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  1. Proteophosphoglycan confers resistance of Leishmania major to midgut digestive enzymes induced by blood feeding in vector sand flies.

    Science.gov (United States)

    Secundino, Nagila; Kimblin, Nicola; Peters, Nathan C; Lawyer, Phillip; Capul, Althea A; Beverley, Stephen M; Turco, Salvatore J; Sacks, David

    2010-07-01

    Leishmania synthesize abundant phosphoglycan-containing molecules made up of [Gal-Man-PO(4)] repeating units, including the surface lipophosphoglycan (LPG), and the surface and secreted proteophosphoglycan (PPG). The vector competence of Phlebotomus duboscqi and Lutzomyia longipalpis sand flies was tested using L. major knockout mutants deficient in either total phosphoglycans (lpg2(-) or lpg5A(-)/5B(-)) or LPG alone (lpg1(-)) along with their respective gene add-back controls. Our results confirm that LPG, the major cell surface molecule of Leishmania promastigotes known to mediate attachment to the vector midgut, is necessary to prevent the loss of infection during excretion of the blood meal remnants from a natural vector, P. duboscqi, but not an unnatural vector, L. longipalpis. Midgut digestive enzymes induced by blood feeding pose another potential barrier to parasite survival. Our results show that 36-72 h after the infective feed, all parasites developed well except the lpg2(-) and lpg5A(-)/5B(-) mutants, which showed significantly reduced survival and growth. Protease inhibitors promoted the early survival and growth of lpg2(-) in the blood meal. PPG was shown to be the key molecule conferring resistance to midgut digestive enzymes, as it prevented killing of lpg2(-) promastigotes exposed to midgut lysates prepared from blood-fed flies. The protection was not associated with inhibition of enzyme activities, but with cell surface acquisition of the PPG, which appears to function similar to mammalian mucins to protect the surface of developing promastigotes against proteolytic damage. PMID:20088949

  2. Blood feeding by the Rocky Mountain spotted fever vector, Dermacentor andersoni, induces interleukin-4 expression by cognate antigen responding CD4+ T cells

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    Wikel Stephen K

    2009-10-01

    Full Text Available Abstract Background Tick modulation of host defenses facilitates both blood feeding and pathogen transmission. Several tick species deviate host T cell responses toward a Th2 cytokine profile. The majority of studies of modulation of T cell cytokine expression by ticks were performed with lymphocytes from infested mice stimulated in vitro with polyclonal T cell activators. Those reports did not examine tick modulation of antigen specific responses. We report use of a transgenic T cell receptor (TCR adoptive transfer model reactive with influenza hemagglutinin peptide (110-120 to examine CD4+ T cell intracellular cytokine responses during infestation with the metastriate tick, Dermacentor andersoni, or exposure to salivary gland extracts. Results Infestation with pathogen-free D. andersoni nymphs or administration of an intradermal injection of female or male tick salivary gland extract induced significant increases of IL-4 transcripts in skin and draining lymph nodes of BALB/c mice as measured by quantitative real-time RT-PCR. Furthermore, IL-10 transcripts were significantly increased in skin while IL-2 and IFN-γ transcripts were not significantly changed by tick feeding or intradermal injection of salivary gland proteins, suggesting a superimposed Th2 response. Infestation induced TCR transgenic CD4+ T cells to divide more frequently as measured by CFSE dilution, but more notably these CD4+ T cells also gained the capacity to express IL-4. Intracellular levels of IL-4 were significantly increased. A second infestation administered 14 days after a primary exposure to ticks resulted in partially reduced CFSE dilution with no change in IL-4 expression when compared to one exposure to ticks. Intradermal inoculation of salivary gland extracts from both male and female ticks also induced IL-4 expression. Conclusion This is the first report of the influence of a metastriate tick on the cytokine profile of antigen specific CD4+ T cells. Blood feeding

  3. Dengue virus infection of the Aedes aegypti salivary gland and chemosensory apparatus induces genes that modulate infection and blood-feeding behavior.

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    Shuzhen Sim

    Full Text Available The female Aedes aegypti salivary gland plays a pivotal role in bloodmeal acquisition and reproduction, and thereby dengue virus (DENV transmission. It produces numerous immune factors, as well as immune-modulatory, vasodilatory, and anti-coagulant molecules that facilitate blood-feeding. To assess the impact of DENV infection on salivary gland physiology and function, we performed a comparative genome-wide microarray analysis of the naïve and DENV infection-responsive A. aegypti salivary gland transcriptomes. DENV infection resulted in the regulation of 147 transcripts that represented a variety of functional classes, including several that are essential for virus transmission, such as immunity, blood-feeding, and host-seeking. RNAi-mediated gene silencing of three DENV infection-responsive genes--a cathepsin B, a putative cystatin, and a hypothetical ankyrin repeat-containing protein--significantly modulated DENV replication in the salivary gland. Furthermore, silencing of two DENV infection-responsive odorant-binding protein genes (OBPs resulted in an overall compromise in blood acquisition from a single host by increasing the time for initiation of probing and the probing time before a successful bloodmeal. We also show that DENV established an extensive infection in the mosquito's main olfactory organs, the antennae, which resulted in changes of the transcript abundance of key host-seeking genes. DENV infection, however, did not significantly impact probing initiation or probing times in our laboratory infection system. Here we show for the first time that the mosquito salivary gland mounts responses to suppress DENV which, in turn, modulates the expression of chemosensory-related genes that regulate feeding behavior. These reciprocal interactions may have the potential to affect DENV transmission between humans.

  4. Toxic Effect of Blood Feeding in Male Mosquitoes

    OpenAIRE

    Nikbakhtzadeh, Mahmood R.; Garrison K. Buss; Leal, Walter S.

    2016-01-01

    Blood- and sugar feeding of female mosquitoes has been frequently observed in the laboratory and in the field, but only sugar feeding of males has been reported. Here, we describe for the first time that Culex quinquefasciatus males feed on blood as well. Blood feeding easily happened on a blood-soaked cotton roll and, to a lesser extent, through a thin artificial layer. Mating history of a male specimen does not affect his blood feeding behavior. Male mosquitoes feed on blood even when they ...

  5. Sotalol-induced bradycardia reversed by glucagon.

    OpenAIRE

    Fernandes, C. M.; Daya, M. R.

    1995-01-01

    Glucagon is considered the drug of choice for treating bradycardia and hypotension encountered during beta-blocker poisoning. Its potential usefulness in reversing adverse effects encountered during therapeutic dosing with beta-blockers has not been well characterized. We present a case of sotalol-induced bradycardia reversed by glucagon.

  6. The role of cystatins in tick physiology and blood feeding

    Czech Academy of Sciences Publication Activity Database

    Schwarz, Alexandra; Valdés, James J.; Kotsyfakis, Michalis

    2012-01-01

    Roč. 3, č. 3 (2012), s. 117-127. ISSN 1877-959X R&D Projects: GA ČR GAP502/12/2409 Institutional research plan: CEZ:AV0Z60220518 Keywords : Cystatin * Cysteine proteases * Tick * Immunomodulators * Blood feeding * Midgut * Physiology Subject RIV: EC - Immunology Impact factor: 2.353, year: 2012

  7. Reversible Posterior Leukoencephalopathy Syndrome Induced by Pazopanib

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    Chelis Leonidas

    2012-10-01

    Full Text Available Abstract Background The reversible posterior leukoencephalopathy syndrome is a clinical/radiological syndrome characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging findings. There are several reports in the literature that depict its occurrence in cancer patients. The list of common anticancer and supportive care drugs that predispose to reversible posterior leukoencephalopathy syndrome is expanding and includes not only a large number of chemotherapeutic agents but also an increased number of new targeted drugs, particularly angiogenesis inhibitors such as bevacizumab,sorefenib and sunitinib. Pazopanib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit which after a positive phase III randomized clinical trial in patients with advanced renal cell cancer received FDA approval for the treatment of advanced renal cell carcinoma. Until now no cases of reversible posterior leukoencephalopathy syndrome induced by pazopanib have been reported. Case report We present the case of a 40 years old female patient with heavily pre-treated metastatic renal cell carcinoma who received pazopanib as salvage treatment. After 21 days of pazopanib therapy the patient referred to the emergency department with epileptic seizure, impaired vision at both eyes and headache. MRI of the brain revealed subcortical oedema at the occipital and parietal lobes bilaterally. She was treated with anticonvulsants, i.v. administration of mannitol and antihypertensives and she recovered completely from her symptoms and was discharged on the tenth hospital day. A brain MRI performed 3 weeks after showed that the subcortical oedema had been subsided. Conclusion In conclusion this is the first case of pazopanib induced reversible posterior leukoencephalopathy syndrome. Although usually reversible, this syndrome is a serious and

  8. Reversible Posterior Leukoencephalopathy Syndrome Induced by Pazopanib

    International Nuclear Information System (INIS)

    The reversible posterior leukoencephalopathy syndrome is a clinical/radiological syndrome characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging findings. There are several reports in the literature that depict its occurrence in cancer patients. The list of common anticancer and supportive care drugs that predispose to reversible posterior leukoencephalopathy syndrome is expanding and includes not only a large number of chemotherapeutic agents but also an increased number of new targeted drugs, particularly angiogenesis inhibitors such as bevacizumab,sorefenib and sunitinib. Pazopanib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit which after a positive phase III randomized clinical trial in patients with advanced renal cell cancer received FDA approval for the treatment of advanced renal cell carcinoma. Until now no cases of reversible posterior leukoencephalopathy syndrome induced by pazopanib have been reported. We present the case of a 40 years old female patient with heavily pre-treated metastatic renal cell carcinoma who received pazopanib as salvage treatment. After 21 days of pazopanib therapy the patient referred to the emergency department with epileptic seizure, impaired vision at both eyes and headache. MRI of the brain revealed subcortical oedema at the occipital and parietal lobes bilaterally. She was treated with anticonvulsants, i.v. administration of mannitol and antihypertensives and she recovered completely from her symptoms and was discharged on the tenth hospital day. A brain MRI performed 3 weeks after showed that the subcortical oedema had been subsided. In conclusion this is the first case of pazopanib induced reversible posterior leukoencephalopathy syndrome. Although usually reversible, this syndrome is a serious and potentially life threatening adverse effect, if untreated, that should

  9. Multitasking roles of mosquito labrum in oviposition and blood feeding

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    Young-Moo eChoo

    2015-10-01

    with 4EP, i.e., they engaged more rapidly in continuous blood feeding as compared to untreated blood. The time of engagement for feeding in skatole-containing blood vs. untreated blood did not differ significantly. Taken together, these data suggest that 4EP reception by the labrum is important not only for oviposition decisions, but also for reducing probing and initiation of blood feeding.

  10. A novel olfactory pathway is essential for fast and efficient blood-feeding in mosquitoes

    OpenAIRE

    Je Won Jung; Seung-Jae Baeck; Haribalan Perumalsamy; Bill S Hansson; Young-Joon Ahn; Hyung Wook Kwon

    2015-01-01

    In mosquitoes, precise and efficient finding of a host animal is crucial for survival. One of the poorly understood aspects of mosquito blood-feeding behavior is how these insects target an optimal site in order to penetrate the skin and blood vessels without alerting the host animal. Here we provide new findings that a piercing structure of the mouthpart of the mosquitoes, the stylet, is an essential apparatus for the stage in blood feeding. Indeed, the stylet possesses a number of sensory h...

  11. Proteolytic system of blood-feeding ticks: An update on protein structures

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Zuzana; Hobizalová, Radka; Žebrakovská, Iva; Brynda, Jiří; Řezáčová, Pavlína; Horn, Martin; Mareš, Michael

    2015-01-01

    Roč. 22, č. 1 (2015), s. 43-44. ISSN 1211-5894. [Discussions in Structural Molecular Biology. Annual Meeting of the Czech Society for Structural Biology /13./. 19.03.2015-21.03.2015, Nové Hrady] Institutional support: RVO:61388963 ; RVO:68378050 Keywords : blood-feeding ticks * protein structure * proteolytic system Subject RIV: CE - Biochemistry

  12. Wolbachia infection reduces blood-feeding success in the dengue fever mosquito, Aedes aegypti.

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    Andrew P Turley

    Full Text Available BACKGROUND: The mosquito Aedes aegypti was recently transinfected with a life-shortening strain of the endosymbiont Wolbachia pipientis (wMelPop as the first step in developing a biocontrol strategy for dengue virus transmission. In addition to life-shortening, the wMelPop-infected mosquitoes also exhibit increased daytime activity and metabolic rates. Here we sought to quantify the blood-feeding behaviour of Wolbachia-infected females as an indicator of any virulence or energetic drain associated with Wolbachia infection. METHODOLOGY/PRINCIPAL FINDINGS: In a series of blood-feeding trials in response to humans, we have shown that Wolbachia-infected mosquitoes do not differ in their response time to humans, but that as they age they obtain fewer and smaller blood meals than Wolbachia-uninfected controls. Lastly, we observed a behavioural characteristic in the Wolbachia infected mosquitoes best described as a "bendy" proboscis that may explain the decreased biting success. CONCLUSIONS/SIGNIFICANCE: Taken together the evidence suggests that wMelPop infection may be causing tissue damage in a manner that intensifies with mosquito age and that leads to reduced blood-feeding success. These behavioural changes require further investigation with respect to a possible physiological mechanism and their role in vectorial capacity of the insect. The selective decrease of feeding success in older mosquitoes may act synergistically with other Wolbachia-associated traits including life-shortening and viral protection in biocontrol strategies.

  13. Optimization of sugar and blood feeding regimen in Anopheles gambiae mass production system

    International Nuclear Information System (INIS)

    The sterile insect technique (SIT) is being developed for the control of malaria transmitting mosquitoes. Critical to the success of applying the SIT is the establishment of standardized mass production systems for the target species. As part of efforts to develop standardised mass production systems for malaria vectors, this project sought to optimize adult blood and sugar feeding in a mass production system. Different sugar types (glucose, sucrose and honey) were evaluated at 6% and 10% concentrations in water to determine the best sugar diet and concentration for feeding adult An. gambiae. Different blood feeding methods, restrained Guinea pig, anaesthetised Guinea pig and human arm feeding were evaluated. Adult survival, female insemination and egg production were used as criteria to determine optimum sugar and blood feeding. The effect of anaesthetics on blood feeding response and egg production of female An. gambiae was determined by comparing feeding response and egg production of females fed with anaesthetised Guinea pigs as against physically restrained Guinea pigs (Control). The specific effect of different anaesthetic agents on blood feeding response and egg production of female mosquitoes were was also determined by comparing the feeding response and egg production of females fed with either Ketamine/Xylazine anaesthetised Guinea pigs or Ketamine/Diazepam anaesthetised Guinea pigs. Effects due to sugar types and concentrations on percentage survival of male and female mosquitoes were observed to be significant at (p 0.05). However, human ann feeding (HAP) method and Ketamine/Xylazine (KX) anaesthetics fed for 25 minutes recorded higher percentage feeding (76.0% and 68.0% respectively) and egg production of 19.0% and 20.8% respectively. Anaesthetised Guinea pig feeding (AGF) of adults for 15 minutes followed closely with 60.0% and 15.1% blood feeding and egg production respectively whilst restrained Guinea pig feeding (RGF) method and Ketamine

  14. Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

    Energy Technology Data Exchange (ETDEWEB)

    Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

    1984-04-01

    The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

  15. Comparative studies on the biology and filarial susceptibility of selected blood-feeding and autogenous Aedes togoi sub-colonies

    OpenAIRE

    Anuluck Junkum; Wej Choochote; Atchariya Jitpakdi; Somjai Leemingsawat; Narumon Komalamisra; Narissara Jariyapan; Chavalit Boonyatakorn

    2003-01-01

    Blood-feeding and autogenous sub-colonies were selected from a laboratory, stock colony of Aedes togoi, which was originally collected from Koh Nom Sao, Chanthaburi province, Southeast Thailand. Comparative biology and filarial susceptibility between the two sub-colonies (blood-feeding: F11, F13; autogeny: F38, F40) were investigated to evaluate their viability and vectorial capacity. The results of comparison on biology revealed intraspecific differences, i.e., the average egg deposition/gra...

  16. Gene expression patterns associated with blood-feeding in the malaria mosquito Anopheles gambiae

    OpenAIRE

    Hogan James R; Lobo Neil F; Harker Brent W; Hillenmeyer Maureen E; Kern Marcia K; Hong Young S; Dana Ali N; Romans Patricia; Collins Frank H

    2005-01-01

    Abstract Background Blood feeding, or hematophagy, is a behavior exhibited by female mosquitoes required both for reproduction and for transmission of pathogens. We determined the expression patterns of 3,068 ESTs, representing ~2,000 unique gene transcripts using cDNA microarrays in adult female Anopheles gambiae at selected times during the first two days following blood ingestion, at 5 and 30 min during a 40 minute blood meal and at 0, 1, 3, 5, 12, 16, 24 and 48 hours after completion of t...

  17. Gene expression patterns associated with blood-feeding in the malaria mosquito Anopheles gambiae

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    Hogan James R

    2005-01-01

    Full Text Available Abstract Background Blood feeding, or hematophagy, is a behavior exhibited by female mosquitoes required both for reproduction and for transmission of pathogens. We determined the expression patterns of 3,068 ESTs, representing ~2,000 unique gene transcripts using cDNA microarrays in adult female Anopheles gambiae at selected times during the first two days following blood ingestion, at 5 and 30 min during a 40 minute blood meal and at 0, 1, 3, 5, 12, 16, 24 and 48 hours after completion of the blood meal and compared their expression to transcript levels in mosquitoes with access only to a sugar solution. Results In blood-fed mosquitoes, 413 unique transcripts, approximately 25% of the total, were expressed at least two-fold above or below their levels in the sugar-fed mosquitoes, at one or more time points. These differentially expressed gene products were clustered using k-means clustering into Early Genes, Middle Genes, and Late Genes, containing 144, 130, and 139 unique transcripts, respectively. Several genes from each group were analyzed by quantitative real-time PCR in order to validate the microarray results. Conclusion The expression patterns and annotation of the genes in these three groups (Early, Middle, and Late genes are discussed in the context of female mosquitoes' physiological responses to blood feeding, including blood digestion, peritrophic matrix formation, egg development, and immunity.

  18. Reversible disruption of pre-pulse inhibition in hypomorphic-inducible and reversible CB1-/- mice.

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    Maria Franca Marongiu

    Full Text Available Although several genes are implicated in the pathogenesis of schizophrenia, in animal models for such a severe mental illness only some aspects of the pathology can be represented (endophenotypes. Genetically modified mice are currently being used to obtain or characterize such endophenotypes. Since its cloning and characterization CB1 receptor has increasingly become of significant physiological, pharmacological and clinical interest. Recently, its involvement in schizophrenia has been reported. Among the different approaches employed, gene targeting permits to study the multiple roles of the endocannabinoid system using knockout ((-/- mice represent a powerful model but with some limitations due to compensation. To overcome such a limitation, we have generated an inducible and reversible tet-off dependent tissue-specific CB1(-/- mice where the CB1R is re-expressed exclusively in the forebrain at a hypomorphic level due to a mutation (IRh-CB1(-/- only in absence of doxycycline (Dox. In such mice, under Dox(+ or vehicle, as well as in wild-type (WT and CB1(-/-, two endophenotypes motor activity (increased in animal models of schizophrenia and pre-pulse inhibition (PPI of startle reflex (disrupted in schizophrenia were analyzed. Both CB1(-/- and IRh-CB1(-/- showed increased motor activity when compared to WT animals. The PPI response, unaltered in WT and CB1(-/- animals, was on the contrary highly and significantly disrupted only in Dox(+ IRh-CB1(-/- mice. Such a response was easily reverted after either withdrawal from Dox or haloperidol treatment. This is the first Inducible and Reversible CB1(-/- mice model to be described in the literature. It is noteworthy that the PPI disruption is not present either in classical full CB1(-/- mice or following acute administration of rimonabant. Such a hypomorphic model may provide a new tool for additional in vivo and in vitro studies of the physiological and pathological roles of cannabinoid system in

  19. Inducing sex reversal of the urogenital system of marsupials.

    Science.gov (United States)

    Renfree, Marilyn B; Chew, Keng Yih; Shaw, Geoff

    2014-01-01

    Marsupials differ from eutherian mammals in their reproductive strategy of delivering a highly altricial young after a short gestation. The young, with its undeveloped organ systems completes its development post-natally, usually within a pouch. The young is dependent on milk with a composition that varies through lactation to support its growth and changing needs as it matures over a lengthy period. Gonadal differentiation occurs after birth, providing a unique opportunity to examine the effects of hormonal manipulations on its sexual differentiation of the highly accessible young. In marsupials a difference in the migration of the urinary ducts around the genital ducts from eutherian mammals results in the unique tammar reproductive tract which has three vaginae and two cervices, and two distinctly separate uteri. In the tammar wallaby, a small member of the kangaroo family, we showed that virilisation of the Wolffian duct, prostate and phallus depends on an alternate androgen pathway, which has now been shown to be important for virilisation in humans. Through hormonal manipulations over differing time periods we have achieved sex reversal of both ovaries and testes, germ cells, genital ducts, prostate and phallus. Whilst we understand many of the mechanisms behind sexual differentiation there are still many lessons to be learned from understanding how sex reversal is achieved by using a model such as the tammar wallaby. This will help guide investigations into the major questions of how and why sex determination is achieved in other species. This review discusses the control and development of the marsupial urogenital system, largely drawn from our studies in the tammar wallaby and our ability to manipulate this system to induce sex reversal. PMID:24433705

  20. Strain-induced time-reversal odd superconductivity in graphene

    Science.gov (United States)

    Juricic, Vladimir; Roy, Bitan

    2014-03-01

    I will discuss the possibility of realizing a time-reversal-symmetry breaking superconducting state that exhibits an f + is pairing symmetry in strained graphene. Although the underlying attractive interactions need to be sufficiently strong and comparable in pristine graphene to support such pairing state, I will argue that strain can be conducive for its formation even for weak interactions. I will show that quantum-critical behavior near the transition is controlled by a fermionic multicritical point, characterized by various critical exponents computed in the framework of an ɛ-expansion near four spacetime dimensions. I will then discuss the scaling of the superconducting gap with the strain-induced axial pseudo-magnetic field. Furthermore, a vortex in this mixed superconducting state hosts a pair of Majorana fermions supporting a quartet of insulating and superconducting orders, among which quantum spin Hall topological insulator. Finally, I will mention some experimental signatures of this f + is time-reversal odd superconductor. These findings suggest that strained graphene could provide a platform for the realization of exotic superconducting states of Dirac fermions. VJ is supported by the Netherlands Organization for Scientific Research (NWO).

  1. Comparative studies on the biology and filarial susceptibility of selected blood-feeding and autogenous Aedes togoi sub-colonies

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    Anuluck Junkum

    2003-06-01

    Full Text Available Blood-feeding and autogenous sub-colonies were selected from a laboratory, stock colony of Aedes togoi, which was originally collected from Koh Nom Sao, Chanthaburi province, Southeast Thailand. Comparative biology and filarial susceptibility between the two sub-colonies (blood-feeding: F11, F13; autogeny: F38, F40 were investigated to evaluate their viability and vectorial capacity. The results of comparison on biology revealed intraspecific differences, i.e., the average egg deposition/gravid female (F11/F38; F13/F40, embryonation rate (F13/F40, hatchability rate (F11/F38; F13/F40, egg width (F11/F38, wing length of females (F13/F40, and wing length and width of males (F11/F38 in the blood-feeding sub-colony were significantly greater than that in the autogenous sub-colony; and egg length (F11/F38 and width (F13/F40, and mean longevity of adult females (F11/F38 and males (F13/F40 in the blood-feeding sub-colony were significantly less than that in the autogenous sub-colony. The results of comparison on filarial susceptibility demonstrated that both sub-colonies yielded similar susceptibilities to Brugia malayi [blood-feeding/autogeny = 56.7% (F11/53.3%(F38, 60%(F13/83.3%(F40] and Dirofilaria immitis [blood-feeding/autogeny = 85.7%(F11/75%(F38, 45%(F13/29.4%(F40], suggesting autogenous Ae. togoi sub-colony was an efficient laboratory vector in study of filariasis.

  2. Current induced magnetization reversal in spin valves with Heusler alloys

    International Nuclear Information System (INIS)

    Current induced magnetization reversal using current-perpendicular-to-plane (CPP) spin valves devises with Co2MnGe, Co2FeSi, and Co75Fe25 alloys were investigated. Film stacks of Si/SiO2/Cu/IrMn/Heusler-pinned-layer/Cu/Heusler-free-layer were deposited by DC magnetron sputtering followed by post-annealing. Saturation magnetization (B s) of Co2MnGe, Co2FeSi, and Co75Fe25 are 12.7, 14.0, and 25 kg, respectively and magnetoresistance (MR) ratios of spin valves with the Co2MnGe, Co2FeSi, and Co75Fe25 are 3.6%, 3.5%, and 2.2%, respectively. The B s values and MR ratios obtained for Co2MnGe and Co2FeSi spin valves were smaller and larger, respectively, than those obtained for Co75Fe25. We speculated that the large MR ratios could be attributed to larger spin polarization of Heusler alloys. J c0 of Co2MnGe, Co2FeSi, and Co75Fe25 spin valves were 1.6x107, 2.7x107, and 5.1x107 A/cm2, respectively. The thermal factors of Co2MnGe, Co2FeSi, and Co75Fe25 were 65, 48, and 55, respectively. Using the Heusler alloys, we successfully reduced the intrinsic critical current without degrading the thermal factor

  3. Tyrosine Detoxification Is an Essential Trait in the Life History of Blood-Feeding Arthropods.

    Science.gov (United States)

    Sterkel, Marcos; Perdomo, Hugo D; Guizzo, Melina G; Barletta, Ana Beatriz F; Nunes, Rodrigo D; Dias, Felipe A; Sorgine, Marcos H F; Oliveira, Pedro L

    2016-08-22

    Blood-feeding arthropods are vectors of infectious diseases such as dengue, Zika, Chagas disease, and malaria [1], and vector control is essential to limiting disease spread. Because these arthropods ingest very large amounts of blood, a protein-rich meal, huge amounts of amino acids are produced during digestion. Previous work on Rhodnius prolixus, a vector of Chagas disease, showed that, among all amino acids, only tyrosine degradation enzymes were overexpressed in the midgut compared to other tissues [2]. Here we demonstrate that tyrosine detoxification is an essential trait in the life history of blood-sucking arthropods. We found that silencing Rhodnius tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD), the first two enzymes of the phenylalanine/tyrosine degradation pathway, caused the death of insects after a blood meal. This was confirmed by using the HPPD inhibitor mesotrione, which selectively killed hematophagous arthropods but did not affect non-hematophagous insects. In addition, mosquitoes and kissing bugs died after feeding on mice that had previously received a therapeutic effective oral dose (1 mg/kg) of nitisinone, another HPPD inhibitor used in humans for the treatment of tyrosinemia type I [3]. These findings indicate that HPPD (and TAT) can be a target for the selective control of blood-sucking disease vector populations. Because HPPD inhibitors are extensively used as herbicides and in medicine, these compounds may provide an alternative less toxic to humans and more environmentally friendly than the conventional neurotoxic insecticides that are currently used, with the ability to affect only hematophagous arthropods. PMID:27476595

  4. Dynamics of digestive proteolytic system during blood feeding of the hard tick Ixodes ricinus

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    Sojka Daniel

    2010-12-01

    Full Text Available Abstract Background Ticks are vectors of a wide variety of pathogens causing severe diseases in humans and domestic animals. Intestinal digestion of the host blood is an essential process of tick physiology and also a limiting factor for pathogen transmission since the tick gut represents the primary site for pathogen infection and proliferation. Using the model tick Ixodes ricinus, the European Lyme disease vector, we have previously demonstrated by genetic and biochemical analyses that host blood is degraded in the tick gut by a network of acidic peptidases of the aspartic and cysteine classes. Results This study reveals the digestive machinery of the I. ricinus during the course of blood-feeding on the host. The dynamic profiling of concentrations, activities and mRNA expressions of the major digestive enzymes demonstrates that the de novo synthesis of peptidases triggers the dramatic increase of the hemoglobinolytic activity along the feeding period. Overall hemoglobinolysis, as well as the activity of digestive peptidases are negligible at the early stage of feeding, but increase dramatically towards the end of the slow feeding period, reaching maxima in fully fed ticks. This finding contradicts the established opinion that blood digestion is reduced at the end of engorgement. Furthermore, we show that the digestive proteolysis is localized intracellularly throughout the whole duration of feeding. Conclusions Results suggest that the egressing proteolytic system in the early stage of feeding and digestion is a potential target for efficient impairment, most likely by blocking its components via antibodies present in the host blood. Therefore, digestive enzymes are promising candidates for development of novel 'anti-tick' vaccines capable of tick control and even transmission of tick-borne pathogens.

  5. Thermally-Activated Magnetic Reversal Induced by a Spin-Polarized Current

    OpenAIRE

    Myers, E. B.; Albert, F. J.; Saneky, J. C.; Bonet, E.; Buhrman, R. A.; Ralph, D. C.

    2002-01-01

    We have measured the statistical properties of magnetic reversal in nanomagnets driven by a spin-polarized current. Like reversal induced by a magnetic field, spin-transfer-driven reversal near room temperature exhibits the properties of thermally-activated escape over an effective barrier. However, the spin-transfer effect produces qualitatively different behaviors than an applied magnetic field. We discuss an effective current vs. field phase diagram. If the current and field are tuned so t...

  6. Web-building spiders and blood-feeding flies as prey of the notch-eared bat (Myotis emarginatus)

    OpenAIRE

    Kervyn, Thierry; Godin, Marie Céline; Jocqué, Rudy; Grootaert, Patrick; Libois, Roland

    2012-01-01

    Conservation of the endangered notch-eared bat (M. emarginatus) requires a specific action plan based on precise ecological requirements of this species. The analysis of the diet of three colonies in southern Belgium revealed: (1) spatial and seasonal variations of the diet; (2) the consumption of web-building spiders (Araneus diadematus, A. triguttatus, Cyclosa conica, Enoplognatha sp., Larinioides patagiatus, Neriene emphana); (3) the predominance of blood-feeding dipterans in the diet (Sto...

  7. Silicon-induced reversibility of cadmium toxicity in rice.

    Science.gov (United States)

    Farooq, Muhammad Ansar; Detterbeck, Amelie; Clemens, Stephan; Dietz, Karl-Josef

    2016-05-01

    Silicon (Si) modulates tolerance to abiotic stresses, but little is known about the reversibility of stress effects by supplementing previously stressed plants with Si. This is surprising since recovery experiments might allow mechanisms of Si-mediated amelioration to be addressed. Rice was exposed to 10 µM CdCl2 for 4 d in hydroponics, followed by 0.6mM Si(OH)4 supplementation for 4 d. Si reversed the effects of Cd, as reflected in plant growth, photosynthesis, elemental composition, and some biochemical parameters. Cd-dependent deregulation of nutrient homeostasis was partially reversed by Si supply. Photosynthetic recovery within 48h following Si supply, coupled with strong stimulation of the ascorbate-glutathione system, indicates efficient activation of defense. The response was further verified by transcript analyses with emphasis on genes encoding members of the stress-associated protein (SAP) family. The transcriptional response to Cd was mostly reversed following Si supply. Reprogramming of the Cd response was obvious for Phytochelatin synthase 1, SAP1 , SAP14, and the transcription factor genes AP2/Erf020, Hsf31, and NAC6 whose transcript levels were strongly activated in roots of Cd-stressed rice, but down-regulated in the presence of Si. These findings, together with changes in biochemical parameters, highlight the significance of Si in growth recovery of Cd-stressed rice and indicate a decisive role for readjusting cell redox homeostasis. PMID:27122572

  8. Cyclosporin-A induced Posterior Reversible Encephalopathy Syndrome

    Directory of Open Access Journals (Sweden)

    Saeed Bassam

    2008-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is a recently proposed clinico-neuroradiological entity observed in a variety of clinical settings such as cyclosporin A (CsA neurotoxicity. We report a 3.5-year-old Syrian boy in whom steroid-resistant focal segmental glomerulosclerosis (FSGS was recently diagnosed. The patient remitted his nephrotic syndrome after 10 days of CsA administration. However, he shortly developed altered mental status, visual impairment, focal neurological deficits and seizures. We discontinued CsA that resulted in complete reversal of the patient′s encephalopathical condition over a period of 4 months. We conclude that PRES should be suspected in immunosuppresed patients with kidney disease if they have a sudden episode of neurological symptoms.

  9. Current-induced reversal in magnetic nanopillars passivated by silicon

    OpenAIRE

    Urazhdin, Sergei; Tabor, Phillip

    2008-01-01

    We demonstrate that magnetic multilayer nanopillars can be efficiently protected from oxidation by coating with silicon. Both the protected and the oxidized nanopillars exhibit an increase of reversal current at cryogenic temperatures. However the magnetic excitation onset current increases only in the oxidized samples. We show that oxidized nanopillars exhibit anomalous switching statistics at low temperature, providing a simple test for the quality of magnetic nanodevices.

  10. Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

    OpenAIRE

    Adebiyi, Oluwafeyisetan O.; Olubunmi A. Adebiyi; Owira, Peter M. O.

    2015-01-01

    Nucleoside Reverse Transcriptase Inhibitors (NRTIs) have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin’s effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7) were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT) (groups I, II III), 50 mg/kg stavudine (d4T) (groups IV, V, VI) an...

  11. Magnetization reversal induced by irregular shape nanodots in square arrays

    Energy Technology Data Exchange (ETDEWEB)

    Redondo, C.; Sierra, B.; Moralejo, S.; Castano, F., E-mail: f.castano@ehu.e

    2010-07-15

    Ni{sub 80}Fe{sub 20} nanodots in square arrays of irregular shape (C{sub 1h}(m) and x-, y-translations symmetry) and circular shape (D{sub 4h} (4/mmm)) nanodots of the same area were fabricated under controlled exposure conditions by e-beam lithography, ion beam sputtering coating and further lift-off. The center-to-center nearest dot distances was 700 nm in all the measured arrays. An unpatterned film was fabricated in the same IBS batch for comparison purposes. Structures and magnetic properties were characterized using AFM, SEM and high-sensitivity focused magneto-optical Kerr effect (MOKE). The mechanism of the magnetization reversal of arrays is discussed in two different scenarios: vortex and single-domain. It has been shown that circular dots reverse only through vortex configuration whereas the irregular does either via single-domain and vortex configuration, depending of the dot size. Variable domain phases are confirmed by OOMMF (Object Oriented Micromagnetic Framework) micromagnetic simulations.

  12. Reversible tobramycin-induced bilateral high-frequency vestibular toxicity.

    Science.gov (United States)

    Walsh, R M; Bath, A P; Bance, M L

    2000-01-01

    We report an unusual case of tobramycin-induced bilateral high-frequency vestibular toxicity with subsequent clinical and objective evidence of functional recovery. In those patients with a clinical presentation suggestive of aminoglycoside-induced bilateral vestibular toxicity (ataxia and oscillopsia) and normal low-frequency (ENG-caloric) responses, high-frequency rotation chair testing should be performed to exclude a high-frequency vestibular deficit. PMID:10810261

  13. Piracetam reverses haloperidol-induced catalepsy in mice

    OpenAIRE

    SALAM, Omar Abdel; NADA, Somaia

    2011-01-01

    To investigate the memory-enhancing drugs piracetam, vinpocetine, and ginkgo biloba for their ability to reduce catalepsy in mice treated with haloperidol. Haloperidol is a classic neuroleptic drug that induces motor abnormalities and cognitive impairment due to a blockade of dopamine D2 receptors in the striatum. Materials and methods: Catalepsy was induced by intraperitoneal haloperidol (2 mg/kg) administration. The drugs being tested were either administered intraperitoneally (IP) along ...

  14. Susceptibility of adult female Aedes aegypti (Diptera: Culicidae to the entomopathogenic fungus Metarhizium anisopliae is modified following blood feeding

    Directory of Open Access Journals (Sweden)

    Samuels Richard I

    2011-05-01

    Full Text Available Abstract Background The mosquito Aedes aegypti, vector of dengue fever, is a target for control by entomopathogenic fungi. Recent studies by our group have shown the susceptibility of adult A. aegypti to fungal infection by Metarhizium anisopliae. This fungus is currently being tested under field conditions. However, it is unknown whether blood-fed A. aegypti females are equally susceptible to infection by entomopathogenic fungi as sucrose fed females. Insect populations will be composed of females in a range of nutritional states. The fungus should be equally efficient at reducing survival of insects that rest on fungus impregnated surfaces following a blood meal as those coming into contact with fungi before host feeding. This could be an important factor when considering the behavior of A. aegypti females that can blood feed on multiple hosts over a short time period. Methods Female A. aegypti of the Rockefeller strain and a wild strain were infected with two isolates of the entomopathogenic fungus M. anisopliae (LPP 133 and ESALQ 818 using an indirect contact bioassay at different times following blood feeding. Survival rates were monitored on a daily basis and one-way analysis of variance combined with Duncan's post-hoc test or Log-rank survival curve analysis were used for statistical comparisons of susceptibility to infection. Results Blood feeding rapidly reduced susceptibility to infection, determined by the difference in survival rates and survival curves, when females were exposed to either of the two M. anisopliae isolates. Following a time lag which probably coincided with digestion of the blood meal (96-120 h post-feeding, host susceptibility to infection returned to pre-blood fed (sucrose fed levels. Conclusions Reduced susceptibility of A. aegypti to fungi following a blood meal is of concern. Furthermore, engorged females seeking out intra-domicile resting places post-blood feeding, would be predicted to rest for prolonged

  15. Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

    Directory of Open Access Journals (Sweden)

    Oluwafeyisetan O. Adebiyi

    2015-12-01

    Full Text Available Nucleoside Reverse Transcriptase Inhibitors (NRTIs have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin’s effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7 were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT (groups I, II III, 50 mg/kg stavudine (d4T (groups IV, V, VI and 3 mL/kg of distilled water (group VII. Additionally, rats in groups II and V were similarly treated with 50 mg/kg naringin, while groups III and VI were treated with 45 mg/kg vitamin E. AZT or d4T treatment significantly reduced body weight and plasma high density lipoprotein concentrations but increased liver weights, plasma triglycerides and total cholesterol compared to controls, respectively. Furthermore, AZT or d4T treatment significantly increased oxidative stress, adiposity index and expression of Bax protein, but reduced Bcl-2 protein expression compared to controls, respectively. However, either naringin or vitamin E significantly mitigated AZT- or d4T-induced weight loss, dyslipidemia, oxidative stress and hepatocyte apoptosis compared to AZT- or d4T-only treated rats. Our results suggest that naringin reverses metabolic complications associated with NRTIs by ameliorating oxidative stress and apoptosis. This implies that naringin supplements could mitigate lipodystrophy and dyslipidemia associated with NRTI therapy.

  16. Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications.

    Science.gov (United States)

    Adebiyi, Oluwafeyisetan O; Adebiyi, Olubunmi A; Owira, Peter M O

    2015-12-01

    Nucleoside Reverse Transcriptase Inhibitors (NRTIs) have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin's effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7) were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT) (groups I, II III), 50 mg/kg stavudine (d4T) (groups IV, V, VI) and 3 mL/kg of distilled water (group VII). Additionally, rats in groups II and V were similarly treated with 50 mg/kg naringin, while groups III and VI were treated with 45 mg/kg vitamin E. AZT or d4T treatment significantly reduced body weight and plasma high density lipoprotein concentrations but increased liver weights, plasma triglycerides and total cholesterol compared to controls, respectively. Furthermore, AZT or d4T treatment significantly increased oxidative stress, adiposity index and expression of Bax protein, but reduced Bcl-2 protein expression compared to controls, respectively. However, either naringin or vitamin E significantly mitigated AZT- or d4T-induced weight loss, dyslipidemia, oxidative stress and hepatocyte apoptosis compared to AZT- or d4T-only treated rats. Our results suggest that naringin reverses metabolic complications associated with NRTIs by ameliorating oxidative stress and apoptosis. This implies that naringin supplements could mitigate lipodystrophy and dyslipidemia associated with NRTI therapy. PMID:26690471

  17. Modeling large reversible electric-field-induced strain in ferroelectric materials using 90° orientation switching

    Institute of Scientific and Technical Information of China (English)

    Roderick; V.; N.; MELNIK

    2009-01-01

    Reversible large electric-field-induced strain caused by reversible orientation switchings in BaTiO3 is modeled using the Landau’s theory of phase transition. A triple well free energy function is constructed. Each of its minima is associated with one of the polarization orientations involved. Nonlinear constitu- tive laws accounting for reversible orientation switchings and electrostriction effects are obtained by using thermodynamic equilibrium conditions. Hysteretic dynamics of one-dimensional structures is described by coupled nonlinear differential equations. Double hysteretic loops in the electric and me- chanic fields are both successfully modeled. Giant reversible electrostriction is modeled as a conse-quence of reversible orientation switchings via electro-mechanical couplings. Comparisons with ex-perimental results reported in literatures are presented.

  18. Modeling large reversible electric-field-induced strain in ferroelectric materials using 90° orientation switching

    Institute of Scientific and Technical Information of China (English)

    WANG LinXiang; LIU Rong; Roderick V.N.MELNIK

    2009-01-01

    Reversible large electric-field-induced strain caused by reversible orientation switchings in BaTiO3 is modeled using the Landau's theory of phase transition. A triple well free energy function is constructed, Each of its minima is associated with one of the polarization orientations involved, Nonlinear constitu-tive laws accounting for reversible orientation switchings and electrostriction effects are obtained by using thermodynamic equilibrium conditions. Hysteretic dynamics of one-dimensional structures is described by coupled nonlinear differential equations. Double hysteretic loops in the electric and me-chanic fields are both successfully modeled. Giant reversible electrostriction is modeled as a conse-quence of reversible orientation switchings via electro-mechanical couplings. Comparisons with ex-perimental results reported in literatures are presented.

  19. 3, 4-methylenedioximethamphetamin reverses anxiety induced by chronic mild stress

    Directory of Open Access Journals (Sweden)

    Laura Andrea León A

    2013-01-01

    Full Text Available Here we report the effects of subchronic 3, 4 methylenedioximethamphetamine (MDMA on the elevated plusmaze, a widely used animal model of anxiety. Rats exposed to a mild chronic stress (MCS protocol received intracerebroventricular microinjections of the selective serotonin reuptake inhibitor (SSRI – fluoxetine (2.0 ug/ul or MDMA, (2.0 ug/ul for seven days. On the eighth day rats were tested in the elevated plus-maze. Our results showed that sub chronic MDMA interacted with MCS leading to a decrease in anxiety related behaviors including: percentage of open arms entries (F [2, 26] = 4.00; p = 0.031, time spent in the open arms (F [2, 26] = 3.656; p = 0.040 and time spent in the open arms extremities (F [2, 26] = 5.842; p = 0.008. These results suggest a potential effect of MDMA in the reversion of the emotional significance of aversive stimuli.

  20. Pressure-induced reversible phase transition in thiourea dioxide crystal

    International Nuclear Information System (INIS)

    The effect of high pressure on the crystal structure of thiourea dioxide has been investigated by Raman spectroscopy and angle-dispersive X-ray diffraction (ADXRD) in a diamond anvil cell up to 10.3 GPa. The marked changes in the Raman spectra at 3.7 GPa strongly indicated a structural phase transition associated with the distortions of hydrogen bonding. There were no further changes up to the maximum pressure of 10.3 GPa and the observed transition was completely reversible when the system was brought back to ambient pressure. This transition was further confirmed by the changes of ADXRD spectra. The high-pressure phase was indexed and refined to an orthorhombic structure with a possible space group Pbam. The results from the first-principles calculations suggested that this phase transition was mainly related to the changes of hydrogen-bonded networks in thiourea dioxide

  1. Pressure-induced reversible phase transition in thiourea dioxide crystal

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qinglei; Yan, Tingting; Zhu, Hongyang; Cui, Qiliang; Zou, Bo, E-mail: kaiwang@jlu.edu.cn, E-mail: zoubo@jlu.edu.cn [State Key Laboratory of Superhard Materials, Jilin University, Changchun 130012 (China); Wang, Kai, E-mail: kaiwang@jlu.edu.cn, E-mail: zoubo@jlu.edu.cn [State Key Laboratory of Superhard Materials, Jilin University, Changchun 130012 (China); College of Chemistry, Jilin University, Changchun 130012 (China)

    2015-06-28

    The effect of high pressure on the crystal structure of thiourea dioxide has been investigated by Raman spectroscopy and angle-dispersive X-ray diffraction (ADXRD) in a diamond anvil cell up to 10.3 GPa. The marked changes in the Raman spectra at 3.7 GPa strongly indicated a structural phase transition associated with the distortions of hydrogen bonding. There were no further changes up to the maximum pressure of 10.3 GPa and the observed transition was completely reversible when the system was brought back to ambient pressure. This transition was further confirmed by the changes of ADXRD spectra. The high-pressure phase was indexed and refined to an orthorhombic structure with a possible space group Pbam. The results from the first-principles calculations suggested that this phase transition was mainly related to the changes of hydrogen-bonded networks in thiourea dioxide.

  2. Carcinogens induce reversion of the mouse pink-eyed unstable mutation

    OpenAIRE

    Schiestl, Robert H.; Aubrecht, Jiri; Khogali, Fathia; Carls, Nicholas

    1997-01-01

    Deletions and other genome rearrangements are associated with carcinogenesis and inheritable diseases. The pink-eyed unstable (pun) mutation in the mouse is caused by duplication of a 70-kb internal fragment of the p gene. Spontaneous reversion events in homozygous pun/pun mice occur through deletion of a duplicated sequence. Reversion events in premelanocytes in the mouse embryo detected as black spots on the gray fur of the offspring were inducible by the carcinogen x-rays, ethyl methanesul...

  3. Phenylephrine-induced reversible cataract in the mouse.

    OpenAIRE

    Claoué, C M

    1987-01-01

    Topical 10% phenylephrine will produce lens opacities in several strains of mouse. These lens opacities resolve spontaneously within 24 hours, leaving an apparently normal eye. Phenylephrine-induced lens opacification in the mouse can be prevented by covering the eye with ointment, suggesting that the underlying mechanism is transcorneal dehydration.

  4. Reversal of Warfarin-Induced Hemorrhage in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Sean O Henderson

    2011-05-01

    Full Text Available Warfarin, an oral vitamin K antagonist, is used to prevent arterial and venous thromboembolism in patients suffering from a multitude of diseases. In 2004, 31 million warfarin prescriptions were dispensed in the United States. Warfarin inhibits the activation of the vitamin K–dependent clotting factors (Factors II, VII, IX, and X and regulatory proteins (proteins C, S, and Z. It is one of the leading drugs implicated in emergency room visits for adverse drug reactions. Annually the frequency of bleeding complications associated with overanticoagulation is 15% to 20%, with fatal bleeds measuring as high as 1% to 3%. The most effective method of warfarin reversal involves the use of Four Factor Prothrombin Complex Concentrate (PCC, which is widely used throughout Europe but is unavailable in the United States. The current therapies available to emergency room physicians in the United States are fresh frozen plasma, recombinant Factor VIIa (rFVIIa, Factor Eight Inhibitory Bypassing Activity, or Three Factor PCC concomitantly administered with vitamin K. We review the advantages and disadvantages of these therapies and recommend Three Factor PCC with small doses of rFVIIa and with vitamin K in life-threatening situations if Four Factor PCC is unavailable. [West J Emerg Med. 2011;12(4:386–392.

  5. The mutation reversion of induced waxy gene of rice in Indica

    International Nuclear Information System (INIS)

    Some induced waxy gene lines such as Nanhui 175wxR, Xianghui 288wxR, Minghui 86wxR, Shuhui 527wxR, Minghui 63wxR, II-32wxB, Longtepu wxB and D62wxB, which developed through irradiation induction of the parents of hybrid rice in indica, were selected as the materials, and the properties of endosperm of their inbred descendant brown rice were identified by visual estimation and by the method of 1% KI-I2 determination. It was the first time to discover the reversion of induced waxy mutants (waxy endosperm reversed to non-waxy ones) in rice, and the reversion frequency was between 0 to 6.34 x 10-5, with a average of 3.74 x 10-5 Genetic analysis indicated that induced waxy mutants reversion gene was dominant. Except for 1000-grain weight, no significant difference in other traits was found among the induced waxy mutants, the waxy mutants reversion and the wilds. A new core seed production and seed purity control techniques of the parents of waxy hybrid rice was also put forward in this paper. (authors)

  6. The saliva proteome of the blood-feeding insect Triatoma infestans is rich in platelet-aggregation inhibitors

    Science.gov (United States)

    Charneau, Sébastien; Junqueira, Magno; Costa, Camila M.; Pires, Daniele L.; Fernandes, Ellen S.; Bussacos, Ana C.; Sousa, Marcelo V.; Ricart, Carlos André O.; Shevchenko, Andrej; Teixeira, Antonio R. L.

    2007-12-01

    The saliva of the bloodsucking bug Triatoma infestans vector of Chagas disease contains an anti-hemostatic molecular cocktail that prevents coagulation, vasoconstriction and platelet aggregation in a vertebrate prey. In order to characterize T. infestans saliva proteome, we separated the secreted saliva by two-dimensional gel electrophoresis (2-DE). More than 200 salivary proteins were detected on the 2-DE map, mainly in the alkaline region. By nanoLC-MS/MS analysis using a LTQ-Orbitrap equipment followed by a combination of conventional and sequence-similarity searches, we identified 58 main protein spots. Most of such proteins possess potential blood-feeding associated functions, particularly anti-platelet aggregation proteins belonging to lipocalin and apyrase families. The saliva protein composition indicates a highly specific molecular mechanism of early response to platelet aggregation. This first proteome analysis of the T. infestans secreted saliva provides a basis for a better understanding of this fluid protein composition highly directed to counterpart hemostasis of the prey, thus promoting the bug's blood-feeding.

  7. The effect of photoperiod on life history and blood-feeding activity in Aedes albopictus and Aedes aegypti (Diptera: Culicidae).

    Science.gov (United States)

    Costanzo, K S; Schelble, S; Jerz, K; Keenan, M

    2015-06-01

    Several studies have examined how climatic variables such as temperature and precipitation may affect life history traits in mosquitoes that are important to disease transmission. Despite its importance as a seasonal cue in nature, studies investigating the influence of photoperiod on such traits are relatively few. This study aims to investigate how photoperiod alters life history traits, survival, and blood-feeding activity in Aedes albopictus (Skuse) and Aedes aegypti (Linnaeus). We performed three experiments that tested the effects of day length on female survival, development time, adult size, fecundity, adult life span, and propensity to blood feed in Ae. albopictus and Ae. aegypti. Each experiment had three photoperiod treatments: 1) short-day (10L:14D), 2) control (12L:12D), and 3) long-day (14L:10D). Aedes albopictus adult females were consistently larger in size when reared in short-day conditions. Aedes aegypti adult females from short-day treatments lived longer and were more likely to take a blood meal compared to other treatments. We discuss how species-specific responses may reflect alternative strategies evolved to increase survival during unfavorable conditions. We review the potential impacts of these responses on seasonal transmission patterns, such as potentially increasing vectorial capacity of Ae. aegypti during periods of shorter day lengths. PMID:26047197

  8. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results. PMID:26105141

  9. Evolutionary Changes in Sensitivity to Hormonally Induced Gonadal Sex Reversal in a Frog Species.

    Science.gov (United States)

    Miura, Ikuo; Ohtani, Hiromi; Ogata, Mitsuaki; Ezaz, Tariq

    2016-01-01

    The Japanese frog Glandirana rugosa is unique in that it shows geographic variation in sex chromosome differentiation and heterogametic sex determination. To elucidate the cause of interpopulation differences in gonadal sex differentiation, we investigated hormonally induced sex reversal and the expression patterns of genes associated with sex determination during early tadpole development. We found that sex reversal was easily induced in XX females and XY males of 2 forms (West-Japan and East-Japan) of G. rugosa with the ancestral homomorphic sex chromosomes under male heterogametic sex determination. During sex reversal, expression of CYP19 and/or FOXL2 was dependent on the phenotypic sex of the gonad. In contrast, sex reversal was not induced in ZW females of a population with a heteromorphic ZW sex chromosome system or in XX females or XY males in a population with a heteromorphic XY sex chromosome system. The latter 2 populations are evolutionarily derived forms. These results indicate an evolutionary direction for the gonadal sex differentiation mechanism. The original system was highly sensitive to sex hormones and allowed almost complete sex reversal. From this ancestral form, a new system evolved that was resistant to hormones and showed a change in the heterogametic sex and the sex chromosome differentiation mechanism. PMID:27160089

  10. Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Cianfoni, A., E-mail: acianfoni@hotmail.com [Neuroradiology, Neurocenter of Italian Switzerland–Ospedale regionale Lugano, Via Tesserete 46, Lugano, 6900, CH (Switzerland); Caulo, M., E-mail: caulo@unich.it [Department of Neuroscience and Imaging, University of Chieti, Via dei Vestini 33, 6610 Chieti. Italy (Italy); Cerase, A., E-mail: alfonsocerase@gmail.com [Unit of Neuroimaging and Neurointervention NINT, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”, V.le Bracci 16, Siena (Italy); Della Marca, G., E-mail: dellamarca@rm.unicatt.it [Neurology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Falcone, C., E-mail: carlo_falc@libero.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Di Lella, G.M., E-mail: gdilella@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Gaudino, S., E-mail: sgaudino@sirm.org [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Edwards, J., E-mail: edwardjc@musc.edu [Neuroscience Dept., Medical University of South Carolina, 96J Lucas st, 29425, Charleston, SC (United States); Colosimo, C., E-mail: colosimo@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy)

    2013-11-01

    Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

  11. Split-dose atropine versus glycopyrrolate with neostigmine for reversal of gallamine-induced neuromuscular blockade

    DEFF Research Database (Denmark)

    Wetterslev, J; Jarnvig, I; Jørgensen, L N;

    1991-01-01

    The effects of a split-dose of atropine sulphate versus a single dose of glycopyrrolate given with neostigmine for the reversal of gallamine-induced neuromuscular blockade were studied in 55 patients undergoing gynaecological surgery. The patients were randomized to receive either a single dose of......, whereas none occurred in the glycopyrrolate group (P less than 0.05). It is concluded that a split-dose of atropine has similar chronotropic effects to a single dose of glycopyrrolate for the reversal of gallamine-induced neuromuscular blockade. However, the finding of a higher incidence of cardiac...... arrhythmias in the atropine group suggests that this reversal regime should be reserved for patients without cardiac disease....

  12. Reversal of cisplatin-induced delay in gastric emptying in rats by ginger (Zingiber officinale).

    Science.gov (United States)

    Sharma, S S; Gupta, Y K

    1998-08-01

    Cisplatin causes nausea, vomiting and inhibition of gastric emptying. We have demonstrated the antiemetic effect of the acetone and ethanolic extract of ginger (Zingiber officinale, Roscoe, Zingiberacae) against cisplatin-induced emesis in dogs. In the present study, the acetone and 50% ethanolic extract of ginger in the doses of 100, 200 and 500 mg/kg (p.o.) and ginger juice, in the doses of 2 and 4 ml/kg, were investigated against cisplatin effect on gastric emptying in rats. All three ginger preparations significantly reversed cisplatin-induced delay in gastric emptying. The ginger juice and acetone extract were more effective than the 50% ethanolic extract. The reversal produced by the ginger acetone extract was similar to that caused by the 5-HT3 receptor antagonist ondansetron; however, ginger juice produced better reversal than ondansetron. Therefore, ginger, an antiemetic for cancer chemotherapy, may also be useful in improving the gastrointestinal side effects of cancer chemotherapy. PMID:9720611

  13. Reversible Age-Related Phenotypes Induced during Larval Quiescence in C. elegans.

    Science.gov (United States)

    Roux, Antoine E; Langhans, Kelley; Huynh, Walter; Kenyon, Cynthia

    2016-06-14

    Cells can enter quiescent states in which cell cycling and growth are suspended. We find that during a long developmental arrest (quiescence) induced by starvation, newly hatched C. elegans acquire features associated with impaired proteostasis and aging: mitochondrial fission, ROS production, protein aggregation, decreased proteotoxic-stress resistance, and at the organismal level, decline of mobility and high mortality. All signs of aging but one, the presence of protein aggregates, were reversed upon return to development induced by feeding. The endoplasmic reticulum receptor IRE-1 is completely required for recovery, and the downstream transcription factor XBP-1, as well as a protein kinase, KGB-1, are partially required. Interestingly, kgb-1(-) mutants that do recover fail to reverse aging-like mitochondrial phenotypes and have a short adult lifespan. Our study describes the first pathway that reverses phenotypes of aging at the exit of prolonged quiescence. PMID:27304510

  14. Exercise training reverses aging-induced impairment of myogenic constriction in skeletal muscle arterioles

    OpenAIRE

    Ghosh, Payal; Mora Solis, Fredy R.; Dominguez, James M.; Spier, Scott A.; Donato, Anthony J.; Delp, Michael D.; Muller-Delp, Judy M.

    2015-01-01

    To investigate whether exercise training can reverse age-related impairment of myogenic vasoconstriction in skeletal muscle arterioles, young (4 mo) and old (22 mo) male Fischer 344 rats were randomly assigned to either sedentary or exercise-trained groups. The roles of the endothelium and Kv1 channels in age- and exercise training-induced adaptations of myogenic responses were assessed through evaluation of pressure-induced constriction in endothelium-intact and denuded soleus muscle arterio...

  15. The NIT1 Promoter Allows Inducible and Reversible Silencing of Centrin in Chlamydomonas reinhardtii

    OpenAIRE

    Koblenz, Bettina; Lechtreck, Karl-Ferdinand

    2005-01-01

    An inverted repeat corresponding to parts of the centrin gene of Chlamydomonas reinhardtii was placed downstream of the NIT1 promoter, which is induced by ammonium starvation. After induction, transformants developed centrin deficiency as assayed by immunofluorescence, Western blotting, and Northern blotting. The effect was reversible, demonstrating that the NIT1 promoter allowed controlled RNA interference in Chlamydomonas reinhardtii.

  16. Photo-induced reversible structural transition of cationic diphenylalanine peptide self-assembly.

    Science.gov (United States)

    Ma, Hongchao; Fei, Jinbo; Li, Qi; Li, Junbai

    2015-04-17

    The photo-induced self-assembly of a cationic diphenylalanine peptide (CDP) is investigated using a photoswitchable sulfonic azobenzene as the manipulating unit. A reversible structural transition between a branched structure and a vesicle-like structure is observed by alternating between UV and visible light irradiation. PMID:25405602

  17. Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice

    Science.gov (United States)

    Sustained pressure overload causes cardiac hypertrophy and the transition to heart failure. We show here that dietary supplementation with physiologically relevant levels of copper (Cu) reverses pre-established hypertrophic cardiomyopathy in the presence of pressure overload induced by ascending aor...

  18. Solvent-induced reversible solid-state colour change of an intramolecular charge-transfer complex.

    Science.gov (United States)

    Li, Ping; Maier, Josef M; Hwang, Jungwun; Smith, Mark D; Krause, Jeanette A; Mullis, Brian T; Strickland, Sharon M S; Shimizu, Ken D

    2015-10-11

    A dynamic intramolecular charge-transfer (CT) complex was designed that displayed reversible colour changes in the solid-state when treated with different organic solvents. The origins of the dichromatism were shown to be due to solvent-inclusion, which induced changes in the relative orientations of the donor pyrene and acceptor naphthalenediimide units. PMID:26299357

  19. Enhancement of light-induced degradation under reverse bias in hydrogenated nanocrystalline silicon solar cells

    International Nuclear Information System (INIS)

    The nature of light- and current-induced metastabilities under electrical bias in hydrogenated nanocrystalline silicon (nc-Si:H) solar cells has been found to be different from those in hydrogenated amorphous silicon (a-Si:H)-based solar cells. First, a forward-bias current injection in the dark does not cause any degradation in nc-Si:H cell performance. The phenomenon is explained by the percolation transport through crystalline paths, where the excess carrier recombination does not cause degradation. Second, a reverse bias does not reduce, but enhances the light-induced degradation in the nc-Si:H cell performance. The enhancement increases with the magnitude of the applied reverse bias. By measuring the quantum efficiency losses and color (blue, wavelength=390 nm and red, wavelength=670 nm) fill factors, we suggest that the reverse-bias-enhanced defect generation mostly takes place in the grain-boundary regions. Light-soaking experiments using light with different spectra show that a reverse bias under white light causes more enhancement in the degradation than under blue light (wavelength shorter than 650 nm). No degradation occurs under red light (wavelength longer than 665 nm) in either open-circuit or reverse-bias condition. A ''back-to-back'' diode model is proposed to explain these phenomena in terms of the heterogeneity of the material structure

  20. Current-induced magnetization reversal in a (Ga,Mn)As-based magnetic tunnel junction

    OpenAIRE

    Moriya, R.; Hamaya, K.; Oiwa, A.; Munekata, H.

    2004-01-01

    We report current-induced magnetization reversal in a ferromagnetic semiconductor-based magnetic tunnel junction (Ga,Mn)As/AlAs/(Ga,Mn)As prepared by molecular beam epitaxy on a p-GaAs(001) substrate. A change in magneto-resistance that is asymmetric with respect to the current direction is found with the excitation current of 10^6 A/cm^2. Contributions of both unpolarized and spin-polarized components are examined, and we conclude that the partial magnetization reversal occurs in the (Ga,Mn)...

  1. High magnetic field induced charge density waves and sign reversal of the Hall coefficient in graphite

    International Nuclear Information System (INIS)

    We report on the investigation of magnetic field induced charge density waves and Hall coefficient sign reversal in a quasi-two-dimensional electronic system of highly oriented pyrolytic graphite under very strong magnetic field. The change of Hall sign coefficient from negative to positive occurs at low temperature and high magnetic field just after the charge density wave transition, suggesting the role of hole-like quasi-particles in this effect. Angular dependent measurements show that the charge density wave transition and Hall sign reversal fields follow the magnetic field component along the c-axis of graphite.

  2. Mouth reversal extinguishes mismatch negativity induced by the McGurk illusion

    DEFF Research Database (Denmark)

    Eskelund, Kasper; Andersen, Tobias

    2013-01-01

    cortex. Mismatch Negativity (MMN) is a component in the auditory Event-Related Potential (ERP) that is elicited by a change in the auditory percept. It has been shown that the McGurk illusion can induce a MMN. We conducted an experiment in which the MMN could be elicited by the McGurk illusion induced by...... visual speech with either upright (unaltered) or vertically reversed mouth area. In a preliminary analysis, we found a Mismatch Negativity component induced by the McGurk illusion for 6 of 17 participants at electrode Cz when the mouth area was upright. In comparison, these participants produced no...

  3. Effects of spin-polarized current on pulse field-induced precessional magnetization reversal

    Directory of Open Access Journals (Sweden)

    Guang-fu Zhang

    2012-12-01

    Full Text Available We investigate effects of a small DC spin-polarized current on the pulse field-induced precessional magnetization reversal in a thin elliptic magnetic element by micromagnetic simulations. We find that the spin-polarized current not only broadens the time window of the pulse duration, in which a successful precessional reversal is achievable, but also significantly suppresses the magnetization ringing after the reversal. The pulse time window as well as the decay rate of the ringing increase with increasing the current density. When a spin-polarized current with 5 MA/cm2 is applied, the time window increases from 80 ps to 112 ps, and the relaxation time of the ringing decreases from 1.1 ns to 0.32 ns. Our results provide useful information to achieve magnetic nanodevices based on precessional switching.

  4. Magnetic field induced flow pattern reversal in a ferrofluidic Taylor-Couette system

    Science.gov (United States)

    Altmeyer, Sebastian; Do, Younghae; Lai, Ying-Cheng

    2015-12-01

    We investigate the dynamics of ferrofluidic wavy vortex flows in the counter-rotating Taylor-Couette system, with a focus on wavy flows with a mixture of the dominant azimuthal modes. Without external magnetic field flows are stable and pro-grade with respect to the rotation of the inner cylinder. More complex behaviors can arise when an axial or a transverse magnetic field is applied. Depending on the direction and strength of the field, multi-stable wavy states and bifurcations can occur. We uncover the phenomenon of flow pattern reversal as the strength of the magnetic field is increased through a critical value. In between the regimes of pro-grade and retrograde flow rotations, standing waves with zero angular velocities can emerge. A striking finding is that, under a transverse magnetic field, a second reversal in the flow pattern direction can occur, where the flow pattern evolves into pro-grade rotation again from a retrograde state. Flow reversal is relevant to intriguing phenomena in nature such as geomagnetic reversal. Our results suggest that, in ferrofluids, flow pattern reversal can be induced by varying a magnetic field in a controlled manner, which can be realized in laboratory experiments with potential applications in the development of modern fluid devices.

  5. Magnetic field induced flow pattern reversal in a ferrofluidic Taylor-Couette system

    Science.gov (United States)

    Altmeyer, Sebastian; Do, Younghae; Lai, Ying-Cheng

    2015-01-01

    We investigate the dynamics of ferrofluidic wavy vortex flows in the counter-rotating Taylor-Couette system, with a focus on wavy flows with a mixture of the dominant azimuthal modes. Without external magnetic field flows are stable and pro-grade with respect to the rotation of the inner cylinder. More complex behaviors can arise when an axial or a transverse magnetic field is applied. Depending on the direction and strength of the field, multi-stable wavy states and bifurcations can occur. We uncover the phenomenon of flow pattern reversal as the strength of the magnetic field is increased through a critical value. In between the regimes of pro-grade and retrograde flow rotations, standing waves with zero angular velocities can emerge. A striking finding is that, under a transverse magnetic field, a second reversal in the flow pattern direction can occur, where the flow pattern evolves into pro-grade rotation again from a retrograde state. Flow reversal is relevant to intriguing phenomena in nature such as geomagnetic reversal. Our results suggest that, in ferrofluids, flow pattern reversal can be induced by varying a magnetic field in a controlled manner, which can be realized in laboratory experiments with potential applications in the development of modern fluid devices. PMID:26687638

  6. Antivenom reversal of biochemical alterations induced by black scorpion Heterometrus fastigiousus Couzijn venom in mice

    Directory of Open Access Journals (Sweden)

    MK Chaubey

    2009-01-01

    Full Text Available In the present study, Heterometrus fastigiousus venom (HFV was employed as antigen to produce species-specific scorpion antivenom (SAV in albino mice (NIH strain. To determine SAV efficacy, it was pre-incubated with 10 LD50 of HFV and then injected subcutaneously into mice. Subsequently, mortality was observed after 24 hours. Minimum effective dose (MED was 12.5 LD50 of HFV/mL of SAV. SAV effectiveness to reverse HFV-induced biochemical alterations in mice was analyzed by challenge method. Simultaneously, mice received subcutaneously 40% of 24-hour-LD50 of HFV and intravenously SAV. After four hours, changes in serum glucose, free amino acids, uric acids, pyruvic acid, cholesterol, total protein, alkaline phosphatase, acid phosphatase, lactic dehydrogenase and glutamate-pyruvate transaminase enzyme level were determined. Treatment with species-specific SAV resulted in the reversal of HFV-induced biochemical alterations.

  7. PANIC-ATTAC: A Mouse Model for Inducible and Reversible β-Cell Ablation

    OpenAIRE

    Wang, Zhao V.; Mu, James; Schraw, Todd D.; Gautron, Laurent; Elmquist, Joel K.; Zhang, Bei B.; Brownlee, Michael; Scherer, Philipp E

    2008-01-01

    OBJECTIVE—Islet transplantations have been performed clinically, but their practical applications are limited. An extensive effort has been made toward the identification of pancreatic β-cell stem cells that has yielded many insights to date, yet targeted reconstitution of β-cell mass remains elusive. Here, we present a mouse model for inducible and reversible ablation of pancreatic β-cells named the PANIC-ATTAC (pancreatic islet β-cell apoptosis through targeted activation of caspase 8) mous...

  8. Current induced magnetization reversal on the surface of a topological insulator

    OpenAIRE

    Yokoyama, Takehito

    2011-01-01

    We study dynamics of the magnetization coupled to the surface Dirac fermions of a three di- mensional topological insulator. By solving the Landau-Lifshitz-Gilbert equation in the presence of charge current, we find current induced magnetization dynamics and discuss the possibility of mag- netization reversal. The torque from the current injection depends on the transmission probability through the ferromagnet and shows nontrivial dependence on the exchange coupling. The mag- netization dynam...

