of using endogenous L-tri-iodothyronine corrections in the Scatchard analytical computations of the nuclear L-tri-iodothyronine receptor binding characteristics has been demonstrated, being particularly more important for affinity constant than maximum binding capacity. (author)

Endogenous glutamine production in critically ill patients: the effect of exogenous glutamine supplementation.

Science.gov (United States)

Mori, Maiko; Rooyackers, Olav; Smedberg, Marie; Tjäder, Inga; Norberg, Ake; Wernerman, Jan

2014-04-14

Glutamine rate of appearance (Ra) may be used as an estimate of endogenous glutamine production. Recently a technique employing a bolus injection of isotopically labeled glutamine was introduced, with the potential to allow for multiple assessments of the glutamine Ra over time in critically ill patients, who may not be as metabolically stable as healthy individuals. Here the technique was used to evaluate the endogenous glutamine production in critically ill patients in the fed state with and without exogenous glutamine supplementation intravenously. Mechanically ventilated patients (n = 11) in the intensive care unit (ICU) were studied on two consecutive days during continuous parenteral feeding. To allow the patients to be used as their own controls, they were randomized for the reference measurement during basal feeding without supplementation, before or after the supplementation period. Glutamine Ra was determined by a bolus injection of 13C-glutamine followed by a period of frequent sampling to establish the decay-curve for the glutamine tracer. Exogenous glutamine supplementation was given by intravenous infusion of a glutamine containing dipeptide, L-alanyl-L-glutamine, 0.28 g/kg during 20 hours. A 14% increase of endogenous glutamine Ra was seen at the end of the intravenous supplementation period as compared to the basal measurements (P = 0.009). The bolus injection technique to measure glutamine Ra to estimate the endogenous production of glutamine in critically ill patients was demonstrated to be useful for repetitive measurements. The hypothesized attenuation of endogenous glutamine production during L-alanyl-L-glutamine infusion given as a part of full nutrition was not seen.

Central canal ependymal cells proliferate extensively in response to traumatic spinal cord injury but not demyelinating lesions.

Directory of Open Access Journals (Sweden)

Steve Lacroix

Full Text Available The adult mammalian spinal cord has limited regenerative capacity in settings such as spinal cord injury (SCI and multiple sclerosis (MS. Recent studies have revealed that ependymal cells lining the central canal possess latent neural stem cell potential, undergoing proliferation and multi-lineage differentiation following experimental SCI. To determine whether reactive ependymal cells are a realistic endogenous cell population to target in order to promote spinal cord repair, we assessed the spatiotemporal dynamics of ependymal cell proliferation for up to 35 days in three models of spinal pathologies: contusion SCI using the Infinite Horizon impactor, focal demyelination by intraspinal injection of lysophosphatidylcholine (LPC, and autoimmune-mediated multi-focal demyelination using the active experimental autoimmune encephalomyelitis (EAE model of MS. Contusion SCI at the T9-10 thoracic level stimulated a robust, long-lasting and long-distance wave of ependymal proliferation that peaked at 3 days in the lesion segment, 14 days in the rostral segment, and was still detectable at the cervical level, where it peaked at 21 days. This proliferative wave was suppressed distal to the contusion. Unlike SCI, neither chemical- nor autoimmune-mediated demyelination triggered ependymal cell proliferation at any time point, despite the occurrence of demyelination (LPC and EAE, remyelination (LPC and significant locomotor defects (EAE. Thus, traumatic SCI induces widespread and enduring activation of reactive ependymal cells, identifying them as a robust cell population to target for therapeutic manipulation after contusion; conversely, neither demyelination, remyelination nor autoimmunity appears sufficient to trigger proliferation of quiescent ependymal cells in models of MS-like demyelinating diseases.

