WorldWideScience

Sample records for underlying mechanisms involved

  1. Coral bleaching under thermal stress: putative involvement of host/symbiont recognition mechanisms

    Directory of Open Access Journals (Sweden)

    Tambutte Sylvie

    2009-08-01

    Full Text Available Abstract Background Coral bleaching can be defined as the loss of symbiotic zooxanthellae and/or their photosynthetic pigments from their cnidarian host. This major disturbance of reef ecosystems is principally induced by increases in water temperature. Since the beginning of the 1980s and the onset of global climate change, this phenomenon has been occurring at increasing rates and scales, and with increasing severity. Several studies have been undertaken in the last few years to better understand the cellular and molecular mechanisms of coral bleaching but the jigsaw puzzle is far from being complete, especially concerning the early events leading to symbiosis breakdown. The aim of the present study was to find molecular actors involved early in the mechanism leading to symbiosis collapse. Results In our experimental procedure, one set of Pocillopora damicornis nubbins was subjected to a gradual increase of water temperature from 28°C to 32°C over 15 days. A second control set kept at constant temperature (28°C. The differentially expressed mRNA between the stressed states (sampled just before the onset of bleaching and the non stressed states (control were isolated by Suppression Subtractive Hybridization. Transcription rates of the most interesting genes (considering their putative function were quantified by Q-RT-PCR, which revealed a significant decrease in transcription of two candidates six days before bleaching. RACE-PCR experiments showed that one of them (PdC-Lectin contained a C-Type-Lectin domain specific for mannose. Immunolocalisation demonstrated that this host gene mediates molecular interactions between the host and the symbionts suggesting a putative role in zooxanthellae acquisition and/or sequestration. The second gene corresponds to a gene putatively involved in calcification processes (Pdcyst-rich. Its down-regulation could reflect a trade-off mechanism leading to the arrest of the mineralization process under stress

  2. Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity

    International Nuclear Information System (INIS)

    Cattani, Daiane; Oliveira Cavalli, Liz Vera Lúcia de; Heinz Rieg, Carla Elise; Domingues, Juliana Tonietto; Dal-Cim, Tharine; Tasca, Carla Inês; Mena Barreto Silva, Fátima Regina; Zamoner, Ariane

    2014-01-01

    Graphical abstract: - Highlights: • Roundup ® induces Ca 2+ influx through L-VDCC and NMDA receptor activation. • The mechanisms underlying Roundup ® neurotoxicity involve glutamatergic excitotoxicity. • Kinase pathways participate in Roundup ® -induced neural toxicity. • Roundup ® alters glutamate uptake, release and metabolism in hippocampal cells. - Abstract: Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neurotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. The aim of this study was to investigate whether Roundup ® (a glyphosate-based herbicide) leads to neurotoxicity in hippocampus of immature rats following acute (30 min) and chronic (pregnancy and lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally with 1% Roundup ® (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal slices from 15 day old rats were acutely exposed to Roundup ® (0.00005–0.1%) during 30 min and experiments were carried out to determine whether glyphosate affects 45 Ca 2+ influx and cell viability. Moreover, we investigated the pesticide effects on oxidative stress parameters, 14 C-α-methyl-amino-isobutyric acid ( 14 C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism. Results showed that acute exposure to Roundup ® (30 min) increases 45 Ca 2+ influx by activating NMDA receptors and voltage-dependent Ca 2+ channels, leading to oxidative stress and neural cell death. The mechanisms underlying Roundup ® -induced neurotoxicity also involve the activation of CaMKII and ERK. Moreover, acute exposure to Roundup ® increased 3 H-glutamate released into the synaptic cleft, decreased GSH content and increased the lipoperoxidation, characterizing excitotoxicity and oxidative damage. We also observed that both acute and chronic exposure to Roundup ® decreased 3 H-glutamate uptake and

  3. Phytochemicals in regulating fatty acid β-oxidation: Potential underlying mechanisms and their involvement in obesity and weight loss.

    Science.gov (United States)

    Rupasinghe, H P Vasantha; Sekhon-Loodu, Satvir; Mantso, Theodora; Panayiotidis, Mihalis I

    2016-09-01

    Excessive accumulation of fat as the result of more energy intake and less energy expenditure is known as obesity. Lipids are essential components in the human body and are vital for maintaining homeostasis and physiological as well as cellular metabolism. Fatty acid synthesis and catabolism (by fatty acid oxidation) are normal part of basic fuel metabolism in animals. Fatty acids are degraded in the mitochondria by a biochemical process called β-oxidation in which two-carbon fragments are produced in each cycle. The increase in fatty acid β-oxidation is negatively correlated with body mass index. Although healthy life style, avoiding Western diet, dieting and strenuous exercise are the commonly used methods to lose weight, they are not considered a permanent solution in addition to risk attenuation of basal metabolic rate (BMR). Pharmacotherapy offers benefits of weight loss by altering the satiety and lowering absorption of fat from the food; however, its side effects may outweigh the benefits of weight loss. Alternatively, dietary phytochemicals and natural health products offer great potential as an efficient weight loss strategy by modulating lipid metabolism and/or increasing BMR and thermogenesis. Specifically, polyphenols such as citrus flavonoids, green tea epigallocatechin gallate, resveratrol, capsaicin and curcumin, have been reported to increase lipolysis and induce fatty acid β-oxidation through modulation of hormone sensitive lipase, acetyl-coA carboxylase, carnitine acyl transferase and peroxisome proliferator-activated receptor gamma coactivator-1. In this review article, we discuss selected phytochemicals in relation to their integrated functionalities and specific mechanisms for weight loss. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Child abuse: underlying mechanisms

    OpenAIRE

    Martínez, Gladys S.

    2009-01-01

    Exposure to traumatic stress during childhood, in the form of abuse or neglect, is related to an increased vulnerability resulting in the development of several pathologies, this relation has been confi rmed by epidemiological studies; however, the neural mechanisms underlying such abnormalities are still unknown. Most of the research done has focused on the effects in the infant, and only recently it has begun to focus on the neurobiological changes in the abusive parents. In this article, I...

  5. IL-13 may be involved in the development of CAD via different mechanisms under different conditions in a Chinese Han population.

    Science.gov (United States)

    Zha, Ling-Feng; Nie, Shao-Fang; Chen, Qian-Wen; Liao, Yu-Hua; Zhang, Hong-Song; Dong, Jiang-Tao; Xie, Tian; Wang, Fan; Tang, Ting-Ting; Xia, Ni; Xu, Cheng-Qi; Zhou, Ying-Chao; Zeng, Zhi-Peng; Jiao, Jiao; Wang, Peng-Yun; Wang, Qing K; Tu, Xin; Cheng, Xiang

    2018-04-18

    Interleukin-13 (IL-13) has important functions in atherosclerosis, but its role in coronary artery disease (CAD) is unclear. Here, we studied the genetic role of IL-13 in CAD in a Chinese Han population using tag SNPs covering the whole IL13 gene (i.e., rs1881457, rs2069744 and rs20541) and a two-stage cohort containing 1863 CAD cases and 1841 controls. Traditional risk factors for CAD, such as age, BMI, and other factors, were used as covariates in logistic regression analysis. In the total population, we found that two haplotypes of IL13 (ATG and ATA, ordered rs1881457 C -rs2069744 T -rs20541 A ) significantly contributed to the risk of CAD with adjusted p values less than 0.05 (p adj  = 0.019 and p adj  = 0.042, respectively). In subgroup population analyses, the variant rs1881457 C was found to significantly contribute to a nearly two fold increase in the risk of CAD in men (p adj  = 0.023, OR = 1.91, 95% CI: 1.09-3.33). The variant rs1881457 C also significantly contributed to a nearly twofold risk of late-onset CAD (p adj  = 0.024, OR = 1.93, 95% CI: 1.09-3.42). In conclusion, IL13 might be involved in CAD via different mechanisms under different conditions in the Chinese Han population.

  6. Salvianolic Acid B inhibits platelet adhesion under conditions of flow by a mechanism involving the collagen receptor alpha 2 beta 1

    NARCIS (Netherlands)

    Wu, Ya Ping; Zhao, Xiao Min; Pan, Shao Dong; Guo, De An; Wei, Ran; Han, Ji Ju; Kainoh, Mie; Xia, Zuo Li; de Groot, Philip G.; Lisman, Ton

    2008-01-01

    Salvianolic acid B (SAB) is a component of Danshen, a herb widely used in Chinese medicine, and was previously shown to exert a number of biological activities including inhibition of platelet function, but the exact mechanisms involved are unclear. SAB dose-dependently inhibited platelet deposition

  7. Mechanisms underlying developmental changes in the expression of metabotropic glutamate receptors in cultured cerebellar granule cells: homologous desensitization and interactive effects involving N-methyl-D-aspartate receptors

    NARCIS (Netherlands)

    Aronica, E.; Dell'Albani, P.; Condorelli, D. F.; Nicoletti, F.; Hack, N.; Balázs, R.

    1993-01-01

    Glutamate receptors coupled to polyphosphoinositide (PPI) hydrolysis (metabotropic glutamate receptors, mGluR), are highly efficient during the early stages of postnatal life and are thought to be involved in developmental plasticity. The dramatic decrease with age in mGluR activity suggests the

  8. Underlying Mechanisms Affecting Institutionalisation of ...

    African Journals Online (AJOL)

    This paper discusses the underlying causal mechanisms that enabled or constrained institutionalisation of environmental education in 12 institutions in eight countries in southern Africa. The study was carried out in the context of the Southern Africa Development Community Regional Environmental Education Support ...

  9. Underlying Mechanisms Affecting Institutionalisation of ...

    African Journals Online (AJOL)

    doctoral study and draws on critical realism as the ontological lens. Data analysis was done by means of a retroductive mode of inference, as articulated by Danermark, Ekström, Jakosben and Karlsson (2002). The paper demonstrates that there are a number of underlying causal mechanisms, which may enable or.

  10. Molecular mechanisms underlying bacterial persisters

    DEFF Research Database (Denmark)

    Maisonneuve, Etienne; Gerdes, Kenn

    2014-01-01

    All bacteria form persisters, cells that are multidrug tolerant and therefore able to survive antibiotic treatment. Due to the low frequencies of persisters in growing bacterial cultures and the complex underlying molecular mechanisms, the phenomenon has been challenging to study. However, recent...

  11. Evidence for the involvement of hydraulic root or shoot adjustments as mechanisms underlying water deficit tolerance in two Sorghum bicolor genotypes.

    Science.gov (United States)

    Sutka, Moira R; Manzur, Milena E; Vitali, Victoria A; Micheletto, Sandra; Amodeo, Gabriela

    2016-03-15

    Sorghum bicolor (L.) Moench is an ancient drought-tolerant crop with potential to sustain high yields even in those environments where water is limiting. Understanding the performance of this species in early phenological stages could be a useful tool for future yield improvement programs. The aim of this work was to study the response of Sorghum seedlings under water deficit conditions in two genotypes (RedLandB2 and IS9530) that are currently employed in Argentina. Morphological and physiological traits were studied to present an integrated analysis of the shoot and root responses. Although both genotypes initially developed a conserved and indistinguishable response in terms of drought tolerance parameters (growth rate, biomass reallocation, etc.), water regulation displayed different underlying strategies. To avoid water loss, both genotypes adjusted their plant hydraulic resistance at different levels: RedLandB2 regulated shoot resistance through stomata (isohydric strategy), while IS9530 controlled root resistance (anisohydric strategy). Moreover, only in IS9530 was root hydraulic conductance restricted in the presence of HgCl2, in agreement with water movement through cell-to-cell pathways and aquaporins activity. The different responses between genotypes suggest a distinct strategy at the seedling stage and add new information that should be considered when evaluating Sorghum phenotypic plasticity in changing environments. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. Molecular mechanisms involved in the pathogenesis of septic shock.

    Science.gov (United States)

    López-Bojórquez, Lucia Nikolaia; Dehesa, Alejandro Zentella; Reyes-Terán, Gustavo

    2004-01-01

    Pathogenesis of the development of sepsis is highly complex and has been the object of study for many years. The inflammatory phenomena underlying septic shock are described in this review, as well as the enzymes and genes involved in the cellular activation that precedes this condition. The most important molecular aspects are discussed, ranging from the cytokines involved and their respective transduction pathways to the cellular mechanisms related to accelerated catabolism and multi-organic failure.

  13. Molecular Mechanisms Underlying Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Christian Trepo

    2009-11-01

    Full Text Available Hepatocarcinogenesis is a complex process that remains still partly understood. That might be explained by the multiplicity of etiologic factors, the genetic/epigenetic heterogeneity of tumors bulks and the ignorance of the liver cell types that give rise to tumorigenic cells that have stem cell-like properties. The DNA stress induced by hepatocyte turnover, inflammation and maybe early oncogenic pathway activation and sometimes viral factors, leads to DNA damage response which activates the key tumor suppressive checkpoints p53/p21Cip1 and p16INK4a/pRb responsible of cell cycle arrest and cellular senescence as reflected by the cirrhosis stage. Still obscure mechanisms, but maybe involving the Wnt signaling and Twist proteins, would allow pre-senescent hepatocytes to bypass senescence, acquire immortality by telomerase reactivation and get the last genetic/epigenetic hits necessary for cancerous transformation. Among some of the oncogenic pathways that might play key driving roles in hepatocarcinogenesis, c-myc and the Wnt/β-catenin signaling seem of particular interest. Finally, antiproliferative and apoptosis deficiencies involving TGF-β, Akt/PTEN, IGF2 pathways for instance are prerequisite for cancerous transformation. Of evidence, not only the transformed liver cell per se but the facilitating microenvironment is of fundamental importance for tumor bulk growth and metastasis.

  14. Neurobiological mechanisms involved in sleep bruxism.

    Science.gov (United States)

    Lavigne, G J; Kato, T; Kolta, A; Sessle, B J

    2003-01-01

    Sleep bruxism (SB) is reported by 8% of the adult population and is mainly associated with rhythmic masticatory muscle activity (RMMA) characterized by repetitive jaw muscle contractions (3 bursts or more at a frequency of 1 Hz). The consequences of SB may include tooth destruction, jaw pain, headaches, or the limitation of mandibular movement, as well as tooth-grinding sounds that disrupt the sleep of bed partners. SB is probably an extreme manifestation of a masticatory muscle activity occurring during the sleep of most normal subjects, since RMMA is observed in 60% of normal sleepers in the absence of grinding sounds. The pathophysiology of SB is becoming clearer, and there is an abundance of evidence outlining the neurophysiology and neurochemistry of rhythmic jaw movements (RJM) in relation to chewing, swallowing, and breathing. The sleep literature provides much evidence describing the mechanisms involved in the reduction of muscle tone, from sleep onset to the atonia that characterizes rapid eye movement (REM) sleep. Several brainstem structures (e.g., reticular pontis oralis, pontis caudalis, parvocellularis) and neurochemicals (e.g., serotonin, dopamine, gamma aminobutyric acid [GABA], noradrenaline) are involved in both the genesis of RJM and the modulation of muscle tone during sleep. It remains unknown why a high percentage of normal subjects present RMMA during sleep and why this activity is three times more frequent and higher in amplitude in SB patients. It is also unclear why RMMA during sleep is characterized by co-activation of both jaw-opening and jaw-closing muscles instead of the alternating jaw-opening and jaw-closing muscle activity pattern typical of chewing. The final section of this review proposes that RMMA during sleep has a role in lubricating the upper alimentary tract and increasing airway patency. The review concludes with an outline of questions for future research.

  15. Brain mechanisms underlying human communication

    NARCIS (Netherlands)

    Noordzij, M.L.; Newman-Norlund, S.E.; Ruiter, J.P.A. de; Hagoort, P.; Levinson, S.C.; Toni, I.

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the "mirror neurons system"). However, this view does not explain how these conventions could develop in the first place. Here we

  16. Brain mechanisms underlying human communication

    NARCIS (Netherlands)

    Noordzij, Matthijs Leendert; Newman-Norlund, Sarah E.; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C.; Toni, Ivan

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”). However, this view does not explain how these conventions could develop in the first place. Here we

  17. Molecular mechanisms involved in convergent crop domestication.

    Science.gov (United States)

    Lenser, Teresa; Theißen, Günter

    2013-12-01

    Domestication has helped to understand evolution. We argue that, vice versa, novel insights into evolutionary principles could provide deeper insights into domestication. Molecular analyses have demonstrated that convergent phenotypic evolution is often based on molecular changes in orthologous genes or pathways. Recent studies have revealed that during plant domestication the causal mutations for convergent changes in key traits are likely to be located in particular genes. These insights may contribute to defining candidate genes for genetic improvement during the domestication of new plant species. Such efforts may help to increase the range of arable crops available, thus increasing crop biodiversity and food security to help meet the predicted demands of the continually growing global population under rapidly changing environmental conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Juliana Pereira Borges

    2015-01-01

    Full Text Available Background: Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate. Objective: To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury. Methods: A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies. Results: The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review. Conclusion: On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions.

  19. Brain mechanisms underlying human communication

    Directory of Open Access Journals (Sweden)

    Matthijs L Noordzij

    2009-07-01

    Full Text Available Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”. However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender and recognizing the communicative intention of the same actions (by a receiver relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus. The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

  20. Metacognitive mechanisms underlying lucid dreaming.

    Science.gov (United States)

    Filevich, Elisa; Dresler, Martin; Brick, Timothy R; Kühn, Simone

    2015-01-21

    Lucid dreaming is a state of awareness that one is dreaming, without leaving the sleep state. Dream reports show that self-reflection and volitional control are more pronounced in lucid compared with nonlucid dreams. Mostly on these grounds, lucid dreaming has been associated with metacognition. However, the link to lucid dreaming at the neural level has not yet been explored. We sought for relationships between the neural correlates of lucid dreaming and thought monitoring. Human participants completed a questionnaire assessing lucid dreaming ability, and underwent structural and functional MRI. We split participants based on their reported dream lucidity. Participants in the high-lucidity group showed greater gray matter volume in the frontopolar cortex (BA9/10) compared with those in the low-lucidity group. Further, differences in brain structure were mirrored by differences in brain function. The BA9/10 regions identified through structural analyses showed increases in blood oxygen level-dependent signal during thought monitoring in both groups, and more strongly in the high-lucidity group. Our results reveal shared neural systems between lucid dreaming and metacognitive function, in particular in the domain of thought monitoring. This finding contributes to our understanding of the mechanisms enabling higher-order consciousness in dreams. Copyright © 2015 the authors 0270-6474/15/351082-07$15.00/0.

  1. Deciphering the Cognitive and Neural Mechanisms Underlying ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Deciphering the Cognitive and Neural Mechanisms Underlying Auditory Learning. This project seeks to understand the brain mechanisms necessary for people to learn to perceive sounds. Neural circuits and learning. The research team will test people with and without musical training to evaluate their capacity to learn ...

  2. On transport mechanisms in solar cells involving organic semiconductors

    OpenAIRE

    Nolasco Montaño, Jairo César

    2011-01-01

    The knowledge of transport mechanisms in solar cells is useful to determine electrical losses. In my doctoral thesis we studied the transport mechanisms in solar cells involving organic semiconductors. We show that models which have been used to study amorphous inorganic solar cells can be applied on organic ones. We conclude that: multitunelling capture emission and tunelling-enhanced interface recombination mechanisms contribute to the dark current characteristics in P3HT/Si, Pc/C60 and P3H...

  3. Observing the Forces Involved in Static Friction under Static Situations

    Science.gov (United States)

    Kaplan, Daniel

    2013-01-01

    Static friction is an important concept in introductory physics. Later in the year students apply their understanding of static friction under more complex conditions of static equilibrium. Traditional lab demonstrations in this case involve exceeding of the maximum level of static friction, resulting in the "onset of motion." (Contains…

  4. Mechanical buckling of artery under pulsatile pressure.

    Science.gov (United States)

    Liu, Qin; Han, Hai-Chao

    2012-04-30

    Tortuosity that often occurs in carotid and other arteries has been shown to be associated with high blood pressure, atherosclerosis, and other diseases. However the mechanisms of tortuosity development are not clear. Our previous studies have suggested that arteries buckling could be a possible mechanism for the initiation of tortuous shape but artery buckling under pulsatile flow condition has not been fully studied. The objectives of this study were to determine the artery critical buckling pressure under pulsatile pressure both experimentally and theoretically, and to elucidate the relationship of critical pressures under pulsatile flow, steady flow, and static pressure. We first tested the buckling pressures of porcine carotid arteries under these loading conditions, and then proposed a nonlinear elastic artery model to examine the buckling pressures under pulsatile pressure conditions. Experimental results showed that under pulsatile pressure arteries buckled when the peak pressures were approximately equal to the critical buckling pressures under static pressure. This was also confirmed by model simulations at low pulse frequencies. Our results provide an effective tool to predict artery buckling pressure under pulsatile pressure. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Molecular mechanisms involved in taste learning and memory

    Directory of Open Access Journals (Sweden)

    Andrés Molero-Chamizo

    2017-09-01

    Full Text Available Taste learning, and particularly conditioned taste aversion (CTA, is an adaptive learning involving complex brain mechanisms and molecular pathways. Taste learning and CTA are critical behaviors for survival, and the knowledge of the molecular bases involved in the acquisition, retention and extinction of CTA can help to understand the brain mechanisms of normal and altered taste learning. The aim of this review is to describe recent findings on the molecular mechanisms of taste learning, from the genetic, receptors, and intracellular and extracellular signaling biological levels. We can conclude that some molecular pathways and processes for the acquisition of taste learning and the formation of taste memories are well identified. However, new molecular, neurobiological and behavioral studies are needed to thoroughly elucidate the complexity of the taste system and the neural mechanisms of CTA.

  6. Amorphization of ice under mechanical stresses

    Science.gov (United States)

    Bordonskii, G. S.; Krylov, S. D.

    2017-11-01

    The dielectric parameters of freshly produced freshwater ice in the microwave range are investigated. It is established that this kind of ice contains a noticeable amount of amorphous ice. Its production is associated with plastic deformation under mechanical stresses. An assessment of the dielectric-permeability change caused by amorphous ice in the state of a slowly flowing medium is given.

  7. Gas Bubble Dynamics under Mechanical Vibrations

    Science.gov (United States)

    Mohagheghian, Shahrouz; Elbing, Brian

    2017-11-01

    The scientific community has a limited understanding of the bubble dynamics under mechanical oscillations due to over simplification of Navier-Stockes equation by neglecting the shear stress tensor and not accounting for body forces when calculating the acoustic radiation force. The current work experimental investigates bubble dynamics under mechanical vibration and resulting acoustic field by measuring the bubble size and velocity using high-speed imaging. The experimental setup consists of a custom-designed shaker table, cast acrylic bubble column, compressed air injection manifold and an optical imaging system. The mechanical vibrations resulted in accelerations between 0.25 to 10 times gravitational acceleration corresponding to frequency and amplitude range of 8 - 22Hz and 1 - 10mm respectively. Throughout testing the void fraction was limited to definition of Bjerknes force in combination with Rayleigh-Plesset equation. Physical behavior of the system was capture and classified. Bubble size, velocity as well as size and spatial distribution will be presented.

  8. DNA under Force: Mechanics, Electrostatics, and Hydration

    Directory of Open Access Journals (Sweden)

    Jingqiang Li

    2015-02-01

    Full Text Available Quantifying the basic intra- and inter-molecular forces of DNA has helped us to better understand and further predict the behavior of DNA. Single molecule technique elucidates the mechanics of DNA under applied external forces, sometimes under extreme forces. On the other hand, ensemble studies of DNA molecular force allow us to extend our understanding of DNA molecules under other forces such as electrostatic and hydration forces. Using a variety of techniques, we can have a comprehensive understanding of DNA molecular forces, which is crucial in unraveling the complex DNA functions in living cells as well as in designing a system that utilizes the unique properties of DNA in nanotechnology.

  9. Epigenetic mechanisms underlying nervous system diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2018-01-01

    Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing. These mechanisms are intimately involved in executing fundamental genomic programs, including gene transcription, posttranscriptional RNA processing and transport, translation, X-chromosome inactivation, genomic imprinting, retrotransposon regulation, DNA replication, and DNA repair and the maintenance of genomic stability. For the nervous system, epigenetics offers a novel and robust framework for explaining how brain development and aging occur, neural cellular diversity is generated, synaptic and neural network connectivity and plasticity are mediated, and complex cognitive and behavioral phenotypes are inherited transgenerationally. Epigenetic factors and processes are, not surprisingly, implicated in nervous system disease pathophysiology through several emerging paradigms - mutations and genetic variation in genes encoding epigenetic factors; impairments in epigenetic factor expression, localization, and function; epigenetic mechanisms modulating disease-associated factors and pathways; and the presence of deregulated epigenetic profiles in central and peripheral tissues. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. [Ocular involvement in spondylarthritis--new mechanisms, new therapies].