  9. Charge-induced reversible bending in nanoporous alumina-aluminum composite

    Science.gov (United States)

    Cheng, Chuan; Ngan, A. H. W.

    2013-05-01

    Upon electrical charging, reversible bending was found in nanoporous anodic alumina-aluminum foil composites, as directly observed by an optical microscope and detected by in situ nanoindentation. The bending is thought to be the result of charge-induced surface stresses in the nanoporous alumina. The results suggest the possibility of a type of composite foil materials for applications as micro-scale actuators to transform electrical energy into mechanical energy.

  10. High magnetic field induced charge density waves and sign reversal of the Hall coefficient in graphite

    OpenAIRE

    Kumar, Amit; POUMIROL, Jean-Marie; Escoffier, Walter; Goiran, Michel; Raquet, Bertrand; Pivin, Jean Claude

    2010-01-01

    We report on the investigation of magnetic field induced charge density wave and Hall coefficient sign reversal in a quasi-two dimensional electronic system of highly oriented pyrolytic graphite under very strong magnetic field. The change of Hall sign coefficient from negative to positive occurs at low temperature and high magnetic field just after the charge density wave transition, suggesting the role of hole-like quasi-particles in this effect. Angular dependent measurements show that the...

  11. Evolution, expansion and expression of the Kunitz/BPTI gene family associated with long-term blood feeding in Ixodes Scapularis

    Directory of Open Access Journals (Sweden)

    Dai Shao-Xing

    2012-01-01

    Full Text Available Abstract Background Recent studies of the tick saliva transcriptome have revealed the profound role of salivary proteins in blood feeding. Kunitz/BPTI proteins are abundant in the salivary glands of ticks and perform multiple functions in blood feeding, such as inhibiting blood coagulation, regulating host blood supply and disrupting host angiogenesis. However, Kunitz/BPTI proteins in soft and hard ticks have different functions and molecular mechanisms. How these differences emerged and whether they are associated with the evolution of long-term blood feeding in hard ticks remain unknown. Results In this study, the evolution, expansion and expression of Kunitz/BPTI family in Ixodes scapularis were investigated. Single- and multi-domain Kunitz/BPTI proteins have similar gene structures. Single-domain proteins were classified into three groups (groups I, II and III based on their cysteine patterns. Group I represents the ancestral branch of the Kunitz/BPTI family, and members of this group function as serine protease inhibitors. The group I domain was used as a module to create multi-domain proteins in hard ticks after the split between hard and soft ticks. However, groups II and III, which evolved from group I, are only present and expanded in the genus Ixodes. These lineage-specific expanded genes exhibit significantly higher expression during long-term blood feeding in Ixodes scapularis. Interestingly, functional site analysis suggested that group II proteins lost the ability to inhibit serine proteases and evolved a new function of modulating ion channels. Finally, evolutionary analyses revealed that the expansion and diversification of the Kunitz/BPTI family in the genus Ixodes were driven by positive selection. Conclusions These results suggest that the differences in the Kunitz/BPTI family between soft and hard ticks may be linked to the evolution of long-term blood feeding in hard ticks. In Ixodes, the lineage-specific expanded genes

  12. Reversal-mechanism of perpendicular switching induced by an in-plane current

    Energy Technology Data Exchange (ETDEWEB)

    Bi, Chong, E-mail: cbi@email.arizona.edu; Liu, Ming, E-mail: liuming@ime.ac.cn

    2015-05-01

    We propose a magnetization reversal model to explain the perpendicular switching of a single ferromagnetic layer induced by an in-plane current. Contrary to previously proposed reversal mechanisms that such magnetic switching is directly from the Rashba or spin Hall effects, we suggest that this type of switching arises from the current-induced chirality dependent domain wall motion. By measuring the field dependent switching behaviors, we show that such switching can also be achieved between any two multidomain states, and all of these switching behaviors can be well explained by this model. This model indicates that the spin Hall angle in such structures may be overestimated and also predicts similar switching behaviors in other ferromagnetic structures with chiral domain walls or skyrmions. - Highlights: • A reversal model is proposed to explain current-induced perpendicular switching. • Chirality-dependent domain nucleation and expansion dominate switching behaviors. • The switching between any two multidomain states was observed. • Similar switching behaviors are predicted for chiral domain walls or skyrmions.

  13. Orexin A reverses propofol and thiopental induced cytoskeletal rearrangement in rat neurons.

    Science.gov (United States)

    Turina, D; Gerhardsson, H; Bjornstrom, K

    2014-08-01

    Orexin A (OA) is an endogenous peptide regulating awakefulness, known to reduce anaesthesia in animals, but on cellular level its mechanisms to reverse anaesthetics are unknown. Primary cortical cell cultures from newborn rat brains are used and live cell light microscopy is performed to measure 1) neurite retraction after propofol, thiopental, barbituric acid and ketamine exposure and 2) the effect of OA application either before or after anaesthetics. Cytoskeletal reorganization is evaluated with fluorescence microscopy, protein changes are detected with Western blots and mass spectrometry is used to identify proteins after treatment with anaesthetics and/or OA. Adult rats are anaesthesized with propofol, and the cytoskeletal morphology is studied. Orexin A reverses and inhibits neurite retraction and actin ring formation induced by propofol and thiopental. No effect on retraction or actin rings was seen for ketamine (not active on gamma-aminobutiric acid A (GABA(A)) receptors), the non-anaesthetic barbituric acid, OA or solvents used. OA increases the tyrosine phosphorylation of a 50 kDa protein, identified as vimentin. Propofol induces an immediate granular appearance of vimentin, which OAreverses to a smooth distribution. Cytoskeletal morphology changes are also induced by propofol in vivo. All OA effects are blocked with an orexin receptor1 (OX1) antagonist. We conclude that OA reverses the GABAA receptor mediated cellular effects of both propofol and thiopental in rat brain cells. The morphologic changes of actin and vimentin caused by propofol and thiopental, and the subsequent reversal by OA, deepens our understanding of the mechanisms of anaesthesia. PMID:25179085

  14. Structure and Ligand-Binding Mechanism of a Cysteinyl Leukotriene-Binding Protein from a Blood-Feeding Disease Vector.

    Science.gov (United States)

    Jablonka, Willy; Pham, Van; Nardone, Glenn; Gittis, Apostolos; Silva-Cardoso, Lívia; Atella, Georgia C; Ribeiro, José M C; Andersen, John F

    2016-07-15

    Blood-feeding disease vectors mitigate the negative effects of hemostasis and inflammation through the binding of small-molecule agonists of these processes by salivary proteins. In this study, a lipocalin protein family member (LTBP1) from the saliva of Rhodnius prolixus, a vector of the pathogen Trypanosoma cruzi, is shown to sequester cysteinyl leukotrienes during feeding to inhibit immediate inflammatory responses. Calorimetric binding experiments showed that LTBP1 binds leukotrienes C4 (LTC4), D4 (LTD4), and E4 (LTE4) but not biogenic amines, adenosine diphosphate, or other eicosanoid compounds. Crystal structures of ligand-free LTBP1 and its complexes with LTC4 and LTD4 reveal a conformational change during binding that brings Tyr114 into close contact with the ligand. LTC4 is cleaved in the complex, leaving free glutathione and a C20 fatty acid. Chromatographic analysis of bound ligands showed only intact LTC4, suggesting that cleavage could be radiation-mediated. PMID:27124118

  15. Detection of multiple blood feeding in Aedes aegypti (Diptera: Culicidae) during a single gonotrophic cycle using a histologic technique.

    Science.gov (United States)

    Scott, T W; Clark, G G; Lorenz, L H; Amerasinghe, P H; Reiter, P; Edman, J D

    1993-01-01

    We evaluated a histologic technique for its usefulness in detecting multiple blood feeding by Aedes aegypti (L.) in a single gonotrophic cycle. To standardize the procedure, we carried out a laboratory study in which 166 mosquitoes imbibed two blood meals at known intervals. Eighty percent (78/98) of the multiple meals were detected when the interval between meals was from 1 to mosquitoes took their last meal the day before capture, and most multiple feeders fed twice on consecutive days. A dark line of digested blood, or heme, around the first meal and a physical separation between meals were the most useful histologic parameters for detecting multiple feeding in wild Ae. aegypti. An association of multiple feeding with advanced stages of oocyte development suggests that, at the time of collection, most Ae. aegypti from the study site had fed twice in each gonotrophic cycle. We conclude that, although it is labor intensive, histologic examination is an appropriate technique for a longitudinal, community-wide survey of multiple feeding by Ae. aegypti. PMID:8433350

  16. De novo assembly and annotation of the salivary gland transcriptome of Rhipicephalus appendiculatus male and female ticks during blood feeding.

    Science.gov (United States)

    de Castro, Minique H; de Klerk, Daniel; Pienaar, Ronel; Latif, Abdalla A; Rees, D Jasper G; Mans, Ben J

    2016-06-01

    Tick secretory proteins modulate haemostasis, inflammation and immune responses of the host and are attractive recombinant anti-tick vaccine candidates. Yet, many of the proteins have not been characterised due to the limited sequence availability for ticks and other arthropods for homology-based annotation. To address this limitation, we sequenced the salivary glands of the economically important adult male and female Rhipicephalus appendiculatus ticks during feeding. The quality-filtered Illumina sequencing reads were de novo assembled to generate a R. appendiculatus sialotranscriptome of 21,410 transcripts. A non-redundant set of 12,761 R. appendiculatus proteins was predicted from the transcripts, including 2134 putative secretory and 8237 putative housekeeping proteins. Secretory proteins accounted for most of the expression in the salivary gland transcriptome (63%). Of the secretory protein class, the Glycine-rich superfamily contributed 66% and the Lipocalin family 12% of the transcriptome expression. Differential expression analysis identified 1758 female and 2346 male up-regulated transcripts, suggesting varying blood-feeding mechanisms employed between female and male ticks. The sialotranscriptome assembled in this work, greatly improves on the sequence information available for R. appendiculatus and is a valuable resource for potential future vaccine candidate selection. PMID:26830274

  17. Reversal of CRF- and stress-induced anorexia by an ayurvedic formulation

    Directory of Open Access Journals (Sweden)

    V. S. Kulkarni

    2012-04-01

    Full Text Available Trikatu churna is one of the commonly used Ayurvedic formulations in the traditional system of medicine in India for the treatment of agnimandya, i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of Zingiber officinale Roscoe (Zingiberaceae and fruits of Piper longum L. and Piper nigrum L. (Piperaceae. The chief objective of the study was to determine the antianorectic effects of three drugs individually and to compare these effects with the effect of Trikatu. The activity of the drugs was studied after anorexia was induced in rats by (1 physical stress arising from immobilization for 60 min; (2 intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 100 μg/kg body weight; and (3 intraperitoneal administration of fluoxetine (8 mg/kg body weight. Similar doses of the extracts were tested on freely feeding rats and on rats that had been deprived of food for 20 h. Corticotrophin-releasing factor (CRF, 0.3 μg/rat can induce anxiogenic-like behavior and reduced food intake. This model was also studied, and the results were compared. The components of Trikatu churna failed to individually reverse the inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-, fluoxetine- and CRF-induced anorexia. The study provides strong evidence of the synergistic action of Ayurvedic formulas and also proves the ability of Trikatu churna to reduce stress and CRF-induced anorexia.

  18. Cladribine and Fludarabine Nucleotides Induce Distinct Hexamers Defining a Common Mode of Reversible RNR Inhibition.

    Science.gov (United States)

    Wisitpitthaya, Somsinee; Zhao, Yi; Long, Marcus J C; Li, Minxing; Fletcher, Elaine A; Blessing, William A; Weiss, Robert S; Aye, Yimon

    2016-07-15

    The enzyme ribonucleotide reductase (RNR) is a major target of anticancer drugs. Until recently, suicide inactivation in which synthetic substrate analogs (nucleoside diphosphates) irreversibly inactivate the RNR-α2β2 heterodimeric complex was the only clinically proven inhibition pathway. For instance, this mechanism is deployed by the multifactorial anticancer agent gemcitabine diphosphate. Recently reversible targeting of RNR-α-alone coupled with ligand-induced RNR-α-persistent hexamerization has emerged to be of clinical significance. To date, clofarabine nucleotides are the only known example of this mechanism. Herein, chemoenzymatic syntheses of the active forms of two other drugs, phosphorylated cladribine (ClA) and fludarabine (FlU), allow us to establish that reversible inhibition is common to numerous drugs in clinical use. Enzyme inhibition and fluorescence anisotropy assays show that the di- and triphosphates of the two nucleosides function as reversible (i.e., nonmechanism-based) inhibitors of RNR and interact with the catalytic (C site) and the allosteric activity (A site) sites of RNR-α, respectively. Gel filtration, protease digestion, and FRET assays demonstrate that inhibition is coupled with formation of conformationally diverse hexamers. Studies in 293T cells capable of selectively inducing either wild-type or oligomerization-defective mutant RNR-α overexpression delineate the central role of RNR-α oligomerization in drug activity, and highlight a potential resistance mechanism to these drugs. These data set the stage for new interventions targeting RNR oligomeric regulation. PMID:27159113

  19. Magnetic-field-induced ferroelectric polarization reversal in magnetoelectric composites revealed by piezoresponse force microscopy

    Science.gov (United States)

    Miao, Hongchen; Zhou, Xilong; Dong, Shuxiang; Luo, Haosu; Li, Faxin

    2014-07-01

    Controlling electric polarization (or magnetization) in multiferroic materials with external magnetic fields (or electric fields) is very important for fundamental physics and spintronic devices. Although there has been some progress on magnetic-field-induced polarization reversal in single-phase multiferroics, such behavior has so far never been realized in composites. Here we show that it is possible to reverse ferroelectric polarization using magnetic fields in a bilayer Terfenol-D/PMN-33%PT composite. We realized this by ferroelectric domain imaging using piezoresponse force microscopy (PFM) under applied magnetic field loading. The internal electric field caused by the magnetoelectric (ME) effect in the PMN-PT crystal is considered as the driving force for the 180° polarization switching, and its existence is verified by switching spectroscopy PFM testing under a series of external magnetic fields. A quantitative method is further suggested to estimate the local ME coefficient based on the switching spectroscopy PFM testing results.

  20. Reversible antibiotic tolerance induced in Staphylococcus aureus by concurrent drug exposure

    DEFF Research Database (Denmark)

    Haaber, Jakob Krause; Friberg, Cathrine; McCreary, Mark;

    2015-01-01

    antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram......-negative pathogens. We show that colistin-induced vancomycin tolerance persists only as long as the inducer is present and is accompanied by gene expression changes similar to those resulting from mutations that produce stably inherited reduction of vancomycin sensitivity (vancomycin-intermediate S. aureus [VISA......] strains). As colistin-induced vancomycin tolerance is reversible, it may not be detected by routine sensitivity testing and may be responsible for treatment failure at vancomycin doses expected to be clinically effective based on such routine testing. IMPORTANCE: Commonly, antibiotic resistance is...

  1. A cognitive deficit induced in rats by chronic intermittent cold stress is reversed by chronic antidepressant treatment

    OpenAIRE

    Danet, M.; Lapiz-Bluhm, S.; Morilak, David A

    2010-01-01

    We have previously reported that 14-days of chronic intermittent cold (CIC) stress induced a cognitive deficit in reversal learning on the rat attentional set-shifting test. This effect may be related to dysregulation of 5-HT function in orbitofrontal cortex, as a model of cognitive dysfunction in depression. To test the ability of chronic antidepressant drug treatment to reverse the cognitive deficit induced by CIC, it was first necessary to assess the temporal characteristics of the CIC-ind...

  2. Pituitary Adenylate Cyclase-Activating Polypeptide Reverses Ammonium Metavanadate-Induced Airway Hyperresponsiveness in Rats

    Directory of Open Access Journals (Sweden)

    Mounira Tlili

    2015-01-01

    Full Text Available The rate of atmospheric vanadium is constantly increasing due to fossil fuel combustion. This environmental pollution favours vanadium exposure in particular to its vanadate form, causing occupational bronchial asthma and bronchitis. Based on the well admitted bronchodilator properties of the pituitary adenylate cyclase-activating polypeptide (PACAP, we investigated the ability of this neuropeptide to reverse the vanadate-induced airway hyperresponsiveness in rats. Exposure to ammonium metavanadate aerosols (5 mg/m3/h for 15 minutes induced 4 hours later an array of pathophysiological events, including increase of bronchial resistance and histological alterations, activation of proinflammatory alveolar macrophages, and increased oxidative stress status. Powerfully, PACAP inhalation (0.1 mM for 10 minutes alleviated many of these deleterious effects as demonstrated by a decrease of bronchial resistance and histological restoration. PACAP reduced the level of expression of mRNA encoding inflammatory chemokines (MIP-1α, MIP-2, and KC and cytokines (IL-1α and TNF-α in alveolar macrophages and improved the antioxidant status. PACAP reverses the vanadate-induced airway hyperresponsiveness not only through its bronchodilator activity but also by counteracting the proinflammatory and prooxidative effects of the metal. Then, the development of stable analogs of PACAP could represent a promising therapeutic alternative for the treatment of inflammatory respiratory disorders.

  3. Proteophosphoglycan confers resistance of Leishmania major to midgut digestive enzymes induced by blood feeding in vector sand flies

    OpenAIRE

    Secundino, Nagila; Kimblin, Nicola; Peters, Nathan C.; Lawyer, Phillip; Capul, Althea A.; Beverley, Stephen M.; Turco, Salvatore J.; Sacks, David

    2010-01-01

    Leishmania synthesize abundant phosphoglycan-containing molecules made up of [Gal-Man-PO4] repeating units, including the surface lipophosphoglycan (LPG), and the surface and secreted proteophosphoglycan (PPG). The vector competence of Phlebotomus duboscqi and Lutzomyia longipalpis sand flies was tested using L. major knockout mutants deficient in either total phosphoglycans (lpg2− or lpg5A−/5B−) or LPG alone (lpg1−) along with their respective gene add-back controls. Our results confirm that...

  4. Reversibility of disobutamide-induced clear cytoplasmic vacoules in cultured cells following withdrawal of drug

    International Nuclear Information System (INIS)

    When cultured rat urinary bladder carcinoma cells are incubated with medium containing disobutamide (D), they take up D intracellularly and form clear cytoplasmic vacoules (CCV) which apparently are distended lysosomes containing D. To determine whether CCV are reversible, the authors incubated cells with 10-3M 14C-labelled D for 25 hr and cells became full of CCV. Then, cells were incubated in medium free of D and examined at 0,2,4,6,24,48,72 and 144 hr of D withdrawal for radioactivity (600 DPM = 1 μD), and in situ by phase light microscopy for presence of CCV. The DPM counts at these time points were: 1832, 1539, 1564, 1443, 1073, 738, 481 and 84, respectively. This gradual decrease in cellular content of D parallelled a diminution in size and number of CCV. By 72 hr (481 DPM = 0.93 up D) only few small CCB had remained, and by 144 hr (84 DPM = 0.16 μg D) CCV had entirely disappeared. Mass spectrometric analysis of the culture medium at 144 hr showed presence of D. These results indicate that (1) the induced CCV are reversible (2) reversibility is associated is associated with release of D from cells (3) the principle compound released from cells is D and not its metabolite(s). The results support the interpretation that CCV are formed as a result of intracellular storage of D

  5. Short environmental enrichment in adulthood reverses anxiety and basolateral amygdala hypertrophy induced by maternal separation.

    Science.gov (United States)

    Koe, A S; Ashokan, A; Mitra, R

    2016-01-01

    Maternal separation during early childhood results in greater sensitivity to stressors later in adult life. This is reflected as greater propensity to develop stress-related disorders in humans and animal models, including anxiety and depression. Environmental enrichment (EE) reverses some of the damaging effects of maternal separation in rodent models when provided during peripubescent life, temporally proximal to the separation. It is presently unknown if EE provided outside this critical window can still rescue separation-induced anxiety and neural plasticity. In this report we use a rat model to demonstrate that a single short episode of EE in adulthood reduced anxiety-like behaviour in maternally separated rats. We further show that maternal separation resulted in hypertrophy of dendrites and increase in spine density of basolateral amygdala neurons in adulthood, long after initial stress treatment. This is congruent with prior observations showing centrality of basolateral amygdala hypertrophy in anxiety induced by stress during adulthood. In line with the ability of the adult enrichment to rescue stress-induced anxiety, we show that enrichment renormalized stress-induced structural expansion of the amygdala neurons. These observations argue that behavioural plasticity induced by early adversity can be rescued by environmental interventions much later in life, likely mediated by ameliorating effects of enrichment on basolateral amygdala plasticity. PMID:26836417

  6. Reversible suppression of cyclooxygenase 2 (COX-2 expression in vivo by inducible RNA interference.

    Directory of Open Access Journals (Sweden)

    Anne K Zaiss

    Full Text Available Prostaglandin-endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase 2 (COX-2, plays a critical role in many normal physiological functions and modulates a variety of pathological conditions. The ability to turn endogenous COX-2 on and off in a reversible fashion, at specific times and in specific cell types, would be a powerful tool in determining its role in many contexts. To achieve this goal, we took advantage of a recently developed RNA interference system in mice. An shRNA targeting the Cox2 mRNA 3'untranslated region was inserted into a microRNA expression cassette, under the control of a tetracycline response element (TRE promoter. Transgenic mice containing the COX-2-shRNA were crossed with mice encoding a CAG promoter-driven reverse tetracycline transactivator, which activates the TRE promoter in the presence of tetracycline/doxycycline. To facilitate testing the system, we generated a knockin reporter mouse in which the firefly luciferase gene replaces the Cox2 coding region. Cox2 promoter activation in cultured cells from triple transgenic mice containing the luciferase allele, the shRNA and the transactivator transgene resulted in robust luciferase and COX-2 expression that was reversibly down-regulated by doxycycline administration. In vivo, using a skin inflammation-model, both luciferase and COX-2 expression were inhibited over 80% in mice that received doxycycline in their diet, leading to a significant reduction of infiltrating leukocytes. In summary, using inducible RNA interference to target COX-2 expression, we demonstrate potent, reversible Cox2 gene silencing in vivo. This system should provide a valuable tool to analyze cell type-specific roles for COX-2.

  7. Origin of reversible photo-induced phase separation in hybrid perovskites

    CERN Document Server

    Bischak, Connor G; Wu, Hao; Aloni, Shaul; Ogletree, D Frank; Limmer, David T; Ginsberg, Naomi S

    2016-01-01

    Nonequilibrium processes occurring in functional materials can significantly impact device efficiencies and are often difficult to characterize due to the broad range of length and time scales involved. In particular, mixed halide hybrid perovskites are promising for optoelectronics, yet the halides reversibly phase separate when photo-excited, significantly altering device performance. By combining nanoscale imaging and multiscale modeling, we elucidate the mechanism underlying this phenomenon, demonstrating that local strain induced by photo-generated polarons promotes halide phase separation and leads to nucleation of light-stabilized iodide-rich clusters. This effect relies on the unique electromechanical properties of hybrid materials, characteristic of neither their organic nor inorganic constituents alone. Exploiting photo-induced phase separation and other nonequilibrium phenomena in hybrid materials, generally, could enable new opportunities for expanding the functional applications in sensing, photo...

  8. Estrogen leads to reversible hair cycle retardation through inducing premature catagen and maintaining telogen.

    Directory of Open Access Journals (Sweden)

    Hui-min Hu

    Full Text Available Estrogen dysregulation causes hair disorder. Clinical observations have demonstrated that estrogen raises the telogen/anagen ratio and inhibits hair shaft elongation of female scalp hair follicles. In spite of these clinical insights, the properties of estrogen on hair follicles are poorly dissected. In the present study, we show that estrogen induced apoptosis of precortex cells and caused premature catagen by up-regulation of TGF β2. Immediately after the premature catagen, the expression of anagen chalone BMP4 increased. The up-regulation of BMP4 may further function to prevent anagen transition and maintain telogen. Interestingly, the hair follicle stem cell niche was not destructed during these drastic structural changes caused by estrogen. Additionally, dermal papilla cells, the estrogen target cells in hair follicles, kept their signature gene expressions as well as their hair inductive potential after estrogen treatment. Retention of the characteristics of both hair follicle stem cells and dermal papilla cells determined the reversibility of the hair cycle suppression. These results indicated that estrogen causes reversible hair cycle retardation by inducing premature catagen and maintaining telogen.

  9. Thermally Induced Charge Reversal of Layer-by-Layer Assembled Single-Component Polymer Films.

    Science.gov (United States)

    Richardson, Joseph J; Tardy, Blaise L; Ejima, Hirotaka; Guo, Junling; Cui, Jiwei; Liang, Kang; Choi, Gwan H; Yoo, Pil J; De Geest, Bruno G; Caruso, Frank

    2016-03-23

    Temperature can be harnessed to engineer unique properties for materials useful in various contexts and has been shown to affect the layer-by-layer (LbL) assembly of polymer thin films and cause physical changes in preassembled polymer thin films. Herein we demonstrate that exposure to relatively low temperatures (≤ 100 °C) can induce physicochemical changes in cationic polymer thin films. The surface charge of polymer films containing primary and secondary amines reverses after heating (from positive to negative), and different characterization techniques are used to show that the change in surface charge is related to oxidation of the polymer that specifically occurs in the thin film state. This charge reversal allows for single-polymer LbL assembly to be performed with poly(allylamine) hydrochloride (PAH) through alternating heat/deposition steps. Furthermore, the negative charge induced by heating reduces the fouling and cell-association of PAH-coated planar and particulate substrates, respectively. This study highlights a unique property of thin films which is relevant to LbL assembly and biofouling and is of interest for the future development of thin polymer films for biomedical systems. PMID:26953514

  10. Glucose supplement reverses the fasting-induced suppression of cellular immunity in Mongolian gerbils (Meriones unguiculatus).

    Science.gov (United States)

    Xu, De-Li; Wang, De-Hua

    2011-10-01

    Glucose plays an important role in immunity. Three day fasting will decrease cellular immunity and blood glucose levels in Mongolian gerbils (Meriones unguiculatus). In the present study, we tested the hypothesis that glucose supplement can reverse the fasting-induced suppression in cellular immunity in gerbils. Twenty-eight male gerbils were selected and randomly divided into fed and fasting groups. Half of the gerbils in each group were then provided with either 10% glucose water or pure water. After 66 h, each gerbil was injected with phytohaemagglutinin (PHA) solution to challenge cellular immunity. Results showed that glucose supplement restored blood glucose levels in fasted gerbils to those of the fed controls. It also recovered cellular immunity, body fat mass and serum leptin levels in fasted gerbils to the values of the fed controls. Blood glucose levels were positively correlated with body fat mass, leptin levels and cellular immune responses. Thymus and spleen masses, and white blood cells in fasted gerbils were not affected by glucose supplement. In general, our data demonstrate that glucose supplement could reverse fasting-induced suppression of cellular immunity in Mongolian gerbils. PMID:21885265

  11. Cadmium induces apoptosis in anterior pituitary cells that can be reversed by treatment with antioxidants

    International Nuclear Information System (INIS)

    Cadmium (Cd2+) is an ubiquitous toxic metal that is involved in a variety of pathological conditions. Several reports indicate that Cd2+ alters normal pituitary hormone secretion; however, little is known about the mechanisms that induce this misregulation. This paper reports the effect of Cd2+ on anterior pituitary cell viability and its relation to prolactin secretion. Cd2+ concentrations above 10 μM were found to be cytotoxic for pituitary cells. Morphological studies as well as DNA ladder fragmentation and caspase activation showed that Cd2+-treated cells undergo apoptosis. Even though several hours were needed to detect Cd2+-induced cytotoxicity, the effect of the metal became irreversible very quickly, requiring only 3 h of treatment. Prolactin release (measured at 48 h) was inhibited when the cells were exposed to Cd2+ for 1 h, before any change in cell viability was observed. The antioxidants N-acetyl-cysteine and Trolox (a hydrosoluble derivative of vitamin E), but not ascorbic acid, reversed both Cd2+-mediated cytotoxicity and the inhibition of prolactin release, supporting the involvement of oxidative stress in the mechanism of Cd2+ action. In summary, the present work demonstrates that Cd2+ is cytotoxic for anterior pituitary cells, that this effect is due to an induction of apoptosis, and that it can be reversed by antioxidants

  12. Temperature-induced reversible self-assembly of diphenylalanine peptide and the structural transition from organogel to crystalline nanowires

    OpenAIRE

    Huang, Renliang; Wang, Yuefei; Qi, Wei; Su, Rongxin; He, Zhimin

    2014-01-01

    Controlling the self-assembly of diphenylalanine peptide (FF) into various nanoarchitectures has received great amounts of attention in recent years. Here, we report the temperature-induced reversible self-assembly of diphenylalanine peptide to microtubes, nanowires, or organogel in different solvents. We also find that the organogel in isopropanol transforms into crystalline flakes or nanowires when the temperature increases. The reversible self-assembly in polar solvents may be mainly contr...

  13. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study

    DEFF Research Database (Denmark)

    Sorgenfrei, Iben F; Norrild, Kathrine; Larsen, Per Bo;

    2006-01-01

    Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.......Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block....

  14. Chronic liquid nutrition intake induces obesity and considerable but reversible metabolic alterations in Wistar rats.

    Science.gov (United States)

    Mikuska, Livia; Vrabcova, Michaela; Tillinger, Andrej; Balaz, Miroslav; Ukropec, Jozef; Mravec, Boris

    2016-06-01

    We have previously described the development of substantial, but reversible obesity in Wistar rats fed with palatable liquid nutrition (Fresubin). In this study, we investigated changes in serum hormone levels, glycemia, fat mass, adipocyte size, and gene expression of adipokines and inflammatory markers in adipose tissue of Wistar rats fed by Fresubin (i) for 5 months, (ii) up to 90 days of age, or (iii) after 90 days of age to characterize metabolic alterations and their reversibility in rats fed with Fresubin. An intra-peritoneal glucose tolerance test was also performed to determine levels of serum leptin, adiponectin, insulin, and C-peptide in 2- and 4-month-old animals. In addition, mesenteric and epididymal adipose tissue weight, adipocyte diameter, and gene expression of pro- and anti-inflammatory adipokines and other markers were determined at the end of the study. Chronic Fresubin intake significantly increased adipocyte diameter, reduced glucose tolerance, and increased serum leptin, adiponectin, insulin, and C-peptide levels. Moreover, gene expression of leptin, adiponectin, CD68, and nuclear factor kappa B was significantly increased in mesenteric adipose tissue of Fresubin fed rats. Monocyte chemotactic protein 1 messenger RNA (mRNA) levels increased in mesenteric adipose tissue only in the group fed Fresubin during the entire experiment. In epididymal adipose tissue, fatty acid binding protein 4 mRNA levels were significantly increased in rats fed by Fresubin during adulthood. In conclusion, chronic Fresubin intake induced complex metabolic alterations in Wistar rats characteristic of metabolic syndrome. However, transition of rats from Fresubin to standard diet reversed these alterations. PMID:26939586

  15. Reversion of pH-induced physiological drug resistance: a novel function of copolymeric nanoparticles.

    Directory of Open Access Journals (Sweden)

    Rutian Li

    Full Text Available AIMS: The extracellular pH of cancer cells is lower than the intracellular pH. Weakly basic anticancer drugs will be protonated extracellularly and display a decreased intracellular concentration. In this study, we show that copolymeric nanoparticles (NPs are able to overcome this "pH-induced physiological drug resistance" (PIPDR by delivering drugs to the cancer cells via endocytosis rather than passive diffussion. MATERIALS AND METHODS: As a model nanoparticle, Tetradrine (Tet, Pka 7.80 was incorporated into mPEG-PCL. The effectiveness of free Tet and Tet-NPs were compared at different extracellular pHs (pH values 6.8 and 7.4, respectively by MTT assay, morphological observation and apoptotic analysis in vitro and on a murine model by tumor volume measurement, PET-CT scanning and side effect evaluation in vivo. RESULTS: The cytotoxicity of free Tet decreased prominently (P<0.05 when the extracellular pH decreased from 7.4 to 6.8. Meanwhile, the cytotoxicity of Tet-NPs was not significantly influenced by reduced pH. In vivo experiment also revealed that Tet-NPs reversed PIPDR more effectively than other existing methods and with much less side effects. CONCLUSION: The reversion of PIPDR is a new discovered mechanism of copolymeric NPs. This study emphasized the importance of cancer microenvironmental factors in anticancer drug resistance and revealed the superiority of nanoscale drug carrier from a different aspect.

  16. Evaluation of deformation-induced transformation and reversion processes of stainless steel by acoustic microscope

    Science.gov (United States)

    Kasuga, Yukio; Endo, Tomio; Miyasaka, Chiaki; Kasano, Hideaki

    1999-02-01

    Deformation-induced martensite and reversed austenite of a metastable austenitic stainless steel sheet were evaluated by a scanning acoustic microscope with frequencies 600MHz and 800 MHz. The sheet was elongated up to 40 percent at and below the room temperature to produce martensite, followed by annealing for reversion. First martensite content was measured by a Feritscope. Next using a complex V(z) curve, leaky Rayleigh wave velocity was measured. The deformed and annealed grain structure s were observed with the frequency 800MHz and compared with those by the optical microscope. Rayleigh wave velocity is dependent on the elongation and ambient temperature in elongation and the annealing temperature, which agrees well with the one by the Feritscope. Deformed grains are more clearly observed by the scanning acoustic microscope with 800MHz. The measured value of the velocity is compared with the theoretical one which can be calculated by Young's modulus, Poisson's ratio and the density. The measured Rayleigh wave velocity is well agreement with the theoretical one.

  17. A reversible strain-induced electrical conductivity in cup-stacked carbon nanotube

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, T [Shinshu University; Morokuma, Keiji [ORNL; Meunier, Vincent [ORNL; Meunier, V. [Rensselaer Polytechnic Institute (RPI); Terrones Maldonado, Mauricio [ORNL; Muramatsu, H [Shinshu University; Sumpter, Bobby G [ORNL; Kim, Y A [Shinshu University

    2013-01-01

    We have used in-situ current-voltage measurements of cup-stacked carbon nanotubes (CSCNTs) to establish a reversible strain induced (compressive bending) semiconducting to metallic behavior. The corresponding electrical resistance decreases by two orders of magnitude during the process, and reaches values comparable to those of highly crystalline multi-walled carbon nanotube (MWCNT) and graphite. Joule heating experiments on the same CSCNTs showed that the edges of individual cups merge to form loops induced by the heating process. The resistance of these looped CSCNTs was close to that of highly deformed CSCNTs (and crystalline MWCNTs), thus suggesting that a similar conduction mechanism took place in both cases. Using a combination of molecular dynamics and first-principles calculations based on density functional theory, we conclude that an edge-to-edge interlayer transport mechanism results in conduction channels at the compressed side of the CSCNTs due to electronic density overlap between individual cups, thus making CSCNT more conducting. This strain-induced CSCNT semiconductor to metal transition could potentially be applied to enabling functional composite materials (e.g. mechanical sensors) with enhanced and tunable conducting properties upon compression.

  18. Induced Pluripotent Stem Cell Models of Progranulin-Deficient Frontotemporal Dementia Uncover Specific Reversible Neuronal Defects

    Directory of Open Access Journals (Sweden)

    Sandra Almeida

    2012-10-01

    Full Text Available The pathogenic mechanisms of frontotemporal dementia (FTD remain poorly understood. Here we generated multiple induced pluripotent stem cell lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel heterozygous GRN mutation (progranulin [PGRN] S116X. In neurons and microglia differentiated from PGRN S116X induced pluripotent stem cells, the levels of intracellular and secreted PGRN were reduced, establishing patient-specific cellular models of PGRN haploinsufficiency. Through a systematic screen of inducers of cellular stress, we found that PGRN S116X neurons, but not sporadic FTD neurons, exhibited increased sensitivity to staurosporine and other kinase inhibitors. Moreover, the serine/threonine kinase S6K2, a component of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, was specifically downregulated in PGRN S116X neurons. Both increased sensitivity to kinase inhibitors and reduced S6K2 were rescued by PGRN expression. Our findings identify cell-autonomous, reversible defects in patient neurons with PGRN deficiency, and provide a compelling model for studying PGRN-dependent pathogenic mechanisms and testing potential therapies.

  19. Field-induced reversible magnetocaloric effect in CoCl2

    International Nuclear Information System (INIS)

    Research highlights: The electronic structure and magnetic properties of CoCl2 have been investigated by several groups, but the magnetocaloric effect was not reported. In this paper, we study the magnetic and magnetocaloric properties of the antiferromagnet CoCl2 at low temperatures. A large negative magnetic-entropy change and a large cooling power are found together with a field-induced MCE conversion (the MCE changes its sign in the applied magnetic field). - Abstract: A sign change of the magnetocaloric effect is induced by a magnetic field, which is related to a field-induced transition from the antiferromagnetic to the ferromagnetic state below the Neel temperature of CoCl2 nanoparticles. The reversible magnetic-entropy change -ΔSm (4.1 and 11.5 J kg-1 K-1 at 27 K for a field change of 3 and 7 T, respectively) almost without hysteresis and the large cooling power (83.4 and 148 J kg-1, correspondingly) indicates that CoCl2 is a potential candidate for application in magnetic refrigeration in the low-temperature range.

  20. Investigation of blast-induced fracture in rock mass using reversed vertical seismic profiling

    Science.gov (United States)

    Zou, D. H.; Wu, Y. K.

    2001-10-01

    The rock mass on quarry and pit wall surfaces is usually fractured during production blasting. Quantitative investigations of the fractured zones are needed for stabilization of the rock walls. In this study, the principle of reversed vertical seismic profiling (RVSP) was applied. A set of seismic geophones were arranged on the horizontal bench surface and seismic signals were generated along the vertical rock wall using a free-swinging hammer. The travel times of seismic rays were recorded and the P-wave velocities of the rock mass were analyzed using the Simultaneous Iterative Reconstruction Technique (SIRT). A series of site tests have been carried out on the rock walls at a granite quarry that are characterized by fractures. The fracture depth at various locations on the wall surface is thereby determined. The results indicate that RVSP provides an easy and reliable method to quantitatively evaluate the blasting-induced fractures in the rock mass.

  1. Strategies for reversing the effects of metabolic disorders induced as a consequence of developmental programming

    Directory of Open Access Journals (Sweden)

    MarkHVickers

    2012-07-01

    Full Text Available Obesity and the metabolic syndrome have reached epidemic proportions worldwide with far-reaching health care and economic implications. The rapid increase in the prevalence of these disorders suggests that environmental and behavioural influences, rather than genetic causes, are fuelling the epidemic. The developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal and early infant phases of life and the subsequent development of metabolic disorders in later life. In particular, the impact of poor maternal nutrition on susceptibility to later life metabolic disease in offspring is now well documented. Several studies have now shown, at least in experimental animal models, that some components of the metabolic syndrome, induced as a consequence of developmental programming, are potentially reversible by nutritional or targeted therapeutic interventions during windows of developmental plasticity. This review will focus on critical windows of development and possible therapeutic avenues that may reduce metabolic and obesogenic risk following an adverse early life environment.

  2. Hall magnetohydrodynamics simulations of end-shorting induced rotation in field-reversed configurations

    International Nuclear Information System (INIS)

    End-shorting of the open field lines that surround a field-reversed configuration (FRC) is believed to contribute to its observed rotation. In this study, nonlinear extended magnetohydrodynamics (MHD) simulations were performed that detail the end-shorting process and the resulting spin-up of the FRC. The tangential component of the electric field ET is set to zero at the axial boundaries in an extended MHD model that includes the Hall and ∇Pe terms. This shorting of the electric field leads to the generation of toroidal fields on the open field lines, which apply a torque leading to a rotation of the ions on the open field lines. The FRC then gains angular momentum through a viscous transfer from the open field line region. In addition, it is shown that spin-up is still induced when insulating boundaries are assumed

  3. Lipophilic porphyrin microparticles induced by AOT reverse micelles: a fluorescence lifetime imaging study.

    Science.gov (United States)

    Togashi, Denisio M; Costa, Sílvia M B; Sobral, Abílio J F N

    2006-01-20

    Fluorescence Lifetime Imaging Microscopy (FLIM) technique was applied to investigate the fluorescence dynamics and structural features of large colloidal aggregates of meso-tetra(N-dodecyl-4-amino sulfonyl-phenyl)porphyrin (PC12) induced by Sodium 1,4-bis(2-ethyl hexyl)sulfosuccinate (AOT) reverse micelles. The aggregate's particle sizes (down to 1 microm) obtained from the confocal fluorescence images matched with the particle sizes measured in the images obtained from Scanning Electron Microscopy (SEM). The fluorescence decays for those aggregates in the micro spatial domain show triexponential fluorescence lifetimes (tau1 approximately 12 ns, tau2 approximately 3 ns and tau3 approximately 1 ns) which are independent of the aggregate's size. PMID:16154681

  4. Identification of island-induced Alfvén eigenmodes in a reversed field pinch

    Science.gov (United States)

    Cook, C. R.; Hegna, C. C.; Anderson, J. K.; McCollam, K. J.; Boguski, J.; Feng, R.; Koliner, J. J.; Spong, D. A.; Hirshman, S. P.

    2016-05-01

    The modification of the shear Alfvén spectrum due to a core resonant magnetic island is used to explain the Alfvénic activity observed on the Madison symmetric torus (MST) reversed-field pinch during neutral beam injection. Theoretical studies show that the Alfvén continua in the core of the island provide a gap in which the observed Alfvénic bursts reside. Numerical simulations using a new code called SIESTAlfvén have identified the bursts as the first observation of an island-induced Alfvén eigenmode (IAE) in an RFP. The IAE arises from a helical coupling of harmonics due to the magnetic island.

  5. Sulforaphane reverses glucocorticoid-induced apoptosis in osteoblastic cells through regulation of the Nrf2 pathway

    Directory of Open Access Journals (Sweden)

    Lin H

    2014-07-01

    Full Text Available Hao Lin,1,* Bo Wei,1,* Guangsheng Li,1 Jinchang Zheng,1 Jiecong Sun,1 Jiaqi Chu,2 Rong Zeng,1 Yanru Niu21Department of Spinal Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People’s Republic of China; 2Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Apoptosis of osteoblasts triggered by high-dose glucocorticoids (GCs has been identified as a major cause of osteoporosis. However, the underlying molecular mechanisms accounting for this action remain elusive, which has impeded the prevention and cure of this side effect. Sulforaphane (SFP is a naturally occurring isothiocyanate that has huge health benefits for humans. In this study, by using osteoblastic MC3T3-E1 cells as a model, we demonstrate the protective effects of SFP against dexamethasone (Dex-induced apoptosis and elucidate the underlying molecular mechanisms. The results show that SFP could effectively inhibit the Dex-induced growth inhibition and release of lactate dehydrogenase in MC3T3-E1 cells. Treatment with Dex induced caspase-dependent apoptosis in MC3T3-E1 cells, as evidenced by an increase in the Sub-G1 phase, chromatin condensation, and deoxyribonucleic acid fragmentation, which were significantly suppressed by coincubation with SFP. Mitochondria-mediated apoptosis pathway contributed importantly to Dex-induced apoptosis, as revealed by the activation of caspase-3/-9 and subsequent cleavage of poly adenosine diphosphate ribose polymerase, which was also effectively blocked by SFP. Moreover, treatments of Dex strongly induced overproduction of reactive oxygen species and inhibited the expression of nuclear factor erythroid 2-related factor 2 (Nrf2 and the downstream effectors HO1 and NQO1. However, cotreatment with SFP effectively reversed this action of Dex. Furthermore, silencing of Nrf2 by

  6. Telomerase Activity and Telomerase Reverse Transcriptase Expression Induced by Selenium in Rat Hepatocytes

    Institute of Scientific and Technical Information of China (English)

    RI-AN YU; HUA-JIE CHEN; LING-FEI HE; BING CHEN; XUE-MIN CHEN

    2009-01-01

    Objectives To investigate the effects of sodium selenite on telomerase activity, apoptosis and expression of TERT, c-myc and p53 in rat hepatocytes. Methods Selenium at doses of 2.5, 5.0, and 10μmol/kg was given to SD rats by garage. In rat hepatocytes, telomerase activity was measured by the telomeric repeat amplification protocol (TRAP), apoptosis was detected by flow cytometry, and expressions of telomerase reverse transcriptase (TERT), c-myc and p53 were analyzed by reverse transcription-polymerase chain reaction (RT-PCR).c-Myc and P53 proteins were detected by immunochemistry. Results Selenium at doses of 2.5, 5.0, and 10μmol/kg significantly increased hepatocellular telomerase activity and induced apoptosis in a close-dependent manner. Although selenium at doses of 2.5, 5.0, and 10μmol/kg displayed no obvious enhancing effect on the TERT mRNA expression in rat hepatocytes (P>0.05), it significantly increased the c-myc mRNA and p53 mRNA expression at the dose of 10μmol/kg (p<0.05). Selenium at doses of 5.0 and 10μmol/kg obviously increased the content of P53 protein in rat hepatocytes, but only at the dose of 10μmol/kg, it significantly promoted the value of c-Myc protein in them. Conclusion Selenium can slightly increase telomerase activity and TERT expression, and significantly induce apoptosis and over-expression of c-myc and p53 at relatively high doses. The beneficial effects of selenium on senescence and aging may be mediated by telomerase activation and expression of TERT, c-myc, and p53 in rat hepatocytes.

  7. Bacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1.

    LENUS (Irish Health Repository)

    Li, Chong Hui

    2012-03-01

    Tolerance to bacterial cell wall components including bacterial lipoprotein (BLP) represents an essential regulatory mechanism during bacterial infection. Reduced Toll-like receptor 2 (TLR2) and IL-1 receptor-associated kinase 1 (IRAK-1) expression is a characteristic of the downregulated TLR signaling pathway observed in BLP-tolerised cells. In this study, we attempted to clarify whether TLR2 and\\/or IRAK-1 are the key molecules responsible for BLP-induced tolerance. Transfection of HEK293 cells and THP-1 cells with the plasmid encoding TLR2 affected neither BLP tolerisation-induced NF-κB deactivation nor BLP tolerisation-attenuated pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) production, indicating that BLP tolerance develops despite overexpression of TLR2 in these cells. In contrast, overexpression of IRAK-1 reversed BLP-induced tolerance, as transfection of IRAK-1 expressing vector resulted in a dose-dependent NF-κB activation and TNF-α release in BLP-tolerised cells. Furthermore, BLP-tolerised cells exhibited markedly repressed NF-κB p65 phosphorylation and impaired binding of p65 to several pro-inflammatory cytokine gene promoters including TNF-α and interleukin-6 (IL-6). Overexpression of IRAK-1 restored the nuclear transactivation of p65 at both TNF-α and IL-6 promoters. These results indicate a crucial role for IRAK-1 in BLP-induced tolerance, and suggest IRAK-1 as a potential target for manipulation of the TLR-mediated inflammatory response during microbial sepsis.

  8. Zinc and imipramine reverse the depression-like behavior in mice induced by chronic restraint stress.

    Science.gov (United States)

    Ding, Qin; Li, Hongxia; Tian, Xue; Shen, Zhilei; Wang, Xiaoli; Mo, Fengfeng; Huang, Junlong; Shen, Hui

    2016-06-01

    Depression is a common psychopathological disorders. Studies of depression have indicated that zinc play a role in the depression pathophysiology and treatment. In present study, we examined the effects of zinc and imipramine supplement alone or combination of zinc and imipramine in mice induced by chronic restraint stress (CRS). Moreover, the possible roles of zinc receptor (G protein-coupled receptor 39, GPR39)-related pathway was investigated. Decreased weight and increased corticosterone (CORT) were observed after 3 weeks CRS exposure. It was shown that CRS induced lower serum zinc, higher hippocampal zinc, increased immobility time in tail suspension test and decreased movement distance in spontaneous activity test, which could be normalized by zinc (30mg/kg) and imipramine (20mg/kg) supplement alone and combination of zinc (15mg/kg) and imipramine (5mg/kg) for 3 weeks after CRS exposure. Moreover, the changes in mRNA expressions of GPR39, cAMP-response element binding protein (CREB), brain-derived neurotropic factor (BDNF) and n-methytl-d-aspartate receptors (NMDAR) could be reversed by the same treatment mentioned above. These results suggested that zinc dyshomeostasis in serum and hippocampus and depression-like behavior in CRS exposure animals observed in present study could be normalized by zinc and imipramine. The combination of zinc and imipramine in low dose has synergetic effects. The possible mechanism might be correlated to GPR39 receptor-related pathway. PMID:26985741

  9. Ginkgo biloba extract reverses CCl4-induced liver fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    Yan-Jun Luo; Jie-Ping Yu; Zhao-Hong Shi; Li Wang

    2004-01-01

    AIM: To study the reversing effect of Ginkgo biloba extract (GbE) on established liver fibrosis in rats.METHODS: Following confirmation of CCl4-induced liver fibrosis, GbE or saline was administrated to the rats for 4 weeks. The remaining rats received neither CCl4 nor GbE as normal control. The four groups were compared in terms of serum enzymes, tissue damage, expression of αSMA and tissue inhibitor-1 of metalloproteinase (TIMP-1) and metalloproteinase-1 (MMP-1).RESULTS: Compared with saline-treated group, liver fibrosis rats treated with GbE had decreased serum total bilirubin (P<0.01) and aminotransferase levels (P<0.01) and increased levels of serum albumin (P<0.01). Microscopic studies revealed that the livers of rats receiving GbE showed allieviation in fibrosis (P<0.05) as well as expression of αSMA (P<0.01). The liver collagen and reticulum contents were lower in rats treated with GbE than saline-treated group (P<0.01). RT-PCR revealed that the level of TIMP-1 decreased while the level of MMP-1 increased in GbE group.CONCLUSION: Administration of GbE improved CCl4-induced liver fibrosis. It is possibly attributed to its effect of inhibiting the expression of TIMP-1 and promoting the apoptosis of hepatic stellate cells.

  10. GM1 ganglioside reverses the cognitive deficits induced by MK801 in mice.

    Science.gov (United States)

    Ni, Yu-Fei; Zhang, Wei; Bao, Xiao-Feng; Wang, Wei; Song, Lu; Jiang, Bo

    2016-08-01

    Cognitive deficits are core symptoms of schizophrenia, but effective treatments are still lacking. Previous studies have reported that the brain-derived neurotrophic factor (BDNF) signaling is closely involved in learning and memory. Monosialotetrahexosylganglioside (GM1) is a ganglioside with wide-ranging pharmacologic effects that enhances the BDNF signaling cascade. This study aimed to assess the effects of GM1 on schizophrenia-related cognitive impairments. A brief disruption of N-methyl-D-aspartate receptors with MK801 was used to generate the animal model for cognitive deficits in schizophrenia. It was found that MK801-treated mice showed significant deficits in memory ability compared with control mice in different behavior tests, and this was accompanied by decreased hippocampal BDNF signaling pathway. Consecutive administration of GM1 fully restored the MK801-induced cognitive deficits and the impaired BDNF signaling in the hippocampus. Furthermore, a BDNF system inhibitor abolished the effects of GM1 in the MK801 model. Taken together, our results show that GM1 could reverse the MK801-induced cognitive deficits, suggesting a potential usefulness of GM1 in treating the schizophrenia-related cognitive impairments. PMID:26960162

  11. Recombinant TCR ligand reverses clinical signs and CNS damage of EAE induced by recombinant human MOG.

    Science.gov (United States)

    Sinha, Sushmita; Subramanian, Sandhya; Emerson-Webber, Ashley; Lindner, Maren; Burrows, Gregory G; Grafe, Marjorie; Linington, Christopher; Vandenbark, Arthur A; Bernard, Claude C A; Offner, Halina

    2010-06-01

    Increasing evidence suggests that in addition to T cell-dependent effector mechanisms, autoantibodies are also involved in the pathogenesis of MS, including demyelinating antibodies specific for myelin oligodendrocyte glycoprotein (MOG). Our previous studies have demonstrated that recombinant T cell receptor ligands (RTLs) are very effective for treating T cell-mediated experimental autoimmune encephalomyelitis (EAE). In order to expand the scope of RTL therapy in MS patients, it was of interest to study RTL treatment of EAE involving a demyelinating antibody component. Therefore, we evaluated the therapeutic effects of RTL551, specific for T cells reactive to mouse (m)MOG-35-55 peptide, on EAE induced with recombinant human (rh)MOG in C57BL/6 mice. We report that RTL551 therapy can reverse disease progression and reduce demyelination and axonal damage induced by rhMOG without suppressing the anti-MOG antibody response. This result suggests that T cell-mediated inflammation and associated blood-brain barrier dysfunction are the central contributors to EAE pathogenesis and that successful regulation of these key players restricts potential damage by demyelinating antibodies. The results of our study lend support for the use of RTL therapy for treatment of MS subjects whose disease includes inflammatory T cells as well as those with an additional antibody component. PMID:19789980

  12. GSK-3β inhibitors reverse cocaine-induced synaptic transmission dysfunction in the nucleus accumbens.

    Science.gov (United States)

    Zhao, Rui; Chen, Jiaojiao; Ren, Zhaoxiang; Shen, Hui; Zhen, Xuechu

    2016-11-01

    Nucleus accumbens receives glutamatergic projection from the prefrontal cortex (PFC) and dopaminergic input from the Ventral tegmental area (VTA). Recent studies have suggested a critical role for serine/threonine kinase glycogen synthase kinase 3β (GSK3β) in cocaine-induced hyperactivity; however, the effect of GSK3β on the modulation of glutamatergic and dopaminergic afferents is unclear. In this study, we found that the GSK3 inhibitors, LiCl (100 mg/kg, i.p.) or SB216763 (2.5 mg/kg, i.p.), blocked the cocaine-induced hyperlocomotor activity in rats. By employing single-unit recordings in vivo, we found that pretreatment with either SB216763 or LiCl for 15 min reversed the cocaine-inhibited firing frequency of medium spiny neuron (MSN) in the nucleus accumbens (NAc). Preperfusion of SB216763 (5 μM) ameliorated the inhibitory effect of cocaine on both the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (up to 99 ± 6.8% inhibition) and N-methyl-D-aspartic acid receptor (NMDAR)-mediate EPSC (up to 73 ± 9.7% inhibition) in the NAc in brain slices. The effect of cocaine on AMPA and NMDA receptor-mediate excitatory postsynaptic current (EPSC) were mimicked by the D1 -like receptor agonist SKF 38393 and blocked by the D1 -like receptor antagonist SCH 23390, whereas D2 -like receptor agonist or antagonist failed to mimic or to block the action of cocaine. Preperfusion of SB216763 for 5 min also ameliorated the inhibitory effect of SKF38393 on both AMPA and NMDA receptor-mediated components of EPSC, indicate the effect of SB216763 on cocaine was via the D1 -like receptor. Moreover, cocaine inhibited the presynaptic release of glutamate in the NAc, and SB216763 reversed this effect. In conclusion, D1 receptor-GSK3β pathway, which mediates glutamatergic transmission in the NAc core through a presynaptic mechanism, plays an important role in acute cocaine-induced hyperlocomotion. PMID:27377051

  13. Is Western Diet-Induced Nonalcoholic Steatohepatitis in Ldlr-/- Mice Reversible?

    Directory of Open Access Journals (Sweden)

    Kelli A Lytle

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a major public health burden in western societies. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH, is characterized by hepatosteatosis, inflammation, oxidative stress, and hepatic damage that can progress to fibrosis and cirrhosis; risk factors for hepatocellular carcinoma. Given the scope of NASH, validating treatment protocols (i.e., low fat diets and weight loss is imperative.We evaluated the efficacy of two diets, a non-purified chow (NP and purified (low-fat low-cholesterol, LFLC diet to reverse western diet (WD-induced NASH and fibrosis in Ldlr-/- mice.Mice fed WD for 22-24 weeks developed robust hepatosteatosis with mild fibrosis, while mice maintained on the WD an additional 7-8 weeks developed NASH with moderate fibrosis. Returning WD-fed mice to the NP or LFLC diets significantly reduced body weight and plasma markers of metabolic syndrome (dyslipidemia, hyperglycemia and hepatic gene expression markers of inflammation (Mcp1, oxidative stress (Nox2, fibrosis (Col1A, LoxL2, Timp1 and collagen crosslinking (hydroxyproline. Time course analyses established that plasma triglycerides and hepatic Col1A1 mRNA were rapidly reduced following the switch from the WD to the LFLC diet. However, hepatic triglyceride content and fibrosis did not return to normal levels 8 weeks after the change to the LFLC diet. Time course studies further revealed a strong association (r2 ≥ 0.52 between plasma markers of inflammation (TLR2 activators and hepatic fibrosis markers (Col1A, Timp1, LoxL2. Inflammation and fibrosis markers were inversely associated (r2 ≥ 0.32 with diet-induced changes in hepatic ω3 and ω6 polyunsaturated fatty acids (PUFA content.These studies establish a temporal link between plasma markers of inflammation and hepatic PUFA and fibrosis. Low-fat low-cholesterol diets promote reversal of many, but not all, features associated with WD-induced NASH and fibrosis in Ldlr

  14. Gabapentin reverses central pain sensitization following a collagenase-induced intrathalamic hemorrhage in rats

    Directory of Open Access Journals (Sweden)

    Castel A

    2013-12-01

    Full Text Available Aude Castel, Pascal VachonFaculty of Veterinary Medicine, Department of Veterinary Biomedicine, University of Montreal, Saint-Hyacinthe, QC, CanadaPurpose: The treatment of central neuropathic pain remains amongst the biggest challenges for pain specialists. The main objective of this study was to assess gabapentin (GBP, amitriptyline (AMI, and carbamazepine (CARBA for the treatment of a rodent central neuropathic pain model.Methods: Male Sprague Dawley rats were trained on the rotarod, Hargreaves, Von Frey and acetone behavioral tests, and baseline values were obtained prior to surgery. A stereotaxic injection of either a collagenase solution or saline was made in the right ventral posterolateral thalamic nucleus. The rats were tested on days 2, 4, 8, and 11 postsurgery. They were retested at regular intervals from day 15 to day 25 postsurgery, after oral administration of either the vehicle (n=7 and n=8 rats with intracerebral injections of collagenase and saline, respectively or the different drugs (GBP [60 mg/kg], AMI [10 mg/kg], CARBA [100 mg/kg]; n=8 rats/drug.Results: A significant decrease in the mechanical thresholds and no change in heat threshold were observed in both hind limbs in the collagenase group, as we had previously shown elsewhere. Reversal of the mechanical hypersensitivity was achieved only with GBP (P<0.05. AMI and CARBA, at the dosages used, failed to show any effect on mechanical thresholds. Transient cold allodynia was observed in some collagenase-injected rats but failed to be statistically significant.Conclusion: Intrathalamic hemorrhaging in the ventrolateral thalamic nucleus induced a bilateral mechanical allodynia, which was reversed by GBP but not AMI or CARBA.Keywords: central pain, thalamus, amitriptyline, carbamazepine

  15. Reversibility of ecstasy-induced reduction in serotonin transporter availability in polydrug ecstasy users

    International Nuclear Information System (INIS)

    Animal data suggest that the synthetic drug ecstasy may damage brain serotonin neurons. Previously we reported protracted reductions in the availability of the serotonin transporter (SERT), an index of integrity of the axon terminals of brain serotonergic neurons, in SERT-rich brain regions in current human ecstasy users. Comparison of current ecstasy users and former ecstasy users yielded some evidence that this reduction might be reversible. However, participant selection effects could not be ruled out. Therefore, follow-up examinations were performed in these subjects to test the following a priori hypothesis in a prospective longitudinal design that eliminates participant selection effects to a large extent: availability of the SERT increases towards normal levels when ecstasy use is stopped, and remains unchanged or is further decreased if use is continued. Two follow-up positron emission tomography measurements using the SERT ligand [11C](+)McN5652 were completed by 15 current and nine former ecstasy users. All subjects used illicit drugs other than ecstasy, too. The time interval between repeated measurements was about 1 year. The time course of the availability of the SERT was analysed in the following SERT-rich regions: mesencephalon, putamen, caudate and thalamus. Current ecstasy users showed a consistent increase in the availability of the SERT in the mesencephalon during the study (Friedman test: p=0.010), which most likely was caused by a decrease in the intensity of ecstasy consumption (Spearman correlation coefficient -0.725, p=0.002). Former ecstasy users showed a consistent increase in SERT availability in the thalamus (Friedman test: p=0.006). Ecstasy-induced protracted alterations in the availability of the SERT might be reversible. (orig.)

  16. Reversibility of ecstasy-induced reduction in serotonin transporter availability in polydrug ecstasy users

    Energy Technology Data Exchange (ETDEWEB)

    Buchert, Ralph; Wilke, Florian; Nebeling, Bruno; Clausen, Malte [University Medical Center Hamburg-Eppendorf, Department of Nuclear Medicine, Hamburg (Germany); Thomasius, Rainer; Petersen, Kay; Obrocki, Jost; Wartberg, Lutz; Zapletalova, Pavlina [University Medical Center Hamburg-Eppendorf, Departments of Psychiatry and Psychotherapy, Hamburg (Germany)

    2006-02-01

    Animal data suggest that the synthetic drug ecstasy may damage brain serotonin neurons. Previously we reported protracted reductions in the availability of the serotonin transporter (SERT), an index of integrity of the axon terminals of brain serotonergic neurons, in SERT-rich brain regions in current human ecstasy users. Comparison of current ecstasy users and former ecstasy users yielded some evidence that this reduction might be reversible. However, participant selection effects could not be ruled out. Therefore, follow-up examinations were performed in these subjects to test the following a priori hypothesis in a prospective longitudinal design that eliminates participant selection effects to a large extent: availability of the SERT increases towards normal levels when ecstasy use is stopped, and remains unchanged or is further decreased if use is continued. Two follow-up positron emission tomography measurements using the SERT ligand [{sup 11}C](+)McN5652 were completed by 15 current and nine former ecstasy users. All subjects used illicit drugs other than ecstasy, too. The time interval between repeated measurements was about 1 year. The time course of the availability of the SERT was analysed in the following SERT-rich regions: mesencephalon, putamen, caudate and thalamus. Current ecstasy users showed a consistent increase in the availability of the SERT in the mesencephalon during the study (Friedman test: p=0.010), which most likely was caused by a decrease in the intensity of ecstasy consumption (Spearman correlation coefficient -0.725, p=0.002). Former ecstasy users showed a consistent increase in SERT availability in the thalamus (Friedman test: p=0.006). Ecstasy-induced protracted alterations in the availability of the SERT might be reversible. (orig.)

  17. Solvent-induced helical assembly and reversible chiroptical switching of chiral cyclic-dipeptide-functionalized naphthalenediimides.

    Science.gov (United States)

    Manchineella, Shivaprasad; Prathyusha, V; Priyakumar, U Deva; Govindaraju, T

    2013-12-01

    Understanding the roles of various parameters in orchestrating the preferential chiral molecular organization in supramolecular self-assembly processes is of great significance in designing novel molecular functional systems. Cyclic dipeptide (CDP) chiral auxiliary-functionalized naphthalenediimides (NCDPs 1-6) have been prepared and their chiral self-assembly properties have been investigated. Detailed photophysical and circular dichroism (CD) studies have unveiled the crucial role of the solvent in the chiral aggregation of these NCDPs. NCDPs 1-3 form supramolecular helical assemblies and exhibit remarkable chiroptical switching behaviour (M- to P-type) depending on the solvent composition of HFIP and DMSO. The strong influence of solvent composition on the supramolecular chirality of NCDPs has been further corroborated by concentration and solid-state thin-film CD studies. The chiroptical switching between supramolecular aggregates of opposite helicity (M and P) has been found to be reversible, and can be achieved through cycles of solvent removal and redissolution in solvent mixtures of specific composition. The control molecular systems (NCDPs 4-6), with an achiral or D-isomer second amino acid in the CDP auxiliary, did not show chiral aggregation properties. The substantial roles of hydrogen bonding and π-π interactions in the assembly of the NCDPs have been validated through nuclear magnetic resonance (NMR), photophysical, and computational studies. Quantum chemical calculations at the ab initio, semiempirical, and density functional theory levels have been performed on model systems to understand the stabilities of the right (P-) and left (M-) handed helical supramolecular assemblies and the nature of the intermolecular interactions. This study emphasizes the role of CDP chiral auxiliaries on the solvent-induced helical assembly and reversible chiroptical switching of naphthalenediimides. PMID:24281809

  18. Cognitive defects are reversible in inducible mice expressing pro-aggregant full-length human Tau

    Science.gov (United States)

    Sydow, Astrid; Hofmann, Anne; Wu, Dan; Messing, Lars; Balschun, Detlef; D'Hooge, Rudi; Mandelkow, Eva-Maria

    2016-01-01

    Neurofibrillary lesions of abnormal Tau are hallmarks of Alzheimer´s disease and frontotemporal dementias. Our regulatable (Tet-OFF) mouse models of tauopathy express variants of human full-length Tau in the forebrain (CaMKIIα promoter) either with mutation ΔK280 (pro-aggregant) or ΔK280/I277P/I308P (anti-aggregant). Co-expression of luciferase enables in vivo quantification of gene expression by bioluminescence imaging. Pro-aggregant mice develop synapse loss and Tau pathology including missorting, phosphorylation and early pretangle formation, whereas anti-aggregant mice do not. We correlated hippocampal Tau pathology with learning/memory performance and synaptic plasticity. Pro-aggregant mice at 16 months of gene expression exhibited severe cognitive deficits in Morris water-maze and in passive-avoidance paradigms, whereas anti-aggregant mice were comparable to controls. Cognitive impairment of pro-aggregant mice was accompanied by loss of hippocampal LTP in CA1 and CA3 areas and by a reduction of synaptic proteins and dendritic spines, although no neuronal loss was observed. Remarkably, memory and LTP recovered when pro-aggregant Tau was switched-OFF for ∼4 months, Tau phosphorylation and missorting were reversed, and synapses recovered. Moreover soluble and insoluble pro-aggregant hTau40 disappeared while insoluble mouse Tau was still present. This study links early Tau pathology without neurofibrillary tangles and neuronal death to cognitive decline and synaptic dysfunction. It demonstrates that Tau-induced impairments are reversible after switching-OFF pro-aggregant Tau. Therefore our mouse model may mimic an early phase of AD when the hippocampus does not yet suffer from irreversible cell death but cognitive deficits are already striking. It offers potential to evaluate drugs with regard to learning and memory performance. PMID:22532069

  19. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents

    DEFF Research Database (Denmark)

    Bubser, Michael; Bridges, Thomas M; Dencker, Ditte;

    2014-01-01

    . VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant-induced...... antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that enhanced cholinergic activity may also improve cognitive function and reverse deficits observed with reduced signaling through the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) in the central...... nervous system. Prior to this study, the M1 mAChR subtype was viewed as the primary candidate for these actions relative to the other mAChR subtypes. Here we describe the discovery of a novel M4 PAM, VU0467154, with enhanced in vitro potency and improved pharmacokinetic properties relative to other M4...