Isobutanol production in Synechocystis PCC 6803 using heterologous and endogenous alcohol dehydrogenases

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Rui Miao

2017-12-01

Full Text Available Isobutanol is a flammable compound that can be used as a biofuel due to its high energy density and suitable physical and chemical properties. In this study, we examined the capacity of engineered strains of Synechocystis PCC 6803 containing the α-ketoisovalerate decarboxylase from Lactococcus lactis and different heterologous and endogenous alcohol dehydrogenases (ADH for isobutanol production. A strain expressing an introduced kivd without any additional copy of ADH produced 3 mg L−1 OD750−1 isobutanol in 6 days. After the cultures were supplemented with external addition of isobutyraldehyde, the substrate for ADH, 60.8 mg L−1 isobutanol was produced after 24 h when OD750 was 0.8. The in vivo activities of four different ADHs, two heterologous and two putative endogenous in Synechocystis, were examined and the Synechocystis endogenous ADH encoded by slr1192 showed the highest efficiency for isobutanol production. Furthermore, the strain overexpressing the isobutanol pathway on a self-replicating vector with the strong Ptrc promoter showed significantly higher gene expression and isobutanol production compared to the corresponding strains expressing the same operon introduced on the genome. Hence, this study demonstrates that Synechocystis endogenous AHDs have a high capacity for isobutanol production, and identifies kivd encoded α-ketoisovalerate decarboxylase as one of the likely bottlenecks for further isobutanol production.

Attention and predictions: control of spatial attention beyond the endogenous-exogenous dichotomy

Directory of Open Access Journals (Sweden)

Emiliano eMacaluso

2013-10-01

Full Text Available The mechanisms of attention control have been extensively studied with a variety of methodologies in animals and in humans. Human studies using non-invasive imaging techniques highlighted a remarkable difference between the pattern of responses in dorsal fronto-parietal regions vs. ventral fronto-parietal regions, primarily lateralized to the right hemisphere. Initially, this distinction at the neuro-physiological level has been related to the distinction between cognitive processes associated with strategic/endogenous vs. stimulus-driven/exogenous of attention control. Nonetheless, quite soon it has become evident that, in almost any situation, attention control entails a complex combination of factors related to both the current sensory input and endogenous aspects associated with the experimental context. Here, we review several of these aspects first discussing the joint contribution of endogenous and stimulus-driven factors during spatial orienting in complex environments and, then, turning to the role of expectations and predictions in spatial re-orienting. We emphasize that strategic factors play a pivotal role for the activation of the ventral system during stimulus-driven control, and that the dorsal system makes use of stimulus-driven signals for top-down control. We conclude that both the dorsal and the ventral fronto-parietal networks integrate endogenous and exogenous signals during spatial attention control and that future investigations should manipulate both these factors concurrently, so as to reveal to full extent of these interactions.

Attention and predictions: control of spatial attention beyond the endogenous-exogenous dichotomy

Science.gov (United States)

Macaluso, Emiliano; Doricchi, Fabrizio

2013-01-01

The mechanisms of attention control have been extensively studied with a variety of methodologies in animals and in humans. Human studies using non-invasive imaging techniques highlighted a remarkable difference between the pattern of responses in dorsal fronto-parietal regions vs. ventral fronto-parietal (vFP) regions, primarily lateralized to the right hemisphere. Initially, this distinction at the neuro-physiological level has been related to the distinction between cognitive processes associated with strategic/endogenous vs. stimulus-driven/exogenous of attention control. Nonetheless, quite soon it has become evident that, in almost any situation, attention control entails a complex combination of factors related to both the current sensory input and endogenous aspects associated with the experimental context. Here, we review several of these aspects first discussing the joint contribution of endogenous and stimulus-driven factors during spatial orienting in complex environments and, then, turning to the role of expectations and predictions in spatial re-orienting. We emphasize that strategic factors play a pivotal role for the activation of the ventral system during stimulus-driven control, and that the dorsal system makes use of stimulus-driven signals for top-down control. We conclude that both the dorsal and the vFP networks integrate endogenous and exogenous signals during spatial attention control and that future investigations should manipulate both these factors concurrently, so as to reveal to full extent of these interactions. PMID:24155707

Attention and predictions: control of spatial attention beyond the endogenous-exogenous dichotomy.