    Science.gov (United States)

    Itulescu, T C M; Alexandrescu, Cristina; Voinea, Liliana-Mary

    2014-01-01

    Spondyloarthrites (SPA) represent a group of heterogenous rheumatic diseases (ankylosing spondylitis/SA, psoriatic arthritis/PsA, reactive arthritis/ReA, spondyloarthritis in bowel inflammatory diseases/BID, undifferentiated spondyloarthritis/undif SpA) with distinct clinical features and common genetic predisposition (HLA-B27). SpA may also affect other organs, ocular involvement, represented by uveitis and conjunctivitis, being one of the most important extraskeletal manifestations. Pathogenic mechanisms of ocular involment in SpA are not entirely known; nevertheless, the inflammatory process which characterizes the main rheumatic diseases seems to be responsible for this extraskeletal manifestation. SpA treatment targeted at clinical remission has a favourable effect not only on articular but also on ocular involvement. The discovery of new pathogenic mechanisms of both rheumatic and eye disease in SpA have contributed to identification of new pathogenic therapies. The interdisciplinary team work of rheumatologists and ophtalmologists have prove essential for the management of SpA patients with ocular manifestations.

  11. Evolved Mechanisms Versus Underlying Conditional Relations

    Directory of Open Access Journals (Sweden)

    Astorga Miguel López

    2015-03-01

    Full Text Available The social contracts theory claims that, in social exchange circumstances, human reasoning is not necessarily led by logic, but by certain evolved mental mechanisms that are useful for catching offenders. An emblematic experiment carried out with the intention to prove this thesis is the first experiment described by Fiddick, Cosmides, and Tooby in their paper of 2000. Lopez Astorga has questioned that experiment claiming that its results depend on an underlying conditional logical form not taken into account by Fiddick, Cosmides, and Tooby. In this paper, I propose an explanation alternative to that of Lopez Astorga, which does not depend on logical forms and is based on the mental models theory. Thus, I conclude that this other alternative explanation is one more proof that the experiment in question does not demonstrate the fundamental thesis of the social contracts theory.

  12. Mechanisms underlying UV-induced immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Ullrich, Stephen E. [Department of Immunology, University of Texas, MD Anderson Cancer Center, South Campus Research Building 1, 7455 Fannin St., P.O. Box 301402, Houston, TX 77030-1903 (United States)]. E-mail: sullrich@mdanderson.org

    2005-04-01

    Skin cancer is the most prevalent form of human neoplasia. Estimates suggest that in excess of one million new cases of skin cancer will be diagnosed this year alone in the United States (www.cancer.org/statistics). Fortunately, because of their highly visible location, skin cancers are more rapidly diagnosed and more easily treated than other types of cancer. Be that as it may, approximately 10,000 Americans a year die from skin cancer. The cost of treating non-melanoma skin cancer is estimated to be in excess of US$ 650 million a year [J.G. Chen, A.B. Fleischer, E.D. Smith, C. Kancler, N.D. Goldman, P.M. Williford, S.R. Feldman, Cost of non-melanoma skin cancer treatment in the United States, Dermatol. Surg. 27 (2001) 1035-1038], and when melanoma is included, the estimated cost of treating skin cancer in the United States is estimated to rise to US$ 2.9 billion annually (www.cancer.org/statistics). Because the morbidity and mortality associated with skin cancer is a major public health problem, it is important to understand the mechanisms underlying skin cancer development. The primary cause of skin cancer is the ultraviolet (UV) radiation found in sunlight. In addition to its carcinogenic potential, UV radiation is also immune suppressive. In fact, data from studies with both experimental animals and biopsy proven skin cancer patients suggest that there is an association between the immune suppressive effects of UV radiation and its carcinogenic potential. The focus of this manuscript will be to review the mechanisms underlying the induction of immune suppression following UV exposure. Particular attention will be directed to the role of soluble mediators in activating immune suppression.

  13. Mechanisms underlying UV-induced immune suppression

    International Nuclear Information System (INIS)

    Ullrich, Stephen E.

    2005-01-01

    Skin cancer is the most prevalent form of human neoplasia. Estimates suggest that in excess of one million new cases of skin cancer will be diagnosed this year alone in the United States (www.cancer.org/statistics). Fortunately, because of their highly visible location, skin cancers are more rapidly diagnosed and more easily treated than other types of cancer. Be that as it may, approximately 10,000 Americans a year die from skin cancer. The cost of treating non-melanoma skin cancer is estimated to be in excess of US$ 650 million a year [J.G. Chen, A.B. Fleischer, E.D. Smith, C. Kancler, N.D. Goldman, P.M. Williford, S.R. Feldman, Cost of non-melanoma skin cancer treatment in the United States, Dermatol. Surg. 27 (2001) 1035-1038], and when melanoma is included, the estimated cost of treating skin cancer in the United States is estimated to rise to US$ 2.9 billion annually (www.cancer.org/statistics). Because the morbidity and mortality associated with skin cancer is a major public health problem, it is important to understand the mechanisms underlying skin cancer development. The primary cause of skin cancer is the ultraviolet (UV) radiation found in sunlight. In addition to its carcinogenic potential, UV radiation is also immune suppressive. In fact, data from studies with both experimental animals and biopsy proven skin cancer patients suggest that there is an association between the immune suppressive effects of UV radiation and its carcinogenic potential. The focus of this manuscript will be to review the mechanisms underlying the induction of immune suppression following UV exposure. Particular attention will be directed to the role of soluble mediators in activating immune suppression

  14. Two distinct neural mechanisms underlying indirect reciprocity.

    Science.gov (United States)

    Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

    2014-03-18

    Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards.

  15. Numerical and Experimental Study of Mechanisms Involved in Boiling Histotripsy.

    Science.gov (United States)

    Pahk, Ki Joo; Gélat, Pierre; Sinden, David; Dhar, Dipok Kumar; Saffari, Nader

    2017-12-01

    The aim of boiling histotripsy is to mechanically fractionate tissue as an alternative to thermal ablation for therapeutic applications. In general, the shape of a lesion produced by boiling histotripsy is tadpole like, consisting of a head and a tail. Although many studies have demonstrated the efficacy of boiling histotripsy for fractionating solid tumors, the exact mechanisms underpinning this phenomenon are not yet well understood, particularly the interaction of a boiling vapor bubble with incoming incident shockwaves. To investigate the mechanisms involved in boiling histotripsy, a high-speed camera with a passive cavitation detection system was used to observe the dynamics of bubbles produced in optically transparent tissue-mimicking gel phantoms exposed to the field of a 2.0-MHz high-intensity focused ultrasound (HIFU) transducer. We observed that boiling bubbles were generated in a localized heated region and cavitation clouds were subsequently induced ahead of the expanding bubble. This process was repeated with HIFU pulses and eventually resulted in a tadpole-shaped lesion. A simplified numerical model describing the scattering of the incident ultrasound wave by a vapor bubble was developed to help interpret the experimental observations. Together with the numerical results, these observations suggest that the overall size of a lesion induced by boiling histotripsy is dependent on the sizes of (i) the heated region at the HIFU focus and (ii) the backscattered acoustic field by the original vapor bubble. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  16. Complement involvement in periodontitis: molecular mechanisms and rational therapeutic approaches

    Science.gov (United States)

    Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D.

    2015-01-01

    The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis. PMID:26306443

  17. Quantum-Mechanical Calculations on Molecular Substructures Involved in Nanosystems

    Directory of Open Access Journals (Sweden)

    Beata Szefler

    2014-09-01

    Full Text Available In this review article, four ideas are discussed: (a aromaticity of fullerenes patched with flowers of 6-and 8-membered rings, optimized at the HF and DFT levels of theory, in terms of HOMA and NICS criteria; (b polybenzene networks, from construction to energetic and vibrational spectra computations; (c quantum-mechanical calculations on the repeat units of various P-type crystal networks and (d construction and stability evaluation, at DFTB level of theory, of some exotic allotropes of diamond D5, involved in hyper-graphenes. The overall conclusion was that several of the yet hypothetical molecular nanostructures herein described are serious candidates to the status of real molecules.

  18. Dissociable cognitive mechanisms underlying human path integration.

    Science.gov (United States)

    Wiener, Jan M; Berthoz, Alain; Wolbers, Thomas

    2011-01-01

    Path integration is a fundamental mechanism of spatial navigation. In non-human species, it is assumed to be an online process in which a homing vector is updated continuously during an outward journey. In contrast, human path integration has been conceptualized as a configural process in which travelers store working memory representations of path segments, with the computation of a homing vector only occurring when required. To resolve this apparent discrepancy, we tested whether humans can employ different path integration strategies in the same task. Using a triangle completion paradigm, participants were instructed either to continuously update the start position during locomotion (continuous strategy) or to remember the shape of the outbound path and to calculate home vectors on basis of this representation (configural strategy). While overall homing accuracy was superior in the configural condition, participants were quicker to respond during continuous updating, strongly suggesting that homing vectors were computed online. Corroborating these findings, we observed reliable differences in head orientation during the outbound path: when participants applied the continuous updating strategy, the head deviated significantly from straight ahead in direction of the start place, which can be interpreted as a continuous motor expression of the homing vector. Head orientation-a novel online measure for path integration-can thus inform about the underlying updating mechanism already during locomotion. In addition to demonstrating that humans can employ different cognitive strategies during path integration, our two-systems view helps to resolve recent controversies regarding the role of the medial temporal lobe in human path integration.

  19. Mechanics of carbon nanotube scission under sonication.

    Science.gov (United States)

    Stegen, J

    2014-06-28

    As-produced carbon nanotubes come in bundles that must be exfoliated for practical applications in nanocomposites. Sonication not only causes the exfoliation of nanotube bundles but also unwanted scission. An understanding of how precisely sonication induces the scission and exfoliation of nanotubes will help maximising the degree of exfoliation while minimising scission. We present a theoretical study of the mechanics of carbon nanotube scission under sonicaton, based on the accepted view that it is caused by strong gradients in the fluid velocity near a transiently collapsing bubble. We calculate the length-dependent scission rate by taking the actual movement of the nanotube during the collapse of a bubble into account, allowing for the prediction of the temporal evolution of the length distribution of the nanotubes. We show that the dependence of the scission rate on the sonication settings and the nanotube properties results in non-universal, experiment-dependent scission kinetics potentially explaining the variety in experimentally observed scission kinetics. The non-universality arises from the dependence of the maximum strain rate of the fluid experienced by a nanotube on its length. The maximum strain rate that a nanotube experiences increases with decreasing distance to the bubble. As short nanotubes are dragged along more easily by the fluid flow they experience a higher maximum strain rate than longer nanotubes. This dependence of the maximum strain rate on nanotube length affects the scaling of tensile strength with terminal length. We find that the terminal length scales with tensile strength to the power of 1/1.16 instead of with an exponent of 1/2 as found when nanotube motion is neglected. Finally, we show that the mechanism we propose responsible for scission can also explain the exfoliation of carbon nanotube bundles.

  20. Mechanisms involved in the antiplatelet effect of C-phycocyanin.

    Science.gov (United States)

    Chiu, Hui-Fen; Yang, Shih-Ping; Kuo, Yu-Ling; Lai, Yuan-Shu; Chou, Tz-Chong

    2006-02-01

    C-phycocyanin (cpc), a biliprotein isolated from Spirulina platensis, has been reported to exert many therapeutic and nutritional values. In the present study, we examined whether cpc has an antiplatelet activity in vitro and further investigated the possible anti-aggregatory mechanisms involved. Our results showed that preincubation of cpc (1-50 microg/ml) with rabbit washed platelets dose-dependently inhibited the platelet aggregation induced by collagen (10 microg/ml) or arachidonic acid (100 microm), with an IC50 of about 10 microg/ml. Furthermore, the thromboxane B2 formation caused by collagen or arachidonic acid was significantly inhibited by cpc due to suppression of cyclooxygenase and thromboxane synthase activity. Similarly, the rise of platelet intracellular calcium level stimulated by arachidonic acid and collagen-induced platelet membrane surface glycoprotein IIb/IIIa expression were also attenuated by cpc. In addition, cpc itself significantly increased the platelet membrane fluidity and the cyclic AMP level through inhibiting cyclic AMP phosphodiesterase activity. These findings strongly demonstrate that cpc is an inhibitor of platelet aggregation, which may be associated with mechanisms including inhibition of thromboxane A2 formation, intracellular calcium mobilization and platelet surface glycoprotein IIb/IIIa expression accompanied by increasing cyclic AMP formation and platelet membrane fluidity.

  1. Vascular Adventitia Calcification and Its Underlying Mechanism.

    Directory of Open Access Journals (Sweden)

    Na Li

    Full Text Available Previous research on vascular calcification has mainly focused on the vascular intima and media. However, we show here that vascular calcification may also occur in the adventitia. The purpose of this work is to help elucidate the pathogenic mechanisms underlying vascular calcification. The calcified lesions were examined by Von Kossa staining in ApoE-/- mice which were fed high fat diets (HFD for 48 weeks and human subjects aged 60 years and older that had died of coronary heart disease, heart failure or acute renal failure. Explant cultured fibroblasts and smooth muscle cells (SMCswere obtained from rat adventitia and media, respectively. After calcification induction, cells were collected for Alizarin Red S staining. Calcified lesions were observed in the aorta adventitia and coronary artery adventitia of ApoE-/-mice, as well as in the aorta adventitia of human subjects examined. Explant culture of fibroblasts, the primary cell type comprising the adventitia, was successfully induced for calcification after incubation with TGF-β1 (20 ng/ml + mineralization media for 4 days, and the phenotype conversion vascular adventitia fibroblasts into myofibroblasts was identified. Culture of SMCs, which comprise only a small percentage of all cells in the adventitia, in calcifying medium for 14 days resulted in significant calcification.Vascular calcification can occur in the adventitia. Adventitia calcification may arise from the fibroblasts which were transformed into myofibroblasts or smooth muscle cells.

  2. Proteoglycans remodeling in cancer: Underlying molecular mechanisms.

    Science.gov (United States)

    Theocharis, Achilleas D; Karamanos, Nikos K

    2017-11-08

    Extracellular matrix is a highly dynamic macromolecular network. Proteoglycans are major components of extracellular matrix playing key roles in its structural organization and cell signaling contributing to the control of numerous normal and pathological processes. As multifunctional molecules, proteoglycans participate in various cell functions during morphogenesis, wound healing, inflammation and tumorigenesis. Their interactions with matrix effectors, cell surface receptors and enzymes enable them with unique properties. In malignancy, extensive remodeling of tumor stroma is associated with marked alterations in proteoglycans' expression and structural variability. Proteoglycans exert diverse functions in tumor stroma in a cell-specific and context-specific manner and they mainly contribute to the formation of a permissive provisional matrix for tumor growth affecting tissue organization, cell-cell and cell-matrix interactions and tumor cell signaling. Proteoglycans also modulate cancer cell phenotype and properties, the development of drug resistance and tumor stroma angiogenesis. This review summarizes the proteoglycans remodeling and their novel biological roles in malignancies with particular emphasis to the underlying molecular mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Temporomandibular disorders and painful comorbidities: clinical association and underlying mechanisms.

    Science.gov (United States)

    Costa, Yuri Martins; Conti, Paulo César Rodrigues; de Faria, Flavio Augusto Cardoso; Bonjardim, Leonardo Rigoldi

    2017-03-01

    The association between temporomandibular disorders (TMDs) and headaches, cervical spine dysfunction, and fibromyalgia is not artefactual. The aim of this review is to describe the comorbid relationship between TMD and these three major painful conditions and to discuss the clinical implications and the underlying pain mechanisms involved in these relationships. Common neuronal pathways and central sensitization processes are acknowledged as the main factors for the association between TMD and primary headaches, although the establishment of cause-effect mechanisms requires further clarification and characterization. The biomechanical aspects are not the main factors involved in the comorbid relationship between TMD and cervical spine dysfunction, which can be better explained by the neuronal convergence of the trigeminal and cervical spine sensory pathways as well as by central sensitization processes. The association between TMD and fibromyalgia also has supporting evidence in the literature, and the proposed main mechanism underlying this relationship is the impairment of the descending pain inhibitory system. In this particular scenario, a cause-effect relationship is more likely to occur in one direction, that is, fibromyalgia as a risk factor for TMD. Therefore, clinical awareness of the association between TMD and painful comorbidities and the support of multidisciplinary approaches are required to recognize these related conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Mechanical behaviour of nuclear fuel under irradiation

    International Nuclear Information System (INIS)

    Guerin, Y.

    1985-01-01

    The main mechanical properties (fracture, thermal and irradiation creep) of oxide and carbide fuels are summarised and discussed. Some examples are given of the influence of these mechanical properties on the in-pile behaviour of fuel pins [fr

  5. Mechanisms and factors involved in hip injuries during frontal crashes.

    Science.gov (United States)

    Yoganandan, N; Pintar, F A; Gennarelli, T A; Maltese, M R; Eppinger, R H

    2001-11-01

    This study was conducted to collect data and gain insights relative to the mechanisms and factors involved in hip injuries during frontal crashes and to study the tolerance of hip injuries from this type of loading. Unembalmed human cadavers were seated on a standard automotive seat (reinforced) and subjected to knee impact test to each lower extremity. Varying combinations of flexion and adduction/abduction were used for initial alignment conditions and pre-positioning. Accelerometers were fixed to the iliac wings and twelfth thoracic vertebral spinous process. A 23.4-kg padded pendulum impacted the knee at velocities ranging from 4.3 to 7.6 m/s. The impacting direction was along the anteroposterior axis, i.e., the global X-axis, in the body-fixed coordinate system. A load cell on the front of the pendulum recorded the impact force. Peak impact forces ranged from 2,450 to 10,950 N. The rate of loading ranged from 123 to 7,664 N/msec. The impulse values ranged from 12.4 to 31.9 Nsec. Injuries were not apparent in three tests. Eight tests resulted in trauma. Fractures involving the pelvis including the acetabulum and proximal femur occurred in five out of the eight tests, and distal femoral bone fracture occurred in one test. These results underscore the importance of leg pre-positioning and the orientation of the impacting axis to produce specific types of trauma to the pelvic region of the lower extremity.

  6. Mechanisms involved in BACE upregulation associated to stress.

    Science.gov (United States)

    Martisova, Eva; Solas, Maite; Gerenu, Gorka; Milagro, Fermin I; Campion, Javier; Ramirez, Maria J

    2012-09-01

    The objective of the present work was to study a purported involvement of stress in amyloid pathology through the modulation of BACE expression. Early-life stressed rats (maternal separation, MS) showed significant increases in corticosterone levels, BACE expression and Aβ levels. The CpG7 site of the BACE promoter was significantly hypomethylated in MS, and corticosterone levels negatively correlated to the methylation status of CpG7. The activation of the stress-activated protein kinase JNK was also increased in MS rats. In SHSY-5Y neuroblastoma cells, corticosterone induced a rapid increase in BACE expression that was abolished by specific inhibiton of JNK activation or by spironolactone, a mineralocorticoid receptor antagonist, but not by mifepristone, a glucocorticoid receptor antagonist. Corticosterone was also able to increase pJNK expression and this effect was fully reverted by spironolactone. Mice chronically treated with corticosterone showed increased BACE and pJNK expression. These increases were reverted by treatment with spironolactone or with a JNK inhibitor. It is suggested that increased corticosterone levels associated to stress lead to increase BACE transcription both through epigenetic mechanisms and activation of JNK.

  7. Mechanical Design of AM Fabricated Prismatic Rods under Torsion

    Directory of Open Access Journals (Sweden)

    Manzhirov Alexander V.

    2017-01-01

    Full Text Available We study the stress-strain state of viscoelastic prismatic rods fabricated or repaired by additive manufacturing technologies under torsion. An adequate description of the processes involved is given by methods of a new scientific field, mechanics of growing solids. Three main stages of the deformation process (before the beginning of growth, in the course of growth, and after the termination of growth are studied. Two versions of statement of two problems are given: (i given the torque, find the stresses, displacements, and torsion; (ii given the torsion, find the stresses, displacements, and torque. Solution methods using techniques of complex analysis are presented. The results can be used in mechanical and instrument engineering.

  8. Factors Involved in Sludge Granulation under Anaerobic Conditions

    Directory of Open Access Journals (Sweden)

    Jalal Shayegan

    2011-03-01

    Full Text Available This paper investigates the effects of factors involved in sludge anaerobic granulation. Granulated sludge formation is the main parameter contributing to the success of UASB reactors. Anaerobic granulation leads to reduced reactor size, space requirement, and investment costs. Operation costs are also greatly reduced due to lack of aeration. An important parameter affecting process performance is the size of sludge granules; the factors involved in granule size will be investigated. Some of the important parameters of anaerobic sludge granulation are: existence of growth cores as inert particles or granulated sludge, process operational conditions (Sludge Loading Rate and Organic Loading Rate, Loading rate increase and …, and environment conditions (nutrients, temperature, pH, combination and ….

  9. Autophagy as a Possible Underlying Mechanism of Nanomaterial Toxicity

    Directory of Open Access Journals (Sweden)

    Vanessa Cohignac

    2014-07-01

    Full Text Available The rapid development of nanotechnologies is raising safety concerns because of the potential effects of engineered nanomaterials on human health, particularly at the respiratory level. Since the last decades, many in vivo studies have been interested in the pulmonary effects of different classes of nanomaterials. It has been shown that some of them can induce toxic effects, essentially depending on their physico-chemical characteristics, but other studies did not identify such effects. Inflammation and oxidative stress are currently the two main mechanisms described to explain the observed toxicity. However, the exact underlying mechanism(s still remain(s unknown and autophagy could represent an interesting candidate. Autophagy is a physiological process in which cytoplasmic components are digested via a lysosomal pathway. It has been shown that autophagy is involved in the pathogenesis and the progression of human diseases, and is able to modulate the oxidative stress and pro-inflammatory responses. A growing amount of literature suggests that a link between nanomaterial toxicity and autophagy impairment could exist. In this review, we will first summarize what is known about the respiratory effects of nanomaterials and we will then discuss the possible involvement of autophagy in this toxicity. This review should help understand why autophagy impairment could be taken as a promising candidate to fully understand nanomaterials toxicity.

  10. The mechanism underlying fast germination of tomato cultivar LA2711.

    Science.gov (United States)

    Yang, Rongchao; Chu, Zhuannan; Zhang, Haijun; Li, Ying; Wang, Jinfang; Li, Dianbo; Weeda, Sarah; Ren, Shuxin; Ouyang, Bo; Guo, Yang-Dong

    2015-09-01

    Seed germination is important for early plant morphogenesis as well as abiotic stress tolerance, and is mainly controlled by the phytohormones abscisic acid (ABA) and gibberellic acid (GA). Our previous studies identified a salt-tolerant tomato cultivar, LA2711, which is also a fast-germinating genotype, compared to its salt-sensitive counterpart, ZS-5. In an effort to further clarify the mechanism underlying this phenomenon, we compared the dynamic levels of ABA and GA4, the transcript abundance of genes involved in their biosynthesis and catabolism as well as signal transduction between the two cultivars. In addition, we tested seed germination sensitivity to ABA and GAs. Our results revealed that insensitivity of seed germination to exogenous ABA and low ABA content in seeds are the physiological mechanisms conferring faster germination rates of LA2711 seeds. SlCYP707A2, which encodes an ABA catabolic enzyme, may play a decisive role in the fast germination rate of LA2711, as it showed a significantly higher level of expression in LA2711 than ZS-5 at most time points tested during germination. The current results will enable us to gain insight into the mechanism(s) regarding seed germination of tomato and the role of fast germination in stress tolerance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Mechanisms underlying stage-1 TRPL channel translocation in Drosophila photoreceptors.

    Directory of Open Access Journals (Sweden)

    Minh-Ha Lieu

    Full Text Available TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere, TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels.We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content.Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protein transport, and not degradation/re-synthesis. Re-localization from each stage to the rhabdomere likely involves different strategies. Since TRPL channels can translocate to stage-1 in the absence of ATP, with no major requirement of the cytoskeleton, we suggest that stage-1 translocation involves simple diffusion through the apical membrane, which may be regulated by release of a light-dependent anchor in the rhabdomere.

  12. An investigation into the mechanism underlying enhanced ...

    African Journals Online (AJOL)

    The solubilisation of primary sewage sludge under sulphate reducing conditions was conducted in controlled flask studies and previously reported findings of enhanced hydrolysis were confirmed. The maximum percentage solubilisation obtained in this study over a 10-day period was 31% and 64% for the methanogenic ...