  20. Magnetic-field-induced reverse transformation in a NiCoMnSn high temperature ferromagnetic shape memory alloy

    International Nuclear Information System (INIS)

    The magnetic field induced reverse martensitic transformation was studied in polycrystalline Ni40Co10Mn41Sn9 with a high martensitic transformation start temperature (Ms, about 410 K). The reverse transformation start temperature (As) dropped by about 34 K when exposed to a magnetic field of 7 T. At room temperature, the microstructure consisted of 14M martensite and γ phase. - Highlights: • The paper demonstrates a magnetic field induced reverse transformation (MFIRT) occurring at high temperature (above 373 K) in polycrystalline Ni40Co10Mn41Sn9. • This high temperature MFIRT, to our knowledge, not reported in the literature for Ni–Co–Mn–Sn and other metamagnetic shape memory alloys. • The study would be expected to extend the practical application of Ni–Co–Mn–Sn alloy

  1. Oxytocin reversed MK-801-induced social interaction and aggression deficits in zebrafish.

    Science.gov (United States)

    Zimmermann, Fernanda Francine; Gaspary, Karina Vidarte; Siebel, Anna Maria; Bonan, Carla Denise

    2016-09-15

    Changes in social behavior occur in several neuropsychiatric disorders such as schizophrenia and autism. The interaction between individuals is an essential aspect and an adaptive response of several species, among them the zebrafish. Oxytocin is a neuroendocrine hormone associated with social behavior. The aim of the present study was to investigate the effects of MK-801, a non-competitive antagonist of glutamate NMDA receptors, on social interaction and aggression in zebrafish. We also examined the modulation of those effects by oxytocin, the oxytocin receptor agonist carbetocin and the oxytocin receptor antagonist L-368,899. Our results showed that MK-801 induced a decrease in the time spent in the segment closest to the conspecific school and in the time spent in the segment nearest to the mirror image, suggesting an effect on social behavior. The treatment with oxytocin after the exposure to MK-801 was able to reestablish the time spent in the segment closest to the conspecific school, as well as the time spent in the segment nearest to the mirror image. In addition, in support of the role of the oxytocin pathway in modulating those responses, we showed that the oxytocin receptor agonist carbetocin reestablished the social and aggressive behavioral deficits induced by MK-801. However, the oxytocin receptor antagonist L-368,899 was not able to reverse the behavioral changes induced by MK-801. This study supports the critical role for NMDA receptors and the oxytocinergic system in the regulation of social behavior and aggression which may be relevant for the mechanisms associated to autism and schizophrenia. PMID:27247142

  2. Comparison of neostigmine induced reversal of vecuronium in normal weight, overweight and obese female patients

    Directory of Open Access Journals (Sweden)

    Shilpa Bhimasen Joshi

    2015-01-01

    Full Text Available Background and Aims: Obese patients are more vulnerable to residual neuromuscular block (NMB and its associated complications in the post-operative period. This study was carried out to compare neostigmine induced reversal of vecuronium in normal weight, overweight and obese female patients, objectively using neuromuscular (NM monitoring. Methods: Twenty female patients each belonging to normal weight, overweight and obese, based on body mass index, requiring general anaesthesia were recruited for this prospective cross sectional study. NMB was induced with vecuronium (0.1 mg/kg dose based on patient′s real body weight (RBW and monitored using acceleromyographic train of four (TOF. All patients received neostigmine 40 μg/kg and glycopyrrolate 10 μg/kg at 25% of spontaneous recovery of first twitch height (T1 of TOF (DUR 25% and were allowed to recover to TOF ratio of 0.9. Statistical analysis was done using analysis of variance test. Results: Recovery of TOF ratio to 0.5 was comparable in all three groups. Recovery of TOF ratio to 0.7 was delayed in obese (9.82 ± 3.21 min compared with normal weight group (7.50 ± 2.52 min. Recovery of TOF to 0.9 was significantly delayed in both overweight (12.18 ± 4.29 min and obese patients (13.78 ± 4.30 min. DUR 25% was significantly longer in overweight (mean, standard deviation [range]; 30.10 [19-40 min] and obese (28.8 [12-45 min] compared with normal weight patients (22.75 [16-30 min]. Conclusion: In overweight and obese patients, when vecuronium induction dose is based on RBW, neostigmine induced recovery of NMB is delayed in late phases (TOF 0.7-0.9, which may result in vulnerability for associated complications of incomplete recovery. Ensuring safe recovery thus requires objective NM monitoring.

  3. Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes.

    Science.gov (United States)

    Bianchi, María S; Bianchi, Stefanía; Hernado-Insúa, Andrés; Martinez, Leandro M; Lago, Néstor; Libertun, Carlos; Chasseing, Norma A; Montaner, Alejandro D; Lux-Lantos, Victoria A

    2016-08-01

    Type 1 diabetes (T1D) originates from autoimmune β-cell destruction. IMT504 is an immunomodulatory oligonucleotide that increases mesenchymal stem cell cloning capacity and reverts toxic diabetes in rats. Here, we evaluated long-term (20 doses) and short-term (2-6 doses) effects of IMT504 (20 mg·kg(-1)·day(-1) sc) in an immunodependent diabetes model: multiple low-dose streptozotocin-injected BALB/c mice (40 mg·kg(-1)·day(-1) ip for 5 consecutive days). We determined blood glucose, glucose tolerance, serum insulin, islet morphology, islet infiltration, serum cytokines, progenitor cell markers, immunomodulatory proteins, proliferation, apoptosis, and islet gene expression. IMT504 reduced glycemia, induced β-cell recovery, and impaired islet infiltration. IMT504 induced early blood glucose decrease and infiltration inhibition, increased β-cell proliferation and decreased apoptosis, increased islet indoleamine 2,3-dioxygenase (IDO) expression, and increased serum tumor necrosis factor and interleukin-6 (IL-6). IMT504 affected islet gene expression; preproinsulin-2, proglucagon, somatostatin, nestin, regenerating gene-1, and C-X-C motif ligand-1 cytokine (Cxcl1) increased in islets from diabetic mice and were decreased by IMT504. IMT504 downregulated platelet endothelial cell adhesion molecule-1 (Pecam1) in islets from control and diabetic mice, whereas it increased regenerating gene-2 (Reg2) in islets of diabetic mice. The IMT504-induced increase in IL-6 and islet IDO expression and decreased islet Pecam1 and Cxcl1 mRNA expression could participate in keeping leukocyte infiltration at bay, whereas upregulation of Reg2 may mediate β-cell regeneration. We conclude that IMT504 effectively reversed immunodependent diabetes in mice. Corroboration of these effects in a model of autoimmune diabetes more similar to human T1D could provide promising results for the treatment of this disease. PMID:27329801

  4. Sugammadex 4.0 mg kg-1 reversal of deep rocuronium-induced neuromuscular blockade

    DEFF Research Database (Denmark)

    Yu, Buwei; Wang, Xiangrui; Hansen, Søren Helbo;

    2014-01-01

    Objective: Maintenance of deep Neuro Muscular Blockade (NMB) until the end of surgery may be beneficial in some surgical procedures. The selective relaxant binding agent sugammadex rapidly reverses deep levels of rocuronium-induced NMB. The purpose of this study was to evaluate the efficacy and s...

  5. L -Carnitine and Melatonin Reverse CCl4 Induced Liver Fibrosis In Rats (Histological and Histochemical Studies

    Directory of Open Access Journals (Sweden)

    Fatma, A. Morsy, Abdel Razik, H. Farrag and Sonya, L. El-Sharkawy

    2004-12-01

    Full Text Available Carbontetrachloride (CCl4 is closely related chemically to chloroform and likewise in hepatic poisons. This study was designed to evaluate the effects of carbon tetrachloride on liver of male rats and the reversing effects of L-carnitine and melatonin on established liver fibrosis. A total of 72 adult male albino rats were used in this study. The animals were divided into six groups. Group (1 animals of the first group were kept as control andtreated with paraffin oil twice weekly for eight weeks. Group (2 rats of the second group were injected with CCl4 intraperitoneally at 0.15 ml per rats (diluted 1:1 in liquid paraffin twice weekly for eight weeks to produced liver fibrosis. Group (3 following establishment with CCl4 which induced liver fibrosis, the rats were treated with L-carnitine at a dose level of 50 mg/kg for four weeks. Group (4 rats with liver fibrosis were injected intraperitoneally with melatonin at dose level of 10 mg/kg for four weeks. The fifth and sixth groups were given L-carnitine and/or melatonin at dose levels of 50 mg/kg and 10 mg/kg respectively for four weeks. Histological changes in the liver of rats treated with CCl4 including liver fibrosis, architecture distortion and appearance of many pseudolobule. The fibrous tissues run in septa between the nodules. The liver damage varied from one area to another and varied from moderate fibrosis to cirrhosis. Quantitative measurement of the severity of liver fibrosis (area damage was achieved by using computerized image analysis (Leica image showed that highly significant increase in area of fibrosis was recorded in the case of rats treated with CCl4 only. Quantitative DNA image analysis showed that 3% of aneuploid cells could be noticed in liver of rats treated with CCl4 only. Histochemical results of rats treated with CCl4 showed highly significant increase in grey level of mucopolysaccharides and protein levels. No histological and histochemical changes could be noticed in

  6. The Influence of Insecticide Resistance, Age, Sex, and Blood Feeding Frequency on Thermal Tolerance of Wild and Laboratory Phenotypes of Anopheles funestus (Diptera: Culicidae).

    Science.gov (United States)

    Lyons, C L; Oliver, S V; Hunt, R H; Coetzee, M

    2016-03-01

    Resistance to insecticides is a global phenomenon and is increasing at an unprecedented rate. How resistant and susceptible strains of malaria vectors might differ in terms of life history and basic biology is often overlooked, despite the potential importance of such information in light of changing climates. Here, we investigated the upper thermal limits (ULT50) of wild and laboratory strains of Anopheles funestus Giles mosquitoes, including resistance status, sex, age, and blood feeding status as potential factors influencing ULT50. No significant differences in ULT50 were observed between strains displaying different resistance patterns, nor was there a significant difference between wild and laboratory strains. In some instances, strains showed a senescence response, displaying decreased ULT50 with an increase in age, and differences between males and females (females displaying higher ULT50 than males). Blood feeding did not seem to influence ULT50 in any way. For An. funestus, it seems evident that there is no cost to resistance despite what is displayed in other anopheline species. This could have significant impacts for vector control, with resistant populations of An. funestus performing just as well, if not better, than susceptible strains, especially under changing environmental conditions such as those expected to occur with climate change. PMID:26718714

  7. Structure and ligand-binding properties of the biogenic amine-binding protein from the saliva of a blood-feeding insect vector of Trypanosoma cruzi

    International Nuclear Information System (INIS)

    Biogenic amine-binding proteins mediate the anti-inflammatory and antihemostatic activities of blood-feeding insect saliva. The structure of the amine-binding protein from R. prolixus reveals the interaction of biogenic amine ligands with the protein. Proteins that bind small-molecule mediators of inflammation and hemostasis are essential for blood-feeding by arthropod vectors of infectious disease. In ticks and triatomine insects, the lipocalin protein family is greatly expanded and members have been shown to bind biogenic amines, eicosanoids and ADP. These compounds are potent mediators of platelet activation, inflammation and vascular tone. In this paper, the structure of the amine-binding protein (ABP) from Rhodnius prolixus, a vector of the trypanosome that causes Chagas disease, is described. ABP binds the biogenic amines serotonin and norepinephrine with high affinity. A complex with tryptamine shows the presence of a binding site for a single ligand molecule in the central cavity of the β-barrel structure. The cavity contains significant additional volume, suggesting that this protein may have evolved from the related nitrophorin proteins, which bind a much larger heme ligand in the central cavity

  8. Structure and ligand-binding properties of the biogenic amine-binding protein from the saliva of a blood-feeding insect vector of Trypanosoma cruzi

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xueqing; Chang, Bianca W. [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States); Mans, Ben J. [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States); Agricultural Research Council, Onderstepoort 0110 (South Africa); Ribeiro, Jose M. C.; Andersen, John F., E-mail: jandersen@niaid.nih.gov [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States)

    2013-01-01

    Biogenic amine-binding proteins mediate the anti-inflammatory and antihemostatic activities of blood-feeding insect saliva. The structure of the amine-binding protein from R. prolixus reveals the interaction of biogenic amine ligands with the protein. Proteins that bind small-molecule mediators of inflammation and hemostasis are essential for blood-feeding by arthropod vectors of infectious disease. In ticks and triatomine insects, the lipocalin protein family is greatly expanded and members have been shown to bind biogenic amines, eicosanoids and ADP. These compounds are potent mediators of platelet activation, inflammation and vascular tone. In this paper, the structure of the amine-binding protein (ABP) from Rhodnius prolixus, a vector of the trypanosome that causes Chagas disease, is described. ABP binds the biogenic amines serotonin and norepinephrine with high affinity. A complex with tryptamine shows the presence of a binding site for a single ligand molecule in the central cavity of the β-barrel structure. The cavity contains significant additional volume, suggesting that this protein may have evolved from the related nitrophorin proteins, which bind a much larger heme ligand in the central cavity.

  9. Sugammadex reversal of rocuronium-induced neuromuscular block in a patient with ataxia-telangiectasia

    International Nuclear Information System (INIS)

    A 17-year-old adolescent with ataxia-telangiectasia was scheduled to have laparoscopic colectomy for a resection of colon cancer. He had symptoms and signs of dyspnea, generalized dystonia, dysmetria, ataxia, and telangiectasia on the orbit. General anesthesia was performed, and rocuronium 30 mg was administered for muscle relaxation. Deep neuromuscular block (post-tetanic count: 0-8) was maintained for 95 minutes without additional rocuronium. On completion of surgery, sugammadex 80 mg was injected and train-of-four ratio was 0.93 at 210 seconds after administration. The tracheal tube was removed 5 min after the end of surgery. He recovered full spontaneous respiration and voluntary movements within 1 minute after extubation. After the surgery, he transferred to the intensive care unit and discharged 14 days after the surgery without any concrete problem. The reversal of rocuronium induced neuromuscular block by sugammadex was fast, complete, and recovered to the initial preoperative level of neuromuscular function in this patient. (author)

  10. Cannabinoid receptor activation reverses kainate-induced synchronized population burst firing in rat hippocampus

    Directory of Open Access Journals (Sweden)

    Rob Mason

    2009-06-01

    Full Text Available Cannabinoids have been shown to possess anticonvulsant properties in whole animal models of epilepsy. The present investigation sought to examine the effects of cannabinoid receptor activation on kainic acid (KA-induced epileptiform neuronal excitability. Under urethane anesthesia, acute KA treatment (10 mg/kg, i.p. entrained the spiking mode of simultaneously recorded neurons from random firing to synchronous bursting (% change in burst rate. Injection of the high-affinity cannabinoid agonist (--11-hydroxy-8-tetrahydrocannabinol-dimethyl-heptyl (HU210, 100 µg/kg, i.p. following KA markedly reduced the burst frequency (% decrease in burst frequency and reversed synchronized firing patterns back to baseline levels. Pre-treatment with the central cannabinoid receptor (CB1 antagonist N-piperidino-5-(4-clorophenyl-1-(2,4-dichlorophenyl-4-methyl-3-pyrazole-carboxamide (rimonabant, SR141716A 3 mg/kg, i.p. completely prevented the actions of HU210. The present results indicate that cannabinoids exert their antiepileptic effects by impeding pathological synchronization of neuronal networks in the hippocampus.

  11. Cannabinoid receptor activation reverses kainate-induced synchronized population burst firing in rat hippocampus.

    Science.gov (United States)

    Mason, Rob; Cheer, Joseph F

    2009-01-01

    Cannabinoids have been shown to possess anticonvulsant properties in whole animal models of epilepsy. The present investigation sought to examine the effects of cannabinoid receptor activation on kainic acid (KA)-induced epileptiform neuronal excitability. Under urethane anesthesia, acute KA treatment (10 mg kg(-1), i.p.) entrained the spiking mode of simultaneously recorded neurons from random firing to synchronous bursting (% change in burst rate). Injection of the high-affinity cannabinoid agonist (-)-11-hydroxy-8-tetrahydrocannabinol-dimethyl-heptyl (HU210, 100 mug kg(-1), i.p.) following KA markedly reduced the burst frequency (% decrease in burst frequency) and reversed synchronized firing patterns back to baseline levels. Pre-treatment with the central cannabinoid receptor (CB1) antagonist N-piperidino-5-(4-clorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (rimonabant, SR141716A 3 mg kg(-1), i.p.) completely prevented the actions of HU210. The present results indicate that cannabinoids exert their antiepileptic effects by impeding pathological synchronization of neuronal networks in the hippocampus. PMID:19562087

  12. Localization of Reversion-Induced LIM Protein (RIL) in the Rat Central Nervous System

    International Nuclear Information System (INIS)

    Reversion-induced LIM protein (RIL) is a member of the ALP (actinin-associated LIM protein) subfamily of the PDZ/LIM protein family. RIL serves as an adaptor protein and seems to regulate cytoskeletons. Immunoblotting suggested that RIL is concentrated in the astrocytes in the central nervous system. We then examined the expression and localization of RIL in the rat central nervous system and compared it with that of water channel aquaporin 4 (AQP4). RIL was concentrated in the cells of ependyma lining the ventricles in the brain and the central canal in the spinal cord. In most parts of the central nervous system, RIL was expressed in the astrocytes that expressed AQP4. Double-labeling studies showed that RIL was concentrated in the cytoplasm of astrocytes where glial fibrillary acidic protein was enriched as well as in the AQP4-enriched regions such as the endfeet or glia limitans. RIL was also present in some neurons such as Purkinje cells in the cerebellum and some neurons in the brain stem. Differential expression of RIL suggests that it may be involved in the regulation of the central nervous system

  13. Reversal of haloperidol-induced tardive vacuous chewing movements and supersensitive somatodendritic serotonergic response by imipramine in rats

    International Nuclear Information System (INIS)

    The study was designed to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-HT-1A receptors by co- administration of imipramine could reverse the induction of VCMs and supersensitivity at 5-HT-IA receptors by haloperidol. Rats treated with haloperidol 0.2mg/rat/day for 2 weeks induced VCMs with twitching of facial musculature that increased in a time dependent manner as the treatment continued to 5 weeks. Co administration of imipramine (5mg/kg/m1) attenuated haloperidol-induced VCMs after 2 weeks and completely reversed it after 5 weeks. The intensity of 8-hydroxy -2-di(n-propyleamino)tetraline (8-OH-DPAT)-induced locomotion and forepaw treading were greater in saline+haloperidol injected but not in imipramine+haloperidol injected animals. 8-OH-DPAT induced decreases of 5-HT metabolism were greater in saline+haloperidol injected animals but not in imipramine+haloperidol injected animals. The mechanism involved in reversal/attenuation of haloperidol-induced tardive dyskinesia by imipramine is discussed. (author)

  14. Post-irradiation modification of radiation-induced heteroallelic reversion in diploid yeast: effect of nutrient broth

    International Nuclear Information System (INIS)

    The effect of post-irradiation growth in complete rich medium on the expression of the reversion to arginine-independence induced by gamma and alpha radiation in a heteroallelic diploid yeast strain (Saccharomyces cerevisiae BZ34) has been studied. During the post-irradiation treatment the reversion frequency increased, reached a peak at about 90 minutes and decreased thereafter reaching a constant value for treatment periods exceeding 6h. As determined by the increase in number of budding cells, extensive DNA synthesis took place in cells incubated only in the nutrient medium and not in the omission medium. Hence the observed increase in the reversion frequency is explained on the basis that post-irradiation DNA synthesis is necessary for the expression of gene conversion. The decrease in the reversion frequency for continued treatment with yeast extract, peptone, dextrose (YEPD) is related to the fact that only one daughter of the post-irradiation first cell division is a revertant. The broth effect was not lost when the irradiated cells were first incubated for 90 min in arginine-less medium and then transferred to the broth. Similarly, the broth effect even persisted at doses high enough to induce considerable division delay. These results suggest that the radiation-induced pre-conversional lesions are not susceptible to repair by alternative pathways

  15. Noise-induced effects in high-speed reversal of magnetic dipole

    OpenAIRE

    Pankratov, A. L.; S. N. VDOVICHEV; Nefedov, I. M.

    2008-01-01

    The effect of noise on the reversal of a magnetic dipole is investigated on the basis of computer simulation of the Landau-Lifshits equation. It is demonstrated that at the reversal by the pulse with sinusoidal shape, there exists the optimal duration, which minimizes the mean reversal time (MRT) and the standard deviation (jitter). Both the MRT and the jitter significantly depend on the angle between the reversal magnetic field and the anisotropy axis. At the optimal angle the MRT can be dec...

  16. MRI study on reversible and irreversible electroporation induced blood brain barrier disruption.

    Directory of Open Access Journals (Sweden)

    Mohammad Hjouj

    Full Text Available Electroporation, is known to induce cell membrane permeabilization in the reversible (RE mode and cell death in the irreversible (IRE mode. Using an experimental system designed to produce a continuum of IRE followed by RE around a single electrode we used MRI to study the effects of electroporation on the brain. Fifty-four rats were injected with Gd-DOTA and treated with a G25 electrode implanted 5.5 mm deep into the striata. MRI was acquired immediately after treatment, 10 min, 20 min, 30 min, and up to three weeks following the treatment using: T1W, T2W, Gradient echo (GE, serial SPGR (DCE-MRI with flip angles ranging over 5-25°, and diffusion-weighted MRI (DWMRI. Blood brain barrier (BBB disruption was depicted as clear enhancement on T1W images. The average signal intensity in the regions of T1-enhancement, representing BBB disruption, increased from 1887±83 (arbitrary units immediately post treatment to 2246±94 20 min post treatment, then reached a plateau towards the 30 min scan where it reached 2289±87. DWMRI at 30 min showed no significant effects. Early treatment effects and late irreversible damage were clearly depicted on T2W. The enhancing volume on T2W has increased by an average of 2.27±0.27 in the first 24-48 hours post treatment, suggesting an inflammatory tissue response. The permanent tissue damage, depicted as an enhancing region on T2W, 3 weeks post treatment, decreased to an average of 50±10% of the T2W enhancing volumes on the day of the treatment which was 33±5% of the BBB disruption volume. Permanent tissue damage was significantly smaller than the volume of BBB disruption, suggesting, that BBB disruption is associated with RE while tissue damage with IRE. These results demonstrate the feasibility of applying reversible and irreversible electroporation for transient BBB disruption or permanent damage, respectively, and applying MRI for planning/monitoring disruption volume/shape by optimizing electrode positions

  17. Reversible switching between pressure-induced amorphization and thermal-driven recrystallization in VO2(B) nanosheets.

    Science.gov (United States)

    Wang, Yonggang; Zhu, Jinlong; Yang, Wenge; Wen, Ting; Pravica, Michael; Liu, Zhenxian; Hou, Mingqiang; Fei, Yingwei; Kang, Lei; Lin, Zheshuai; Jin, Changqing; Zhao, Yusheng

    2016-01-01

    Pressure-induced amorphization (PIA) and thermal-driven recrystallization have been observed in many crystalline materials. However, controllable switching between PIA and a metastable phase has not been described yet, due to the challenge to establish feasible switching methods to control the pressure and temperature precisely. Here, we demonstrate a reversible switching between PIA and thermally-driven recrystallization of VO2(B) nanosheets. Comprehensive in situ experiments are performed to establish the precise conditions of the reversible phase transformations, which are normally hindered but occur with stimuli beyond the energy barrier. Spectral evidence and theoretical calculations reveal the pressure-structure relationship and the role of flexible VOx polyhedra in the structural switching process. Anomalous resistivity evolution and the participation of spin in the reversible phase transition are observed for the first time. Our findings have significant implications for the design of phase switching devices and the exploration of hidden amorphous materials. PMID:27426219

  18. Utilization of the Donnan potential induced by reverse salt flux in pressure retarded osmosis systems.

    Science.gov (United States)

    Park, Chul Ho; Kwak, Sung Jo; Nam, Joo-Youn; Jang, Moon Seok; Lee, Jung-Hyun

    2016-09-14

    Pressure retarded osmosis (PRO) generates energy from salinity gradients. Reverse salt flux through a semi-permeable PRO membrane reduces the energy efficiency. We demonstrate for the first time the direct conversion of the reverse salt flux into electrochemical potential, recovering >7% positive net power using a single electrochemical PRO membrane. PMID:27523633

  19. Hydrogen Sulfide Prevents and Partially Reverses Ozone-Induced Features of Lung Inflammation and Emphysema in Mice.

    Science.gov (United States)

    Li, Feng; Zhang, Pengyu; Zhang, Min; Liang, Li; Sun, Xiaoyuan; Li, Min; Tang, Yueqin; Bao, Aihua; Gong, Jicheng; Zhang, Junfeng; Adcock, Ian; Chung, Kian Fan; Zhou, Xin

    2016-07-01

    Hydrogen sulfide (H2S), a novel signaling gasotransmitter in the respiratory system, may have antiinflammatory properties in the lung. We examined the preventive and therapeutic effects of H2S on ozone-induced features of lung inflammation and emphysema. C57/BL6 mice were exposed to ozone or filtered air over 6 weeks. Sodium hydrogen sulfide (NaHS), an H2S donor, was administered to the mice either before ozone exposure (preventive effect) or after completion of 6 weeks of ozone exposure (therapeutic effect). The ozone-exposed mice developed emphysema, measured by micro-computed tomography and histology, airflow limitation, measured by the forced maneuver system, and increased lung inflammation with augmented IL-1β, IL-18, and matrix metalloproteinase-9 (MMP-9) gene expression. Ozone-induced changes were associated with increased Nod-like receptor pyrin domain containing 3 (NLRP3)-caspase-1 activation and p38 mitogen-activated protein kinase phosphorylation and decreased Akt phosphorylation. NaHS both prevented and reversed lung inflammation and emphysematous changes in alveolar space. In contrast, NaHS prevented, but did not reverse, ozone-induced airflow limitation and bronchial structural remodeling. In conclusion, NaHS administration prevented and partially reversed ozone-induced features of lung inflammation and emphysema via regulation of the NLRP3-caspase-1, p38 mitogen-activated protein kinase, and Akt pathways. PMID:26731380

  20. Developing tTA Transgenic Rats for Inducible and Reversible Gene Expression

    Directory of Open Access Journals (Sweden)

    Hongxia Zhou, Cao Huang, Min Yang, Carlisle P Landel, Pedro Yuxing Xia, Yong-Jian Liu, Xu Gang Xia

    2009-01-01

    Full Text Available To develop transgenic lines for conditional expression of desired genes in rats, we generated several lines of the transgenic rats carrying the tetracycline-controlled transactivator (tTA gene. Using a vigorous, ubiquitous promoter to drive the tTA transgene, we obtained widespread expression of tTA in various tissues. Expression of tTA was sufficient to strongly activate its reporter gene, but was below the toxicity threshold. We examined the dynamics of Doxycycline (Dox-regulated gene expression in transgenic rats. In the two transmittable lines, tTA-mediated activation of the reporter gene was fully subject to regulation by Dox. Dox dose-dependently suppressed tTA-activated gene expression. The washout time for the effects of Dox was dose-dependent. We tested a complex regime of Dox administration to determine the optimal effectiveness and washout duration. Dox was administered at a high dose (500 μg/ml in drinking water for two days to reach the effective concentration, and then was given at a low dose (20 μg/ml to maintain effectiveness. This regimen of Dox administration can achieve a quick switch between ON and OFF statuses of tTA-activated gene expression. In addition, administration of Dox to pregnant rats fully suppressed postnatal tTA-activated gene expression in their offspring. Sufficient levels of Dox are present in mother's milk to produce maximal efficacy in nursing neonates. Administration of Dox to pregnant or nursing rats can provide a continual suppression of tTA-dependent gene expression during embryonic and postnatal development. The tTA transgenic rat allows for inducible and reversible gene expression in the rat; this important tool will be valuable in the development of genetic rat models of human diseases.

  1. Developing tTA transgenic rats for inducible and reversible gene expression.

    Science.gov (United States)

    Zhou, Hongxia; Huang, Cao; Yang, Min; Landel, Carlisle P; Xia, Pedro Yuxing; Liu, Yong-Jian; Xia, Xu Gang

    2009-01-01

    To develop transgenic lines for conditional expression of desired genes in rats, we generated several lines of the transgenic rats carrying the tetracycline-controlled transactivator (tTA) gene. Using a vigorous, ubiquitous promoter to drive the tTA transgene, we obtained widespread expression of tTA in various tissues. Expression of tTA was sufficient to strongly activate its reporter gene, but was below the toxicity threshold. We examined the dynamics of Doxycycline (Dox)-regulated gene expression in transgenic rats. In the two transmittable lines, tTA-mediated activation of the reporter gene was fully subject to regulation by Dox. Dox dose-dependently suppressed tTA-activated gene expression. The washout time for the effects of Dox was dose-dependent. We tested a complex regime of Dox administration to determine the optimal effectiveness and washout duration. Dox was administered at a high dose (500 microg/ml in drinking water) for two days to reach the effective concentration, and then was given at a low dose (20 microg/ml) to maintain effectiveness. This regimen of Dox administration can achieve a quick switch between ON and OFF statuses of tTA-activated gene expression. In addition, administration of Dox to pregnant rats fully suppressed postnatal tTA-activated gene expression in their offspring. Sufficient levels of Dox are present in mother's milk to produce maximal efficacy in nursing neonates. Administration of Dox to pregnant or nursing rats can provide a continual suppression of tTA-dependent gene expression during embryonic and postnatal development. The tTA transgenic rat allows for inducible and reversible gene expression in the rat; this important tool will be valuable in the development of genetic rat models of human diseases. PMID:19214245

  2. Opioid-induced respiratory depression: reversal by non-opioid drugs.

    Science.gov (United States)

    van der Schier, Rutger; Roozekrans, Margot; van Velzen, Monique; Dahan, Albert; Niesters, Marieke

    2014-01-01

    The human body is critically dependent on the ventilatory control system for adequate uptake of oxygen and removal of carbon dioxide (CO2). Potent opioid analgesics, through their actions on μ-opioid receptor (MOR) expressed on respiratory neurons in the brainstem, depress ventilation. Opioid-induced respiratory depression (OIRD) is potentially life threatening and the cause of substantial morbidity and mortality. One possible way of prevention of OIRD is by adding a respiratory stimulant to the opioid treatment, which through activation of non-opioidergic pathways will excite breathing and consequently will offset OIRD and should not affect analgesia. Various new respiratory stimulants are currently under investigation including (a) potassium channel blockers acting at the carotid bodies, and (b) ampakines and (c) serotonin receptor agonists acting within the brainstem. (a) GAL-021 targets BKCa-channels. Initial animal and human experimental evidence indicates that this potassium channel blocker is a potent respiratory stimulant that reverses OIRD without affecting antinociception. GAL021 is safe and better tolerated than the older K(+)-channel blocker doxapram and more efficacious in its effect on respiration. (b) Ampakines modulate glutamatergic respiratory neurons in brainstem respiratory centers. Various ampakines have been studied showing their ability to increase respiratory drive during OIRD by increasing respiratory rate. Currently, CX717 is the most promising ampakine for use in humans as it is safe and does not affect opioid analgesia. (c) While animal studies show that serotonin receptor agonists increase respiratory drive via activation of serotonin receptors in brainstem respiratory centers, human studies are without success. Further clinical studies are required to improve our care of patients that are treated with potent opioid analgesics. The use of non-opioid adjuvants may reduce the probability of OIRD but does never relieve us of our duty to

  3. Ganglioside GM3 synthase depletion reverses neuropathic pain and small fiber neuropathy in diet-induced diabetic mice

    Science.gov (United States)

    Jayaraj, Nirupa D; Wilson, Heather M; Ren, Dongjun; Flood, Kelsey; Wang, Xiao-Qi; Shum, Andrew; Miller, Richard J; Paller, Amy S

    2016-01-01

    Background Small fiber neuropathy is a well-recognized complication of type 2 diabetes and has been shown to be responsible for both neuropathic pain and impaired wound healing. In previous studies, we have demonstrated that ganglioside GM3 depletion by knockdown of GM3 synthase fully reverses impaired wound healing in diabetic mice. However, the role of GM3 in neuropathic pain and small fiber neuropathy in diabetes is unknown. Purpose Determine whether GM3 depletion is able to reverse neuropathic pain and small fibers neuropathy and the mechanism of the reversal. Results We demonstrate that GM3 synthase knockout and the resultant GM3 depletion rescues the denervation in mouse footpad skin and fully reverses the neuropathic pain in diet-induced obese diabetic mice. In cultured dorsal root ganglia from diet-induced diabetic mice, GM3 depletion protects against increased intracellular calcium influx in vitro. Conclusions These studies establish ganglioside GM3 as a new candidate responsible for neuropathic pain and small fiber neuropathy in diabetes. Moreover, these observations indicate that systemic or topically applied interventions aimed at depleting GM3 may improve both the painful neuropathy and the wound healing impairment in diabetes by protecting against nerve end terminal degeneration, providing a disease-modifying approach to this common, currently intractable medical issue. PMID:27590073

  4. A joined role of canopy and reversal cells in bone remodeling - Lessons from glucocorticoid-induced osteoporosis

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Hauge, Ellen-Margrethe;

    2015-01-01

    Successful bone remodeling demands that osteoblasts restitute the bone removed by osteoclasts. In human cancellous bone, a pivotal role in this restitution is played by the canopies covering the bone remodeling surfaces, since disruption of canopies in multiple myeloma, postmenopausal- and...... glucocorticoid-induced osteoporosis is associated with the absence of progression of the remodeling cycle to bone formation, i.e. uncoupling. An emerging concept explaining this critical role of canopies is that they represent a reservoir of osteoprogenitors to be delivered to reversal surfaces. In...... postmenopausal osteoporosis, this concept is supported by the coincidence between the absence of canopies and scarcity of cells on reversal surfaces together with abortion of the remodeling cycle. Here we tested whether this concept holds true in glucocorticoid-induced osteoporosis. A histomorphometric analysis...

  5. Lipid Emulsions Enhance the Norepinephrine-Mediated Reversal of Local Anesthetic-Induced Vasodilation at Toxic Doses

    OpenAIRE

    Lee, Soo Hee; Sung, Hui-Jin; Ok, Seong-Ho; Yu, Jongsun; Choi, Mun-Jeoung; Lim, Jin Soo; Sohn, Ju-Tae

    2013-01-01

    Purpose Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. Materials and Methods The effects of lipid e...

  6. Temperature-induced sign reversal of biaxiality observed by conoscopy in some ferroelectric Sm- C* liquid crystals

    OpenAIRE

    Fukuda, Atsuo; VIJ, JAGDISH KUMAR

    2007-01-01

    PUBLISHED Article number 011709 We have studied various ferroelectric liquid crystals to find the average molecular direction of the shortest axis in the perfectly unwound state by using tilted conoscopic measurements. We find that there exist two types of temperature dependencies of the biaxiality. Some materials exhibit increasing biaxiality while others show decreasing biaxiality with increasing temperature. The former shows a temperature-induced sign reversal of biaxiality. Three di...

  7. Strain-induced transitions to quantum chaos and effective time-reversal symmetry breaking in triangular graphene nanoflakes

    OpenAIRE

    Rycerz, Adam

    2013-01-01

    We investigate the effect of strain-induced gauge fields on statistical distribution of energy levels of triangular graphene nanoflakes with zigzag edges. In the absence of strain fields but in the presence of weak potential disorder such systems were found in Ref. [1] to display the spectral statistics of the Gaussian unitary ensemble (GUE) due to the effective time-reversal (symplectic) symmetry breaking. Here show that, in the absence of disorder, strain fields may solely lead to spectral ...

  8. INCREASES IN ANXIETY-LIKE BEHAVIOR INDUCED BY ACUTE STRESS ARE REVERSED BY ETHANOL IN ADOLESCENT BUT NOT ADULT RATS

    OpenAIRE

    Varlinskaya, Elena I.; Spear, Linda P.

    2011-01-01

    Repeated exposure to stressors has been found to increase anxiety-like behavior in laboratory rodents, with the social anxiety induced by repeated restraint being extremely sensitive to anxiolytic effects of ethanol in both adolescent and adult rats. No studies, however, have compared social anxiogenic effects of acute stress or the capacity of ethanol to reverse this anxiety in adolescent and adult animals. Therefore, the present study was designed to investigate whether adolescent [postnata...

  9. Abacavir-induced reversible Fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodeficiency syndrome

    OpenAIRE

    Ahmad M

    2006-01-01

    There are several reports of Fanconi syndrome (FS) with or without nephrogenic diabetes insipidus (NDI) in patients with human immunodeficiency virus (HIV) infection, treated with various antiretroviral medications like cidofovir, adefovir, didenosine and tenofovir. But neither FS nor NDI has been documented with abacavir therapy. We are reporting the first case of abacavir-induced reversible FS with NDI in a patient with acquired immunodeficiency syndrome, who recovered completely with suppo...

  10. IL-12-based vaccination therapy reverses liver-induced systemic tolerance in a mouse model of hepatitis B virus carrier.

    Science.gov (United States)

    Zeng, Zhutian; Kong, Xiaohui; Li, Fenglei; Wei, Haiming; Sun, Rui; Tian, Zhigang

    2013-10-15

    Liver-induced systemic immune tolerance that occurs during chronic hepadnavirus infection is the biggest obstacle for effective viral clearance. Immunotherapeutic reversal of this tolerance is a promising strategy in the clinic but remains to be explored. In this study, using a hepatitis B virus (HBV)-carrier mouse model, we report that IL-12-based vaccination therapy can efficiently reverse systemic tolerance toward HBV. HBV-carrier mice lost responsiveness to hepatitis B surface Ag (HBsAg) vaccination, and IL-12 alone could not reverse this liver-induced immune tolerance. However, after IL-12-based vaccination therapy, the majority of treated mice became HBsAg(-) in serum; hepatitis B core Ag was also undetectable in hepatocytes. HBV clearance was dependent on HBsAg vaccine-induced anti-HBV immunity. Further results showed that IL-12-based vaccination therapy strongly enhanced hepatic HBV-specific CD8(+) T cell responses, including proliferation and IFN-γ secretion. Systemic HBV-specific CD4(+) T cell responses were also restored in HBV-carrier mice, leading to the arousal of HBsAg-specific follicular Th-germinal center B cell responses and anti-hepatitis B surface Ag Ab production. Recovery of HBsAg-specific responses also correlated with both reduced CD4(+)Foxp3(+) regulatory T cell frequency and an enhanced capacity of effector T cells to overcome inhibition by regulatory T cells. In conclusion, IL-12-based vaccination therapy may reverse liver-induced immune tolerance toward HBV by restoring systemic HBV-specific CD4(+) T cell responses, eliciting robust hepatic HBV-specific CD8(+) T cell responses, and facilitating the generation of HBsAg-specific humoral immunity; thus, this therapy may become a viable approach to treating patients with chronic hepatitis B. PMID:24048897

  11. Lactobacillus rhamnosus GG Reverses Insulin Resistance but Does Not Block Its Onset in Diet-Induced Obese Mice.

    Science.gov (United States)

    Park, Kun-Young; Kim, Bobae; Hyun, Chang-Kee

    2015-05-01

    Recently, Lactobacillus rhamnosus GG (LGG) was shown to exert insulin-sensitizing and adiposity-reducing effects in high-fat (HF) diet-fed mice. In the present study, we observed that the effects were correlated with the extent of dysbiosis induced by HF diet feeding before LGG administration. LGG-treated mice were protected from HF diet-induced adiposity and/ or insulin resistance when LGG was treated after, not along with, HF diet feeding. Results indicate that, under HF dietary condition, supplemented LGG reverses insulin resistance, but does not block its onset. PMID:25433553

  12. Electric fields induce reversible changes in the surface to volume ratio of micropipette-aspirated erythrocytes.

    OpenAIRE

    Katnik, C; Waugh, R

    1990-01-01

    Micropipette-aspirated erythrocytes exhibit reversible changes in sphericity (surface-to-volume ratio) in response to applied electric fields. The potentials were applied between the shaft of the pipette and the bathing medium using Ag-AgCl electrodes and current clamping electronics. The change in surface-to-volume ratio is evidenced as a reversible change in the length of the cell projection in the pipette at constant aspiration pressure and changing voltage. The magnitude of the changes de...

  13. Estimation of neutral-beam-induced field reversal in MFTF by an approximate scaling law

    Energy Technology Data Exchange (ETDEWEB)

    Shearer, J.W.

    1980-04-28

    Scaling rules are derived for field-reversed plasmas whose dimensions are common multiples of the ion gyroradius in the vacuum field. These rules are then applied to the tandem MFTF configuration, and it is shown that field reversal appears to be possible for neutral beam currents of the order of 150 amperes, provided that the electron temperature is at least 500 eV.

  14. Coherence-Induced Reversibility and Collective Operation of Quantum Heat Machines via Coherence Recycling

    Science.gov (United States)

    Uzdin, Raam

    2016-08-01

    Collective behavior, where a set of elements interact and generate effects that are beyond the reach of the individual noninteracting elements, is always of great interest in physics. Quantum collective effects that have no classical analog are even more intriguing. In this work, we show how to construct collective quantum heat machines and explore their performance boosts with respect to regular machines. Without interactions between the machines, the individual units operate in a stochastic, nonquantum manner. The construction of the collective machine becomes possible by introducing two simple quantum operations: coherence extraction and coherence injection. Together, these operations can harvest coherence from one engine and use it to boost the performance of a slightly different engine. For weakly driven engines, we show that the collective work output scales quadratically with the number of engines rather than linearly. Eventually, the boost saturates and then becomes linear. Nevertheless, even in saturation, work is still significantly boosted compared to individual operation. To study the reversibility of the collective machine, we introduce the "entropy-pollution" measure. It is shown that there is a regime where the collective machine is N times more reversible while producing N times more work, compared to the individual operation of N units. Moreover, the collective machine can even be more reversible than the most reversible unit in the collective. This high level of reversibility becomes possible due to a special symbiotic mechanism between engine pairs.

  15. PKMzeta inhibition reverses learning-induced increases in hippocampal synaptic strength and memory during trace eyeblink conditioning.

    Directory of Open Access Journals (Sweden)

    Noelia Madroñal

    Full Text Available A leading candidate in the process of memory formation is hippocampal long-term potentiation (LTP, a persistent enhancement in synaptic strength evoked by the repetitive activation of excitatory synapses, either by experimental high-frequency stimulation (HFS or, as recently shown, during actual learning. But are the molecular mechanisms for maintaining synaptic potentiation induced by HFS and by experience the same? Protein kinase Mzeta (PKMzeta, an autonomously active atypical protein kinase C isoform, plays a key role in the maintenance of LTP induced by tetanic stimulation and the storage of long-term memory. To test whether the persistent action of PKMzeta is necessary for the maintenance of synaptic potentiation induced after learning, the effects of ZIP (zeta inhibitory peptide, a PKMzeta inhibitor, on eyeblink-conditioned mice were studied. PKMzeta inhibition in the hippocampus disrupted both the correct retrieval of conditioned responses (CRs and the experience-dependent persistent increase in synaptic strength observed at CA3-CA1 synapses. In addition, the effects of ZIP on the same associative test were examined when tetanic LTP was induced at the hippocampal CA3-CA1 synapse before conditioning. In this case, PKMzeta inhibition both reversed tetanic LTP and prevented the expected LTP-mediated deleterious effects on eyeblink conditioning. Thus, PKMzeta inhibition in the CA1 area is able to reverse both the expression of trace eyeblink conditioned memories and the underlying changes in CA3-CA1 synaptic strength, as well as the anterograde effects of LTP on associative learning.

  16. Visually induced self-motion sensation adapts rapidly to left-right reversal of vision

    Science.gov (United States)

    Oman, C. M.; Bock, O. L.

    1981-01-01

    Three experiments were conducted using 15 adult volunteers with no overt oculomotor or vestibular disorders. In all experiments, left-right vision reversal was achieved using prism goggles, which permitted a binocular field of vision subtending approximately 45 deg horizontally and 28 deg vertically. In all experiments, circularvection (CV) was tested before and immediately after a period of exposure to reversed vision. After one to three hours of active movement while wearing vision-reversing goggles, 10 of 15 (stationary) human subjects viewing a moving stripe display experienced a self-rotation illusion in the same direction as seen stripe motion, rather than in the opposite (normal) direction, demonstrating that the central neural pathways that process visual self-rotation cues can undergo rapid adaptive modification.

  17. Proton exchange membrane fuel cell reversible performance loss induced by carbon monoxide produced during operation

    Science.gov (United States)

    Decoopman, B.; Vincent, R.; Rosini, S.; Paganelli, G.; Thivel, P.-X.

    2016-08-01

    Cyclic voltammetry measurements at the anode have been carried out and reveal the presence of carbon monoxide in steady-state operation, with pure hydrogen. Experiments have been performed both in single cell and in stack to find out its origin. The contamination of the anode catalyst is partly due the reverse-water gas shift (RWGS) with carbon dioxide from the cathode. However, this study shows a temperature-activated and time-related corrosion mechanism which appears under humidified hydrogen. Due to this degradation mechanism, a reversible 25 mV-loss of performances is observed and can be recovered by oxidizing carbon monoxide on the anode.

  18. 5-FU induced acute toxic leukoencephalopathy: early recognition and reversibility on DWI-MRI.

    Science.gov (United States)

    Maheen Anwar, Shayan Sirat; Mubarak, Fatima; Sajjad, Zafar; Azeemuddin, Muhammad

    2014-03-01

    Acute toxic leukoencephalopathy (ATL) is a rare adverse effect of 5-Fluorouracil (5-FU) chemotherapeutic agent. It is imperative for the radiologist to confidently identify the white matter changes caused by this agent in case of toxicity. This will help in early detection and appropriate management of patient, as the condition is reversible both clinically and on imaging. We report a case of a 29 years old gentleman, known case of carcinoma of esophagus who suffered from acute toxic leukoencephalopathy secondary to leukotoxic therapeutic agent 5-FU, and illustrate the reversible imaging findings of this condition on withdrawal of the inciting agent. PMID:24718016

  19. Chemical alloying induced collapse of reversibility windows in ternary As-S-I glasses*

    Science.gov (United States)

    Wang, Fei; Boolchand, P.

    2006-03-01

    Thermally reversing windows represent glass compositions across which glass transitions are thermally reversing in character. These windows have been observed in several chalcogenide glasses, and are identified^1 with self-organized phases of glassy networks. Upon alloying halogen (iodine) in base chalcogenide glasses (Ge-Se, Ge-S), the reversibility windows collapse^2 about the mean-field rigidity transition. We attempt to understand this behavior better. We have now synthesized ternary glass compositions of the type, (AsI3)x(As0.30S0.70)1-x and (AsI3)y (As2S3)1-y over wide composition ranges of x and y, and have examined them systematically in Raman scattering and MDSC experiments. Along with earlier results^3 on binary AszS1-z glasses, the present results permit mapping the reversibility window over the glass forming range of the present As-S-I ternary. The results show the window region to be of nearly triangular shape, with a base extending in the 0.20 85,3823 (2005). 2. Y. Wang et al. Phys. Rev. Lett. 87, 18, 5503 (2001) 3. D.G. Georgiev, Ph.D. Thesis , Univ. of Cincinnati (2003) unpublished

  20. Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Christian Hafner; Stefanie Meyer; Ilja Hagen; Bernd Becker; Alexander Roesch; Michael Landthaler; Thomas Vogt

    2005-01-01

    AIM: Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells.METHODS: Upon stimulation of ephrin-B pathways in IFC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix(R) rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase (FAK) activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy.RESULTS: Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes.Furthermore, we show that the expression of repairrelated genes is also accompanied by activation of the ERK1/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution.CONCLUSION: Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

  1. The entomopathogenic fungus Beauveria bassiana reduces instantaneous blood feeding in wild multi-insecticide-resistant Culex quinquefasciatus mosquitoes in Benin, West Africa

    Directory of Open Access Journals (Sweden)

    Howard Annabel FV

    2010-09-01

    Full Text Available Abstract Background Mosquito-borne diseases are still a major health risk in many developing countries, and the emergence of multi-insecticide-resistant mosquitoes is threatening the future of vector control. Therefore, new tools that can manage resistant mosquitoes are required. Laboratory studies show that entomopathogenic fungi can kill insecticide-resistant malaria vectors but this needs to be verified in the field. Methods The present study investigated whether these fungi will be effective at infecting, killing and/or modifying the behaviour of wild multi-insecticide-resistant West African mosquitoes. The entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana were separately applied to white polyester window netting and used in combination with either a permethrin-treated or untreated bednet in an experimental hut trial. Untreated nets were used because we wanted to test the effect of fungus alone and in combination with an insecticide to examine any potential additive or synergistic effects. Results In total, 1125 female mosquitoes were collected during the hut trial, mainly Culex quinquefasciatus Say. Unfortunately, not enough wild Anopheles gambiae Giles were collected to allow the effect the fungi may have on this malaria vector to be analysed. None of the treatment combinations caused significantly increased mortality of Cx. quinquefasciatus when compared to the control hut. The only significant behaviour modification found was a reduction in blood feeding by Cx. quinquefasciatus, caused by the permethrin and B. bassiana treatments, although no additive effect was seen in the B. bassiana and permethrin combination treatment. Beauveria bassiana did not repel blood foraging mosquitoes either in the laboratory or field. Conclusions This is the first time that an entomopathogenic fungus has been shown to reduce blood feeding of wild mosquitoes. This behaviour modification indicates that B. bassiana could potentially be a new

  2. Elasticity-induced force reversal between active spinning particles in dense passive media.

    Science.gov (United States)

    Aragones, J L; Steimel, J P; Alexander-Katz, A

    2016-01-01

    The self-organization of active particles is governed by their dynamic effective interactions. Such interactions are controlled by the medium in which such active agents reside. Here we study the interactions between active agents in a dense non-active medium. Our system consists of actuated, spinning, active particles embedded in a dense monolayer of passive, or non-active, particles. We demonstrate that the presence of the passive monolayer alters markedly the properties of the system and results in a reversal of the forces between active spinning particles from repulsive to attractive. The origin of such reversal is due to the coupling between the active stresses and elasticity of the system. This discovery provides a mechanism for the interaction between active agents in complex and structured media, opening up opportunities to tune the interaction range and directionality via the mechanical properties of the medium. PMID:27112961

  3. Disulfiram-induced reversible hypertension: A prospective case series and review of the literature

    Directory of Open Access Journals (Sweden)

    Ranganath R Kulkarni

    2014-01-01

    Full Text Available Disulfiram (DSF is one of the recommended aids in the management of selected patients with alcohol dependence. Hypertension (HTN as an adverse effect of DSF therapy is less understood. In our prospective case series of 7 subjects with co-morbid alcohol and nicotine dependence, a temporal, dose-dependent, and reversible grade 1-3 HTN within 1-6 weeks of initiation of DSF therapy (125-500 mg/day with no other detectable causes of HTN was noted. Challenges and strategies surrounding diagnosis and treatment along with mean change and percentage rise in blood pressure are described. Literature review and clinical description of case series may suggest neurobiological role in its causation. HTN may be a clinically significant, dose-dependent, and reversible adverse effect of DSF therapy, especially in co-morbid alcohol and nicotine-dependent patients. Awareness amongst clinicians may render better health care delivery to subjects with alcohol dependence.

  4. Chronic Intra-Renal Insulin Replacement Reverses Diabetes-Induced Natriuresis and Diuresis

    OpenAIRE

    Manhiani, M. Marlina; Duggan, A. Daniel; Wilson, Hunter; Brands, Michael W.

    2012-01-01

    We recently showed that sustained natriuresis in Type I diabetic dogs was due to the decrease in insulin rather than the hyperglycemia alone. The sodium retaining action of insulin appeared to require hyperglycemia and it completely reversed the diabetic natriuresis and diuresis. This study tested whether the sodium retaining effect was due to direct intrarenal actions of insulin. Alloxan-treated dogs (D; n=7) were maintained normoglycemic using 24hr/day i.v. insulin replacement. After contro...

  5. Lyophilization-induced reversible changes in the secondary structure of proteins.

    OpenAIRE

    Griebenow, K; Klibanov, A M

    1995-01-01

    Changes in the secondary structure of some dozen different proteins upon lyophilization of their aqueous solutions have been investigated by means of Fourier-transform infrared spectroscopy in the amide III band region. Dehydration markedly (but reversibly) alters the secondary structure of all the proteins studied, as revealed by both the quantitative analysis of the second derivative spectra and the Gaussian curve fitting of the original infrared spectra. Lyophilization substantially increa...

  6. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia

    DEFF Research Database (Denmark)

    Duvaldestin, Philippe; Kuizenga, Karel; Saldien, Vera;

    2010-01-01

    Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...... blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium.......Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...

  7. Glytube: a conical tube and parafilm M-based method as a simplified device to artificially blood-feed the dengue vector mosquito, Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    André Luis Costa-da-Silva

    Full Text Available Aedes aegypti, the main vector of dengue virus, requires a blood meal to produce eggs. Although live animals are still the main blood source for laboratory colonies, many artificial feeders are available. These feeders are also the best method for experimental oral infection of Ae. aegypti with Dengue viruses. However, most of them are expensive or laborious to construct. Based on principle of Rutledge-type feeder, a conventional conical tube, glycerol and Parafilm-M were used to develop a simple in-house feeder device. The blood feeding efficiency of this apparatus was compared to a live blood source, mice, and no significant differences (p = 0.1189 were observed between artificial-fed (51.3% of engorgement and mice-fed groups (40.6%. Thus, an easy to assemble and cost-effective artificial feeder, designated "Glytube" was developed in this report. This simple and efficient feeding device can be built with common laboratory materials for research on Ae. aegypti.

  8. Blood feeding patterns of Nyssomyia intermedia and Nyssomyia neivai (Diptera, Psychodidae in a cutaneous leishmaniasis endemic area of the Ribeira Valley, State of São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Ana Maria Marassa

    2013-09-01

    Full Text Available Introduction The aim of this study was to identify the blood feeding sources of Nyssomyia intermedia (Ny. intermedia and Nyssomyia neivai (Ny. neivai, which are Leishmania vectors and the predominant sandfly species in the Ribeira Valley, State of São Paulo, Brazil, an endemic area for cutaneous leishmaniasis. Methods Specimens were captured monthly between February 2001 and December 2003 on a smallholding and a small farm situated in the Serra district in the Iporanga municipality. The blood meals of 988 engorged females were tested using the avidin-biotin immunoenzymatic enzyme-linked immunosorbent assay (ELISA. Seven blood meal sources were investigated: human, dog, chicken, bovine, pig, horse and rat. Results The results showed that among the females that fed on one or more blood sources, the respective percentages for Ny. intermedia and Ny. neivai, respectively, were as follows: human (23% and 36.8%, pig (47.4% and 26.4%, chicken (25.7% and 36.8% and dog (3.9% and 0%, and the differences in the blood sources between the two species were statistically significant (p = 0.043. Conclusions Both species had predominant reactivity for one or two blood sources, and few showed reactivity indicating three or four sources. Many different combinations were observed among the females that showed reactivity for more than one source, which indicated their opportunistic habits and eclecticism regarding anthropic environmental conditions.

  9. INHALATION OF OZONE AND DIESEL EXHAUST PARTICLES (DEP) INDUCES ACUTE AND REVERSIBLE CARDIAC GENE EXPRESSION CHANGES

    Science.gov (United States)

    We have recently shown that episodic but not acute exposure to ozone or DEP induces vascular effects that are associated with the loss of cardiac mitochondrial phospholipid fatty acids (DEP 2.0 mg/m3 > ozone, 0.4 ppm). In this study we determined ozone and DEP-induced cardiac gen...

  10. Synthesis and Pressure-induced Reversible Phase Transition of a Crystalline Solid Europium Germanate NaEuGeO4

    Institute of Scientific and Technical Information of China (English)

    赵鑫光; 王凯; 颜婷婷; 颜岩; 邹勃; 于吉红; 徐如人

    2012-01-01

    The crystalline solid europium germanate NaEuGeO4 was prepared under hydrothermal conditions. The in-situ photoluminescence spectroscopic measurement and the synchrotron X-ray diffraction analysis in a diamond anvil cell (DAC) under high pressure were performed to study the pressure-induced phase transition of NaEuGeO4 as well as changes of the luminescent properties of Eu3+ ions. Photoluminescence spectroscopic studies revealed that a phase transition occurred at a pressure range of 6.5--10 GPa and the high-pressure phase of NaEuGeO4 (NaEu- GeO4-HP) was still stable when the pressure raised up to about 20 GPa. As the pressure was released, the spectra returned to the original state, revealing that the pressure-induced phase transition is a completely reversible process. The synchrotron X-ray diffraction analysis demonstrated that the structure of NaEuGeO4 transformed to an uniden- tified phase NaEuGeO4-HP at a pressure higher than 10 GPa, and the phase transition is reversible. This result is consisted with that obtained by photoluminescence spectra analysis.

  11. β-Asarone Reverses Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior and Promotes Hippocampal Neurogenesis in Rats

    Directory of Open Access Journals (Sweden)

    Haiying Dong

    2014-04-01

    Full Text Available In this study, we investigated the influence of β-asarone, the major ingredient of Acorus tatarinowii Schott, on depressive-like behavior induced by the chronic unpredictable mild stresses (CUMS paradigm and to clarify the underlying mechanisms. The results show that β-asarone treatment partially reversed the CUMS-induced depression-like behaviors in both the forced swim and sucrose preference tests. The behavioral effects were associated with increased hippocampal neurogenesis indicated by bromodeoxyuridine (BrdU immunoreactivity. β-Asarone treatment significantly increased the expression of brain-derived neurotrophic factor (BDNF at levels of transcription and translation. Moreover, CUMS caused significant reduction in ERK1/2 and CREB phosphorylation, both of which were partially attenuated by β-asarone administration. It is important to note that β-asarone treatment had no effect on total levels or phosphorylation state of any of the proteins examined in ERK1/2-CREB pathway in no stress rats, suggesting that β-asarone acts in a stress-dependent manner to block ERK1/2-CREB signaling. We did not observe a complete reversal of depression-like behaviors to control levels by β-asarone. To our knowledge, the present study is the first to demonstrate that adult neurogenesis is involved in the antidepressant-like behavioral effects of β-asarone, suggesting that β-asarone is a promising candidate for the treatment of depression.

  12. Levetiracetam induced acute reversible psychosis in a patient with uncontrolled seizures

    OpenAIRE

    Nithin Kumar; H S Swaroop; Ananya Chakraborty; Suhas Chandran

    2014-01-01

    Levetiracetam (LEV) is a relatively newer antiepileptic drug with novel mechanism of action. It was introduced to the market in the year 2000. Pre-marketing clinical trials of the drug reported good tolerability with a wide safety margin. On post-marketing updates, there are few reports of psychosis after treatment with the drug. Here, we report a case of 52-year-old epileptic man who developed acute, reversible psychosis within 3 days of initiation of treatment. The drug was prescribed at a ...

  13. Severe reversible toxic encephalopathy induced by cisplatin in a patient with cervical carcinoma receiving combined radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Sterzing, F.; Grehn, C.; Dinkel, J.; Krempien, R.; Hartung, G.; Debus, J.; Harms, W. [University of Heidelberg Medical School (Germany). Dept. of Radiation Oncology

    2007-09-15

    Case Report: A 45-year-old patient with cervix carcinoma received combined radiochemotherapy including cisplatin. After a cumulative dose of 240 mg/m{sup 2} the patient suddenly became somnolent and developed a severe tetraparesis and generalized seizures. After ruling out intracranial bleeding, cerebral metastases as well as infectious and metabolic causes of this condition, a severe toxic encephalopathy was diagnosed based on the clinical findings and MRI scans. After symptomatic treatment on the intensive care unit all symptoms were completely reversible. Conclusion: Toxic encephalopathy is a rare but dramatic complication of various cytostatic drugs. With the widespread use of cisplatin this rare disorder should be kept in mind. (orig.)

  14. Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

    International Nuclear Information System (INIS)

    Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in 45Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker

  15. Steam-cooking rapidly destroys and reverses onion-induced antiplatelet activity

    Directory of Open Access Journals (Sweden)

    Hansen Emilie A

    2012-09-01

    Full Text Available Abstract Background Foods in the diet that can aid in the prevention of diseases are of major interest. Onions are key ingredients in many cuisines around the world and moreover, onion demand has trended higher over the past three decades. An important pharmacological aspect of onion is the ability to inhibit platelet aggregation. Raw onions inhibit platelet aggregation; however, when onions are boiled or heated, antiplatelet activity may be abolished. Methods Onion quarters were steamed for 0, 1, 3, 6, 10, and 15 min. The in vitro antiplatelet activity of a yellow hybrid storage onion was examined at these times on the blood of 12 human subjects using in vitro whole blood aggregometry. Results Contrary to findings reported for boiling, antiplatelet activity was destroyed between 3 and 6 min of steaming, and at 10 min of steaming, cooked onions stimulated platelet activity. Extracts from cooked onion had the potential to reverse the inhibitory effect on blood platelets by 25%. Responses were consistent across all donors. Total polyphenolic concentration and soluble solids were not affected by steaming time. Conclusions The potential value of cooked onion preparations may result in destruction or reversal of antiplatelet activity, without affecting the polyphenolic concentration.

  16. Observation on the repeated blood?feeding habit of Aedes albopictus in Shenzhen%深圳市白纹伊蚊重复吸血习性观察

    Institute of Scientific and Technical Information of China (English)

    张韶华; 刘强; 刘阳; 梁焯南; 唐秀娟

    2015-01-01

    目的 研究深圳市白纹伊蚊吸血、产卵习性,探讨其传播登革热的风险.方法 在实验室饲养白纹伊蚊,定时人工饲血,记录吸血及产卵时间、频次、产卵量等.结果 白纹伊蚊一生吸血次数中位数为9,最多吸血16次;一生产卵次数中位数为4,最多产卵7次;一生平均产卵数204枚,最多372枚;一个产次内吸血次数中位数为2,最多为10次;一个产次内产卵数为13~142枚,中位数为56;一个产次内第一次吸血到产卵天数为2~17 d,中位数为4.结论 深圳市白纹伊蚊普遍存在多次吸血、多次产卵的现象,对登革热的传播有较重要意义.%Objective To study the blood?feeding and oviposition habits of Aedes albopictus, and discuss the risk of dengue fever transmission in Shenzhen. Methods Aedes albopictus were raised in laboratory by feeding blood regularly, the time and frequency of blood?feeding and oviposition were recorded, as well as the egg production and other indicators. Results The median of blood feeding times was 9 in the lifetime of Ae. albopictus, while the maximum was 16, the median oviposition times was 4 in the lifetime, while the maximum was 7, the average of egg production is 204, while the maximum was 372. The median of blood feedings was 2 in one parity,while the maximum was 10,The median of egg production was 56 in one parity(range:13-142). The median days from first blood feeding to oviposition was 4 in one parity(range:2-17). Conclusion The habits of blood feeding and oviposition repeatedly was widespread among the Ae. albopictus populations in Shenzhen,this habits could be important significance for the spread of dengue fever.

  17. Reversible structural alterations of undifferentiated and differentiated human neuroblastoma cells induced by phorbol ester.

    OpenAIRE

    Tint, I S; Bonder, E. M.; Feder, H. H.; Reboulleau, C P; Vasiliev, J M; Gelfand, I M

    1992-01-01

    Morphological alterations in the structure of undifferentiated and morphologically differentiated human neuroblastoma cells induced by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, were examined by video microscopy and immunomorphology. In undifferentiated cells, PMA induced the formation of motile actin-rich lamellas and of stable cylindrical processes rich in microtubules. Formation of stable processes resulted either from the collapse of lamellas or the movement ...

  18. Heritability and Reversibility of DNA Methylation Induced by in vitro Grafting between Brassica juncea and B. oleracea.

    Science.gov (United States)

    Cao, Liwen; Yu, Ningning; Li, Junxing; Qi, Zhenyu; Wang, Dan; Chen, Liping

    2016-01-01

    Grafting between tuber mustard and red cabbage produced a chimeric shoot apical meristem (SAM) of TTC, consisting of Layers I and II from Tuber mustard and Layer III from red Cabbage. Phenotypic variations, which mainly showed in leaf shape and SAM, were observed in selfed progenies GSn (GS = grafting-selfing, n = generations) of TTC. Here the heritability of phenotypic variation and its association with DNA methylation changes in GSn were investigated. Variation in leaf shape was found to be stably inherited to GS5, but SAM variation reverted over generations. Subsequent measurement of DNA methylation in GS1 revealed 5.29-6.59% methylation changes compared with tuber mustard (TTT), and 31.58% of these changes were stably transmitted to GS5, but the remainder reverted to the original status over generations, suggesting grafting-induced DNA methylation changes could be both heritable and reversible. Sequence analysis of differentially methylated fragments (DMFs) revealed methylation mainly changed within transposons and exon regions, which further affected the expression of genes, including flowering time- and gibberellin response-related genes. Interestingly, DMFs could match differentially expressed siRNA of GS1, GS3 and GS5, indicating that grafting-induced DNA methylation could be directed by siRNA changes. These results suggest grafting-induced DNA methylation may contribute to phenotypic variations induced by grafting. PMID:27257143

  19. Inhibition of phosphodiesterase-4 reverses the cognitive dysfunction and oxidative stress induced by Aβ25-35 in rats.

    Science.gov (United States)

    Zhuo, Yeye; Guo, Haibiao; Cheng, Yufang; Wang, Chuang; Wang, Canmao; Wu, Jingang; Zou, Zhengqiang; Gan, Danna; Li, Yiwen; Xu, Jiangping

    2016-08-01

    Phosphodiesterase-4 (PDE4) inhibitors prevent the breakdown of the second messenger cAMP and have been demonstrated to improve learning in several animal models of cognition. In this study, we explored the antioxidative effects of rolipram in Alzheimer's disease (AD) by using bilateral Aβ25-35 injection into the hippocampus of rats, which were used as an AD model. Rats received 3 intraperitoneal (i.p.) doses of rolipram (0.1, 0.5 and 1.25 mg/kg) daily after the injection of Aβ25-35 for 25 days. Chronic administration of rolipram prevented the memory impairments induced by Aβ25-35, as assessed using the passive avoidance test and the Morris water maze test. Furthermore, rolipram significantly reduced the oxidative stress induced by Aβ25-35, as evidenced by the decrease in the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and restored the reduced GSH levels and superoxide dismutase (SOD) activity. Moreover, western blotting and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis showed that rolipram remarkably upregulated thioredoxin (Trx) and inhibited the inducible nitric oxide synthase/nitric oxide (iNOS/NO) pathway in the hippocampus. These results demonstrated that rolipram improved the learning and memory abilities in an Aβ25-35-induced AD rat model. The mechanism underlying these effects may be due to the noticeable antioxidative effects of rolipram. PMID:26920899

  20. The atypical antipsychotic blonanserin reverses (+)-PD-128907- and ketamine-induced deficit in executive function in common marmosets.

    Science.gov (United States)

    Kotani, Manato; Enomoto, Takeshi; Murai, Takeshi; Nakako, Tomokazu; Iwamura, Yoshihiro; Kiyoshi, Akihiko; Matsumoto, Kenji; Matsumoto, Atsushi; Ikejiri, Masaru; Nakayama, Tatsuo; Ogi, Yuji; Ikeda, Kazuhito

    2016-05-15

    Antagonism of the dopamine D3 receptor is considered a promising strategy for the treatment of cognitive impairment associated with schizophrenia. We have previously reported that the atypical antipsychotic blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptor antagonist, highly occupies dopamine D3 receptors at its antipsychotic dose range in rats. In the present study, we evaluated the effects of blonanserin on executive function in common marmosets using the object retrieval with detour (ORD) task. The dopamine D3 receptor-preferring agonist (+)-PD-128907 at 1mg/kg decreased success rate in the difficult trial, but not in the easy trial. Since the difference between the two trials is only cognitive demand, our findings indicate that excess activation of dopamine D3 receptors impairs executive function in common marmosets. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by (+)-PD-128907 in the difficult trial. This finding indicates that blonanserin has beneficial effect on executive function deficit induced by activation of the dopamine D3 receptor in common marmosets. Next, and based on the glutamatergic hypothesis of schizophrenia, the common marmosets were treated with the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine. Ketamine at sub-anesthetic doses decreased success rate in the difficult trial, but not in the easy trial. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by ketamine in the difficult trial. The findings of this study suggest that blonanserin might have beneficial effect on executive dysfunction in patients with schizophrenia. PMID:26970575

  1. Berberine reverses free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM:To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-LI adipocytes.METHODS:The model of insulin resistance in 3T3-L1 adipocytes was established by adding palmic acid (0.5 mmol/L) to the culture medium.Berberine treatment was performed at the same time.Glucose uptake rate was determined by the 2-deoxy-[3H]-Dglucose method.The levels of IkB kinase beta (IKKβ)Ser181 phosphorylation,insulin receptor substrate1(IRS-1) Ser307 phosphorylation,expression of IKKβ,IRS-1,nuclear transcription factor kappaB p65 (NF-κB p65),phosphatidylinositol-3-kinase p85(PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting.The distribution of NF-κB p65 proteins inside the adipocytes was observed through confocal laser scanning microscopy(CLSM).RESULTS:After the intervention of palmic acid for 24 h,the insulin-stimulated glucose transport in 3T3-L1 adipocytes was inhibited by 67%.Meanwhile,the expression of IRS-1 and PI-3K p85 protein was reduced,while the levels of IKKβ Ser181 and IRS-1 Ser307 phosphorylation,and nuclear translocation of NF-κB p65 protein were increased.However,the above indexes,which indicated the existence of insulin resistance,were reversed by berberine although the expression of GLUT4,IKKβ and total NF-κB p65 protein were not changed during this study.CONCLUSION:Insulin resistance induced by FFAs in 3T3-L1 adipocytes can be improved by berberine.Berberine reversed free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ.