Science.gov (United States)

Macaluso, Emiliano; Doricchi, Fabrizio

2013-01-01

The mechanisms of attention control have been extensively studied with a variety of methodologies in animals and in humans. Human studies using non-invasive imaging techniques highlighted a remarkable difference between the pattern of responses in dorsal fronto-parietal regions vs. ventral fronto-parietal (vFP) regions, primarily lateralized to the right hemisphere. Initially, this distinction at the neuro-physiological level has been related to the distinction between cognitive processes associated with strategic/endogenous vs. stimulus-driven/exogenous of attention control. Nonetheless, quite soon it has become evident that, in almost any situation, attention control entails a complex combination of factors related to both the current sensory input and endogenous aspects associated with the experimental context. Here, we review several of these aspects first discussing the joint contribution of endogenous and stimulus-driven factors during spatial orienting in complex environments and, then, turning to the role of expectations and predictions in spatial re-orienting. We emphasize that strategic factors play a pivotal role for the activation of the ventral system during stimulus-driven control, and that the dorsal system makes use of stimulus-driven signals for top-down control. We conclude that both the dorsal and the vFP networks integrate endogenous and exogenous signals during spatial attention control and that future investigations should manipulate both these factors concurrently, so as to reveal to full extent of these interactions.

A sensitive competitive binding assay for exogenous and endogenous heparins

International Nuclear Information System (INIS)

Dawes, J.; Pepper, D.S.

1982-01-01

A new type of assay for heparins has been devised, in which the test material competes with 125 I-labelled heparin for binding to protamine-Sepharose. The assay is very sensitive and will measure heparin concentrations down to 10 ng ml-1. It responds to both the degree of sulphation and the molecular weight of acidic polysaccharides, but is independent of their biological activities. It can be used to quantitate heparins in biological fluids after pretreatment of the samples with protease. In this way endogenous heparins were measured in normal human serum, plasma and urine. The assay is extremely versatile and has great potential for the investigation of endogenous and exogenous heparins

Endogenous attention modulates early selective attention in psychopathy: An ERP investigation.

Science.gov (United States)

Krusemark, Elizabeth A; Kiehl, Kent A; Newman, Joseph P

2016-10-01

Psychopathic individuals are prone to act on urges without adequate consideration of future consequences or the rights of other individuals. One interpretation of this behavior is that it reflects abnormal selective attention (i.e., a failure to process information that is incongruent with their primary focus of attention; Hiatt, Schmitt, & Newman, Neuropsychology, 18, 50-59, 2004). Unfortunately, it is unclear whether this selective attention abnormality reflects top-down endogenous influences, such as the strength or specificity of attention focus (i.e., top-down set) apart from other, more exogenous (bottom-up), effects on attention. To explore this question, we used an early visual event-related potential (N2pc) in combination with a modified visual search task designed to assess the effect of early endogenous (i.e., top-down) attention on the processing of set-congruent information. The task was administered to a sample of 70 incarcerated adult males, who were assigned to high, intermediate, and low psychopathy groups using Hare's Psychopathy Checklist-Revised (Hare, 2003). Based on the assumption that their failure to process set-incongruent information reflects the exaggerated effects of endogenous attention, we predicted that participants with high psychopathy scores would show an exaggerated N2pc response to set-congruent information. The results supported the hypothesis and provide novel electrophysiological evidence that psychopathy is associated with exaggerated endogenous attention effects during early stages of processing. Further research is needed to examine the implications of this finding for the well-established failure of psychopathic individuals to process set-incongruent information and inhibit inappropriate responses.

The time-course relationship between endogenous spleen colony formation and marrow cellularity after midlethal irradiation of mice

International Nuclear Information System (INIS)

Koch, I.; Wiktor-Jedrzejczak, W.; Wojskowa Akademia Medyczna, Warsaw

1981-01-01

The kinetics of appearance and disappearance of endogenous spleen colonies following 4 and 6 Gy of X-irradiation was compared with the kinetics of changes of cellular contents of femur cavities. Additionally, the effect of postirradiation bleeding and this way of the subsequent increase in the level of endogenous erythropoietin was studied. It was found that the kinetics of endogenous haemopoietic recovery in the marrow follows the same characteristic biphasic pattern as in the spleen although it is slightly delayed in time. First wave of regeneration corresponded in time with the formation of transient endogenous spleen colonies 4-7 days postirradiation, and the 2nd wave corresponded in time witn the formation of classical haemopoietic stem-cell derived endogenous spleen colonies 9-12 days following irradiation. Postirradiation bleeding markedly stimulated particularly the first wave of regeneration both in the marrow and in the spleen. (orig.) [de

Endogenous antispermatogenic agents: prospects for male contraception.