  13. Supersymmetric quantum mechanics under point singularities

    International Nuclear Information System (INIS)

    Uchino, Takashi; Tsutsui, Izumi

    2003-01-01

    We provide a systematic study on the possibility of supersymmetry (SUSY) for one-dimensional quantum mechanical systems consisting of a pair of lines R or intervals [-l, l] each having a point singularity. We consider the most general singularities and walls (boundaries) at x = ±l admitted quantum mechanically, using a U(2) family of parameters to specify one singularity and similarly a U(1) family of parameters to specify one wall. With these parameter freedoms, we find that for a certain subfamily the line systems acquire an N = 1 SUSY which can be enhanced to N = 4 if the parameters are further tuned, and that these SUSY are generically broken except for a special case. The interval systems, on the other hand, can accommodate N = 2 or N = 4 SUSY, broken or unbroken, and exhibit a rich variety of (degenerate) spectra. Our SUSY systems include the familiar SUSY systems with the Dirac δ(x)-potential, and hence are extensions of the known SUSY quantum mechanics to those with general point singularities and walls. The self-adjointness of the supercharge in relation to the self-adjointness of the Hamiltonian is also discussed

  14. Neural mechanisms and models underlying joint action.

    Science.gov (United States)

    Chersi, Fabian

    2011-06-01

    Humans, in particular, and to a lesser extent also other species of animals, possess the impressive capability of smoothly coordinating their actions with those of others. The great amount of work done in recent years in neuroscience has provided new insights into the processes involved in joint action, intention understanding, and task sharing. In particular, the discovery of mirror neurons, which fire both when animals execute actions and when they observe the same actions done by other individuals, has shed light on the intimate relationship between perception and action elucidating the direct contribution of motor knowledge to action understanding. Up to date, however, a detailed description of the neural processes involved in these phenomena is still mostly lacking. Building upon data from single neuron recordings in monkeys observing the actions of a demonstrator and then executing the same or a complementary action, this paper describes the functioning of a biologically constraint neural network model of the motor and mirror systems during joint action. In this model, motor sequences are encoded as independent neuronal chains that represent concatenations of elementary motor acts leading to a specific goal. Action execution and recognition are achieved through the propagation of activity within specific chains. Due to the dual property of mirror neurons, the same architecture is capable of smoothly integrating and switching between observed and self-generated action sequences, thus allowing to evaluate multiple hypotheses simultaneously, understand actions done by others, and to respond in an appropriate way.

  15. Polymers under mechanical stress- an NMR investigation

    Energy Technology Data Exchange (ETDEWEB)

    Boehme, Ute; Scheler, Ulrich [Leibniz Institute of Polymer Research Dresden (Germany); Xu, Bo; Leisen, Johannes; Beckham, Haskell W. [Georgia Institute of Technology, Atlanta, Georgia (United States)

    2010-07-01

    Low-field NMR using permanent magnets in Halbach arrangements permit NMR investigation without the limits present in high-field NMR. The lower field in conjunction with confined stray field permit the application of NMR, in particular relaxation NMR in a stretching apparatus and a rheometer. Crystalline and amorphous fraction of semi-crystalline polymers are distinguished by their transverse relaxation times. Upon mechanical load the relaxation times of the amorphous fraction changes as seen in in-situ measurements on polypropylene rods. During the formation of a neck the crystalline fraction becomes more prominent.

  16. Mechanisms Underlying Sex Differences in Cannabis Use.

    Science.gov (United States)

    Calakos, Katina C; Bhatt, Shivani; Foster, Dawn W; Cosgrove, Kelly P

    2017-12-01

    Cannabis is the most commonly used illicit substance worldwide. In recent decades, highly concentrated products have flooded the market, and prevalence rates have increased. Gender differences exist in cannabis use, as men have higher prevalence of both cannabis use and cannabis use disorder (CUD), while women progress more rapidly from first use to CUD. This paper reviews findings from preclinical and human studies examining the sex-specific neurobiological underpinnings of cannabis use and CUD, and associations with psychiatric symptoms. Sex differences exist in the endocannabinoid system, in cannabis exposure effects on brain structure and function, and in the co-occurrence of cannabis use with symptoms of anxiety, depression and schizophrenia. In female cannabis users, anxiety symptoms correlate with larger amygdala volume and social anxiety disorder symptoms correlate with CUD symptoms. Female cannabis users are reported to be especially vulnerable to earlier onset of schizophrenia, and mixed trends emerge in the correlation of depressive symptoms with cannabis exposure in females and males. As prevalence of cannabis use may continue to increase given the shifting policy landscape regarding marijuana laws, understanding the neurobiological mechanisms of cannabis exposure in females and males is key. Examining these mechanisms may help inform future research on sex-specific pharmacological and behavioral interventions for women and men with high-risk cannabis use, comorbid psychiatric disease, and CUD.

  17. Habitats under Mechanical and Herbicide Management Regimes

    Directory of Open Access Journals (Sweden)

    Wendy-Ann P. Isaac

    2012-01-01

    Full Text Available Commelina diffusa is a colonising species of banana orchard habitats in St. Vincent in the Windward Islands of the Caribbean. In the present study, the population dynamics of C. diffusa were investigated in response to mechanical weed management with either a rotary string trimmer or glufosinate in ruderal and banana habitats. The study focused on density and size distribution of the weed over time and their response to two weed management strategies. The population dynamics of C. diffusa differed between the two habitats. Seedling establishment appeared to be an important factor influencing the dynamics of C. diffusa in banana orchards as there was little recruitment of seeds with less flower production compared with ruderal habitats where plants produced more flowers. Plants of C. diffusa in the banana orchard habitat had a longer growth cycle. In the banana orchard habitat, the C. diffusa population was greater and the plants were shorter with mechanical management than in areas treated with glufosinate. The results suggest that it is possible to manipulate the dynamics of C. diffusa in banana orchards as there is less chance of seed recruitment. Further research is necessary to refine an IPM approach for the management of C. diffusa.

  18. Physical and chemical mechanisms underlying hematoma evolution

    International Nuclear Information System (INIS)

    Cho, K.J.; Fanders, B.L.; Smid, A.R.; McLaughlin, P.

    1986-01-01

    Angiostat, a new collagen embolic material supplied at a concentration of 35 mg/ml (Target Therapeutics, Los Angeles) was used for flow-directed hepatic artery embolization in a series of rabbits to examine its acute effects on hepatic microcirculation. Arteriograms were obtained both before and after embolization. The aorta and portal vein were perfused with two different colors of Microfil after the animals were killed,. Cleared liver specimens were examined under a dissection microscope. Extent of dearterialization, status of portal sinusoidal perfusion, and collateral formation after embolization with Angiostat were evaluated. Results will be compared with results achieved using other liquid and particulate embolic agents

  19. [INVOLVEMENT OF PLANT CYTOSKELETON INTO CELLULAR MECHANISMS OF METALS TOXICITY].

    Science.gov (United States)

    Horiunova, L; Krasylenko, Yu A; Yemets, A I; Blume, Ya B

    2016-01-01

    This review summarizes published date and the results of the author's own researches cantering the participation of plant cells cytoskeleton. It is considered cytotoxic impact of metals on the cytoskeleton's components, including microtubules and actin filaments. Particular attention is paid to the cellular and molecular mechanisms of influence of metals on cytoskeleton. We discussed the most probable binding sites of heavy metals and alternative mechanisms of their impact on the cytoskeleton.

  20. Environmental genotoxicity: Probing the underlying mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Shugart, L. [Oak Ridge National Lab., TN (United States); Theodorakis, C. [Tennessee Univ., Knoxville, TN (United States)

    1993-12-31

    Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organismal levels. Past studies in genetic toxicology at the Oak Ridge National Laboratory have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community and ecosystem levels, current studies in genetic ecotoxicology are attempting to characterize the biological mechanisms at the gene level that regulate and limit the response of an individual organism to genotoxic factors in their environment.

  1. Sensing mechanisms involved in Ca2+ and Mg2+ homeostasis

    NARCIS (Netherlands)

    Ferre, S.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2012-01-01

    Calcium (Ca(2+)) and magnesium (Mg(2+)) ions are involved in many vital physiological functions. In the human body, Ca(2+) and Mg(2+) homeostatic systems rely on three components: (i) tissues (re)absorbing or storing Ca(2+) and Mg(2+), mainly kidney, intestine, and bone; (ii) hormones that modulate

  2. Mechanisms Involved in Nematode Control by Endophytic Fungi.

    Science.gov (United States)

    Schouten, Alexander

    2016-08-04

    Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood but most likely multifactorial. This knowledge gap obstructs the progress regarding the development of endophytes or endophyte-derived constituents into biocontrol agents. In part, this may be caused by the fact that endophytic fungi form a rather heterogeneous group. By combining the knowledge of the currently characterized antagonistic endophytic fungi and their effects on nematode behavior and biology with the knowledge of microbial competition and induced plant defenses, the various mechanisms by which this nematode antagonism operates or may operate are discussed. Now that new technologies are becoming available and more accessible, the currently unresolved mechanisms can be studied in greater detail than ever before.

  3. Understanding and imitating unfamiliar actions: distinct underlying mechanisms.

    Directory of Open Access Journals (Sweden)

    Joana C Carmo

    Full Text Available The human "mirror neuron system" has been proposed to be the neural substrate that underlies understanding and, possibly, imitating actions. However, since the brain activity with mirror properties seems insufficient to provide a good description for imitation of actions outside one's own repertoire, the existence of supplementary processes has been proposed. Moreover, it is unclear whether action observation requires the same neural mechanisms as the explicit access to their meaning. The aim of this study was two-fold as we investigated whether action observation requires different processes depending on 1 whether the ultimate goal is to imitate or understand the presented actions and 2 whether the to-be-imitated actions are familiar or unfamiliar to the subject. Participants were presented with both meaningful familiar actions and meaningless unfamiliar actions that they had to either imitate or discriminate later. Event-related Potentials were used as differences in brain activity could have been masked by the use of other techniques with lower temporal resolution. In the imitation task, a sustained left frontal negativity was more pronounced for meaningless actions than for meaningful ones, starting from an early time-window. Conversely, observing unfamiliar versus familiar actions with the intention of discriminating them led to marked differences over right centro-posterior scalp regions, in both middle and latest time-windows. These findings suggest that action imitation and action understanding may be sustained by dissociable mechanisms: while imitation of unfamiliar actions activates left frontal processes, that are likely to be related to learning mechanisms, action understanding involves dedicated operations which probably require right posterior regions, consistent with their involvement in social interactions.

  4. Physiological mechanisms underlying animal social behaviour.

    Science.gov (United States)

    Seebacher, Frank; Krause, Jens

    2017-08-19

    Many species of animal live in groups, and the group represents the organizational level within which ecological and evolutionary processes occur. Understanding these processes, therefore, relies on knowledge of the mechanisms that permit or constrain group formation. We suggest that physiological capacities and differences in physiology between individuals modify fission-fusion dynamics. Differences between individuals in locomotor capacity and metabolism may lead to fission of groups and sorting of individuals into groups with similar physiological phenotypes. Environmental impacts such as hypoxia can influence maximum group sizes and structure in fish schools by altering access to oxygenated water. The nutritional environment determines group cohesion, and the increase in information collected by the group means that individuals should rely more on social information and form more cohesive groups in uncertain environments. Changing environmental contexts require rapid responses by individuals to maintain group coordination, which are mediated by neuroendocrine signalling systems such as nonapeptides and steroid hormones. Brain processing capacity may constrain social complexity by limiting information processing. Failure to evaluate socially relevant information correctly limits social interactions, which is seen, for example, in autism. Hence, functioning of a group relies to a large extent on the perception and appropriate processing of signals from conspecifics. Many if not all physiological systems are mechanistically linked, and therefore have synergistic effects on social behaviour. A challenge for the future lies in understanding these interactive effects, which will improve understanding of group dynamics, particularly in changing environments.This article is part of the themed issue 'Physiological determinants of social behaviour in animals'. © 2017 The Author(s).

  5. Mechanisms Involved in Nematode Control by Endophytic Fungi

    NARCIS (Netherlands)

    Schouten, Sander

    2016-01-01

    Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood

  6. Mechanisms of molecular mimicry involving the microbiota in neurodegeneration.

    Science.gov (United States)

    Friedland, Robert P

    2015-01-01

    The concept of molecular mimicry was established to explain commonalities of structure which developed in response to evolutionary pressures. Most examples of molecular mimicry in medicine have involved homologies of primary protein structure which cause disease. Molecular mimicry can be expanded beyond amino acid sequence to include microRNA and proteomic effects which are either pathogenic or salutogenic (beneficial) in regard to Parkinson's disease, Alzheimer's disease, and related disorders. Viruses of animal or plant origin may mimic nucleotide sequences of microRNAs and influence protein expression. Both Parkinson's and Alzheimer's diseases involve the formation of transmissible self-propagating prion-like proteins. However, the initiating factors responsible for creation of these misfolded nucleating factors are unknown. Amyloid patterns of protein folding are highly conserved through evolution and are widely distributed in the world. Similarities of tertiary protein structure may be involved in the creation of these prion-like agents through molecular mimicry. Cross-seeding of amyloid misfolding, altered proteostasis, and oxidative stress may be induced by amyloid proteins residing in bacteria in our microbiota in the gut and in the diet. Pathways of molecular mimicry induced processes induced by bacterial amyloid in neurodegeneration may involve TLR 2/1, CD14, and NFκB, among others. Furthermore, priming of the innate immune system by the microbiota may enhance the inflammatory response to cerebral amyloids (such as amyloid-β and α-synuclein). This paper describes the specific molecular pathways of these cross-seeding and neuroinflammatory processes. Evolutionary conservation of proteins provides the opportunity for conserved sequences and structures to influence neurological disease through molecular mimicry.

  7. General mechanism for helium blistering involving displaced atom transport

    Energy Technology Data Exchange (ETDEWEB)

    McDonell, W.R.

    1979-01-01

    A mechanism developed to account for formation of vertically elongated blisters in high displacement environments produced by /sup 252/Cf alpha particles and fission fragments has been extended to formation of done-shaped blisters in the low displacement environments produced by simple helium ion beams. In this mechanism, transport of displaced atoms to relieve compressive stresses in the helium-implanted layer allows interconnections of small, subsurface bubbles to form the blister cavity. The same transport may cause thickening of the blister caps at low implantation energies. The transition from dome-shaped to vertically elongated blistering occurs between the 300 and 3000 displacements per helium atom produced by simple helium ions and /sup 252/Cf radiations respectively.

  8. Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

    Directory of Open Access Journals (Sweden)

    Roberto G. Pozner

    2013-01-01

    Full Text Available Viral hemorrhagic fevers (VHFs caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

  9. Identification of genes involved in regulatory mechanism of pigments in broiler chickens.

    Science.gov (United States)

    Tarique, T M; Yang, S; Mohsina, Z; Qiu, J; Yan, Z; Chen, G; Chen, A

    2014-09-05

    Chicken is an important model organism that unites the evolutionary gap between mammals and other vertebrates and provide major source of protein from meat and eggs for all over the world population. However, specific genes underlying the regulatory mechanism of broiler pigmentation have not yet been determined. In order to better understand the genes involved in the mechanism of pigmentation in the muscle tissues of broilers, the Affymetrix microarray hybridization experiment platform was used to identify gene expression profiles at 7 weeks of age. Broilers fed canthaxanthin, natural lutein, and orangeII pigments (100 mg/kg) were used to explore gene expression profiles). Our data showed that the 7th week of age was a very important phase with regard to gene expression profiles. We identified a number of differentially expressed genes; in canthaxanthin, natural lutein, and orangeII, there were 54 (32 upregulated and 22 downregulated), 23 (15 upregulated and 8 downregulated), and 7 (5 upregulated and 2 downregulated) known genes, respectively. Our data indicate that the numbers of differentially expressed genes were more upregulated than downregulated, and several genes showed conserved signaling to previously known functions. Thus, functional characterization of differentially expressed genes revealed several categories that are involved in important biological processes, including pigmentation, growth, molecular mechanisms, fat metabolism, cell proliferation, immune response, lipid metabolism, and protein synthesis and degradation. The results of the present study demonstrate that the genes associated with canthaxanthin, natural lutein, and orangeII are key regulatory genes that control the regulatory mechanisms of pigmentation.

  10. Studies on Acinetobacter baumannii involving multiple mechanisms of carbapenem resistance.

    Science.gov (United States)

    Sen, B; Joshi, S G

    2016-03-01

    Characterize the genetic type and resistance mechanisms of 16 carbapenem-resistant Acinetobacter baumannii (CRAB) isolates recovered between January 2010 and March 2011 from US tertiary-care hospital. A modified Hodge test demonstrated the presence of carbapenemases, but meropenem and ethylenediaminetetraacetic acid (EDTA) double-disc synergy tests and PCR for metallo-β-lactamase (MBL) genes were negative. The genes of ampC β-lactamase and efflux pump of adeABC and adeIJK were detected. The presence of oxacillinase (OXA)-like genes, blaOXA-51-like , blaOXA-23-like and blaOXA-40-like genes, and insertion sequence ISAba1 in promoter region of blaOXA-51-like and blaOXA-23-like genes were detected; and confirmed by RT-PCR analyses. The sequencing of blaOXA-51-like genes revealed two major alleles, blaOXA-66-like (blaOXA-82 ) and blaOXA-113 from 31·2 to 68·8% of isolates respectively. The blaOXA-23 and blaOXA-72 genes showed high expression and found co-harbouring blaOXA-51-like gene preceded by ISAba-1. All CRAB isolates revealed significant reduction in carO transcription, indicated downregulation of CarO porin system, a potentially independent mechanism of carbapenam resistance. Sequencing of carO gene from representative isolates showed no ISAba1 insertional inactivation. Pulsed-field gel electrophoresis revealed a clonal relationship. CRAB exhibited diversity of mechanisms of carbapenem resistance, and clonal relationship. Studies on distinct outbreaks of CRAB are alarming situation for clinicians. © 2015 The Society for Applied Microbiology.

  11. Involvement of thiol-based mechanisms in plant development.

    Science.gov (United States)

    Rouhier, Nicolas; Cerveau, Delphine; Couturier, Jérémy; Reichheld, Jean-Philippe; Rey, Pascal

    2015-08-01

    Increasing knowledge has been recently gained regarding the redox regulation of plant developmental stages. The current state of knowledge concerning the involvement of glutathione, glutaredoxins and thioredoxins in plant development is reviewed. The control of the thiol redox status is mainly ensured by glutathione (GSH), a cysteine-containing tripeptide and by reductases sharing redox-active cysteines, glutaredoxins (GRXs) and thioredoxins (TRXs). Indeed, thiol groups present in many regulatory proteins and metabolic enzymes are prone to oxidation, ultimately leading to post-translational modifications such as disulfide bond formation or glutathionylation. This review focuses on the involvement of GSH, GRXs and TRXs in plant development. Recent studies showed that the proper functioning of root and shoot apical meristems depends on glutathione content and redox status, which regulate, among others, cell cycle and hormone-related processes. A critical role of GRXs in the formation of floral organs has been uncovered, likely through the redox regulation of TGA transcription factor activity. TRXs fulfill many functions in plant development via the regulation of embryo formation, the control of cell-to-cell communication, the mobilization of seed reserves, the biogenesis of chloroplastic structures, the metabolism of carbon and the maintenance of cell redox homeostasis. This review also highlights the tight relationships between thiols, hormones and carbon metabolism, allowing a proper development of plants in relation with the varying environment and the energy availability. GSH, GRXs and TRXs play key roles during the whole plant developmental cycle via their antioxidant functions and the redox-regulation of signaling pathways. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Underlying Mechanisms of Tinnitus: Review and Clinical Implications

    Science.gov (United States)

    Henry, James A.; Roberts, Larry E.; Caspary, Donald M.; Theodoroff, Sarah M.; Salvi, Richard J.

    2016-01-01

    Background The study of tinnitus mechanisms has increased tenfold in the last decade. The common denominator for all of these studies is the goal of elucidating the underlying neural mechanisms of tinnitus with the ultimate purpose of finding a cure. While these basic science findings may not be immediately applicable to the clinician who works directly with patients to assist them in managing their reactions to tinnitus, a clear understanding of these findings is needed to develop the most effective procedures for alleviating tinnitus. Purpose The goal of this review is to provide audiologists and other health-care professionals with a basic understanding of the neurophysiological changes in the auditory system likely to be responsible for tinnitus. Results It is increasingly clear that tinnitus is a pathology involving neuroplastic changes in central auditory structures that take place when the brain is deprived of its normal input by pathology in the cochlea. Cochlear pathology is not always expressed in the audiogram but may be detected by more sensitive measures. Neural changes can occur at the level of synapses between inner hair cells and the auditory nerve and within multiple levels of the central auditory pathway. Long-term maintenance of tinnitus is likely a function of a complex network of structures involving central auditory and nonauditory systems. Conclusions Patients often have expectations that a treatment exists to cure their tinnitus. They should be made aware that research is increasing to discover such a cure and that their reactions to tinnitus can be mitigated through the use of evidence-based behavioral interventions. PMID:24622858

  13. Water involvement in the mechanisms of retina electrical activity

    International Nuclear Information System (INIS)

    Chirieri-Kovacs, E.; Vasilescu, V.

    1982-01-01

    Retina is an excitable system containing approximately 90% water. As we found that deuteration selectively changes amplitudes and latencies of retina biopotentials, specifically the ON and OFF responses, we used it to probe the role of water in those processes. A study of the retina deuteration kinetics was simultaneously performed. This revealed the existence of at least two retinal water compartments. The data suggested a third compartment also, with a lower motional ''degree of freedom,'' existing where H 2 O-D 2 O exchange becomes important only after saturation by D 2 O of the first two compartments. Correlation of the electrophysiological effects of D 2 O with the kinetic data suggests that the ON response is related to the first water compartment and the OFF response to the third. The results point to independence on the ON and OFF response mechanisms and, very probably, to their different morphological origins

  14. Kinetics and mechanisms of reactions involving small aromatic reactive intermediates

    Energy Technology Data Exchange (ETDEWEB)

    Lin, M.C. [Emory Univ., Atlanta, GA (United States)

    1993-12-01

    Small aromatic radicals such as C{sub 6}H{sub 5}, C{sub 6}H{sub 5}O and C{sub 6}H{sub 4} are key prototype species of their homologs. C{sub 6}H{sub 5} and its oxidation product, C{sub 6}H{sub 5}O are believed to be important intermediates which play a pivotal role in hydrocarbon combustion, particularly with regard to soot formation. Despite their fundamental importance, experimental data on the reaction mechanisms and reactivities of these species are very limited. For C{sub 6}H{sub 5}, most kinetic data except its reactions with NO and NO{sub 2}, were obtained by relative rate measurements. For C{sub 6}H{sub 5}O, the authors have earlier measured its fragmentation reaction producing C{sub 5}H{sub 5} + CO in shock waves. For C{sub 6}H{sub 4}, the only rate constant measured in the gas phase is its recombination rate at room temperature. The authors have proposed to investigate systematically the kinetics and mechanisms of this important class of molecules using two parallel laser diagnostic techniques--laser resonance absorption (LRA) and resonance enhanced multiphoton ionization mass spectrometry (REMPI/MS). In the past two years, study has been focused on the development of a new multipass adsorption technique--the {open_quotes}cavity-ring-down{close_quotes} technique for kinetic applications. The preliminary results of this study appear to be quite good and the sensitivity of the technique is at least comparable to that of the laser-induced fluorescence method.

  15. Simulated airplane headache: a proxy towards identification of underlying mechanisms.

    Science.gov (United States)

    Bui, Sebastian Bao Dinh; Petersen, Torben; Poulsen, Jeppe Nørgaard; Gazerani, Parisa

    2017-12-01

    Airplane Headache (AH) occurs during flights and often appears as an intense, short lasting headache during take-off or landing. Reports are limited on pathological mechanisms underlying the occurrence of this headache. Proper diagnosis and treatments would benefit from identification of potential pathways involved in AH pathogenesis. This study aimed at providing a simulated airplane headache condition as a proxy towards identification of its underlying mechanisms. Fourteen participants including 7 volunteers suffering from AH and 7 healthy matched controls were recruited after meeting the diagnostic and safety criteria based on an approved study protocol. Simulation of AH was achieved by entering a pressure chamber with similar characteristics of an airplane flight. Selected potential biomarkers including salivary prostaglandin E 2 (PGE 2 ), cortisol, facial thermo-images, blood pressure, pulse, and saturation pulse oxygen (SPO) were defined and values were collected before, during and after flight simulation in the pressure chamber. Salivary samples were analyzed with ELISA techniques, while data analysis and statistical tests were handled with SPSS version 22.0. All participants in the AH-group experienced a headache attack similar to AH experience during flight. The non-AH-group did not experience any headaches. Our data showed that the values for PGE 2 , cortisol and SPO were significantly different in the AH-group in comparison with the non-AH-group during the flight simulation in the pressure chamber. The pressure chamber proved useful not only to provoke AH-like attack but also to study potential biomarkers for AH in this study. PGE 2 , and cortisol levels together with SPO presented dysregulation during the simulated AH-attack in affected individuals compared with healthy controls. Based on these findings we propose to use pressure chamber as a model to induce AH, and thus assess new potential biomarkers for AH in future studies.