  2. Reverse lung clearance of Tc-99m DTPA induced by postural changes

    International Nuclear Information System (INIS)

    The lung clearance of Tc 99m DTPA is generally attributed to the degree of distension of the interepithelial junctions and thus of the alveoli. To assess this hypothesis a submicronic aerosol of Tc 99m DTPA (0.5 μ mass median diameter) was inhaled by eight non smoking volunteers placed in left lateral decubitus (LLD) where the alveoli of the left lung are compressed and those of the right lung expanded. The lung radioactivity was followed with a gamma camera 15 minutes in LLD, then 15 minutes in right lateral decubitus (RLD) to reverse the relative distension of the alveoli. Regional clearances were computed on each lung divided in three horizontal slices. These results suggest that alveolar distension has a major role in the DTPA clearance which is relatively independent of the initial deposition of the aerosol

  3. Resonance, Multi-resonance, and Reverse-resonance Induced by Multiplicative Dichotomous Noise

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A constant-potential system driven by multiplicative dichotomous noise and subject to an input oscillatory signal is investigated. Two phenomena of stochastic resonance are observed. One is the response as a function of the noise's parameters; the other is that as a function of the input signal frequency. A phenomenon of multi-resonance (there are three or four peaks) is found for the response as a function of a parameter of the noise. A phenomenon of reverse-resonance is found, for which the response of the system to the signal can be weakened by the presence of the noise (there is an optimal minimum). These results help in studies of the systems with multiplicative dichotomous noise, such as the semiconductor, the proteins motor, the chemical reaction, and so on.

  4. Diffusivity induced by vortex-like coherent structures in Reversed Field Pinch plasmas

    International Nuclear Information System (INIS)

    Coherent structures emerging from the background turbulence have been detected by electrostatic measurements in the edge region of two Reversed Field Pinch experiments, RFX (Padua) and Extrap-T2R (Stockholm). Measurements have been performed by arrays of Langmuir probes which allowed simultaneous measurements of temperature, potential and density to be carried out. These structures have been interpreted as a dynamic balance of dipolar and unipolar vortices, whose relative population are found to depend on the local mean E x B flow shear. The contribution to the anomalous transport of these structures has been investigated and it has been found that the corresponding diffusion coefficient accounts up to 50% of the total diffusivity. The experimental findings indicate that the diffusion coefficient associated to the coherent structures depends on the relative population of the two types of vortices and is minimum when the two populations are equal. An interpretive model is proposed to explain this feature. (authors)

  5. Reversible-Deactivation Radical Polymerization of Methyl Methacrylate Induced by Photochemical Reduction of Various Copper Catalysts

    Directory of Open Access Journals (Sweden)

    Jaroslav Mosnáček

    2014-11-01

    Full Text Available Photochemically mediated reversible-deactivation radical polymerization of methyl methacrylate was successfully performed using 50–400 ppm of various copper compounds such as CuSO4·5H2O, copper acetate, copper triflate and copper acetylacetonate as catalysts. The copper catalysts were reduced in situ by irradiation at wavelengths of 366–546 nm, without using any additional reducing agent. Bromopropionitrile was used as an initiator. The effects of various solvents and the concentration and structure of ligands were investigated. Well-defined polymers were obtained when at least 100 or 200 ppm of any catalyst complexed with excess tris(2-pyridylmethylamine as a ligand was used in dimethyl sulfoxide as a solvent.

  6. Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lep(ob)) mice

    Science.gov (United States)

    Winters, B.; Mo, Z.; Brooks-Asplund, E.; Kim, S.; Shoukas, A.; Li, D.; Nyhan, D.; Berkowitz, D. E.

    2000-01-01

    Obesity is a major health care problem and is associated with significant cardiovascular morbidity. Leptin, a neuroendocrine hormone released by adipose tissue, is important in modulating obesity by signaling satiety and increasing metabolism. Moreover, leptin receptors are expressed on vascular endothelial cells (ECs) and mediate angiogenesis. We hypothesized that leptin may also play an important role in vasoregulation. We investigated vasoregulatory mechanisms in the leptin-deficient obese (ob/ob) mouse model and determined the influence of leptin replacement on endothelial-dependent vasorelaxant responses. The direct effect of leptin on EC nitric oxide (NO) production was also tested by using 4, 5-diaminofluorescein-2 diacetate staining and measurement of nitrate and nitrite concentrations. Vasoconstrictor responses to phenylephrine, norepinephrine, and U-46619 were markedly enhanced in aortic rings from ob/ob mice and were modulated by NO synthase inhibition. Vasorelaxant responses to ACh were markedly attenuated in mesenteric microvessels from ob/ob mice. Leptin replacement resulted in significant weight loss and reversal of the impaired endothelial-dependent vasorelaxant responses observed in ob/ob mice. Preincubation of ECs with leptin enhanced the release of NO production. Thus leptin-deficient ob/ob mice demonstrate marked abnormalities in vasoregulation, including impaired endothelial-dependent vasodilation, which is reversed by leptin replacement. These findings may be partially explained by the direct effect of leptin on endothelial NO production. These vascular abnormalities are similar to those observed in obese, diabetic, leptin-resistant humans. The ob/ob mouse may, therefore, be an excellent new model for the study of the cardiovascular effects of obesity.

  7. Carvacrol partially reverses symptoms of diabetes in STZ-induced diabetic rats

    OpenAIRE

    Bayramoglu, Gokhan; Senturk, Hakan; Bayramoglu, Aysegul; Uyanoglu, Mustafa; Colak, Suat; Ozmen, Ayse; Kolankaya, Durdane

    2013-01-01

    Little is known about the protective effects of carvacrol on the symptoms of streptozotocin induced diabetes in rats. Hence, this present study was designed to evaluate the protective effect of the strong antioxidant, carvacrol, on the symptoms of streptozotocin induced diabetes in rats. Carvacrol at the doses of 25 and 50 mg/kg body weight were orally administered to diabetic rats for a period of 7 days after the onset of diabetes. Food-water intake and body weight changes were daily recorde...

  8. Prevention and reversal by cocaine esterase of cocaine-induced cardiovascular effects in rats

    OpenAIRE

    Wood, Susan K.; Narasimhan, Diwahar; Cooper, Ziva; Sunahara, Roger K; Woods, James H.

    2009-01-01

    The present study is the first to utilize bacterial cocaine esterase (CocE) to increase elimination of a lethal dose of cocaine and evaluate its cardioprotective effects. Rats received one of 5 treatments: CocE 1 min after saline; CocE 1 min after a lethal i.p. dose of cocaine; saline 1 min after a lethal i.p. dose of cocaine; CocE immediately after observing a cocaine-induced convulsion; and CocE 1 min after observing a cocaine-induced convulsion. Measures were taken of ECG, blood pressure, ...

  9. Magnetization reversal induced by in-plane current in Ta/CoFeB/MgO structures with perpendicular magnetic easy axis

    International Nuclear Information System (INIS)

    We investigate in-plane current-induced magnetization reversal under an in-plane magnetic field in Hall bar shaped devices composed of Ta/CoFeB/MgO structures with perpendicular magnetic easy axis. The observed relationship between the directions of current and magnetization switching and Ta thickness dependence of magnetization switching current are accordance with those for magnetization reversal by spin transfer torque originated from the spin Hall effect in the Ta layer

  10. Weight loss reversed obesity-induced HGF/c-Met pathway and basal-like breast cancer progression

    Directory of Open Access Journals (Sweden)

    Sneha eSundaram

    2014-07-01

    Full Text Available Epidemiologic studies demonstrate that obesity is associated with an aggressive subtype of breast cancer called basal-like breast cancer (BBC. Using the C3(1-TAg murine model of BBC, we previously demonstrated that mice displayed an early onset of tumors when fed obesogenic diets in the adult window of susceptibility. Obesity was also shown to elevate mammary gland expression and activation of hepatocyte growth factor (HGF/c-Met compared to lean controls, a pro-tumorigenic pathway associated with BBC in patients. Epidemiologic studies estimate that weight loss could prevent a large proportion of BBC. We sought to investigate whether weight loss in adulthood prior to tumor onset would protect mice from accelerated tumorigenesis observed in obese mice. Using a life-long model of obesity, C3(1-TAg mice were weaned onto and maintained on an obesogenic high fat diet. Obese mice displayed significant elevations in tumor progression, but not latency or burden. Tumor progression was significantly reversed when obese mice were induced to lose weight by switching to a control low fat diet prior to tumor onset compared to mice maintained on obesogenic diet. It is likely that other factors regulated tumor progression, hence we investigated the HGF/c-Met pathway known to regulate tumorigenesis. Importantly, HGF/c-Met expression in normal mammary glands and c-Met in tumors was elevated with obesity and was significantly reversed with weight loss. Changes in tumor growth could not be explained by measures of HGF action including phospho-AKT or phospho-S6. Other mediators associated with oncogenesis such as hyperinsulinemia and a high leptin/adiponectin ratio were elevated by obesity and reduced with weight loss. In sum, weight loss significantly blunted the obesity-responsive pro-tumorigenic HGF/c-Met pathway and improved several metabolic risk factors associated with BBC, which together may have contributed to the dramatic reversal of obesity-driven tumor

  11. Peripheral kisspeptin reverses short photoperiod-induced gonadal regression in Syrian hamsters by promoting GNRH release

    DEFF Research Database (Denmark)

    Ansel, L; Bentsen, A H; Ancel, C;

    2011-01-01

    of hamsters kept in SD was reactivated by two daily i.p. injections of Kp54 but not by chronic subcutaneous delivery of the same peptide via mini-pumps. Acute i.p. injection of Kp54-induced FOS (c-Fos) expression in a large number of GNRH neurons and pituitary gonadotrophs together with a strong...

  12. Vagotomy Reverses Established Allergen-Induced Airway Hyperreactivity to Methacholine in the Mouse

    Science.gov (United States)

    We evaluated the role of vagal reflexes in a mouse model of allergen-induced airway hyperreactivity. Mice were actively sensitized to ovalbumin then exposed to the allergen via inhalation. Prior to ovalbumin inhalation, mice also received intratracheally-instilled particulate ma...

  13. Reversion by ozone treatment of acute nephrotoxicity induced by cisplatin in rats

    Directory of Open Access Journals (Sweden)

    Ricardo González

    2004-01-01

    Full Text Available BACKGROUND: Ozone therapy has become a useful treatment for pathological processes, in which the damage mediated by reactive oxygen species is involved. Several lines of evidence suggest that cisplatin-induced acute nephrotoxicity is partially mediated by reactive oxygen species.

  14. Loxapine for Reversal of Antipsychotic-Induced Metabolic Disturbances: A Chart Review

    Science.gov (United States)

    Jain, Seema; Andridge, Rebecca; Hellings, Jessica A.

    2016-01-01

    Loxapine substitution is a promising option for patients with autism spectrum disorder (ASD) who develop antipsychotic-induced metabolic illness. We performed a chart review of 15 adolescents and adults meeting DSM-IV-TR criteria for ASD, all with antipsychotic-associated weight gain, who received low dose loxapine in an attempt to taper or…

  15. The unfolded protein response mediates reversible tau phosphorylation induced by metabolic stress

    NARCIS (Netherlands)

    van der Harg, J. M.; Nolle, A.; Zwart, R.; Boerema, A. S.; van Haastert, E. S.; Strijkstra, A. M.; Hoozemans, J. J. M.; Scheper, W.

    2014-01-01

    The unfolded protein response (UPR) is activated in neurodegenerative tauopathies such as Alzheimer's disease (AD) in close connection with early stages of tau pathology. Metabolic disturbances are strongly associated with increased risk for AD and are a potent inducer of the UPR. Here, we demonstra

  16. Further characterization of the reverse transcriptase associated with porcine (radiation-induced) retroviruses

    International Nuclear Information System (INIS)

    Differential centrifugation and affinity chromatography were used to purify the porcine, radiation-induced retrovirus, RNA-dependent DNA polymerase. The purified RDDP was taken differentiated from cellular DNA polymerase γ by its template specificity, chromatographic characteristics, and the optimum reaction conditions required for DNA synthesis

  17. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    Science.gov (United States)

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. PMID:26364584

  18. Reversal of morphine-induced respiratory depression by doxapram in anesthetized rats.

    Science.gov (United States)

    Haji, Akira; Kimura, Satoko; Ohi, Yoshiaki

    2016-06-01

    The present study was undertaken to investigate whether doxapram, a blocker of tandem pore K(+) (TASK-1/-3) channels, is a useful tool for recovery from morphine-induced ventilatory disturbances. Spontaneous ventilation and the hind leg withdrawal response against noxious thermal stimulation were recorded simultaneously in anesthetized rats. Morphine (1.0mg/kg, i.v.) decreased the minute volume resulting from depression of the ventilatory rate and tracheal airflow. Concomitantly, it prolonged the latency of withdrawal response against the thermal stimulation. Subsequent intravenous injection of doxapram recovered the morphine-induced ventilatory depression. This effect of doxapram declined rapidly after a single injection (1.0-3.0mg/kg, i.v.) but persisted with a continuous infusion (0.33mg/kg/min). Neither single injection nor continuous infusion of doxapram had any detectable effect on the analgesic potency of morphine. The central respiratory activity was recorded from the phrenic nerve in anesthetized, vagotomized, paralyzed and artificially ventilated rats. Morphine (3.0mg/kg, i.v.) induced respiratory depression, characterized by a prolonged plateau-like inspiratory discharge (apneustic discharge) in the phrenic nerve. Doxapram (10mg/kg, i.v.) restored the morphine-induced apneustic discharge to an augmenting inspiratory discharge. This study demonstrated that doxapram counteracted morphine-induced respiratory depression by stimulating the central respiratory network without compromising morphine antinociception. These results support the clinical use of doxapram for amelioration of ventilatory disturbances in patients treated with opioids. PMID:27038521

  19. Go-6976 reverses hyperglycemia-induced insulin resistance independently of cPKC inhibition in adipocytes.

    Science.gov (United States)

    Robinson, Katherine A; Hegyi, Krisztina; Hannun, Yusuf A; Buse, Maria G; Sethi, Jaswinder K

    2014-01-01

    Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used "specific" inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not -β) was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway. PMID:25330241

  20. Temperature-induced reversible self-assembly of diphenylalanine peptide and the structural transition from organogel to crystalline nanowires.

    Science.gov (United States)

    Huang, Renliang; Wang, Yuefei; Qi, Wei; Su, Rongxin; He, Zhimin

    2014-01-01

    Controlling the self-assembly of diphenylalanine peptide (FF) into various nanoarchitectures has received great amounts of attention in recent years. Here, we report the temperature-induced reversible self-assembly of diphenylalanine peptide to microtubes, nanowires, or organogel in different solvents. We also find that the organogel in isopropanol transforms into crystalline flakes or nanowires when the temperature increases. The reversible self-assembly in polar solvents may be mainly controlled by electronic and aromatic interactions between the FF molecules themselves, which is associated with the dissociation equilibrium and significantly influenced by temperature. We found that the organogel in the isopropanol solvent made a unique transition to crystalline structures, a process that is driven by temperature and may be kinetically controlled. During the heating-cooling process, FF preferentially self-assembles to metastable nanofibers and organogel. They further transform to thermodynamically stable crystal structures via molecular rearrangement after introducing an external energy, such as the increasing temperature used in this study. The strategy demonstrated in this study provides an efficient way to controllably fabricate smart, temperature-responsive peptide nanomaterials and enriches the understanding of the growth mechanism of diphenylalanine peptide nanostructures. PMID:25520600

  1. Molecular characterization and immunolocalization of the olfactory co-recepter Orco from two blood-feeding muscid flies, the stable fly (Stomoxys calcitrans, L.) and the horn fly (Haematobia irritans irritans, L.)

    OpenAIRE

    Olafson, Pia Untalan

    2013-01-01

    Biting flies are economically important, blood-feeding pests of medical and veterinary significance. Chemosensory-based biting fly behaviors, such as host/nutrient source localization and ovipositional site selection, are intriguing targets for the development of supplemental control strategies. In an effort to expand our understanding of biting fly chemosensory pathways, transcripts encoding the highly conserved insect odorant co-receptor (Orco) were isolated from two representative biting f...

  2. Frequent blood-feeding and restrictive sugar-feeding behavior enhance the malaria vector potential of Anopheles gambiae s.l. and An. funestus (Diptera:Culicidae) in western Kenya.

    Science.gov (United States)

    Beier, J C

    1996-07-01

    Natural blood-feeding and sugar-feeding behaviors were investigated for populations of Anopheles gambiae s.l. and An. funestus Giles at 2 sites in western Kenya. During peak levels of malaria parasite transmission, > 85% of 1,569 indoor-resting females contained fresh blood meals. Findings that up to 55.4% of blood-fed resting females and 72.0% of host-seeking females had either stage IV or V oocytes provided strong evidence that females were refeeding before oviposition. Such gonotrophic discordance was common throughout the year for both An. gambiae s.l. and An. funestus. Determinations of gonotrophic cycles for freshly blood-fed mosquitoes collected inside houses indicated that only 60.0% of 1,287 An. gambiae s.l. and 60.0% of 974 An. funestus oviposited eggs after a single blood meal. The timing of oviposition was irregular as indicated by relatively high coefficients of variation for An. gambiae s.l. (44.0%) and An. funestus (35.9%). Associated with frequent blood feeding was a surprisingly low rate of sugar feeding; only 6.3% of 1,183 indoor-resting and only 14.4% of 236 host-seeking anophelines were positive for fructose. Natural patterns of frequent blood feeding, year-round gonotrophic discordance, irregular oviposition cycles, and limited sugar feeding illustrate that anopheline mosquitoes have complex behavioral and physiologic means for adapting to their environment. In western Kenya, for example, adaptations for frequent blood feeding by An. gambiae s.l. and An. funestus potentiates their ability to transmit malaria parasites, well beyond that predicted by standard measures of vectorial capacity. PMID:8699456

  3. In situ photoluminescence/Raman study of reversible photo-induced structural transformation of nc-Si

    International Nuclear Information System (INIS)

    A cubic-to-hexagonal phase transition in Si nanocrystals (NCs) is observed in situ by recording their Raman and photoluminescence (PL) spectra simultaneously. The formation of the hexagonal structure is concluded from the appearance of characteristic Raman peaks and intense PL with spectral positions reported previously for hexagonal Si. The phase transition occurs due to heating of the NCs by the laser beam, but it is supposed to be a photo-induced effect, as it does not occur as a consequence of solely thermal heating. Both the structural transition and concomitant switching of the bright PL emission are reversible and are supposed to be of interest from the viewpoint of application. (paper)

  4. Laser Induced Reverse Transfer with metal and hybrid material prepared with sol–gel process used on glass substrate

    International Nuclear Information System (INIS)

    This article presents a possible use of Laser Induced Reverse Transfer (LIRT) for metal deposition combined with hybrid material prepared using the sol–gel process. The goal was to obtain two dimensional metal gratings with inorganic–organic hybrid material protection on low cost glass substrates. The hybrid material using the sol–gel material is employed here to give better adhesion of metal deposited by LIRT on glass substrates, and also to possibly cover the metal structure. The hybrid material was an organically modified silicate glass based on methacryloxypropyltri-methoxysilane (MATPMS) and zirconium propoxide. The proposed process permits to prototype rapidly small diffractive structure in amplitude mode or to mark two dimensional complicated patterns without complex technologies employing a focalized and computer controlled Nd–YAG laser at 1064 nm. The different steps of the technology are also discussed.

  5. Electric Field Induced Reversible Phase Transition in Li Doped Phosphorene: Shape Memory Effect and Superelasticity.

    Science.gov (United States)

    Deng, Junkai; Chang, Zhenyue; Zhao, Tong; Ding, Xiangdong; Sun, Jun; Liu, Jefferson Zhe

    2016-04-13

    Phosphorene, the single-layer form of black phosphorus, as a new member of atomically thin material family, has unique puckered atomistic structure and remarkable physical and chemical properties. In this paper, we report a discovery of an unexpected electromechanical energy conversion phenomenon-shape memory effect-in Li doped phosphorene P4Li2, using ab initio density functional theory simulations. Two stable phases are found for the two-dimensional (2D) P4Li2 crystal. Applying an external electric field can turn on or off the unique adatom switches in P4Li2 crystals, leading to a reversible structural phase transition and thereby the shape memory effect with an tunable strain output as high as 2.06%. Our results demonstrate that multiple temporary shapes are attainable in one piece of P4Li2 material, offering programmability that is particularly useful for device designs. Additionally, the P4Li2 displays superelasticity that can generate a pseudoelastic tensile strain up to 6.2%. The atomic thickness, superior flexibility, excellent electromechanical strain output, the special shape memory phenomenon, and the programmability feature endow P4Li2 with great application potential in high-efficient energy conversion at nanoscale and flexible nanoelectromechanical systems. PMID:27043220

  6. Reversal of DNA damage induced Topoisomerase 2 DNA–protein crosslinks by Tdp2

    Science.gov (United States)

    Schellenberg, Matthew J.; Perera, Lalith; Strom, Christina N.; Waters, Crystal A.; Monian, Brinda; Appel, C. Denise; Vilas, Caroline K.; Williams, Jason G.; Ramsden, Dale A.; Williams, R. Scott

    2016-01-01

    Mammalian Tyrosyl-DNA phosphodiesterase 2 (Tdp2) reverses Topoisomerase 2 (Top2) DNA–protein crosslinks triggered by Top2 engagement of DNA damage or poisoning by anticancer drugs. Tdp2 deficiencies are linked to neurological disease and cellular sensitivity to Top2 poisons. Herein, we report X-ray crystal structures of ligand-free Tdp2 and Tdp2-DNA complexes with alkylated and abasic DNA that unveil a dynamic Tdp2 active site lid and deep substrate binding trench well-suited for engaging the diverse DNA damage triggers of abortive Top2 reactions. Modeling of a proposed Tdp2 reaction coordinate, combined with mutagenesis and biochemical studies support a single Mg2+-ion mechanism assisted by a phosphotyrosyl-arginine cation-π interface. We further identify a Tdp2 active site SNP that ablates Tdp2 Mg2+ binding and catalytic activity, impairs Tdp2 mediated NHEJ of tyrosine blocked termini, and renders cells sensitive to the anticancer agent etoposide. Collectively, our results provide a structural mechanism for Tdp2 engagement of heterogeneous DNA damage that causes Top2 poisoning, and indicate that evaluation of Tdp2 status may be an important personalized medicine biomarker informing on individual sensitivities to chemotherapeutic Top2 poisons. PMID:27060144

  7. Reversal of DNA damage induced Topoisomerase 2 DNA-protein crosslinks by Tdp2.

    Science.gov (United States)

    Schellenberg, Matthew J; Perera, Lalith; Strom, Christina N; Waters, Crystal A; Monian, Brinda; Appel, C Denise; Vilas, Caroline K; Williams, Jason G; Ramsden, Dale A; Williams, R Scott

    2016-05-01

    Mammalian Tyrosyl-DNA phosphodiesterase 2 (Tdp2) reverses Topoisomerase 2 (Top2) DNA-protein crosslinks triggered by Top2 engagement of DNA damage or poisoning by anticancer drugs. Tdp2 deficiencies are linked to neurological disease and cellular sensitivity to Top2 poisons. Herein, we report X-ray crystal structures of ligand-free Tdp2 and Tdp2-DNA complexes with alkylated and abasic DNA that unveil a dynamic Tdp2 active site lid and deep substrate binding trench well-suited for engaging the diverse DNA damage triggers of abortive Top2 reactions. Modeling of a proposed Tdp2 reaction coordinate, combined with mutagenesis and biochemical studies support a single Mg(2+)-ion mechanism assisted by a phosphotyrosyl-arginine cation-π interface. We further identify a Tdp2 active site SNP that ablates Tdp2 Mg(2+) binding and catalytic activity, impairs Tdp2 mediated NHEJ of tyrosine blocked termini, and renders cells sensitive to the anticancer agent etoposide. Collectively, our results provide a structural mechanism for Tdp2 engagement of heterogeneous DNA damage that causes Top2 poisoning, and indicate that evaluation of Tdp2 status may be an important personalized medicine biomarker informing on individual sensitivities to chemotherapeutic Top2 poisons. PMID:27060144

  8. Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Wen-Zhu [Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013 (China); Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China); Miao, Yu-Liang [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Guo, Wen-Zhi [Department of Anesthesiology, Beijing Military General Hospital of Chinese People’s Liberation Army, Beijing 100700 (China); Wu, Wei, E-mail: wwzwgk@163.com [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); Li, Bao-Wei [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); An, Li-Na [Department of Anesthesiology, Armed Police General Hospital, Beijing 100039 (China); Fang, Wei-Wu [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Mi, Wei-Dong, E-mail: elite2005gg@163.com [Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China)

    2014-04-25

    Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.

  9. Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

    International Nuclear Information System (INIS)

    Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors

  10. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring.

    Science.gov (United States)

    Buffington, Shelly A; Di Prisco, Gonzalo Viana; Auchtung, Thomas A; Ajami, Nadim J; Petrosino, Joseph F; Costa-Mattioli, Mauro

    2016-06-16

    Maternal obesity during pregnancy has been associated with increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), in offspring. Here, we report that maternal high-fat diet (MHFD) induces a shift in microbial ecology that negatively impacts offspring social behavior. Social deficits and gut microbiota dysbiosis in MHFD offspring are prevented by co-housing with offspring of mothers on a regular diet (MRD) and transferable to germ-free mice. In addition, social interaction induces synaptic potentiation (LTP) in the ventral tegmental area (VTA) of MRD, but not MHFD offspring. Moreover, MHFD offspring had fewer oxytocin immunoreactive neurons in the hypothalamus. Using metagenomics and precision microbiota reconstitution, we identified a single commensal strain that corrects oxytocin levels, LTP, and social deficits in MHFD offspring. Our findings causally link maternal diet, gut microbial imbalance, VTA plasticity, and behavior and suggest that probiotic treatment may relieve specific behavioral abnormalities associated with neurodevelopmental disorders. VIDEO ABSTRACT. PMID:27315483

  11. Chlorophyll a fluorescence lifetime reveals reversible UV-induced photosynthetic activity in the green algae Tetraselmis

    OpenAIRE

    Kristoffersen, Arne Skodvin; Hamre, Børge; Frette, Øyvind; Erga, Svein Rune

    2015-01-01

    The fluorescence lifetime is a very useful parameter for investigating biological materials on the molecular level as it is mostly independent of the fluorophore concentration. The green alga Tetraselmis blooms in summer, and therefore its response to UV irradiation is of particular interest. In vivo fluorescence lifetimes of chlorophyll a were measured under both normal and UV-stressed conditions of Tetraselmis. Fluorescence was induced by two-photon excitation using a femtosecond laser and ...

  12. Hepatic Glucagon Action Is Essential for Exercise-Induced Reversal of Mouse Fatty Liver

    OpenAIRE

    Berglund, Eric D.; Lustig, Daniel G.; Baheza, Richard A.; Hasenour, Clinton M.; Lee-Young, Robert S.; Donahue, E. Patrick; Lynes, Sara E.; Swift, Larry L.; Charron, Maureen J; Damon, Bruce M.; Wasserman, David H

    2011-01-01

    OBJECTIVE Exercise is an effective intervention to treat fatty liver. However, the mechanism(s) that underlie exercise-induced reductions in fatty liver are unclear. Here we tested the hypothesis that exercise requires hepatic glucagon action to reduce fatty liver. RESEARCH DESIGN AND METHODS C57BL/6 mice were fed high-fat diet (HFD) and assessed using magnetic resonance, biochemical, and histological techniques to establish a timeline for fatty liver development over 20 weeks. Glucagon recep...

  13. Chlorfenapyr-induced toxic leukoencephalopathy with radiologic reversibility: A case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Byung Hyun; Kim, Seul Kee; Yoon, Woong; Heo, Tae Wook; Lee, Yun Young [Dept. of Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of); Kang, Heonung Keun [Dept. of Radiology, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of)

    2016-04-15

    Chlorfenapyr is a widely used, moderately hazardous pesticide. Previous reports have indicated that chlorfenapyr intoxication can be fatal in humans. We reported the first non-fatal case of chlorfenapyr-induced toxic leukoencephalopathy in a 44-year-old female with resolution of extensive and abnormal signal intensities in white matter tracts throughout the brain, brain stem, and spinal cord on serial magnetic resonance imaging.

  14. Cannabinoid receptor activation reverses kainate-induced synchronized population burst firing in rat hippocampus

    OpenAIRE

    Rob Mason; Cheer, Joseph F

    2009-01-01

    Cannabinoids have been shown to possess anticonvulsant properties in whole animal models of epilepsy. The present investigation sought to examine the effects of cannabinoid receptor activation on kainic acid (KA)-induced epileptiform neuronal excitability. Under urethane anesthesia, acute KA treatment (10 mg/kg, i.p.) entrained the spiking mode of simultaneously recorded neurons from random firing to synchronous bursting (% change in burst rate). Injection of the high-affinity cannabinoid a...

  15. Cannabinoid Receptor Activation Reverses Kainate-Induced Synchronized Population Burst Firing in Rat Hippocampus

    OpenAIRE

    Mason, Rob; Cheer, Joseph F

    2009-01-01

    Cannabinoids have been shown to possess anticonvulsant properties in whole animal models of epilepsy. The present investigation sought to examine the effects of cannabinoid receptor activation on kainic acid (KA)-induced epileptiform neuronal excitability. Under urethane anesthesia, acute KA treatment (10 mg kg−1, i.p.) entrained the spiking mode of simultaneously recorded neurons from random firing to synchronous bursting (% change in burst rate). Injection of the high-affinity cannabinoid a...

  16. Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids

    OpenAIRE

    Sousa, Nuno; Rodrigues, Ana João; Leão, Pedro; Pego, José Miguel; Cardona, Diana; de Carvalho, Miguel; Oliveira, Mário; Costa, Bruno; Carvalho, Ana Franky; Morgado, Pedro; Araújo, David; Palha, Joana; Almeida, Osborne

    2011-01-01

    Abstract Stress and exposure to glucocorticoids (GC) during early life render individuals vulnerable to brain disorders by inducing structural and chemical alterations in specific neural substrates. Here we show that adult rats that had been exposed to intrauterine glucocorticoids (iuGC) display increased preference for opiates and ethanol, and are more responsive to the psychostimulatory actions of morphine. These animals presented prominent changes in the nucleus accumbens (NAcc)...

  17. Opiate-induced suppression of rat hypoglossal motoneuron activity and its reversal by ampakine therapy.

    Directory of Open Access Journals (Sweden)

    Amanda R Lorier

    Full Text Available BACKGROUND: Hypoglossal (XII motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity while maintaining analgesia. Ampakines accentuate alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA receptor responses. The AMPA family of glutamate receptors mediate excitatory transmission to XII motoneurons. Therefore the objectives were to determine whether the depressant actions of mu-opioid receptor activation on inspiratory activity includes a direct inhibitory action at the inspiratory premotoneuron to XII motoneuron synapse, and to identify underlying mechanism(s. We then examined whether ampakines counteract opioid-induced depression of XII motoneuron activity. METHODOLOGY/PRINCIPAL FINDINGS: A medullary slice preparation from neonatal rat that produces inspiratory-related output in vitro was used. Measurements of inspiratory burst amplitude and frequency were made from XII nerve roots. Whole-cell patch recordings from XII motoneurons were used to measure membrane currents and synaptic events. Application of the mu-opioid receptor agonist, DAMGO, to the XII nucleus depressed the output of inspiratory XII motoneurons via presynaptic inhibition of excitatory glutamatergic transmission. Ampakines (CX614 and CX717 alleviated DAMGO-induced depression of XII MN activity through postsynaptic actions on XII motoneurons. CONCLUSIONS/SIGNIFICANCE: The inspiratory-depressant actions of opioid analgesics include presynaptic inhibition of XII motoneuron output. Ampakines counteract mu-opioid receptor-mediated depression of XII motoneuron inspiratory activity. These results suggest that ampakines may be beneficial in countering opiate-induced

  18. Opioid-induced respiratory depression: reversal by non-opioid drugs

    OpenAIRE

    van der Schier, Rutger; Roozekrans, Margot; van Velzen, Monique; Dahan, Albert; Niesters, Marieke

    2014-01-01

    The human body is critically dependent on the ventilatory control system for adequate uptake of oxygen and removal of carbon dioxide (CO2). Potent opioid analgesics, through their actions on μ-opioid receptor (MOR) expressed on respiratory neurons in the brainstem, depress ventilation. Opioid-induced respiratory depression (OIRD) is potentially life threatening and the cause of substantial morbidity and mortality. One possible way of prevention of OIRD is by adding a respiratory stimulant to ...

  19. Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

    International Nuclear Information System (INIS)

    Lansoprazole is an acid proton-pump inhibitor that is similar to omeprazole. It is used to treat duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease (GERD) or Zollinger-Ellison syndrome. Common adverse effects of lansoprazole are diarrhea, abdominal pain, skin rash and/or itching. Information from U.S. National Library of Medicine warns that this drug can on rare occasion cause cough or cold-like symptoms. The pathophysiological mechanisms of lansoprazole-related pulmonary symptoms are not yet understood. In particular, there are no known reports regarding lansoprazole-induced interstitial lung diseases. We report here a case of interstitial lung disease (ILD) induced by oral administration of lansoprazole, which showed a pattern of nonspecific interstitial pneumonia (NSIP) as detected from a video-assisted thoracoscopic lung biopsy. We believe that this is the first report of a case of pathologically proven lansoprazole-induced ILD for which a surgical lung biopsy was performed. To the best of our knowledge, this is the first description of DI-ILD caused by lansoprazole. The diagnosis was made by considering the radiological, histopathological and clinical findings, including the close temporal relationship between lansoprazole exposure and symptom severity. Other possible causes were excluded due to a lack of a temporal relationship between the symptoms and work history or prednisolone therapy, and no other history of specific allergen exposure. When there is diffuse interstitial lung disease with an unknown etiology, it is important to remember that drugs can be the cause of pulmonary symptoms and it is crucial to take a careful patient history. If there is a recent history of taking lansoprazole in a patient with clinical and radiological findings of diffuse interstitial lung disease, we recommend stopping the medication to see if there is clinical and radiological improvement. That way, one can avoid using invasive procedures to

  20. Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation

    OpenAIRE

    Bluett, R J; Gamble-George, J C; Hermanson, D J; Hartley, N D; Marnett, L J; Patel, S.

    2014-01-01

    Stress is a major risk factor for the development of mood and anxiety disorders; elucidation of novel approaches to mitigate the deleterious effects of stress could have broad clinical applications. Pharmacological augmentation of central endogenous cannabinoid (eCB) signaling may be an effective therapeutic strategy to mitigate the adverse behavioral and physiological consequences of stress. Here we show that acute foot-shock stress induces a transient anxiety state measured 24 h later using...

  1. Establishment and characterization of buffalo fetal fibroblasts induced with human telomerase reverse transcriptase.

    Science.gov (United States)

    Zhang, Shun; Guan, Xiaomei; Lu, Fenghua; Jiang, Jianrong; Deng, Yanfei; Luo, Chan; Shi, Deshun

    2016-10-01

    Fetal fibroblasts are often used as donor cells for SCNT, but their short lifespan greatly limits this application. To provide stable and long-lifespan cells, buffalo fetal fibroblasts (BFFs) transfected with human telomerase reverse transcriptase (hTERT). The hTERT-transfected BFFs (hTERT-BFFs) were evaluated by qRT-PCR, Western blot, karyotype analysis, telomerase activity assay, growth curve assay, flow cytometry, and soft agar assay. The development of SCNT embryos derived from hTERT-BFFs was also assessed in vitro. The morphology of hTERT-BFFs was similar to the nontransfected BFFs, and the karyotype of hTERT-BFFs was normal at passage 30. The hTERT-BFFs at passage 4 and 30 had higher telomerase activity and extended proliferative lifespan with an increase in cell population at S phase when compared with nontransfected BFFs at passage 5 and 30. The mRNA expression of p53 in hTERT-BFFs at passage 5 and 30 remained unchanged when compared with nontransfected BFFs at passage 5, whereas the mRNA expression of p53 in the nontransfected BFFs at passage 30 was increased. Soft agar assay showed that hTERT-BFFs at passage 30 were not a malignant phenotype. Significantly, more SCNT embryos derived from hTERT-BFFs at passage 5 and 30 developed to blastocysts in comparison with BFFs at passage 30. The Caudal type homeobox 2 and Connexin 43 genes were indicated to involve in the development of cloned embryos. These results indicate that transfection of BFFs with hTERT can extend their lifespan and retain their basic and key biological characteristics in the status of primary BFFs. PMID:27388808

  2. Docosahexaenoic acid reverses cyclosporin A-induced changes in membrane structure and function.

    Science.gov (United States)

    Thakkar, R R; Wang, O L; Zerouga, M; Stillwell, W; Haq, A; Kissling, R; Pierce, W M; Smith, N B; Miller, F N; Ehringer, W D

    2000-04-01

    The use of a fish oil vehicle for cyclosporin A (CsA) can decrease the toxic effects of CsA but the mechanism is unclear. Here we examine the mechanism by which docosahexaenoic acid (DHA), a fish oil-derived polyunsaturated fatty acid, can alter the toxic effects of CsA on mouse organ function, endothelial macromolecular permeability, and membrane bilayer function. Mice given CsA and fish oil showed increased liver toxicity, kidney toxicity, incorporation of DHA, and evidence of oxidized fatty acids compared to control animals. We hypothesized that the toxic effects of CsA were primarily a result of membrane perturbation, which could be decreased if DHA were not oxidized. The presence of CsA (10 mol%) alone increased dipalmitoylphosphatidylcholine membrane permeability by seven fold over control (no CsA, no DHA). However, if non-oxidized DHA (15 mol%) and CsA were added to the membrane, the permeability returned to control levels. Interestingly, if the DHA was oxidized, the antagonistic effect of DHA on CsA was completely lost. While CsA alone increased endothelial permeability to albumin, the combination of non-oxidized DHA and CsA had no effect on endothelial macromolecular permeability. However the combination of oxidized DHA and CsA was no different than the effects of CsA only. CsA increased the fluorescence anisotropy of DPH in the liquid crystalline state of DPPC, while DHA decreased fluorescence anisotropy. However the combination of CsA and DHA was no different than DHA alone. We conclude that non-oxidized DHA can reverse the membrane perturbing effects of CsA, and the increases in endothelial macromolecular permeability, which may explain how fish oil is capable of decreasing the toxicity of CsA. PMID:10742598

  3. Phosphatidylcholine Reverses Ethanol-Induced Increase in Transepithelial Endotoxin Permeability and Abolishes Transepithelial Leukocyte Activation

    DEFF Research Database (Denmark)

    Mitzscherling, Katja; Volynets, Valentina; Parlesak, Alexandr

    2009-01-01

    Chronic alcohol abuse increases both intestinal bacterial overgrowth and intestinal permeability to macromolecules. Intestinal permeability of endotoxin, a component of the outer cell membrane of Gram-negative bacteria, plays a crucial role in the development of alcohol-induced liver disease (ALD......). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent transepithelial...

  4. Crowding-Induced Mixing Behavior of Lipid Bilayers: Examination of Mixing Energy, Phase, Packing Geometry, and Reversibility.

    Science.gov (United States)

    Zeno, Wade F; Rystov, Alice; Sasaki, Darryl Y; Risbud, Subhash H; Longo, Marjorie L

    2016-05-10

    In an effort to develop a general thermodynamic model from first-principles to describe the mixing behavior of lipid membranes, we examined lipid mixing induced by targeted binding of small (Green Fluorescent Protein (GFP)) and large (nanolipoprotein particles (NLPs)) structures to specific phases of phase-separated lipid bilayers. Phases were targeted by incorporation of phase-partitioning iminodiacetic acid (IDA)-functionalized lipids into ternary lipid mixtures consisting of DPPC, DOPC, and cholesterol. GFP and NLPs, containing histidine tags, bound the IDA portion of these lipids via a metal, Cu(2+), chelating mechanism. In giant unilamellar vesicles (GUVs), GFP and NLPs bound to the Lo domains of bilayers containing DPIDA, and bound to the Ld region of bilayers containing DOIDA. At sufficiently large concentrations of DPIDA or DOIDA, lipid mixing was induced by bound GFP and NLPs. The validity of the thermodynamic model was confirmed when it was found that the statistical mixing distribution as a function of crowding energy for smaller GFP and larger NLPs collapsed to the same trend line for each GUV composition. Moreover, results of this analysis show that the free energy of mixing for a ternary lipid bilayer consisting of DOPC, DPPC, and cholesterol varied from 7.9 × 10(-22) to 1.5 × 10(-20) J/lipid at the compositions observed, decreasing as the relative cholesterol concentration was increased. It was discovered that there appears to be a maximum packing density, and associated maximum crowding pressure, of the NLPs, suggestive of circular packing. A similarity in mixing induced by NLP1 and NLP3 despite large difference in projected areas was analytically consistent with monovalent (one histidine tag) versus divalent (two histidine tags) surface interactions, respectively. In addition to GUVs, binding and induced mixing behavior of NLPs was also observed on planar, supported lipid multibilayers. The mixing process was reversible, with Lo domains

  5. Carvacrol partially reverses symptoms of diabetes in STZ-induced diabetic rats.

    Science.gov (United States)

    Bayramoglu, Gokhan; Senturk, Hakan; Bayramoglu, Aysegul; Uyanoglu, Mustafa; Colak, Suat; Ozmen, Ayse; Kolankaya, Durdane

    2014-03-01

    Little is known about the protective effects of carvacrol on the symptoms of streptozotocin induced diabetes in rats. Hence, this present study was designed to evaluate the protective effect of the strong antioxidant, carvacrol, on the symptoms of streptozotocin induced diabetes in rats. Carvacrol at the doses of 25 and 50 mg/kg body weight were orally administered to diabetic rats for a period of 7 days after the onset of diabetes. Food-water intake and body weight changes were daily recorded. Biochemical parameters such as serum glucose, insulin, total cholesterol, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were measured. Although treatment of diabetic rats with oral administration of carvacrol resulted in a slight reduction in serum glucose level and significant reduction in serum total cholesterol, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase in comparison with diabetic control rats, there were no significant differences in serum insulin levels, food-water intake values and body weight changes. Despite the inadequacy of carvacrol on diabetes treatments, it was determined to have at least a partially protective role on liver enzymes. PMID:23579248

  6. Minocycline-induced hyperpigmentation: comparison of 3 Q-switched lasers to reverse its effects

    Directory of Open Access Journals (Sweden)

    Nisar MS

    2013-05-01

    Full Text Available Mahrukh S Nisar,1 Karthik Iyer,1 Robert T Brodell,2 Jenifer R Lloyd,3 Thuzar M Shin,3 Asad Ahmad4 1Northeast Ohio Medical University, Rootstown, OH, USA; 2Division of Dermatology, University of Mississippi Medical Center, Jackson, MS, USA; 3Case Western Reserve University School of Medicine, Cleveland, OH, USA; 4Northside Medical Center, Youngstown, OH, USA Abstract: Minocycline is a tetracycline derivative antibiotic commonly prescribed for acne, rosacea, and other inflammatory skin disorders. Minocycline turns black when oxidized, leading to discoloration of the skin, nails, bulbar conjunctiva, oral mucosa, teeth, bones, and thyroid gland. Hyperpigmentation has been reported after long-term minocycline therapy with at least 100 mg/day. Three types of minocycline-induced cutaneous hyperpigmentation can result. Type I is the most common, and is associated with blue-black discoloration in areas of previous inflammation and scarring. Type II most commonly affects the legs and is characterized by blue-gray pigmentation of previously normal skin. Type III is the least common and is characterized by diffuse muddy-brown discoloration predominantly on sun exposed skin. Minocycline-induced hyperpigmentation may be cosmetically disfiguring and prompt identification is essential. Without treatment, symptoms may take several months, to years to resolve, after discontinuation of the drug. However, the pigmentation may never completely disappear. In fact, there have been few reports of complete resolution associated with any therapeutic intervention. We report a case of a patient on long-term minocycline therapy utilized as an anti-inflammatory agent to control symptoms of rheumatoid arthritis, which led to minocycline-induced hyperpigmentation of the face. To remove the blue-gray cutaneous deposits, 3 Q-switched lasers (Neodymium: yttrium aluminum garnet (Nd:YAG 1064 nm, Alexandrite 755 nm, and Ruby 694 nm were used in test areas. The Alexandrite 755 nm

  7. Gamma radiation induced synthesis of poly(N-isopropylacrylamide) mediated by Reversible Addition-Fragmentation Chain Transfer (RAFT) process

    Science.gov (United States)

    Kiraç, Feyza; Güven, Olgun

    2015-07-01

    Poly(N-isopropylacrylamide) (PNiPAAm) is synthesized by gamma radiation induced Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization. The monomer is polymerized in the presence of two different trithiocarbonate-based RAFT agents i.e., Cyanomethyldodecyltrithiocarbonate (CDTC) and 2-(Dodecylthiocarbonothioylthio)-2-methylpropionic acid (DMPA) in dimethylformamide (DMF) at room temperature under nitrogen atmosphere. Number-average molecular weights (Mn) and dispersities of the polymers were determined by Size Exclusion Chromatography (SEC). Dispersities (Ɖ) of the resulting polymers are narrow, i.e., Ɖ≤1.18, indicating the occurrence of well-controlled polymerization via radiation induced RAFT process. %Conversion is determined by gravimetric method and also confirmed by Proton Nuclear Magnetic Resonance (1H-NMR) Spectroscopy. By selecting proper [Monomer]/[RAFT] ratio and controlling conversion it is possible to synthesize PNiPAAm in the molecular weight range of 2400-72400 with extremely low molecular weight distributions with the anticipation of preparing corresponding size-controlled nanogels. The phase transition of PNiPAAm with low dispersity synthesized by RAFT is sharper than PNiPAAm synthesized by free radical polymerization.

  8. Preventing and Reversing Vacuum-Induced Optical Losses in High-Finesse Tantalum (V) Oxide Mirror Coatings

    CERN Document Server

    Gangloff, Dorian; Wu, Tailin; Bylinskii, Alexei; Braverman, Boris; Gutierrez, Michael; Nichols, Rosanna; Li, Junru; Aichholz, Kai; Cetina, Marko; Karpa, Leon; Jelenković, Branislav; Chuang, Isaac; Vuletić, Vladan

    2015-01-01

    We study the vacuum-induced degradation of high-finesse optical cavities with mirror coatings composed of SiO$_2$-Ta$_{2}$O$_{5}$ dielectric stacks, and present methods to protect these coatings and to recover their initial quality factor. For separate coatings with reflectivities centered at 370 nm and 422 nm, a vacuum-induced continuous increase in optical loss occurs if the surface-layer coating is made of Ta$_{2}$O$_{5}$, while it does not occur if it is made of SiO$_2$. The incurred optical loss can be reversed by filling the vacuum chamber with oxygen at atmospheric pressure, and the recovery rate can be strongly accelerated by continuous laser illumination at 422 nm. Both the degradation and the recovery processes depend strongly on temperature. We find that a 1 nm-thick layer of SiO$_2$ passivating the Ta$_{2}$O$_{5}$ surface layer is sufficient to reduce the degradation rate by more than a factor of 10, strongly supporting surface oxygen depletion as the primary degradation mechanism.

  9. Preventing and reversing vacuum-induced optical losses in high-finesse tantalum (V) oxide mirror coatings

    Science.gov (United States)

    Gangloff, Dorian; Shi, Molu; Wu, Tailin; Bylinskii, Alexei; Braverman, Boris; Gutierrez, Michael; Nichols, Rosanna; Li, Junru; Aichholz, Kai; Cetina, Marko; Karpa, Leon; Jelenković, Branislav; Chuang, Isaac; Vuletić, Vladan

    2015-07-01

    We study the vacuum-induced degradation of high-finesse optical cavities with mirror coatings composed of SiO$_2$-Ta$_{2}$O$_{5}$ dielectric stacks, and present methods to protect these coatings and to recover their initial quality factor. For separate coatings with reflectivities centered at 370 nm and 422 nm, a vacuum-induced continuous increase in optical loss occurs if the surface-layer coating is made of Ta$_{2}$O$_{5}$, while it does not occur if it is made of SiO$_2$. The incurred optical loss can be reversed by filling the vacuum chamber with oxygen at atmospheric pressure, and the recovery rate can be strongly accelerated by continuous laser illumination at 422 nm. Both the degradation and the recovery processes depend strongly on temperature. We find that a 1 nm-thick layer of SiO$_2$ passivating the Ta$_{2}$O$_{5}$ surface layer is sufficient to reduce the degradation rate by more than a factor of 10, strongly supporting surface oxygen depletion as the primary degradation mechanism.

  10. Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro

    Science.gov (United States)

    Lin, Jiajia; Huang, Ling; Yu, Jie; Xiang, Siying; Wang, Jialing; Zhang, Jinrong; Yan, Xiaojun; Cui, Wei; He, Shan; Wang, Qinwen

    2016-01-01

    Fucoxanthin, a natural carotenoid abundant in edible brown seaweeds, has been shown to possess anti-cancer, anti-oxidant, anti-obesity and anti-diabetic effects. In this study, we report for the first time that fucoxanthin effectively protects against scopolamine-induced cognitive impairments in mice. In addition, fucoxanthin significantly reversed the scopolamine-induced increase of acetylcholinesterase (AChE) activity and decreased both choline acetyltransferase activity and brain-derived neurotrophic factor (BDNF) expression. Using an in vitro AChE activity assay, we discovered that fucoxanthin directly inhibits AChE with an IC50 value of 81.2 μM. Molecular docking analysis suggests that fucoxanthin likely interacts with the peripheral anionic site within AChE, which is in accordance with enzymatic activity results showing that fucoxanthin inhibits AChE in a non-competitive manner. Based on our current findings, we anticipate that fucoxanthin might exhibit great therapeutic efficacy for the treatment of Alzheimer’s disease by acting on multiple targets, including inhibiting AChE and increasing BDNF expression. PMID:27023569

  11. Flow mechanism of self-induced reversed limit-cycle wing rock for a chined forebody configuration

    Science.gov (United States)

    Shi, Wei; Deng, Xueying; Wang, Yankui; Li, Qian

    2015-11-01

    The wing rock phenomenon reduces the maneuverability and affects the flight safety of modern advanced fighters, such as the F-35, which have chined forebodies. Understanding the flow mechanism is critical to suppressing this phenomenon. In this study, experiments were conducted to reveal the motion and flow behavior over a chined forebody configuration. The tests were performed in a wind tunnel at an angle of attack of 50∘ with a Reynolds number of 1.87 × 105. Reversed limit-cycle oscillation was discovered in the free-to-roll tests. The unstable rolling moment around zero roll angle in the static case suggests that the model tends to be driven away from zero roll angle. Thus, the model cannot maintain its equilibrium at zero roll angle during free-to-roll motion. The unstable rolling moment is generated by the wing vortex structure above the upward wing, which is induced by the forebody asymmetric vortices. During wing rock, the wing vortex structure appears above the upward wing at a large roll angle after crossing zero roll angle owing to a time lag in the forebody vortex position, which is conducive to the motion. The forebody asymmetric vortices are thus the key to induce and maintain the motion.

  12. Strain-induced transitions to quantum chaos and effective time-reversal symmetry breaking in triangular graphene nanoflakes

    Science.gov (United States)

    Rycerz, Adam

    2013-05-01

    We investigate the effect of strain-induced gauge fields on statistical distribution of energy levels of triangular graphene nanoflakes with zigzag edges. In the absence of strain fields but in the presence of weak potential disorder such systems were found by Rycerz [Phys. Rev. BPRBMDO1098-012110.1103/PhysRevB.85.245424 85, 245424 (2012)] to display the spectral statistics of the Gaussian unitary ensemble (GUE) due to the effective time-reversal (symplectic) symmetry breaking. Here we show that in the absence of disorder, strain fields may solely lead to spectral fluctuations of GUE providing a nanoflake is deformed such that all its geometric symmetries are broken. In a particular case when a single mirror symmetry is preserved the spectral statistics follow the Gaussian orthogonal ensemble (GOE) rather then GUE. The corresponding transitions to quantum chaos are rationalized by means of additive random-matrix models and the analogy between strain-induced gauge fields and real magnetic fields is discussed.

  13. Immunological features of T cells induced by human telomerase reverse transcriptase-derived peptides in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Mizukoshi, Eishiro; Nakagawa, Hidetoshi; Kitahara, Masaaki; Yamashita, Tatsuya; Arai, Kuniaki; Sunagozaka, Hajime; Fushimi, Kazumi; Kobayashi, Eiji; Kishi, Hiroyuki; Muraguchi, Atsushi; Kaneko, Shuichi

    2015-08-10

    Human telomerase reverse transcriptase (hTERT) is a catalytic enzyme required for telomere elongation. In this study, we investigated the safety and immunogenicity of an hTERT-derived peptide (hTERT461) as a vaccine and characterized the hTERT-specific T cell responses induced. Fourteen hepatocellular carcinoma (HCC) patients were enrolled in the study. The hTERT-derived peptide was emulsified in incomplete Freund's adjuvant and administered via subcutaneous immunization three times biweekly. The maximum toxicity observed was grade 2 according to the common terminology criteria and mainly consisted of skin reactions at the site of vaccination. The vaccination induced hTERT-specific immunity in 71.4% of patients and 57.1% of patients administered with hTERT461 peptide-specific T cells could prevent HCC recurrence after vaccination. In phenotypic analysis, the post-vaccinated increase in hTERT-specific T cells was due to an increase in cells with the effector memory phenotype, with the potential to produce multiple cytokines. Seven hTERT-specific T cell receptors were obtained from the vaccinated patients, showing their cytotoxic activities to hTERT-derived peptide-bearing cells. In conclusion, the safety and effects of immune boosting by hTERT461 peptide have shown the potential of the peptide to provide clinical benefits in HCC patients. PMID:25982205

  14. Administration of Chinpi, a Component of the Herbal Medicine Ninjin-Youei-To, Reverses Age-Induced Demyelination

    Directory of Open Access Journals (Sweden)

    Nanako Sato

    2011-01-01

    Full Text Available The disruption of myelin causes severe neurological diseases. An understanding of the mechanism of myelination and remyelination is essential for the development of therapeutic strategies for demyelination diseases. Our previous findings indicated that the FcRγ/Fyn cascade is a potential therapeutic target for remyelination caused by the Chinese/Japanese traditional herbal (Kampo medicine ninjin’youeito (Ninjin-youei-to, NYT, which is a hot-water extract made from 12 medicinal herbs. To identify which constituents of NYT are involved in the reversal of demyelination and to examine the potential therapeutic effect, we tested several of the chemical constituents of NYT. Here, we report that Chinpi, a constituent of NYT, upregulates the FcRγ/Fyn signaling cascade resulting in a potentially therapeutic effect against age-induced demyelination. In addition, we observed that phosphorylated (activated FcRγ/Fyn upregulated the expression of the 21.5 kDa isoform of myelin basic protein, inducing rapid morphological differentiation, when oligodendrocyte precursor cells (OPCs were cultured in the presence of hesperidin and/or narirutin (the major active constituents of Chinpi. These results suggest that hesperidin and narirutin participate in the FcRγ/Fyn signaling pathway in OPCs causing these cells to differentiate into myelinating oligodendrocytes.

  15. Hydrogen-bond effects induced by alcohol on the structure and dynamics of ionic reverse micelles

    Science.gov (United States)

    Bardez, E.; Giordano, R.; Jannelli, M. P.; Migliardo, P.; Wanderlingh, U.

    1996-09-01

    In this work we report how the structure of Zn(AOT) 2/H 2O/d-cyclohexane microemulsions is affected by the presence of alcohol (normal pentanol) molecules as cosurfactant. The systems are investigated by small-angle neutron scattering (SANS) and by Fourier transform IR (FTIR) spectroscopy. The SANS technique allows the study of the evolution of the size, the shape and the possible correlation length of concentration fluctuations as a function of water and alcohol content. Moreover FTIR spectra, in the OH stretching region, is quite sensitive to the structural changes of the water, induced by the polarization effects of the polar heads of the micelle surface and the positive counterions and by the presence of the alcohol.

  16. Transgene Reactivation in Induced Pluripotent Stem Cell Derivatives and Reversion to Pluripotency of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Galat, Vasiliy; Galat, Yekaterina; Perepitchka, Mariana; Jennings, Lawrence J; Iannaccone, Philip M; Hendrix, Mary J C

    2016-07-15

    Induced pluripotent stem cells (iPSCs) have enormous potential in regenerative medicine and disease modeling. It is now felt that clinical trials should be performed with iPSCs derived with nonintegrative constructs. Numerous studies, however, including those describing disease models, are still being published using cells derived from iPSCs generated with integrative constructs. Our experimental work presents the first evidence of spontaneous transgene reactivation in vitro in several cellular types. Our results show that the transgenes were predominantly silent in parent iPSCs, but in mesenchymal and endothelial iPSC derivatives, the transgenes experienced random upregulation of Nanog and c-Myc. Additionally, we provide evidence of spontaneous secondary reprogramming and reversion to pluripotency in mesenchymal stem cells derived from iPSCs. These findings strongly suggest that the studies, which use cellular products derived from iPSCs generated with retro- or lentiviruses, should be evaluated with consideration of the possibility of transgene reactivation. The in vitro model described here provides insight into the earliest events of culture transformation and suggests the hypothesis that reversion to pluripotency may be responsible for the development of tumors in cell replacement experiments. The main goal of this work, however, is to communicate the possibility of transgene reactivation in retro- or lenti-iPSC derivatives and the associated loss of cellular fidelity in vitro, which may impact the outcomes of disease modeling and related experimentation. PMID:27193052

  17. Corticosteroids reverse cytokine-induced block of survival and differentiation of oligodendrocyte progenitor cells from rats

    Directory of Open Access Journals (Sweden)

    Marx Romy

    2008-09-01

    Full Text Available Abstract Background Periventricular leukomalacia (PVL is a frequent complication of preterm delivery. Proinflammatory cytokines, such as interferon-γ (IFN-γ and tumor necrosis factor α (TNF-α released from astrocytes and microglia activated by infection or ischemia have previously been shown to impair survival and maturation of oligodendrocyte progenitors and could thus be considered as potential factors contributing to the generation of this disease. The first goal of the present study was to investigate whether exposure of oligodendrocyte precursors to these cytokines arrests the maturation of ion currents in parallel to its effects on myelin proteins and morphological maturation. Secondly, in the search for agents, that can protect differentiating oligodendrocyte precursor cells from cytokine-induced damage we investigated effects of coapplications of corticosteroids with proinflammatory cytokines on the subsequent survival and differentiation of oligodendrocyte progenitor cells. Methods To exclude influences from factors released from other cell types purified cultures of oligodendrocyte precursors were exposed to cytokines and/or steroids and allowed to differentiate for further 6 days in culture. Changes in membrane surface were investigated with capacitance recordings and Scanning Ion Conductance Microscopy. Na+- and K+- currents were investigated using whole cell patch clamp recordings. The expression of myelin specific proteins was investigated using western blots and the precursor cells were identified using immunostaining with A2B5 antibodies. Results Surviving IFN-γ and TNF-α treated cells continued to maintain voltage-activated Na+- and K+ currents characteristic for the immature cells after 6 days in differentiation medium. Corticosterone, dihydrocorticosterone and, most prominently dexamethasone, counteracted the deleterious effects of IFN-γ and TNF-α on cell survival, A2B5-immunostaining and expression of myelin basic

  18. Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells.

    Directory of Open Access Journals (Sweden)

    Mini Balakrishnan

    Full Text Available HIV-1 integrase (IN is the target for two classes of antiretrovirals: i the integrase strand-transfer inhibitors (INSTIs and ii the non-catalytic site integrase inhibitors (NCINIs. NCINIs bind at the IN dimer interface and are thought to interfere primarily with viral DNA (vDNA integration in the target cell by blocking IN-vDNA assembly as well as the IN-LEDGF/p75 interaction. Herein we show that treatment of virus-producing cells, but not of mature virions or target cells, drives NCINI antiviral potency. NCINIs target an essential late-stage event in HIV replication that is insensitive to LEDGF levels in the producer cells. Virus particles produced in the presence of NCINIs displayed normal Gag-Pol processing and endogenous reverse transcriptase activity, but were defective at initiating vDNA synthesis following entry into the target cell. NCINI-resistant virus carrying a T174I mutation in the IN dimer interface was less sensitive to the compound-induced late-stage effects, including the reverse transcription block. Wild-type, but not T174I virus, produced in the presence of NCINIs exhibited striking defects in core morphology and an increased level of IN oligomers that was not observed upon treatment of mature cell-free particles. Collectively, these results reveal that NCINIs act through a novel mechanism that is unrelated to the previously observed inhibition of IN activity or IN-LEDGF interaction, and instead involves the disruption of an IN function during HIV-1 core maturation and assembly.

  19. Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells.

    Science.gov (United States)

    Balakrishnan, Mini; Yant, Stephen R; Tsai, Luong; O'Sullivan, Christopher; Bam, Rujuta A; Tsai, Angela; Niedziela-Majka, Anita; Stray, Kirsten M; Sakowicz, Roman; Cihlar, Tomas

    2013-01-01

    HIV-1 integrase (IN) is the target for two classes of antiretrovirals: i) the integrase strand-transfer inhibitors (INSTIs) and ii) the non-catalytic site integrase inhibitors (NCINIs). NCINIs bind at the IN dimer interface and are thought to interfere primarily with viral DNA (vDNA) integration in the target cell by blocking IN-vDNA assembly as well as the IN-LEDGF/p75 interaction. Herein we show that treatment of virus-producing cells, but not of mature virions or target cells, drives NCINI antiviral potency. NCINIs target an essential late-stage event in HIV replication that is insensitive to LEDGF levels in the producer cells. Virus particles produced in the presence of NCINIs displayed normal Gag-Pol processing and endogenous reverse transcriptase activity, but were defective at initiating vDNA synthesis following entry into the target cell. NCINI-resistant virus carrying a T174I mutation in the IN dimer interface was less sensitive to the compound-induced late-stage effects, including the reverse transcription block. Wild-type, but not T174I virus, produced in the presence of NCINIs exhibited striking defects in core morphology and an increased level of IN oligomers that was not observed upon treatment of mature cell-free particles. Collectively, these results reveal that NCINIs act through a novel mechanism that is unrelated to the previously observed inhibition of IN activity or IN-LEDGF interaction, and instead involves the disruption of an IN function during HIV-1 core maturation and assembly. PMID:24040198

  20. THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki; Isern, Nancy G.; Olson, Aaron

    2013-06-07

    Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

  1. Gamma radiation induced synthesis of poly(N-isopropylacrylamide) mediated by Reversible Addition–Fragmentation Chain Transfer (RAFT) process

    International Nuclear Information System (INIS)

    Poly(N-isopropylacrylamide) (PNiPAAm) is synthesized by gamma radiation induced Reversible Addition–Fragmentation Chain Transfer (RAFT) polymerization. The monomer is polymerized in the presence of two different trithiocarbonate-based RAFT agents i.e., Cyanomethyldodecyltrithiocarbonate (CDTC) and 2-(Dodecylthiocarbonothioylthio)-2-methylpropionic acid (DMPA) in dimethylformamide (DMF) at room temperature under nitrogen atmosphere. Number-average molecular weights (Mn) and dispersities of the polymers were determined by Size Exclusion Chromatography (SEC). Dispersities (Ɖ) of the resulting polymers are narrow, i.e., Ɖ≤1.18, indicating the occurrence of well-controlled polymerization via radiation induced RAFT process. %Conversion is determined by gravimetric method and also confirmed by Proton Nuclear Magnetic Resonance (1H-NMR) Spectroscopy. By selecting proper [Monomer]/[RAFT] ratio and controlling conversion it is possible to synthesize PNiPAAm in the molecular weight range of 2400–72400 with extremely low molecular weight distributions with the anticipation of preparing corresponding size-controlled nanogels. The phase transition of PNiPAAm with low dispersity synthesized by RAFT is sharper than PNiPAAm synthesized by free radical polymerization. - Highlights: • Poly(N-isopropylacrylamide) is synthesized by RAFT-mediated radiation induced polymerization. • Dispersities of polymers are narrow Ɖ≤1.18, proving the controlled fashion of polymerization. • By proper selection of [monomer]/[RAFT] ratio and conversion, MW range of 2400–72400 was achieved. • Phase transition of PNiPAAm synthesized by RAFT is sharper than PNiPAAm synthesized by free radical polymerization

  2. Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction.

    Science.gov (United States)

    Kim, D-M; Leem, Y-H

    2016-06-01

    Chronic stress has a detrimental effect on neurological insults, psychiatric deficits, and cognitive impairment. In the current study, chronic stress was shown to impair learning and memory functions, in addition to reducing in hippocampal Adenosine monophosphate-activated protein kinase (AMPK) activity. Similar reductions were also observed for brain-derived neurotrophic factor (BDNF), synaptophysin, and post-synaptic density-95 (PSD-95) levels, all of which was counter-regulated by a regime of regular and prolonged exercise. A 21-day restraint stress regimen (6 h/day) produced learning and memory deficits, including reduced alternation in the Y-maze and decreased memory retention in the water maze test. These effects were reversed post-administration by a 3-week regime of treadmill running (19 m/min, 1 h/day, 6 days/week). In hippocampal primary culture, phosphorylated-AMPK (phospho-AMPK) and BDNF levels were enhanced in a dose-dependent manner by 5-amimoimidazole-4-carboxamide riboside (AICAR) treatment, and AICAR-treated increase was blocked by Compound C. A 7-day period of AICAR intraperitoneal injections enhanced alternation in the Y-maze test and reduced escape latency in water maze test, along with enhanced phospho-AMPK and BDNF levels in the hippocampus. The intraperitoneal injection of Compound C every 4 days during exercise intervention diminished exercise-induced enhancement of memory improvement during the water maze test in chronically stressed mice. Also, chronic stress reduced hippocampal neurogenesis (lower Ki-67- and doublecortin-positive cells) and mRNA levels of BDNF, synaptophysin, and PSD-95. Our results suggest that regular and prolonged exercise can alleviate chronic stress-induced hippocampal-dependent memory deficits. Hippocampal AMPK-engaged BDNF induction is at least in part required for exercise-induced protection against chronic stress. PMID:26975895

  3. Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity.

    Science.gov (United States)

    Charbonneau, M; Strasser, J; Lock, E A; Turner, M J; Swenberg, J A

    1989-06-01

    Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet formation and cell proliferation in male but not in female rat kidneys. These protein droplets contained, alpha 2u-globulin, a male rat-specific low-molecular-weight protein and 2,4,4-trimethyl-2-pentanol, a metabolite of TMP that was reversibly bound to this protein. Studies were undertaken to determine if 1,4-DCB produced similar effects; 1,2-DCB was used for comparison since it did not produce renal carcinogenesis in male rats. Gel filtration chromatography of a 116,000g supernatant prepared from kidneys of 1,4-[14C]DCB-treated rats showed that radiolabel coeluted with alpha 2u-globulin as one sharp peak as opposed to a multipeak pattern observed for 1,2-[14C]DCB; the maximal quantity of radiolabel for 1,4-DCB was twice that for 1,2-DCB. Equilibrium dialysis of kidney cytosol in the presence or absence of sodium dodecyl sulfate demonstrated that the radiolabel was reversibly bound to alpha 2u-globulin; the amount for 1,4-[14C]DCB-treated rats was almost twice as much as that for 1,2-[14C]DCB-treated rats. 1,2-DCB was also shown to be covalently bound to renal alpha 2u-globulin, and covalently bound to liver and plasma high-molecular-weight proteins. 1,4-DCB and, to a minor extent, 2,5-dichlorophenol, the major metabolite of 1,4-DCB, were reversibly bound to renal alpha 2u-globulin from 1,4-DCB-treated rats. 1,4-DCB increased protein droplet formation in male but not in female rat kidneys, whereas equimolar doses of 1,2-DCB showed no effect in either sex. Renal cell proliferation, measured by [3H]thymidine incorporation into renal DNA, was increased after 1,4-DCB but not after 1,2-DCB treatment. Nephrotoxicity and biochemical alterations induced by

  4. The reversibility of the glutathionyl-quercetin adduct spreads oxidized quercetin-induced toxicity

    International Nuclear Information System (INIS)

    Quercetin is one of the most prominent dietary antioxidants. During its antioxidant activity, quercetin becomes oxidized into its o-quinone/quinone methide QQ. QQ is toxic since it instantaneously reacts with thiols of, e.g., proteins. In cells, QQ will initially form an adduct with glutathione (GSH), giving GSQ. We have found that GSQ is not stable; it dissociates continuously into GSH and QQ with a half life of 2 min. Surprisingly, GSQ incubated with 2-mercapto-ethanol (MSH), a far less reactive thiol, results in the conversion of GSQ into the MSH-adduct MSQ. A similar conversion of GSQ into relatively stable protein thiol-quercetin adducts is expected. With the dithiol dihydrolipoic acid (L(SH)2), quercetin is formed out of GSQ. These results indicate that GSQ acts as transport and storage of QQ. In that way, the initially highly focussed toxicity of QQ is dispersed by the formation of GSQ that finally spreads QQ-induced toxicity, probably even over cells

  5. Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart.