Science.gov (United States)

Ewing, L L; Robaire, B

1978-01-01

A review of endogenous antispermatogenic agents as prospects for male contraception is reported. It is demonstrated that endogenous compounds exert regulatory influences at 4 major levels in the male: 1) between germ cells; 2) between Sertoli and germ cells; 3) between Leydig cells and seminiferous tubules; and 4) between the central nervous system and the testis. Efforts to interrupt spermatogenesis have failed to find application as male contraceptives for various reasons: 1) some investigators ignored the vulnerable control points by utilizing nonspecific agents; 2) others attacked a vulnerable control point but used synthetic drugs that had deleterious side effects; and 3) still others attacked a vulnerable control point with a relatively innocuous drug but used an impractical mode of drug administration. The potential for devising innovative techniques for administering relatively innocuous drugs at dosages sufficient to produce sterility without causing deleterious side effects is demonstrated. The most promising solution for the development of an antispermatogenic male contraceptive is the interference with the adenohypophyseal-gonadal axis via the subcutaneous sustained release of steroid formulations containing either androgen-danazol, androgen-progestin, or androgen-estrogen formulations. Another promising agent would be luteinizing releasing hormone agonist-androgen formulation.

Studies on the pathogenesis of fever. VIII. Further observations on the role of endogenous pyrogen in endotoxin fever.

Science.gov (United States)

GILLMAN, S M; BORNSTEIN, D L; WOOD, W B

1961-11-01

Rabbits made granulocytopenic with nitrogen mustard have been shown to generate serum endogenous pyrogen when given a fever-producing dose of bacterial endotoxin. This finding is in accord with the hypothesis that endogenous pyrogen plays a central role in the pathogenesis of endotoxin fever. The fact that leucopenic animals produce less serum-endogenous pyrogen than normal animals given the same dose of endotoxin has also been confirmed and suggests that polymorphonuclear leucocytes constitute a major source of the endogenous pyrogen which is demonstrable in the circulation during endotoxin fever.

Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress

Science.gov (United States)

Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S.

2016-01-01

Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

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Therese Wilhelm

2016-05-01

Full Text Available Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es. Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3% rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing, and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and

Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

Science.gov (United States)

Wilhelm, Therese; Ragu, Sandrine; Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S

2016-05-01

Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

Proliferation of endogenous retroviruses in the early stages of a host germ line invasion.

Science.gov (United States)

Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D; Roca, Alfred L

2015-01-01

Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire-dam-progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5'- and 3'-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5'-LTR sequence was identical to the 3'-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200-49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Secondary Diabetes Mellitus in Patients with Endogenous Cushing’s Syndrome - Clinical Characteristics at Diagnosis

OpenAIRE

Căpăţînă Cristina; Baciu Ionela; Greere Daniela; Caragheorgheopol Andra; Poiană Cătălina

2018-01-01

Background and aims. Endogenous Cushing’s syndrome is a rare disease associated with severe morbidity and increased mortality if untreated. Diabetes mellitus is a frequent initial complaint of these patients. Our aim was to investigate the clinical characteristics at the time of diagnosis in a cohort of patients with endogenous Cushing’s syndrome (CS).

Risk factors predictive of endogenous endophthalmitis among hospitalized patients with hematogenous infections in the United States.

Science.gov (United States)

Vaziri, Kamyar; Pershing, Suzann; Albini, Thomas A; Moshfeghi, Darius M; Moshfeghi, Andrew A

2015-03-01

To identify potential risk factors associated with endogenous endophthalmitis among hospitalized patients with hematogenous infections. Retrospective cross-sectional study. MarketScan Commercial Claims and Encounters, and Medicare Supplemental and Coordination of Benefit inpatient databases from the years 2007-2011 were obtained. Utilizing ICD-9 codes, logistic regression was used to identify potential predictors/comorbidities for developing endophthalmitis in patients with hematogenous infections. Among inpatients with hematogenous infections, the overall incidence rate of presumed endogenous endophthalmitis was 0.05%-0.4% among patients with fungemia and 0.04% among patients with bacteremia. Comorbid human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) (OR = 4.27; CI, 1.55-11.8; P = .005), tuberculosis (OR = 8.5; CI, 1.2-61.5; P = .03), endocarditis (OR = 8.3; CI, 4.9-13.9; P endogenous endophthalmitis. Patients aged 0-17 years (OR = 2.61; CI, 1.2-5.7; P = .02), 45-54 years (OR = 3.4; CI, 2.0-5.4; P endogenous endophthalmitis. Endogenous endophthalmitis is rare among hospitalized patients in the United States. Among patients with hematogenous infections, odds of endogenous endophthalmitis were higher for children and middle-aged patients, and for patients with endocarditis, bacterial meningitis, lymphoma/leukemia, HIV/AIDS, internal organ abscess, diabetes with ophthalmic manifestations, skin cellulitis/abscess, pyogenic arthritis, tuberculosis, longer hospital stays, and/or ICU/NICU admission. Published by Elsevier Inc.