  16. Possible mechanism involved in sleep deprivation-induced memory dysfunction.

    Science.gov (United States)

    Kalonia, H; Bishnoi, M; Kumar, A

    2008-09-01

    Sleep deprivation disrupts various vital biological and metabolic processes that are necessary for health. The present study was designed to investigate the possible mechanisms of sleep deprivation-induced memory dysfunction by using different behavioral, biochemical and neurochemical parameters. Male Wistar rats were sleep deprived for 72 h using a grid suspended over water. Elevated plus maze, passive avoidance and Morris water maze tests were used to assess memory retention in 72-h sleep-deprived animals. Various electrophysiological (sleep-wake cycle), biochemical (lipid peroxidation, reduced glutathione, nitrite, catalase, acetylcholinesterase) and neurochemical parameters (norepinephrine, dopamine and serotonin) were also assessed. Sleep deprivation resulted in memory dysfunction in all the behavioral paradigms, alteration in the sleep-wake cycle (delayed sleep latency, shortening of rapid eye movement [REM] and non-REM [NREM] sleep and increased waking period) and oxidative stress (increased lipid peroxidation and nitrite levels, depletion of reduced glutathione and catalase activity). In addition, increased levels of acetylcholinesterase (AChE; the enzyme responsible for the degradation of acetylcholine) and reduction in norepinephrine and dopamine levels were seen in 72-h sleep-deprived animals. In conclusion, sleep deprivation-induced memory deficits may possibly be due to the combined effect of oxidative damage and alterations in neurotransmitter levels. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

  17. Mechanisms involved in alternariol-induced cell cycle arrest

    Energy Technology Data Exchange (ETDEWEB)

    Solhaug, A., E-mail: Anita.Solhaug@vetinst.no [Norwegian Veterinary Institute, Oslo (Norway); Vines, L.L. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Ivanova, L.; Spilsberg, B. [Norwegian Veterinary Institute, Oslo (Norway); Holme, J.A. [Norwegian Institute of Public Health, Division of Environmental Medicine, Oslo (Norway); Pestka, J. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Collins, A. [University of Oslo, Department of Nutrition, Faculty of Medicine, Oslo (Norway); Eriksen, G.S. [Norwegian Veterinary Institute, Oslo (Norway)

    2012-10-15

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15-30 {mu}M almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 {mu}M) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 {mu}M for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  18. Molecular mechanisms involved in Bacillus subtilis biofilm formation

    Science.gov (United States)

    Mielich-Süss, Benjamin; Lopez, Daniel

    2014-01-01

    Summary Biofilms are the predominant lifestyle of bacteria in natural environments, and they severely impact our societies in many different fashions. Therefore, biofilm formation is a topic of growing interest in microbiology, and different bacterial models are currently studied to better understand the molecular strategies that bacteria undergo to build biofilms. Among those, biofilms of the soil-dwelling bacterium Bacillus subtilis are commonly used for this purpose. Bacillus subtilis biofilms show remarkable architectural features that are a consequence of sophisticated programs of cellular specialization and cell-cell communication within the community. Many laboratories are trying to unravel the biological role of the morphological features of biofilms, as well as exploring the molecular basis underlying cellular differentiation. In this review, we present a general perspective of the current state of knowledge of biofilm formation in B. subtilis. In particular, a special emphasis is placed on summarizing the most recent discoveries in the field and integrating them into the general view of these truly sophisticated microbial communities. PMID:24909922

  19. Modeling and Compensatory Processes Underlying Involvement in Child Care among Kibbutz-Reared Fathers

    Science.gov (United States)

    Gaunt, Ruth; Bassi, Liat

    2012-01-01

    This study examined modeling and compensatory processes underlying the effects of an early paternal model on father involvement in child care. Drawing on social learning theory, it was hypothesized that father-son relationships would moderate the association between a father's involvement and his own father's involvement. A sample of 136 kibbutz…

  20. Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

    International Nuclear Information System (INIS)

    Kawano, Michinao; Ariyoshi, Wataru; Iwanaga, Kenjiro; Okinaga, Toshinori; Habu, Manabu; Yoshioka, Izumi; Tominaga, Kazuhiro; Nishihara, Tatsuji

    2011-01-01

    Research highlights: → In this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. → MG63 cells were incubated with BMP-2 and HA for various time periods. → Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. → HA enhanced BMP-2 induces osteoblastic differentiation in MG63 cells via down-regulation of BMP-2 antagonists and ERK phosphorylation. -- Abstract: Objectives: Bone morphogenetic protein-2 (BMP-2) is expected to be utilized to fill bone defects and promote healing of fractures. However, it is unable to generate an adequate clinical response for use in bone regeneration. Recently, it was reported that glycosaminoglycans, including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and hyaluronic acid (HA), regulate BMP-2 activity, though the mechanism by which HA regulates osteogenic activities has not been fully elucidated. The aim of this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. Materials and methods: Monolayer cultures of osteoblastic lineage MG63 cells were incubated with BMP-2 and HA for various time periods. To determine osteoblastic differentiation, alkaline phosphatase (ALP) activity in the cell lysates was quantified. Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by Western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. To further elucidate the role of HA in enhancement of BMP-2-induced Smad signaling, mRNA expressions of the BMP-2 receptor antagonists noggin and follistatin were detected using real-time RT-PCR. Results: BMP-2-induced ALP activation, Smad 1/5/8 phosphorylation, and nuclear translocation

  1. Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Michinao [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Iwanaga, Kenjiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Okinaga, Toshinori [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Habu, Manabu [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Yoshioka, Izumi [Division of Oral and Maxillofacial Surgery, Department of Medicine of Sensory and Motor Organs, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Tominaga, Kazuhiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan)

    2011-02-25

    Research highlights: {yields} In this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. {yields} MG63 cells were incubated with BMP-2 and HA for various time periods. {yields} Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. {yields} HA enhanced BMP-2 induces osteoblastic differentiation in MG63 cells via down-regulation of BMP-2 antagonists and ERK phosphorylation. -- Abstract: Objectives: Bone morphogenetic protein-2 (BMP-2) is expected to be utilized to fill bone defects and promote healing of fractures. However, it is unable to generate an adequate clinical response for use in bone regeneration. Recently, it was reported that glycosaminoglycans, including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and hyaluronic acid (HA), regulate BMP-2 activity, though the mechanism by which HA regulates osteogenic activities has not been fully elucidated. The aim of this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. Materials and methods: Monolayer cultures of osteoblastic lineage MG63 cells were incubated with BMP-2 and HA for various time periods. To determine osteoblastic differentiation, alkaline phosphatase (ALP) activity in the cell lysates was quantified. Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by Western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. To further elucidate the role of HA in enhancement of BMP-2-induced Smad signaling, mRNA expressions of the BMP-2 receptor antagonists noggin and follistatin were detected using real-time RT-PCR. Results: BMP-2-induced ALP activation, Smad 1/5/8 phosphorylation, and

  2. Mechanism(S) Involved in the Colon-Specific Expression of the Thiamine Pyrophosphate (Tpp) Transporter.

    Science.gov (United States)

    Nabokina, Svetlana M; Ramos, Mel Brendan; Said, Hamid M

    2016-01-01

    Microbiota of the large intestine synthesizes considerable amount of vitamin B1 (thiamine) in the form of thiamine pyrophosphate (TPP). We have recently demonstrated the existence of an efficient and specific carrier-mediated uptake process for TPP in human colonocytes, identified the TPP transporter (TPPT) involved (product of the SLC44A4 gene), and shown that expression of TPPT along the gastrointestinal (GI) tract is restricted to the colon. Our aim in this study was to determine the molecular basis of the colon-specific expression of TPPT focusing on a possible epigenetic mechanism. Our results showed that the CpG island predicted in the SLC44A4 promoter is non-methylated in the human colonic epithelial NCM460 cells, but is hyper-methylated in the human duodenal epithelial HuTu80 cells (as well as in the human retinal pigment epithelial ARPE19 cells). In the mouse (where TPPT expression in the GI tract is also restricted to the colon), the CpG island predicted in the Slc44a4 promoter is non-methylated in both the jejunum and colon, thus arguing against possible contribution of DNA methylation in the colon-specific expression of TPPT. A role for histone modifications in the tissue-specific pattern of Slc44a4 expression, however, was suggested by the findings that in mouse colon, histone H3 in the 5'-regulatory region of Slc44a4 is tri-methylated at lysine 4 and acetylated at lysine 9, whereas the tri-methylation at lysine 27 modification was negligible. In contrast, in the mouse jejunum, histone H3 is hyper-trimethylated at lysine 27 (repressor mark). Similarly, possible involvement of miRNA(s) in the tissue-specific expression of TPPT was also suggested by the findings that the 3'-UTR of SLC44A4 is targeted by specific miRNAs/RNA binding proteins in non-colonic, but not in colonic, epithelial cells. These studies show, for the first time, epigenetic mechanisms (histone modifications) play a role in determining the tissue-specific pattern of expression of TPPT

  3. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

    2010-01-01

    This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...

  4. Underlying Mechanisms of Improving Physical Activity Behavior after Rehabilitation

    NARCIS (Netherlands)

    van der Ploeg, Hidde P.; Streppel, Kitty R.M.; van der Beek, Allard J.; Woude, Luc H.V.; van Harten, Willem H.; Vollenbroek-Hutten, Miriam Marie Rosé; van Mechelen, Willem

    2008-01-01

    Background: Regular physical activity is beneficial for the health and functioning of people with a disability. Effective components of successful physical activity promotion interventions should be identified and disseminated. Purpose: To study the underlying mechanisms of the combined sport

  5. Stress analysis in a functionally graded disc under mechanical loads ...

    Indian Academy of Sciences (India)

    Stress analysis in a functionally graded disc under mechanical loads and a steady state temperature distribution. HASAN ÇALLIO ˘GLU. Department of Mechanical Engineering, Pamukkale University, 20070,. Denizli, Turkey e-mail: hcallioglu@pau.edu.tr. MS received 25 November 2009; revised 12 August 2010; accepted.

  6. Molecular mechanisms underlying phosphate sensing, signaling, and adaptation in plants.

    Science.gov (United States)

    Zhang, Zhaoliang; Liao, Hong; Lucas, William J

    2014-03-01

    As an essential plant macronutrient, the low availability of phosphorus (P) in most soils imposes serious limitation on crop production. Plants have evolved complex responsive and adaptive mechanisms for acquisition, remobilization and recycling of phosphate (Pi) to maintain P homeostasis. Spatio-temporal molecular, physiological, and biochemical Pi deficiency responses developed by plants are the consequence of local and systemic sensing and signaling pathways. Pi deficiency is sensed locally by the root system where hormones serve as important signaling components in terms of developmental reprogramming, leading to changes in root system architecture. Root-to-shoot and shoot-to-root signals, delivered through the xylem and phloem, respectively, involving Pi itself, hormones, miRNAs, mRNAs, and sucrose, serve to coordinate Pi deficiency responses at the whole-plant level. A combination of chromatin remodeling, transcriptional and posttranslational events contribute to globally regulating a wide range of Pi deficiency responses. In this review, recent advances are evaluated in terms of progress toward developing a comprehensive understanding of the molecular events underlying control over P homeostasis. Application of this knowledge, in terms of developing crop plants having enhanced attributes for P use efficiency, is discussed from the perspective of agricultural sustainability in the face of diminishing global P supplies. © 2014 Institute of Botany, Chinese Academy of Sciences.

  7. Mechanisms underlying the antihypertensive effects of garlic bioactives.

    Science.gov (United States)

    Shouk, Reem; Abdou, Aya; Shetty, Kalidas; Sarkar, Dipayan; Eid, Ali H

    2014-02-01

    Cardiovascular disease remains the leading cause of death worldwide with hypertension being a major contributing factor to cardiovascular disease-associated mortality. On a population level, non-pharmacological approaches, such as alternative/complementary medicine, including phytochemicals, have the potential to ameliorate cardiovascular risk factors, including high blood pressure. Several epidemiological studies suggest an antihypertensive effect of garlic (Allium sativum) and of many its bioactive components. The aim of this review is to present an in-depth discussion regarding the molecular, biochemical and cellular rationale underlying the antihypertensive properties of garlic and its bioactive constituents with a primary focus on S-allyl cysteine and allicin. Key studies, largely from PubMed, were selected and screened to develop a comprehensive understanding of the specific role of garlic and its bioactive constituents in the management of hypertension. We also reviewed recent advances focusing on the role of garlic bioactives, S-allyl cysteine and allicin, in modulating various parameters implicated in the pathogenesis of hypertension. These parameters include oxidative stress, nitric oxide bioavailability, hydrogen sulfide production, angiotensin converting enzyme activity, expression of nuclear factor-κB and the proliferation of vascular smooth muscle cells. This review suggests that garlic and garlic derived bioactives have significant medicinal properties with the potential for ameliorating hypertension and associated morbidity; however, further clinical and epidemiological studies are required to determine completely the specific physiological and biochemical mechanisms involved in disease prevention and management. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Astrocytes are involved in trigeminal dynamic mechanical allodynia: potential role of D-serine.

    Science.gov (United States)

    Dieb, W; Hafidi, A

    2013-09-01

    Trigeminal neuropathic pain affects millions of people worldwide. Despite decades of study on the neuronal processing of pain, mechanisms underlying enhanced pain states after injury remain unclear. N-methyl-D-aspartate (NMDA) receptor-dependent changes play a critical role in triggering central sensitization in neuropathic pain. These receptors are regulated at the glycine site through a mandatory endogenous co-agonist D-serine, which is synthesized by astrocytes. Therefore, the present study was carried out to determine whether astrocytes are involved, through D-serine secretion, in dynamic mechanical allodynia (DMA) obtained after chronic constriction of the infraorbital nerve (CCI-IoN) in rats. Two weeks after CCI-IoN, an important reaction of astrocytes was present in the medullary dorsal horn (MDH), as revealed by an up-regulation of glial fibrillary acidic protein (GFAP) in allodynic rats. In parallel, an increase in D-serine synthesis, which co-localized with its synthesis enzyme serine racemase, was strictly observed in astrocytes. Blocking astrocyte metabolism by intracisternal delivery of fluorocitrate alleviated DMA. Furthermore, the administration of D-amino-acid oxidase (DAAO), a D-serine-degrading enzyme, or that of L-serine O-sulfate (LSOS), a serine racemase inhibitor, significantly decreased pain behavior in allodynic rats. These results demonstrate that astrocytes are involved in the modulation of orofacial post-traumatic neuropathic pain via the release of the gliotransmitter D-serine.

  9. Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression

    OpenAIRE

    Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

    2015-01-01

    Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical ...

  10. Amount of fear extinction changes its underlying mechanisms.

    Science.gov (United States)

    An, Bobae; Kim, Jihye; Park, Kyungjoon; Lee, Sukwon; Song, Sukwoon; Choi, Sukwoo

    2017-07-03

    There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that.

  11. Mechanisms involved in extraterritorial facial pain following cervical spinal nerve injury in rats

    Directory of Open Access Journals (Sweden)

    Imamura Yoshiki

    2011-02-01

    Full Text Available Abstract Background The aim of this study is to clarify the neural mechanisms underlying orofacial pain abnormalities after cervical spinal nerve injury. Nocifensive behavior, phosphorylated extracellular signal-regulated kinase (pERK expression and astroglial cell activation in the trigeminal spinal subnucleus caudalis (Vc and upper cervical spinal dorsal horn (C1-C2 neurons were analyzed in rats with upper cervical spinal nerve transection (CNX. Results The head withdrawal threshold to mechanical stimulation of the lateral facial skin and head withdrawal latency to heating of the lateral facial skin were significantly lower and shorter respectively in CNX rats compared to Sham rats. These nocifensive effects were apparent within 1 day after CNX and lasted for more than 21 days. The numbers of pERK-like immunoreactive (LI cells in superficial laminae of Vc and C1-C2 were significantly larger in CNX rats compared to Sham rats following noxious and non-noxious mechanical or thermal stimulation of the lateral facial skin at day 7 after CNX. Two peaks of pERK-LI cells were observed in Vc and C1-C2 following mechanical and heat stimulation of the lateral face. The number of pERK-LI cells in C1-C2 was intensity-dependent and increased when the mechanical and heat stimulations of the face were increased. The decrements of head withdrawal latency to heat and head withdrawal threshold to mechanical stimulation were reversed during intrathecal (i.t. administration of MAPK/ERK kinase 1/2 inhibitor PD98059. The area of activated astroglial cells was significantly higher in CNX rats (at day 7 after CNX. The heat and mechanical nocifensive behaviors were significantly depressed and the number of pERK-LI cells in Vc and C1-C2 following noxious and non-noxious mechanical stimulation of the face was also significantly decreased following i.t. administration of the astroglial inhibitor fluoroacetate. Conclusions The present findings have demonstrated that

  12. Afferent control mechanisms involved in the development of soleus fiber alterations in simulated hypogravity

    Science.gov (United States)

    Shenkman, B. S.; Nemirovskaya, T. L.; Shapovalova, K. B.; Podlubnaya, Z. A.; Vikhliantsev, I. M.; Moukhina, A. M.; Kozlovskaya, I. B.

    2007-02-01

    It was recently established that support withdrawal (withdrawal of support reaction force) in microgravity provokes a sequence of functional shifts in the activity of motor units (inactivation of slow ones) and peripheral muscle apparatus which lead to the decline of postural muscle contractility and alterations in fiber characteristics. However, mechanisms involved in inactivation of the slow motor units and appropriate slow-twitch muscle fiber disuse under the supportless conditions remained unknown. We show here that artificial inactivation of muscles-antagonists (which are known to be hyperactive during unloading) counteracts some of the unloading-induced events in the rat soleus (fiber size reduction, slow-to-fast fiber-type transition and decline of titin and nebulin content). It was also demonstrated that direct activation of the muscarinic receptors of the neostriatum neurons prevented slow-to-fast fiber-type transformation in soleus of hindlimb suspended rats.

  13. TGF-β2 is involved in the preservation of the chondrocyte phenotype under hypoxic conditions

    NARCIS (Netherlands)

    Das, R.; Timur, U. T.; Edip, S.; Haak, E.; Wruck, C.; Weinans, H.; Jahr, H.

    2015-01-01

    Culturing chondrocytes under oxygen tension closely resembling their in vivo environment has been shown to have positive effects on matrix synthesis. In redifferentiation of expanded chondrocytes, hypoxia increased collagen type II expression. However, the mechanism by which hypoxia enhances

  14. Mechanisms underlying prorenin actions on hypothalamic neurons implicated in cardiometabolic control

    Directory of Open Access Journals (Sweden)

    Soledad Pitra

    2016-10-01

    Conclusions: We identified novel neuronal targets and cellular mechanisms underlying PR/PRR actions in critical hypothalamic neurons involved in cardiometabolic regulation. This fundamental mechanistic information regarding central PR/PRR actions is essential for the development of novel RAS-based therapeutic targets for the treatment of cardiometabolic disorders in obesity and hypertension.

  15. Mechanical Property Analysis of Circular Polymer Membrane under Uniform Pressure

    OpenAIRE

    Jianbing, Sang; Xiang, Li; Sufang, Xing; Wenjia, Wang

    2017-01-01

    Mechanical property analysis of circular hyperelastic polymer membrane under uniform pressure has been researched in this work. The polymer membrane material is assumed to be homogeneous and isotropic and incompressibility of materials has been considered. Based on the modified stain energy function from Gao and nonmomental theory of axial symmetry thin shell, finite deformation analysis of polymer membrane under uniform pressure has been proposed in current configuration and governing equati...

  16. Emotional responses to music: the need to consider underlying mechanisms.

    Science.gov (United States)

    Juslin, Patrik N; Västfjäll, Daniel

    2008-10-01

    Research indicates that people value music primarily because of the emotions it evokes. Yet, the notion of musical emotions remains controversial, and researchers have so far been unable to offer a satisfactory account of such emotions. We argue that the study of musical emotions has suffered from a neglect of underlying mechanisms. Specifically, researchers have studied musical emotions without regard to how they were evoked, or have assumed that the emotions must be based on the "default" mechanism for emotion induction, a cognitive appraisal. Here, we present a novel theoretical framework featuring six additional mechanisms through which music listening may induce emotions: (1) brain stem reflexes, (2) evaluative conditioning, (3) emotional contagion, (4) visual imagery, (5) episodic memory, and (6) musical expectancy. We propose that these mechanisms differ regarding such characteristics as their information focus, ontogenetic development, key brain regions, cultural impact, induction speed, degree of volitional influence, modularity, and dependence on musical structure. By synthesizing theory and findings from different domains, we are able to provide the first set of hypotheses that can help researchers to distinguish among the mechanisms. We show that failure to control for the underlying mechanism may lead to inconsistent or non-interpretable findings. Thus, we argue that the new framework may guide future research and help to resolve previous disagreements in the field. We conclude that music evokes emotions through mechanisms that are not unique to music, and that the study of musical emotions could benefit the emotion field as a whole by providing novel paradigms for emotion induction.

  17. Study on Mechanical Properties of Barite Concrete under Impact Load

    Science.gov (United States)

    Chen, Z. F.; Cheng, K.; Wu, D.; Gan, Y. C.; Tao, Q. W.

    2018-03-01

    In order to research the mechanical properties of Barite concrete under impact load, a group of concrete compression tests was carried out under the impact load by using the drop test machine. A high-speed camera was used to record the failure process of the specimen during the impact process. The test results show that:with the increase of drop height, the loading rate, the peak load, the strain under peak load, the strain rate and the dynamic increase factor (DIF) all increase gradually. The ultimate tensile strain is close to each other, and the time of impact force decreases significantly, showing significant strain rate effect.

  18. Damage mechanisms in PBT-GF30 under thermo-mechanical cyclic loading

    International Nuclear Information System (INIS)

    Schaaf, A.; De Monte, M.; Hoffmann, C.; Vormwald, M.; Quaresimin, M.

    2014-01-01

    The scope of this paper is the investigation of damage mechanisms at microscopic scale on a short glass fiber reinforced polybutylene terephthalate (PBT-GF30) under thermo-mechanical cyclic loading. In addition the principal mechanisms are verified through micro mechanical FE models. In order to investigate the fatigue behavior of the material both isothermal strain controlled fatigue (ISCF) tests at three different temperatures and thermo-mechanical fatigue (TMF) tests were conducted on plain and notched specimens, manufactured by injection molding. The goal of the work is to determine the damage mechanisms occurring under TMF conditions and to compare them with the mechanisms occurring under ISCF. For this reason fracture surfaces of TMF and ISCF samples loaded at different temperature levels were analyzed using scanning electron microscopy. Furthermore, specimens that failed under TMF were examined on microsections revealing insight into both crack initiation and crack propagation. The findings of this investigation give valuable information about the main damage mechanisms of PBT-GF30 under TMF loading and serve as basis for the development of a TMF life estimation methodology

  19. Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

    Science.gov (United States)

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

  20. Molecular characterization of HIV-1 subtype C gp-120 regions potentially involved in virus adaptive mechanisms.

    Directory of Open Access Journals (Sweden)

    Alessandra Cenci

    Full Text Available The role of variable regions of HIV-1 gp120 in immune escape of HIV has been investigated. However, there is scant information on how conserved gp120 regions contribute to virus escaping. Here we have studied how molecular sequence characteristics of conserved C3, C4 and V3 regions of clade C HIV-1 gp120 that are involved in HIV entry and are target of the immune response, are modulated during the disease course. We found an increase of "shifting" putative N-glycosylation sites (PNGSs in the α2 helix (in C3 and in C4 and an increase of sites under positive selection pressure in the α2 helix during the chronic stage of disease. These sites are close to CD4 and to co-receptor binding sites. We also found a negative correlation between electric charges of C3 and V4 during the late stage of disease counteracted by a positive correlation of electric charges of α2 helix and V5 during the same stage. These data allow us to hypothesize possible mechanisms of virus escape involving constant and variable regions of gp120. In particular, new mutations, including new PNGSs occurring near the CD4 and CCR5 binding sites could potentially affect receptor binding affinity and shield the virus from the immune response.

  1. A cascade of recently discovered molecular mechanisms involved in abiotic stress tolerance of plants.

    Science.gov (United States)

    Saeed, Muhammad; Dahab, Abdel hafiz Adam; Wangzhen, Guo; Tianzhen, Zhang

    2012-04-01

    Today, agriculture is facing a tremendous threat from the climate change menace. As human survival is dependent on a constant supply of food from plants as the primary producers, we must aware of the underlying molecular mechanisms that plants have acquired as a result of molecular evolution to cope this rapidly changing environment. This understanding will help us in designing programs aimed at developing crop plant cultivars best suited to our needs of a sustainable agriculture. The field of systems biology is rapidly progressing, and new insight is coming out about the molecular mechanisms involved in abiotic stress tolerance. There is a cascade of changes in transcriptome, proteome, and metabolome of plants during these stress responses. We have tried to cover most pronounced recent developments in the field of "omics" related to abiotic stress tolerance of plants. These changes are very coordinated, and often there is crosstalk between different components of stress tolerance. The functions of various molecular entities are becoming more clear and being associated with more precise biological phenomenon.

  2. A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.

    Directory of Open Access Journals (Sweden)

    Chen Xie

    Full Text Available BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(- and HCO(3(-, in mediating prostate HCO(3(- secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II, along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3(- content (>50 mM, rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3(- on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3(- secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3(- secretion may be up-regulated in prostatitis as a host defense mechanism.

  3. Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program.