    Science.gov (United States)

    Chouabe, C; Amsellem, J; Espinosa, L; Ribaux, P; Blaineau, S; Mégas, P; Bonvallet, R

    2002-04-01

    Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities. PMID:11893582

  6. Reversal of statin-induced memory dysfunction by co-enzyme Q10: a case report

    Directory of Open Access Journals (Sweden)

    Okeahialam BN

    2015-11-01

    Full Text Available Basil N Okeahialam Cardiology Sub-Unit 1, Department of Medicine, Jos University Teaching Hospital, Jos, Nigeria Abstract: Statins are useful in the armamentarium of the clinician dealing with dyslipidemia, which increases cardiovascular morbi-mortality in hypertensive and diabetic patients among others. Dyslipidemia commonly exists as a comorbidity factor in the development of atherosclerotic cardiovascular disease. Use of statins is however associated with side effects which at times are so disabling as to interfere with activities of daily living. There are various ways of dealing with this, including use of more water-soluble varieties, intermittent dosing, or use of statin alternatives. Of late, use of co-enzyme Q10 has become acceptable for the muscle side effects. Only one report of any benefit on the rarely reported memory side effect was encountered by the author in the search of English medical literature. This is a report of a documented case of a Nigerian woman with history of statin intolerance in this case, memory dysfunction despite persisting dyslipidemia comorbidity. Her memory dysfunction side effect which interfered with activities of daily living and background muscle pain cleared when coenzyme Q10 was administered alongside low dose statin. Her lipid profile normalized and has remained normal. It is being recommended for use when statin side effects (muscle- and memory-related impair quality of life and leave patient at dyslipidemia-induced cardiovascular morbi-mortality. Keywords: statin, memory dysfunction, co-enzyme Q10, improvement

  7. Chronic unpredictable stress induces a reversible change of PER2 rhythm in the suprachiasmatic nucleus.

    Science.gov (United States)

    Jiang, Wen-Gao; Li, Su-Xia; Zhou, Shuang-Jiang; Sun, Yan; Shi, Jie; Lu, Lin

    2011-07-01

    Many clinical studies have shown that circadian rhythm abnormalities are strongly associated with major depression. The master clock of the circadian system in mammals is located in the suprachiasmatic nucleus (SCN) within the anterior hypothalamus, where Per1 and Per2 are essential core components of circadian rhythm oscillation. Chronic unpredictable stress (CUS) is a reliable animal model of depression with good face, predictive, and constructive validity. In the present study, we investigated the effects of CUS on the circadian expression of PER1 and PER2 in the SCN. We found that CUS led to depressive-like behavior and reduced the amplitude of PER2 oscillation in the SCN, which were blocked by 3 weeks of desipramine (DMI) treatment. 2 weeks after termination of CUS, the decreased peak of PER2 expression returned to control levels, whereas depressive-like behavior remained unchanged. Our findings suggest that the dampened amplitude of PER2 expression in the SCN may participate in the development of depressive-like behavior induced by CUS but is unlikely involved in the long-lasting effects of CUS on depressive-like behavior. PMID:21621196

  8. Light-induced, dark-reversible colour shifts in petals of Phlox

    International Nuclear Information System (INIS)

    Flowers of some Phlox (Phlox x paniculata L.) varieties undergo daily colour shifts, being blue in the early morning, turning red during the day, and returning to blue in the evening. The colour shift, which occurs only in the upper (adaxial) petal surfaces, is due to the daily changes in ambient light. In the laboratory, colour shifts could be induced by 2.5 h of ultraviolet, visible or far-red light and recorded by reflectance spectrophotometry. There are indications that irradiations with different kinds of light cause qualitatively different colour shifts, and that thus more than one photoreceptor pigment and more than one primary light reaction may be involved. The presence of phytochrome was demonstrated in petals of white Phlox flowers by in vivo transmission spectrophotometry. It is therefore possible that colour shifts in coloured Phlox flowers are mediated by phytochrome. Possibly the movement of ions (e.g. hydrogen ions) into or out of the vacuole (where the visible pigments are located) is affected by light absorption in a pigment in the tonoplast

  9. Study on the immune responses against pancreatic cancer induced by mucin 4 and human telomerase reverse transcriptase mRNA co-transfected dendritic cells in vitro

    Institute of Scientific and Technical Information of China (English)

    陈江

    2014-01-01

    Objective To investigate the anti-tumor immune response induced by human pancreatic cancer mucin 4mRNA and human telomerase reverse transcriptase(hTERT)mRNA cotransfected dendritic cells(DC),and to provide the experimental evidences for the treatment of pancreatic cancer with multi-epitope loaded DC vaccine.Methods DC were isolated from peripheral DC.

  10. Histamine reverses IL-5-Afforded human eosinophil survival by inducing apoptosis: Pharmacological evidence for a novel mechanism of action of histamine

    OpenAIRE

    Hasala, Hannele; Giembycz, Mark A.; Janka-Junttila, Mirkka; Moilanen, Eeva; Kankaanranta, Hannu

    2008-01-01

    Histamine reverses IL-5-Afforded human eosinophil survival by inducing apoptosis: Pharmacological evidence for a novel mechanism of action of histamine correspondence: Corresponding author. Tel.: +358335517318; fax: +358335518082. (Kankaanranta, Hannu) (Kankaanranta, Hannu) The Immunopharmacology Research Group--> , Medical School--> , University of Tampere--> , Tampere--> - FINLAND (Hasala, H...

  11. Growth hormone reverses excitotoxic damage induced by kainic acid in the green iguana neuroretina.

    Science.gov (United States)

    Ávila-Mendoza, José; Mora, Janeth; Carranza, Martha; Luna, Maricela; Arámburo, Carlos

    2016-08-01

    It is known that growth hormone (GH) is expressed in extrapituitary tissues, including the nervous system and ocular tissues, where it is involved in autocrine/paracrine actions related to cell survival and anti-apoptosis in several vertebrates. Little is known, however, in reptiles, so we analyzed the expression and distribution of GH in the eye of green iguana and its potential neuroprotective role in retinas that were damaged by the intraocular administration of kainic acid (KA). It was found, by Western blotting, that GH-immunoreactivity (GH-IR) was expressed as two isoforms (15 and 26kDa, under reducing conditions) in cornea, vitreous, retina, crystalline, iris and sclera, in varying proportions. Also, two bands for the growth hormone receptor (GHR)-IR were observed (70 and 44kDa, respectively) in the same tissues. By immunofluorescence, GH-IR was found in neurons present in several layers of the neuroretina (inner nuclear [INL], outer nuclear [ONL] and ganglion cell [GCL] layers) as determined by its co-existence with NeuN, but not in glial cells. In addition, GH and GHR co-expression was found in the same cells, suggesting paracrine/autocrine interactions. KA administration induced retinal excitotoxic damage, as determined by a significant reduction of the cell density and an increase in the appearance of apoptotic cells in the INL and GCL. In response to KA injury, both endogenous GH and Insulin-like Growth Factor I (IGF-I) expression were increased by 70±1.8% and 33.3±16%, respectively. The addition of exogenous GH significantly prevented the retinal damage produced by the loss of cytoarchitecture and cell density in the GCL (from 4.9±0.79 in the control, to 1.45±0.2 with KA, to 6.35±0.49cell/mm(2) with KA+GH) and in the INL (19.12±1.6, 10.05±1.9, 21.0±0.8cell/mm(2), respectively) generated by the long-term effect of 1mM KA intraocular administration. The co-incubation with a specific anti-GH antibody, however, blocked the protective effect of GH

  12. REM sleep deprivation reverses neurochemical and other depressive-like alterations induced by olfactory bulbectomy.

    Science.gov (United States)

    Maturana, Maira J; Pudell, Cláudia; Targa, Adriano D S; Rodrigues, Laís S; Noseda, Ana Carolina D; Fortes, Mariana H; Dos Santos, Patrícia; Da Cunha, Cláudio; Zanata, Sílvio M; Ferraz, Anete C; Lima, Marcelo M S

    2015-02-01

    There is compelling evidence that sleep deprivation (SD) is an effective strategy in promoting antidepressant effects in humans, whereas few studies were performed in relevant animal models of depression. Acute administration of antidepressants in humans and rats generates a quite similar effect, i.e., suppression of rapid eye movement (REM) sleep. Then, we decided to investigate the neurochemical alterations generated by a protocol of rapid eye movement sleep deprivation (REMSD) in the notably known animal model of depression induced by the bilateral olfactory bulbectomy (OBX). REMSD triggered antidepressant mechanisms such as the increment of brain-derived neurotrophic factor (BDNF) levels, within the substantia nigra pars compacta (SNpc), which were strongly correlated to the swimming time (r = 0.83; P < 0.0001) and hippocampal serotonin (5-HT) content (r = 0.66; P = 0.004). Moreover, there was a strong correlation between swimming time and hippocampal 5-HT levels (r = 0.70; P = 0.003), strengthen the notion of an antidepressant effect associated to REMSD in the OBX rats. In addition, REMSD robustly attenuated the hippocampal 5-HT deficiency produced by the OBX procedure. Regarding the rebound (REB) period, we observed the occurrence of a sustained antidepressant effect, indicated mainly by the swimming and climbing times which could be explained by the maintenance of the increased nigral BDNF expression. Hence, hippocampal 5-HT levels remained enhanced in the OBX group after this period. We suggested that the neurochemical complexity inflicted by the OBX model, counteracted by REMSD, is directly correlated to the nigral BDNF expression and hippocampal 5-HT levels. The present findings provide new information regarding the antidepressant mechanisms triggered by REMSD. PMID:24826915

  13. Heavy metal induced oxidative stress & its possible reversal by chelation therapy.

    Science.gov (United States)

    Flora, S J S; Mittal, Megha; Mehta, Ashish

    2008-10-01

    Exposure to heavy metals is a common phenomenon due to their environmental pervasiveness. Metal intoxication particularly neurotoxicity, genotoxicity, or carcinogenicity is widely known. This review summarizes our current understanding about the mechanism by which metalloids or heavy metals (particularly arsenic, lead, cadmium and mercury) induce their toxic effects. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. The toxic manifestations of these metals are caused primarily due to imbalance between pro-oxidant and antioxidant homeostasis which is termed as oxidative stress. Besides these metals have high affinity for thiol groups containing enzymes and proteins, which are responsible for normal cellular defense mechanism. Long term exposure to these metals could lead to apoptosis. Signaling components affected by metals include growth factor receptors, G-proteins, MAP kinases and transcription factors. Chelation therapy with chelating agents like calcium disodium ethylenediamine tetra acetic acid (CaNa(2)EDTA), British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3-dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against metal poisoning. Despite many years of research we are still far away from effective treatment against toxicity caused due to exposure to heavy metals/metalloids. The treatment with these chelating agents is compromised with number of serious side-effects. Studies show that supplementation of antioxidants along-with a chelating agent prove to be a better treatment regimen than monotherapy with chelating agents. This review attempts a comprehensive account of recent developments in the research on heavy metal poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a

  14. Silica nanoparticles induce reversible damage of spermatogenic cells via RIPK1 signal pathways in C57 mice

    Science.gov (United States)

    Ren, Lihua; Zhang, Jin; Zou, Yang; Zhang, Lianshuang; Wei, Jialiu; Shi, Zhixiong; Li, Yanbo; Guo, Caixia; Sun, Zhiwei; Zhou, Xianqing

    2016-01-01

    The reproductive toxicity of silica nanoparticles (SiNPs) is well known, but the underlying mechanism is still not clear. To investigate the toxic mechanism of SiNPs on spermatogenic cells, 60 C57 male mice were randomly and equally divided into three groups (the control group, the saline control group, and the SiNPs group) with two observed time points (45 days and 75 days). The mice in the SiNPs group were administered with SiNPs 2 mg/kg diluted in normal saline, and the mice of the saline control group were given equivoluminal normal saline by tracheal perfusion every 3 days for 45 days (in total 15 times). The control group mice were bred without treatment. In each group, a half number of the mice were sacrificed on the 45th day after the first dose, and the remaining half were sacrificed on the 75th day. The results showed that SiNPs increased the malformation of sperms and decreased the motility and concentration of sperms in epididymis on the 45th day after the first dose. SiNPs induced oxidative stress in testis and led to apoptosis and necroptosis of the spermatogenic cells. Furthermore, SiNPs increased the expression of Fas/FasL/RIPK1/FADD/caspase-8/caspase-3 and RIPK3/MLKL on the 45th day after the first dose. However, compared with the saline control group, the index of sperms and the expression of Fas/FasL/RIPK1/FADD/caspase-8/caspase-3/RIPK3/MLKL showed no significant changes in the SiNPs group on the 75th day after the first dose. These data suggested that SiNPs could induce apoptosis and necroptosis in the spermatogenic cells by activating the RIPK1 pathway resulting from oxidative stress in male mice. SiNPs-induced damage recovered on the 75th day after the first dose, which suggested that SiNPs-induced toxicity is reversible.

  15. The Combined Use of Known Antiviral Reverse Transcriptase Inhibitors AZT and DDI Induce Anticancer Effects at Low Concentrations

    Directory of Open Access Journals (Sweden)

    Thomas Aschacher

    2012-01-01

    Full Text Available A hallmark of tumor cell survival is the maintenance of elongated telomeres. It is known that antiviral reverse transcriptase inhibitors (RTIs such as azidothymidine (AZT and didanosine (ddI lead to telomere shortening at high, potentially toxic concentrations. We hypothesized that those drugs might have synergistic effects enabling successful therapy with low, nontoxic concentrations. Biologic effects of AZT and ddI were analyzed at concentrations that correspond to minimal plasma levels achieved during human immunodeficiency virus therapy. Long-term coapplication of low-dose AZT and ddI induced a significant shortening of telomeres in the tumor cell lines HCT-116, SkMel-28, MelJuso, and Jurkat. Treatment of cells with both RTI, but not with single RTI, led to a significant accumulation of γH2AX, to p53 phosphorylation, and to cell apoptosis in all cell lines. Oral low-dose dual RTI application but not low-dose single RTI application was associated with a significantly reduced tumor growth of HCT-116 cells in mice. This antiproliferative activity of the combined use of AZT and ddI at low, clinically applicable concentrations warrants clinical testing in human solid cancer.

  16. Synaptic Impairment in Layer 1 of the Prefrontal Cortex Induced by Repeated Stress During Adolescence is Reversed in Adulthood

    Science.gov (United States)

    Negrón-Oyarzo, Ignacio; Dagnino-Subiabre, Alexies; Muñoz Carvajal, Pablo

    2015-01-01

    Chronic stress is a risk factor for the development of psychiatric disorders, some of which involve dysfunction of the prefrontal cortex (PFC). There is a higher prevalence of these chronic stress-related psychiatric disorders during adolescence, when the PFC has not yet fully matured. In the present work we studied the effect of repeated stress during adolescence on synaptic function in the PFC in adolescence and adulthood. To this end, adolescent Sprague-Dawley rats were subjected to seven consecutive days of restraint stress. Afterward, both synaptic transmission and short- and long-term synaptic plasticity were evaluated in layer 1 of medial-PFC (mPFC) slices from adolescent and adult rats. We found that repeated stress significantly reduced the amplitude of evoked field excitatory post-synaptic potential (fEPSP) in the mPFC. Isolation of excitatory transmission reveled that lower-amplitude fEPSPs were associated with a reduction in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated transmission. We also found that repeated stress significantly decreased long-term depression (LTD). Interestingly, AMPA/kainate receptor-mediated transmission and LTD were recovered in adult animals that experienced a three-week stress-free recovery period. The data indicates that the changes in synaptic transmission and plasticity in the mPFC induced by repeated stress during adolescence are reversed in adulthood after a stress-free period. PMID:26617490

  17. A trypsin inhibitor from rambutan seeds with antitumor, anti-HIV-1 reverse transcriptase, and nitric oxide-inducing properties.

    Science.gov (United States)

    Fang, Evandro Fei; Ng, Tzi Bun

    2015-04-01

    Nephelium lappaceum L., commonly known as "rambutan," is a typical tropical tree and is well known for its juicy and sweet fruit which has an exotic flavor. Chemical studies on rambutan have led to the identification of various components such as monoterpene lactones and volatile compounds. Here, a 22.5-kDa trypsin inhibitor (N . lappaceum trypsin inhibitor (NLTI)) was isolated from fresh rambutan seeds using liquid chromatographical techniques. NLTI reduced the proteolytic activities of both trypsin and α-chymotrypsin. Dithiothreitol reduced the trypsin inhibitory activity of NLTI at a concentration of 1 mM, indicating that an intact disulfide bond is essential to the activity. NLTI inhibited HIV-1 reverse transcriptase with an IC50 of 0.73 μM. In addition, NLTI manifested a time- and dose-dependent inhibitory effect on growth in many tumor cells. NLTI is one of the few trypsin inhibitors with nitric oxide-inducing activity and may find application in tumor therapy. PMID:25820360

  18. LHCSR1 induces a fast and reversible pH-dependent fluorescence quenching in LHCII in Chlamydomonas reinhardtii cells.

    Science.gov (United States)

    Dinc, Emine; Tian, Lijin; Roy, Laura M; Roth, Robyn; Goodenough, Ursula; Croce, Roberta

    2016-07-01

    To avoid photodamage, photosynthetic organisms are able to thermally dissipate the energy absorbed in excess in a process known as nonphotochemical quenching (NPQ). Although NPQ has been studied extensively, the major players and the mechanism of quenching remain debated. This is a result of the difficulty in extracting molecular information from in vivo experiments and the absence of a validation system for in vitro experiments. Here, we have created a minimal cell of the green alga Chlamydomonas reinhardtii that is able to undergo NPQ. We show that LHCII, the main light harvesting complex of algae, cannot switch to a quenched conformation in response to pH changes by itself. Instead, a small amount of the protein LHCSR1 (light-harvesting complex stress related 1) is able to induce a large, fast, and reversible pH-dependent quenching in an LHCII-containing membrane. These results strongly suggest that LHCSR1 acts as pH sensor and that it modulates the excited state lifetimes of a large array of LHCII, also explaining the NPQ observed in the LHCSR3-less mutant. The possible quenching mechanisms are discussed. PMID:27335457

  19. Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E.

    Science.gov (United States)

    Ni, Yinhua; Nagashimada, Mayumi; Zhuge, Fen; Zhan, Lili; Nagata, Naoto; Tsutsui, Akemi; Nakanuma, Yasuni; Kaneko, Shuichi; Ota, Tsuguhito

    2015-01-01

    Hepatic insulin resistance and nonalcoholic steatohepatitis (NASH) could be caused by excessive hepatic lipid accumulation and peroxidation. Vitamin E has become a standard treatment for NASH. However, astaxanthin, an antioxidant carotenoid, inhibits lipid peroxidation more potently than vitamin E. Here, we compared the effects of astaxanthin and vitamin E in NASH. We first demonstrated that astaxanthin ameliorated hepatic steatosis in both genetically (ob/ob) and high-fat-diet-induced obese mice. In a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat diet, astaxanthin alleviated excessive hepatic lipid accumulation and peroxidation, increased the proportion of M1-type macrophages/Kupffer cells, and activated stellate cells to improve hepatic inflammation and fibrosis. Moreover, astaxanthin caused an M2-dominant shift in macrophages/Kupffer cells and a subsequent reduction in CD4(+) and CD8(+) T cell recruitment in the liver, which contributed to improved insulin resistance and hepatic inflammation. Importantly, astaxanthin reversed insulin resistance, as well as hepatic inflammation and fibrosis, in pre-existing NASH. Overall, astaxanthin was more effective at both preventing and treating NASH compared with vitamin E in mice. Furthermore, astaxanthin improved hepatic steatosis and tended to ameliorate the progression of NASH in biopsy-proven human subjects. These results suggest that astaxanthin might be a novel and promising treatment for NASH. PMID:26603489

  20. Reversible superconductor-insulator transition in LiTi2O4 induced by Li-ion electrochemical reaction.

    Science.gov (United States)

    Yoshimatsu, K; Niwa, M; Mashiko, H; Oshima, T; Ohtomo, A

    2015-01-01

    Transition metal oxides display various electronic and magnetic phases such as high-temperature superconductivity. Controlling such exotic properties by applying an external field is one of the biggest continuous challenges in condensed matter physics. Here, we demonstrate clear superconductor-insulator transition of LiTi2O4 films induced by Li-ion electrochemical reaction. A compact electrochemical cell of pseudo-Li-ion battery structure is formed with a superconducting LiTi2O4 film as an anode. Li content in the film is controlled by applying a constant redox voltage. An insulating state is achieved by Li-ion intercalation to the superconducting film by applying reduction potential. In contrast, the superconducting state is reproduced by applying oxidation potential to the Li-ion intercalated film. Moreover, superconducting transition temperature is also recovered after a number of cycles of Li-ion electrochemical reactions. This complete reversible transition originates in difference in potentials required for deintercalation of initially contained and electrochemically intercalated Li(+) ions. PMID:26541508

  1. Acoustic cavitation-based monitoring of the reversibility and permeability of ultrasound-induced blood-brain barrier opening

    Science.gov (United States)

    Sun, Tao; Samiotaki, Gesthimani; Wang, Shutao; Acosta, Camilo; Chen, Cherry C.; Konofagou, Elisa E.

    2015-12-01

    Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n  =  60). The stable and inertial cavitation activities were monitored during sonication. Contrast-enhanced MRI was performed immediately after sonication and every 24 h up to 6 d thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: (1) the duration of the BBB opening (r2  =  0.77) (2) the permeability of the opened BBB (r2  =  0.82) (3) the likelihood of safe opening (P  brain and assessing the pharmacokinetics of the compounds delivered can also be achieved by monitoring and controlling the stable cavitation emissions.

  2. Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement.

    Science.gov (United States)

    Hearing, Matthew C; Jedynak, Jakub; Ebner, Stephanie R; Ingebretson, Anna; Asp, Anders J; Fischer, Rachel A; Schmidt, Clare; Larson, Erin B; Thomas, Mark John

    2016-01-19

    Drug-evoked plasticity at excitatory synapses on medium spiny neurons (MSNs) of the nucleus accumbens (NAc) drives behavioral adaptations in addiction. MSNs expressing dopamine D1 (D1R-MSN) vs. D2 receptors (D2R-MSN) can exert antagonistic effects in drug-related behaviors, and display distinct alterations in glutamate signaling following repeated exposure to psychostimulants; however, little is known of cell-type-specific plasticity induced by opiates. Here, we find that repeated morphine potentiates excitatory transmission and increases GluA2-lacking AMPA receptor expression in D1R-MSNs, while reducing signaling in D2-MSNs following 10-14 d of forced abstinence. In vivo reversal of this pathophysiology with optogenetic stimulation of infralimbic cortex-accumbens shell (ILC-NAc shell) inputs or treatment with the antibiotic, ceftriaxone, blocked reinstatement of morphine-evoked conditioned place preference. These findings confirm the presence of overlapping and distinct plasticity produced by classes of abused drugs within subpopulations of MSNs that may provide targetable molecular mechanisms for future pharmacotherapies. PMID:26739562

  3. Nano/ultrafine grained austenitic stainless steel through the formation and reversion of deformation-induced martensite: Mechanisms, microstructures, mechanical properties, and TRIP effect

    Energy Technology Data Exchange (ETDEWEB)

    Shirdel, M., E-mail: mshirdel1989@ut.ac.ir [School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, P.O. Box 11155-4563, Tehran (Iran, Islamic Republic of); Mirzadeh, H., E-mail: hmirzadeh@ut.ac.ir [School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, P.O. Box 11155-4563, Tehran (Iran, Islamic Republic of); Advanced Metalforming and Thermomechanical Processing Laboratory, School of Metallurgy and Materials Engineering, University of Tehran, Tehran (Iran, Islamic Republic of); Parsa, M.H., E-mail: mhparsa@ut.ac.ir [School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, P.O. Box 11155-4563, Tehran (Iran, Islamic Republic of); Center of Excellence for High Performance Materials, School of Metallurgy and Materials Engineering, University of Tehran, Tehran (Iran, Islamic Republic of); Advanced Metalforming and Thermomechanical Processing Laboratory, School of Metallurgy and Materials Engineering, University of Tehran, Tehran (Iran, Islamic Republic of)

    2015-05-15

    A comprehensive study was carried out on the strain-induced martensitic transformation, its reversion to austenite, the resultant grain refinement, and the enhancement of strength and strain-hardening ability through the transformation-induced plasticity (TRIP) effect in a commercial austenitic 304L stainless steel with emphasis on the mechanisms and the microstructural evolution. A straightforward magnetic measurement device, which is based on the measurement of the saturation magnetization, for evaluating the amount of strain-induced martensite after cold rolling and reversion annealing in metastable austenitic stainless steels was used, which its results were in good consistency with those of the X-ray diffraction (XRD) method. A new parameter called the effective reduction in thickness was introduced, which corresponds to the reasonable upper bound on the obtainable martensite fraction based on the saturation in the martensitic transformation. By means of thermodynamics calculations, the reversion mechanisms were estimated and subsequently validated by experimental results. The signs of thermal martensitic transformation at cooling stage after reversion at 850 °C were found, which was attributed to the rise in the martensite start temperature due to the carbide precipitation. After the reversion treatment, the average grain sizes were around 500 nm and the nanometric grains of the size of ~ 65 nm were also detected. The intense grain refinement led to the enhanced mechanical properties and observation of the change in the work-hardening capacity and TRIP effect behavior. A practical map as a guidance for grain refining and characterizing the stability against grain growth was proposed, which shows the limitation of the reversion mechanism for refinement of grain size. - Graphical abstract: Display Omitted - Highlights: • Nano/ultrafine grained austenitic stainless steel through martensite treatment • A parameter descriptive of a reasonable upper bound on

  4. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial

    DEFF Research Database (Denmark)

    Pühringer, Friedrich K; Rex, Christopher; Sielenkämper, Andreas W;

    2008-01-01

    Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evaluated....

  5. Nanoscale Deformation Behavior of Phase-Reversion Induced Austenitic Stainless Steels: The Interplay Between Grain Size from Nano-Grain Regime to Coarse-Grain Regime

    Science.gov (United States)

    Misra, R. D. K.; Venkatsurya, P. K. C.; Somani, M. C.; Karjalainen, L. P.

    2012-12-01

    We have used the recently adopted concept of phase reversion to obtain grain size from the nanograined/ultrafine-grained (NG/UFG) to fine grain (FG) regime by varying temperature-time annealing sequence of cold deformed metastable austenite. The phase-reversion induced NG/UFG structure was characterized by high strength-high ductility combination. The concept of phase reversion involves severe cold deformation of metastable austenite to generate strain-induced martensite. Upon annealing, martensite transforms back to austenite through a diffusional reversion mechanism with NG/UFG, sub-micron grains (SMG) or FG structure, depending on the annealing condition. Depth-sensing nanoindentation experiments were combined with electron microscopy to elucidate the dependence of grain size from nanograin/ultrafine-grain (NG/UFG) to coarse grain (CG) regime on the deformation mechanisms. There was distinct transition in the deformation mechanism from intense mechanical twinning and stacking faults in NG/UFG structure to strain-induced martensite formation at the intersection of shear bands in the CG structure. The transition in the deformation mechanism is discussed in terms of increase in austenite stability with decrease in grain size.

  6. Magnetically induced electric polarization reversal in multiferroic TbMn$_2$O$_5$: Terbium spin reorientation studied by resonant x-ray diffraction

    OpenAIRE

    Johnson, R. D.; Mazzoli, C.; Bland, S. R.; Du, C-H.; Hatton, P. D.

    2011-01-01

    In multiferroic TbMn$_2$O$_5$, the behavior of the terbium ions forms a crucial part of the magneto-electric coupling. The result is a magnetically induced reversal of the electric polarization at 2 T. In this article we present the first direct measurement of the terbium magnetic structure under applied magnetic fields. Contrary to the current interpretation of the magnetic properties of \\tmo, we show that upon the electric polarization reversal the terbium sub-lattice adopts a canted antife...

  7. The effect of nitrogen on the formation of phase reversion-induced nanograined/ultrafine-grained structure and mechanical behavior of a Cr-Ni-N steel

    International Nuclear Information System (INIS)

    Research highlights: → We describe here an electron microscopy study of microstructural evolution associated with martensitic shear phase reversion-induced nanograined/ultrafine-grained (NG/UFG) structure in an experimental Fe-17Cr-7Ni alloy with nitrogen. The primary objective is to understand and obtain fundamental insights on the influence of degree of austenite stability and interstitial elements (nitrogen) in terms of phase reversion process, microstructural evolution during reversion annealing. - Abstract: In the study described here, we have used the concept of phase reversion involving combination of cold working and annealing to examine the effect of nitrogen on the reversion transformation of strain-induced martensite to austenite and tensile behavior of a Cr-Ni-N steel. The behavior is compared with that of a Cr-Ni steel with extremely low levels of interstitial elements C and N. Consistent with the high metastability of the investigated Cr-Ni-N steel, only 40% cold rolling reduction was adequate to transform 100% austenite to martensite, while Cr-Ni steel required ∼73% reduction for the complete transformation. The cold deformed austenite was characterized by a combination of lath and dislocation cell-type martensite. On annealing in the temperature range of 800-900 deg. C for 1-100 s, the phase reversion of martensite to austenite occurred by shear mechanism involving the following steps: (a) transformation of strain-induced martensite to lath-type austenite grains with high dislocation density, (b) refinement of reverted austenite grains due to recovery, i.e., dislocation cell formation to produce defect-free austenite subgrains, and (c) finally recrystallization of austenite grains following coalescence of sub-grains to form NG/UFG structure with grain size in the range of ∼200-600 nm. Some nucleation of secondary precipitates also occurred. Interestingly, the phase reversion mechanism was similar to that of the Cr-Ni steel. In spite of the

  8. Reversible and Irreversible Drought-Induced Changes in the Anther Proteome of Rice(Oryza sativa L.)Genotypes IR64 and Moroberekan

    Institute of Scientific and Technical Information of China (English)

    Jian-Xiang Liu; John Bennett

    2011-01-01

    Crop yield is most sensitive to water deficit during the reproductive stage.For rice,the most sensitive yield component is spikelet fertility and the most sensitive stage is immediately before heading.Here,we examined the effect of drought on the anther proteome of two rice genotypes:Moroberekan and IR64.Water was withheld for 3 d before heading(3DBH)in well watered controls for 5 d until the flag leaf relative water content(RWC)had declined to 45-50%.Plants were then re-watered and heading occurred 2-3 d later,representing a delay of 4-5 d relative to controls.The anther proteins were separated at 3 DBH,at the end of the stress period,and at heading in stressed/re-watered plants and controls by two-dimensional(2-D)gel electrophoresis,and 93 protein spots were affected reproducibly in abundance by drought during the experiment across two rice genotypes.After drought stress,upon re-watering,expressions of 24 protein spots were irreversible in both genotypes,60 protein spots were irreversible in IR64 but reversible in Moroberekan,only nine protein spots were irreversible in Moroberekan while reversible in IR64.Among them,there were 14 newly drought-induced protein spots in IR64;none of them was reversible on re-watering.However,there were 13 newly drought-induced protein spots in Moroberekan,10 of them were reversible on re-watering,including six drought-induced protein spots that were not reversed in IR64.Taken together,our proteomics data reveal that drought-tolerant genotype Moroberekan possessed better recovery capability following drought and re-watering at the anther proteome level than the drought-sensitive genotype IR64.The disruptions of drought to rice anther development and pollen cell functions are also discussed in the paper.

  9. Radiation-induced forward and reverse specific locus mutations and dominant cataract mutations in treated strain BALB/c and DBA/2 male mice

    International Nuclear Information System (INIS)

    In the present experiments the genotype of the X-irradiated male mouse was varied. Males were mated to untreated, standard Test-stock females. Mutagenic effects were determined for treated stem cell spermatogonia. Since stem cell spermatogonia are repair competent, should genetic variability in the DNA repair processes exist it would be evident in the induced mutation rates. Based upon the above-mentioned sensitivity to induced killing, reduction in female fecundity, dominant lethal mutation frequency and unscheduled DNA synthesis, strain BALB/c was chosen as sensitive to radiation-induced mutagenesis and strain DBA/2 was chosen as repair competent. The mutation rates to recessive specific locus and dominant cataract alleles were determined. Additionally, employing treated BALB/c and DBA/2 male mice allowed, for the first time, the determination of the radiation-induced reverse mutation rate at 4 specific loci. Results indicate no effect of genotype on the radiation-induced forward mutation rate at the specific loci, although a possibly higher radiation induced mutation rate to dominant cataract alleles was observed in treated DBA/2 mice as compared to treated BALB/c or (101/E1 x C3H/E1)F1 mice but these results require confirmation, and the reverse mutation rate at the a and d loci following paternal irradiation was higher than the spontaneous frequency. (Auth.)

  10. TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation

    Directory of Open Access Journals (Sweden)

    Belarbi Karim

    2012-01-01

    Full Text Available Abstract Background Chronic neuroinflammation is a hallmark of several neurological disorders associated with cognitive loss. Activated microglia and secreted factors such as tumor necrosis factor (TNF-α are key mediators of neuroinflammation and may contribute to neuronal dysfunction. Our study was aimed to evaluate the therapeutic potential of a novel analog of thalidomide, 3,6'-dithiothalidomide (DT, an agent with anti-TNF-α activity, in a model of chronic neuroinflammation. Methods Lipopolysaccharide or artificial cerebrospinal fluid was infused into the fourth ventricle of three-month-old rats for 28 days. Starting on day 29, animals received daily intraperitoneal injections of DT (56 mg/kg/day or vehicle for 14 days. Thereafter, cognitive function was assessed by novel object recognition, novel place recognition and Morris water maze, and animals were euthanized 25 min following water maze probe test evaluation. Results Chronic LPS-infusion was characterized by increased gene expression of the proinflammatory cytokines TNF-α and IL-1β in the hippocampus. Treatment with DT normalized TNF-α levels back to control levels but not IL-1β. Treatment with DT attenuated the expression of TLR2, TLR4, IRAK1 and Hmgb1, all genes involved in the TLR-mediated signaling pathway associated with classical microglia activation. However DT did not impact the numbers of MHC Class II immunoreactive cells. Chronic neuroinflammation impaired novel place recognition, spatial learning and memory function; but it did not impact novel object recognition. Importantly, treatment with DT restored cognitive function in LPS-infused animals and normalized the fraction of hippocampal neurons expressing the plasticity-related immediate-early gene Arc. Conclusion Our data demonstrate that the TNF-α synthesis inhibitor DT can significantly reverse hippocampus-dependent cognitive deficits induced by chronic neuroinflammation. These results suggest that TNF-α is a

  11. Chronic administration of brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus reverses obesity induced by high-fat diet

    OpenAIRE

    Wang, Chuanfeng; Godar, Rebecca J.; Billington, Charles J.; Kotz, Catherine M.

    2010-01-01

    An acute injection of brain-derived neurotrophic factor (BDNF) in the hypothalamic paraventricular nucleus (PVN) reduces body weight by decreasing feeding and increasing energy expenditure (EE), in animals on standard laboratory chow. Animals have divergent responses to a high-fat diet (HFD) exposure, with some developing obesity and others remaining lean. In the current study, we tested two hypotheses: 1) BDNF in the PVN reverses HFD-induced obesity, and 2) animals with higher body fat have ...

  12. Toxin ζ Reversible Induces Dormancy and Reduces the UDP-N-Acetylglucosamine Pool as One of the Protective Responses to Cope with Stress

    OpenAIRE

    Mariangela Tabone; Silvia Ayora; Alonso, Juan C.

    2014-01-01

    Toxins of the ζ/PezT family, found in the genome of major human pathogens, phosphorylate the peptidoglycan precursor uridine diphosphate-N-acetylglucosamine (UNAG) leading to unreactive UNAG-3P. Transient over-expression of a PezT variant impairs cell wall biosynthesis and triggers autolysis in Escherichia coli. Conversely, physiological levels of ζ reversibly induce dormancy produce a sub-fraction of membrane-compromised cells, and a minor subpopulation of Bacillus subtilis cells become tol...

  13. Investigation of elemene-induced reversal of tamoxifen resistance in MCF-7 cells through oestrogen receptor α (ERα) re-expression.

    Science.gov (United States)

    Zhang, Bin; Zhang, Xia; Tang, Bo; Zheng, Peishi; Zhang, Yang

    2012-11-01

    Endocrine therapy is an important therapeutic approach for the treatment of oestrogen receptor (ER)-positive breast cancer. However, a number of these endocrine therapies can fail when the tumour loses its ER expression during treatment. To date, few studies have explored the potential clinical significance of traditional Chinese medicine in inducing the reversal of resistance to endocrine therapy in breast cancers. We used the ERα-negative MCF7 breast cancer cell line to create a tamoxifen (TAM)-resistant cell line, MCF7/TAM cells. After treating MCF7/TAM cells with ELE to induce the re-expression of ERα, we investigated the role and molecular mechanisms by which elemene (ELE) promotes the reversal of resistance to endocrine therapy. We discovered that treatment with 10 μg/ml ELE restored the sensitivity of MCF7/TAM cells to TAM. RT-PCR analysis revealed that ELE treatment upregulated ERα mRNA levels in MCF7/TAM cells, and immunohistochemistry confirmed the upregulation of ERα expression. Western blot analysis revealed that ELE treatment decreased the protein expression levels of Ras, MEK1/2 and p-ERK1/2 in MCF7/TAM cells. The loss of ERα expression was the primary reason for TAM resistance in MCF7 cells. The ELE-induced reversal of TAM resistance was mediated by the upregulation of ERα mRNA and the re-expression of ERα through the MAPK pathway. PMID:23053650

  14. Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression.

    Science.gov (United States)

    de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; Vasconcelos, Germana Silva; Silva, Márcia Calheiros Chaves; da Silva, Jéssica Calheiros; Macêdo, Danielle; de Lucena, David Freitas; Vasconcelos, Silvânia Maria Mendes

    2015-12-15

    Brain derived neurotrophic factor (BDNF) is linked to the pathophysiology of depression. We hypothesized that BDNF is one of the neurobiological pathways related to the augmentation effect of alpha-lipoic acid (ALA) when associated with antidepressants. Female mice were administered vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days the animals were divided in groups that were further administered: vehicle, desvenlafaxine (DVS) 10 or 20mg/kg, ALA 100 or 200mg/kg or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200 or DVS20+ALA200. ALA or DVS alone or in combination reversed CORT-induced increase in immobility time in the forced swimming test and decrease in sucrose preference, presenting, thus, an antidepressant-like effect. DVS10 alone reversed CORT-induced decrease in BDNF in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The same was observed in the HC and ST of ALA200 treated animals. The combination of DVS and ALA200 reversed CORT-induced alterations in BDNF and even, in some cases, increased the levels of this neurotrophin when compared to vehicle-treated animals in HC and ST. Taken together, these results suggest that the combination of the DVS+ALA may be valuable for treating conditions in which BDNF levels are decreased, such as depression. PMID:26350703

  15. Relationship between first-twitch depression and train-of-four ratio during sugammadex reversal of rocuronium-induced neuromuscular blockade

    Science.gov (United States)

    Oh, You Na; Kim, Tae Yeon; Oh, Song Yee; Sin, Yeong Hun

    2016-01-01

    Background The primary outcome of sugammadex reversal for rocuronium-induced neuromuscular block (NMB) is a train-of-four ratio (TOFR) of 0.9, not first twitch (T1) height. We investigated whether the recovery of TOFR or T1 differs based on the reversal of NMB with neostigmine or sugammadex. Methods The acceleromyographic responses from 0.6 mg/kg of rocuronium were monitored supramaximally in 80 patients after induction of anesthesia. The TOFR and T1 height were recorded, and saved in a personal computer using TOF-Watch SX Monitor software in all patients. Patients were randomly assigned to 2 groups to receive either neostigmine 50 µg/kg with glycopyrrolate 10 µg/kg (neostigmine group, n = 40) or sugammadex 2.0 mg/kg (sugammadex group, n = 40). The primary objective was to determine the difference of recovery time between TOFR to 0.9 and T1 to 0.9 after sugammadex or neostigmine administration during moderate rocuronium-induced NMB. Results The recovery pattern of the TOFR 2 min after sugammadex administration was 1.0 or more, but that of T1 was less than 90% (T1 / control value) up to 6 min after drug was injected. The recovery pattern of TOFR and T1 was similar during the 20 min after reversal with neostigmine. Conclusions If you have not performed the T1 monitoring, both TOFR and T1 should be considered to confirm suitable recovery during the 6 min after reversal with sugammadex during rocuronium-induced moderate NMB.

  16. Reversible cAMP-induced translocation of cytoskeleton-associated 300- to 350-kDa proteins from nucleus to cytoplasm

    International Nuclear Information System (INIS)

    The authors previously reported that treatment of SV-3Y1 cells in an exponential growth state with db-cAMP plus theophylline induced reversible disappearance of nuclear dots stained by monoclonal anti-microtubule-associated protein (MAP)-1 antibody. In the present study, the authors examined the relation between the intracellular localization and phosphorylation of 300- to 350-kDa proteins that are intracellular antigens for our anti-Map-1 and -2 antibodies. Treatment with db-cAMP plus theophylline was found to result in a reversible decrease in immunofluorescent staining of the nucleus with polyclonal MAP-1 or -2 antibody, and a reversible increase in that of the cytoplasm. Simultaneous treatment with colchicine, colcemid, putrescine, or α-naphthyl phosphate in the presence of db-cAMP plus theophylline almost prevented this effect of db-cAMP plus theophylline. They examined the cytoplasmic and nuclear fractions by immunoperoxidase staining, immunoprecipitation, and 125I-protein A with anti-MAP-1 and -2 antibodies. The present research indicated that treatment with db-cAMP plus theophylline resulted in the reversible translocation of 300- to 350-kDa proteins from the nucleus to the cytoplasm accompanied by the dephosphorylation of these proteins

  17. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Wu, C-W.; Biggar, K.K.; Storey, K.B. [Carleton University, Department of Biology, Institute of Biochemistry, Ottawa, ON (Canada)

    2013-01-28

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans.

  18. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    International Nuclear Information System (INIS)

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans

  19. Reversal of rocuronium-induced neuromuscular block by sugammadex is independent of renal perfusion in anesthetized cats

    NARCIS (Netherlands)

    Staals, L.M.; Boer, H.D. de; Egmond, J. van; Hope, F.; Pol, F.M. van de; Bom, A.H.; Driessen, J.J.; Booij, L.H.D.J.

    2011-01-01

    PURPOSE: Sugammadex is a selective relaxant binding agent designed to encapsulate the aminosteroidal neuromuscular blocking agent rocuronium, thereby reversing its effect. Both sugammadex and the sugammadex-rocuronium complex are eliminated by the kidneys. This study investigated the effect of sugam

  20. Effects of Acidification and Alkalinization on the Lipid Emulsion-Mediated Reversal of Toxic Dose Levobupivacaine-Induced Vasodilation in the Isolated Rat Aorta.

    Science.gov (United States)

    Ok, Seong-Ho; Kim, Won Ho; Yu, Jongsun; Lee, Youngju; Choi, Mun-Jeoung; Lim, Dong Hoon; Hwang, Yeran; Kim, Yeon A; Sohn, Ju-Tae

    2016-01-01

    The goal of this in vitro study was to examine the effects of pre-acidification and pre-akalinization on the lipid emulsion-mediated reversal of toxic dose levobupivacaine-induced vasodilation in isolated rat aorta. Isolated aortic rings with and without the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) were exposed to four types of Krebs solution (pH 7.0, 7.2, 7.4, and 7.6), followed by the addition of 60 mM potassium chloride. When the toxic dose of levobupivacaine (3 × 10(-4) M) produced a stable and sustained vasodilation in the isolated aortic rings that were precontracted with 60 mM potassium chloride, increasing lipid emulsion concentrations (SMOFlipid(®): 0.24, 0.48, 0.95 and 1.39%) were added to generate concentration-response curves. The effects of mild pre-acidification alone and mild pre-acidification in combination with a lipid emulsion on endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells were investigated by Western blotting. Mild pre-acidification caused by the pH 7.2 Krebs solution enhanced the lipid emulsion-mediated reversal of levobupivacaine-induced vasodilation in isolated endothelium-intact aortic rings, whereas mild pre-acidification caused by the pH 7.2 Krebs solution did not significantly alter the lipid emulsion-mediated reversal of the levobupivacaine-induced vasodilation in isolated endothelium-denuded aortic rings or endothelium-intact aortic rings with L-NAME. A lipid emulsion attenuated the increased eNOS phosphorylation induced by the pH 7.2 Krebs solution. Taken together, these results suggest that mild pre-acidification enhances the lipid emulsion-mediated reversal of toxic dose levobupivacaine-induced vasodilation in the endothelium-intact aorta via the inhibition of nitric oxide. PMID:26917987

  1. Reverse Engineering

    International Nuclear Information System (INIS)

    This book gives descriptions of reverse engineering with principle and structure of it, including what reverse engineering is, prospect and concerned laws, basic knowledge for reverse engineering like manual and back to user mode, using tool such as IDA installation, dependency walker and dump bin, network monitoring and universal extractor. It indicates analysis of malignant code, giving explanations of file virus, spy ware, an infection way of malignant code, anti debugging like Find window.

  2. Reversible strain-induced magnetization switching in FeGa nanomagnets: Pathway to a rewritable, non-volatile, non-toggle, extremely low energy straintronic memory

    Science.gov (United States)

    Ahmad, Hasnain; Atulasimha, Jayasimha; Bandyopadhyay, Supriyo

    2015-12-01

    We report reversible strain-induced magnetization switching between two stable/metastable states in ~300 nm sized FeGa nanomagnets delineated on a piezoelectric PMN-PT substrate. Voltage of one polarity applied across the substrate generates compressive strain in a nanomagnet and switches its magnetization to one state, while voltage of the opposite polarity generates tensile strain and switches the magnetization back to the original state. The two states can encode the two binary bits, and, using the right voltage polarity, one can write either bit deterministically. This portends an ultra-energy-efficient non-volatile “non-toggle” memory.

  3. Effects of Acidification and Alkalinization on the Lipid Emulsion-Mediated Reversal of Toxic Dose Levobupivacaine-Induced Vasodilation in the Isolated Rat Aorta

    OpenAIRE

    Ok, Seong-Ho; Kim, Won Ho; Yu, Jongsun; Lee, Youngju; Choi, Mun-Jeoung; Lim, Dong Hoon; Hwang, Yeran; Kim, Yeon A.; Sohn, Ju-Tae

    2016-01-01

    The goal of this in vitro study was to examine the effects of pre-acidification and pre-akalinization on the lipid emulsion-mediated reversal of toxic dose levobupivacaine-induced vasodilation in isolated rat aorta. Isolated aortic rings with and without the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) were exposed to four types of Krebs solution (pH 7.0, 7.2, 7.4, and 7.6), followed by the addition of 60 mM potassium chloride. When the toxic dose of levobupivacai...

  4. Magnolol treatment reversed the glial pathology in an unpredictable chronic mild stress-induced rat model of depression.

    Science.gov (United States)

    Li, Lu-Fan; Yang, Jie; Ma, Shi-Ping; Qu, Rong

    2013-07-01

    Growing evidence indicates that glia atrophy contributes to the pathophysiology and the pathogenesis of major depressive disorder. Magnolol is the main constituent identified in the bark of Magnolia officinalis, which has been used for the treatment of mental disorders, including depression, in Asian countries. In this study, we investigated the antidepressant-like effect and the possible mechanisms of magnolol in rats subjected to unpredictable chronic mild stress (UCMS). The ameliorative effect of magnolol on depression symptoms was investigated through behavior tests, including sucrose preference test, open-field test and forced-swimming test. In addition, the levels of glial fibrillary acidic protein (GFAP), an astrocyte marker, in the hippocampus and prefrontal cortex were determined by immunohistochemistry, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR). Exposure to UCMS resulted in a decrease of behavioral activity, whereas magnolol (20, 40 mg/kg) and fluoxetine (20mg/kg) administration significantly reversed the depressive-like behaviors (P<0.05).Moreover, treatment with magnolol effectively increased GFAP mRNA and protein levels in UCMS rats. These results confirmed the antidepressant-like effect of magnolol, which maybe primarily mediated by reversing the glial atrophy in the UCMS rat brain. PMID:23632393

  5. p53-dependent manner of persistent activation of the radiation-induced reversion in the pink-eyed unstable mouse embryo

    International Nuclear Information System (INIS)

    Full text: We previously reported that radiation has an ability to induce genomic instability which causes delayed and untargeted mutation. These mutations aren't accounted for by the usual relationship between DNA damages and repair. However, the mechanisms of a long-term memory of DNA damage and the persistence of up-regulated recombination activity have yet to be elucidated. The mouse pink-eyed unstable (pun) mutation is due to an intragenic duplication of the pink-eyed dilution locus and frequently reverts black to the wild type in germ cells as well as somatic cells. The frequency of reversion was estimated by counting cluster of pigment cells in retinal pigment epithelium. Twice increase of the reversion was observed in F1 mice born to 6Gy irradiated male at spermatozoa stage, but not at other spermatogenesis stages( -tid, -cyte, -gonia ). Trans-genarational effect in F2 mice also didn't observe. Therefore, this phenomenon only occurs under the restricted germ cell stage. Additionally, the reversion frequency of p53 deficient F1 mouse born to irradiated sperm was less than irradiated wild mouse. 5aza-dc chemical agent, which is DNA methylation emzyme inhibitor, also suppressed pun allele recombination in mouse embryo. These data indicate that p53 contributes delayed and untargeted mutation, perhaps, by regulation of DNA metylation status

  6. Energy Spectrum of La3Lu2Ga3O12:Cr3+ and Its Pressure-Induced R-Line-Shift Reversal

    Science.gov (United States)

    Ma, Dong-Ping; Chen, Ju-Rong

    2005-12-01

    By means of both the theory for pressure-induced shifts (PS) of energy spectra and the theory for shifts of energy spectra due to electron-phonon interaction (EPI), the normal-pressure energy spectra of α and β centers of Cr3+ ions for LLGG:Cr3+ and the PS's of R1 lines and U band of these centers have been calculated at 10 K, respectively. The total calculated results are in very good agreement with the experimental data. For LLGG:Cr3+, the pressure-induced low-high crystal-field transition and the reversal of R1-line PS take place. The pressure-dependent variation of Rmixel (2E-4T2) [mixing-degree of |t22(3T1)e4T2 rangle and |t23 2Erangle base-wavefunctions in the wavefunction of R1 state without EPI] plays a key role for the reversal of R1-line PS. The behavior of the pure electronic PS of R1 line is quite different from that of the PS of R1 line due to EPI. It is the combined effect of them that gives rise to the total PS of R1 line. The comparison between R1-line PS's of GSGG:Cr3+ and LLGG:Cr3+ has been made. It is found that a peak of R1-line PS appears at Rmixel (2E-4T2) ≈ 0.08.

  7. Reversible and irreversible temperature-induced changes in exchange-biased planar Hall effect bridge (PHEB) magnetic field sensors

    DEFF Research Database (Denmark)

    Rizzi, G.; Lundtoft, N.C.; Østerberg, F.W.;

    2012-01-01

    We investigate the changes of planar Hall effect bridge magnetic field sensors upon exposure to temperatures between 25° C and 90°C. From analyses of the sensor response vs. magnetic fields we extract the exchange bias field Hex, the uniaxial anisotropy field HK and the anisotropic...... magnetoresistance (AMR) of the exchange biased thin film at a given temperature and by comparing measurements carried out at elevated temperatures T with measurements carried out at 25° C after exposure to T, we can separate the reversible from the irreversible changes of the sensor. The results are not only...

  8. Electric field-induced, reversible lotus-to-rose transition in nanohybrid shish kebab paper with hierarchical roughness.

    Science.gov (United States)

    Laird, Eric D; Bose, Ranjita K; Qi, Hao; Lau, Kenneth K S; Li, Christopher Y

    2013-11-27

    Nature uses a variety of strategies to tune wetting behavior for biological applications. By artificially mimicking these strategies, a variety of different wetting conditions can be achieved. Numerous examples exist of designed surfaces that can mimic the wetting behavior of lotus leaves or rose petals, but few surfaces that may reversibly transition between the two have been reported. In this paper, a combination of topological control over conductive, carbon-based nanomaterials and low surface energy coating was used to tune the wetting properties between "lotus" and "rose." The topological control was imparted by a hierarchical "nanohybrid shish kebab" structure, which uses solution-grown polymer single crystals on carbon nanotubes to tune the surface roughness of the latter. The low surface energy polytetrafluoroethylene (PTFE) coating was deposited by the initiated chemical vapor deposition technique. Application of electric potential on these unique nanostructures allows the surfaces to reversibly transition between "lotus" and "rose" behavior. A further irreversible transition between "rose" and the fully wetted Wenzel wetting state was also predicted and shown. These materials show remarkable promise for lab-on-a-chip devices and surface passivation for biological studies. PMID:24164111

  9. CM156, a Sigma Receptor Ligand, Reverses Cocaine-Induced Place Conditioning and Transcriptional Responses in the Brain

    OpenAIRE

    Xu, Yan-Tong; Robson, Matthew J.; Szeszel-Fedorowicz, Wioletta; Patel, Divyen; Rooney, Robert; Christopher R. McCurdy; Matsumoto, Rae R.

    2011-01-01

    Repeated exposure to cocaine induces neuroadaptations which contribute to the rewarding properties of cocaine. Using cocaine-induced conditioned place preference (CPP) as an animal model of reward, earlier studies have shown that sigma (σ) receptor ligands can attenuate the acquisition, expression and reactivation of CPP. However, the underlying molecular mechanisms that are associated with these changes are not yet understood. In the present study, CM156, a novel antagonist with high selecti...

  10. Evaluation of toxicological and antioxidant potential of Nardostachys jatamansi in reversing haloperidol-induced catalepsy in rats

    OpenAIRE

    Rasheed, A S; Venkataraman, S.; K N Jayaveera; Fazil, A Mohammed; Yasodha, K J; Aleem, M A; Mohammed, M.; Khaja, Z; Ushasri, B; Pradeep, H A; Ibrahim, M.

    2010-01-01

    An aqueous root extract from Nardostachys jatamansi was investigated for its antioxidant and anticataleptic effects in the haloperidol-induced catalepsy rat model of the disease by measuring various behavioral and biochemical parameters. Catalepsy was induced by administration of haloperidol (1 mg/kg, ip) in male albino rats. A significant (P < 0.01) reduction in the cataleptic scores were observed in all the drug-treated groups as compared to the haloperidol-treated group; with maximum reduc...

  11. Hyperammonemia induces glial activation, neuroinflammation and alters neurotransmitter receptors in hippocampus, impairing spatial learning: reversal by sulforaphane

    OpenAIRE

    Hernández-Rabaza, Vicente; Cabrera-Pastor, Andrea; Taoro-González, Lucas; Malaguarnera, Michele; Agustí, Ana; Llansola, Marta; Felipo, Vicente

    2016-01-01

    Background Patients with liver cirrhosis and minimal hepatic encephalopathy (MHE) show mild cognitive impairment and spatial learning dysfunction. Hyperammonemia acts synergistically with inflammation to induce cognitive impairment in MHE. Hyperammonemia-induced neuroinflammation in hippocampus could contribute to spatial learning impairment in MHE. Two main aims of this work were: (1) to assess whether chronic hyperammonemia increases inflammatory factors in the hippocampus and if this is as...

  12. Liraglutide prevents and reverses monocrotaline-induced pulmonary arterial hypertension by suppressing ET-1 and enhancing eNOS/sGC/PKG pathways

    Science.gov (United States)

    Lee, Mei-Yueh; Tsai, Kun-Bow; Hsu, Jong-Hau; Shin, Shyi-Jang; Wu, Jiunn-Ren; Yeh, Jwu-Lai

    2016-01-01

    Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is widely used to treat diabetes. However, its effect on pulmonary arterial hypertension (PAH) is unknown. In this study, we investigated its effects on rats with monocrotaline (MCT)-induced PAH and mechanisms on rat pulmonary artery smooth muscle cells (PASMCs). Liraglutide was investigated for both prevention and treatment of MCT-induced PAH. The hemodynamic and body weight changes, right heart hypertrophy, lung morphology, immune-reactivity of endothelial nitric oxide synthase (eNOS), endothelin-1 and cyclic guanosine monophosphate (cGMP) levels, protein expressions of eNOS, soluble guanylyl cyclase (sGCα), protein kinase G (PKG) and Rho kinase (ROCK) II pathway were measured in both in vivo and in vitro. Cell migration and cell cycle were also determined. Liraglutide both prevented and reversed MCT-induced PAH, right ventricle hypertrophy and pulmonary vascular wall remodeling. Protein expression of ROCK II was increased while eNOS, sGC and PKG were decreased. Pretreatment with liraglutide inhibited platelet-derived growth factor (PDGF)-BB stimulated PASMCs migration, which were associated with cell-cycle arrest at G0/G1 phase. Liraglutide may have both preventive and therapeutic effects on MCT-induced PAH, through the eNOS/sGC/PKG and Rho kinase pathways. Thus, liraglutide may have a therapeutic role in pulmonary vascular remodelling. PMID:27581840

  13. Vasectomy Reversal

    Medline Plus

    Full Text Available ... is a realistic option for many patients. Today we are going to go to the operating room and show you microsurgical vasectomy reversal. We start the procedure by localizing the site of ...

  14. Vasectomy Reversal

    Medline Plus

    Full Text Available ... keep the vas well vascularized because ischemia will cause fibrosis and scarring and prevent the vasectomy reversal ... to make sure that we don't inadvertently cause any vascular to the vas or even to ...

  15. Vasectomy Reversal

    Medline Plus

    Full Text Available ... improving health. Hello, my name is Harris Nagler. I'm the Chairman of the Sol and Margaret ... Israel Medical Center in New York City. Today I'm going to perform a vasectomy reversal using ...

  16. Vasectomy Reversal

    Medline Plus

    Full Text Available ... Today we are going to go to the operating room and show you microsurgical vasectomy reversal. We ... vas and that will be examined under the operating- under the microscope to see if there’s sperm ...

  17. Reversible Sterilization

    Science.gov (United States)

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  18. Vasectomy Reversal

    Medline Plus

    Full Text Available Vasectomy Reversal Beth Israel Medical Center, New York, NY February 19, 2009 Welcome to this "OR Live" Webcast presentation premiering from Beth Israel Medical Center in New York City. ...

  19. Vasectomy Reversal

    Medline Plus

    Full Text Available Vasectomy Reversal Beth Israel Medical Center, New York, NY February 19, 2009 Welcome to this "OR Live" Webcast presentation premiering from Beth Israel Medical Center in New York City. During the ...

  20. Reversal of oxidative stress-induced apoptosis in T and B lymphocytes by Coenzyme Q10 (CoQ10)

    Science.gov (United States)

    Gollapudi, Sastry; Gupta, Sudhir

    2016-01-01

    Coenzyme Q10, (CoQ10) an electron transporter and an antioxidant, protects a variety of cell types against oxidative stress and apoptosis. However, protective effect of CoQ10 on oxidative stress-induced apoptosis in lymphocytes has not been studied in detail. In this study, we investigated the effect of CoQ10 on oxidative stress-induced apoptosis in lymphocytes. An exposure of peripheral blood lymphocytes to oxidative stressors, rotenone or hydrogen peroxide, lead to apoptosis. Pre-treatment of lymphocytes with CoQ10 resulted in a significantly reduced level of oxidative stress-induced apoptosis, which was associated with decreased reactive oxygen species production, an inhibition of mitochondrial membrane depolarization, and inhibition of activation of caspase-9 and caspase-3. Furthermore, CoQ10 inhibited oxidative stress induced apoptosis in both CD4+ T, and CD8+ T, and CD19+ B cells. Our findings suggest that CoQ10 may provide new therapeutic strategies for preventing oxidative stress-induced cell death and dysfunction in lymphocytes and lymphocyte subsets.

  1. The impairment in endothelial function induced by non-esterified fatty acids can be reversed by insulin.

    Science.gov (United States)

    Lind, L; Fugmann, A; Branth, S; Vessby, B; Millgård, J; Berne, C; Lithell, H

    2000-09-01

    Dyslipidaemia, with elevations of circulating triacylglycerols (triglycerides) and non-esterified (free) fatty acids, and hyperinsulinaemia are often found in the same subjects, the so-called 'insulin resistance syndrome'. The present study aims to investigate how elevated levels of non-esterified fatty acids, hyperinsulinaemia and the combination of these factors affects endothelium-dependent vasodilatation (EDV). Ten volunteers were examined on two occasions. Intralipid (plus heparin) or saline (0.9% NaCl) was infused for 4 h. During the final 2 h, euglycaemic hyperinsulinaemia (80+/-4 m-units/l) was imposed. EDV and endothelium-independent vasodilatation were evaluated in the forearm by local intra-arterial infusion of methacholine or sodium nitroprusside at baseline and after 2 and 4 h. Forearm blood flow was measured by venous occlusion plethysmography. Lipid oxidation was determined by measuring plasma malondialdehyde levels. Infusion of Intralipid plus heparin increased the concentration of non-esterified fatty acids to 2.6+/-1.2 mmol/l and decreased EDV from 27.6+/-8.7 to 21.0+/-5.7 ml x min(-1) x 100 ml(-1) tissue (P < 0.01). This effect was completely reversed by hyperinsulinaemia (P < 0.01). Hyperinsulinaemia alone increased EDV (to 30.4+/-9.5 ml x min(-1) x 100 ml(-1) tissue; P < 0.01), while endothelium-independent vasodilatation was unaltered by the interventions. Infusion of Intralipid plus heparin increased malondialdehyde levels from 0.67+/-0.22 to 1.2+/-0.37 micromol/l (P < 0.001), while hyperinsulinaemiadid not change the malondialdehyde level. In conclusion, an acute increase in serum levels of non-esterified fatty acids increased lipid oxidation and decreased EDV. The effect on EDV of non-esterified fatty acids could be reversed by hyperinsulinaemia. PMID:10954686

  2. Preventing and reversing vacuum-induced optical losses in high-finesse tantalum (V) oxide mirror coatings

    OpenAIRE

    Gangloff, Dorian; Shi, Molu; Wu, Tailin; Bylinskii, Alexei; Braverman, Boris; Nichols, Rosanna; Li, Junru; Aichholz, Kai; Cetina, Marko; Karpa, Leon; Chuang, Isaac; Gutierrez, Michael Steven; Jelenkovic, Branislav; Vuletic, Vladan

    2015-01-01

    High-finesse optical cavities placed under vacuum are foundational platforms in quantum information science with photons and atoms. We study the vacuum-induced degradation of high-finesse optical cavities with mirror coatings composed of SiO[subscript 2]-Ta[subscript 2]O[subscript 5] dielectric stacks, and present methods to protect these coatings and to recover their initial low loss levels. For separate coatings with reflectivities centered at 370 nm and 422 nm, a vacuum-induced continuous ...

  3. Preventing and Reversing Vacuum-Induced Optical Losses in High-Finesse Tantalum (V) Oxide Mirror Coatings

    OpenAIRE

    Gangloff, Dorian; Shi, Molu; Wu, Tailin; Bylinskii, Alexei; Braverman, Boris; Gutierrez, Michael; Nichols, Rosanna; Li, Junru; Aichholz, Kai; Cetina, Marko; Karpa, Leon; Jelenković, Branislav; Chuang, Isaac; Vuletić, Vladan

    2015-01-01

    We study the vacuum-induced degradation of high-finesse optical cavities with mirror coatings composed of SiO$_2$-Ta$_{2}$O$_{5}$ dielectric stacks, and present methods to protect these coatings and to recover their initial quality factor. For separate coatings with reflectivities centered at 370 nm and 422 nm, a vacuum-induced continuous increase in optical loss occurs if the surface-layer coating is made of Ta$_{2}$O$_{5}$, while it does not occur if it is made of SiO$_2$. The incurred opti...

  4. Genome-wide association mapping combined with reverse genetics identifies new effectors of low water potential-induced proline accumulation in Arabidopsis.

    Science.gov (United States)

    Verslues, Paul E; Lasky, Jesse R; Juenger, Thomas E; Liu, Tzu-Wen; Kumar, M Nagaraj

    2014-01-01

    Arabidopsis (Arabidopsis thaliana) exhibits natural genetic variation in drought response, including varying levels of proline (Pro) accumulation under low water potential. As Pro accumulation is potentially important for stress tolerance and cellular redox control, we conducted a genome-wide association (GWAS) study of low water potential-induced Pro accumulation using a panel of natural accessions and publicly available single-nucleotide polymorphism (SNP) data sets. Candidate genomic regions were prioritized for subsequent study using metrics considering both the strength and spatial clustering of the association signal. These analyses found many candidate regions likely containing gene(s) influencing Pro accumulation. Reverse genetic analysis of several candidates identified new Pro effector genes, including thioredoxins and several genes encoding Universal Stress Protein A domain proteins. These new Pro effector genes further link Pro accumulation to cellular redox and energy status. Additional new Pro effector genes found include the mitochondrial protease LON1, ribosomal protein RPL24A, protein phosphatase 2A subunit A3, a MADS box protein, and a nucleoside triphosphate hydrolase. Several of these new Pro effector genes were from regions with multiple SNPs, each having moderate association with Pro accumulation. This pattern supports the use of summary approaches that incorporate clusters of SNP associations in addition to consideration of individual SNP probability values. Further GWAS-guided reverse genetics promises to find additional effectors of Pro accumulation. The combination of GWAS and reverse genetics to efficiently identify new effector genes may be especially applicable for traits difficult to analyze by other genetic screening methods. PMID:24218491

  5. L-Arginine reverses the impairment of nitric oxide-dependent collateral perfusion in dietary-induced hypercholesterolaemia in the rabbit

    International Nuclear Information System (INIS)

    1. We have used an isolated, buffer-perfused, rabbit ear model of acute arterial occlusion to investigate the effects of exogenous L-arginine on the severe impairment of collateral perfusion associated with dietary-induced hypercholesterolaemia. The effects of L-arginine on hypercholesterolaemia-related impairment of endothelium-dependent relaxations to acetylcholine were also investigated in unligated, isolated rabbit ears perfused with buffer. 2. Cholesterol feeding for 8 weeks (blood cholesterol level 66.5 +/- 5.3 versus 1.4 +/- 0.2 mmol/l, P < 0.001) was associated with almost complete impairment of collateral perfusion, an effect previously observed after inhibition of nitric oxide synthesis. The impairment of collateral perfusion found in hypercholesterolaemia was completely reversed by the addition of 10 mmol/l L-arginine to the perfusion fluid. In control preparations from rabbits fed a normal diet, the addition of 10 mmol/l L-arginine did not influence collateral perfusion. 3. Endothelium-dependent relaxation to acetylcholine was impaired in preparations from the rabbits fed the high cholesterol diet for 8 weeks: the maximum relaxation of tone was 24.6 +/- 0.8% and was significantly (P < 0.01) less than that in the controls (70.3 +/- 2.4%). Addition of L-arginine to the perfusion fluid caused a modest improvement in the endothelium-dependent relaxations to acetylcholine, with a maximum response of 43.2 +/- 1.3%. 4. We conclude that nitric oxide-dependent collateral perfusion is severely impaired in hypercholesterolaemia and that the addition of exogenous L-arginine fully reverses these changes. Endothelium-dependent relaxations to acetylcholine are similarly impaired by hypercholesterolaemia; however, this deficit was only partially reversed by L-arginine

  6. Semaphorin-7a reverses the ERF-induced inhibition of EMT in Ras-dependent mouse mammary epithelial cells.

    Science.gov (United States)

    Allegra, Maryline; Zaragkoulias, Andreas; Vorgia, Elena; Ioannou, Marina; Litos, Gabriele; Beug, Hartmut; Mavrothalassitis, George

    2012-10-01

    Epithelial-to-mesenchymal transition (EMT) is a key process in cancer progression and metastasis, requiring cooperation of the epidermal growth factor/Ras with the transforming growth factor-β (TGF-β) signaling pathway in a multistep process. The molecular mechanisms by which Ras signaling contributes to EMT, however, remain elusive to a large extent. We therefore examined the transcriptional repressor Ets2-repressor factor (ERF)-a bona fide Ras-extracellular signal-regulated kinase/mitogen-activated protein kinase effector-for its ability to interfere with TGF-β-induced EMT in mammary epithelial cells (EpH4) expressing oncogenic Ras (EpRas). ERF-overexpressing EpRas cells failed to undergo TGF-β-induced EMT, formed three-dimensional tubular structures in collagen gels, and retained expression of epithelial markers. Transcriptome analysis indicated that TGF-β signaling through Smads was mostly unaffected, and ERF suppressed the TGF-β-induced EMT via Semaphorin-7a repression. Forced expression of Semaphorin-7a in ERF-overexpressing EpRas cells reestablished their ability to undergo EMT. In contrast, inhibition of Semaphorin-7a in the parental EpRas cells inhibited their ability to undergo TGF-β-induced EMT. Our data suggest that oncogenic Ras may play an additional role in EMT via the ERF, regulating Semaphorin-7a and providing a new interconnection between the Ras- and the TGF-β-signaling pathways. PMID:22875994

  7. Novel Evidence for a Reversible Dissociation of Light-harvesting Complex Ⅱ from Photosystem Ⅱ Reaction Center Complex Induced by Saturating Light Illumination in Soybean Leaves

    Institute of Scientific and Technical Information of China (English)

    Yi Liao; Da-Quan Xu

    2007-01-01

    After saturating light illumination for 3 h the potential photochemical efficiency of photosystem Ⅱ (PSⅡ) (Fv/Fm, the ratio of variable to maximal fluorescence) decreased markedly and recovered basically to the level before saturating light illumination after dark recovery for 3 h in both soybean and wheat leaves, indicating that the decline in Fv/Fm is a reversible down-regulation. Also, the saturating light illumination led to significant decreases in the low temperature (77 K) chlorophyll fluorescence parameters F685 (chlorophyll a fluorescence peaked at 685 nm ) and F685/F735 (F735, chlorophyll a fluorescence peaked at 735 nm) in soybean leaves but not in wheat leaves. Moreover,trypsin (a protease) treatment resulted in a remarkable decrease in the amounts of PsbS protein (a nuclear gene psbS-encoded 22 kDa protein) in the thylakoids from saturating light-illuminated (SI), but not in those from darkadapted (DT) and dark-recovered (DRT) soybean leaves. However, the treatment did not cause such a decrease in amounts of the PsbS protein in the thylakoids from saturating light-illuminated wheat leaves. These results support the conclusion that saturating light illumination induces a reversible dissociation of some light-harvesting complex Ⅱ (LHCⅡ) from PSⅡ reaction center complex in soybean leaf but not in wheat leaf.