Quantification of endogenous metabolites by the postcolumn infused-internal standard method combined with matrix normalization factor in liquid chromatography-electrospray ionization tandem mass spectrometry.

Science.gov (United States)

Liao, Hsiao-Wei; Chen, Guan-Yuan; Wu, Ming-Shiang; Liao, Wei-Chih; Tsai, I-Lin; Kuo, Ching-Hua

2015-01-02

Quantification of endogenous metabolites has enabled the discovery of biomarkers for diagnosis and provided for an understanding of disease etiology. The standard addition and stable isotope labeled-internal standard (SIL-IS) methods are currently the most widely used approaches to quantifying endogenous metabolites, but both have some limitations for clinical measurement. In this study, we developed a new approach for endogenous metabolite quantification by the postcolumn infused-internal standard (PCI-IS) method combined with the matrix normalization factor (MNF) method. MNF was used to correct the difference in MEs between standard solution and biofluids, and PCI-IS additionally tailored the correction of the MEs for individual samples. Androstenedione and testosterone were selected as test articles to verify this new approach to quantifying metabolites in plasma. The repeatability (n=4 runs) and intermediate precision (n=3 days) in terms of the peak area of androstenedione and testosterone at all tested concentrations were all less than 11% relative standard deviation (RSD). The accuracy test revealed that the recoveries were between 95.72% and 113.46%. The concentrations of androstenedione and testosterone in fifty plasma samples obtained from healthy volunteers were quantified by the PCI-IS combined with the MNF method, and the quantification results were compared with the results of the SIL-IS method. The Pearson correlation test showed that the correlation coefficient was 0.98 for both androstenedione and testosterone. We demonstrated that the PCI-IS combined with the MNF method is an effective and accurate method for quantifying endogenous metabolites. Copyright © 2014 Elsevier B.V. All rights reserved.

Calculations for Adjusting Endogenous Biomarker Levels During Analytical Recovery Assessments for Ligand-Binding Assay Bioanalytical Method Validation.

Science.gov (United States)

Marcelletti, John F; Evans, Cindy L; Saxena, Manju; Lopez, Adriana E

2015-07-01

It is often necessary to adjust for detectable endogenous biomarker levels in spiked validation samples (VS) and in selectivity determinations during bioanalytical method validation for ligand-binding assays (LBA) with a matrix like normal human serum (NHS). Described herein are case studies of biomarker analyses using multiplex LBA which highlight the challenges associated with such adjustments when calculating percent analytical recovery (%AR). The LBA test methods were the Meso Scale Discovery V-PLEX® proinflammatory and cytokine panels with NHS as test matrix. The NHS matrix blank exhibited varied endogenous content of the 20 individual cytokines before spiking, ranging from undetectable to readily quantifiable. Addition and subtraction methods for adjusting endogenous cytokine levels in %AR calculations are both used in the bioanalytical field. The two methods were compared in %AR calculations following spiking and analysis of VS for cytokines having detectable endogenous levels in NHS. Calculations for %AR obtained by subtracting quantifiable endogenous biomarker concentrations from the respective total analytical VS values yielded reproducible and credible conclusions. The addition method, in contrast, yielded %AR conclusions that were frequently unreliable and discordant with values obtained with the subtraction adjustment method. It is shown that subtraction of assay signal attributable to matrix is a feasible alternative when endogenous biomarkers levels are below the limit of quantitation, but above the limit of detection. These analyses confirm that the subtraction method is preferable over that using addition to adjust for detectable endogenous biomarker levels when calculating %AR for biomarker LBA.