    Science.gov (United States)

    Andersson, Ulrika; Henriksson, Emma; Ström, Kristoffer; Alenfall, Jan; Göransson, Olga; Holm, Cecilia

    2011-01-01

    The aim of this study was to investigate the metabolic effects of a dietary supplement of powdered rose hip to C57BL/6J mice fed a high-fat diet (HFD). Two different study protocols were used; rose hip was fed together with HFD to lean mice for 20 wk (prevention study) and to obese mice for 10 wk (intervention study). Parameters related to obesity and glucose tolerance were monitored, and livers were examined for lipids and expression of genes and proteins related to lipid metabolism and gluconeogenesis. A supplement of rose hip was capable of both preventing and reversing the increase in body weight and body fat mass imposed by a HFD in the C57BL/6J mouse. Oral and intravenous glucose tolerance tests together with lower basal levels of insulin and glucose showed improved glucose tolerance in mice fed a supplement of rose hip compared with control mice. Hepatic lipid accumulation was reduced in mice fed rose hip compared with control, and the expression of lipogenic proteins was downregulated, whereas AMP-activated protein kinase and other proteins involved in fatty acid oxidation were unaltered. Rose hip intake lowered total plasma cholesterol as well as the low-density lipoprotein-to-high-density lipoprotein ratio via a mechanism not involving altered gene expression of sterol regulatory element-binding protein 2 or 3-hydroxymethylglutaryl-CoA reductase. Taken together, these data show that a dietary supplement of rose hip prevents the development of a diabetic state in the C57BL/6J mouse and that downregulation of the hepatic lipogenic program appears to be at least one mechanism underlying the antidiabetic effect of rose hip.

  4. Decentralized control mechanism underlying interlimb coordination of millipedes.

    Science.gov (United States)

    Kano, Takeshi; Sakai, Kazuhiko; Yasui, Kotaro; Owaki, Dai; Ishiguro, Akio

    2017-04-04

    Legged animals exhibit adaptive and resilient locomotion through interlimb coordination. The long-term goal of this study is to clarify the relationship between the number of legs and the inherent decentralized control mechanism for interlimb coordination. As a preliminary step, the study focuses on millipedes as they represent the species with the greatest number of legs among various animal species. A decentralized control mechanism involving local force feedback was proposed based on the qualitative findings of behavioural experiments in which responses to the removal of part of the terrain and leg amputation were observed. The proposed mechanism was implemented in a developed millipede-like robot to demonstrate that the robot can adapt to the removal of the part of the terrain and leg amputation in a manner similar to that in behavioural experiments.

  5. Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

    International Nuclear Information System (INIS)

    Kaneuji, Takeshi; Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro; Takahashi, Tetsu; Nishihara, Tatsuji

    2011-01-01

    Highlights: → Effect of compressive force on osteoblasts were examined. → Compressive force induced OPG expression and suppressed osteoclastogenesis. → This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm 2 ) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-κB ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of IκBα, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca 2+ pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-κB) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt/Ca 2+ pathway.

  6. A possible realization of Einstein's causal theory underlying quantum mechanics

    International Nuclear Information System (INIS)

    Yussouff, M.

    1979-06-01

    It is shown that a new microscopic mechanics formulated earlier can be looked upon as a possible causal theory underlying quantum mechanics, which removes Einstein's famous objections against quantum theory. This approach is free from objections raised against Bohm's hidden variable theory and leads to a clear physical picture in terms of familiar concepts, if self interactions are held responsible for deviations from classical behaviour. The new level of physics unfolded by this approach may reveal novel frontiers in high-energy physics. (author)

  7. Permeability and mechanical properties of cracked glass under pressure

    International Nuclear Information System (INIS)

    Ougier-Simonin, A.

    2010-01-01

    Crack initiation and growth in brittle solids under tension have been extensively studied by various experimental, theoretical and numerical approaches. If has been established that dynamic brittle fracture is related to fundamental physical parameters and processes, such as crack speed, crack branching, surface roughening, and dynamic instabilities. On the other hand, less studies have been done in the area of compressive fracture despite its vital importance in geology, material science and engineering applications (such as the improvement and the insurance of the nuclear wastes storage). The present work aims to investigate thermo-mechanical cracking effects on elastic wave velocities, mechanical strength and permeability und r pressure to evaluate damage evolution, brittle failure and transport properties on a synthetic glass (SON 68), and to highlight the very different behavior of the glass amorphous structure compared to any rock structure. The original glass, produced in ideal conditions of slow cooling that prevent from any crack formation, exhibits a linear and reversible mechanical behavior and isotropic elastic velocities, as expected. It also presents a high strength as it fails at about 700 MPa of deviatoric stress for a confining pressure of 15 MPa. We choose to apply to some original glass samples a reproducible method (thermal treatment with a thermal shock of T=100,200 and 300 C) which creates cracks with a homogeneous distribution. The impact of the thermal treatment is clearly visible through the elastic wave velocity measurements as we observe crack closure under hydrostatic conditions (at about 30 MPa). For T ≥ 200 C, the glass mechanical behavior becomes non linear and records an irreversible damage. The total damage observed with the acoustic emissions in these samples underlines the combination of the thermal and the mechanical cracks which drive to the sample failure. The results obtained with pore fluid pressure show a very small

  8. Mechanism(s) involved in opioid drug abuse modulation of HAND.

    Science.gov (United States)

    Dutta, Raini; Roy, Sabita

    2012-07-01

    Drug abuse and HIV infection are interlinked. From the onset of the HIV/AIDS epidemic, the impact of illicit drug use on HIV disease progression has been a focus of many investigations. Both laboratory-based and epidemiological studies strongly indicate that drug abuse may exacerbate HIV disease progression and increase mortality and morbidity in these patients. Increase susceptibility to opportunistic infection has been implicated as one of the major causes for this detriment. Furthermore, opioids are known to elicit prevalence of neurodegenerative disorders in HIV-infected patients. Numerous authors have delineated various molecular as well as cellular mechanisms associated with neurological complications in these patients. This review gives an overview of these findings. Understanding the mechanisms will allow for the development of targeted therapies aimed at reducing the progression of neurocognitive decline in the drug abusing HIV infected individuals.

  9. Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia.

    Science.gov (United States)

    Ali, Bassam R; Ben-Rebeh, Imen; John, Anne; Akawi, Nadia A; Milhem, Reham M; Al-Shehhi, Nouf A; Al-Ameri, Mouza M; Al-Shamisi, Shamma A; Al-Gazali, Lihadh

    2011-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant genetic condition affecting the vascular system and is characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. This disorder affects approximately 1 in 8,000 people worldwide. Significant morbidity is associated with this condition in affected individuals, and anaemia can be a consequence of repeated haemorrhages from telangiectasia in the gut and nose. In the majority of the cases reported, the condition is caused by mutations in either ACVRL1 or endoglin genes, which encode components of the TGF-beta signalling pathway. Numerous missense mutations in endoglin have been reported as causative defects for HHT but the exact underlying cellular mechanisms caused by these mutations have not been fully established despite data supporting a role for the endoplasmic reticulum (ER) quality control machinery. For this reason, we examined the subcellular trafficking of twenty-five endoglin disease-causing missense mutations. The mutant proteins were expressed in HeLa and HEK293 cell lines, and their subcellular localizations were established by confocal fluorescence microscopy alongside the analysis of their N-glycosylation profiles. ER quality control was found to be responsible in eight (L32R, V49F, C53R, V125D, A160D, P165L, I271N and A308D) out of eleven mutants located on the orphan extracellular domain in addition to two (C363Y and C382W) out of thirteen mutants in the Zona Pellucida (ZP) domain. In addition, a single intracellular domain missense mutant was examined and found to traffic predominantly to the plasma membrane. These findings support the notion of the involvement of the ER's quality control in the mechanism of a significant number, but not all, missense endoglin mutants found in HHT type 1 patients. Other mechanisms including loss of interactions with signalling partners as well as adverse effects on functional residues are likely

  10. Mechanism of oxidative stress involved in the toxicity of ZnO nanoparticles against eukaryotic cells

    Directory of Open Access Journals (Sweden)

    M. Saliani

    2016-01-01

    Full Text Available ZnO NPs (zinc oxide nanoparticles has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications.

  11. Frictional behaviour of polymer films under mechanical and electrostatic loads

    International Nuclear Information System (INIS)

    Ginés, R; Christen, R; Motavalli, M; Bergamini, A; Ermanni, P

    2013-01-01

    Different polymer foils, namely polyimide, FEP, PFA and PVDF were tested on a setup designed to measure the static coefficient of friction between them. The setup was designed according to the requirements of a damping device based on electrostatically tunable friction. The foils were tested under different mechanically applied forces and showed reproducible results for the static coefficient of friction. With the same setup the measurements were performed under an electric field as the source of the normal force. Up to a certain electric field the values were in good agreement. Beyond this field discrepancies were found. (paper)

  12. Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Kaneuji, Takeshi [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Takahashi, Tetsu [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan)

    2011-04-29

    Highlights: {yields} Effect of compressive force on osteoblasts were examined. {yields} Compressive force induced OPG expression and suppressed osteoclastogenesis. {yields} This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm{sup 2}) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-{kappa}B ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of I{kappa}B{alpha}, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca{sup 2+} pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-{kappa}B) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt

  13. Reliability Issues and Solutions in Flexible Electronics Under Mechanical Fatigue

    Science.gov (United States)

    Yi, Seol-Min; Choi, In-Suk; Kim, Byoung-Joon; Joo, Young-Chang

    2018-03-01

    Flexible devices are of significant interest due to their potential expansion of the application of smart devices into various fields, such as energy harvesting, biological applications and consumer electronics. Due to the mechanically dynamic operations of flexible electronics, their mechanical reliability must be thoroughly investigated to understand their failure mechanisms and lifetimes. Reliability issue caused by bending fatigue, one of the typical operational limitations of flexible electronics, has been studied using various test methodologies; however, electromechanical evaluations which are essential to assess the reliability of electronic devices for flexible applications had not been investigated because the testing method was not established. By employing the in situ bending fatigue test, we has studied the failure mechanism for various conditions and parameters, such as bending strain, fatigue area, film thickness, and lateral dimensions. Moreover, various methods for improving the bending reliability have been developed based on the failure mechanism. Nanostructures such as holes, pores, wires and composites of nanoparticles and nanotubes have been suggested for better reliability. Flexible devices were also investigated to find the potential failures initiated by complex structures under bending fatigue strain. In this review, the recent advances in test methodology, mechanism studies, and practical applications are introduced. Additionally, perspectives including the future advance to stretchable electronics are discussed based on the current achievements in research.

  14. Control of a perturbed under-actuated mechanical system

    KAUST Repository

    Zayane, Chadia

    2015-11-05

    In this work, the trajectory tracking problem for an under-actuated mechanical system in presence of unknown input disturbances is addressed. The studied inertia wheel inverted pendulum falls in the class of non minimum phase systems. The proposed high order sliding mode control architecture including a controller and differentiator allows to track accurately the predefined trajectory and to stabilize the internal dynamics. The robustness of the proposed approach is illustrated through different perturbation and output noise configurations.

  15. Neural mechanisms underlying morphine withdrawal in addicted patients: a review

    Directory of Open Access Journals (Sweden)

    Nima Babhadiashar

    2015-06-01

    Full Text Available Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.

  16. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  17. Giant panda׳s tooth enamel: Structure, mechanical behavior and toughening mechanisms under indentation.

    Science.gov (United States)

    Weng, Z Y; Liu, Z Q; Ritchie, R O; Jiao, D; Li, D S; Wu, H L; Deng, L H; Zhang, Z F

    2016-12-01

    The giant panda׳s teeth possess remarkable load-bearing capacity and damage resistance for masticating bamboos. In this study, the hierarchical structure and mechanical behavior of the giant panda׳s tooth enamel were investigated under indentation. The effects of loading orientation and location on mechanical properties of the enamel were clarified and the evolution of damage in the enamel under increasing load evaluated. The nature of the damage, both at and beneath the indentation surfaces, and the underlying toughening mechanisms were explored. Indentation cracks invariably were seen to propagate along the internal interfaces, specifically the sheaths between enamel rods, and multiple extrinsic toughening mechanisms, e.g., crack deflection/twisting and uncracked-ligament bridging, were active to shield the tips of cracks from the applied stress. The giant panda׳s tooth enamel is analogous to human enamel in its mechanical properties, yet it has superior hardness and Young׳s modulus but inferior toughness as compared to the bamboo that pandas primarily feed on, highlighting the critical roles of the integration of underlying tissues in the entire tooth and the highly hydrated state of bamboo foods. Our objective is that this study can aid the understanding of the structure-mechanical property relations in the tooth enamel of mammals and further provide some insight on the food habits of the giant pandas. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Mechanical properties of graphene nanoribbons under uniaxial tensile strain

    Science.gov (United States)

    Yoneyama, Kazufumi; Yamanaka, Ayaka; Okada, Susumu

    2018-03-01

    Based on the density functional theory with the generalized gradient approximation, we investigated the mechanical properties of graphene nanoribbons in terms of their edge shape under a uniaxial tensile strain. The nanoribbons with armchair and zigzag edges retain their structure under a large tensile strain, while the nanoribbons with chiral edges are fragile against the tensile strain compared with those with armchair and zigzag edges. The fracture started at the cove region, which corresponds to the border between the zigzag and armchair edges for the nanoribbons with chiral edges. For the nanoribbons with armchair edges, the fracture started at one of the cove regions at the edges. In contrast, the fracture started at the inner region of the nanoribbons with zigzag edges. The bond elongation under the tensile strain depends on the mutual arrangement of covalent bonds with respect to the strain direction.

  19. Studies on Molecular Mechanisms Underlying Spinocerebellar Ataxia Type 3

    DEFF Research Database (Denmark)

    Kristensen, Line Vildbrad

    The polyglutamine (polyQ) disorders comprise nine diseases characterized by an expanded polyQ tract within the respective proteins. These disorders are rare but include the well-known Huntington’s disease, and several spinocerebellar ataxias (SCAs). The diseases usually strike midlife and progress....... Even though a range of mechanisms contributing to polyQ diseases have been uncovered, there is still no treatment available. One of the more common polyQ diseases is SCA3, which is caused by a polyQ expansion in the ataxin-3 protein that normally functions as a deubiquitinating enzyme involved...

  20. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  1. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    Science.gov (United States)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  2. Mechanical properties of a collagen fibril under simulated degradation.

    Science.gov (United States)

    Malaspina, David C; Szleifer, Igal; Dhaher, Yasin

    2017-11-01

    Collagen fibrils are a very important component in most of the connective tissue in humans. An important process associated with several physiological and pathological states is the degradation of collagen. Collagen degradation is usually mediated by enzymatic and non-enzymatic processes. In this work we use molecular dynamics simulations to study the influence of simulated degradation on the mechanical properties of the collagen fibril. We applied tensile stress to the collagen fiber at different stages of degradation. We compared the difference in the fibril mechanical priorities due the removal of enzymatic crosslink, surface degradation and volumetric degradation. As anticipated, our results indicated that, regardless of the degradation scenario, fibril mechanical properties is reduced. The type of degradation mechanism (crosslink, surface or volumetric) expressed differential effect on the change in the fibril stiffness. Our simulation results showed dramatic change in the fibril stiffness with a small amount of degradation. This suggests that the hierarchical structure of the fibril is a key component for the toughness and is very sensitive to changes in the organization of the fibril. The overall results are intended to provide a theoretical framework for the understanding the mechanical behavior of collagen fibrils under degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    OpenAIRE

    Lozano-Cuenca, J.; González-Hernández, A.; López-Canales, O.A.; Villagrana-Zesati, J.R.; Rodríguez-Choreão, J.D.; Morín-Zaragoza, R.; Castillo-Henkel, E.F.; López-Canales, J.S.

    2017-01-01

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10?9?10?5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-...

  4. Neural Correlates of Successful and Unsuccessful Strategical Mechanisms Involved in Uncertain Decision-Making.

    Directory of Open Access Journals (Sweden)

    Julie Giustiniani

    Full Text Available The ability to develop successful long-term strategies in uncertain situations relies on complex neural mechanisms. Although lesion studies have shown some of the mechanisms involved, it is still unknown why some healthy subjects are able to make the right decision whereas others are not. The aim of our study was to investigate neurophysiological differences underlying this ability to develop a successful strategy in a group of healthy subjects playing a monetary card game called the Iowa Gambling Task (IGT. In this task, subjects have to win and earn money by choosing between four decks of cards, two were advantageous in the long term and two disadvantageous. Twenty healthy right-handed subjects performed the IGT while their cerebral activity was recorded by electroencephalography. Based on their behavioral performances, two groups of subjects could clearly be distinguished: one who selected the good decks and thus succeeded in developing a Favorable strategy (9 subjects and one who remained Undecided (11 subjects. No neural difference was found between each group before the selection of a deck, but in both groups a greater negativity was found emerging from the right superior frontal gyrus 600 ms before a disadvantageous selection. During the processing of the feedback, an attenuation of the P200 and P300 waveforms was found for the Undecided group, and a P300 originating from the medial frontal gyrus was found in response to a loss only in the Favorable group. Our results suggest that undecided subjects are hyposensitive to the valence of the cards during gambling, which affects the feedback processing.

  5. Failure Mechanisms of Brittle Rocks under Uniaxial Compression

    Directory of Open Access Journals (Sweden)

    Liu Taoying

    2017-09-01

    Full Text Available The behaviour of a rock mass is determined not only by the properties of the rock matrix, but mostly by the presence and properties of discontinuities or fractures within the mass. The compression test on rock-like specimens with two prefabricated transfixion fissures, made by pulling out the embedded metal inserts in the pre-cured period was carried out on the servo control uniaxial loading tester. The influence of the geometry of pre-existing cracks on the cracking processes was analysed with reference to the experimental observation of crack initiation and propagation from pre-existing flaws. Based on the rock fracture mechanics and the stress-strain curves, the evolution failure mechanism of the fissure body was also analyzed on the basis of exploring the law of the compression-shear crack initiation, wing crack growth and rock bridge connection. Meanwhile, damage fracture mechanical models of a compression-shear rock mass are established when the rock bridge axial transfixion failure, tension-shear combined failure, or wing crack shear connection failure occurs on the specimen under axial compression. This research was of significance in studying the failure mechanism of fractured rock mass.

  6. Mechanisms underlying HIV-1 Vpu-mediated viral egress

    Directory of Open Access Journals (Sweden)

    Nicolas eRoy

    2014-05-01

    Full Text Available Viruses such as lentiviruses that are responsible for long lasting infections, have to evade several level of cellular immune mechanisms to persist and efficiently disseminate in the host. Over the past decades, many evidences have emerged regarding the major role of accessory proteins of primate lentiviruses (Human (HIV and simian immunodeficiency viruses (SIV in viral evasion from the host immune defense. This short review will provide an overview of the mechanism whereby the accessory protein Vpu contributes to this escape. Vpu is a multifunctional protein that was shown to contribute to viral egress by down-regulating several mediators of the immune system such as CD4, CD1d, NTB-A and the restriction factor BST2. The mechanisms underlying its activity are not fully characterized but rely on its ability to interfere with the host machinery regulating proteins turnover and vesicular trafficking. This review will focus on our current understanding of the mechanisms whereby Vpu down-regulates CD4 and BST2 expression level to favour viral egress.

  7. Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

    Science.gov (United States)

    Wei, Min; Li, Song; Le, Weidong

    2017-10-25

    Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

  8. Mechanisms involved in the transport of mercuric ions in target tissues

    Science.gov (United States)

    Bridges, Christy C.; Zalups, Rudolfs K.

    2016-01-01

    Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are taken up by and accumulate in numerous organs, including brain, intestine, kidney, liver, and placenta. In order to understand the toxicological effects of exposure to mercury, a thorough understanding of the mechanisms that facilitate entry of mercuric ions into target cells must first be obtained. A number of mechanisms for the transport of mercuric ions into target cells and organs have been proposed in recent years. However, the ability of these mechanisms to transport mercuric ions and the regulatory features of these carriers have not been characterized completely. The purpose of this review is to summarize the current findings related to the mechanisms that may be involved in the transport of inorganic and organic forms of mercury in target tissues and organs. This review will describe mechanisms known to be involved in the transport of mercury and will also propose additional mechanisms that may potentially be involved in the transport of mercuric ions into target cells. PMID:27422290

  9. Neural mechanism underlying autobiographical memory modulated by remoteness and emotion

    Science.gov (United States)

    Ge, Ruiyang; Fu, Yan; Wang, DaHua; Yao, Li; Long, Zhiying

    2012-03-01

    Autobiographical memory is the ability to recollect past events from one's own life. Both emotional tone and memory remoteness can influence autobiographical memory retrieval along the time axis of one's life. Although numerous studies have been performed to investigate brain regions involved in retrieving processes of autobiographical memory, the effect of emotional tone and memory age on autobiographical memory retrieval remains to be clarified. Moreover, whether the involvement of hippocampus in consolidation of autobiographical events is time dependent or independent has been controversial. In this study, we investigated the effect of memory remoteness (factor1: recent and remote) and emotional valence (factor2: positive and negative) on neural correlates underlying autobiographical memory by using functional magnetic resonance imaging (fMRI) technique. Although all four conditions activated some common regions known as "core" regions in autobiographical memory retrieval, there are some other regions showing significantly different activation for recent versus remote and positive versus negative memories. In particular, we found that bilateral hippocampal regions were activated in the four conditions regardless of memory remoteness and emotional valence. Thus, our study confirmed some findings of previous studies and provided further evidence to support the multi-trace theory which believes that the role of hippocampus involved in autobiographical memory retrieval is time-independent and permanent in memory consolidation.

  10. Age differences in the underlying mechanisms of stereotype threat effects.

    Science.gov (United States)

    Popham, Lauren E; Hess, Thomas M

    2015-03-01

    The goals of the present study were to (a) examine whether age differences exist in the mechanisms underlying stereotype threat effects on cognitive performance and (b) examine whether emotion regulation abilities may buffer against threat effects on performance. Older and younger adults were exposed to positive or negative age-relevant stereotypes, allowing us to examine the impact of threat on regulatory focus and working memory. Self-reported emotion regulation measures were completed prior to the session. Older adults' performance under threat suggested a prevention-focused approach to the task, indexed by increased accuracy and reduced speed. The same pattern was observed in younger adults, but the effects were not as strong. Age differences emerged when examining the availability of working memory resources under threat, with young adults showing decrements, whereas older adults did not. Emotion regulation abilities moderated threat effects in young adults but not in older adults. The results provide support for the notion that stereotype threat may lead to underperformance through somewhat different pathways in older and younger adults. Future research should further examine whether the underlying reason for this age difference is rooted in age-related improvements in emotion regulation. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. A theoretical study of the molecular mechanism of the GAPDH Trypanosoma cruzi enzyme involving iodoacetate inhibitor

    Science.gov (United States)

    Carneiro, Agnaldo Silva; Lameira, Jerônimo; Alves, Cláudio Nahum

    2011-10-01

    The glyceraldehyde-3-phosphate dehydrogenase enzyme (GAPDH) is an important biological target for the development of new chemotherapeutic agents against Chagas disease. In this Letter, the inhibition mechanism of GAPDH involving iodoacetate (IAA) inhibitor was studied using the hybrid quantum mechanical/molecular mechanical (QM/MM) approach and molecular dynamic simulations. Analysis of the potential energy surface and potential of mean force show that the covalent attachment of IAA inhibitor to the active site of the enzyme occurs as a concerted process. In addition, the energy terms decomposition shows that NAD+ plays an important role in stabilization of the reagents and transition state.

  12. The central anorexigenic mechanism of adrenocorticotropic hormone involves the caudal hypothalamus in chicks.

    Science.gov (United States)

    Shipp, Steven L; Yi, Jiaqing; Dridi, Sami; Gilbert, Elizabeth R; Cline, Mark A

    2015-10-01

    Adrenocorticotropic hormone (ACTH), consisting of 39 amino acids, is most well-known for its involvement in an organism's response to stress. It also participates in satiety, as exogenous ACTH causes decreased food intake in rats. However, its anorexigenic mechanism is not well understood in any species and its effect on appetite is not reported in the avian class. Thus, the present study was designed to evaluate central ACTH's effect on food intake and to elucidate the mechanism mediating this response using broiler chicks. Chicks that received intracerebroventricular (ICV) injection of 1, 2, or 4 nmol of ACTH reduced food intake, under both ad libitum and 180 min fasted conditions. Water intake was also reduced in ACTH-injected chicks under both feeding conditions, but when measured without access to feed it was not affected. Blood glucose was not affected in either feeding condition. Following ACTH injection, c-Fos immunoreactivity was quantified in key appetite-associated hypothalamic nuclei including the ventromedial hypothalamus (VMH), dorsomedial hypothalamus, lateral hypothalamus (LH), arcuate nucleus (ARC) and the parvo- and magno-cellular portions of the paraventricular nucleus. ACTH-injected chicks had increased c-Fos immunoreactivity in the VMH, LH, and ARC. Hypothalamus was collected at 1h post-injection, and real-time PCR performed to measure mRNA abundance of some appetite-associated factors. Neuropeptide Y, pro-opiomelanocortin, glutamate decarboxylase 1, melanocortin receptors 2-5, and urocortin 3 mRNA abundance was not affected by ACTH treatment. However, expression of corticotropin releasing factor (CRF), urotensin 2 (UT), agouti-related peptide (AgRP), and orexin (ORX), and melanocortin receptor 1 (MC1R) mRNA decreased in the hypothalamus of ACTH-injected chicks. In conclusion, ICV ACTH causes decreased food intake in chicks, and is associated with VMH, LH, and ARC activation, and a decrease in hypothalamic mRNA abundance of CRF, UT, AgRP, ORX

  13. Hierarchy of mechanisms involved in generating Na/K-ATPase polarity in MDCK epithelial cells

    NARCIS (Netherlands)

    Mays, R.W.; Siemers, K.A.; Fritz, B.A.; Lowe, A.W.; van Meer, G.; Nelson, W.J.