  8. Reversibility of dopamine receptor antagonist-induced hyperprolactinemia and associated histological changes in Tg RasH2 wild-type mice.

    Science.gov (United States)

    Krishna, Gopala; Ganiger, Shivaputhrappa; Kannan, Kamala; Gopalakrishnan, Gopa; Goel, Saryu

    2015-12-01

    The purpose of this study was to better understand the biological effects of increased prolactin levels induced in mice by dopamine D2 receptor antagonist molindone treatment. Toxicokinetics, prolactin levels, and reproductive tissue histology were evaluated in Tg rasH2 wild-type mice treated orally with molindone at 0, 5, 15, and 50mg/kg/day for 6 months, followed by a 2-month posttreatment recovery period. A greater than dose-proportional increase in molindone exposure ([AUC]0‒24) was observed on Day 180 for both sexes. Statistically significant (Ptreatment groups compared with controls at 0.5h postdose on Days 1 and 180. Prolactin levels returned to baseline levels during the recovery period. Microscopic changes attributable to hyperprolactinemia, including corpora lutea enlargement and interstitial cell atrophy in the ovaries, and atrophy of the uterus and vagina were observed on Day 180. These changes were reversed during the recovery period in the 5- and 15-mg/kg/day treatment groups. Mice receiving molindone at 50mg/kg/day also showed signs of reversal on histologic examination. PMID:26327279

  9. Investigation on the Neff reverse annealing effect using TSC/I-DLTS: relationship between neutron induced microscopic defects and silicon detector electrical degradations

    International Nuclear Information System (INIS)

    Neutron induced defect levels in high resistivity silicon detectors have been studied using a current-based macroscopic defect analysis system: thermally stimulated current (TSC) and current deep level transient spectroscopy (I-DLTS). These studies have been correlated to the traditional C-V, I-V, and transient current and charge techniques (TCT/TChT) after neutron radiation and subsequent thermal anneals. It has been found that the increases of the space charge density, Neff, in irradiated detectors after thermal anneals (Neff reverse anneal) correspond to the increases of deep levels in the silicon bandgap. In particular, increases of the double vacancy center (V-V and V-V--) and/or Ci-Oi level have good correlations with the Neff reverse anneal. It has also been observed that the leakage current of highly irradiated (Φn>1013 n/cm2) detectors increases after thermal anneals, which is different from the leakage current annealing behavior of slightly irradiated (Φn13 n/cm2) detectors. It is apparent that V-V center and/or Ci-Oi level play important roles in both Neff and leakage current degradations for highly irradiated high resistivity silicon detectors. (orig.)

  10. Toxin ζ Reversible Induces Dormancy and Reduces the UDP-N-Acetylglucosamine Pool as One of the Protective Responses to Cope with Stress

    Directory of Open Access Journals (Sweden)

    Mariangela Tabone

    2014-09-01

    Full Text Available Toxins of the ζ/PezT family, found in the genome of major human pathogens, phosphorylate the peptidoglycan precursor uridine diphosphate-N-acetylglucosamine (UNAG leading to unreactive UNAG-3P. Transient over-expression of a PezT variant impairs cell wall biosynthesis and triggers autolysis in Escherichia coli. Conversely, physiological levels of ζ reversibly induce dormancy produce a sub-fraction of membrane-compromised cells, and a minor subpopulation of Bacillus subtilis cells become tolerant of toxin action. We report here that purified ζ is a strong UNAG-dependent ATPase, being GTP a lower competitor. In vitro, ζ toxin phosphorylates a fraction of UNAG. In vivo, ζ-mediated inactivation of UNAG by phosphorylation does not deplete the active UNAG pool, because expression of the toxin enhances the efficacy of genuine cell wall inhibitors (fosfomycin, vancomycin or ampicillin. Transient ζ expression together with fosfomycin treatment halt cell proliferation, but ε2 antitoxin expression facilitates the exit of ζ-induced dormancy, suggesting that there is sufficient UNAG for growth. We propose that ζ induces diverse cellular responses to cope with stress, being the reduction of the UNAG pool one among them. If the action of ζ is not inhibited, e.g., by de novo ε2 antitoxin synthesis, the toxin markedly enhances the efficacy of antimicrobial treatment without massive autolysis in Firmicutes.

  11. Toxin ζ reversible induces dormancy and reduces the UDP-N-acetylglucosamine pool as one of the protective responses to cope with stress.

    Science.gov (United States)

    Tabone, Mariangela; Ayora, Silvia; Alonso, Juan C

    2014-09-01

    Toxins of the ζ/PezT family, found in the genome of major human pathogens, phosphorylate the peptidoglycan precursor uridine diphosphate-N-acetylglucosamine (UNAG) leading to unreactive UNAG-3P. Transient over-expression of a PezT variant impairs cell wall biosynthesis and triggers autolysis in Escherichia coli. Conversely, physiological levels of ζ reversibly induce dormancy produce a sub-fraction of membrane-compromised cells, and a minor subpopulation of Bacillus subtilis cells become tolerant of toxin action. We report here that purified ζ is a strong UNAG-dependent ATPase, being GTP a lower competitor. In vitro, ζ toxin phosphorylates a fraction of UNAG. In vivo, ζ-mediated inactivation of UNAG by phosphorylation does not deplete the active UNAG pool, because expression of the toxin enhances the efficacy of genuine cell wall inhibitors (fosfomycin, vancomycin or ampicillin). Transient ζ expression together with fosfomycin treatment halt cell proliferation, but ε2 antitoxin expression facilitates the exit of ζ-induced dormancy, suggesting that there is sufficient UNAG for growth. We propose that ζ induces diverse cellular responses to cope with stress, being the reduction of the UNAG pool one among them. If the action of ζ is not inhibited, e.g., by de novo ε2 antitoxin synthesis, the toxin markedly enhances the efficacy of antimicrobial treatment without massive autolysis in Firmicutes. PMID:25238046

  12. EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT

    Science.gov (United States)

    Xiaokaiti, Yilixiati; Wu, Haoming; Chen, Ya; Yang, Haopeng; Duan, Jianhui; Li, Xin; Pan, Yan; Tie, Lu; Zhang, Liangren; Li, Xuejun

    2015-07-01

    Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment. EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound. In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells. We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase. We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay. As the natural inhibitor of neutrophil elastase, α1-antitrypsin is synthesized in tumor cells. We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastase-treated A549 cells. We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the PI3K/Akt pathway. Overall, our results suggest that EGCG ameliorates the neutrophil elastase-induced migration of A549 cells. The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway.

  13. Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer's disease model via canonical Wnt/β-catenin pathway.

    Science.gov (United States)

    Tiwari, Shashi Kant; Agarwal, Swati; Seth, Brashket; Yadav, Anuradha; Nair, Saumya; Bhatnagar, Priyanka; Karmakar, Madhumita; Kumari, Manisha; Chauhan, Lalit Kumar Singh; Patel, Devendra Kumar; Srivastava, Vikas; Singh, Dhirendra; Gupta, Shailendra Kumar; Tripathi, Anurag; Chaturvedi, Rajnish Kumar; Gupta, Kailash Chand

    2014-01-28

    Neurogenesis, a process of generation of new neurons, is reported to be reduced in several neurodegenerative disorders including Alzheimer's disease (AD). Induction of neurogenesis by targeting endogenous neural stem cells (NSC) could be a promising therapeutic approach to such diseases by influencing the brain self-regenerative capacity. Curcumin, a neuroprotective agent, has poor brain bioavailability. Herein, we report that curcumin-encapsulated PLGA nanoparticles (Cur-PLGA-NPs) potently induce NSC proliferation and neuronal differentiation in vitro and in the hippocampus and subventricular zone of adult rats, as compared to uncoated bulk curcumin. Cur-PLGA-NPs induce neurogenesis by internalization into the hippocampal NSC. Cur-PLGA-NPs significantly increase expression of genes involved in cell proliferation (reelin, nestin, and Pax6) and neuronal differentiation (neurogenin, neuroD1, neuregulin, neuroligin, and Stat3). Curcumin nanoparticles increase neuronal differentiation by activating the Wnt/β-catenin pathway, involved in regulation of neurogenesis. These nanoparticles caused enhanced nuclear translocation of β-catenin, decreased GSK-3β levels, and increased promoter activity of the TCF/LEF and cyclin-D1. Pharmacological and siRNA-mediated genetic inhibition of the Wnt pathway blocked neurogenesis-stimulating effects of curcumin. These nanoparticles reverse learning and memory impairments in an amyloid beta induced rat model of AD-like phenotypes, by inducing neurogenesis. In silico molecular docking studies suggest that curcumin interacts with Wif-1, Dkk, and GSK-3β. These results suggest that curcumin nanoparticles induce adult neurogenesis through activation of the canonical Wnt/β-catenin pathway and may offer a therapeutic approach to treating neurodegenerative diseases such as AD, by enhancing a brain self-repair mechanism. PMID:24467380

  14. Transgenic expression of Telomerase reverse transcriptase (Tert) improves cell proliferation of primary cells and enhances reprogramming efficiency into the induced pluripotent stem cell.

    Science.gov (United States)

    Hidema, Shizu; Fukuda, Tomokazu; Date, Shiori; Tokitake, Yuko; Matsui, Yasuhisa; Sasaki, Hiroki; Nishimori, Katsuhiko

    2016-10-01

    The enzymatic activity of telomerase is important for the extension of the telomere repeat sequence and overcoming cellular senescence. We generated a conditional transgenic mouse line, carrying the telomerase reverse transcriptase (Tert) expression cassette, controlled by the Cre-loxP-mediated recombination. In our study, Cre recombinase expression efficiently activated Tert expression, resulting in its increased enzymatic activity, which extended the period of cellular proliferation until the keratinocytes entered senescence. This suggests that transgenic Tert expression is effective in enhancing primary cell proliferation. Notably, Tert expression increased colony formation of induced pluripotent stem (iPS) cells after the introduction of four reprogramming factors, Oct-4, klf4, SOX-2, and c-Myc into the transgenic fibroblasts. To the best of our knowledge, this is the first study to show that the transgenic Tert expression enhances reprogramming efficiency of iPS cells, which indicates a critical role for Tert in the reprogramming process. PMID:27297181

  15. Engineering and Scaling the Spontaneous Magnetization Reversal of Faraday Induced Magnetic Relaxation in Nano-Sized Amorphous Ni Coated on Crystalline Au

    Directory of Open Access Journals (Sweden)

    Wen-Hsien Li

    2016-05-01

    Full Text Available We report on the generation of large inverse remanent magnetizations in nano-sized core/shell structure of Au/Ni by turning off the applied magnetic field. The remanent magnetization is very sensitive to the field reduction rate as well as to the thermal and field processes before the switching off of the magnetic field. Spontaneous reversal in direction and increase in magnitude of the remanent magnetization in subsequent relaxations over time were found. All of the various types of temporal relaxation curves of the remanent magnetizations are successfully scaled by a stretched exponential decay profile, characterized by two pairs of relaxation times and dynamic exponents. The relaxation time is used to describe the reduction rate, while the dynamic exponent describes the dynamical slowing down of the relaxation through time evolution. The key to these effects is to have the induced eddy current running beneath the amorphous Ni shells through Faraday induction.

  16. RADIATION-INDUCED PROGRESSIVE DECREASINGIN THE EXPRESSION OF REVERSE TRANSCRIPTASE GENE OF hEST2 AND TELOMERASE ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    朱涵能; 熊思东; 程文英

    2001-01-01

    Objectites. In order to identify the relationship between telomerase and the biological effect of radiation injury, and investigate the role of human telomerase catalytic subunit gene (hEST2) reverse tranacriptase(RT) seg-ment in the expression of telomerase activity. Methods. Tumor FIeLa cells, KB cells and A431 cells were employed to measure the change in telomeraseactivity after 60Co-ray irradiation at RNA level and protein level. Quantitative PCR and Northern blotting wereused to determine the expression of bEST2 RT segment that encodes seven motifs of the human telomeres, a PCR-besed telomeric repeat amplification protocol (TRAP)was used to assay telomerase activity after exposure toradiation. Results. Both of telomerase activity and the expression hEST2 RT segment were decreased with increasingdosage of radiation. In addition, testing the expression of motifs domain is similar to the measurement of telomerase activity. Conclusion. The detection of the hEST2 BT segment by Northern blotting and quantitative PCR are new methods for testing Uflomerase activity. Furthermore, radiation can cause a dose-dependent decrease in telomerase activity. The effect of radiation on telomerase is one possible reason for the death of cancer ceils after irradiation.

  17. RADIATION INDUCED PROGRESSIVE DECREASING IN THE EXPRESSION OF REVERSE TRANSCRIPTASE GENE OF hEST2 AND TELOMERASE ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objectives. In order to identify the relationship between telomerase and the biological effect of radiation injury,and investigate the role of human telomerase catalytic subunit gene (hEST2) reverse transcriptase(RT) segment in the expression of telomerase activity. Methods. Tumor HeLa cells, KB cells and A431 cells were employed to measure the change in telomerase activity after 60Co ray irradiation at RNA level and protein level. Quantitative PCR and Northern blotting were used to determine the expression of hEST2 RT segment that encodes seven motifs of the human telomeres, a PCR based telomeric repeat amplification protocol (TRAP)was used to assay telomerase activity after exposure to radiation. Results. Both of telomerase activity and the expression hEST2 RT segment were decreased with increasing dosage of radiation. In addition, testing the expression of motifs domain is similar to the measurement of telomerase activity. Conclusion. The detection of the hEST2 RT segment by Northern blotting and quantitative PCR are new methods for testing telomerase activity. Furthermore, radiation can cause a dose dependent decrease in telomerase activity. The effect of radiation on telomerase is one possible reason for the death of cancer cells after irradiation.

  18. Electric field controlled strain induced reversible switching of magnetization in Galfenol nanomagnets delineated on PMN-PT substrate

    Science.gov (United States)

    Ahmad, Hasnain; Atulasimha, Jayasimha; Bandyopadhyay, Supriyo

    We report a non-volatile converse magneto-electric effect in elliptical Galfenol (FeGa) nanomagnets of ~300 nm lateral dimensions and ~10nm thickness delineated on a PMN-PT substrate. This effect can be harnessed for energy-efficient non-volatile memory. The nanomagnets are fabricated with e-beam lithography and sputtering. Their major axes are aligned parallel to the direction in which the substrate is poled and they are magnetized in this direction with a magnetic field. An electric field in the opposite direction generates compressive strain in the piezoelectric substrate which is partially transferred to the nanomagnets and rotates their magnetization away from the major axes to metastable orientations. There they remain after the field is removed, resulting in non-volatility. Reversing the electric field generates tensile strain which returns the magnetization to the original state. The two states can encode two binary bits which can be written using the correct voltage polarity, resulting in non-toggle behavior. Scaled memory fashioned on this effect can exhibit write energy dissipation of only ~2 aJ. Work is supported by NSF under ECCS-1124714 and CCF-1216614. Sputtering was carried out at NIST Gaithersburg.

  19. Verteporfin can Reverse the Paclitaxel Resistance Induced by YAP Over-Expression in HCT-8/T Cells without Photoactivation through Inhibiting YAP Expression

    Directory of Open Access Journals (Sweden)

    Wang Pan

    2016-07-01

    Full Text Available Background/Aims: Paclitaxel (PTX is one of the most effective anti-cancer drugs. However, multiple drug resistance is still the main factor that hinders the effective treatment of cancer with PTX. Several factors including YAP over-expression can cause PTX resistance. In this study, we aimed to verify the role YAP plays in PTX resistance, explore the reversal of PTX resistance by verteporfin (VP and investigate the effect of combination therapy of PTX and VP on the PTX resistant colon cancer cells (HCT-8/T. Methods: To study the relationship between YAP and PTX resistance, a stable YAP-over-expression or YAP silencing cell line was generated by transfected with YAP-plasmids or siYAP-RNA. WST-1 assay was performed to detect the cytotoxicity of PTX on HCT-8 and HCT-8/T cells. Clone formation assay and Transwell assay was preformed to determine the cell proliferation and invasion ability respectively. Immunofluorescence and Western blot analysis was performed for protein detection. Results: YAP was stronger expressed in HCT-8/T than in HCT-8, and PTX resistance was positively correlated with the level of YAP expression. VP, a strongly YAP inhibitor, could reduce the PTX resistance on HCT-8/T cells without light activation by inhibiting YAP. Beside, VP and PTX combination therapy showed synergism on inhibition of YAP and cytotoxicity to HCT-8/T. Moreover, verteporfin and PTX combination therapy affect the invasion and colony formation ability and induce apoptosis of HCT-8/T cells. Conclusions: VP can reverse the PTX resistance induced by YAP over-expression in HCT-8/T cells without photoactivation through inhibiting YAP expression.

  20. DNA damage-induced ephrin-B2 reverse signaling promotes chemoresistance and drives EMT in colorectal carcinoma harboring mutant p53.

    Science.gov (United States)

    Alam, S K; Yadav, V K; Bajaj, S; Datta, A; Dutta, S K; Bhattacharyya, M; Bhattacharya, S; Debnath, S; Roy, S; Boardman, L A; Smyrk, T C; Molina, J R; Chakrabarti, S; Chowdhury, S; Mukhopadhyay, D; Roychoudhury, S

    2016-04-01

    Mutation in the TP53 gene positively correlates with increased incidence of chemoresistance in different cancers. In this study, we investigated the mechanism of chemoresistance and epithelial-to-mesenchymal transition (EMT) in colorectal cancer involving the gain-of-function (GOF) mutant p53/ephrin-B2 signaling axis. Bioinformatic analysis of the NCI-60 data set and subsequent hub prediction identified EFNB2 as a possible GOF mutant p53 target gene, responsible for chemoresistance. We show that the mutant p53-NF-Y complex transcriptionally upregulates EFNB2 expression in response to DNA damage. Moreover, the acetylated form of mutant p53 protein is recruited on the EFNB2 promoter and positively regulates its expression in conjunction with coactivator p300. In vitro cell line and in vivo nude mice data show that EFNB2 silencing restores chemosensitivity in mutant p53-harboring tumors. In addition, we observed high expression of EFNB2 in patients having neoadjuvant non-responder colorectal carcinoma compared with those having responder version of the disease. In the course of deciphering the drug resistance mechanism, we also show that ephrin-B2 reverse signaling induces ABCG2 expression after drug treatment that involves JNK-c-Jun signaling in mutant p53 cells. Moreover, 5-fluorouracil-induced ephrin-B2 reverse signaling promotes tumorigenesis through the Src-ERK pathway, and drives EMT via the Src-FAK pathway. We thus conclude that targeting ephrin-B2 might enhance the therapeutic potential of DNA-damaging chemotherapeutic agents in mutant p53-bearing human tumors. PMID:26494468

  1. Reversal by Dithiothreitol Treatment of the Block in Murine Leukemia Virus Maturation Induced by Disulfide Cross-Linking

    OpenAIRE

    Campbell, Stephen; Oshima, Masamichi; Mirro, Jane; Nagashima, Kunio; Rein, Alan

    2002-01-01

    We previously reported that if murine leukemia virus particles are produced in the presence of the mild oxidizing agent disulfide-substituted benzamide-2, they fail to undergo the normal process of virus maturation. We now show that treatment of these immature particles with a reducing agent (dithiothreitol) induces their maturation in vitro, as evidenced by proteolytic cleavage of Gag, Gag-Pol, and Env proteins and by their morphology. The identification of partial cleavage products in these...

  2. Glucocorticoid receptor blockade in the posterior interpositus nucleus reverses maternal separation-induced deficits in adult eyeblink conditioning

    OpenAIRE

    Wilber, Aaron A.; Lin, Grant L.; Wellman, Cara L.

    2010-01-01

    Previously, we showed that neonatal maternal separation impaired eyeblink conditioning in adult rats. This impairment is correlated with increased glucocorticoid receptor (GR) expression in the cerebellar posterior interpositus nucleus, a critical site of learning-related plasticity. To assess whether increased GR expression is responsible for the separation-induced learning impairment, we infused a GR antagonist (mifepristone) or vehicle into the posterior interpositus during eyeblink condit...

  3. Reversal of Cadmium-induced Oxidative Stress in Chicken by Herbal Adaptogens Withania Somnifera and Ocimum Sanctum

    OpenAIRE

    K Bharavi; Reddy, A. Gopala; G S Rao; Reddy, A. Rajasekhara; Rao, S. V. Rama

    2010-01-01

    The present study was carried out to evaluate the herbal adaptogens Withania somnifera and Ocimum sanctum on cadmium-induced oxidative toxicity in broiler chicken. Cadmium administration at the rate of 100 ppm orally along with feed up to 28 days produced peroxidative damage, as indicated by increase in TBARS, reduction in glutathione (GSH) concentration in liver and kidney, and increase in catalase (CAT) and superoxide dismutase (SOD) of erythrocytes. Herbal adaptogens Withania somnifera roo...

  4. Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E

    OpenAIRE

    Yinhua Ni; Mayumi Nagashimada; Fen Zhuge; Lili Zhan; Naoto Nagata; Akemi Tsutsui; Yasuni Nakanuma; Shuichi Kaneko; Tsuguhito Ota

    2015-01-01

    Hepatic insulin resistance and nonalcoholic steatohepatitis (NASH) could be caused by excessive hepatic lipid accumulation and peroxidation. Vitamin E has become a standard treatment for NASH. However, astaxanthin, an antioxidant carotenoid, inhibits lipid peroxidation more potently than vitamin E. Here, we compared the effects of astaxanthin and vitamin E in NASH. We first demonstrated that astaxanthin ameliorated hepatic steatosis in both genetically (ob/ob) and high-fat-diet-induced obese ...

  5. Rapid reversal of heart failure in a patient with pheochromocytoma and catecholamine-induced myocarditis/cardiomyopathy

    International Nuclear Information System (INIS)

    Pheochromocytoma is rare and usually presents as paroxysal or sustained hypertension, nonetheless, it can also cause severe acute pulmonary edema in normotensive individuals. We present a case with pheochromocytoma and severe left ventricular failure caused by catecholamine induced myocarditis/cardiomyopathy. Severe left ventricular failure resolved rapidly and left ventricular systolic function became normal within two weeks of medical treatment. Later, patient underwent elective and uneventful surgical removal of pheochromocytoma. (author)

  6. PKM zeta Inhibition Reverses Learning-Induced Increases in Hippocampal Synaptic Strength and Memory during Trace Eyeblink Conditioning

    OpenAIRE

    Noelia Madroñal; Agnès Gruart; Sacktor, Todd C.; Delgado-García, José M.

    2010-01-01

    A leading candidate in the process of memory formation is hippocampal long-term potentiation (LTP), a persistent enhancement in synaptic strength evoked by the repetitive activation of excitatory synapses, either by experimental high-frequency stimulation (HFS) or, as recently shown, during actual learning. But are the molecular mechanisms for maintaining synaptic potentiation induced by HFS and by experience the same? Protein kinase Mzeta (PKMzeta), an autonomously active atypical protein ki...

  7. Carnosine Reduces Oxidative Stress and Reverses Attenuation of Righting and Postural Reflexes in Rats with Thioacetamide-Induced Liver Failure

    OpenAIRE

    Milewski, Krzysztof; Hilgier, Wojciech; Fręśko, Inez; Polowy, Rafał; Podsiadłowska, Anna; Zołocińska, Ewa; Grymanowska, Aneta W.; Robert K Filipkowski; Albrecht, Jan; Zielińska, Magdalena

    2016-01-01

    Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of l-histidine (His) attenuates OS in brain of HE animal models, but the underlying mechanism is complex and not sufficiently understood. Here we tested the hypothesis that dipeptide carnosine (β-alanyl-l-histidine, Car) may be neuroprotective in thioacetamide (TAA)-induced liver failure in rats and that, being His metabolite, may mediate the w...

  8. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus- indica mucilage

    Institute of Scientific and Technical Information of China (English)

    Ricardo Vázquez-Ramírez; Marisela Olguín-Martínez; Carlos Kubli-Garfias; Rolando Hernández-Mu(n)oz

    2006-01-01

    AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats.METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5'-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined.Histological studies of gastric samples from the experimental groups were included.RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes.Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect.The activity of 5'-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes.CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids,mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

  9. Establishing a human pancreatic stem cell line and transplanting induced pancreatic islets to reverse experimental diabetes in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The major obstacle in using pancreatic islet transplantation to cure type I and some type II diabetes is the shortage of the donors. One of ways to overcome such obstacle is to isolate and clone pancreatic stem cells as "seed cells" and induce their differentiation into functional islets as an abundant trans-plantation source. In this study, a monoclonal human pancreatic stem cell (mhPSC) line was obtained from abortive fetal pancreatic tissues. Pancreatic tissues were taken from abortive fetus by sterile procedures, and digested into single cells and cell clusters with 0.1% type IV collagenase. Cultured in modified glucose-low DMEM with 10% fetal bovine serum (FBS), these single cells and cell clusters adhered to culture dishes, and then primary epidermal-like pancreatic stem cells started to clone. After digesting with 0.25% trypsin and 0.04% EDTA, fibroblasts and other cells were gradually eliminated and epithelioid pancreatic stem cells were gradually purified during generations. Using clone-ring selection, the mhPSCs were obtained. After addition of 10 ng/mL epidermal growth factor (EGF) in cell culture medium, the mhPSCs quickly grew and formed a gravelstone-like monolayer. Continuously proliferated, a mhPSC line, which was derived from a male abortive fetus of 4 months old, has been passed through 50 generations. More than 1×109 mhPSCs were cryo-preserved in liquid nitrogen. Karyotype analysis showed that the chromosome set of the mhPSC line was normal diploid. Immunocytochemistry results demonstrated that the mhPSC line was positive for the pdx1, glucagon, nestin and CK19, and negative for the insulin, CD34, CD44 and CD45 protein expression. RT-PCR revealed further that the mhPSCs expressed transcription factors of the pdx1, glucagon, nestin and CK19. Also, in vitro induced with β-mercaptoethanol, the mhPSCs differentiated into nerve cells that expressed the NF protein. Induced with nicotinamide, the mhPSCs differentiated into functional islet

  10. Reversible resistance induced by FLT3 inhibition: a novel resistance mechanism in mutant FLT3-expressing cells.

    Directory of Open Access Journals (Sweden)

    Ellen Weisberg

    Full Text Available Clinical responses achieved with FLT3 kinase inhibitors in acute myeloid leukemia (AML are typically transient and partial. Thus, there is a need for identification of molecular mechanisms of clinical resistance to these drugs. In response, we characterized MOLM13 AML cell lines made resistant to two structurally-independent FLT3 inhibitors.MOLM13 cells were made drug resistant via prolonged exposure to midostaurin and HG-7-85-01, respectively. Cell proliferation was determined by Trypan blue exclusion. Protein expression was assessed by immunoblotting, immunoprecipitation, and flow cytometry. Cycloheximide was used to determine protein half-life. RT-PCR was performed to determine FLT3 mRNA levels, and FISH analysis was performed to determine FLT3 gene expression.We found that MOLM13 cells readily developed cross-resistance when exposed to either midostaurin or HG-7-85-01. Resistance in both lines was associated with dramatically elevated levels of cell surface FLT3 and elevated levels of phosphor-MAPK, but not phospho-STAT5. The increase in FLT3-ITD expression was at least in part due to reduced turnover of the receptor, with prolonged half-life. Importantly, the drug-resistant phenotype could be rapidly reversed upon withdrawal of either inhibitor. Consistent with this phenotype, no significant evidence of FLT3 gene amplification, kinase domain mutations, or elevated levels of mRNA was observed, suggesting that protein turnover may be part of an auto-regulatory pathway initiated by FLT3 kinase activity. Interestingly, FLT3 inhibitor resistance also correlated with resistance to cytosine arabinoside. Over-expression of FLT3 protein in response to kinase inhibitors may be part of a novel mechanism that could contribute to clinical resistance.

  11. Nitrated Fatty Acids Reverse Cigarette Smoke-Induced Alveolar Macrophage Activation and Inhibit Protease Activity via Electrophilic S-Alkylation

    Science.gov (United States)

    Reddy, Aravind T.; Lakshmi, Sowmya P.; Muchumarri, Ramamohan R.; Reddy, Raju C.

    2016-01-01

    Nitrated fatty acids (NFAs), endogenous products of nonenzymatic reactions of NO-derived reactive nitrogen species with unsaturated fatty acids, exhibit substantial anti-inflammatory activities. They are both reversible electrophiles and peroxisome proliferator-activated receptor γ (PPARγ) agonists, but the physiological implications of their electrophilic activity are poorly understood. We tested their effects on inflammatory and emphysema-related biomarkers in alveolar macrophages (AMs) of smoke-exposed mice. NFA (10-nitro-oleic acid or 12-nitrolinoleic acid) treatment downregulated expression and activity of the inflammatory transcription factor NF-κB while upregulating those of PPARγ. It also downregulated production of inflammatory cytokines and chemokines and of the protease cathepsin S (Cat S), a key mediator of emphysematous septal destruction. Cat S downregulation was accompanied by decreased AM elastolytic activity, a major mechanism of septal destruction. NFAs downregulated both Cat S expression and activity in AMs of wild-type mice, but only inhibited its activity in AMs of PPARγ knockout mice, pointing to a PPARγ-independent mechanism of enzyme inhibition. We hypothesized that this mechanism was electrophilic S-alkylation of target Cat S cysteines, and found that NFAs bind directly to Cat S following treatment of intact AMs and, as suggested by in silico modeling and calculation of relevant parameters, elicit S-alkylation of Cys25 when incubated with purified Cat S. These results demonstrate that NFAs’ electrophilic activity, in addition to their role as PPARγ agonists, underlies their protective effects in chronic obstructive pulmonary disease (COPD) and support their therapeutic potential in this disease. PMID:27119365

  12. Ductility enhancement in ultrafine-grained Fe-Ni-Mn martensitic steel by stress-induced reverse transformation

    International Nuclear Information System (INIS)

    Research highlights: Fe-10Ni-7Mn age-hardenable martensitic steel in the strain-free, aged condition shows premature fracture and zero ductility. By Large strain deformation, nano-grained wire could be fabricated. Ultrahigh straining improved the ultimate tensile stress up to 2540 MPa and strain up to 7%. X-ray and TEM observations determined reverse transformation of martensite to austenite to epsilon martensite in nanostructured Fe-Ni-Mn steel. As a result and as shown by X-ray diffraction and SFE calculation, deformation of austenite could lead to ε-martensite formation by stacking fault mechanism in nano-grains. These transformations could be the reasons for further mechanical properties improvement. - Abstract: The effect of large strain deformation on the mechanical properties was investigated in a martensitic Fe-Ni-Mn alloy. After a combined deformation route (cold rolling plus wire drawing), the mechanical properties improved. The tensile strength of alloy in this study reaches to 2540 MPa and total tensile strain to 7% which are much higher than our previous study which after cold rolling and aging tensile strength was 1840 MPa with total tensile strain of 2.8%, although in both cases the improvement are significant for this brittle alloy. The enhancement of ductility after aging might be attributed to the effective role of grain refining down to nanoscale and the formation of austenite during deformation process and stabilization of that austenite in the aged wire. The austenite transforms to ε-martensite during tensile testing because of its low stacking fault energy (SFE) and increases the total measured tensile strain more. X-ray diffraction (XRD) analyses and transmission electron microscopic (TEM) images clarified the suggested reason for this ductility enhancement.

  13. Carnosine Reduces Oxidative Stress and Reverses Attenuation of Righting and Postural Reflexes in Rats with Thioacetamide-Induced Liver Failure.

    Science.gov (United States)

    Milewski, Krzysztof; Hilgier, Wojciech; Fręśko, Inez; Polowy, Rafał; Podsiadłowska, Anna; Zołocińska, Ewa; Grymanowska, Aneta W; Filipkowski, Robert K; Albrecht, Jan; Zielińska, Magdalena

    2016-02-01

    Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of L-histidine (His) attenuates OS in brain of HE animal models, but the underlying mechanism is complex and not sufficiently understood. Here we tested the hypothesis that dipeptide carnosine (β-alanyl-L-histidine, Car) may be neuroprotective in thioacetamide (TAA)-induced liver failure in rats and that, being His metabolite, may mediate the well documented anti-OS activity of His. Amino acids [His or Car (100 mg/kg)] were administrated 2 h before TAA (i.p., 300 mg/kg 3× in 24 h intervals) injection into Sprague-Dawley rats. The animals were thus tested for: (i) brain prefrontal cortex and blood contents of Car and His, (ii) amount of reactive oxygen species (ROS), total antioxidant capacity (TAC), GSSG/GSH ratio and thioredoxin reductase (TRx) activity, and (iii) behavioral changes (several models were used, i.e. tests for reflexes, open field, grip test, Rotarod). Brain level of Car was reduced in TAA rats, and His administration significantly elevated Car levels in control and TAA rats. Car partly attenuated TAA-induced ROS production and reduced GSH/GSSG ratio, whereas the increase of TRx activity in TAA brain was not significantly modulated by Car. Further, Car improved TAA-affected behavioral functions in rats, as was shown by the tests of righting and postural reflexes. Collectively, the results support the hypothesis that (i) Car may be added to the list of neuroprotective compounds of therapeutic potential on HE and that (ii) Car mediates at least a portion of the OS-attenuating activity of His in the setting of TAA-induced liver failure. PMID:26801175

  14. Postincubation with aclarubicin reverses topoisomerase II mediated DNA cleavage, strand breaks, and cytotoxicity induced by VP-16

    DEFF Research Database (Denmark)

    Petersen, L N; Jensen, P B; Sørensen, B S; Engelholm, S A; Spang-Thomsen, M

    1994-01-01

    In previous studies, we found that VP-16 (etoposide) induced cytotoxicity and protein-concealed strand break formation was prevented in a small cell lung cancer (SCLC) cell line, when the cells were incubated with aclarubicin prior to treatment with VP-16. In the present work, we studied the effe...... the antagonism to topo-II targeting drugs both when administered prior to and after the topo-II targeting agents. Thus, our data suggest that sequential rather than simultaneous administration of aclarubicin and topo-II targeting agents may be superior with respect to net...

  15. Calmodulin kinase II interacts with the dopamine transporter C terminus to regulate amphetamine-induced reverse transport

    DEFF Research Database (Denmark)

    Fog, Jacob U; Khoshbouei, Habibeh; Holy, Marion;

    2006-01-01

    Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the d...... response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT N terminus and mediates amphetamine-induced dopamine efflux....

  16. Calmodulin Kinase II Interacts with the Dopamine Transporter C Terminus to Regulate Amphetamine-Induced Reverse Transport

    DEFF Research Database (Denmark)

    Fog, Jacob U; Khoshbouei, Habibeh; Holy, Marion;

    2006-01-01

    Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the d...... response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT N terminus and mediates amphetamine-induced dopamine efflux....

  17. Virus-induced gene silencing (VIGS) as a reverse genetic tool to study development of symbiotic root nodules

    DEFF Research Database (Denmark)

    Kjær, Gabriela Didina Constantin; Grønlund, Mette; Stougaard, Jens; Lund, Ole Søgaard

    2008-01-01

    mediated by agroinfiltration and, 2 weeks later, a Rhizobium leguminosarum bv. viceae culture was added in order to induce root nodulation. At this time point, it was estimated that systemic silencing was established because leaves of reference plants inoculated with PEBV carrying a fragment of Phytoene...... desaturase displayed photo bleaching. Three weeks after Rhizobium spp. application, plants inoculated with a control vector nodulated normally, whereas nodulation was almost eliminated in plants inoculated with a vector carrying PsNinA and PsNinC. For plants inoculated with a vector carrying Ps...

  18. Reversal of diabetic retinopathy in streptozotocin induced diabetic rats using traditional Indian anti-diabetic plant,Azadirachta indica (L.)

    OpenAIRE

    Ali Hussain, Halim Eshrat M.

    2002-01-01

    This study was carried out to investigate the effect of oral feeding of water extract of fresh leaves ofAzadirachta indica (Fam:Meliaceae) in streptozotocin induced diabetes and its associated retinopathy in rats. Treatment of the diabetic rats with aqueous extract of leaves ofA. indica at a dose of 250 mg/kg body weight for 16 weeks resulted in gradual but significant fall in blood glucose and improvement in serum total, LDL and HDL cholesterol and triacylglycerol which increased in diabetic...

  19. The antineoplastic drug flavopiridol reverses memory impairment induced by Amyloid-ß1-42 oligomers in mice.

    Science.gov (United States)

    Leggio, Gian Marco; Catania, Maria Vincenza; Puzzo, Daniela; Spatuzza, Michela; Pellitteri, Rosalia; Gulisano, Walter; Torrisi, Sebastiano Alfio; Giurdanella, Giovanni; Piazza, Cateno; Impellizzeri, Agata Rita; Gozzo, Lucia; Navarria, Andrea; Bucolo, Claudio; Nicoletti, Ferdinando; Palmeri, Agostino; Salomone, Salvatore; Copani, Agata; Caraci, Filippo; Drago, Filippo

    2016-04-01

    The ectopic re-activation of cell cycle in neurons is an early event in the pathogenesis of Alzheimer's disease (AD), which could lead to synaptic failure and ensuing cognitive deficits before frank neuronal death. Cytostatic drugs that act as cyclin-dependent kinase (CDK) inhibitors have been poorly investigated in animal models of AD. In the present study, we examined the effects of flavopiridol, an inhibitor of CDKs currently used as antineoplastic drug, against cell cycle reactivation and memory loss induced by intracerebroventricular injection of Aß1-42 oligomers in CD1 mice. Cycling neurons, scored as NeuN-positive cells expressing cyclin A, were found both in the frontal cortex and in the hippocampus of Aβ-injected mice, paralleling memory deficits. Starting from three days after Aβ injection, flavopiridol (0.5, 1 and 3mg/kg) was intraperitoneally injected daily, for eleven days. Here we show that a treatment with flavopiridol (0.5 and 1mg/kg) was able to rescue the loss of memory induced by Aβ1-42, and to prevent the occurrence of ectopic cell-cycle events in the mouse frontal cortex and hippocampus. This is the first evidence that a cytostatic drug can prevent cognitive deficits in a non-transgenic animal model of AD. PMID:26875816

  20. Bufalin Reverses HGF-Induced Resistance to EGFR-TKIs in EGFR Mutant Lung Cancer Cells via Blockage of Met/PI3k/Akt Pathway and Induction of Apoptosis

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Kang

    2013-01-01

    Full Text Available The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs, such as gefitinib and erlotinib, have shown promising therapeutic efficacy in nonsmall cell lung cancer (NSCLC patients harboring epidermal growth factor receptor- (EGFR- activating mutation. However, the inevitable recurrence resulting from acquired resistance has limited the clinical improvement in therapy outcomes. Many studies demonstrate that hepatocyte growth factor- (HGF- Met axis plays an important role in tumor progression and drug sensitivity. HGF may induce resistance to EGFR-TKIs in EGFR mutant lung cancer cells by Met/PI3K/Akt signaling. The purpose of this study was to determine whether bufalin, a major bioactive component of Venenum Bufonis, could reverse HGF-induced resistance to reversible and irreversible EGFR-TKIs in mutant lung cancer cells PC-9, HCC827, and H1975. Our studies showed that bufalin could reverse resistance to reversible and irreversible EGFR-TKIs induced by exogenous HGF in EGFR mutant lung cancer cells by inhibiting the Met/PI3K/Akt pathway and inducing death signaling. These results suggested that bufalin might have a potential to overcome HGF-induced resistance to molecular-targeted drugs for lung cancer.

  1. Tesofensine induces appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Jensen, Majbrit M; Overgaard, Agnete;

    2013-01-01

    clarified. Tesofensine effectively induces appetite suppression in the diet-induced obese (DIO) rat partially being ascribed to an indirect stimulation of central dopamine receptor function subsequent to blocked dopamine transporter activity. This is interesting, as obese patients have reduced central...... dopaminergic activity thought to provide a drive for compensatory overeating, but whether treatment with an uptake inhibitor counteracts these changes or not has not been investigated. Tesofensine treatment (2.0mg/kg/day for 14days) caused a pronounced anorexigenic and weight-reducing response in DIO rats as...

  2. Inducible and reversible suppression of Npm1 gene expression using stably integrated small interfering RNA vector in mouse embryonic stem cells

    International Nuclear Information System (INIS)

    The tetracycline (Tc)-inducible small interference RNA (siRNA) is a powerful tool for studying gene function in mammalian cells. However, the system is infrequently utilized in embryonic stem (ES) cells. Here, we present First application of the Tc-inducible, stably integrated plasmid-based siRNA system in mouse ES cells to down-regulate expression of Npm1, an essential gene for embryonic development. The physiological role of Npm1 in ES cells has not been defined. Our data show that the knock-down of Npm1 expression by this siRNA system was not only highly efficient, but also Tc- dose- and induction time-dependent. Particularly, the down-regulation of Npm1 expression was reversible. Importantly, suppression of Npm1 expression in ES cells resulted in reduced cell proliferation. Taken together, this system allows for studying gene function in a highly controlled manner, otherwise difficult to achieve in ES cells. Moreover, our results demonstrate that Npm1 is essential for ES cell proliferation

  3. Reversing hypoxic cell chemoresistance in vitro using genetic and small molecule approaches targeting hypoxia inducible factor-1

    DEFF Research Database (Denmark)

    Brown, Louisa M; Cowen, Rachel L; Debray, Camille;

    2006-01-01

    The resistance of hypoxic cells to conventional chemotherapy is well documented. Using both adenovirus-mediated gene delivery and small molecules targeting hypoxia-inducible factor-1 (HIF-1), we evaluated the impact of HIF-1 inhibition on the sensitivity of hypoxic tumor cells to etoposide. The...... genetic therapy exploited a truncated HIF-1alpha protein that acts as a dominant-negative HIF-1alpha (HIF-1alpha-no-TAD). Its functionality was validated in six human tumor cell lines using HIF-1 reporter assays. An EGFP-fused protein demonstrated that the dominant-negative HIF-1alpha was nucleus......-localized and constitutively expressed irrespective of oxygen tension. The small molecules studied were quinocarmycin monocitrate (KW2152), its analog 7-cyanoquinocarcinol (DX-52-1), and topotecan. DX-52-1 and topotecan have been previously established as HIF-1 inhibitors. HT1080 and HCT116 cells were treated...

  4. Delayed reversible methotrexate-induced leucoencephalopathy in a four-year-old child with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Amrita Roy

    2013-01-01

    Full Text Available Intravenous/intrathecal methotrexate (MTX has been implicated as a major cause of treatment-related neurotoxicity particularly leukoencephalopathy in children with hematological malignancy. We report a 4-year-old boy who presented with apathy and aphasia for 1 day while on the maintenance-phase chemotherapy according to MCP 841 protocol. MRI of brain revealed bilateral symmetrical FLAIR hyperintensities in caudate and putaminal region with FLAIR hypersignal in subcortical U-fiber in left frontal lobe consistent with MTX-induced toxic leucoencephalopathy. There was spontaneous resolution of symptoms within 1 week of onset. So, in Pre-B acute lymphoblastic leukemia patients with subtle neurological deficit, this diagnosis should be kept in mind and further treatment with MTX should be carefully decided.

  5. Parkinson's disease managing reversible neurodegeneration.

    Science.gov (United States)

    Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

    2016-01-01

    Traditionally, the Parkinson's disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient's PD symptoms. PMID:27103805

  6. Epigenetic modifications by inhibiting histone deacetylases reverse memory impairment in insulin resistance induced cognitive deficit in mice.

    Science.gov (United States)

    Sharma, Sorabh; Taliyan, Rajeev

    2016-06-01

    Insulin resistance has been reported as a strong risk factor for Alzheimer's disease. However the molecular mechanisms of association between these still remain elusive. Various studies have highlighted the involvement of histone deacetylases (HDACs) in insulin resistance and cognitive deficits. Thus, the present study was designed to investigate the possible neuroprotective role of HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) in insulin resistance induced cognitive impairment in mice. Mice were subjected to either normal pellet diet (NPD) or high fat diet (HFD) for 8 weeks. HFD fed mice were treated with SAHA at 25 and 50 mg/kg i.p. once daily for 2 weeks. Serum insulin, glucose, triglycerides, total cholesterol and HDL-cholesterol levels were measured. A battery of behavioral parameters was performed to assess cognitive functions. Level of tumour necrosis factor (TNF-α) was measured in hippocampus to assess neuroinflammation. To further explore the molecular mechanisms we measured the histone H3 acetylation and brain derived neurotrophic factor (BDNF) level. HFD fed mice exhibit characteristic features of insulin resistance. These mice also showed a severe deficit in learning and memory along with reduced histone H3 acetylation and BDNF levels. In contrast, the mice treated with SAHA showed significant and dose dependent improvement in insulin resistant condition. These mice also showed improved learning and memory performance. SAHA treatment ameliorates the HFD induced reduction in histone H3 acetylation and BDNF levels. Based upon these results, it could be suggested that HDAC inhibitors exert neuroprotective effects by increasing H3 acetylation and subsequently BDNF level. PMID:26805421

  7. Reversal of TMS-induced motor twitch by training is associated with a reduction in excitability of the antagonist muscle

    Directory of Open Access Journals (Sweden)

    Fregni Felipe

    2011-08-01

    Full Text Available Abstract Background A single session of isolated repetitive movements of the thumb can alter the response to transcranial magnetic stimulation (TMS, such that the related muscle twitch measured post-training occurs in the trained direction. This response is attributed to transient excitability changes in primary motor cortex (M1 that form the early part of learning. We investigated; (1 whether this phenomenon might occur for movements at the wrist, and (2 how specific TMS activation patterns of opposing muscles underlie the practice-induced change in direction. Methods We used single-pulse suprathreshold TMS over the M1 forearm area, to evoke wrist movements in 20 healthy subjects. We measured the preferential direction of the TMS-induced twitch in both the sagittal and coronal plane using an optical goniometer fixed to the dorsum of the wrist, and recorded electromyographic (EMG activity from the flexor carpi radialis (FCR and extensor carpi radialis (ECR muscles. Subjects performed gentle voluntary movements, in the direction opposite to the initial twitch for 5 minutes at 0.2 Hz. We collected motor evoked potentials (MEPs elicited by TMS at baseline and for 10 minutes after training. Results Repetitive motor training was sufficient for TMS to evoke movements in the practiced direction opposite to the original twitch. For most subjects the effect of the newly-acquired direction was retained for at least 10 minutes before reverting to the original. Importantly, the direction change of the movement was associated with a significant decrease in MEP amplitude of the antagonist to the trained muscle, rather than an increase in MEP amplitude of the trained muscle. Conclusions These results demonstrate for the first time that a TMS-twitch direction change following a simple practice paradigm may result from reduced corticospinal drive to muscles antagonizing the trained direction. Such findings may have implications for training paradigms in

  8. Thresholds and gradients in a semi-arid grassland: long-term grazing treatments induce slow, continuous, and reversible vegetation change

    Science.gov (United States)

    Semiarid ecosystems can exhibit non-reversible shifts among alternative stable ecosystem states (thresholds and hysteresis), but can also be characterized by slow, continuous, and reversible changes in plant composition (successional gradients). Conceptual state-and-transition models (STMs) attempt ...

  9. An insert-based enzymatic cell culture system to rapidly and reversibly induce hypoxia: investigations of hypoxia-induced cell damage, protein expression and phosphorylation in neuronal IMR-32 cells

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2013-11-01

    Ischemia-reperfusion injury and tissue hypoxia are of high clinical relevance because they are associated with various pathophysiological conditions such as myocardial infarction and stroke. Nevertheless, the underlying mechanisms causing cell damage are still not fully understood, which is at least partially due to the lack of cell culture systems for the induction of rapid and transient hypoxic conditions. The aim of the study was to establish a model that is suitable for the investigation of cellular and molecular effects associated with transient and long-term hypoxia and to gain insights into hypoxia-mediated mechanisms employing a neuronal culture system. A semipermeable membrane insert system in combination with the hypoxia-inducing enzymes glucose oxidase and catalase was employed to rapidly and reversibly generate hypoxic conditions in the culture medium. Hydrogen peroxide assays, glucose measurements and western blotting were performed to validate the system and to evaluate the effects of the generated hypoxia on neuronal IMR-32 cells. Using the insert-based two-enzyme model, hypoxic conditions were rapidly induced in the culture medium. Glucose concentrations gradually decreased, whereas levels of hydrogen peroxide were not altered. Moreover, a rapid and reversible (onoff generation of hypoxia could be performed by the addition and subsequent removal of the enzyme-containing inserts. Employing neuronal IMR-32 cells, we showed that 3 hours of hypoxia led to morphological signs of cellular damage and significantly increased levels of lactate dehydrogenase (a biochemical marker of cell damage. Hypoxic conditions also increased the amounts of cellular procaspase-3 and catalase as well as phosphorylation of the pro-survival kinase Akt, but not Erk1/2 or STAT5. In summary, we present a novel framework for investigating hypoxia-mediated mechanisms at the cellular level. We claim that the model, the first of its kind, enables researchers to rapidly and

  10. Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites

    International Nuclear Information System (INIS)

    Highlights: ► Chimpanzees, horses and humans have regions of similarity on TLR4 and MD2 promoters. ► Rodents have few regions of similarity on TLR4 promoter when compared to primates. ► Conserved NFkB binding sites were found in the promoters of TLR4 and MD2. ► LPS-induced inhibition of TLR4 transcription is reversed by dexamethasone. ► LPS-induced transcription of MD2 is inhibited by dexamethasone. -- Abstract: Engagement of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explaining these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species (human, chimpanzee, and horse) and low similarity with LPS-resistant species (mouse and rat). Four conserved nuclear factor kappa B (NFκB) binding sites were found in the tlr4 promoter and two in the md2 promoter sequences that are likely to be targets for dexamethasone regulation. In vitro treatment of equine peripheral blood mononuclear cells (eqPBMC) with LPS decreased transcripts of tlr4 and increased transcription of md2 (myeloid differentiation factor 2) and cd14 (cluster of differentiation 14). Treatment with dexamethasone rescued transcription of tlr4 after LPS inhibition. LPS-induced transcription of md2 was inhibited in the presence of dexamethasone. Dexamethasone alone did not affect transcription of tlr4 and md2

  11. Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Bonin, Camila P., E-mail: mila_bonin@yahoo.com.br [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900 (Brazil); Baccarin, Raquel Y.A., E-mail: baccarin@usp.br [Department of Clinics, School of Veterinary Medicine, University of São Paulo, São Paulo 05508-900 (Brazil); Nostell, Katarina, E-mail: katarina.nostell@slu.se [Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, 750 07 Uppsala (Sweden); Nahum, Laila A., E-mail: laila@nahum.com.br [Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte 30190-002 (Brazil); Faculdade Infórium de Tecnologia, Belo Horizonte 30130-180 (Brazil); Fossum, Caroline, E-mail: caroline.fossum@bvf.slu.se [Department of Biomedicine and Veterinary Public Health, Section for Immunology, Swedish University of Agricultural Sciences, BMC, Box 588, SE 751 23 Uppsala (Sweden); Camargo, Maristela M. de, E-mail: mmcamar@usp.br [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900 (Brazil)

    2013-03-08

    Highlights: ► Chimpanzees, horses and humans have regions of similarity on TLR4 and MD2 promoters. ► Rodents have few regions of similarity on TLR4 promoter when compared to primates. ► Conserved NFkB binding sites were found in the promoters of TLR4 and MD2. ► LPS-induced inhibition of TLR4 transcription is reversed by dexamethasone. ► LPS-induced transcription of MD2 is inhibited by dexamethasone. -- Abstract: Engagement of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explaining these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species (human, chimpanzee, and horse) and low similarity with LPS-resistant species (mouse and rat). Four conserved nuclear factor kappa B (NFκB) binding sites were found in the tlr4 promoter and two in the md2 promoter sequences that are likely to be targets for dexamethasone regulation. In vitro treatment of equine peripheral blood mononuclear cells (eqPBMC) with LPS decreased transcripts of tlr4 and increased transcription of md2 (myeloid differentiation factor 2) and cd14 (cluster of differentiation 14). Treatment with dexamethasone rescued transcription of tlr4 after LPS inhibition. LPS-induced transcription of md2 was inhibited in the presence of dexamethasone. Dexamethasone alone did not affect transcription of tlr4 and md2.

  12. Faunal distribution of fleas and their blood-feeding preferences using enzyme-linked immunosorbent assays from farm animals and human shelters in a new rural region of southern Iran.

    Science.gov (United States)

    Moemenbellah-Fard, Mohammad Djaefar; Shahriari, Bahador; Azizi, Kourosh; Fakoorziba, Mohammad Reza; Mohammadi, Jalal; Amin, Masoume

    2016-03-01

    Blood sucking insects, such as fleas, are responsible for the transmission of many infectious disease-causing agents which impose an intolerable burden on the health of people living particularly in endemic parts of the world. Fleas (Insecta: Siphonaptera) are found in many parts of the world including Iran. Both adult male and female fleas are obligatory ectoparasites. They are one of the main public health concerns as a result of their nuisance or the potential to act as vectors of a number of medically-important pathogens. The current study was conducted to examine the geographical distribution and fauna of fleas and their anthropophagic index in part of Fars province, southern Iran. This study was the first to be done in Iran. A total of 20 villages were randomly selected. From October 2011 to May 2012, adult fleas were collected by direct hand catch from human to animal shelters. Overall 848 fleas, most of which were blood-fed, were captured from the floor or the body of farm animal hosts (cattle, sheep, goat and hens). Only two different genera of fleas were identified, the main species (99.76 %) was human flea, Pulex irritans. The village of Shamsabad was the most heavily infested area. P. irritans had an anthropophagic index of 15 % using indirect enzyme-linked immunosorbent assays (ELISA). It could be concluded that P. irritans is widely distributed in this area. Based on their blood feeding activity, fleas thus posed a serious health threat to residents and their economically important livestock in this part of Iran. PMID:27065620

  13. Cichoric Acid Reverses Insulin Resistance and Suppresses Inflammatory Responses in the Glucosamine-Induced HepG2 Cells.

    Science.gov (United States)

    Zhu, Di; Wang, Yutang; Du, Qingwei; Liu, Zhigang; Liu, Xuebo

    2015-12-30

    Cichoric acid, a caffeic acid derivative found in Echinacea purpurea, basil, and chicory, has been reported to have bioactive effects, such as anti-inflammatory, antioxidant, and preventing insulin resistance. In this study, to explore the effects of CA on regulating insulin resistance and chronic inflammatory responses, the insulin resistance model was constructed by glucosamine in HepG2 cells. CA stimulated glucosamine-mediated glucose uptake by stimulating translocation of the glucose transporter 2. Moreover, the production of reactive oxygen, the expression of COX-2 and iNOS, and the mRNA levels of TNF-α and IL-6 were attenuated. Furthermore, CA was verified to promote glucosamine-mediated glucose uptake and inhibited inflammation through PI3K/Akt, NF-κB, and MAPK signaling pathways in HepG2 cells. These results implied that CA could increase glucose uptake, improve insulin resistance, and attenuate glucosamine-induced inflammation, suggesting that CA is a potential natural nutraceutical with antidiabetic properties and anti-inflammatory effects. PMID:26592089

  14. Antioxidative Diet Supplementation Reverses High-Fat Diet-Induced Increases of Cardiovascular Risk Factors in Mice

    Directory of Open Access Journals (Sweden)

    Hilda Vargas-Robles

    2015-01-01

    Full Text Available Obesity is a worldwide epidemic that is characterized not only by excessive fat deposition but also by systemic microinflammation, high oxidative stress, and increased cardiovascular risk factors. While diets enriched in natural antioxidants showed beneficial effects on oxidative stress, blood pressure, and serum lipid composition, diet supplementation with synthetic antioxidants showed contradictive results. Thus, we tested in C57Bl/6 mice whether a daily dosage of an antioxidative mixture consisting of vitamin C, vitamin E, L-arginine, eicosapentaenoic acid, and docosahexaenoic acid (corabion would affect cardiovascular risk factors associated with obesity. Obese mice showed increased serum triglyceride and glucose levels and hypertension after eight weeks of being fed a high-fat diet (HFD. Importantly, corabion ameliorated all of these symptoms significantly. Oxidative stress and early signs of systemic microinflammation already developed after two weeks of high-fat diet and were significantly reduced by daily doses of corabion. Of note, the beneficial effects of corabion could not be observed when applying its single antioxidative components suggesting that a combination of various nutrients is required to counteract HFD-induced cardiovascular risk factors. Thus, daily consumption of corabion may be beneficial for the management of obesity-related cardiovascular complications.

  15. Reversible dementias

    OpenAIRE

    Tripathi, Manjari; Vibha, Deepti

    2009-01-01

    In recent years, more attention has been given to the early diagnostic evaluation of patients with dementia which is essential to identify patients with cognitive symptoms who may have treatable conditions. Guidelines suggest that all patients presenting with dementia or cognitive symptoms should be evaluated with a range of laboratory tests, and with structural brain imaging with computed tomography (CT) or magnetic resonance imaging (MRI). While many of the disorders reported as ‘reversible...

  16. Single dose of intra-muscular platelet rich plasma reverses the increase in plasma iron levels in exercise-induced muscle damage:A pilot study

    Institute of Scientific and Technical Information of China (English)

    Zekine Punduk; Onur Oral; Nadir Ozkayin; Khalid Rahman; Rana Varol

    2016-01-01

    administration improves inflammation by reversing the increase in the iron levels post-exercise without displaying any myotoxicity and may have a role to play in the recovery of exercise-induced muscle damage.

  17. Reversal effects of crocin on amyloid β-induced memory deficit: Modification of autophagy or apoptosis markers.

    Science.gov (United States)

    Asadi, Farideh; Jamshidi, Amir Hossein; Khodagholi, Fariba; Yans, Asal; Azimi, Leila; Faizi, Mehrdad; Vali, Leila; Abdollahi, Mohammad; Ghahremani, Mohammad Hossein; Sharifzadeh, Mohammad

    2015-12-01

    Crocin, as a carotenoid, is one of the main and active constituents of saffron stigmas (Crocus sativus L.) that is widely used in folk medicine. Several studies have pointed out the potent antioxidant and neuroprotective properties of crocin which may have therapeutic values for management of neurodegenerative disorders such as Alzheimer's disease. Alzheimer's disease is the most common form of dementia among the elderly and is characterized by massive neuronal loss and progressive cognitive impairment. Beta amyloid hypothesis is the main theoretical research framework for Alzheimer's disease which states that extracellular aggregation of beta amyloid results in synaptic loss and eventually cell apoptosis. Recent findings suggest that autophagy and apoptosis are extensively involved in Alzheimer's disease. In order to investigate therapeutic values of crocin, we examined the effect of crocin on memory, cell apoptosis, and autophagy using in vivo models of Alzheimer's disease. We also compared the effect of crocin administration on spatial memory with nicotine as positive control. Morris water maze results show that intra-peritoneal and intra-hippocampal administration of crocin significantly improve spatial memory indicators such as escape latency, traveled distance and time spent in target quadrant when compared to beta amyloid injection. Furthermore, we measured certain biomarkers of cell autophagy and apoptosis using Western blot analysis. Our results reveal that crocin administration does not cause any significant alteration in Beclin-1 and ratio of LC3-II/LC3-I compared to the group received beta amyloid by hippocampal injection. However, in contrast to autophagy, crocin administration significantly decreases Bax/Bcl-2 ratio and cleaved Caspase-3 level. This demonstrates that crocin inhibits beta amyloid induced apoptosis, which is possibly associated with its antioxidant properties. Our results further confirm the neuroprotective properties of crocin as a

  18. Reversible Low-Light Induced Photoswitching of Crowned Spiropyran-DO3A Complexed with Gadolinium(III Ions

    Directory of Open Access Journals (Sweden)

    André Knoesen

    2012-05-01

    Full Text Available Photoswitchable spiropyran has been conjugated to the crowned ring system DO3A, which improves its solubility in dipolar and polar media and stabilizes the merocyanine isomer. Adding the lanthanide ion gadolinium(III to the macrocyclic ring system leads to a photoresponsive magnetic resonance imaging contrast agent that displays an increased spin-lattice relaxation time (T1 upon visible light stimulation. In this work, the photoresponse of this photochromic molecule to weak light illumination using blue and green light emitting diodes was investigated, simulating the emission spectra from bioluminescent enzymes. Photon emission rate of the light emitting diodes was changed, from 1.75 × 1016 photons·s−1 to 2.37 × 1012 photons·s−1. We observed a consistent visible light-induced isomerization of the merocyanine to the spiropyran form with photon fluxes as low as 2.37 × 1012 photons·s−1 resulting in a relaxivity change of the compound. This demonstrates the potential for use of the described imaging probes in low light level applications such as sensing bioluminescence enzyme activity. The isomerization behavior of gadolinium(III-ion complexed and non-complexed spiropyran-DO3A was analyzed in water and ethanol solution in response to low light illumination and compared to the emitted photon emission rate from over-expressed Gaussia princeps luciferase.

  19. C-peptide reverses TGF-beta1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy.

    Science.gov (United States)

    Hills, Claire E; Al-Rasheed, Nawal; Al-Rasheed, Nouf; Willars, Gary B; Brunskill, Nigel J

    2009-03-01

    The crucial pathology underlying progressive chronic kidney disease in diabetes is tubulointerstitial fibrosis. Central to this process is epithelial-mesenchymal transformation (EMT) of proximal tubular epithelial cells driven by maladaptive transforming growth factor-beta1 (TGF-beta1) signaling. Novel signaling roles for C-peptide have recently been discovered with evidence emerging that C-peptide may mitigate microvascular complications of diabetes. We studied the potential for C-peptide to interrupt injurious TGF-beta1 signaling pathways and thus block development of EMT in HK2 human kidney proximal tubular cells. Cells were incubated with TGF-beta1 either alone or with C-peptide in low or high glucose. Changes in cell morphology, TGF-beta1 receptor expression, vimentin, E-cadherin, and phosphorylated Smads were assessed. Luciferase reporters were used to assess Smad activity. The cytoskeleton was visualized by TRITC-phalloidin staining. The typical TGF-beta1-stimulated, EMT-associated morphological alterations of proximal tubular cells, including increased vimentin expression, decreased E-cadherin expression, and cytoskeletal rearrangements, were prevented by C-peptide treatment. C-peptide also blocked TGF-beta1-induced upregulation of expression of both type I and type II TGF-beta1 receptors and attenuated TGF-beta1-mediated Smad phosphorylation and Smad transcriptional activity. These effects of C-peptide were inhibited by pertussis toxin. The results demonstrate that C-peptide almost completely reversed the morphological changes in PT cells induced by TGF-beta1 and suggest a role or C-peptide as a renoprotective agent in diabetic nephropathy. PMID:19091788

  20. Interleukin-32α inactivates JAK2/STAT3 signaling and reverses interleukin-6-induced epithelial-mesenchymal transition, invasion, and metastasis in pancreatic cancer cells.

    Science.gov (United States)

    Chen, Jingfeng; Wang, Silu; Su, Jiadong; Chu, Guanyu; You, Heyi; Chen, Zongjing; Sun, Hongwei; Chen, Bicheng; Zhou, Mengtao

    2016-01-01

    Interleukin (IL)-32 is a newly discovered cytokine that has multifaceted roles in inflammatory bowel disease, cancer, and autoimmune diseases and participates in cell apoptosis, cancer cell growth inhibition, accentuation of inflammation, and angiogenesis. Here, we investigated the potential effects of IL-32α on epithelial-mesenchymal transition, metastasis, and invasion, and the JAK2/STAT3 signaling pathway in pancreatic cancer cells. The human pancreatic cancer cell lines PANC-1 and SW1990 were used. Epithelial-mesenchymal transition-related markers, including E-cadherin, N-cadherin, Vimentin, Snail, and Zeb1, as well as extracellular matrix metalloproteinases (MMPs), including MMP2, MMP7, and MMP9, were detected by immunofluorescence, Western blotting, and real-time polymerase chain reaction. The activation of JAK2/STAT3 signaling proteins was detected by Western blotting. Wound healing assays, real-time polymerase chain reaction, and Western blotting were performed to assess cell migration and invasion. The effects of IL-32α on the IL-6-induced activation of JAK2/STAT3 were also evaluated. In vitro, we found that IL-32α inhibits the expressions of the related markers N-cadherin, Vimentin, Snail, and Zeb1, as well as JAK2/STAT3 proteins, in a dose-dependent manner in pancreatic cancer cell lines. Furthermore, E-cadherin expression was increased significantly after IL-32α treatment. IL-32α downregulated the expression of MMPs, including MMP2, MMP7, and MMP9, and decreased wound healing in pancreatic cancer cells. These consistent changes were also found in IL-6-induced pancreatic cancer cells following IL-32α treatment. This study showed that reversion of epithelial-mesenchymal transition, inhibition of invasiveness and metastasis, and activation of the JAK2/STAT3 signaling pathway could be achieved through the application of exogenous IL-32α. PMID:27471397

  1. Survival or revival: long-term preservation induces a reversible viable but non-culturable state in methane-oxidizing bacteria.

    Directory of Open Access Journals (Sweden)

    Sven Hoefman

    Full Text Available Knowledge on long-term preservation of micro-organisms is limited and research in the field is scarce despite its importance for microbial biodiversity and biotechnological innovation. Preservation of fastidious organisms such as methane-oxidizing bacteria (MOB has proven difficult. Most MOB do not survive lyophilization and only some can be cryopreserved successfully for short periods. A large-scale study was designed for a diverse set of MOB applying fifteen cryopreservation or lyophilization conditions. After three, six and twelve months of preservation, the viability (via live-dead flow cytometry and culturability (via most-probable number analysis and plating of the cells were assessed. All strains could be cryopreserved without a significant loss in culturability using 1% trehalose in 10-fold diluted TSB (TT as preservation medium and 5% DMSO as cryoprotectant. Several other cryopreservation and lyophilization conditions, all of which involved the use of TT medium, also allowed successful preservation but showed a considerable loss in culturability. We demonstrate here that most of these non-culturables survived preservation according to viability assessment indicating that preservation induces a viable but non-culturable (VBNC state in a significant fraction of cells. Since this state is reversible, these findings have major implications shifting the emphasis from survival to revival of cells in a preservation protocol. We showed that MOB cells could be significantly resuscitated from the VBNC state using the TT preservation medium.