[Physico-chemical characteristics of endogenous regulatory oligopeptides].

Science.gov (United States)

Zamiatnin, A A

1990-01-01

Analysis of amino acid residue content in endogenous regulatory oligopeptides possessing a preset spectrum of functional activity has been made. It has been shown that compared to proteins the oligopeptides contain a greater number of positively charged and cyclic radicals. All 525 oligopeptides with the preset spectrum of functional activity contained in EROP-Moscow data bank were found to have the same physicochemical characteristics.

Endogenous Growth, Monetary Shocks and Nominal Rigidities

OpenAIRE

Annicchiarico, Barbara; Pelloni, Alessandra; Lorenza, Rossi

2010-01-01

We introduce endogenous growth in an otherwise standard NK model with staggered prices and wages. Some results follow: (i) monetary volatility negatively affects long-run growth; (ii) the relation between nominal volatility and growth depends on the persistence of the nominal shocks and on the Taylor rule considered; (iii) a Taylor rule with smoothing increases the negative effect of nominal volatility on mean growth.

[Endogenous pyrogen formation by bone marrow cells].

Science.gov (United States)

Efremov, O M; Sorokin, A V; El'kina, O A

1978-01-01

The cells of the rabbit bone marrow produced endogenous pyrogen in response to stimulation with bacterial lipopolysaccharide. Incubation of the cells in medium No 199 containing a 15% homologous serum is optimal for the release of pyrogen. It is supposed that the cells of the bone marrow take part in the formation of endgenous pyrogen and in the mechanism of pyrexia in the organism.

THE PRESENCE OF ENDOGENOUS PYROGEN IN NORMAL RABBIT TISSUES.

Science.gov (United States)

SNELL, E S; ATKINS, E

1965-06-01

Saline extracts of homogenized, uninfected, rabbit tissues produced febrile responses when injected intravenously into rabbits. Extracts of muscle, lung, and heart evoked fevers that were similar to those induced by leucocyte pyrogen; extracts of spleen, liver, and kidney caused more sustained fevers. The minimal pyrogenic dose appeared to be between 1.5 and 3 gm wet weight of tissue. Evidence is presented that neither Gram-negative bacterial endotoxin nor polymorphonuclear leucocytes (circulating or sequestered in the tissues) can be implicated as the source of pyrogen in tissue extracts. It seems likely, therefore, that a pyrogenic material of truly endogenous origin is widely distributed in tissues. Tissue pyrogen appears to be a large molecule which is relatively resistant to treatment with acid but not with alkali. Possible pathological roles for this endogenous agent (or agents) are briefly indicated.

Firm Dynamics and Markup Variations: Implications for Sunspot Equilibria and Endogenous Economic Fluctuation

OpenAIRE

Nir Jaimovich

2007-01-01

This paper analyzes how the interaction between firms’ entry-and-exit decisions and variations in competition gives rise to self-fulfilling, expectation-driven fluctuations in aggregate economic activity and in measured total factor productivity (TFP). The analysis is based on a dynamic general equilibrium model in which net business formation is endogenously procyclical and leads to endogenous countercyclical variations in markups. This interaction leads to indeterminacy in which economic fl...

Why Don’t People Pay Attention?: Endogenous Sticky Information in a DSGE Model

OpenAIRE

Dräger, Lena

2010-01-01

Building on the models of sticky information, we endogenize the probability of obtaining new information by introducing a switching mechanism allowing agents to choose between costly rational expectations and costless expectations under sticky information. Thereby, the share of agents with rational expectations becomes endogenous and timevarying. While central results of sticky information models are retained, we find that the share of rational expectations is positively correlated with the v...

The effect of emotional responses on endogenous dynamics of activity-travel behavior: numerical simulation results

NARCIS (Netherlands)

Psarra, I.; Arentze, T.A.; Timmermans, H.J.P.

2014-01-01

The current study aims at developing a model of endogenous dynamics of activity-travel behavior. Endogenous dynamics are induced by stress, which is regarded as dissatisfaction with current habits. It is assumed that people try to alleviate stress by hierarchically trying short-term and then

The Endogeneity Bias in the Relation Between Cost-of-Debt Capital and Corporate Disclosure Policy

NARCIS (Netherlands)

Nikolaev, V.; van Lent, L.A.G.M.