    1995-01-01

    We have studied mechanisms involved in generating a polarized distribution of Na/K-ATPase in the basal-lateral membrane of two clones of MDCK II cells. Both clones exhibit polarized distributions of marker proteins of the apical and basal-lateral membranes, including Na/K-ATPase, at steady state.

  14. Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury

    Science.gov (United States)

    Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injuryHenriquez, A.1, Snow, S.2, Miller, D1.,Schladweiler, M.2 and Kodavanti, U2.1 Curriculum in Toxicology, UNC, Chapel Hill, NC. 2 EPHD/NHEERL, US EPA, RTP, Durham, NC. ...

  15. Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia.

    Directory of Open Access Journals (Sweden)

    Bassam R Ali

    Full Text Available Hereditary haemorrhagic telangiectasia (HHT is an autosomal dominant genetic condition affecting the vascular system and is characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. This disorder affects approximately 1 in 8,000 people worldwide. Significant morbidity is associated with this condition in affected individuals, and anaemia can be a consequence of repeated haemorrhages from telangiectasia in the gut and nose. In the majority of the cases reported, the condition is caused by mutations in either ACVRL1 or endoglin genes, which encode components of the TGF-beta signalling pathway. Numerous missense mutations in endoglin have been reported as causative defects for HHT but the exact underlying cellular mechanisms caused by these mutations have not been fully established despite data supporting a role for the endoplasmic reticulum (ER quality control machinery. For this reason, we examined the subcellular trafficking of twenty-five endoglin disease-causing missense mutations. The mutant proteins were expressed in HeLa and HEK293 cell lines, and their subcellular localizations were established by confocal fluorescence microscopy alongside the analysis of their N-glycosylation profiles. ER quality control was found to be responsible in eight (L32R, V49F, C53R, V125D, A160D, P165L, I271N and A308D out of eleven mutants located on the orphan extracellular domain in addition to two (C363Y and C382W out of thirteen mutants in the Zona Pellucida (ZP domain. In addition, a single intracellular domain missense mutant was examined and found to traffic predominantly to the plasma membrane. These findings support the notion of the involvement of the ER's quality control in the mechanism of a significant number, but not all, missense endoglin mutants found in HHT type 1 patients. Other mechanisms including loss of interactions with signalling partners as well as adverse effects on functional

  16. Electrochemical mechanism of tin membrane electrodeposition under ultrasonic waves.

    Science.gov (United States)

    Nan, Tianxiang; Yang, Jianguang; Chen, Bing

    2018-04-01

    Tin was electrodeposited from chloride solutions using a membrane cell under ultrasonic waves. Cyclic voltammetry (CV), linear sweep voltammetry (LSV), chronoamperometry (CHR), and chronopotentiometry were applied to investigate the electrochemical mechanism of tin electrodeposition under ultrasonic field. Chronoamperometry curves showed that the initial process of tin electrodeposition followed the diffusion controlled three-dimensional nucleation and grain growth mechanism. The analysis of the cyclic voltammetry and linear sweep voltammetry diagrams showed that the application of ultrasound can change the tin membrane electro-deposition reaction from diffusion to electrochemical control, and the optimum parameters for tin electrodeposition were H + concentration 3.5 mol·L -1 , temperature 35 °C and ultrasonic power 100 W. The coupling ultrasonic field played a role in refining the grain in this process. The growth of tin crystals showed no orientation preferential, and the tin deposition showed a tendency to form a regular network structure after ultrasonic coupling. While in the absence of ultrasonic coupling, the growth of tin crystals has a high preferential orientation, and the tin deposition showed a tendency to form tin whiskers. Ultrasonic coupling was more favorable for obtaining a more compact and smoother cathode tin layer. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  18. Effects of manual hyperinflation in preterm newborns under mechanical ventilation.

    Science.gov (United States)

    Viana, Camila Chaves; Nicolau, Carla Marques; Juliani, Regina Celia Turola Passos; Carvalho, Werther Brunow de; Krebs, Vera Lucia Jornada

    2016-09-01

    To assess the effects of manual hyperinflation, performed with a manual resuscitator with and without the positive end-expiratory pressure valve, on the respiratory function of preterm newborns under mechanical ventilation. Cross-sectional study of hemodynamically stable preterm newborns with gestational age of less than 32 weeks, under mechanical ventilation and dependent on it at 28 days of life. Manual hyperinflation was applied randomly, alternating the use or not of the positive end-expiratory pressure valve, followed by tracheal aspiration for ending the maneuver. For nominal data, the two-tailed Wilcoxon test was applied at the 5% significance level and 80% power. Twenty-eight preterm newborns, with an average birth weight of 1,005.71 ± 372.16g, an average gestational age of 28.90 ± 1.79 weeks, an average corrected age of 33.26 ± 1.78 weeks, and an average mechanical ventilation time of 29.5 (15 - 53) days, were studied. Increases in inspiratory and expiratory volumes occurred between time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in both the maneuver with the valve (p = 0.001 and p = 0.009) and without the valve (p = 0.026 and p = 0.001), respectively. There was also an increase in expiratory resistance between time-points A5 and C1 (p = 0.044). Lung volumes increased when performing the maneuver with and without the valve, with a significant difference in the first minute after aspiration. There was a significant difference in expiratory resistance between the time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in the first minute after aspiration within each maneuver.

  19. Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Trung Dung; Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au [School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland (Australia)

    2014-05-05

    Based on the characterization by Atomic Force Microscopy, we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young's moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton and the intracellular fluid when the fixed chondrocytes are mainly governed by their intracellular fluid, which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.

  20. Education on invasive mechanical ventilation involving intensive care nurses: a systematic review.

    Science.gov (United States)

    Guilhermino, Michelle C; Inder, Kerry J; Sundin, Deborah

    2018-03-26

    Intensive care unit nurses are critical for managing mechanical ventilation. Continuing education is essential in building and maintaining nurses' knowledge and skills, potentially improving patient outcomes. The aim of this study was to determine whether continuing education programmes on invasive mechanical ventilation involving intensive care unit nurses are effective in improving patient outcomes. Five electronic databases were searched from 2001 to 2016 using keywords such as mechanical ventilation, nursing and education. Inclusion criteria were invasive mechanical ventilation continuing education programmes that involved nurses and measured patient outcomes. Primary outcomes were intensive care unit mortality and in-hospital mortality. Secondary outcomes included hospital and intensive care unit length of stay, length of intubation, failed weaning trials, re-intubation incidence, ventilation-associated pneumonia rate and lung-protective ventilator strategies. Studies were excluded if they excluded nurses, patients were ventilated for less than 24 h, the education content focused on protocol implementation or oral care exclusively or the outcomes were participant satisfaction. Quality was assessed by two reviewers using an education intervention critical appraisal worksheet and a risk of bias assessment tool. Data were extracted independently by two reviewers and analysed narratively due to heterogeneity. Twelve studies met the inclusion criteria for full review: 11 pre- and post-intervention observational and 1 quasi-experimental design. Studies reported statistically significant reductions in hospital length of stay, length of intubation, ventilator-associated pneumonia rates, failed weaning trials and improvements in lung-protective ventilation compliance. Non-statistically significant results were reported for in-hospital and intensive care unit mortality, re-intubation and intensive care unit length of stay. Limited evidence of the effectiveness of

  1. Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

    Science.gov (United States)

    Ikegami, Keisuke; Yoshimura, Takashi

    2016-02-01

    Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Raynaud's Phenomenon: A Brief Review of the Underlying Mechanisms.

    Science.gov (United States)

    Fardoun, Manal M; Nassif, Joseph; Issa, Khodr; Baydoun, Elias; Eid, Ali H

    2016-01-01

    Raynaud's phenomenon (RP) is characterized by exaggerated cold-induced vasoconstriction. This augmented vasoconstriction occurs by virtue of a reflex response to cooling via the sympathetic nervous system as well as by local activation of α 2C adrenoceptors (α 2C -AR). In a cold-initiated, mitochondrion-mediated mechanism involving reactive oxygen species and the Rho/ROCK pathway, cytoskeletal rearrangement in vascular smooth muscle cells orchestrates the translocation of α 2C -AR to the cell membrane, where this receptor readily interacts with its ligand. Different parameters are involved in this spatial and functional rescue of α 2C -AR. Of notable relevance is the female hormone, 17β-estradiol, or estrogen. This is consistent with the high prevalence of RP in premenopausal women compared to age-matched males. In addition to dissecting the role of these various players, the contribution of pollution as well as genetic background to the onset and prevalence of RP are also discussed. Different therapeutic approaches employed as treatment modalities for this disease are also highlighted and analyzed. The lack of an appropriate animal model for RP mandates that more efforts be undertaken in order to better understand and eventually treat this disease. Although several lines of treatment are utilized, it is important to note that precaution is often effective in reducing severity or frequency of RP attacks.

  3. Neural mechanisms underlying social conformity in an ultimatum game

    Directory of Open Access Journals (Sweden)

    Zhenyu eWei

    2013-12-01

    Full Text Available When individuals’ actions are incongruent with those of the group they belong to, they may change their initial behavior in order to conform to the group norm. This phenomenon is known as social conformity. In the present study, we used event-related functional magnetic resonance imaging (fMRI to investigate brain activity in response to group opinion during an ultimatum game. Results showed that participants changed their choices when these choices conflicted with the normative opinion of the group they were members of, especially in conditions of unfair treatment. The fMRI data revealed that a conflict with group norms activated the brain regions involved in norm violations and behavioral adjustment. Furthermore, in the reject-unfair condition, we observed that a conflict with group norms activated the medial frontal gyrus. These findings contribute to recent research examining neural mechanisms involved in detecting violations of social norms, and provide information regarding the neural representation of conformity behavior in an economic game.

  4. Raynaud's Phenomenon: a Brief Review of the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Manal Fardoun

    2016-11-01

    Full Text Available Raynaud's phenomenon (RP is characterized by exaggerated cold-induced vasoconstriction. This augmented vasoconstriction occurs by virtue of a reflex response to cooling via the sympathetic nervous system as well as by local activation of α2C adrenoceptors (α2C-AR. In a cold-initiated, mitochondrion-mediated mechanism involving reactive oxygen species and the Rho/ROCK pathway, cytoskeletal rearrangement in vascular smooth muscle cells (VSMCs orchestrates the translocation of α2C-AR to the cell membrane, where this receptor readily interacts with its ligand. Different parameters are involved in this spatial and functional rescue of α2C-AR. Of notable relevance is the female hormone, 17β-estradiol, or estrogen. This is consistent with the high prevalence of RP in pre-menopausal women compared to age-matched males. In addition to dissecting the role of these various players, the contribution of pollution as well as genetic background to the onset and prevalence of RP are also discussed. Different therapeutic approaches employed as treatment modalities for this disease are also highlighted and analyzed. The lack of an appropriate animal model for RP mandates that more efforts be undertaken in order to better understand and eventually treat this disease. Although several lines of treatment are utilized, it is important to note that precaution is often effective in reducing severity or frequency of RP attacks.

  5. Reliability-based optimization of maintenance scheduling of mechanical components under fatigue.

    Science.gov (United States)

    Beaurepaire, P; Valdebenito, M A; Schuëller, G I; Jensen, H A

    2012-05-01

    This study presents the optimization of the maintenance scheduling of mechanical components under fatigue loading. The cracks of damaged structures may be detected during non-destructive inspection and subsequently repaired. Fatigue crack initiation and growth show inherent variability, and as well the outcome of inspection activities. The problem is addressed under the framework of reliability based optimization. The initiation and propagation of fatigue cracks are efficiently modeled using cohesive zone elements. The applicability of the method is demonstrated by a numerical example, which involves a plate with two holes subject to alternating stress.

  6. The dual role of autophagy under hypoxia-involvement of interaction between autophagy and apoptosis.

    Science.gov (United States)

    Li, Mengmeng; Tan, Jin; Miao, Yuyang; Lei, Ping; Zhang, Qiang

    2015-06-01

    Hypoxia is one of severe cellular stress and it is well known to be associated with a worse outcome since a lack of oxygen accelerates the induction of apoptosis. Autophagy, an important and evolutionarily conserved mechanism for maintaining cellular homeostasis, is closely related to the apoptosis caused by hypoxia. Generally autophagy blocks the induction of apoptosis and inhibits the activation of apoptosis-associated caspase which could reduce cellular injury. However, in special cases, autophagy or autophagy-relevant proteins may help to induce apoptosis, which could aggravate cell damage under hypoxia condition. In addition, the activation of apoptosis-related proteins-caspase can also degrade autophagy-related proteins, such as Atg3, Atg4, Beclin1 protein, inhibiting autophagy. Although the relationship between autophagy and apoptosis has been known for rather complex for more than a decade, the underlying regulatory mechanisms have not been clearly understood. This short review discusses and summarizes the dual role of autophagy and the interaction and molecular regulatory mechanisms between autophagy and apoptosis under hypoxia.

  7. Hypothalamic corticotropin-releasing factor is centrally involved in learning under moderate stress.

    Science.gov (United States)

    Lucas, Morgan; Chen, Alon; Richter-Levin, Gal

    2013-08-01

    The corticotropin-releasing factor (CRF) neuropeptide is found to have a pivotal role in the regulation of the behavioral and neuroendocrine responses to stressful challenges. Here, we studied the involvement of the hypothalamic CRF in learning under stressful conditions. We have used a site-specific viral approach to knockdown (KD) CRF expression in the paraventricular nucleus of the hypothalamus (PVN). The two-way shuttle avoidance (TWSA) task was chosen to assess learning and memory under stressful conditions. Control animals learned to shuttle from one side to the other to avoid electrical foot shock by responding to a tone. Novel object and social recognition tasks were used to assess memory under less stressful conditions. KD of PVN-CRF expression decreased the number of avoidance responses in a TWSA session under moderate (0.8 mA), but not strong (1.5 mA), stimulus intensity compared to control rats. On the other hand, KD of PVN-CRF had no effect on memory performance in the less stressful novel object or social recognition tasks. Interestingly, basal or stress-induced corticosterone levels in CRF KD rats were not significantly different from controls. Taken together, the data suggest that the observed impairment was not a result of alteration in HPA axis activity, but rather due to reduced PVN-CRF activity on other brain areas. We propose that hypothalamic CRF is centrally involved in learning under moderate stressful challenge. Under 'basal' (less stressful) conditions or when the intensity of the stress is more demanding, central CRF ceases to be the determinant factor, as was indicated by performances in the TWSA with higher stimulus intensity or in the less stressful tasks of object and social recognition.

  8. Algorithmic mechanisms for reliable crowdsourcing computation under collusion.

    Science.gov (United States)

    Fernández Anta, Antonio; Georgiou, Chryssis; Mosteiro, Miguel A; Pareja, Daniel

    2015-01-01

    We consider a computing system where a master processor assigns a task for execution to worker processors that may collude. We model the workers' decision of whether to comply (compute the task) or not (return a bogus result to save the computation cost) as a game among workers. That is, we assume that workers are rational in a game-theoretic sense. We identify analytically the parameter conditions for a unique Nash Equilibrium where the master obtains the correct result. We also evaluate experimentally mixed equilibria aiming to attain better reliability-profit trade-offs. For a wide range of parameter values that may be used in practice, our simulations show that, in fact, both master and workers are better off using a pure equilibrium where no worker cheats, even under collusion, and even for colluding behaviors that involve deviating from the game.

  9. Microarray Analysis of the Molecular Mechanism Involved in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Cheng Tan

    2018-01-01

    Full Text Available Purpose. This study aimed to investigate the underlying molecular mechanisms of Parkinson’s disease (PD by bioinformatics. Methods. Using the microarray dataset GSE72267 from the Gene Expression Omnibus database, which included 40 blood samples from PD patients and 19 matched controls, differentially expressed genes (DEGs were identified after data preprocessing, followed by Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analyses. Protein-protein interaction (PPI network, microRNA- (miRNA- target regulatory network, and transcription factor- (TF- target regulatory networks were constructed. Results. Of 819 DEGs obtained, 359 were upregulated and 460 were downregulated. Two GO terms, “rRNA processing” and “cytoplasm,” and two KEGG pathways, “metabolic pathways” and “TNF signaling pathway,” played roles in PD development. Intercellular adhesion molecule 1 (ICAM1 was the hub node in the PPI network; hsa-miR-7-5p, hsa-miR-433-3p, and hsa-miR-133b participated in PD pathogenesis. Six TFs, including zinc finger and BTB domain-containing 7A, ovo-like transcriptional repressor 1, GATA-binding protein 3, transcription factor dp-1, SMAD family member 1, and quiescin sulfhydryl oxidase 1, were related to PD. Conclusions. “rRNA processing,” “cytoplasm,” “metabolic pathways,” and “TNF signaling pathway” were key pathways involved in PD. ICAM1, hsa-miR-7-5p, hsa-miR-433-3p, hsa-miR-133b, and the abovementioned six TFs might play important roles in PD development.

  10. Seminal vesicle intraepithelial involvement by prostate cancer: putative mechanism and clinicopathological significance.

    Science.gov (United States)

    Miyai, Kosuke; Kristiansen, Anna; Egevad, Lars; Pina-Oviedo, Sergio; Divatia, Mukul K; Shen, Steven S; Miles, Brian J; Ayala, Alberto G; Park, Yong Wook; Ro, Jae Y

    2014-09-01

    We have recently shown seminal vesicle intraepithelial involvement of prostate cancer in cases with seminal vesicle invasion (pT3b). Based on the manner of seminal vesicle invasion, there could be 2 possible mechanisms of seminal vesicle intraepithelial involvement: direct intraepithelial invasion from prostate carcinoma in the muscular wall of seminal vesicles or intraepithelial involvement of cancer from the invaginated extraprostatic space (IES)/ejaculatory duct system to extraprostatic seminal vesicle. We aimed to clarify the manner and clinicopathological significance of seminal vesicle intraepithelial involvement. Of 1629 consecutive radical prostatectomies, 109 cases (6.7%) showed seminal vesicle invasion in whole-mounted radical prostatectomy specimens. In these pT3b cases, 18 (17%) showed seminal vesicle intraepithelial involvement by prostate cancer. Stromal invasion of the IES/ejaculatory duct system and ejaculatory duct intraepithelial invasion by prostate cancer were identified in 62 and 5 of 109 pT3b cases, respectively. However, the presence/absence of IES/ejaculatory duct system involvement by prostate cancer does not predict seminal vesicle intraepithelial involvement. No statistically significant correlation was observed between all pathologic parameters/biochemical recurrence and the presence/absence of seminal vesicle intra-epithelial involvement in the pT3b cases. These findings suggest that seminal vesicle intraepithelial involvement is more likely due to direct invasion of carcinoma from the muscular wall of seminal vesicles rather than intraepithelial extension from the ejaculatory duct system in the IES. Further studies with a substantially greater case number are needed to clarify the clinicopathological significance of seminal vesicle intraepithelial involvement in a better manner. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. The mechanisms underlying fructose-induced hypertension: a review

    Science.gov (United States)

    Klein, Alice Victoria; Kiat, Hosen

    2015-01-01

    We are currently in the midst of an epidemic of metabolic disorders, which may, in part, be explained by excess fructose intake. This theory is supported by epidemiological observations as well as experimental studies in animals and humans. Rising consumption of fructose has been matched with growing rates of hypertension, leading to concern from public health experts. At this stage, the mechanisms underlying fructose-induced hypertension have not been fully characterized and the bulk of our knowledge is derived from animal models. Animal studies have shown that high-fructose diets up-regulate sodium and chloride transporters, resulting in a state of salt overload that increases blood pressure. Excess fructose has also been found to activate vasoconstrictors, inactivate vasodilators, and over-stimulate the sympathetic nervous system. Further work is required to determine the relevance of these findings to humans and to establish the level at which dietary fructose increases the risk of developing hypertension PMID:25715094

  12. Degradation Mechanisms of Transparent Polyurethane Interlayer under UV Irradiation

    Directory of Open Access Journals (Sweden)

    OU Yingchun

    2017-01-01

    Full Text Available According to the ageing problem of laminated transparency, the trasparent polyurethane film used as interlayer had been irradiated by fluorescent ultraviolet lamp for 0 h, 200 h, 300 h, and 500 h respectively. With the aid of ultraviolet/visible spectrophotometer, FTIR and SEM etc., the color, structure and morphology of the materials were studied. SEM shows that when the irradiation time is increased to 500 h, the film surface cracks. The UV degradation mechanisms are that -CH2- of the position connecting the O and N from hard segment and the soft segment are easy to oxidize and produce hydrogen peroxide under UV and oxygen, which is furtherly oxidized to CO, and some part of the C-O and C-N bonds is cracked through β scission, and then the materials are fractured.

  13. Nonlinear mechanical response of supercooled melts under applied forces

    Science.gov (United States)

    Cárdenas, Heliana; Frahsa, Fabian; Fritschi, Sebastian; Nicolas, Alexandre; Papenkort, Simon; Voigtmann, Thomas; Fuchs, Matthias

    2017-08-01

    We review recent progress on a microscopic theoretical approach to describe the nonlinear response of glass-forming colloidal dispersions under strong external forcing leading to homogeneous and inhomogeneous flow. Using mode-coupling theory (MCT), constitutive equations for the rheology of viscoelastic shear-thinning fluids are obtained. These are, in suitably simplified form, employed in continuum fluid dynamics, solved by a hybrid-Lattice Boltzmann (LB) algorithm that was developed to deal with long-lasting memory effects. The combined microscopic theoretical and mesoscopic numerical approach captures a number of phenomena far from equilibrium, including the yielding of metastable states, process-dependent mechanical properties, and inhomogeneous pressure-driven channel flow.

  14. POSSIBLE MECHANISMS UNDERLYING THE THERAPEUTIC EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION

    Directory of Open Access Journals (Sweden)

    Alexander eChervyakov

    2015-06-01

    Full Text Available Transcranial magnetic stimulation (TMS is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson's disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation (LTP and long-term depression (LTD. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor (BDNF concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals. It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols.

  15. Involvement of cathepsin B in mitochondrial apoptosis by p-phenylenediamine under ambient UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Goyal, Shruti; Amar, Saroj Kumar [Photobiology Division, CSIR – Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India); Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow (India); Dubey, Divya; Pal, Manish Kumar [Photobiology Division, CSIR – Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India); Singh, Jyoti [Photobiology Division, CSIR – Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India); Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow (India); Verma, Ankit; Kushwaha, Hari Narayan [Photobiology Division, CSIR – Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India); Ray, Ratan Singh, E-mail: ratanray.2011@rediffmail.com [Photobiology Division, CSIR – Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India)

    2015-12-30

    Highlights: • Photodegradation and formation of photoproduct. • Involvement of ROS in PPD phototoxicity. • Role of ROS in DNA damage, CPD and micronuclei formation. • PPD induced lysosomal destabilization and release of cathepsin B. • Cleavage of Bid and activation of mitochondrial apoptosis. - Abstract: Paraphenylenediamine (PPD), a derivative of paranitroaniline has been most commonly used as an ingredient of oxidative hair dye and permanent tattoos. We have studied the phototoxic potential of PPD under ambient ultraviolet radiation. PPD is photodegraded and form a novel photoproduct under UV A exposure. PPD shows a concentration dependent decrease in cell viability of human Keratinocyte cells (HaCaT) through MTT and NRU test. Significant intracellular ROS generation was measured by DCFDA assay. It caused an oxidative DNA damage via single stranded DNA breaks, micronuclei and CPD formation. Both lysosome and mitochondria is main target for PPD induced apoptosis which was proved through lysosomal destabilization and release of cathepsin B by immunofluorescence, real time PCR and western blot analysis. Cathepsin B process BID to active tBID which induces the release of cytochrome C from mitochondria. Mitochondrial depolarization was reported through transmission electron microscopy. The cathepsin inhibitor reduced the release of cytochrome C in PPD treated cells. Thus study suggests that PPD leads to apoptosis via the involvement of lysosome and mitochondria both under ambient UV radiation. Therefore, photosensitizing nature of hair dye ingredients should be tested before coming to market as a cosmetic product for the safety of human beings.

  16. Involvement of cathepsin B in mitochondrial apoptosis by p-phenylenediamine under ambient UV radiation

    International Nuclear Information System (INIS)

    Goyal, Shruti; Amar, Saroj Kumar; Dubey, Divya; Pal, Manish Kumar; Singh, Jyoti; Verma, Ankit; Kushwaha, Hari Narayan; Ray, Ratan Singh

    2015-01-01

    Highlights: • Photodegradation and formation of photoproduct. • Involvement of ROS in PPD phototoxicity. • Role of ROS in DNA damage, CPD and micronuclei formation. • PPD induced lysosomal destabilization and release of cathepsin B. • Cleavage of Bid and activation of mitochondrial apoptosis. - Abstract: Paraphenylenediamine (PPD), a derivative of paranitroaniline has been most commonly used as an ingredient of oxidative hair dye and permanent tattoos. We have studied the phototoxic potential of PPD under ambient ultraviolet radiation. PPD is photodegraded and form a novel photoproduct under UV A exposure. PPD shows a concentration dependent decrease in cell viability of human Keratinocyte cells (HaCaT) through MTT and NRU test. Significant intracellular ROS generation was measured by DCFDA assay. It caused an oxidative DNA damage via single stranded DNA breaks, micronuclei and CPD formation. Both lysosome and mitochondria is main target for PPD induced apoptosis which was proved through lysosomal destabilization and release of cathepsin B by immunofluorescence, real time PCR and western blot analysis. Cathepsin B process BID to active tBID which induces the release of cytochrome C from mitochondria. Mitochondrial depolarization was reported through transmission electron microscopy. The cathepsin inhibitor reduced the release of cytochrome C in PPD treated cells. Thus study suggests that PPD leads to apoptosis via the involvement of lysosome and mitochondria both under ambient UV radiation. Therefore, photosensitizing nature of hair dye ingredients should be tested before coming to market as a cosmetic product for the safety of human beings.