  2. Reversible control of magnetism in La0.67Sr0.33MnO3 through chemically-induced oxygen migration

    Science.gov (United States)

    Grutter, A. J.; Gilbert, D. A.; Alaan, U. S.; Arenholz, E.; Maranville, B. B.; Borchers, J. A.; Suzuki, Y.; Liu, Kai; Kirby, B. J.

    2016-02-01

    We demonstrate reversible control of magnetization and anisotropy in La0.67Sr0.33MnO3 films through interfacial oxygen migration. Gd metal capping layers deposited onto La0.67Sr0.33MnO3 leach oxygen from the film through a solid-state redox reaction to form porous Gd2O3. X-ray absorption and polarized neutron reflectometry measurements show Mn valence alterations consistent with high oxygen vacancy concentrations, resulting in suppressed magnetization and increased coercive fields. Effects of the oxygen migration are observed both at the interface and also throughout the majority of a 40 nm thick film, suggesting extensive diffusion of oxygen vacancies. After Gd-capped La0.67Sr0.33MnO3 is exposed to atmospheric oxygen for a prolonged period of time, oxygen diffuses through the Gd2O3 layer and the magnetization of the La0.67Sr0.33MnO3 returns to the uncapped value. These findings showcase perovskite heterostructures as ideal candidates for developing functional interfaces through chemically-induced oxygen migration.

  3. [Dexamethasone increases the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in lung tissues of bronchial asthmatic mice].

    Science.gov (United States)

    Li, Zhenxing; He, Sheng; Wei, Liping; Lin, Lin; Xiong, Hanzhen; Li, Junhong; Chen, Peifen; Lai, Wenyan

    2016-05-01

    Objective To investigate the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in the lung tissues of bronchial asthmatic mice and the effect of dexamethasone treatment on its expression. Methods Thirty BALB/c mice were randomly divided into three equal groups: a control group, an asthmatic group and a dexamethasone-treated group. The asthmatic mouse models were established by intraperitoneal injection and inhalation with ovalbumin (OVA). The number of eosinophils (EOS) and lymphocytes (Lym) in bronchoalveolar lavage fluid (BALF) were counted. HE staining was used to observe airway inflammation and remodeling. The mRNA and protein expression of RECK were determined by real-time PCR and immunohistochemistry, respectively. Results Compared with the control group and the dexamethasone-treated group, the total cell number and EOS number in the BALF of the asthma group significantly increased. The expression of RECK mRNA in the asthmatic group was significantly lower than that in the control group and the dexamethasone-treated group. Immunohistochemistry showed that RECK was mainly expressed in the airway epithelial cells and inflammatory cells. RECK protein expression was highest in the control group and lowest in the asthmatic group. Conclusion Dexamethasone can increase the expression of RECK in the lung tissues of asthmatic mice. PMID:27126937

  4. Influence of the shape and surface oxidation in the magnetization reversal of thin iron nanowires grown by focused electron beam induced deposition

    Directory of Open Access Journals (Sweden)

    Luis A. Rodríguez

    2015-06-01

    Full Text Available Iron nanostructures grown by focused electron beam induced deposition (FEBID are promising for applications in magnetic sensing, storage and logic. Such applications require a precise design and determination of the coercive field (HC, which depends on the shape of the nanostructure. In the present work, we have used the Fe2(CO9 precursor to grow iron nanowires by FEBID in the thickness range from 10 to 45 nm and width range from 50 to 500 nm. These nanowires exhibit an Fe content between 80 and 85%, thus giving a high ferromagnetic signal. Magneto-optical Kerr characterization indicates that HC decreases for increasing thickness and width, providing a route to control the magnetization reversal field through the modification of the nanowire dimensions. Transmission electron microscopy experiments indicate that these wires have a bell-type shape with a surface oxide layer of about 5 nm. Such features are decisive in the actual value of HC as micromagnetic simulations demonstrate. These results will help to make appropriate designs of magnetic nanowires grown by FEBID.

  5. Reversible focal splenial lesions

    Energy Technology Data Exchange (ETDEWEB)

    Gallucci, Massimo; Limbucci, Nicola [University of L' Aquila, Department of Radiology, S. Salvatore Hospital, L' Aquila (Italy); Paonessa, Amalia [Loreto Nuovo Hospital, Department of Neuroradiology, Napoli (Italy); Caranci, Ferdinando [Federico II University, Department of Neurological Sciences, Napoli (Italy)

    2007-07-15

    Reversible focal lesions in the splenium of the corpus callosum (SCC) have recently been reported.They are circumscribed and located in the median aspect of the SCC. On MRI, they are hyperintense on T2-W and iso-hypointense on T1-W sequences, with no contrast enhancement. On DWI, SCC lesions are hyperintense with low ADC values, reflecting restricted diffusion due to cytotoxic edema. The common element is the disappearance of imaging abnormalities with time, including normalization of DWI. Clinical improvement is often reported. The most established and frequent causes of reversible focal lesions of the SCC are viral encephalitis, antiepileptic drug toxicity/withdrawal and hypoglycemic encephalopathy. Many other causes have been reported, including traumatic axonal injury. The similar clinical and imaging features suggest a common mechanism induced by different pathological events leading to the same results. Edema and diffusion restriction in focal reversible lesions of the SCC have been attributed to excitotoxic mechanisms that can result from different mechanisms; no unifying relationship has been found to explain all the pathologies associated with SCC lesions. In our opinion, the similar imaging, clinical and prognostic aspects of these lesions depend on a high vulnerability of the SCC to excitotoxic edema and are less dependent on the underlying pathology. In this review, the relevant literature concerning reversible focal lesions in the SCC is analyzed and hypotheses about their pathogenesis are proposed. (orig.)

  6. Inhibition of telomerase with human telomerase reverse transcriptase antisense enhances tumor necrosis factor-a-induced apoptosis in bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    GAO Xiao-dong; CHEN Yi-rong

    2007-01-01

    Background Telomerase activity is found in 85%-90% of all human cancers but not in their adjacent normal cells.Human telomerase reverse transcriptase (hTERT) is an essential component in the telomerase complex that plays an important role in telomerase activity. This study investigated the effect of the telomerase inhibition with an hTERT antisense oligodeoxynucleotide (ODN) in bladder cancer cells (T24) on tumor necrosis factor-o (TNF-α)-induced apoptosis.Methods Antisense phosphorothioate oligodeoxynucleotide (AS PS-ODN) was synthesized and purified. Telomerase activity was measured by polymerase chain reaction enzyme-linked immunoassay (PCR-ELISA). hTERT mRNA expression was measured by reverse transcription polymerase chain reaction (RT-PCR) assay and a gel-image system.hTERT protein was detected by immunochemistry and flow cytometry. Cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium (MTT) assay. Cell apoptosis was observed by a morphological method and determined by flow cytometry.Results AS PS-ODN significantly inhibited telomerase activity and decreased the levels of hTERT mRNA which preceded the decline in the telomerase activity. AS PS-ODN significantly reduced the percentage of positive cells expressing hTERT protein following the decline of hTERT mRNA levels. There was no difference seen in the telomerase activity, hTERT mRNA expression or the protein levels between the sense phosphorothioate oligodeoxynucleotide (SPS-ODN) and the control group. AS PS-ODN treatment significantly decreased the cell viability and enhanced the apoptotic rate of T24 cells in response to TNF-α while there was no difference in cell viability and apoptotic rate between the S PS-ODN and the control group.Conclusions AS PS-ODN can significantly inhibit telomerase activity by downregulating the hTERT mRNA and protein expression. Treatment with AS PS-ODN may be a potential and most promising strategy for bladder cancer with telomerase

  7. Ion irradiation induced effects and magnetization reversal mechanism in (Ni{sub 80}Fe{sub 20}){sub 1−x}Co{sub x} nanowires and nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Naeem, E-mail: naeem.ahmad@iiu.edu.pk [Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences (CAS), Beijing 100090 (China); Spintronics Laboratory, Department of Physics, Faculty of Basic and Applied Sciences (FBAS), International Islamic University H-10, Islamabad 44000 (Pakistan); Iqbal, Javed [Laboratory of Nanoscience and Technology, Department of Physics, International Islamic University, H-10, Islamabad,Pakistan (Pakistan); Chen, J.Y. [Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences (CAS), Beijing 100090 (China); Hussain, Asim [Spintronics Laboratory, Department of Physics, Faculty of Basic and Applied Sciences (FBAS), International Islamic University H-10, Islamabad 44000 (Pakistan); Shi, D.W.; Han, X.F. [Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences (CAS), Beijing 100090 (China)

    2015-03-15

    The effect of Co on the ferromagnetic characteristics of the Ni{sub 80}Fe{sub 20} nanocylinders having zero magnetostriction and soft magnetic nature is an interesting field of research. The (Ni{sub 80}Fe{sub 20}){sub 1−x}Co{sub x} nanocylinders have been prepared by electrodeposition into commercially available anodized aluminum oxide (AAO) nanoporous templates. The analysis of magnetization reversal from the angular dependence of coercivity has been studied in detail. This angular dependence of coercivity has shown a transition from curling to nucleation mode as a function of field angle for all (Ni{sub 80}Fe{sub 20}){sub 1−x}Co{sub x} nanocylinders depending upon the critical angle. The shape anisotropy, dipole–dipole interactions, surface effects and magnetocrystalline anisotropy have been found to play an effective role for the spontaneous magnetization in nanowires and nanotubes. It has been interestingly observed that the magnetostatic interactions or dipole–dipole interactions are dominant in nanocylinders regardless of its geometry. Furthermore, the prepared samples have been irradiated with He{sup 2+} ions (energy E=2 MeV, fluence=10{sup 14} ions/cm{sup 2} and ion current=16 nA) at room temperature using a 5-UDH-2pelletron tandem accelerator. The irradiations have created defects and these defects have induced changes in magnetization as a result an increase in coercivity as function of the ion fluences is observed. Such kind of behavior in coercivity enhancement and magnetization reduction can also be attributed to the stress relaxation and percolation in nonuniform states of ferromagnetic alloys, respectively. - Highlights: • We have prepared the ferromagnetic NiFeCo nanowires and nanotubes into anodized aluminum oxide templates (AAO) by electrodeposition method. • We have studied the magnetization reversal mechanism from the angle dependent coercivity measured by a hysteresis loop. • The ion irradiation effects on these nanostructures

  8. Selective killing of human immunodeficiency virus infected cells by non-nucleoside reverse transcriptase inhibitor-induced activation of HIV protease

    Directory of Open Access Journals (Sweden)

    Smeulders Liesbeth

    2010-10-01

    Full Text Available Abstract Background Current antiretroviral therapy against human immunodeficiency virus (HIV-1 reduces viral load and thereby prevents viral spread, but it cannot eradicate proviral genomes from infected cells. Cells in immunological sanctuaries as well as cells producing low levels of virus apparently contribute to a reservoir that maintains HIV persistence in the presence of highly active antiretroviral therapy. Thus, accelerated elimination of virus producing cells may represent a complementary strategy to control HIV infection. Here we sought to exploit HIV protease (PR related cytotoxicity in order to develop a strategy for drug induced killing of HIV producing cells. PR processes the viral Gag and Gag-Pol polyproteins during virus maturation, but is also implicated in killing of virus producing cells through off-target cleavage of host proteins. It has been observed previously that micromolar concentrations of certain non-nucleoside reverse transcriptase inhibitors (NNRTIs can stimulate intracellular PR activity, presumably by enhancing Gag-Pol dimerization. Results Using a newly developed cell-based assay we compared the degree of PR activation displayed by various NNRTIs. We identified inhibitors showing higher potency with respect to PR activation than previously described for NNRTIs, with the most potent compounds resulting in ~2-fold increase of the Gag processing signal at 250 nM. The degree of enhancement of intracellular Gag processing correlated with the compound's ability to enhance RT dimerization in a mammalian two-hybrid assay. Compounds were analyzed for their potential to mediate specific killing of chronically infected MT-4 cells. Levels of cytotoxicity on HIV infected cells determined for the different NNRTIs corresponded to the relative degree of drug induced intracellular PR activation, with CC50 values ranging from ~0.3 μM to above the tested concentration range (10 μM. Specific cytotoxicity was reverted by addition

  9. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit in...... different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved by...

  10. Sorption-induced reversible oxidation of Fe(2) at the smectite/water interface under strictly anoxic conditions. A Moessbauer spectroscopy study

    International Nuclear Information System (INIS)

    sorption at the clay-water interface occurs in a two steps mechanism: sorption of individual Fe(II) cations, followed by an oxidation of some of them. As a first hypothesis, water could be the oxidizing agent. However in this case, the reversibility of the phenomenon cannot be explained. Thus we proposed, as a second hypothesis, that as pH is increased, protons H+ is removed from the clay surface and, more and more of highly reactive sites acquire steric properties that stabilize Fe(III) relative to Fe(II). This differential affinity induces in turn an Fe-to-clay particle electron transfer. The change in surface site local environment is shown by observed large pH induced change in the sorbed Fe(II) quadrupole splitting distributions. (authors)

  11. Valproic acid inhibits the release of soluble CD40L induced by non-nucleoside reverse transcriptase inhibitors in human immunodeficiency virus infected individuals.

    Directory of Open Access Journals (Sweden)

    Donna C Davidson

    Full Text Available Despite the use of highly active antiretroviral therapies (HAART, a majority of Human Immunodeficiency Virus Type 1 (HIV infected individuals continually develop HIV - Associated Neurocognitive Disorders (HAND, indicating that host inflammatory mediators, in addition to viral proteins, may be contributing to these disorders. Consistent with this notion, we have previously shown that levels of the inflammatory mediator soluble CD40 ligand (sCD40L are elevated in the plasma and cerebrospinal fluid (CSF of HIV infected, cognitively impaired individuals, and that excess sCD40L can contribute to blood brain barrier (BBB permeability in vivo, thereby signifying the importance of this inflammatory mediator in the pathogenesis of HAND. Here we demonstrate that the non-nucleoside reverse transcriptase inhibitor (NNRTI efavirenz (EFV induces the release of circulating sCD40L in both HIV infected individuals and in an in vitro suspension of washed human platelets, which are the main source of circulating sCD40L. Additionally, EFV was found to activate glycogen synthase kinase 3 beta (GSK3β in platelets, and we now show that valproic acid (VPA, a known GSK3β inhibitor, was able to attenuate the release of sCD40L in HIV infected individuals receiving EFV, and in isolated human platelets. Collectively these results have important implications in determining the pro-inflammatory role that some antiretroviral regimens may have. The use of antiretrovirals remains the best strategy to prevent HIV-associated illnesses, including HAND, however these drugs have clear limitations to this end, and thus, these results underscore the need to develop adjunctive therapies for HAND that can also minimize the undesired negative effects of the antiretrovirals.

  12. RECK (reversion-inducing cysteine-rich protein with Kazal motifs) regulates migration, differentiation and Wnt/β-catenin signaling in human mesenchymal stem cells.

    Science.gov (United States)

    Mahl, Christian; Egea, Virginia; Megens, Remco T A; Pitsch, Thomas; Santovito, Donato; Weber, Christian; Ries, Christian

    2016-04-01

    The membrane-anchored glycoprotein RECK (reversion-inducing cysteine-rich protein with Kazal motifs) inhibits expression and activity of certain matrix metalloproteinases (MMPs), thereby suppressing tumor cell metastasis. However, RECK's role in physiological cell function is largely unknown. Human mesenchymal stem cells (hMSCs) are able to differentiate into various cell types and represent promising tools in multiple clinical applications including the regeneration of injured tissues by endogenous or transplanted hMSCs. RNA interference of RECK in hMSCs revealed that endogenous RECK suppresses the transcription and biosynthesis of tissue inhibitor of metalloproteinases (TIMP)-2 but does not influence the expression of MMP-2, MMP-9, membrane type (MT)1-MMP and TIMP-1 in these cells. Knockdown of RECK in hMSCs promoted monolayer regeneration and chemotactic migration of hMSCs, as demonstrated by scratch wound and chemotaxis assay analyses. Moreover, expression of endogenous RECK was upregulated upon osteogenic differentiation and diminished after adipogenic differentiation of hMSCs. RECK depletion in hMSCs reduced their capacity to differentiate into the osteogenic lineage whereas adipogenesis was increased, demonstrating that RECK functions as a master switch between both pathways. Furthermore, knockdown of RECK in hMSCs attenuated the Wnt/β-catenin signaling pathway as indicated by reduced stability and impaired transcriptional activity of β-catenin. The latter was determined by analysis of the β-catenin target genes Dickkopf1 (DKK1), axis inhibition protein 2 (AXIN2), runt-related transcription factor 2 (RUNX2) and a luciferase-based β-catenin-activated reporter (BAR) assay. Our findings demonstrate that RECK is a regulator of hMSC functions suggesting that modulation of RECK may improve the development of hMSC-based therapeutical approaches in regenerative medicine. PMID:26459448

  13. Interferon-inducible IFI16, a negative regulator of cell growth, down-regulates expression of human telomerase reverse transcriptase (hTERT gene.

    Directory of Open Access Journals (Sweden)

    Lynda Li Song

    Full Text Available BACKGROUND: Increased levels of interferon (IFN-inducible IFI16 protein (encoded by the IFI16 gene located at 1q22 in human normal prostate epithelial cells and diploid fibroblasts (HDFs are associated with the onset of cellular senescence. However, the molecular mechanisms by which the IFI16 protein contributes to cellular senescence-associated cell growth arrest remain to be elucidated. Here, we report that increased levels of IFI16 protein in normal HDFs and in HeLa cells negatively regulate the expression of human telomerase reverse transcriptase (hTERT gene. METHODOLOGY/PRINCIPAL FINDINGS: We optimized conditions for real-time PCR, immunoblotting, and telomere repeat amplification protocol (TRAP assays to detect relatively low levels of hTERT mRNA, protein, and telomerase activity that are found in HDFs. Using the optimized conditions, we report that treatment of HDFs with inhibitors of cell cycle progression, such as aphidicolin or CGK1026, which resulted in reduced steady-state levels of IFI16 mRNA and protein, was associated with increases in hTERT mRNA and protein levels and telomerase activity. In contrast, knockdown of IFI16 expression in cells increased the expression of c-Myc, a positive regulator of hTERT expression. Additionally, over-expression of IFI16 protein in cells inhibited the c-Myc-mediated stimulation of the activity of hTERT-luc-reporter and reduced the steady-state levels of c-Myc and hTERT. CONCLUSIONS/SIGNIFICANCE: These data demonstrated that increased levels of IFI16 protein in HDFs down-regulate the expression of hTERT gene. Our observations will serve basis to understand how increased cellular levels of the IFI16 protein may contribute to certain aging-dependent diseases.

  14. Acute reversible inactivation of the bed nucleus of stria terminalis induces antidepressant-like effect in the rat forced swimming test

    Directory of Open Access Journals (Sweden)

    Joca Sâmia RL

    2010-06-01

    Full Text Available Abstract Background The bed nucleus of stria terminalis (BNST is a limbic forebrain structure involved in hypothalamo-pituitary-adrenal axis regulation and stress adaptation. Inappropriate adaptation to stress is thought to compromise the organism's coping mechanisms, which have been implicated in the neurobiology of depression. However, the studies aimed at investigating BNST involvement in depression pathophysiology have yielded contradictory results. Therefore, the objective of the present study was to investigate the effects of temporary acute inactivation of synaptic transmission in the BNST by local microinjection of cobalt chloride (CoCl2 in rats subjected to the forced swimming test (FST. Methods Rats implanted with cannulae aimed at the BNST were submitted to 15 min of forced swimming (pretest. Twenty-four hours later immobility time was registered in a new 5 min forced swimming session (test. Independent groups of rats received bilateral microinjections of CoCl2 (1 mM/100 nL before or immediately after pretest or before the test session. Additional groups received the same treatment and were submitted to the open field test to control for unspecific effects on locomotor behavior. Results CoCl2 injection into the BNST before either the pretest or test sessions reduced immobility in the FST, suggesting an antidepressant-like effect. No significant effect of CoCl2 was observed when it was injected into the BNST immediately after pretest. In addition, no effect of BNST inactivation was observed in the open field test. Conclusion These results suggest that acute reversible inactivation of synaptic transmission in the BNST facilitates adaptation to stress and induces antidepressant-like effects.

  15. A diet high in fat and sugar reverses anxiety-like behaviour induced by limited nesting in male rats: Impacts on hippocampal markers.

    Science.gov (United States)

    Maniam, Jayanthi; Antoniadis, Christopher P; Le, Vivian; Morris, Margaret J

    2016-06-01

    Stress exposure during early development is known to produce long-term mental health deficits. Stress promotes poor lifestyle choices such as poor diet. Early life adversity and diets high in fat and sugar (HFHS) are known to affect anxiety and memory. However additive effects of HFHS and stress during early development are less explored. Here, we examined whether early life stress (ELS) simulated by limited nesting (LN) induces anxiety-like behaviour and cognitive deficits that are modulated by HFHS diet. We examined key hippocampal markers involved in anxiety and cognition, testing the hypothesis that post-weaning HFHS following ELS would ameliorate anxiety-like behaviour but worsen memory and associated hippocampal changes. Sprague-Dawley rats were exposed to LN, postnatal days 2-9, and at weaning, male siblings were given unlimited access to chow or HFHS resulting in (Con-Chow, Con-HFHS, LN-Chow, LN-HFHS, n=11-15/group). Anxiety-like behaviour was assessed by Elevated Plus Maze (EPM) at 10 weeks and spatial and object recognition tested at 11 weeks of age. Rats were culled at 13 weeks. Hippocampal mRNA expression was measured using TaqMan(®) Array Micro Fluidic cards (Life Technologies). As expected HFHS diet increased body weight; LN and control rats had similar weights at 13 weeks, energy intake was also similar across groups. LN-Chow rats showed increased anxiety-like behaviour relative to control rats, but this was reversed by HFHS diet. Spatial and object recognition memory were unaltered by LN exposure or consumption of HFHS diet. Hippocampal glucocorticoid receptor (GR) protein was not affected by LN exposure in chow rats, but was increased by 45% in HFHS rats relative to controls. Hippocampal genes involved in plasticity and mood regulation, GSKα and GSKβ were affected, with reductions in GSKβ under both diet conditions, and reduced GSKα only in LN-HFHS versus Con-HFHS. Interestingly, HFHS diet and LN exposure independently reduced expression of

  16. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points - An international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial

    DEFF Research Database (Denmark)

    Puhringer, F.K.; Rex, C.; Sielenkamper, A.W.;

    2008-01-01

    evaluated. Methods: A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0......Background: Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was...... residual neuromuscular blockade. Exploratory analysis revealed that prolongation of the corrected QT interval considered as possibly related to sugammadex occurred in one patient. Another two patients developed markedly abnormal arterial blood pressure after sugammadex that lasted approximately 15 min...

  17. Rat Models of Diet-Induced Obesity and High Fat/Low Dose Streptozotocin Type 2 Diabetes: Effect of Reversal of High Fat Diet Compared to Treatment with Enalapril or Menhaden Oil on Glucose Utilization and Neuropathic Endpoints

    OpenAIRE

    Amey Holmes; Coppey, Lawrence J.; Eric P. Davidson; Yorek, Mark A.

    2015-01-01

    We examined whether reversal of high fat diet, stimulating weight loss, compared to two treatments previously shown to have beneficial effects, could improve glucose utilization and peripheral neuropathy in animal models of obesity and type 2 diabetes. Rats were fed a high fat diet and treated with a low dose of streptozotocin to create models of diet induced obesity or type 2 diabetes, respectively. Afterwards, rats were transferred to a normal diet or treated with enalapril or dietary enric...

  18. Anion- and Solvent-Induced Assembly and Reversible Structural Transformation of d(10)-Metal Coordination Architectures Containing N-(4-(4-Aminophenyloxy)phenyl)isonicotinamide.

    Science.gov (United States)

    Tzeng, Biing-Chiau; Hung, Yu-Ching; Lee, Gene-Hsiang

    2016-01-22

    We set out studies on anion- and solvent-induced assembly based on the ligand N-(4-(4-aminophenyloxy)phenyl)isonicotinamide (papoa), which is synthesized to show a bent and flexible backbone. Reactions of papoa with ZnX2 (X=Cl, Br, and I) gave the dinuclear macrocycles ([ZnX2 (papoa)]2 ; X=Cl (1 a), Br (2 a), I (3)), the structure of which was determined by X-ray diffraction. Notably, the less bulky Cl and Br compounds afforded the coordinated imine in acetone (i.e., [ZnX2 (papoi)]2 , papoi=N-(4-(4-(propan-2-ylideneamino)phenoxy)phenyl)isonicotinamide; X=Cl (1 b), Br (2 b)), whereas the iodine one only gave the coordinated amine compound 3 under the same reaction condition. In fact, the coordinated imine can return to the amine analogue upon exposure to air or in DMSO, which has been monitored by (1)H NMR spectroscopy and powder X-ray diffraction. Both the dinuclear [Zn(papoa)(NO3)2]2 (4 a) and the 1D [Zn(papoa)2(NO3)2]n (4 b) were formed from the reaction of Zn(NO3)2 and papoa in mixed solvents with acetone and acetonitrile, respectively. In addition, Cd(ClO4)2 can react with papoa to give the 1D framework {[Cd(papoa)2 (CH3CN)2](ClO4)2}n (5 a) and the 2D framework [Cd(papoa)2 (ClO4)2]n (5 b), depending on the solvent used, that is, MeOH and CH3CN, respectively. Importantly, the 1D framework with axially coordinated CH3 CN molecules and the 2D framework with axially coordinated ClO4(-) ions can be interconverted by heating and grinding in the presence of CH3CN, respectively. Such a reversible structural transformation process was proven by PXRD studies. PMID:26677168

  19. Sample stacking microemulsion electrokinetic capillary chromatography induced by reverse migrating pseudostationary phase for the quantification of phenobarbital and its p-hydroxyphenobarbital metabolite in rat urine.

    Science.gov (United States)

    Kadi, Adnan; Hefnawy, Mohamed; Julkhuf, Saeed; Abounassif, Mohammed; Mostafa, Gamal; Kassem, Mohamed G; Attia, Sabry; Al-Ghamdi, Ali

    2011-07-01

    For the first time, a capillary electrophoretic (CE) method with sample stacking induced by a reverse migrating pseudostationary phase (SRMP) technique has been developed and validated for sensitive determination of phenobarbital (PB) and its p-hydroxyphenobarbital (PHPB) metabolite in rat urine samples. Separation and determination were optimized on a fused-silica capillary with a total length of 50 cm (effective length 40 cm) and 75 μm ID. The microemulsion background electrolyte consisted of 0.8% (v/v) ethyl acetate, 6.6% (v/v) butan-2-ol, 1.0% (v/v) acetonitrile, 2.0% (w/v) sodium n-dodecyl sulfate (SDS), and 89.6% (v/v) of 7.5 mM ammonium formate at pH 8. When this preconcentration technique was used, the sample stacking and the separation processes took place successively with changing the voltage with an intermediate polarity switching step. For practical application, a solid-phase extraction (SPE), C(18) sorbent with n-hexane/ethyl acetate (1 : 1%, v/v) as the elution solvent was used for sample purification and concentration. The SPE method gave good extraction yields for all the analytes, with absolute recovery values of 96.9% and 99.1% for PB and PHPB, respectively. The regression equations for PB and PHPB showed excellent linearity over a concentration range of 55-1386 ng mL(-1) for PB and PHPB (r = 0.998). The developed microemulsion electrokinetic capillary chromatography (MEEKC) method for separation of the studied compounds with SRMP as the electrophoretic preconcentration technique allowed detection limits in urine samples at 16.8 ng mL(-1) for PB and PHPB which are 15-fold lower than the reported CE method in the literature. The precision results, expressed by the intra-day and inter-day relative standard deviation (RSD) values range from 3.6 to 7.1% (repeatability) and from 3.2 to 7.2% (intermediate precision) for PB and PHPB, respectively, which were in line with Food and Drug Administration (FDA) criteria. PMID:21607283

  20. Nano-mechanical magnetization reversal

    OpenAIRE

    Kovalev, Alexey A.; Bauer, Gerrit E. W.; Brataas, Arne

    2004-01-01

    The dynamics of the ferromagnetic order parameter in thin magnetic films is strongly affected by the magnetomechanical coupling at certain resonance frequencies. By solving the equation of motion of the coupled mechanical and magnetic degrees of freedom we show that the magnetic-field induced magnetization switching can be strongly accelerated by the lattice and illustrate the possibility of magnetization reversal by mechanical actuation.

  1. Optically induced spin-dependent diffusive transport in the presence of spin-orbit interaction for all-optical magnetization reversal

    Science.gov (United States)

    Elyasi, Mehrdad; Yang, Hyunsoo

    2016-07-01

    We have considered the effect of different spin-orbit interaction mechanisms on the process of demagnetization under the influence of short-pulse lasers. All-optical magnetization reversal of perpendicularly magnetized thin films can occur if there are sufficient strong spin-Hall, skew scattering, and Rashba interactions. In the presence of spin-orbit interactions, the transient charge currents provide the generation of transverse-spin currents and accumulations, which eventually exert spin-transfer torque on the magnetization. By combining the optically excited spin-dependent diffusive transport with the spin and charge currents due to skew scattering, spin-Hall, inverse spin-Hall, and Rashba interactions into a numerical model, we demonstrate a possibility of ultrafast all-optical magnetization reversal. This understanding provokes intriguing, more in-depth experimental studies on the role of spin-orbit interaction mechanisms in optimizing structures for all-optical magnetization reversal.

  2. Online Reverse Auctions for Procurement of Services

    OpenAIRE

    Radkevitch, Uladzimir

    2008-01-01

    textabstractOnline reverse auctions, in which a buyer seeks to select a supplier and suppliers compete for contracts by bidding online, revolutionized corporate procurement early this century. Shortly after they had been pioneered by General Electric, many companies rushed to adopt reverse auctions but the adoption soon slowed down due to the negative effects of auction-induced competition. Today, as firms continue to experiment with the reverse auctions, it is important to understand how the...

  3. Imaging the magnetization reversal of step-induced uniaxial magnetic anisotropy in vicinal epitaxial La0.7Sr0.3MnO3 films

    OpenAIRE

    Perna, Paolo; Mechin, Laurence; Saib, Mohammed; Camarero, J.; Flament, Stéphane

    2010-01-01

    International audience The magnetization reversal of La0.7Sr0.3MnO3 (LSMO) epitaxial films deposited on 10 vicinal SrTiO3(001) substrates has been investigated at room temperature by using longitudinal magneto-optical Kerr microscopy. In the case when the magnetic field is applied parallel to the substrate steps, magnetization reversal proceeds first by the nucleation of magnetic domains with well-defined magnetic domain walls (DWs) oriented parallel to the step direction and then by DW pr...

  4. In vitro transfection of the hepatitis B virus PreS2 gene into the human hepatocarcinoma cell line HepG2 induces upregulation of human telomerase reverse transcriptase

    International Nuclear Information System (INIS)

    The preS2 domain is the minimal functional unit of transcription activators that is encoded by the Hepatitis B virus (HBV) surface (S) gene. It is present in more than one-third of the HBV-integrates in HBV induced hepatocarcinoma (HCC). To further understand the functional role of PreS2 in hepatocytes, a PreS2 expression plasmid, pcS2, was constructed and stably transfected into HepG2 cells. We conducted growth curve and colony-forming assays to study the impact of PreS2 expression on cell proliferation. Cells transfected with PreS2 proliferated more rapidly and formed colonies in soft agar. PreS2 expressing cells also induced upregulation of human telomerase reverse transcriptase (hTERT) and telomerase activation by RT-PCR and the modified TRAP assay. Blocking expression of hTERT with antisense oligonuleotide reversed the growth rate in cells stably transfected with PreS2. Our data suggest that PreS2 may increase the malignant transformation of human HCC cell line HepG2 by upregulating hTERT and inducing telomerase activation

  5. Reversible arithmetic logic unit

    OpenAIRE

    zhou, Rigui; Shi, Yang; Zhang, Manqun

    2011-01-01

    Quantum computer requires quantum arithmetic. The sophisticated design of a reversible arithmetic logic unit (reversible ALU) for quantum arithmetic has been investigated in this letter. We provide explicit construction of reversible ALU effecting basic arithmetic operations. By provided the corresponding control unit, the proposed reversible ALU can combine the classical arithmetic and logic operation in a reversible integrated system. This letter provides actual evidence to prove the possib...

  6. Loperamide, an FDA-Approved Antidiarrhea Drug, Effectively Reverses the Resistance of Multidrug Resistant MCF-7/MDR1 Human Breast Cancer Cells to Doxorubicin-Induced Cytotoxicity

    OpenAIRE

    Zhou, Yanfei; Sridhar, Rajagopalan; Shan, Liang; Sha, Wei; Gu, Xinbin; Sukumar, Saraswati

    2011-01-01

    Loperamide is an FDA-approved antidiarrhea drug which acts on the μ-opioid receptors in the mesenteric plexus of large intestine and exhibits limited side effects. We hypothesized that loperamide might reverse the multidrug resistance (MDR) of human cancer cells to chemotherapeutic agents. MCF-7/MDR1 cells express high level of MDR1 and are resistant to doxorubicin. We found that loperamide significantly enhanced the cytotoxicity of doxorubicin to MCF-7/MDR1 cells in a dose-dependent manner. ...

  7. Cold-induced sudden reversible lowering of in vivo chlorophyll fluorescence after saturating light pulses : a sensitive marker for chilling susceptibility.

    Science.gov (United States)

    Larcher, W; Neuner, G

    1989-03-01

    In chilling-sensitive plants (Glycine max, Saintpaulia ionantha, Saccharum officinarum) a sudden reversible drop in chlorophyll fluorescence occurs during photosynthetic induction immediately following saturating light pulses at low temperatures in the range 4 to 8 degrees C. A comparison of two soybean cultivars of different chilling sensitivities revealed that this phenomenon, termed lowwave, indicates specific thresholds of low temperature stress. Its occurrence under controlled chilling can be regarded as a quantitative marker for screening chilling susceptibility in angiosperms. PMID:16666615

  8. Parkinson’s disease managing reversible neurodegeneration

    Science.gov (United States)

    Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

    2016-01-01

    Traditionally, the Parkinson’s disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. PMID:27103805

  9. Analysis on irregular antibody inducing unconformity of forward and reverse ABO blood typing%不规则抗体导致ABO正反定型不符处理探讨

    Institute of Scientific and Technical Information of China (English)

    樊凤艳; 王洪波; 魏少平; 魏利召; 刘晓莉; 祁术元

    2012-01-01

    Objective To investigate the factors of inducing the unconformity of forward and reverse ABO blood typing caused by irregular antibody. Methods The results of serological tests of blood typing in 12 cases were analyzed, and the factors of irregular antibody inducing the unconformity of forward and reverse ABO blood typing were tested for irregular antibody screening and identification and corresponding blood typing determination. Reverse ABO blood typing were repeated with red blood cells which corresponding antigens were negative. Results The amounts of alloantibodies among 12 patients were 4 anti-M,l anti-N, 1 anti-M combined anti-N,l anti- Lea, 1 anti- P1 ,1 anti-I,1 anti-D, 1 anti-E and 1 anti-A1. The result of repeated reverse blood typing with corresponding antigens being negative blood cells matched forward blood typing. Conclusions Samples with unconformity of forward and reverse ABO blood typing caused by irregular antibody can be identified correctly.%目的 探讨不规则抗体导致ABO正反定型不符原因,并提出解决方法.方法 总结分析12例不规则抗体导致ABO正反定型不符血型血清学试验结果,通过不规则抗体筛查、不规则抗体鉴定、相应血型检测明确不规则抗体导致ABO正反定型不符确切原因,用相应抗原阴性红细胞重新进行ABO血型反定型.结果 12例标本中抗-M 4例,抗-N 1例,抗-M合并抗-N 1例,抗-Lea 1例,抗-P1 1例,抗-I 1例,抗-D 1例,抗-E 1例,抗-A1 1例.用相应抗原阴性红细胞重新进行ABO血型反定型,正反定型结果均相符.结论 不规则抗体是导致ABO正反定型不符的常见原因,经过适当处理可以正确鉴定ABO血型.

  10. Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats.

    Science.gov (United States)

    Gong, Meng-Juan; Han, Bin; Wang, Shu-mei; Liang, Sheng-wang; Zou, Zhong-jie

    2016-05-10

    Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction. PMID:26874256

  11. A study of reversible gamma-induced structural transformations in vitreous Ge23.5Sb11.8S64.7 by high-resolution X-ray photoelectron spectroscopy.

    Science.gov (United States)

    Kovalskiy, Andriy; Jain, Himanshu; Miller, Alfred C; Golovchak, Roman Ya; Shpotyuk, Oleh I

    2006-11-16

    The structural origin of reversible gamma-induced effects in vitreous Ge(23.5)Sb(11.8)S(64.7) has been investigated by high-resolution X-ray photoelectron spectroscopy (XPS). The changes in valence band spectrum from gamma-irradiation suggest a decrease of sulfur lone pair electron concentration accompanied by changes in bonding states of S and Ge. The appearance of additional doublets in the core-level XPS spectra of Ge, Sb, and S atoms for gamma-irradiated sample is described by the formation of over- and under-coordinated charged defect pairs (Ge(3)(-)-S(3)(+)) as a result of radiation treatment. The results verify the switching of Ge-S covalent bonds into S-S bonds as the main microstructural mechanism for gamma-induced optical effects in this glass. PMID:17092046

  12. Reversal of muscle atrophy by Zhimu-Huangbai herb-pair via Akt/mTOR/FoxO3 signal pathway in streptozotocin-induced diabetic mice.

    Directory of Open Access Journals (Sweden)

    Jinbao Zhang

    Full Text Available Skeletal muscle atrophy is one of the serious complications of diabetes. Zhimu-Huangbai herb-pair (ZB is widely used in Chinese traditional medicine formulas for treating Xiaoke (known as diabetes and its complications. However, the effect of ZB on reversal of muscle atrophy and the underlying mechanisms remain unknown. In this research, we investigated the effect and possible mechanisms of ZB on skeletal muscle atrophy in diabetic mice. Animal model of diabetic muscle atrophy was developed by high fat diet (HFD feeding plus streptozotocin (STZ injection. After oral adminstration of ZB for 6 weeks, the effects of ZB on reversal of muscle atrophy and the underlying mechanisms were evaluated by biochemical, histological and western blot methods. The skeletal muscle weight, strength, and cross-sectional area of diabetic mice were significantly increased by ZB treatment. Biochemical results showed that ZB treatment reduced the serum glucose level, and elevated the serum insulin-like growth factor 1 (IGF-1 and insulin levels significantly compared with untreated diabetic group. The western blot results showed that ZB activated the mTOR signal pathway, shown as increased phosphorylations (p- of Akt, mTOR, Raptor, S6K1 and reduced Foxo3 expression compared with the model group. ZB could reverse muscle atrophy in diabetic mice. This may be through activation of mTOR signaling pathway that promotes protein synthesis, and inactivation foxo3 protein that inhibits protein degradation. These findings suggested that ZB may be considered as a potential candidate drug in treatment of diabetic muscle atrophy.

  13. Vortioxetine, but not escitalopram or duloxetine, reverses memory impairment induced by central 5-HT depletion in rats: evidence for direct 5-HT receptor modulation

    DEFF Research Database (Denmark)

    Jensen, Jesper Bornø; du Jardin, Kristian Gaarn; Song, Dekun;

    2014-01-01

    reuptake inhibitor escitalopram, or the 5-HT norepinephrine reuptake inhibitor duloxetine. SERT occupancies were estimated by ex vivo autoradiography. PCPA depleted central 5-HT by >90% in tissue and microdialysate, and impaired NOR and SA performance. Restoring central 5-HT with 5-HTP reversed these...... deficits. At similar SERT occupancies (>90%) vortioxetine, but not escitalopram or duloxetine, restored memory performance. Acute fenfluramine significantly increased extracellular 5-HT in control and PCPA-treated rats, while vortioxetine did so only in control rats. Thus, vortioxetine restores 5-HT...

  14. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... you can use for reverse shoulder replacement. The standard delto-pectoral approach, or the superior approach, which ... that are different between a reverse and a standard total is, first of all, we don't ...

  15. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... the height perfectly to get anatomic head tuberosity relationships. If you're doing a reverse for a ... less limited with the superior reverse versus the traditional. And I assume the question means the approach: ...

  16. Sign reversal of the quantum Hall coefficient in the field-induced spin density wave states of quasi-one-dimensional system with periodic potential

    Science.gov (United States)

    Kishigi, Keita; Hasegawa, Yasumasa

    2009-03-01

    The magnetic susceptibility of the quasi-one-dimensional system with the periodic potential such as slow cooled (TMTSF)2ClO4 is studied numerically. The magnitude of the periodic potential is given by V. The imperfect nesting on the Fermi surface originates from higher harmonics (t'b t3, t4) of the tight-binding model. We have found that qx of Q = (2kF +qx, π/b+qy) which gives a maximum of χ0(Q) has a negative value at t3/tb >= 0.007, t4/tb >= 0.0001, and V t4, where t'b/tb is fixed to be 0.1. It means that the negative quantum Hall coefficient is possible in these parameters. Since the sign reversal of the quantum Hall coefficient is observed in (TMTSF)2ClO4, t3, t4 and V should satisfy the above conditions. We also discuss the periodic oscillation of Hall resistance with sign reversal which has been observed by Uji et al.

  17. Reverse cholesterol transport revisited

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde

    2010-01-01

    Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Since the introduction of reverse cholesterol transport in the 1970s, this pathway has been intensively investigated. In this topic highlight, the classical reverse cholesterol transport concepts are discussed and the subject reverse cholesterol transport is revisited.

  18. Ginseng Total Saponins Reverse Corticosterone-Induced Changes in Depression-Like Behavior and Hippocampal Plasticity-Related Proteins by Interfering with GSK-3β-CREB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Lin Chen

    2014-01-01

    Full Text Available This study aimed to explore the antidepressant mechanisms of ginseng total saponins (GTS in the corticosterone-induced mouse depression model. In Experiment 1, GTS (50, 25, and 12.5 mg kg−1 d−1, intragastrically were given for 3 weeks. In Experiment 2, the same doses of GTS were administrated after each corticosterone (20 mg kg−1 d−1, subcutaneously injection for 22 days. In both experiments, mice underwent a forced swimming test and a tail suspension test on day 20 and day 21, respectively, and were sacrificed on day 22. Results of Experiment 1 revealed that GTS (50 and 25 mg kg−1 d−1 exhibited antidepressant activity and not statistically altered hippocampal protein levels of brain-derived neurotrophic factor (BDNF and neurofilament light chain (NF-L. Results of Experiment 2 showed that GTS (50 and 25 mg kg−1 d−1 ameliorated depression-like behavior without normalizing hypercortisolism. The GTS treatments reversed the corticosterone-induced changes in mRNA levels of BDNF and NF-L, and protein levels of BDNF NF-L, phosphor-cAMP response element-binding protein (Ser133, and phosphor-glycogen synthase kinase-3β (Ser9 in the hippocampus. These findings imply that the effect of GTS on corticosterone-induced depression-like behavior may be mediated partly through interfering with hippocampal GSK-3β-CREB signaling pathway and reversing decrease of some plasticity-related proteins.

  19. Use of cyclic current reversal polarization voltammetry for investigating the relationship between corrosion resistance and heat-treatment induced variations in microstructures of 400 C martensitic stainless steels

    Science.gov (United States)

    Ambrose, John R.

    1992-01-01

    Software for running a cyclic current reversal polarization voltammagram has been developed for use with a EG&G Princeton Applied Research Model 273 potentiostat/galvanostat system. The program, which controls the magnitude, direction and duration of an impressed galvanostatic current, will produce data in ASCII spreadsheets (Lotus, Quattro) for graphical representation of CCRPV voltammograms. The program was used to determine differences in corrosion resistance of 440 C martenstic stainless steel produced as a result of changes in microstructure effected by tempering. It was determined that tempering at all temperatures above 400 F resulted in increased polarizability of the material, with the increased likelihood that pitting would be initiated upon exposure to marine environments. These results will be used in development of remedial procedures for lowering the susceptibility of these alloys toward the stress corrosion cracking experienced in bearings used in high pressure oxygen turbopumps used in the main engines of space shuttle orbiters.

  20. Laser-induced reversion of $\\delta^{'}$ precipitates in an Al-Li alloy: Study on temperature rise in pulsed laser atom probe

    CERN Document Server

    Khushaim, Muna; Al-Kassab, Talaat

    2015-01-01

    The influence of tuning the laser energy during the analyses on the resulting microstructure in a specimen utilizing an ultra-fast laser assisted atom probe was demonstrated by a case study of a binary Al-Li alloy. The decomposition parameters, such as the size, number density, volume fraction and composition of $\\delta^{'}$ precipitates, were carefully monitored after each analysis. A simple model was employed to estimate the corresponding specimen temperature for each value of the laser energy. The results indicated that the corresponding temperatures for the laser energy in the range of 10 to 80 pJ are located inside the miscibility gap of the binary Al-Li phase diagram and fall into the metastable equilibrium field. In addition, the corresponding temperature for a laser energy of 100 pJ was in fairly good agreement with reported range of $\\delta^{'}$ solvus temperature, suggesting a result of reversion upon heating due to laser pulsing.

  1. Experimental manipulations blunt time-induced changes in brain monoamine levels and completely reverse stress, but not Pb+/-stress-related modifications to these trajectories.

    Science.gov (United States)

    Cory-Slechta, D A; Virgolini, M B; Rossi-George, A; Weston, D; Thiruchelvam, M

    2009-12-14

    This study sought to further understand how environmental conditions influence the outcomes of early developmental insults. It compared changes in monoamine levels in frontal cortex, nucleus accumbens and striatum of male and female Long-Evans rat offspring subjected to maternal Pb exposure (0, 50 or 150ppm in drinking water from 2 months pre-breeding until pup weaning)+/-prenatal (PS) (restraint on GD16-17) or PS+offspring stress (OS; three variable stress challenges to young adults) determined at 2 months of age and at 6 months of age in littermates subsequently exposed either to experimental manipulations (EM: daily handling and performance on an operant fixed interval (FI) schedule of food reward), or to no experience (NEM; time alone). Time alone (NEM conditions), even in normal (control) animals, modified the trajectory of neurochemical changes between 2 and 6 months across brain regions and monoamines. EM significantly modified the NEM trajectories, and except NE and striatal DA, which increased, blunted the changes in monoamine levels that occurred over time alone. Pb+/-stress modified the trajectory of monoamine changes in both EM and NEM conditions, but these predominated under NEM conditions. Stress-associated modifications, occurring mainly with NEM OS groups, were fully reversed by EM procedures, while reversals of Pb+/-stress-associated modifications occurred primarily in nucleus accumbens, a region critical to mediation of FI response rates. These results extend the known environmental conditions that modify developmental Pb+/-stress insults, which is critical to ultimately understanding whether early insults lead to adaptive or maladaptive behavior and to devising behavioral therapeutic strategies. That time alone and a set of EM conditions typically used as outcome measures in intervention studies can themselves invoke neurochemical changes, moreover, has significant implications for experimental design of such studies. PMID:19631235

  2. Dynamics of Spontaneous Magnetization Reversal in Exchange Biased Heterostructures

    OpenAIRE

    Li, Zhi-Pan; Miller, Casey W.; Roshchin, Igor V.; Schuller, Ivan K.

    2006-01-01

    The dependence of thermally induced spontaneous magnetization reversal on time-dependent cooling protocols was studied. Slower cooling and longer waiting close to the N\\`{e}el temperature of the antiferromagnet ($T_N$) enhances the magnetization reversal. Cycling the temperature around $T_N$ leads to a thermal training effect under which the reversal magnitude increases with each cycle. These results suggest that spontaneous magnetization reversal is energetically favored, contrary to our pre...

  3. Reversal of Dilated Cardiomyopathy After Successful Radio-Frequency Ablation of Frequent Atrial Premature Beats, a New Cause for Arrhythmia-Induced Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Paul Louis Vervueren, MD

    2012-12-01

    Full Text Available Incessant atrial premature beats as a potential cause for tachycardia-induced cardiomyopathy was suspected in a patient presenting with dilated non-ischemic cardiomyopathy and severely altered left ventricular ejection fraction. The elimination of a left atrial focus by percutaneous RF ablation led to normalization of the clinical status, of atrial and ventricular dimensions and left ventricular systolic function.

  4. Chronic co-administration of the cannabinoid receptor agonist WIN55,212-2 during puberty or adulthood reverses 3,4 methylenedioxymetamphetamine (MDMA)-induced deficits in recognition memory but not in effort-based decision making.

    Science.gov (United States)

    Schulz, Sybille; Becker, Thorsten; Nagel, Ulrich; von Ameln-Mayerhofer, Andreas; Koch, Michael

    2013-05-01

    Cannabis and 3,4 methylenedioxymetamphetamine (MDMA, "ecstasy") are the most frequently combined illegal drugs among young adults in western societies. This study examined the effects of chronic co-administration of the cannabinoid receptor agonist WIN55,212-2 (WIN) and MDMA on working memory and effort-based decision making in rats. Treatment consisted of MDMA (7.5 mg/kg), WIN (1.2 mg/kg), a combination of these substances (MDMA+WIN) or vehicle over a period of 25 days during puberty (PD40-65) or adulthood (PD80-105). Ten days after the last treatment, WIN reversed MDMA-induced working memory deficits in the object recognition test in animals treated during adulthood or puberty, but had no influence on impairment of adult rats in the effort-based T-maze task. No differences were observed between groups of pubertally treated rats in the decision making task. During a subsequent acute drug challenge MDMA and MDMA+WIN decreased high reward choices in both age groups, indicating MDMA-induced cost-aversive choice. Differential long-term interactions on the neuronal level in the hippocampus and MDMA-induced disturbances in cortico-limbic connections are suggested. PMID:23541493

  5. Reversal of isoproterenol-induced downregulation of phospholamban and FKBP12.6 by CPU0213-mediated antagonism of endothelin receptors

    Institute of Scientific and Technical Information of China (English)

    Yu FENG; Xiao-yun TANG; De-zai DAI; Yin DAI

    2007-01-01

    Aim:The downregulation of phospholamban (PLB) and FKBPI 2.6 as a result of βreceptor activation is involved in the pathway(s) of congestive heart failure. We hypothesized that the endothelin (ET)-I system may link to downregulated PLB and FKBP12.6. Methods:Rats were subjected to ischemia/reperfusion (I/R) to cause heart failure (HF). 1 mg/kg isoproterenol (ISO) was injected subcutaneously (sc) for 10 d to worsen HF. 30 mg/kg CPU0213 (sc),a dual ET receptor (ETAR/ETBR) antagonist was given from d 6 to d 10. On d 11,cardiac function was assessed together with the determination of mRNA levels of ryanodine receptor 2,calstabin-2 (FKBP12.6),PLB,and sarcoplasmic reticulum Ca2+-ATPase. Isolated adult rat ventricular myocytes were incubated with ISO at lx 10-6 mol/L to set up an in vitro model of HF. Propranolol (PRO),CPU0213,and darusentan (DAR,an ETAR antagonist) were incubated with cardiomyocytes at 1 x 10.5 mol/L or 1 × 10-6mol/L in the presence of ISO (1× 10.6 mol/L). Immunocytochemistry and Western blotting were applied for measuring the protein levels of PLB and FKBP12.6.Results:The worsened hemodynamics produced by I/R were exacerbated by ISO pretreatment. The significant downregulation of the gene expression of PLB and FKBPI 2.6 and worsened cardiac function by ISO were reversed by CPU0213. In vitro ISO lx 10-6 mol/L produced a sharp decline of PLB and FKBP12.6 proteins relative to the control. The downregulation of the protein expression was significantly reversed by the ET receptor antagonist CPU0213 or DAR,comparable to that achieved by PRO. Conclusion:This study demonstrates a role of ET in mediating the downregulation of the cardiac Ca2+-handling protein by ISO.AcknowledgementWe are most grateful to Prof David J TRIGGLE from the State University of New York at Buffalo for assistance in revising the English of the manuscript.

  6. Stimulation of large-conductance calcium-activated potassium channels inhibits neurogenic contraction of human bladder from patients with urinary symptoms and reverses acetic acid-induced bladder hyperactivity in rats.

    Science.gov (United States)

    La Fuente, José M; Fernández, Argentina; Cuevas, Pedro; González-Corrochano, Rocío; Chen, Mao Xiang; Angulo, Javier

    2014-07-15

    We have analysed the effects of large-conductance calcium-activated potassium channel (BK) stimulation on neurogenic and myogenic contraction of human bladder from healthy subjects and patients with urinary symptoms and evaluated the efficacy of activating BK to relief bladder hyperactivity in rats. Bladder specimens were obtained from organ donors and from men with benign prostatic hyperplasia (BPH). Contractions elicited by electrical field stimulation (EFS) and carbachol (CCh) were evaluated in isolated bladder strips. in vivo cystometric recordings were obtained in anesthetized rats under control and acetic acid-induced hyperactive conditions. Neurogenic contractions of human bladder were potentiated by blockade of BK and small-conductance calcium-activated potassium channels (SK) but were unaffected by the blockade of intermediate calcium-activated potassium channels (IK). EFS-induced contractions were inhibited by BK stimulation with NS-8 or NS1619 or by SK/IK stimulation with NS309 (3µM). CCh-induced contractions were not modified by blockade or stimulation of BK, IK or SK. The anti-cholinergic agent, oxybutynin (0.3µM) inhibited either neurogenic or CCh-induced contractions. Neurogenic contractions of bladders from BPH patients were less sensitive to BK inhibition and more sensitive to BK activation than healthy bladders. The BK activator, NS-8 (5mg/kg; i.v.), reversed bladder hyperactivity induced by acetic acid in rats, while oxybutynin was ineffective. NS-8 did not significantly impact blood pressure or heart rate. BK stimulation specifically inhibits neurogenic contractions in patients with urinary symptoms and relieves bladder hyperactivity in vivo without compromising bladder contractile capacity or cardiovascular safety, supporting its potential therapeutic use for relieving bladder overactivity. PMID:24747752

  7. In vivo examination of hydroxyurea and the novel ribonucleotide reductase inhibitors trimidox and didox in combination with the reverse transcriptase inhibitor abacavir: suppression of retrovirus-induced immunodeficiency disease.

    Science.gov (United States)

    Sumpter, L Ryan; Inayat, Mohammed S; Yost, Erin E; Duvall, William; Hagan, Espen; Mayhew, Christopher N; Elford, Howard L; Gallicchio, Vincent S

    2004-06-01

    Inhibition of ribonucleotide reductase (RR) has gained attention as a potential strategy for HIV-1 therapy through the success of hydroxyurea (HU) to potentiate the activity of the nucleoside reverse transcriptase inhibitor (NRTI) didanosine (ddI) in clinical trials. However, the use of HU has been limited by its development of hematopoietic toxicity. In this study, the novel RR inhibitors didox (DX; 3,4-dihydroxybenzohydroxamic acid), and trimidox (TX; 3,4,5-trihydroxybenzamidoxime) were evaluated along with HU for anti-retroviral efficacy in LPBM5-induced retro-viral disease (MAIDS) both as monotherapeutic regimens and in combination with the guanine containing NRTI abacavir (ABC). Anti-retroviral drug efficacy was determined by measuring inhibition of splenomegaly, hypergammaglobulinemia, and splenic levels of proviral DNA. In this study, all RRIs tested showed the ability to improve the efficacy of ABC in the MAIDS model by reducing splenomegaly, hypergammaglobulinemia, and splenic proviral DNA levels. PMID:15130534

  8. Administration of BMP2/7 in utero partially reverses Rubinstein-Taybi syndrome-like skeletal defects induced by Pdk1 or Cbp mutations in mice.

    Science.gov (United States)

    Shim, Jae-Hyuck; Greenblatt, Matthew B; Singh, Anju; Brady, Nicholas; Hu, Dorothy; Drapp, Rebecca; Ogawa, Wataru; Kasuga, Masato; Noda, Tetsuo; Yang, Sang-Hwa; Lee, Sang-Kyou; Rebel, Vivienne I; Glimcher, Laurie H

    2012-01-01

    Mutations in the coactivator CREB-binding protein (CBP) are a major cause of the human skeletal dysplasia Rubinstein-Taybi syndrome (RTS); however, the mechanism by which these mutations affect skeletal mineralization and patterning is unknown. Here, we report the identification of 3-phosphoinositide-dependent kinase 1 (PDK1) as a key regulator of CBP activity and demonstrate that its functions map to both osteoprogenitor cells and mature osteoblasts. In osteoblasts, PDK1 activated the CREB/CBP complex, which in turn controlled runt-related transcription factor 2 (RUNX2) activation and expression of bone morphogenetic protein 2 (BMP2). These pathways also operated in vivo, as evidenced by recapitulation of RTS spectrum phenotypes with osteoblast-specific Pdk1 deletion in mice (Pdk1osx mice) and by the genetic interactions observed in mice heterozygous for both osteoblast-specific Pdk1 deletion and either Runx2 or Creb deletion. Finally, treatment of Pdk1osx and Cbp+/- embryos with BMPs in utero partially reversed their skeletal anomalies at birth. These findings illustrate the in vivo function of the PDK1-AKT-CREB/CBP pathway in bone formation and provide proof of principle for in utero growth factor supplementation as a potential therapy for skeletal dysplasias. PMID:22133875

  9. Reversible de-intercalation and intercalation induced by polymer crystallization and melting in a poly(ethylene oxide)/organoclay nanocomposite.

    Science.gov (United States)

    Sun, Lu; Ertel, Ethan A; Zhu, Lei; Hsiao, Benjamin S; Avila-Orta, Carlos A; Sics, Igors

    2005-06-21

    Semicrystalline polymer/layered silicate nanocomposites were prepared by solution blending of a low molecular weight poly(ethylene oxide) (PEO) with an organically modified montmorillonite, Cloisite 10A (C10A). The intercalation morphology was studied by temperature-dependent synchrotron wide-angle X-ray diffraction (WAXD). Unlike PEO homopolymers, significant secondary crystallization was observed in the PEO/C10A nanocomposites. Reversible de-intercalation and intercalation processes were detected during secondary crystallization and subsequent melting of secondary crystals. On the basis of two-dimensional WAXD results on oriented samples, an interphase layer between the silicate primary particles and PEO lamellar crystals was proposed. Secondary PEO crystallization in the interphase regions was inferred to be the primary driving force for polymer chains to diffuse out of the silicate gallery. This study provided a useful method to investigate polymer diffusion in nanoconfined spaces, which can be controlled by PEO secondary crystallization and melting outside the silicate gallery. PMID:15952806

  10. Elimination of nanovoids induced during electroforming of metallic nanostamps with high-aspect-ratio nanostructures by the pulse reverse current electroforming process

    International Nuclear Information System (INIS)

    We studied a technique for fabricating metallic nanostamps with void-free, high-aspect-ratio nanostructures, using a pulse reverse current (PRC) electroforming process. During conventional electroforming of high-aspect-ratio nanostructures, a high current distribution is concentrated at the top and bottom corners, resulting in relatively fast growth of the nickel electroformed layer. This phenomenon leads to the formation of nanovoids in a metallic nanostamp, causing degradation of the stamp performance. To prevent the formation of nanovoids, we controlled the current waveform during the electroforming process. In this way, the process suppressed the formation of nanovoids, while effectively achieving a uniform current distribution. As practical examples, two types of metallic nanostamps were fabricated via direct current and PRC electroforming processes, one with a pitch of 0.8 µm and a height of 1.8 µm, and another with a pitch of 350 nm and a height of 525 nm. The internal nanovoids developed during the electroforming process were measured and analyzed. (paper)

  11. Saturated- and n-6 Polyunsaturated-Fat Diets Each Induce Ceramide Accumulation in Mouse Skeletal Muscle: Reversal and Improvement of Glucose Tolerance by Lipid Metabolism Inhibitors

    OpenAIRE

    Frangioudakis, G.; J. Garrard; Raddatz, K.; Nadler, J L; Mitchell, T. W.; Schmitz-Peiffer, C.

    2010-01-01

    Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a funct...

  12. Hyperinsulinemia induces a reversible impairment in insulin receptor function leading to diabetes in the sand rat model of non-insulin-dependent diabetes mellitus.

    OpenAIRE

    Kanety, H.; Moshe, S; Shafrir, E; Lunenfeld, B; Karasik, A

    1994-01-01

    The insulin receptor was evaluated at different disease stages in the sand rat (Psammomys obesus), a model for nutrition-induced diabetes. Nondiabetic sand rats showed markedly low receptor number in liver compared with albino rats. Their receptor had an intact tyrosine kinase activity but a higher Km for ATP in the phosphorylation reaction of exogenous substrates. The initial effects of overeating (i.e., development of hyperinsulinemia without hyperglycemia) were associated...

  13. Ashwagandha (Withania somnifera reverses β-amyloid1-42 induced toxicity in human neuronal cells: implications in HIV-associated neurocognitive disorders (HAND.

    Directory of Open Access Journals (Sweden)

    Kesava Rao Venkata Kurapati

    Full Text Available Alzheimer's disease (AD is characterized by progressive dysfunction of memory and higher cognitive functions with abnormal accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles throughout cortical and limbic brain regions. At present no curative treatment is available, and research focuses on drugs for slowing disease progression or providing prophylaxis. Withania somnifera (WS also known as 'ashwagandha' is used widely in Ayurvedic medicine as a nerve tonic and memory enhancer. However, there is a paucity of data on the potential neuroprotective effects of W.somnifera against β-Amyloid (1-42-induced neuropathogenesis. In the present study, we have tested the neuroprotective effects of methanol:Chloroform (3:1 extract of ashwagandha against β-amyloid induced toxicity and HIV-1Ba-L (clade B infection using a human neuronal SK-N-MC cell line. Our results showed that β-amyloid induced cytotoxic effects in SK-N-MC cells as shown by decreased cell growth when tested individually. Also, confocal microscopic analysis showed decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC cells compared to uninfected cells. However, when ashwagandha was added to β-amyloid treated and HIV-1 infected samples, the toxic effects were neutralized. Further, the MTT cell viability assays and the peroxisome proliferator-activated receptor-γ (PPARγ levels supported these observations indicating the neuroprotective effect of WS root extract against β-amyloid and HIV-1Ba-L (clade B induced neuro-pathogenesis.

  14. Radiation-Induced Glycogen Accumulation Detected by Single Cell Raman Spectroscopy Is Associated with Radioresistance that Can Be Reversed by Metformin.

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    Quinn Matthews

    Full Text Available Altered cellular metabolism is a hallmark of tumor cells and contributes to a host of properties associated with resistance to radiotherapy. Detection of radiation-induced biochemical changes can reveal unique metabolic pathways affecting radiosensitivity that may serve as attractive therapeutic targets. Using clinically relevant doses of radiation, we performed label-free single cell Raman spectroscopy on a series of human cancer cell lines and detected radiation-induced accumulation of intracellular glycogen. The increase in glycogen post-irradiation was highest in lung (H460 and breast (MCF7 tumor cells compared to prostate (LNCaP tumor cells. In response to radiation, the appearance of this glycogen signature correlated with radiation resistance. Moreover, the buildup of glycogen was linked to the phosphorylation of GSK-3β, a canonical modulator of cell survival following radiation exposure and a key regulator of glycogen metabolism. When MCF7 cells were irradiated in the presence of the anti-diabetic drug metformin, there was a significant decrease in the amount of radiation-induced glycogen. The suppression of glycogen by metformin following radiation was associated with increased radiosensitivity. In contrast to MCF7 cells, metformin had minimal effects on both the level of glycogen in H460 cells following radiation and radiosensitivity. Our data demonstrate a novel approach of spectral monitoring by Raman spectroscopy to assess changes in the levels of intracellular glycogen as a potential marker and resistance mechanism to radiation therapy.

  15. Radiation-Induced Glycogen Accumulation Detected by Single Cell Raman Spectroscopy Is Associated with Radioresistance that Can Be Reversed by Metformin.

    Science.gov (United States)

    Matthews, Quinn; Isabelle, Martin; Harder, Samantha J; Smazynski, Julian; Beckham, Wayne; Brolo, Alexandre G; Jirasek, Andrew; Lum, Julian J

    2015-01-01

    Altered cellular metabolism is a hallmark of tumor cells and contributes to a host of properties associated with resistance to radiotherapy. Detection of radiation-induced biochemical changes can reveal unique metabolic pathways affecting radiosensitivity that may serve as attractive therapeutic targets. Using clinically relevant doses of radiation, we performed label-free single cell Raman spectroscopy on a series of human cancer cell lines and detected radiation-induced accumulation of intracellular glycogen. The increase in glycogen post-irradiation was highest in lung (H460) and breast (MCF7) tumor cells compared to prostate (LNCaP) tumor cells. In response to radiation, the appearance of this glycogen signature correlated with radiation resistance. Moreover, the buildup of glycogen was linked to the phosphorylation of GSK-3β, a canonical modulator of cell survival following radiation exposure and a key regulator of glycogen metabolism. When MCF7 cells were irradiated in the presence of the anti-diabetic drug metformin, there was a significant decrease in the amount of radiation-induced glycogen. The suppression of glycogen by metformin following radiation was associated with increased radiosensitivity. In contrast to MCF7 cells, metformin had minimal effects on both the level of glycogen in H460 cells following radiation and radiosensitivity. Our data demonstrate a novel approach of spectral monitoring by Raman spectroscopy to assess changes in the levels of intracellular glycogen as a potential marker and resistance mechanism to radiation therapy. PMID:26280348

  16. Design of Reversible Counter

    OpenAIRE

    Md. Selim Al Mamun; B. K. Karmaker

    2014-01-01

    This article presents a research work on the design and synthesis of sequential circuits and flip-flops that are available in digital arena; and describes a new synthesis design of reversible counter that is optimized in terms of quantum cost, delay and garbage outputs compared to the existing designs. We proposed a new model of reversible T flip-flop in designing reversible counter.

  17. "Reverse" Nested Lottery Contests

    OpenAIRE

    Qiang Fu; Jingfeng Lu; Zhewei Wang

    2013-01-01

    This paper proposes a multi-prize "reverse" nested lottery contest model, which can be viewed as the "mirror image" of the conventional nested lottery contest of Clark and Riis (1996a). The reverse-lottery contest model determines winners by selecting losers based on contestants' one-shot effort through a hypothetical sequence of lotteries. We provide a microfoundation for the reverse-lottery contest from a perspective of (simultaneous) noisy performance ranking and establish that the model i...

  18. Posterior Reversible Encephalopathy Syndrome

    OpenAIRE

    J Gordon Millichap

    2013-01-01

    Investigators at Children's Hospital of Montefiore, Albert Einstein College of Medicine, NY, determined the incidence of posterior reversible encephalopathy syndrome (PRES) in a pediatric critical care unit.

  19. Vascular hyporeactivity to angiotensin II induced by Escherichia coli endotoxin is reversed by Nω-Nitro-L-Arginine, an inhibitor of nitric oxide synthase

    Directory of Open Access Journals (Sweden)

    L. A. RODRIGUES

    2009-01-01

    Full Text Available

    Septic shock or sepsis is reported to be one of the major causes of death when followed by systemic infectious trauma in humans and other mammals. Its development leads to a large drop in blood pressure and a reduction in vascular responsiveness to physiological vasoconstrictors which, if not contained, can lead to death. It is proposed that this vascular response is due to the action of bacterial cell wall products released into the bloodstream by the vascular endothelium and is considered a normal response of the body`s defenses against infection. A reduction in vascular reactivity to epinephrine and norepinephrine is observed under these conditions. In the present study in rats, the aim was to assess whether those effects of hypotension and hyporeactivity are also related to another endogenous vasoconstrictor, angiotensin II (AII. We evaluated the variation in the power of this vasoconstrictor over the mean arterial pressure in anesthetized rats, before and after the establishment of hypotension by Escherichia coli endotoxin (Etx. Our results show that in this model of septic shock, there is a reduction in vascular reactivity to AII and this reduction can be reversed by the inhibitor of nitric oxide synthase, Nω-Nitro-L-Arginine (NωNLA. Our results also suggest that other endogenous factors (not yet fully known are involved in the protection of rats against septic shock, in addition to the L-arginine NO pathway. Keywords: vascular hyporeactivity; NO; rat; angiotensin II; NωNLA Escherichia coli endotoxin.