2005-01-01

The purpose of this paper is twofold.First, we provide a discussion of the problems associated with endogeneity in empirical accounting research.We emphasize problems arising when endogeneity is caused by (1) unobservable firm specific factors and (2) omitted variables and discuss the merits and

Endogenous Vascular Endothelial Growth Factor-A (VEGF-A) Maintains Endothelial Cell Homeostasis by Regulating VEGF Receptor-2 Transcription*

Science.gov (United States)

E, Guangqi; Cao, Ying; Bhattacharya, Santanu; Dutta, Shamit; Wang, Enfeng; Mukhopadhyay, Debabrata

2012-01-01

Vascular endothelial growth factor A (VEGF-A) is one of the most important factors controlling angiogenesis. Although the functions of exogenous VEGF-A have been widely studied, the roles of endogenous VEGF-A remain unclear. Here we focused on the mechanistic functions of endogenous VEGF-A in endothelial cells. We found that it is complexed with VEGF receptor 2 (VEGFR-2) and maintains a basal expression level for VEGFR-2 and its downstream signaling activation. Endogenous VEGF-A also controls expression of key endothelial specific genes including VEGFR-2, Tie-2, and vascular endothelial cadherin. Of importance, endogenous VEGF-A differs from exogenous VEGF-A by regulating VEGFR-2 transcription through mediation of FoxC2 binding to the FOX:ETS motif, and the complex formed by endogenous VEGF-A with VEGFR-2 is localized within the EEA1 (early endosome antigen 1) endosomal compartment. Taken together, our results emphasize the importance of endogenous VEGF-A in endothelial cells by regulating key vascular proteins and maintaining the endothelial homeostasis. PMID:22167188

Lipopolysaccharide stimulates endogenous β-glucuronidase via PKC/NF-κB/c-myc signaling cascade: a possible factor in hepatolithiasis formation.

Science.gov (United States)

Yao, Dianbo; Dong, Qianze; Tian, Yu; Dai, Chaoliu; Wu, Shuodong

2017-11-29

Hepatolithiasis is commonly encountered in Southeastern and Eastern Asian countries, but the pathogenesis mechanism of stone formation is still not well understood. Now, the role of endogenous β-glucuronidase in pigment stones formation is being gradually recognized. In this study, the mechanism of increased expression and secretion of endogenous β-glucuronidase during hepatolithiasis formation was investigated. We assessed the endogenous β-glucuronidase, c-myc, p-p65, and p-PKC expression in liver specimens with hepatolithiasis by immunohistochemical staining, and found that compared with that in normal liver samples, the expression of endogenous β-glucuronidase, c-myc, p-p65, and p-PKC in liver specimens with hepatolithiasis significantly increased, and their expressions were positively correlated with each other. Lipopolysaccharide (LPS) induced increased expression of endogenous β-glucuronidase and c-myc in hepatocytes and intrahepatic biliary epithelial cells in a dose- and time-dependent manner, and endogenous β-glucuronidase secretion increased, correspondingly. C-myc siRNA transfection effectively inhibited the LPS-induced expression of endogenous β-glucuronidase. Furthermore, NF-κB inhibitor pyrrolidine dithiocarbamate or PKC inhibitor chelerythrine could effectively inhibit the LPS-induced expression of c-myc and endogenous β-glucuronidase, and the expression of p-p65 was also partly inhibited by chelerythrine. Our clinical observations and experimental data indicate that LPS could induce the increased expression and secretion of endogenous β-glucuronidase via a signaling cascade of PKC/NF-κB/c-myc in hepatocytes and intrahepatic biliary epithelial cells, and endogenous β-glucuronidase might play a possible role in the formation of hepatolithiasis.

Chromatographic analysis of endogenous retinoids in tissues and serum

NARCIS (Netherlands)

Schmidt, C.K.; Brouwer, A.; Nau, H.

2003-01-01

We present a reliable, highly sensitive, and versatile method for the simultaneous determination of endogenous polar (acidic) and apolar (retinol, retinal, and retinyl esters) retinoids in various biological matrices. Following a single liquid extraction of retinoids from tissues or plasma with