  17. Organic food consumption in Taiwan: Motives, involvement, and purchase intention under the moderating role of uncertainty.

    Science.gov (United States)

    Teng, Chih-Ching; Lu, Chi-Heng

    2016-10-01

    Despite the progressive development of the organic food sector in Taiwan, little is known about how consumers' consumption motives will influence organic food decision through various degrees of involvement and whether or not consumers with various degrees of uncertainty will vary in their intention to buy organic foods. The current study aims to examine the effect of consumption motives on behavioral intention related to organic food consumption under the mediating role of involvement as well as the moderating role of uncertainty. Research data were collected from organic food consumers in Taiwan via a questionnaire survey, eventually obtaining 457 valid questionnaires for analysis. This study tested the overall model fit and hypotheses through structural equation modeling method (SEM). The results show that consumer involvement significantly mediates the effects of health consciousness and ecological motives on organic food purchase intention, but not applied to food safety concern. Moreover, the moderating effect of uncertainty is statistical significance, indicating that the relationship between involvement and purchase intention becomes weaker in the condition of consumers with higher degree of uncertainty. Several implications and suggestions are also discussed for organic food providers and marketers. Copyright © 2016. Published by Elsevier Ltd.

  18. Nonlinear Mechanics of MEMS Rectangular Microplates under Electrostatic Actuation

    KAUST Repository

    Saghir, Shahid

    2016-12-01

    The first objective of the dissertation is to develop a suitable reduced order model capable of investigating the nonlinear mechanical behavior of von-Karman plates under electrostatic actuation. The second objective is to investigate the nonlinear static and dynamic behavior of rectangular microplates under small and large actuating forces. In the first part, we present and compare various approaches to develop reduced order models for the nonlinear von-Karman rectangular microplates actuated by nonlinear electrostatic forces. The reduced-order models aim to investigate the static and dynamic behavior of the plate under small and large actuation forces. A fully clamped microplate is considered. Different types of basis functions are used in conjunction with the Galerkin method to discretize the governing equations. First we investigate the convergence with the number of modes retained in the model. Then for validation purpose, a comparison of the static results is made with the results calculated by a nonlinear finite element model. The linear eigenvalue problem for the plate under the electrostatic force is solved for a wide range of voltages up to pull-in. In the second part, we present an investigation of the static and dynamic behavior of a fully clamped microplate. We investigate the effect of different non-dimensional design parameters on the static response. The forced-vibration response of the plate is then investigated when the plate is excited by a harmonic AC load superimposed to a DC load. The dynamic behavior is examined near the primary and secondary (superharmonic and subharmonic) resonances. The microplate shows a strong hardening behavior due to the cubic nonlinearity of midplane stretching. However, the behavior switches to softening as the DC load is increased. Next, near-square plates are studied to understand the effect of geometric imperfections of microplates. In the final part of the dissertation, we investigate the mechanical behavior of

  19. Mechanisms underlying the social enhancement of vocal learning in songbirds.

    Science.gov (United States)

    Chen, Yining; Matheson, Laura E; Sakata, Jon T

    2016-06-14

    Social processes profoundly influence speech and language acquisition. Despite the importance of social influences, little is known about how social interactions modulate vocal learning. Like humans, songbirds learn their vocalizations during development, and they provide an excellent opportunity to reveal mechanisms of social influences on vocal learning. Using yoked experimental designs, we demonstrate that social interactions with adult tutors for as little as 1 d significantly enhanced vocal learning. Social influences on attention to song seemed central to the social enhancement of learning because socially tutored birds were more attentive to the tutor's songs than passively tutored birds, and because variation in attentiveness and in the social modulation of attention significantly predicted variation in vocal learning. Attention to song was influenced by both the nature and amount of tutor song: Pupils paid more attention to songs that tutors directed at them and to tutors that produced fewer songs. Tutors altered their song structure when directing songs at pupils in a manner that resembled how humans alter their vocalizations when speaking to infants, that was distinct from how tutors changed their songs when singing to females, and that could influence attention and learning. Furthermore, social interactions that rapidly enhanced learning increased the activity of noradrenergic and dopaminergic midbrain neurons. These data highlight striking parallels between humans and songbirds in the social modulation of vocal learning and suggest that social influences on attention and midbrain circuitry could represent shared mechanisms underlying the social modulation of vocal learning.

  20. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

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    Nguyen Quoc Vuong Tran

    2017-01-01

    Full Text Available The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD and attention deficit hyperactivity disorder (ADHD, calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates, persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.

  1. Thermal stability of nafion membranes under mechanical stress

    Energy Technology Data Exchange (ETDEWEB)

    Quintilii, M.; Struis, R. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1997-06-01

    The feasibility of adequately modified fluoro-ionomer membranes (NAFION{sup R}) is demonstrated for the selective separation of methanol synthesis products from the raw reactor gas at temperatures around 200{sup o}C. For an economically relevant application of this concept on a technical scale the Nafion membranes should be thin ({approx_equal}10 {mu}m) and thermally stable over a long period of time (1-2 years). In cooperation with industry (Methanol Casale SA, Lugano (CH)), we test the thermal stability of Nafion hollow fibers and supported Nafion thin sheet membranes at temperatures between 160 and 200{sup o}C under mechanical stress by applying a gas pressure difference over the membrane surface ({Delta}P{<=} 40 bar). Tests with the hollow fibers revealed that Nafion has visco-elastic properties. Tests with 50 {mu}m thin Nafion sheets supported by a porous metal carrier at 200{sup o}C and {Delta}P=39 bar showed no mechanical defects over a period of 92 days. (author) 5 figs., 4 refs.

  2. Using Drosophila to discover mechanisms underlying type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ronald W. Alfa

    2016-04-01

    Full Text Available Mechanisms of glucose homeostasis are remarkably well conserved between the fruit fly Drosophila melanogaster and mammals. From the initial characterization of insulin signaling in the fly came the identification of downstream metabolic pathways for nutrient storage and utilization. Defects in these pathways lead to phenotypes that are analogous to diabetic states in mammals. These discoveries have stimulated interest in leveraging the fly to better understand the genetics of type 2 diabetes mellitus in humans. Type 2 diabetes results from insulin insufficiency in the context of ongoing insulin resistance. Although genetic susceptibility is thought to govern the propensity of individuals to develop type 2 diabetes mellitus under appropriate environmental conditions, many of the human genes associated with the disease in genome-wide association studies have not been functionally studied. Recent advances in the phenotyping of metabolic defects have positioned Drosophila as an excellent model for the functional characterization of large numbers of genes associated with type 2 diabetes mellitus. Here, we examine results from studies modeling metabolic disease in the fruit fly and compare findings to proposed mechanisms for diabetic phenotypes in mammals. We provide a systematic framework for assessing the contribution of gene candidates to insulin-secretion or insulin-resistance pathways relevant to diabetes pathogenesis.

  3. Involvement of free radicals followed by the activation of phospholipase A2 in the mechanism that underlies the combined effects of methamphetamine and morphine on subacute toxicity or lethality in mice: Comparison of the therapeutic potential of fullerene, mepacrine, and cooling

    International Nuclear Information System (INIS)

    Mori, Tomohisa; Ito, Shinobu; Namiki, Mizuho; Suzuki, Tadashi; Kobayashi, Shizuko; Matsubayashi, Kenji; Sawaguchi, Toshiko

    2007-01-01

    An increase in polydrug abuse is a major problem worldwide. The coadministration of methamphetamine and morphine increased subacute toxicity or lethality in rodents. However, the underlying mechanisms by which lethality is increased by the coadministration of methamphetamine and morphine are not yet fully understood. Coadministered methamphetamine and morphine induced lethality by more than 80% in BALB/c mice, accompanied by the rupture of cells in the kidney and liver, and an increase in poly (ADP-ribose) polymerase (PARP)-immunoreactive cells in the heart, kidney and liver. The lethal effect and the increase in the incidence of rupture or PARP-immunoreactive cells induced by the coadministration of methamphetamine and morphine was significantly attenuated by pretreatment with mepacrine (phospholipase A 2 inhibitor) or fullerene (a radical scavenger), or by cooling from 30 to 90 min after drug administration. Furthermore, based on the results of the electron spin resonance spin-trapping technique, hydroxyl radicals were increased by the administration of methamphetamine and morphine, and these increased hydroxyl radicals were potently attenuated by fullerene and cooling. These results suggest that hydroxyl radicals plays an important role in the increased lethality induced by the coadministration of methamphetamine plus morphine. The potency of cooling or drugs for decreasing the subacute toxicity or lethality induced by the coadministration of methamphetamine and morphine was in the order fullerene = cooling > mepacrine. These results indicate that fullerene and cooling are beneficial for preventing death that is induced by the coadministration of methamphetamine and morphine

  4. Mechanisms underlying temperature extremes in Iberia: a Lagrangian perspective

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    João A. Santos

    2015-04-01

    Full Text Available The mechanisms underlying the occurrence of temperature extremes in Iberia are analysed considering a Lagrangian perspective of the atmospheric flow, using 6-hourly ERA-Interim reanalysis data for the years 1979–2012. Daily 2-m minimum temperatures below the 1st percentile and 2-m maximum temperatures above the 99th percentile at each grid point over Iberia are selected separately for winter and summer. Four categories of extremes are analysed using 10-d backward trajectories initialized at the extreme temperature grid points close to the surface: winter cold (WCE and warm extremes (WWE, and summer cold (SCE and warm extremes (SWE. Air masses leading to temperature extremes are first transported from the North Atlantic towards Europe for all categories. While there is a clear relation to large-scale circulation patterns in winter, the Iberian thermal low is important in summer. Along the trajectories, air mass characteristics are significantly modified through adiabatic warming (air parcel descent, upper-air radiative cooling and near-surface warming (surface heat fluxes and radiation. High residence times over continental areas, such as over northern-central Europe for WCE and, to a lesser extent, over Iberia for SWE, significantly enhance these air mass modifications. Near-surface diabatic warming is particularly striking for SWE. WCE and SWE are responsible for the most extreme conditions in a given year. For WWE and SCE, strong temperature advection associated with important meridional air mass transports are the main driving mechanisms, accompanied by comparatively minor changes in the air mass properties. These results permit a better understanding of mechanisms leading to temperature extremes in Iberia.

  5. Different neurophysiological mechanisms underlying word and rule extraction from speech.

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    Ruth De Diego Balaguer

    Full Text Available The initial process of identifying words from spoken language and the detection of more subtle regularities underlying their structure are mandatory processes for language acquisition. Little is known about the cognitive mechanisms that allow us to extract these two types of information and their specific time-course of acquisition following initial contact with a new language. We report time-related electrophysiological changes that occurred while participants learned an artificial language. These changes strongly correlated with the discovery of the structural rules embedded in the words. These changes were clearly different from those related to word learning and occurred during the first minutes of exposition. There is a functional distinction in the nature of the electrophysiological signals during acquisition: an increase in negativity (N400 in the central electrodes is related to word-learning and development of a frontal positivity (P2 is related to rule-learning. In addition, the results of an online implicit and a post-learning test indicate that, once the rules of the language have been acquired, new words following the rule are processed as words of the language. By contrast, new words violating the rule induce syntax-related electrophysiological responses when inserted online in the stream (an early frontal negativity followed by a late posterior positivity and clear lexical effects when presented in isolation (N400 modulation. The present study provides direct evidence suggesting that the mechanisms to extract words and structural dependencies from continuous speech are functionally segregated. When these mechanisms are engaged, the electrophysiological marker associated with rule-learning appears very quickly, during the earliest phases of exposition to a new language.

  6. [Genetic and biochemical mechanisms of involvement of antioxidant defense enzymes in the development of bronchial asthma].

    Science.gov (United States)

    Polonikov, A V; Ivanov, V P; Bogomazov, A D; Solodilova, M A

    2015-01-01

    In the present review we have analyzed and summarized recent literature data on genetic and biochemical mechanisms responsible for involvement of antioxidant defense enzymes in the etiology and pathogenesis of bronchial asthma. It has been shown that the mechanisms of asthma development are linked with genetically determined abnormalities in the functioning of antioxidant defense enzymes. These alterations are accompanied by a systemic imbalance between oxidative and anti-oxidative reactions with the shift of the redox state toward increased free radical production and oxidative stress, a key element in the pathogenesis of bronchial asthma.

  7. Mechanical properties and failure mechanisms of graphene under a central load.

    Science.gov (United States)

    Wang, Shuaiwei; Yang, Baocheng; Zhang, Shouren; Yuan, Jinyun; Si, Yubing; Chen, Houyang

    2014-09-15

    By employing molecular dynamics simulations, the evolution of deformation of a monolayer graphene sheet under a central transverse loading are investigated. Dependence of mechanical responses on the symmetry (shape) of the loading domain, on the size of the graphene sheet, and on temperature, is determined. It is found that the symmetry of the loading domain plays a central role in fracture strength and strain. By increasing the size of the graphene sheet or increasing temperature, the tensile strength and fracture strain decrease. The results have demonstrated that the breaking force and breaking displacement are sensitive to both temperature and the symmetry of the loading domain. In addition, we find that the intrinsic strength of graphene under a central load is much smaller than that of graphene under a uniaxial load. By examining the deformation processes, two failure mechanisms are identified namely, brittle bond breaking and plastic relaxation. In the second mechanism, the Stone-Wales transformation occurs. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Microcracking in composite laminates under thermal and mechanical loading. Thesis

    Science.gov (United States)

    Maddocks, Jason R.

    1995-01-01

    Composites used in space structures are exposed to both extremes in temperature and applied mechanical loads. Cracks in the matrix form, changing the laminate thermoelastic properties. The goal of the present investigation is to develop a predictive methodology to quantify microcracking in general composite laminates under both thermal and mechanical loading. This objective is successfully met through a combination of analytical modeling and experimental investigation. In the analysis, the stress and displacement distributions in the vicinity of a crack are determined using a shear lag model. These are incorporated into an energy based cracking criterion to determine the favorability of crack formation. A progressive damage algorithm allows the inclusion of material softening effects and temperature-dependent material properties. The analysis is implemented by a computer code which gives predicted crack density and degraded laminate properties as functions of any thermomechanical load history. Extensive experimentation provides verification of the analysis. AS4/3501-6 graphite/epoxy laminates are manufactured with three different layups to investigate ply thickness and orientation effects. Thermal specimens are cooled to progressively lower temperatures down to -184 C. After conditioning the specimens to each temperature, cracks are counted on their edges using optical microscopy and in their interiors by sanding to incremental depths. Tensile coupons are loaded monotonically to progressively higher loads until failure. Cracks are counted on the coupon edges after each loading. A data fit to all available results provides input parameters for the analysis and shows them to be material properties, independent of geometry and loading. Correlation between experiment and analysis is generally very good under both thermal and mechanical loading, showing the methodology to be a powerful, unified tool. Delayed crack initiation observed in a few cases is attributed to a

  9. Possible participation of endogenous opioid peptides on the mechanism involved in analgesia induced by vouacapan.

    Science.gov (United States)

    Duarte, I D; Ferreira-Alves, D L; Nakamura-Craig, M

    1992-01-01

    The involvement of opioid peptides in the mechanism of action of vouacapan, a new experimental compound extracted from seeds of Pterodon poligalaeflorus Benth, was investigated both in mice utilizing acetic acid writhing response and in rats utilizing inflammatory hyperalgesia induced by carrageenan and modified Randall-Selitto method. Vouacapan, in both models, caused a dose-dependent analgesia when injected p.o., s.c. and i.p. The analgesic effect was partially blocked by naloxone, nalorphine and n-methyl-nalorphine. Significant tolerance to analgesic effect was observed following repeated administration of vouacapan or morphine. On the last day of treatment, cross administration revealed symmetrical and asymmetrical cross-tolerance between vouacapan and morphine, in rats and mice, respectively. We conclude that a release of endorphins could be involved in the analgesic mechanism of vouacapan in both models tudied.

  10. Mechanisms involved in VPAC receptors activation and regulation: lessons from pharmacological and mutagenesis studies.

    Directory of Open Access Journals (Sweden)

    Ingrid eLanger

    2012-10-01

    Full Text Available VIP plays diverse and important role in human physiology and physiopathology and their receptors constitute potential targets for the treatment of several diseases such as neurodegenerative disorder, asthma, diabetes and inflammatory diseases. This article reviews the current knowledge regarding the two VIP receptors, VPAC1 and VPAC2, with respect to mechanisms involved in receptor activation, G protein coupling, signaling, regulation and oligomerization.

  11. Mechanical Modeling of a WIPP Drum Under Pressure

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jeffrey A. [Sandia National Laboratories, Albuquerque, NM (United States)

    2014-11-25

    Mechanical modeling was undertaken to support the Waste Isolation Pilot Plant (WIPP) technical assessment team (TAT) investigating the February 14th 2014 event where there was a radiological release at the WIPP. The initial goal of the modeling was to examine if a mechanical model could inform the team about the event. The intention was to have a model that could test scenarios with respect to the rate of pressurization. It was expected that the deformation and failure (inability of the drum to contain any pressure) would vary according to the pressurization rate. As the work progressed there was also interest in using the mechanical analysis of the drum to investigate what would happen if a drum pressurized when it was located under a standard waste package. Specifically, would the deformation be detectable from camera views within the room. A finite element model of a WIPP 55-gallon drum was developed that used all hex elements. Analyses were conducted using the explicit transient dynamics module of Sierra/SM to explore potential pressurization scenarios of the drum. Theses analysis show similar deformation patterns to documented pressurization tests of drums in the literature. The calculated failure pressures from previous tests documented in the literature vary from as little as 16 psi to 320 psi. In addition, previous testing documented in the literature shows drums bulging but not failing at pressures ranging from 69 to 138 psi. The analyses performed for this study found the drums failing at pressures ranging from 35 psi to 75 psi. When the drums are pressurized quickly (in 0.01 seconds) there is significant deformation to the lid. At lower pressurization rates the deformation of the lid is considerably less, yet the lids will still open from the pressure. The analyses demonstrate the influence of pressurization rate on deformation and opening pressure of the drums. Analyses conducted with a substantial mass on top of the closed drum demonstrate that the

  12. Use of static lung mechanics to identify early pulmonary involvement in patients with ankylosing spondylitis.

    Directory of Open Access Journals (Sweden)

    Aggarwal A

    2001-04-01

    Full Text Available AIM: To assess if a detailed analysis of lung mechanics could help in early recognition of pulmonary abnormalities in patients with ankylosing spondylitis. METHODS: Static pulmonary mechanics were studied in 17 patients (16 men and one woman of ankylosing spondylitis with no obvious clinical or radiological evidence of pulmonary involvement. Lung pressure-volume relationship was generated using a whole body plethysmograph, and a monoexponential equation fitted to this data. RESULTS: Total lung capacity (TLC was reduced in one (5.9% and static lung compliance (Cst in nine (52.9% patients. Four (23.5% patients had normal TLC, yet Cst and shape constant (K were reduced. Five (29.4% patients had reduced TLC and Cst; four of them had low K. One (5.9% patient had normal TLC but elevated Cst and K. CONCLUSIONS: Pulmonary involvement in patients with ankylosing spondylitis is probably diffuse and begins much earlier than generally presumed. Evaluation of static lung mechanics can identify pulmonary involvement early in the course of disease in several of these patients.

  13. Internal insulation failure mechanisms of HV equipment under service conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lokhanin, A.K.; Morozova, T.I. [All-Russian Electrochemical Inst. (Russian Federation); Shneider, G.Y. [Electrozavod Holding Company (Russian Federation); Sokolov, V.V. [Scientific and Engineering Centre, ZTZ Service Research Inst. (Russian Federation); Chornogotsky, V.M. [Ukrainian Transformer Research Inst. (Ukraine)

    2005-09-01

    Failure mechanisms in oil-barrier transformer insulation and oil-paper condenser type insulation of transformers and HV bushing were discussed with reference to typical defects and failure modes of oil-barrier insulation of transformers, shunt reactor, condenser type bushing and instrument current transformers. It was noted that insulation problems predominantly involve the impairment of insulation, and that the relative rate of major failures in shunt reactors is about 1 per cent. It was suggested that bushings can cause about 45 per cent of major transformer failures, with aged mode failure occurring most frequently. The failure rate of 220-500 kV CTs accounts for more than 60 per cent of total instrument transformer failures. Two failure modes were observed: ionisation-mode and aging-mode failures. The reduction of switching surge breakdown voltage due to deposit of insoluble aging products was discussed. A long-term dielectric strength test revealed the following 2 mechanisms of insulation breakdown: accidental breakdown during the first period of aging and wearing mode breakdown due to degradation of materials at the last stage of the calculated terms of aging. Issues concerning the mechanism of the incipient irreversible failure in oil-barrier insulation were discussed, as well as issues concerning creeping discharge and large failures during normal operating conditions. It was suggested that the occurrence of surface discharge is associated with increased voltage due to oil breakdown progressing into insulation destruction and surface discharge as a self-firing phenomenon. Failure modes induced by peculiar oil and staining of internal porcelain were reviewed. It was noted that the discharges across the inner part of the transformer and porcelain were the out-come of a typical aging-mode phenomenon in the bushing. In addition, failure modes induced by staining the outer surface of bottom porcelain were discussed, as well as failure of oil-filled paper

  14. Neural mechanisms underlying melodic perception and memory for pitch.

    Science.gov (United States)

    Zatorre, R J; Evans, A C; Meyer, E

    1994-04-01

    The neural correlates of music perception were studied by measuring cerebral blood flow (CBF) changes with positron emission tomography (PET). Twelve volunteers were scanned using the bolus water method under four separate conditions: (1) listening to a sequence of noise bursts, (2) listening to unfamiliar tonal melodies, (3) comparing the pitch of the first two notes of the same set of melodies, and (4) comparing the pitch of the first and last notes of the melodies. The latter two conditions were designed to investigate short-term pitch retention under low or high memory load, respectively. Subtraction of the obtained PET images, superimposed on matched MRI scans, provides anatomical localization of CBF changes associated with specific cognitive functions. Listening to melodies, relative to acoustically matched noise sequences, resulted in CBF increases in the right superior temporal and right occipital cortices. Pitch judgments of the first two notes of each melody, relative to passive listening to the same stimuli, resulted in right frontal-lobe activation. Analysis of the high memory load condition relative to passive listening revealed the participation of a number of cortical and subcortical regions, notably in the right frontal and right temporal lobes, as well as in parietal and insular cortex. Both pitch judgment conditions also revealed CBF decreases within the left primary auditory cortex. We conclude that specialized neural systems in the right superior temporal cortex participate in perceptual analysis of melodies; pitch comparisons are effected via a neural network that includes right prefrontal cortex, but active retention of pitch involves the interaction of right temporal and frontal cortices.