  20. Reverse translation of phase I biomarker findings links the activity of angiotensin-(1–7 to repression of hypoxia inducible factor-1α in vascular sarcomas

    Directory of Open Access Journals (Sweden)

    Petty W

    2012-09-01

    Full Text Available Abstract Background In a phase I study of angiotensin-(1–7 [Ang-(1–7], clinical benefit was associated with reduction in plasma placental growth factor (PlGF concentrations. The current study examines Ang-(1–7 induced changes in biomarkers according to cancer type and investigates mechanisms of action engaged in vitro. Methods Plasma biomarkers were measured prior to Ang-(1–7 administration as well as 1, 2, 3, 4, and 6 hours after treatment. Tests for interaction were performed to determine the impact of cancer type on angiogenic hormone levels. If a positive interaction was detected, treatment-induced biomarker changes for individual cancer types were assessed. To investigate mechanisms of action, in vitro growth assays were performed using a murine endothelioma cell line (EOMA. PCR arrays were performed to identify and statistically validate genes that were altered by Ang-(1–7 treatment in these cells. Results Tests for interaction controlled for dose cohort and clinical response indicated a significant impact of cancer type on post-treatment VEGF and PlGF levels. Following treatment, PlGF levels decreased over time in patients with sarcoma (P = .007. Treatment of EOMA cells with increasing doses of Ang-(1–7 led to significant growth suppression at doses as low as 100 nM. PCR arrays identified 18 genes that appeared to have altered expression after Ang-(1–7 treatment. Replicate analyses confirmed significant changes in 8 genes including reduction in PlGF (P = .04 and hypoxia inducible factor 1α (HIF-1α expression (P  Conclusions Ang-(1–7 has clinical and pre-clinical activity for vascular sarcomas that is linked to reduced HIF-1α and PlGF expression.

  1. Reverse translation of phase I biomarker findings links the activity of angiotensin-(1–7) to repression of hypoxia inducible factor-1α in vascular sarcomas

    International Nuclear Information System (INIS)

    In a phase I study of angiotensin-(1–7) [Ang-(1–7)], clinical benefit was associated with reduction in plasma placental growth factor (PlGF) concentrations. The current study examines Ang-(1–7) induced changes in biomarkers according to cancer type and investigates mechanisms of action engaged in vitro. Plasma biomarkers were measured prior to Ang-(1–7) administration as well as 1, 2, 3, 4, and 6 hours after treatment. Tests for interaction were performed to determine the impact of cancer type on angiogenic hormone levels. If a positive interaction was detected, treatment-induced biomarker changes for individual cancer types were assessed. To investigate mechanisms of action, in vitro growth assays were performed using a murine endothelioma cell line (EOMA). PCR arrays were performed to identify and statistically validate genes that were altered by Ang-(1–7) treatment in these cells. Tests for interaction controlled for dose cohort and clinical response indicated a significant impact of cancer type on post-treatment VEGF and PlGF levels. Following treatment, PlGF levels decreased over time in patients with sarcoma (P = .007). Treatment of EOMA cells with increasing doses of Ang-(1–7) led to significant growth suppression at doses as low as 100 nM. PCR arrays identified 18 genes that appeared to have altered expression after Ang-(1–7) treatment. Replicate analyses confirmed significant changes in 8 genes including reduction in PlGF (P = .04) and hypoxia inducible factor 1α (HIF-1α) expression (P < .001). Ang-(1–7) has clinical and pre-clinical activity for vascular sarcomas that is linked to reduced HIF-1α and PlGF expression

  2. IL-13R alpha 2 reverses the effects of IL-13 and IL-4 on bronchial reactivity and acetylcholine-induced Ca2+ signaling

    OpenAIRE

    Kellner, Julia; Gamarra, Fernando; Welsch, Ulrich; Joerres, Rudolf A.; Huber, Rudolf M; Bergner, Albrecht

    2007-01-01

    Background: The interleukins IL-4 and IL-13 play a key role in the pathophysiology of asthma. The interleukin receptor IL-13R alpha 2 is believed to act as a decoy receptor, but until now, the functional significance of IL-13R alpha 2 remains vague. Methods: Bronchial reactivity was quantified in murine lung slices by digital video microscopy and acetylcholine (ACH)-induced Ca2+ signaling was measured in human airway smooth muscle cells (ASMC) using fluorescence microscopy. Results: IL-4 or I...

  3. N-acetylcysteine increases the frequency of bone marrow pro-B/pre-B cells, but does not reverse cigarette smoking-induced loss of this subset.

    Directory of Open Access Journals (Sweden)

    Victoria L Palmer

    Full Text Available BACKGROUND: We previously showed that mice exposed to cigarette smoke for three weeks exhibit loss of bone marrow B cells at the Pro-B-to-pre-B cell transition, but the reason for this is unclear. The antioxidant N-acetylcysteine (NAC, a glutathione precursor, has been used as a chemopreventive agent to reduce adverse effects of cigarette smoke exposure on lung function. Here we determined whether smoke exposure impairs B cell development by inducing cell cycle arrest or apoptosis, and whether NAC treatment prevents smoking-induced loss of developing B cells. METHODOLOGY/PRINCIPAL FINDINGS: Groups of normal mice were either exposed to filtered room air or cigarette smoke with or without concomitant NAC treatment for 5 days/week for three weeks. Bone marrow B cell developmental subsets were enumerated, and sorted pro-B (B220(+CD43(+ and pre-B (B220(+CD43(- cell fractions were analyzed for cell cycle status and the percentage of apoptotic cells. We find that, compared to sham controls, smoke-exposed mice have ∼60% fewer pro-B/pre-B cells, regardless of NAC treatment. Interestingly, NAC-treated mice show a 21-38% increase in total bone marrow cellularity and lymphocyte frequency and about a 2-fold increase in the pro-B/pre-B cell subset, compared to sham-treated controls. No significant smoking- or NAC-dependent differences were detected in frequency of apoptotic cells or the percentage cells in the G1, S, or G2 phases of the cycle. CONCLUSIONS/SIGNIFICANCE: The failure of NAC treatment to prevent smoking-induced loss of bone marrow pre-B cells suggests that oxidative stress is not directly responsible for this loss. The unexpected expansion of the pro-B/pre-B cell subset in response to NAC treatment suggests oxidative stress normally contributes to cell loss at this developmental stage, and also reveals a potential side effect of therapeutic administration of NAC to prevent smoking-induced loss of lung function.

  4. Reversal Effect of Intra-Central Amygdala Microinjection of L-Arginine on Place Aversion Induced by Naloxone in Morphine Conditioned Rats

    OpenAIRE

    Karimi, Sara; Karami, Manizheh; Sahraei, Hedayat; Rahimpour, Mahnaz

    2011-01-01

    Background: Role of nitric oxide (NO) on expression of morphine conditioning using a solely classic task has been proposed previously. In this work, the involvement of NO on the expression of opioid-induced conditioning in the task paired with an injection of naloxone was investigated. Methods: Conditioning was established in adult male Wistar rats (weighing 200-250 g) using an unbiased procedure. Naloxone (0.05-0.4 mg/kg, i.p.), a selective antagonist of mu-opioid receptor, was administered ...

  5. Resveratrol Reverses Cadmium Chloride-induced Testicular Damage and Subfertility by Downregulating p53 and Bax and Upregulating Gonadotropins and Bcl-2 gene Expression

    OpenAIRE

    Eleawa, Samy M.; ALKHATEEB, Mahmoud A; ALHASHEM, Fahaid H; BIN-JALIAH, Ismaeel; SAKR, Hussein F; ELREFAEY, Hesham M; ELKARIB, Abbas O; ALESSA, Riyad M; HAIDARA, Mohammad A; Shatoor, Abdullah S.; KHALIL, Mohammad A

    2014-01-01

    This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl2-induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2+NS, E) CdCl2+vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all gr...

  6. Recombinant TCR ligand induces tolerance to myelin oligodendrocyte glycoprotein 35-55 peptide and reverses clinical and histological signs of chronic experimental autoimmune encephalomyelitis in HLA-DR2 transgenic mice.

    Science.gov (United States)

    Vandenbark, Arthur A; Rich, Cathleen; Mooney, Jeff; Zamora, Alex; Wang, Chunhe; Huan, Jianya; Fugger, Lars; Offner, Halina; Jones, Richard; Burrows, Gregory G

    2003-07-01

    In a previous study, we demonstrated that myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide could induce severe chronic experimental autoimmune encephalomyelitis (EAE) in HLA-DR2(+) transgenic mice lacking all mouse MHC class II genes. We used this model to evaluate clinical efficacy and mechanism of action of a novel recombinant TCR ligand (RTL) comprised of the alpha(1) and beta(1) domains of DR2 (DRB1*1501) covalently linked to the encephalitogenic MOG-35-55 peptide (VG312). We found that the MOG/DR2 VG312 RTL could induce long-term tolerance to MOG-35-55 peptide and reverse clinical and histological signs of EAE in a dose- and peptide-dependent manner. Some mice treated with lower doses of VG312 relapsed after cessation of daily treatment, but the mice could be successfully re-treated with a higher dose of VG312. Treatment with VG312 strongly reduced secretion of Th1 cytokines (TNF-alpha and IFN-gamma) produced in response to MOG-35-55 peptide, and to a lesser degree purified protein derivative and Con A, but had no inhibitory effect on serum Ab levels to MOG-35-55 peptide. Abs specific for both the peptide and MHC moieties of the RTLs were also present after treatment with EAE, but these Abs had only a minor enhancing effect on T cell activation in vitro. These data demonstrate the powerful tolerance-inducing therapeutic effects of VG312 on MOG peptide-induced EAE in transgenic DR2 mice and support the potential of this approach to inhibit myelin Ag-specific responses in multiple sclerosis patients. PMID:12816990

  7. Rat exposure in mice with neuropathic pain induces fear and antinociception that is not reversed by 5-HT2C receptor activation in the dorsal periaqueductal gray.

    Science.gov (United States)

    Furuya-da-Cunha, Elke Mayumi; Souza, Rimenez Rodrigues de; Canto-de-Souza, Azair

    2016-07-01

    Previous studies have demonstrated that serotonin 5-HT2C receptors in the dorsal periaqueductal gray (dPAG) mediate both anxiety and antinociception in mice submitted to the elevated plus maze. The present study examined the effects of intra-dPAG infusion of the serotonin 5-HT2C receptor agonist (MK-212) in the defensive reactions and antinociception in mice with neurophatic pain confronted by a predator. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve, and predator confrontation was performed using the rat exposure test (RET). Our results demonstrated that both sham-operated and CCI mice exhibited intense defensive reactions when confronted by rats. However, rat-exposed CCI mice showed reduced pain reactivity in comparison to CCI mice exposed to a toy rat. Intra-dPAG infusion of MK-212 prior to predator exposure did not significantly alter defensive or antinociceptive responses. To our knowledge, our results represent the first evidence of RET-induced antinociception in mice. Moreover, the results of the present study suggest that 5-HT2C receptor activation in the dPAG is not critically involved in the control of predator-evoked fearful or antinociceptive responses. PMID:27059332

  8. Panepoxydone targets NF-kB and FOXM1 to inhibit proliferation, induce apoptosis and reverse epithelial to mesenchymal transition in breast cancer.

    Directory of Open Access Journals (Sweden)

    Ritu Arora

    Full Text Available BACKGROUND: Triple-negative breast cancer (TNBC is a highly diverse group that is associated with an aggressive phenotype. Its treatment has been challenging due to its heterogeneity and absence of well-defined molecular targets. Thus, there is an urgent need to identify novel agents with therapeutic application. NF-κB is over-expressed in many breast cancers; thus, inactivation of the NF-κB pathway could serve as a therapeutic target. Here we report for the first time the anti-tumor activity of panepoxydone (PP, a NF-κB inhibitor isolated from an edible mushroom, in several breast cancer cell lines. METHODS: We investigated the effects of PP on cell growth, migration-invasion, apoptosis and EMT-related proteins expression in MCF-7 and TNBC cell lines MDA-MB-231, MDA-MB-468 and MDA-MB-453. RESULTS: Significant antitumor activity was seen in all cell lines, with differential responses noted in cell-line specific manner. Treatment with PP resulted in significant cytotoxicity, decreased invasion, migration and increased apoptosis in all cell lines tested. Up-regulation of Bax and cleaved PARP and down-regulation of Bcl-2, survivin, cyclin D1 and caspase 3 were noted in PP-treated breast cancer cells. The antitumor effect of PP appeared related to its ability to inhibit the phosphorylation of inhibitor of NF-κB (IκBα with cytoplasmic accumulation. PP treatment also down-regulated FOXM1 which resulted in a reversal of EMT. Similar results were obtained after silencing of NF-kB and FOXM1. CONCLUSION: Altogether, these studies show, for the first time the antitumor activity of PP against breast cancer cells, in particular TNBC cells. Furthermore, it highlights the concept that optimal treatment of TNBC warrants attention to the differential sensitivity of various TNBC subtypes to therapeutic agents. These results suggest that the PP may be a potentially effective chemopreventive or therapeutic agent against breast cancer. However, additional

  9. MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein.

    Science.gov (United States)

    Han, Jinfeng; Liu, Zhongmin; Wang, Nanya; Pan, Weiyun

    2016-07-01

    MicroRNA-874 (miR-874) is downregulated and acts as a tumor suppressor in several types of cancers, whereas the biological function of miR-874 in colorectal cancer (CRC) remains unclear. The aims of the present study were to investigate the clinical significance, biological effects, and the underlying mechanisms of miR-874 in CRC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-874 expression in CRC cell lines and tissue samples. MTT and colony formation assays and flow cytometry were performed to analyze the effects of miR-874 expression on growth, apoptosis and the chemoresistance of CRC cells. Regulation of putative miR-874 targets was determined by dual-luciferase reporter assays. RT-qPCR and western blot assays were performed to detected the levels of X-linked inhibitor of apoptosis protein (XIAP) mRNA and protein expression. It was found that expression of miR-874 was downregulated in CRC tissues and cell lines, and its expression was significantly negatively correlated with TNM stage and lymph node metastasis of the CRC patients. Functional assays revealed that restoration of miR-874 inhibited proliferation, reduced colony formation, enhanced apoptosis, as well as decreased the 5-fluorouracil (5-FU) resistance of the CRC cells. Through luciferase activity assay, RT-qPCR and western blot analysis, XIAP was shown to be a direct target of miR-874. In addition, XIAP expression was significantly increased in the CRC tissues and cell lines, and was inversely correlated with miR-874 expression. Importantly, downregulation of XIAP in CRC cells had an effect similar to that of miR-874 overexpression. Taken together, these data showed that miR-874 inhibits growth, increases apoptosis and enhances chemosensitivity in CRC cells by targeting XIAP, suggesting that miR-874 may be a potential molecular target for the treatment of human CRC. PMID:27221209

  10. Panepoxydone Targets NF-kB and FOXM1 to Inhibit Proliferation, Induce Apoptosis and Reverse Epithelial to Mesenchymal Transition in Breast Cancer

    Science.gov (United States)

    Arora, Ritu; Yates, Clayton; Gary, Bernard D.; McClellan, Steven; Tan, Ming; Xi, Yaguang; Reed, Eddie; Piazza, Gary A.; Owen, Laurie B.; Dean-Colomb, Windy

    2014-01-01

    Background Triple-negative breast cancer (TNBC) is a highly diverse group that is associated with an aggressive phenotype. Its treatment has been challenging due to its heterogeneity and absence of well-defined molecular targets. Thus, there is an urgent need to identify novel agents with therapeutic application. NF-κB is over-expressed in many breast cancers; thus, inactivation of the NF-κB pathway could serve as a therapeutic target. Here we report for the first time the anti-tumor activity of panepoxydone (PP), a NF-κB inhibitor isolated from an edible mushroom, in several breast cancer cell lines. Methods We investigated the effects of PP on cell growth, migration-invasion, apoptosis and EMT-related proteins expression in MCF-7 and TNBC cell lines MDA-MB-231, MDA-MB-468 and MDA-MB-453. Results Significant antitumor activity was seen in all cell lines, with differential responses noted in cell-line specific manner. Treatment with PP resulted in significant cytotoxicity, decreased invasion, migration and increased apoptosis in all cell lines tested. Up-regulation of Bax and cleaved PARP and down-regulation of Bcl-2, survivin, cyclin D1 and caspase 3 were noted in PP-treated breast cancer cells. The antitumor effect of PP appeared related to its ability to inhibit the phosphorylation of inhibitor of NF-κB (IκBα) with cytoplasmic accumulation. PP treatment also down-regulated FOXM1 which resulted in a reversal of EMT. Similar results were obtained after silencing of NF-kB and FOXM1. Conclusion Altogether, these studies show, for the first time the antitumor activity of PP against breast cancer cells, in particular TNBC cells. Furthermore, it highlights the concept that optimal treatment of TNBC warrants attention to the differential sensitivity of various TNBC subtypes to therapeutic agents. These results suggest that the PP may be a potentially effective chemopreventive or therapeutic agent against breast cancer. However, additional studies are required to

  11. Reversal of obesity and insulin resistance by a non-peptidic glucagon-like peptide-1 receptor agonist in diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Min He

    Full Text Available BACKGROUND: Glucagon-like peptide-1 (GLP-1 is recognized as an important regulator of glucose homeostasis. Efforts to utilize GLP-1 mimetics in the treatment of diabetes have yielded clinical benefits. A major hurdle for an effective oral therapy has been the difficulty of finding a non-peptidic GLP-1 receptor (GLP-1R agonist. While its oral bioavailability still poses significant challenges, Boc5, one of the first such compounds, has demonstrated the attainment of GLP-1R agonism in diabetic mice. The present work was to investigate whether subchronic Boc5 treatment can restore glycemic control and induce sustainable weight loss in diet-induced obese (DIO mice, an animal model of human obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: DIO mice were treated three times a week with Boc5 (0.3, 1 and 3 mg for 12 weeks. Body weight, body mass index (BMI, food intake, fasting glucose, intraperitoneal glucose tolerance and insulin induced glucose clearance were monitored regularly throughout the treatment. Glucose-stimulated insulin secretion, β-cell mass, islet size, body composition, serum metabolic profiles, lipogenesis, lipolysis, adipose hypertrophy and lipid deposition in the liver and muscle were also measured after 12 weeks of dosing. Boc5 dose-dependently reduced body weight, BMI and food intake in DIO mice. These changes were associated with significant decreases in fat mass, adipocyte hypertrophy and peripheral tissue lipid accumulation. Boc5 treatment also restored glycemic control through marked improvement of insulin sensitivity and normalization of β-cell mass. Administration of Boc5 (3 mg reduced basal but enhanced insulin-mediated glucose incorporation and noradrenaline-stimulated lipolysis in isolated adipocytes from obese mice. Furthermore, circulating leptin, adiponectin, triglyceride, total cholesterol, nonesterified fatty acid and high-density lipoprotein/low-density lipoprotein ratio were normalized to various

  12. Reversible cerebral vasoconstriction syndrome

    Directory of Open Access Journals (Sweden)

    Saini Monica

    2009-01-01

    Full Text Available Reversible cerebral vasoconstriction syndromes (RCVS are a group of disorders that have in common an acute presentation with headache, reversible vasoconstriction of cerebral arteries, with or without neurological signs and symptoms. In contrast to primary central nervous system vasculitis, they have a relatively benign course. We describe here a patient who was diagnosed with RCVS.

  13. Quantum reverse hypercontractivity

    Energy Technology Data Exchange (ETDEWEB)

    Cubitt, Toby [Department of Computer Science, University College London, London, United Kingdom and Centre for Quantum Information and Foundations, DAMTP, University of Cambridge, Cambridge (United Kingdom); Kastoryano, Michael [NBIA, Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen (Denmark); Montanaro, Ashley [School of Mathematics, University of Bristol, Bristol (United Kingdom); Temme, Kristan [Institute for Quantum Information and Matter, California Institute of Technology, Pasadena, California 91125 (United States)

    2015-10-15

    We develop reverse versions of hypercontractive inequalities for quantum channels. By generalizing classical techniques, we prove a reverse hypercontractive inequality for tensor products of qubit depolarizing channels. We apply this to obtain a rapid mixing result for depolarizing noise applied to large subspaces and to prove bounds on a quantum generalization of non-interactive correlation distillation.

  14. Reversible renal impairment induced by treatment with the angiotensin II receptor antagonist candesartan in a patient with bilateral renal artery stenosis

    Directory of Open Access Journals (Sweden)

    Kjaer Andreas

    2001-05-01

    Full Text Available Abstract Background It is well established that ACE-inhibitors should be avoided in patients with renal artery stenosis. In recent years it has also been recommended that caution should be demonstrated when angiotensin II blockers are used in the same type of patients but the evidence is based only on few cases. Results We describe a case where use of the angiotensin II antagonist candesartan (Atacand induced renal failure in a patient with bilateral renal artery stenosis. The course of the case is enlighted by results from sequential renography, selective renal vein catheterisation for measurement of renin, and angiographic findings. Conclusions In patients with renal artery stenosis the angiotensin II antagonist candesartan should be avoided.

  15. Opioid-induced constipation reversal in response to placebo in a patient with a history of IBS receiving methadone maintenance therapy.

    Science.gov (United States)

    Samokhvalov, Andriy V; Rehm, Jürgen

    2015-01-01

    Opioid-induced constipation (OIC) is one of the major side effects in patients receiving methadone maintenance treatment (MMT). Quite often, constipation becomes a factor significantly affecting therapeutic options and choices. Currently used approaches are symptomatic and in many cases ineffective. At the same time, it is well known that the gastrointestinal system is a subject for psychosomatic influences. In this case report, we describe an unexpected outcome of placebo administration in a patient suffering from OIC since her participation in MMT. The patient participated in a triple-blind randomised placebo-controlled trial of naloxone for treatment of OIC. As part of the study crossover design, the patient received 1 week of placebo followed by 1 week of naloxone, and had significant improvement in her bowel functioning when receiving placebo, then returned to baseline during the second week of the study. PMID:26567239

  16. Saturated- and n-6 polyunsaturated-fat diets each induce ceramide accumulation in mouse skeletal muscle: reversal and improvement of glucose tolerance by lipid metabolism inhibitors.

    Science.gov (United States)

    Frangioudakis, G; Garrard, J; Raddatz, K; Nadler, J L; Mitchell, T W; Schmitz-Peiffer, C

    2010-09-01

    Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg x d), or MYR (0.3 mg/kg x d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated fat diets increased muscle ceramide and induced glucose intolerance. MYR and LSF reduced ceramide levels in saturated and unsaturated fat-fed mice. Both inhibitors also improved glucose tolerance in unsaturated fat-fed mice, but only LSF was effective in saturated fat-fed mice. The discrepancy between ceramide and glucose tolerance suggests these improvements may not be related directly to changes in muscle ceramide and may involve other insulin-responsive tissues. Changes in the expression of LASS1 were, however, inversely correlated with alterations in glucose tolerance. The demonstration that LSF can ameliorate glucose intolerance in vivo independent of the dietary FA type indicates it may be a novel intervention for the treatment of insulin resistance. PMID:20660065

  17. Dipole collapse and reversal precursors in a numerical dynamo

    Science.gov (United States)

    Olson, Peter; Driscoll, Peter; Amit, Hagay

    2009-03-01

    Precursors to extreme geomagnetic field changes are examined in a numerical dynamo with a reversing dipolar magnetic field. A dynamo model with compositional convection in a rotating spherical shell produces a strongly dipolar external magnetic field over 6 Myr of simulated paleomagnetic time, with stable polarity epochs and occasional dipole collapses, some of which result in polarity reversals or dipole axis excursions. We analyze the model behavior during two dipole collapses, one that leads to a polarity reversal and one that does not, focusing on observable precursors. Reversed magnetic field induced in the dynamo interior by intermittent convective variability is the primary cause of dipole collapse. Spots of reversed magnetic flux emerge on the outer boundary at an early stage, then re-emerge with greater intensity at the height of the collapse. The energy in the external field cascades to higher harmonics as these reversed patches appear. Butterfly diagrams showing the reversed and normal flux contributions to the axial dipole reveal poleward migration of the patches during dipole collapse. Axial dipole reduction by precursory reversed flux is several times larger in the reversing case, compared to the non-reversing case. A butterfly diagram of the geomagnetic field since 1840 shows high latitude reversed flux emerging on the core-mantle boundary. Although the reversed geomagnetic flux is presently too weak to be labeled a reversal precursor, it is consistent with early stage dipole collapse in the dynamo model.

  18. Raman spectroscopic detection of rapid, reversible, early-stage inflammatory cytokine-induced apoptosis of adult hippocampal progenitors/stem cells

    CERN Document Server

    Ladiwala, Uma; Thakur, Bhushan; Santhosh, Chidangil; Mathur, Deepak

    2014-01-01

    The role of neuro-inflammation in diverse, acute and chronic brain pathologies is being increasingly recognized. Neuro-inflammation is accompanied by increased levels of both pro- and anti-inflammatory cytokines; these have deleterious as well as protective/reparative effects. Inflammation has varying effects on neurogenesis and is a subject of intense contemporary interest. We show that TNF-alpha and IFN-gamma, used concomitantly, cause apoptosis of adult rat hippocampal progenitor/stem cells in vitro as detected by the TUNEL and MTT assays on time scales of several hours. We have coupled Raman spectroscopy to an optical trap to probe early changes of apoptosis in single, live neural stem cells that have been treated with pro-inflammatory cytokines, TNF-alpha and IFN-gamma. Changes caused by inflammation-induced denaturation of DNA are observed in the Raman spectra that correspond to very early stages of apoptosis, occurring on very fast time scales: as short as 10 minutes. Addition of the anti-inflammatory ...

  19. [Inheritance of reversions to male fertility in male-sterile sorghum hybrids with 9E cytoplasm male sterility induced by environmental conditions].

    Science.gov (United States)

    Elkonin, L A; Gerashchenkov, G A; Domanina, I V; Rozhnova, N A

    2015-03-01

    Heritable phenotypic alterations occurring during plant ontogenesis under the influence of environmental factors are among the most intriguing genetic phenomena. It was found that male-sterile sorghum hybrids in the 9E cytoplasm from the F1 and F2 generations, which were obtained by crossing CMS lines with different fertile lines grown in field conditions, were transferred to greenhouse produce fertile tillers. Lines created by the self-pollination of revertant tillers exhibit complete male fertility upon cultivation under various environments (in the field, Tdry plot,(y) Tirrigated plot(y)). In a number of test-crosses of revertants to CMS lines in the 9E cytoplasm, restoration of male fertility in F1 hybrids was found, indicating that revertants possess functional fertility-restoring genes. A high positive correlation was found between the fertility level of the test-cross hybrids and the hydrothermal coefficient (the ratio of the sum of precipitation to the sum of temperatures) during the booting stage and pollen maturation (r = 0.75...0.91; Psorghum hybrids in the 9E cytoplasm. These data demonstrate that methylation of nuclear genes in sterility-inducing cytoplasm may be one of mechanisms causing the CMS phenomenon. PMID:26027370

  20. L-DOPA Reverses the Increased Free Amino Acids Tissue Levels Induced by Dopamine Depletion and Rises GABA and Tyrosine in the Striatum.

    Science.gov (United States)

    Solís, Oscar; García-Sanz, Patricia; Herranz, Antonio S; Asensio, María-José; Moratalla, Rosario

    2016-07-01

    Perturbations in the cerebral levels of various amino acids are associated with neurological disorders, and previous studies have suggested that such alterations have a role in the motor and non-motor symptoms of Parkinson's disease. However, the direct effects of chronic L-DOPA treatment, that produces dyskinesia, on neural tissue amino acid concentrations have not been explored in detail. To evaluate whether striatal amino acid concentrations are altered in peak dose dyskinesia, 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian mice were treated chronically with L-DOPA and tissue amino acid concentrations were assessed by HPLC analysis. These experiments revealed that neither 6-OHDA nor L-DOPA treatment are able to alter glutamate in the striatum. However, glutamine increases after 6-OHDA and returns back to normal levels with L-DOPA treatment, suggesting increased striatal glutamatergic transmission with lack of dopamine. In addition, glycine and taurine levels are increased following dopamine denervation and restored to normal levels by L-DOPA. Interestingly, dyskinetic animals showed increased levels of GABA and tyrosine, while aspartate striatal tissue levels are not altered. Overall, our results indicate that chronic L-DOPA treatment, besides normalizing the altered levels of some amino acids after 6-OHDA, robustly increases striatal GABA and tyrosine levels which may in turn contribute to the development of L-DOPA-induced dyskinesia. PMID:26966009

  1. In silico reversal of repeat-induced point mutation (RIP identifies the origins of repeat families and uncovers obscured duplicated genes

    Directory of Open Access Journals (Sweden)

    Hane James K

    2010-11-01

    Full Text Available Abstract Background Repeat-induced point mutation (RIP is a fungal genome defence mechanism guarding against transposon invasion. RIP mutates the sequence of repeated DNA and over time renders the affected regions unrecognisable by similarity search tools such as BLAST. Results DeRIP is a new software tool developed to predict the original sequence of a RIP-mutated region prior to the occurrence of RIP. In this study, we apply deRIP to the genome of the wheat pathogen Stagonospora nodorum SN15 and predict the origin of several previously uncharacterised classes of repetitive DNA. Conclusions Five new classes of transposon repeats and four classes of endogenous gene repeats were identified after deRIP. The deRIP process is a new tool for fungal genomics that facilitates the identification and understanding of the role and origin of fungal repetitive DNA. DeRIP is open-source and is available as part of the RIPCAL suite at http://www.sourceforge.net/projects/ripcal.

  2. Epicatechin-3-gallate reverses TGF-β1-induced epithelial-to-mesenchymal transition and inhibits cell invasion and protease activities in human lung cancer cells.

    Science.gov (United States)

    Huang, Shu-Fang; Horng, Chi-Ting; Hsieh, Yih-Shou; Hsieh, Yi-Hsien; Chu, Shu-Chen; Chen, Pei-Ni

    2016-08-01

    Epithelial-to-mesenchymal transition (EMT) and invasion potential have been considered as essential factors in cancer metastasis, which is the major cause of cancer death. EMT is a multi-step process that involves gain invasion, cytoskeleton change, cell adhesion, and proteolytic extracellular matrix degradation. Epicatechin-3-gallate (ECG), which is a natural polyphenolic component of green tea, elicits several antioxidant and anti-inflammatory effects. However, the effects of ECG on cancer invasion and EMT of human lung carcinoma remain unknown. We provided molecular evidence supporting the anti-metastatic effect of ECG. This compound suppressed the invasion (P EMT and upregulated epithelial markers, such as E-cadherin. Conversely, ECG inhibited mesenchymal markers, such as fibronectin and p-FAK. The subcutaneous inoculation of this compound also inhibited the tumor growth of the A549 cells in vivo. Therefore, ECG may be used as an anti-cancer and anti-invasion agent for the adjuvant treatment and metastasis control of human lung cancer cells. ECG may also be administered as an effective chemopreventive agent against TGF-β1-induced EMT. PMID:27224248

  3. Chronic ethanol intake-induced changes in open-field behavior and calcium/calmodulin-dependent protein kinase Ⅳ expression in nucleus accumbens of rats: naloxone reversal

    Institute of Scientific and Technical Information of China (English)

    Jing LI; Wei-liang BIAN; Gui-qin XIE; Sheng-zhong CUI; Mei-ling WU; Yue-hua LI; Ling-li QUE; Xiao-ru YUAN

    2008-01-01

    Aim: To investigate the effects of chronic ethanol intake on the locomotor activity and the levels of calcium/calmodulin-dependent protein kinase Ⅳ (CaM kinase Ⅳ) in the nucleus accumbens (NAc) of rats. Simultaneously, the effects of non-selective opioid antagonist (naloxone) on the CaM kinase Ⅳ expression in the NAc and ethanol consumption of rats were also observed. Methods: Ethanol was administered in drinking water at the concentrations of 6% (v/v), for 28 d. The locomotor activity of rats was investigated in the open-field apparatus. CaM kinase Ⅳ levels in the NAc were analyzed using Western blotting. Results: Rats consuming ethanol solution exhibited a significant decrease of ambulation activity, accompanied by a reduced frequency of explorative rearing in an open-field task on d 7 and d 14 of chronic ethanol ingestion, whereas presumed adaptation to the neurological effects of ethanol was observed on d 28. Chronic ethanol intake elicited a significant decrease of the CaM kinase Ⅳ expression in the nuclei, but not in the cytoplasm of the NAc on d 28. Naloxone treatment significantly attenu-ated ethanol intake of rats and antagonized the decrease of CaM kinase Ⅳ in the nuclei of NAc neurons. The cytosolic CaM kinase Ⅳ protein levels of the NAc also increased in rats exposed to ethanol plus naloxone. Conclusion: Chronic ethanol intake-induced changes in explorative behavior is mediated at least partly by changes in CaM kinase Ⅳ signaling in the nuclei of the NAc, and naloxone attenuates ethanol consumption through antagonizing the downregulation of CaM kinase Ⅳ in the NAc.

  4. Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by dl-{alpha}-lipoic acid

    Energy Technology Data Exchange (ETDEWEB)

    Shila, Samuel; Subathra, Marimuthu; Devi, Muthuswamy Anusuya; Panneerselvam, Chinnakkannu [University of Madras, Department of Medical Biochemistry, Chennai (India)

    2005-03-01

    The purpose of this study was to examine the effects of dl-{alpha}-lipoic acid (LA) on arsenic (As) induced alteration of glutathione (GSH) level and of the activity of glutathione-related enzymes - glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH) - in rat brain regions (cortex, hypothalamus, striatum, cerebellum and hippocampus). Male Wistar rats of 150{+-}10 g weight were divided into four groups: control and three experimental groups supplemented with arsenic (sodium arsenite) alone (100 ppm mixed in drinking water), lipoic acid alone (70 mg kg{sup -1} body weight), arsenic plus lipoic acid (100 ppm arsenic in drinking water plus 70 mg lipoic acid kg{sup -1} body weight). The arsenic content of brain regions was found to increase with the administration of sodium arsenite. Arsenic exposure elicited a significant decline in glutathione content and in the activity of related enzymes, with the greatest decreases seen in the cortex, striatum, and hippocampus, whereas there were no significant differences between control rats and the group treated with lipoic acid alone. Highly elevated content of the thiobarbituric acid-reactive substance malondialdehyde (MDA) in the brain regions of arsenic-exposed rats reflected extensive lipid peroxidation (LPO) processes. Simultaneous lipoic acid treatment was effective in reducing brain regional arsenic levels and lipid peroxidation and in increasing the glutathione content and the activity of its related enzymes. Lipoic acid, by acting as an alternative sulfhydryl nucleophile to glutathione, prevents its oxidation to glutathione disulfide in detoxifying reactions against reactive oxygen species and consequently increases the activity of glutathione-related enzymes. (orig.)

  5. An Algebra of Reversible Computation

    OpenAIRE

    Wang, Yong

    2014-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules, basic reversible processes algebra (BRPA), algebra of reversible communicating processes (ARCP), recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

  6. On the construction of reversible automata for reversible languages

    OpenAIRE

    Lombardy, Sylvain

    2002-01-01

    International audience Reversible languages occur in many different domains. Although the decision for the membership of reversible languages was solved in 1992 by Pin, an effective construction of a reversible automaton for a reversible language was still unknown. We give in this paper a method to compute a reversible automaton from the minimal automaton of a reversible language. With this intention, we use the universal automaton of the language that can be obtained from the minimal auto...

  7. Reversible flowchart languages and the structured reversible program theorem

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    Many irreversible computation models have reversible counterparts, but these are poorly understood at present. We introduce reversible flowcharts with an assertion operator and show that any reversible flowchart can be simulated by a structured reversible flowchart using only three control flow o...... justification for low-level machine code for reversible microprocessors as well as high-level block-structured reversible languages. We give examples for both such languages and illustrate them with a lossless encoder for permutations given by Dijkstra....

  8. Novel Apo E-Derived ABCA1 Agonist Peptide (CS-6253) Promotes Reverse Cholesterol Transport and Induces Formation of preβ-1 HDL In Vitro.

    Science.gov (United States)

    Hafiane, Anouar; Bielicki, John K; Johansson, Jan O; Genest, Jacques

    2015-01-01

    Apolipoprotein (apo) mimetic peptides replicate some aspects of HDL function. We have previously reported the effects of compound ATI-5261 on its ability to replicate many functions of native apo A-I in the process of HDL biogenesis. ATI-5261 induced muscle toxicity in wild type C57Bl/6 mice, increased CPK, ALT and AST and increase in triglyceride (Tg) levels. Aromatic phenylalanine residues on the non-polar face of ATI-5261, together with positively charged arginine residues at the lipid-water interface were responsible for these effects. This information was used to create a novel analog (CS-6253) that was non-toxic. We evaluated this peptide designed from the carboxyl terminus of apo E, in its ability to mimic apo A-I functionality. Our data shows that the lipidated particles generated by incubating cells overexpressing ABCA1 with lipid free CS-6253 enhances the rate of ABCA1 lipid efflux with high affinity interactions with native ABCA1 oligomeric forms and plasma membrane micro-domains. Interaction between ABCA1 and lipid free CS-6253 resulted in formation of nascent HDL-CS-6253 particles that are actively remodeled in plasma. Mature HDL-CS-6253 particles deliver cholesterol to liver cells via SR-BI in-vitro. CS-6253 significantly increases cholesterol efflux in murine macrophages and in human THP-1 macrophage-derived foam cells expressing ABCA1. Addition of CS-6253 to plasma dose-dependently displaced apo A-I from α-HDL particles and led to de novo formation of preβ-1 HDL that stimulates ABCA1 dependent cholesterol efflux efficiently. When incubated with human plasma CS-6253 was also found to bind with HDL and LDL and promoted the transfer of cholesterol from HDL to LDL predominantly. Our data shows that CS-6253 mimics apo A-I in its ability to promote ABCA1-mediated formation of nascent HDL particles, and enhances formation of preβ-1 HDL with increase in the cycling of apo A-I between the preβ and α-HDL particles in-vitro. These mechanisms are

  9. Reversed DNA strand cleavage specificity in initiation of Cre-LoxP recombination induced by the His289Ala active-site substitution.

    Science.gov (United States)

    Gelato, Kathy A; Martin, Shelley S; Baldwin, Enoch P

    2005-11-25

    During the first steps of site-specific recombination, Cre protein cleaves and religates a specific homologous pair of LoxP strands to form a Holliday junction (HJ) intermediate. The HJ is resolved into recombination products through exchange of the second homologous strand pair. CreH289A, containing a His to Ala substitution in the conserved R-H-R catalytic motif, has a 150-fold reduced recombination rate and accumulates HJs. However, to produce these HJs, CreH289A exchanges the opposite set of strands compared to wild-type Cre (CreWT). To investigate how CreH289A and CreWT impose strand exchange order, we characterized their reactivities and strand cleavage preferences toward LoxP duplex and HJ substrates containing 8bp spacer substitutions. Remarkably, CreH289A had different and often opposite strand exchange preferences compared to CreWT with nearly all substrates. CreH289N was much less perturbed, implying that overall recombination rate and strand exchange depend more on His289 hydrogen bonding capability than on its acid/base properties. LoxP substitutions immediately 5' (S1 nucleotide) or 3' (S1' nucleotide) of the scissile phosphate had large effects on substrate utilization and strand exchange order. S1' substitutions, designed to alter base-unstacking events concomitant with Cre-induced LoxP bending, caused HJ accumulation and dramatically inverted the cleavage preferences. That pre-formed HJs were resolved via either strand in vitro suggests that inhibition of the "conformational switch" isomerization required to trigger the second strand exchange accounts for the observed HJ accumulation. Rather than reflecting CreWT behavior, CreH289A accumulates HJs of opposite polarity through a combination of its unique cleavage specificity and an HJ isomerization defect. The overall implication is that cleavage specificity is mediated by sequence-dependent DNA deformations that influence the scissile phosphate positioning and reactivity. A role of His289 may be to

  10. Reversed DNA Strand Cleavage Specificity in Initiation of Cre–LoxP Recombination Induced by the His289Ala Active-site Substitution

    Science.gov (United States)

    Gelato, Kathy A.; Martin, Shelley S.; Baldwin, Enoch P.

    2010-01-01

    During the first steps of site-specific recombination, Cre protein cleaves and religates a specific homologous pair of LoxP strands to form a Holliday junction (HJ) intermediate. The HJ is resolved into recombination products through exchange of the second homologous strand pair. CreH289A, containing a His to Ala substitution in the conserved R-H-R catalytic motif, has a 150-fold reduced recombination rate and accumulates HJs. However, to produce these HJs, CreH289A exchanges the opposite set of strands compared to wild-type Cre (CreWT). To investigate how CreH289A and CreWT impose strand exchange order, we characterized their reactivities and strand cleavage preferences toward LoxP duplex and HJ substrates containing 8 bp spacer substitutions. Remarkably, CreH289A had different and often opposite strand exchange preferences compared to CreWT with nearly all substrates. CreH289N was much less perturbed, implying that overall recombination rate and strand exchange depend more on His289 hydrogen bonding capability than on its acid/base properties. LoxP substitutions immediately 5′(S1 nucleotide) or 3′(S1′nucleotide) of the scissile phosphate had large effects on substrate utilization and strand exchange order. S1′substitutions, designed to alter base-unstacking events concomitant with Cre-induced LoxP bending, caused HJ accumulation and dramatically inverted the cleavage preferences. That pre-formed HJs were resolved via either strand in vitro suggests that inhibition of the “conformational switch” isomerization required to trigger the second strand exchange accounts for the observed HJ accumulation. Rather than reflecting CreWT behavior, CreH289A accumulates HJs of opposite polarity through a combination of its unique cleavage specificity and an HJ isomerization defect. The overall implication is that cleavage specificity is mediated by sequence-dependent DNA deformations that influence the scissile phosphate positioning and reactivity. A role of His289

  11. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... stability and soft tissue envelope. In the early days of reverse arthroplasty, it used to be said ... often we'll drain these patients for a day to try to prevent hematoma formation, especially in ...

  12. Purchasing As Reverse Marketing

    OpenAIRE

    Blenkhorn, D L; Banting, P M

    1989-01-01

    This paper describes a new concept called reverse marketing, which is changing the conventional buyer-seller relationship and has important implications for the traditional role of the industrial marketer.

  13. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... replacement. There are two basic approaches you can use for reverse shoulder replacement. The standard delto-pectoral ... surgery or a deltoid defect because you can use the same incision and repair any deltoid defects ...

  14. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... the reverse allow patients to play tennis or sports where the arm swings backward. Our experience has ... who simply wants to be stronger or play sports better. But in terms of the patients that ...

  15. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... with an intact cuff, we would consider a traditional shoulder replacement. There are two basic approaches you ... less limited with the superior reverse versus the traditional. And I assume the question means the approach: ...

  16. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... in the United States. The indications are a patient with painful arthritis, absent rotator cuff, a less ... reverse arthroplasty is indicated for that type of patient. In a younger patient with an intact cuff, ...

  17. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... reverse shoulder arthroplasty for cuff deficient arthritis. You should be aware that I helped design the system ... the delto- pectoral approach. The three features you should watch for in this video are the things ...

  18. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... the height perfectly to get anatomic head tuberosity relationships. If you're doing a reverse for a ... able to start some gentle mobility of the body and the arm, and have better pain relief. ...

  19. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... a friction bite that if you try to work it around the corner, you can get an ... stability and soft tissue envelope. In the early days of reverse arthroplasty, it used to be said ...

  20. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... We usually lay this just at the inner table of the biceps groove next to the lesser ... is, does the reverse allow patients to play tennis or sports where the arm swings backward. Our ...

  1. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... is essentially a culture medium. So, I use antibiotic-impregnated cement when I do the reverses. I ... minimal. At our institution we keep them on antibiotics for 24 hours. And hopefully the drain output ...

  2. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... case of reverse shoulder arthroplasty for cuff deficient arthritis. You should be aware that I helped design ... in the last decade for cuff deficient shoulder arthritis in the United States. The indications are a ...

  3. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... dislocations, although it's also reported to have a higher rate of getting the components in not perfect ... about infection and other things. There is a higher rate of infection with reverse replacement, probably because ...

  4. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... here in New York to bring you a video of a recent case of reverse shoulder arthroplasty ... helped design the system that's shown in this video, so I receive royalties and therefore have a ...

  5. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... residents and do receive compensation for that, as well. Now, reverse shoulder arthroplasty is a new option ... t see the neck of the humerus as well, but on the other hand, you have a ...

  6. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... terminal range. The other thing to keep in mind is there's a fairly large dead space between ... the height perfectly to get anatomic head tuberosity relationships. If you're doing a reverse for a ...

  7. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... their arm up but they can't do it actively. And the reverse arthroplasty is indicated for ... those. The advantage of a superior approach is it's especially useful if you've had previous open ...

  8. Reverse vending machine update

    Energy Technology Data Exchange (ETDEWEB)

    Rypins, S.; Papke, C.

    1986-02-01

    The document discusses reverse vending machines. Placed outdoors in supermarket parking lots or indoors in the lobby of the grocery market, these hightech machines exchange aluminum cans (or other containers in more specialized machines) for cash, coupons or redeemable receipts. The placement of reverse venders (RV) in or near supermarkets has made recycling more visible and more convenient, although the machines have yet to fully reach industry goals.

  9. PROCESSING REVERSE LOGISTICS INVENTORIES

    OpenAIRE

    Bajor, Ivona; Novačko, Luka; Ogrizović, Dario

    2014-01-01

    Developed logistics systems have organized reverse logistics flows and are continuously analyzing product returns, tending to detect patterns in oscillations of returning products in certain time periods. Inventory management in reverse logistics systems depends on different criteria, regarding goods categories, formed contracts between subjects of supply chains, uncertainty in manufacturer’s quantities of DOA (dead on arrival) products, etc. The developing logistics systems, such as the Croa...

  10. Vasectomy reversal in humans

    OpenAIRE

    Bernie, Aaron M.; Osterberg, E Charles; Stahl, Peter J.; Ramasamy, Ranjith; Goldstein, Marc

    2012-01-01

    Vasectomy is the most common urological procedure in the United States with 18% of men having a vasectomy before age 45. A significant proportion of vasectomized men ultimately request vasectomy reversal, usually due to divorce and/or remarriage. Vasectomy reversal is a commonly practiced but technically demanding microsurgical procedure that restores patency of the male excurrent ductal system in 80–99.5% of cases and enables unassisted pregnancy in 40–80% of couples. The discrepancy between...

  11. On thermodynamic and microscopic reversibility

    Energy Technology Data Exchange (ETDEWEB)

    Crooks, Gavin E.

    2011-07-12

    The word 'reversible' has two (apparently) distinct applications in statistical thermodynamics. A thermodynamically reversible process indicates an experimental protocol for which the entropy change is zero, whereas the principle of microscopic reversibility asserts that the probability of any trajectory of a system through phase space equals that of the time reversed trajectory. However, these two terms are actually synonymous: a thermodynamically reversible process is microscopically reversible, and vice versa.

  12. Parkinson’s disease managing reversible neurodegeneration

    Directory of Open Access Journals (Sweden)

    Hinz M

    2016-04-01

    Full Text Available Marty Hinz,1 Alvin Stein,2 Ted Cole,3 Beth McDougall,4 Mark Westaway5 1Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, 2Stein Orthopedic Associates, Plantation, FL, 3Cole Center for Healing, Cincinnati, OH, 4CLEARCenter of Health, Mill Valley, CA, USA; 5Four Pillars Health, Brendale, QLD, Australia Abstract: Traditionally, the Parkinson’s disease (PD symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. Keywords: Parkinson’s disease, L-dopa, carbidopa, B6, neurodegeneration

  13. Blood-feeding and immunogenic aedes aegypti saliva proteins

    OpenAIRE

    Surasombatpattana, Pornapat; Wasinpiyamongkol, L.; Patramool, Sirilaksana; Luplertlop, N.; Doucouré, Souleymane; Mouchet, François; Seveno, M.; Remoué, Franck; Demettre, E.; Brizard, Jean-Paul; Jouin, P.; Biron, D.G; F. Thomas; Missé, Dorothée

    2010-01-01

    Mosquito-transmitted pathogens pass through the insect's midgut (MG) and salivary gland (SG). What occurs in these organs in response to a blood meal is poorly understood, but identifying the physiological differences between sugar-fed and blood-fed (BF) mosquitoes could shed light on factors important in pathogens transmission. We compared differential protein expression in the MGs and SGs of female Aedes aegypti mosquitoes after a sugar- or blood-based diet. No difference was observed in th...

  14. Logical Reversibility and Physical Reversibility in Quantum Measurement

    OpenAIRE

    Ueda, Masahito

    1997-01-01

    A quantum measurement is logically reversible if the premeasurement density operator of the measured system can be calculated from the postmeasurement density operator and from the outcome of the measurement. This paper analyzes why many quantum measurements are logically irreversible, shows how to make them logically reversible, and discusses reversing measurement that returns the postmeasurement state to the premeasurement state by another measurement (physical reversibility). Reversing mea...

  15. Economic impact of reversion

    International Nuclear Information System (INIS)

    Estimations of the Norwegian hydropower production and various reversion models' market value have been made. The value of the Norwegian hydropower production until 01.01.2007 is estimated to about Nok 289 billion after taxes, or about 2,42 Nok/kWh medium production, given an expected future electricity price of around 0,25 Nok/kWh and a discount rate at 6,5 percent in nominal terms after taxes. The estimate is slightly above the level of prices for Norwegian hydropower plants in the last 8-10 years. The value of reversion in private plants which today have a limited licence time is estimated to Nok 5,5 billion. The value of reversion in public-owned Norwegian hydropower plants are about Nok 21 billion with a 60 year licence period from 01.01.2007, and about 12 billion for 75 years (ml)

  16. Reversed extension flow

    DEFF Research Database (Denmark)

    Nielsen, Jens Kromann; Rasmussen, Henrik K.

    2008-01-01

    Afilament stretching rheometer (FSR) was used for measuring the start-up of uni-axial elongational flow followed by reversed bi-axial flow, both with a constant elongational rate. A narrow molecular mass distribution linear polystyrene with a molecular weight of 145 kg / mole wis subjected to the...... start-up of elongation for three Hencky strain units and subsequently the reversed flow. The integral molecular stress function formulation within the 'interchain pressure' concept agrees with the experiments. In the experiments the Hencky strain at which the str~ss becomes zero (the recovery strain) in...... the reversed flow has been identified. The recovery strain is found to increase with elongational rate, and has a maximum value of approximately 1.45. The Doi Edwards model using any stretch evolution equation is not able to predict the correct level of the recovery strain....

  17. A new deterministic model for chaotic reversals

    CERN Document Server

    Gissinger, Christophe

    2011-01-01

    In this article, we present a new chaotic system of three coupled ordinary differential equations, limited to quadratic terms. A wide variety of dynamical regimes are reported. For some parameters, chaotic reversals of the amplitudes are produced by crisis-induced intermittency, following a mechanism different from what is generally observed in similar deterministic models. Despite its simplicity, this system therefore generates a rich dynamics, able to model more complex physical systems. In particular, a comparison with reversals of the magnetic field of the Earth shows a surprisingly good agreement, and highlights the relevance of deterministic chaos to describe geomagnetic field dynamics.

  18. Reversible deep disposal

    International Nuclear Information System (INIS)

    This presentation, given by the national agency of radioactive waste management (ANDRA) at the meeting of October 8, 2009 of the high committee for the nuclear safety transparency and information (HCTISN), describes the concept of deep reversible disposal for high level/long living radioactive wastes, as considered by the ANDRA in the framework of the program law of June 28, 2006 about the sustainable management of radioactive materials and wastes. The document presents the social and political reasons of reversibility, the technical means considered (containers, disposal cavities, monitoring system, test facilities and industrial prototypes), the decisional process (progressive development and blocked off of the facility, public information and debate). (J.S.)

  19. Reversibility of alcohol-induced immune depression

    DEFF Research Database (Denmark)

    Tønnesen, H; Kaiser, A H; Nielsen, B B;

    1992-01-01

    Alcohol abusers have suppressed cellular immune function. The aim of the study was to investigate the time of sobriety required to normalize immune function. Delayed hypersensitivity was investigated during disulfiram controlled abstinence in ten heavy alcoholics and in seven moderate drinkers...... without liver diseases. For comparison a control group of eight previous drinkers was tested. The skin test responses were modest initially with a median area of response of 12 mm2 (range 0-31) in the heavy alcoholics and 3 mm2 (0-15) in the moderate drinkers. It improved significantly in both groups...... months of abstinence. The results suggest that while 2 weeks of abstinence from alcohol will improve the depressed cellular immunity, 2 months of sobriety is necessary to normalize it....

  20. Characterization of hereditarily reversible posets

    OpenAIRE

    Kukieła, Michał

    2013-01-01

    A poset P is called reversible if every order preserving bijective self map of P is an order automorphism. P is called hereditarily reversible if every subposet of P is reversible. We give a complete characterization of hereditarily reversible posets in terms of forbidden subsets. A similar result is stated also for preordered sets. As a corollary we extend the list of known examples of hereditarily reversible topological spaces.

  1. Time reversal communication system

    Science.gov (United States)

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  2. Reversing insect pollinator decline

    OpenAIRE

    Potts, Simon; Wentworth, Jonathan

    2013-01-01

    Pollination by insects enables the reproduction of flowering plants and is critical to UK agriculture.1 Insect pollinators have declined globally, with implications for food security and wild habitats. This POSTnote summarises the causes for the recent trends, gaps in knowledge and possible strategies for reversing pollinator decline.

  3. Reversal Strategies for NOACs

    DEFF Research Database (Denmark)

    Husted, Steen; Verheugt, Freek; Comuth, Willemijn

    2015-01-01

    , coagulation factor concentrates or NOAC-specific antidotes could be used. Coagulation factor concentrates can be used in patients with haemophilia and to reverse the effect of VKAs but, in NOAC-treated patients, results are inconsistent and these agents could potentially have pro-thrombotic effects. Specific...

  4. Reverse Coherent Information

    Science.gov (United States)

    García-Patrón, Raúl; Pirandola, Stefano; Lloyd, Seth; Shapiro, Jeffrey H.

    2009-05-01

    In this Letter we define a family of entanglement distribution protocols assisted by feedback classical communication that gives an operational interpretation to reverse coherent information, i.e., the symmetric counterpart of the well-known coherent information. This leads to the definition of a new entanglement distribution capacity that exceeds the unassisted capacity for some interesting channels.

  5. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available Reverse Shoulder Arthroplasty Zimmer, Inc. New York City, New York March 17, 2010 Welcome to this OR Live presentation, brought to you by Zimmer. Hi. I'm ... my partner, Brad Parsons. We're here in New York to bring you a video of a ...

  6. Reverse Coherent Information

    OpenAIRE

    García-Patrón, Raúl; Pirandola, Stefano; Lloyd, Seth; Shapiro, Jeffrey H.

    2008-01-01

    In this letter we define a family of entanglement distribution protocols assisted by feedback classical communication that gives an operational interpretation to reverse coherent information, i.e., the symmetric counterpart of the well known coherent information. This lead to the definition of a new entanglement distribution capacity that exceeds the unassisted capacity for some interesting channels.

  7. Reversal of tolerance induced by transplantation of skin expressing the immunodominant T cell epitope of rat type II collagen entitles development of collagen-induced arthritis but not graft rejection

    DEFF Research Database (Denmark)

    Bäcklund, Johan; Treschow, Alexandra; Firan, Mihail; Malmström, Vivianne; Issazadeh-Navikas, Shohreh; Ward, E Sally; Holmdahl, Rikard

    2002-01-01

    collagen (CI), e.g. in skin, are tolerized against rat CII and resistant to CIA. In this study we transplanted skin from TSC transgenic mice onto non-transgenic CIA-susceptible littermates to investigate whether introduction of this epitope to a naïve immune system would lead to T cell priming and graft...... rejection or instead to tolerance and arthritis protection. Interestingly, TSC grafts were accepted and not even immunization of recipient mice with CII in adjuvant induced graft rejection. Instead, TSC skin recipients displayed a reduced T and B cell response to CII and were also protected from arthritis....... However, additional priming could break arthritis protection and was accompanied by an increased T cell response to the grafted epitope. Strikingly, despite the regained T cell response, development of arthritis was not accompanied by graft rejection, showing that these immune-mediated inflammatory...

  8. Novel, selective sample stacking microemulsion electrokinetic capillary chromatography induced by reverse migrating pseudostationary phase for the determination of the new ultra-short acting hypnotic "HIE-124" in mice serum.

    Science.gov (United States)

    Hefnawy, Mohamed; Al-Omar, Mohammed; Julkhuf, Saeed; Attia, Sabry; Abourashed, Ehab; El-Subbagh, Hussein

    2010-07-19

    Microemulsion electrokinetic capillary chromatography (MEEKC) with sample stacking induced by reverse migrating pseudostationary phase (SRMP) technique in a suppressed electro-osmotic flow (EOF) strategy was investigated for analysing the new ultra-short hypnotic HIE-124 in mice serum. The proposed method utilized fused-silica capillary with a total length of 50 cm (effective length 40 cm), applied voltages for stacking and separation were 5.0 kV for 4.30 min and subsequently 25 kV, respectively, with a sample injection of 0.5 psi for 90 s. All the runs were carried out at 25 degrees C and detected at 213 nm. The optimum microemulsion background electrolyte (BGE) solution consisted of 0.8% (v/v) ethyl acetate, 6.6% (v/v) butan-2-ol, 1.0% (v/v) acetonitrile, 2.0% (w/v) sodium dodecyl sulfate (SDS), and 89.6 mL with 25 mM phosphate buffer pH 8. When this preconcentration technique was used, the sample stacking and the separation processes took place successively with changing the voltage with an intermediate polarity switching step. The proposed method was validated carefully with respect to high specificity of the method, good linearity (r=0.9994), fair wide linear concentration range (66-1500 ng mL(-1)), limit of detection and quantitation were 21.6 and 65.5 ng mL(-1), respectively. The mean relative standard deviation (RSD) of the results of intra- and inter-day precision and accuracy were less than 6.0%, and overall recovery higher than 95% of HIE-124 in mice serum. The developed method could be used for the trace analyses of HIE-124 in serum and was finally used for the pharmacokinetic study investigation of HIE-124 in mice serum. PMID:20599035

  9. Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway.

    Science.gov (United States)

    Tiwari, Shashi Kant; Seth, Brashket; Agarwal, Swati; Yadav, Anuradha; Karmakar, Madhumita; Gupta, Shailendra Kumar; Choubey, Vinay; Sharma, Abhay; Chaturvedi, Rajnish Kumar

    2015-11-20

    Neurogenesis involves generation of new neurons through finely tuned multistep processes, such as neural stem cell (NSC) proliferation, migration, differentiation, and integration into existing neuronal circuitry in the dentate gyrus of the hippocampus and subventricular zone. Adult hippocampal neurogenesis is involved in cognitive functions and altered in various neurodegenerative disorders, including Alzheimer disease (AD). Ethosuximide (ETH), an anticonvulsant drug is used for the treatment of epileptic seizures. However, the effects of ETH on adult hippocampal neurogenesis and the underlying cellular and molecular mechanism(s) are yet unexplored. Herein, we studied the effects of ETH on rat multipotent NSC proliferation and neuronal differentiation and adult hippocampal neurogenesis in an amyloid β (Aβ) toxin-induced rat model of AD-like phenotypes. ETH potently induced NSC proliferation and neuronal differentiation in the hippocampus-derived NSC in vitro. ETH enhanced NSC proliferation and neuronal differentiation and reduced Aβ toxin-mediated toxicity and neurodegeneration, leading to behavioral recovery in the rat AD model. ETH inhibited Aβ-mediated suppression of neurogenic and Akt/Wnt/β-catenin pathway gene expression in the hippocampus. ETH activated the PI3K·Akt and Wnt·β-catenin transduction pathways that are known to be involved in the regulation of neurogenesis. Inhibition of the PI3K·Akt and Wnt·β-catenin pathways effectively blocked the mitogenic and neurogenic effects of ETH. In silico molecular target prediction docking studies suggest that ETH interacts with Akt, Dkk-1, and GSK-3β. Our findings suggest that ETH stimulates NSC proliferation and differentiation in vitro and adult hippocampal neurogenesis via the PI3K·Akt and Wnt·β-catenin signaling. PMID:26420483

  10. Formation and reversion of strain induced martensite on Fe-Cr-Ni alloys Formação e reversão da martensita em ligas ferro-cromo-níquel

    Directory of Open Access Journals (Sweden)

    Gabriela Lujan Brollo

    2013-06-01

    Full Text Available Austenitic stainless steels represent a significant portion of the alloys used in the aeronautical, chemical, shipbuilding, food processing and biomechanical industries. They combine good mechanical properties with high corrosion resistance. When subjected to cold deformation, these steels exhibit a metastable phase called: strain induced martensite (ferromagnetic, whose formation increases mechanical strength and formability, allowing for a wide range of applications. Heated from room temperature, the strain induced martensite transforms to austenite (non-magnetic. It is easy to find information in literature about the strain induced martensite for 18Cr/8Ni austenitic steels, but there is no data for high nickel alloys like A286 (26Ni, 15Cr, Incoloy 800 (30-40 Ni, 21Cr and Inconel (50Ni, 19Cr. Therefore, this study aimed to verify the formation of strain induced martensite after cold working in Fe-18Cr base alloys with the addition of up to 60 %Ni. The reversion of this phase to austenite after annealing up to 600 ºC was also studied. Optical microscopy, magnetic characterization tests, and x-ray diffraction were used to analyze the transformations.Os aços inoxidáveis austeníticos são materiais de alto valor agregado, representando uma parcela importante das ligas usadas, principalmente, nas indústrias aeronáutica, química, naval, alimentícia e biomecânica. Apresentam boas propriedades mecânicas aliadas à elevada resistência à corrosão. Quando submetido à deformação a frio, esses aços exibem uma fase metaestável denominada martensita induzida por deformação (ferromagnética, cuja formação aumenta a resistência mecânica e conformabilidade, permitindo sua ampla gama de aplicações. Aquecida acima da temperatura ambiente, a martensita induzida por deformação se transforma em austenita. Existem dados na literatura sobre a formação da martensita induzida por deformação em aços austeníticos 18Cr/8Ni, mas não h

  11. Gridded electron reversal ionizer

    Science.gov (United States)

    Chutjian, Ara (Inventor)

    1993-01-01

    A gridded electron reversal ionizer forms a three dimensional cloud of zero or near-zero energy electrons in a cavity within a filament structure surrounding a central electrode having holes through which the sample gas, at reduced pressure, enters an elongated reversal volume. The resultant negative ion stream is applied to a mass analyzer. The reduced electron and ion space-charge limitations of this configuration enhances detection sensitivity for material to be detected by electron attachment, such as narcotic and explosive vapors. Positive ions may be generated by generating electrons having a higher energy, sufficient to ionize the target gas and pulsing the grid negative to stop the electron flow and pulsing the extraction aperture positive to draw out the positive ions.

  12. Reverse engineering software ecosystems

    OpenAIRE

    Lungu, Mircea F.; Lanza, Michele

    2009-01-01

    Reverse engineering is an active area of research concerned with the development of techniques and tools that support the understanding of software systems. All the techniques that were pro- posed until now study individual systems in isolation. However, software systems are seldom developed in isolation; instead, they are developed together with other projects in the wider context of an organization. We call the collection of projects that are developed in such a con- text a software ...

  13. Time-reversal acoustics

    Energy Technology Data Exchange (ETDEWEB)

    Fink, Mathias [Laboratoire Ondes et Acoustique, Ecole Superieure de Physique et de Chimie Industrielle de la Ville de Paris, Universite Denis Diderot, UMR CNRS 7587, 10 Rue Vauquelin, 75005 Paris (France)], E-mail: mathias.fink@espci.fr

    2008-10-15

    Time-reversal mirrors (TRMs) refocus an incident acoustic field to the position of the original source regardless of the complexity of the propagation medium. TRM's have now been implemented in a variety of physical scenarios from MHz ultrasonics with order centimeter aperture size to hundreds/thousands of Hz in ocean acoustics with order hundred meter aperture size. Common to this broad range of scales is a remarkable robustness exemplified by observations at all scales that the more complex the medium between the probe source and the TRM, the sharper the focus. The relation between the medium complexity and the size of the focal spot is studied in this paper. It is certainly the most exciting property of TRM compared to standard focusing devices. A TRM acts as an antenna that uses complex environments to appears wider than it is, resulting for a broadband pulse in a refocusing quality that does not depend of the TRM aperture. In this paper, we investigate the time-reversal approach in various media of increasing complexity and we discuss the link existing between time-reversal approach and local helioseismology where Green's functions can be extracted from diffusive noise.

  14. Designing Parity Preserving Reversible Circuits

    OpenAIRE

    Paul, Goutam; Chattopadhyay, Anupam; Chandak, Chander

    2013-01-01

    Making a reversible circuit fault-tolerant is much more difficult than classical circuit and there have been only a few works in the area of parity-preserving reversible logic design. Moreover, all of these designs are ad hoc, based on some pre-defined parity preserving reversible gates as building blocks. In this paper, we for the first time propose a novel and systematic approach towards parity preserving reversible circuits design. We provide some related theoretical results and give two a...

  15. A Study on Reverse Logistics

    OpenAIRE

    Reddy, Dhananjaya

    2011-01-01

    In the competitive world of manufacturing, companies are often searching for new ways to improve their process, customer satisfaction and stay ahead in the game with their competitors. Reverse logistics has been considered a strategy to bring these things to life for the past decade or so. This thesis work tries to shed some light on the basics of reverse logistics and how reverse logistics can be used as a management strategy. This paper points out the fundamentals of reverse logistics and l...

  16. Parity and time reversal violating nuclear polarizability

    OpenAIRE

    Flambaum, V. V.; Ginges, J. S. M.; Mititelu, G.

    2000-01-01

    We propose a nuclear mechanism which can induce an atomic electric dipole moment (EDM). Parity and time reversal violating (P,T-odd) nuclear forces generate a mixed P,T-odd nuclear polarizability beta_{ik} (defined by an energy shift U = -beta_{ik} E_{i}H_{k}, E is electric field and H magnetic field). The interaction of atomic electrons with beta_{ik} produces an atomic EDM. We performed an analytical calculation of the P,T-odd nuclear polarizability and estimated the value for the induced a...

  17. Reverse Engineering of RFID devices

    OpenAIRE

    Bokslag, Wouter

    2015-01-01

    This paper discusses the relevance and potential impact of both RFID and reverse engineering of RFID technology, followed by a discussion of common protocols and internals of RFID technology. The focus of the paper is on providing an overview of the different approaches to reverse engineering RFID technology and possible countermeasures that could limit the potential of such reverse engineering attempts.

  18. Reversible brazing process

    Science.gov (United States)

    Pierce, Jim D.; Stephens, John J.; Walker, Charles A.

    1999-01-01

    A method of reversibly brazing surfaces together. An interface is affixed to each surface. The interfaces can be affixed by processes such as mechanical joining, welding, or brazing. The two interfaces are then brazed together using a brazing process that does not defeat the surface to interface joint. Interfaces of materials such as Ni-200 can be affixed to metallic surfaces by welding or by brazing with a first braze alloy. The Ni-200 interfaces can then be brazed together using a second braze alloy. The second braze alloy can be chosen so that it minimally alters the properties of the interfaces to allow multiple braze, heat and disassemble, rebraze cycles.

  19. Reverse engineering SPARQL queries

    OpenAIRE

    Arenas, M; Diaz, GI; Kostylev, E

    2016-01-01

    Semantic Web systems provide open interfaces for end-users to access data via a powerful high-level query language, SPARQL. But users unfamiliar with either the details of SPARQL or properties of the target dataset may find it easier to query by example — give examples of the information they want (or examples of both what they want and what they do not want) and let the system reverse engineer the desired query from the examples. This approach has been heavily used in th...

  20. Reverse Engineering Malicious Applications

    Directory of Open Access Journals (Sweden)

    Ioan Cristian Iacob

    2015-06-01

    Full Text Available Detecting new and unknown malware is a major challenge in today’s software. Security profession. A lot of approaches for the detection of malware using data mining techniques have already been proposed. Majority of the works used static features of malware. However, static detection methods fall short of detecting present day complex malware. Although some researchers proposed dynamic detection methods, the methods did not use all the malware features. In this work, an approach for the detection of new and unknown malware was proposed and implemented. Each sample was reverse engineered for analyzing its effect on the operating environment and to extract the static and behavioral features.