  15. Video analysis of concussion injury mechanism in under-18 rugby

    Science.gov (United States)

    Hendricks, Sharief; O'Connor, Sam; Lambert, Michael; Brown, James C; Burger, Nicholas; Mc Fie, Sarah; Readhead, Clint; Viljoen, Wayne

    2016-01-01

    Background Understanding the mechanism of injury is necessary for the development of effective injury prevention strategies. Video analysis of injuries provides valuable information on the playing situation and athlete-movement patterns, which can be used to formulate these strategies. Therefore, we conducted a video analysis of the mechanism of concussion injury in junior-level rugby union and compared it with a representative and matched non-injury sample. Methods Injury reports for 18 concussion events were collected from the 2011 to 2013 under-18 Craven Week tournaments. Also, video footage was recorded for all 3 years. On the basis of the injury events, a representative ‘control’ sample of matched non-injury events in the same players was identified. The video footage, which had been recorded at each tournament, was then retrospectively analysed and coded. 10 injury events (5 tackle, 4 ruck, 1 aerial collision) and 83 non-injury events were analysed. Results All concussions were a result of contact with an opponent and 60% of players were unaware of the impending contact. For the measurement of head position on contact, 43% had a ‘down’ position, 29% the ‘up and forward’ and 29% the ‘away’ position (n=7). The speed of the injured tackler was observed as ‘slow’ in 60% of injurious tackles (n=5). In 3 of the 4 rucks in which injury occurred (75%), the concussed player was acting defensively either in the capacity of ‘support’ (n=2) or as the ‘jackal’ (n=1). Conclusions Training interventions aimed at improving peripheral vision, strengthening of the cervical muscles, targeted conditioning programmes to reduce the effects of fatigue, and emphasising safe and effective playing techniques have the potential to reduce the risk of sustaining a concussion injury. PMID:27900149

  16. Video analysis of concussion injury mechanism in under-18 rugby.

    Science.gov (United States)

    Hendricks, Sharief; O'Connor, Sam; Lambert, Michael; Brown, James C; Burger, Nicholas; Mc Fie, Sarah; Readhead, Clint; Viljoen, Wayne

    2016-01-01

    Understanding the mechanism of injury is necessary for the development of effective injury prevention strategies. Video analysis of injuries provides valuable information on the playing situation and athlete-movement patterns, which can be used to formulate these strategies. Therefore, we conducted a video analysis of the mechanism of concussion injury in junior-level rugby union and compared it with a representative and matched non-injury sample. Injury reports for 18 concussion events were collected from the 2011 to 2013 under-18 Craven Week tournaments. Also, video footage was recorded for all 3 years. On the basis of the injury events, a representative 'control' sample of matched non-injury events in the same players was identified. The video footage, which had been recorded at each tournament, was then retrospectively analysed and coded. 10 injury events (5 tackle, 4 ruck, 1 aerial collision) and 83 non-injury events were analysed. All concussions were a result of contact with an opponent and 60% of players were unaware of the impending contact. For the measurement of head position on contact , 43% had a 'down' position, 29% the 'up and forward' and 29% the 'away' position (n=7). The speed of the injured tackler was observed as 'slow' in 60% of injurious tackles (n=5). In 3 of the 4 rucks in which injury occurred (75%), the concussed player was acting defensively either in the capacity of 'support' (n=2) or as the 'jackal' (n=1). Training interventions aimed at improving peripheral vision, strengthening of the cervical muscles, targeted conditioning programmes to reduce the effects of fatigue, and emphasising safe and effective playing techniques have the potential to reduce the risk of sustaining a concussion injury.

  17. Mechanisms underlying recovery of zooplankton in Lake Orta after liming

    Directory of Open Access Journals (Sweden)

    Roberta Piscia

    2016-04-01

    Full Text Available The goal of this study was to improve the understanding of the large-scale mechanisms underlying the recovery of the zooplankton of Lake Orta from historical contamination, following reduced input of ammonia and metals and the subsequent 1989/90 liming intervention. The industrial pollution had been severe and long-lasting (1929-1990. Zooplankton biodiversity has improved, but most of the new taxa appearing in our counts are rotifers, while many calanoids and the large cladoceran predators (Bythotrephes and Leptodora that are common in the nearby Lake Maggiore, were still absent from Lake Orta 17 years after liming. To aid understanding of the large-scale mechanisms controlling changes in annual richness, we assessed the annual persistence (P of Crustacea and Rotifera taxa as an estimator of whether propagules that survived introduction, as result of the natural recolonization process, also thrived. We found that the rate of introduction of zooplankton colonists and their persistence in the water column of Lake Orta changed from 1971 to 2007. New rotifer taxa appeared in the lake after the mid-1980s, when discharge of toxic substances decreased, but their annual persistence was low (P<0.5 until the turn of the century. The numerical values of rotifer and crustacean persistence in Lake Orta were unexpectedly high in 2001 and 2007 (0.55 and 0.72 for rotifers, 0.85 and 0.86 for crustacean, respectively, much higher than in limed lakes in Sudbury, Canada, and in adjacent Lake Maggiore. We hypothesize this could be related to the lack of Cladoceran predators and zooplanktivorous fish in the pelagic waters of Lake Orta.

  18. The behavior of the planetary rings under the Kozai Mechanism

    Science.gov (United States)

    Sucerquia, M. A.; Ramírez, C. V.; Zuluaga, J. I.

    2017-07-01

    Rings are one of the main feature of almost all giant planets in the Solar System. Even though thousands of exoplanets have been discovered to date, no evidence of exoplanetary rings have been found despite the effort made in the development and enhancing of techniques and methods for direct or indirect detection. In the transit of a ringed planet, the dynamic of the ring itself could play a meaningful role due to the so called Kozai Mechanism (KM) acting on each particle of it. When some specific initial conditions of the ring are fulfilled (as a ring inclination greater than ˜ 39°), KM generates short periodic changes in the inclination and eccentricity of each particle, leading to a meaningful characteristic collective behavior of the ring: it changes its width, inclination and optical depth. These changes induce periodic variations on the eclipsed area of the parent star, generating slight changes in the observed transit signal. Under this mechanism, light curves depths and shapes oscillate according to the fluctuations of the ring. To show this effect we have performed numerical simulations of the dynamic of a system of particles to asses the ring inclination and width variations over time. We have calculated the expected variations in the transit depth and finally, we have estimated the effect on the light curve of a hypothetical ringed exoplanet affected by the KM. The detection of this effect could be used as an alternative method to detect/confirm exoplanetary rings, and also it could be considered as a way to explain anomalous light curves patterns of exoplanets, as the case of KIC 8462852 star.

  19. Neural Mechanisms Underlying Hyperphagia in Prader-Willi Syndrome

    Science.gov (United States)

    Holsen, Laura M.; Zarcone, Jennifer R.; Brooks, William M.; Butler, Merlin G.; Thompson, Travis I.; Ahluwalia, Jasjit S.; Nollen, Nicole L.; Savage, Cary R.

    2006-01-01

    Objective Prader-Willi syndrome (PWS) is a genetic disorder associated with developmental delay, obesity, and obsessive behavior related to food consumption. The most striking symptom of PWS is hyperphagia; as such, PWS may provide important insights into factors leading to overeating and obesity in the general population. We used functional magnetic resonance imaging to study the neural mechanisms underlying responses to visual food stimuli, before and after eating, in individuals with PWS and a healthy weight control (HWC) group. Research Methods and Procedures Participants were scanned once before (pre-meal) and once after (post-meal) eating a standardized meal. Pictures of food, animals, and blurred control images were presented in a block design format during acquisition of functional magnetic resonance imaging data. Results Statistical contrasts in the HWC group showed greater activation to food pictures in the pre-meal condition compared with the post-meal condition in the amygdala, orbitofrontal cortex, medial prefrontal cortex (medial PFC), and frontal operculum. In comparison, the PWS group exhibited greater activation to food pictures in the post-meal condition compared with the pre-meal condition in the orbitofrontal cortex, medial PFC, insula, hippocampus, and parahippocampal gyrus. Between-group contrasts in the pre- and post-meal conditions confirmed group differences, with the PWS group showing greater activation than the HWC group after the meal in food motivation networks. Discussion Results point to distinct neural mechanisms associated with hyperphagia in PWS. After eating a meal, the PWS group showed hyperfunction in limbic and para-limbic regions that drive eating behavior (e.g., the amygdala) and in regions that suppress food intake (e.g., the medial PFC). PMID:16861608

  20. Neural mechanisms underlying hyperphagia in Prader-Willi syndrome.

    Science.gov (United States)

    Holsen, Laura M; Zarcone, Jennifer R; Brooks, William M; Butler, Merlin G; Thompson, Travis I; Ahluwalia, Jasjit S; Nollen, Nicole L; Savage, Cary R

    2006-06-01

    Prader-Willi syndrome (PWS) is a genetic disorder associated with developmental delay, obesity, and obsessive behavior related to food consumption. The most striking symptom of PWS is hyperphagia; as such, PWS may provide important insights into factors leading to overeating and obesity in the general population. We used functional magnetic resonance imaging to study the neural mechanisms underlying responses to visual food stimuli, before and after eating, in individuals with PWS and a healthy weight control (HWC) group. Participants were scanned once before (pre-meal) and once after (post-meal) eating a standardized meal. Pictures of food, animals, and blurred control images were presented in a block design format during acquisition of functional magnetic resonance imaging data. Statistical contrasts in the HWC group showed greater activation to food pictures in the pre-meal condition compared with the post-meal condition in the amygdala, orbitofrontal cortex, medial prefrontal cortex (medial PFC), and frontal operculum. In comparison, the PWS group exhibited greater activation to food pictures in the post-meal condition compared with the pre-meal condition in the orbitofrontal cortex, medial PFC, insula, hippocampus, and parahippocampal gyrus. Between-group contrasts in the pre- and post-meal conditions confirmed group differences, with the PWS group showing greater activation than the HWC group after the meal in food motivation networks. Results point to distinct neural mechanisms associated with hyperphagia in PWS. After eating a meal, the PWS group showed hyperfunction in limbic and paralimbic regions that drive eating behavior (e.g., the amygdala) and in regions that suppress food intake (e.g., the medial PFC).

  1. Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

    Directory of Open Access Journals (Sweden)

    J.C. Brenes

    2012-04-01

    Full Text Available Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG and inferior colliculus (IC, produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing. These defensive reaction responses are critically mediated by γ-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 μL, a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

  2. Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

    International Nuclear Information System (INIS)

    Brenes, J.C.; Broiz, A.C.; Bassi, G.S.; Schwarting, R.K.W.; Brandão, M.L.

    2012-01-01

    Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by Y -aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG

  3. Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

    Energy Technology Data Exchange (ETDEWEB)

    Brenes, J.C. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Broiz, A.C.; Bassi, G.S. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Schwarting, R.K.W. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Brandão, M.L. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-09

    Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by {sub Y}-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

  4. The Vulnerability of Vessels Involved in the Role of Embolism and Hypoperfusion in the Mechanisms of Ischemic Cerebrovascular Diseases

    Directory of Open Access Journals (Sweden)

    Yong Peng Yu

    2016-01-01

    Full Text Available Accurate definition and better understanding of the mechanisms of stroke are crucial as this will guide the effective care and therapy. In this paper, we review the previous basic and clinical researches on the causes or mechanisms of ischemic cerebrovascular diseases (ICVD and interpret the correlation between embolism and hypoperfusion based on vascular stenosis and arterial intimal lesions. It was suggested that if there is no embolus (dynamic or in situ emboli, there might be no cerebral infarction. Three kinds of different clinical outcomes of TIA were theoretically interpreted based on its mechanisms. We suppose that there is a correlation between embolism and hypoperfusion, and which mechanisms (hypoperfusion or hypoperfusion induced microemboli playing the dominant role in each type of ICVD depends on the unique background of arterial intimal lesions (the vulnerability of vessels. That is to say, the vulnerability of vessels is involved in the role of embolism and hypoperfusion in the mechanisms of ischemic cerebrovascular diseases. This inference might enrich and provide better understandings for the underlying etiologies of ischemic cerebrovascular events.

  5. Dynamic Response and Failure Mechanism of Brittle Rocks Under Combined Compression-Shear Loading Experiments

    Science.gov (United States)

    Xu, Yuan; Dai, Feng

    2018-03-01

    A novel method is developed for characterizing the mechanical response and failure mechanism of brittle rocks under dynamic compression-shear loading: an inclined cylinder specimen using a modified split Hopkinson pressure bar (SHPB) system. With the specimen axis inclining to the loading direction of SHPB, a shear component can be introduced into the specimen. Both static and dynamic experiments are conducted on sandstone specimens. Given carefully pulse shaping, the dynamic equilibrium of the inclined specimens can be satisfied, and thus the quasi-static data reduction is employed. The normal and shear stress-strain relationships of specimens are subsequently established. The progressive failure process of the specimen illustrated via high-speed photographs manifests a mixed failure mode accommodating both the shear-dominated failure and the localized tensile damage. The elastic and shear moduli exhibit certain loading-path dependence under quasi-static loading but loading-path insensitivity under high loading rates. Loading rate dependence is evidently demonstrated through the failure characteristics involving fragmentation, compression and shear strength and failure surfaces based on Drucker-Prager criterion. Our proposed method is convenient and reliable to study the dynamic response and failure mechanism of rocks under combined compression-shear loading.

  6. Mechanisms Underlying HIV-Associated Noninfectious Lung Disease.

    Science.gov (United States)

    Presti, Rachel M; Flores, Sonia C; Palmer, Brent E; Atkinson, Jeffrey J; Lesko, Catherine R; Lau, Bryan; Fontenot, Andrew P; Roman, Jesse; McDyer, John F; Twigg, Homer L

    2017-11-01

    Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for COPD, pulmonary hypertension, and lung cancer even in the era of combination antiretroviral therapy. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggests that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage, which predisposes PLWH to these conditions. Some of the factors that drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome toward pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  7. [Neurophysiologic mechanisms of arterial hypertension under experimental chronic emotional stress].

    Science.gov (United States)

    Baumann, H; Martin, G; Urmantscheeva, T G; Degen, G; Wolter, F; Chasabova, W A; Gurk, C; Hinays, I; Läuter, J

    1976-01-01

    Neurophysiological studies were conducted with subhuman primates (macaca mulatta) in order to obtain an estimate of central nervous effects of socio-emotional stress. This was combined with continuously aggravated conditioning procedures in view of the possible significance of chronic environmental stress escalation for etiology and pathogenesis of an arterial hypertension model. Our conclusions are based on evoked potentials (EP) as integrative characteristics of cerebral information processing. The EPs were recorded by means of electrodes chronically implanted in brain structures of emotional and cardio-vascular relevance. Multivariate mathematico-statistical analyses of average EPs (AEP) provide an objective measure of stress sensibility of the individual, particularly of the effects of acute and chronic environmental stress factors upon the functional organization of the CNS. By means of a quantitative approach to AEP we were able to demonstrate a disjunction between distinct limbic and hypothalamic structures starting under stress conditions of subchronic character. We assume that the constancy of functionally antagonistic hyperactive excitation foci at diencephalic and supradiencephalic levels and their specific interaction with the equally stress related neocortical functional insufficiency constitutes a decisive pathogenetic central mechanism of neurotic behaviour. Long-term changes of amplification of external and internal afferences could be demonstrated on the basis of hypo- and hyperreactive neuroelectric functional patterns. These processes cause cerebro-visceral regulatory diseases as, e. g., a primary arterial hypertension by restriction of neocortical control and the corresponding efferent reactions for re-establishment of the dynamic homeostasis.

  8. Deciphering Molecular Mechanism Underlying Hypolipidemic Activity of Echinocystic Acid

    Directory of Open Access Journals (Sweden)

    Li Han

    2014-01-01

    Full Text Available Our previous study showed that a triterpene mixture, consisting of echinocystic acid (EA and oleanolic acid (OA at a ratio of 4 : 1, dose-dependently ameliorated the hyperlipidemia and atherosclerosis in rabbits fed with high fat/high cholesterol diets. This study was aimed at exploring the mechanisms underlying antihyperlipidemic effect of EA. Molecular docking simulation of EA was performed using Molegro Virtual Docker (version: 4.3.0 to investigate the potential targets related to lipid metabolism. Based on the molecular docking information, isotope labeling method or spectrophotometry was applied to examine the effect of EA on the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, acyl-CoA:cholesterol acyltransferase (ACAT, and diacylglycerol acyltransferase (DGAT in rat liver microsomes. Our results revealed a strong affinity of EA towards ACAT and DGAT in molecular docking analysis, while low binding affinity existed between EA and HMG-CoA reductase as well as between EA and cholesteryl ester transfer protein. Consistent with the results of molecular docking, in vitro enzyme activity assays showed that EA inhibited ACAT and DGAT, with IC50 values of 103 and 139 μM, respectively, and exhibited no significant effect on HMG-CoA reductase activity. The present findings suggest that EA may exert hypolipidemic effect by inhibiting the activity of ACAT and DGAT.

  9. Fatigue life prediction of mechanical structures under stochastic loading

    Directory of Open Access Journals (Sweden)

    Leitner Bohuš

    2018-01-01

    Full Text Available Problems of fatigue life prediction of materials and structures are discussed in the paper. Service loading is assumed as a continuous loading process with possible discontinuous events, which are caused by various operating conditions. The damage in a material is due to a cumulative degradation process. The damaging process is then represented either by rain-flow matrices or by a fatigue damage function which is derived using some hypothesis of a fatigue failure criterion. Presented theoretical procedure enables a very effective estimation of a service life and/or reliable evaluation of residual life of any structures under various types of loading and environmental conditions. This approach creates a good basis for powerful expert systems in structural and mechanical engineering. The aim of the paper is to present briefly some results of analysis of load-bearing steel structure loads of special railway crane PKP 25/20i which was utilized in some specific ad relatively hard operating conditions. Virtual models of the structure were being used in an analysis of acting working dynamics loads influence to be able to forecast fatigue life of load-bearing of the crane jib.

  10. Neural mechanisms underlying the induction and relief of perceptual curiosity

    Directory of Open Access Journals (Sweden)

    Marieke eJepma

    2012-02-01

    Full Text Available Curiosity is one of the most basic biological drives in both animals and humans, and has been identified as a key motive for learning and discovery. Despite the importance of curiosity and related behaviors, the topic has been largely neglected in human neuroscience; hence little is known about the neurobiological mechanisms underlying curiosity. We used functional magnetic resonance imaging (fMRI to investigate what happens in our brain during the induction and subsequent relief of perceptual curiosity. Our core findings were that (i the induction of perceptual curiosity, through the presentation of ambiguous visual input, activated the anterior insula and anterior cingulate cortex, brain regions sensitive to conflict and arousal; (ii the relief of perceptual curiosity, through visual disambiguation, activated regions of the striatum that have been related to reward processing; and (iii the relief of perceptual curiosity was associated with hippocampal activation and enhanced incidental memory. These findings provide the first demonstration of the neural basis of human perceptual curiosity. Our results provide neurobiological support for a classic psychological theory of curiosity, which holds that curiosity is an aversive condition of increased arousal whose termination is rewarding and facilitates memory.

  11. Spread of Epidemic on Complex Networks Under Voluntary Vaccination Mechanism

    Science.gov (United States)

    Xue, Shengjun; Ruan, Feng; Yin, Chuanyang; Zhang, Haifeng; Wang, Binghong

    Under the assumption that the decision of vaccination is a voluntary behavior, in this paper, we use two forms of risk functions to characterize how susceptible individuals estimate the perceived risk of infection. One is uniform case, where each susceptible individual estimates the perceived risk of infection only based on the density of infection at each time step, so the risk function is only a function of the density of infection; another is preferential case, where each susceptible individual estimates the perceived risk of infection not only based on the density of infection but only related to its own activities/immediate neighbors (in network terminology, the activity or the number of immediate neighbors is the degree of node), so the risk function is a function of the density of infection and the degree of individuals. By investigating two different ways of estimating the risk of infection for susceptible individuals on complex network, we find that, for the preferential case, the spread of epidemic can be effectively controlled; yet, for the uniform case, voluntary vaccination mechanism is almost invalid in controlling the spread of epidemic on networks. Furthermore, given the temporality of some vaccines, the waves of epidemic for two cases are also different. Therefore, our work insight that the way of estimating the perceived risk of infection determines the decision on vaccination options, and then determines the success or failure of control strategy.

  12. Phytoremediation potential of the novel atrazine tolerant Lolium multiflorum and studies on the mechanisms involved

    Energy Technology Data Exchange (ETDEWEB)

    Merini, Luciano J. [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina); Bobillo, Cecilia [Servicio de Huellas Digitales Geneticas, Facultad de Farmacia y Bioquimica, Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires, Junin 956, BS As (Argentina); Cuadrado, Virginia [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina); Corach, Daniel [Servicio de Huellas Digitales Geneticas, Facultad de Farmacia y Bioquimica, Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires, Junin 956, BS As (Argentina); Giulietti, Ana M., E-mail: agiule@ffyb.uba.a [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina)

    2009-11-15

    Atrazine impact on human health and the environment have been extensively studied. Phytoremediation emerged as a low cost, environmental friendly biotechnological solution for atrazine pollution in soil and water. In vitro atrazine tolerance assays were performed and Lolium multiflorum was found as a novel tolerant species, able to germinate and grow in the presence of 1 mg kg{sup -1} of the herbicide. L. multiflorum presented 20% higher atrazine removal capacity than the natural attenuation, with high initial degradation rate in microcosms. The mechanisms involved in atrazine tolerance such as mutation in psbA gene, enzymatic detoxification via P{sub 450} or chemical hydrolysis through benzoxazinones were evaluated. It was demonstrated that atrazine tolerance is conferred by enhanced enzymatic detoxification via P{sub 450}. Due to its atrazine degradation capacity in soil and its agronomical properties, L. multiflorum is a candidate for designing phytoremediation strategies for atrazine contaminated agricultural soils, especially those involving run-off avoiding. - Finding of a novel atrazine-tolerant species, as a potential candidate for phytoremediating herbicide-contaminated agriculture soils and elucidation of the mechanisms involved in tolerance.

  13. Phytoremediation potential of the novel atrazine tolerant Lolium multiflorum and studies on the mechanisms involved

    International Nuclear Information System (INIS)

    Merini, Luciano J.; Bobillo, Cecilia; Cuadrado, Virginia; Corach, Daniel; Giulietti, Ana M.

    2009-01-01

    Atrazine impact on human health and the environment have been extensively studied. Phytoremediation emerged as a low cost, environmental friendly biotechnological solution for atrazine pollution in soil and water. In vitro atrazine tolerance assays were performed and Lolium multiflorum was found as a novel tolerant species, able to germinate and grow in the presence of 1 mg kg -1 of the herbicide. L. multiflorum presented 20% higher atrazine removal capacity than the natural attenuation, with high initial degradation rate in microcosms. The mechanisms involved in atrazine tolerance such as mutation in psbA gene, enzymatic detoxification via P 450 or chemical hydrolysis through benzoxazinones were evaluated. It was demonstrated that atrazine tolerance is conferred by enhanced enzymatic detoxification via P 450 . Due to its atrazine degradation capacity in soil and its agronomical properties, L. multiflorum is a candidate for designing phytoremediation strategies for atrazine contaminated agricultural soils, especially those involving run-off avoiding. - Finding of a novel atrazine-tolerant species, as a potential candidate for phytoremediating herbicide-contaminated agriculture soils and elucidation of the mechanisms involved in tolerance.

  14. Biochemical Mechanisms and Microorganisms Involved in Anaerobic Testosterone Metabolism in Estuarine Sediments

    OpenAIRE

    Shih, Chao-Jen; Chen, Yi-Lung; Wang, Chia-Hsiang; Wei, Sean T.-S.; Lin, I-Ting; Ismail, Wael A.; Chiang, Yin-Ru

    2017-01-01

    Current knowledge on the biochemical mechanisms underlying microbial steroid metabolism in anaerobic ecosystems is extremely limited. Sulfate, nitrate, and iron [Fe (III)] are common electron acceptors for anaerobes in estuarine sediments. Here, we investigated anaerobic testosterone metabolism in anaerobic sediments collected from the estuary of Tamsui River, Taiwan. The anaerobic sediment samples were spiked with testosterone (1 mM) and individual electron acceptors (10 mM), including nitra...

  15. Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms.

    Science.gov (United States)

    Maqbool, Faheem; Mostafalou, Sara; Bahadar, Haji; Abdollahi, Mohammad

    2016-01-15

    Endocrine disrupting chemicals (EDC) are released into environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDC have major risks for human by targeting different organs and systems in the body. Multiple mechanisms are involved in targeting the normal system, through estrogen receptors, nuclear receptors and steroidal receptors activation. In this review, different methods by which xenobiotics stimulate signaling pathways and genetic mutation or DNA methylation have been discussed. These methods help to understand the results of xenobiotic action on the endocrine system. Endocrine disturbances in the human body result in breast cancer, ovarian problems, thyroid eruptions, testicular carcinoma, Alzheimer disease, schizophrenia, nerve damage and obesity. EDC characterize a wide class of compounds such as organochlorinated pesticides, industrial wastes, plastics and plasticizers, fuels and numerous other elements that exist in the environment or are in high use during daily life. The interactions and mechanism of toxicity in relation to human general health problems, especially endocrine disturbances with particular reference to reproductive problems, diabetes, and breast, testicular and ovarian cancers should be deeply investigated. There should also be a focus on public awareness of these EDC risks and their use in routine life. Therefore, the aim of this review is to summarize all evidence regarding different physiological disruptions in the body and possible involved mechanisms, to prove the association between endocrine disruptions and human diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. The Role and Mechanisms of Action of Glucocorticoid Involvement in Memory Storage

    Directory of Open Access Journals (Sweden)

    Carmen Sandi

    1998-01-01

    integral aspect of the neurobiological mechanism underlying memory formation. By reviewing the work carried out in different learning models in chicks (passive avoidance learning and rats (spatial orientation in the Morris water maze and contextual fear conditioning, a role for brain corticosterone action through the glucocorticoid receptor type on the mechanisms of memory consolidation is hypothesized. Evidence is also presented to relate post-training corticosterone levels to the strength of memory storage. Finally, the possible molecular mechanisms that might mediate the influences of glucocorticoids in synaptic plasticity subserving long-term memory formation are considered, mainly by focusing on studies implicating a steroid action through (i glutamatergic transmission and (ii cell adhesion molecules.

  17. The Role and Mechanisms of Action of Glucocorticoid Involvement in Memory Storage

    Science.gov (United States)

    Sandi, Carmen

    1998-01-01

    Adrenal steroid hormones modulate learning and memory processes by interacting with specific glucocorticoid receptors at different brain areas. In this article, certain components of the physiological response to stress elicited by learning situations are proposed to form an integral aspect of the neurobiological mechanism underlying memory formation. By reviewing the work carried out in different learning models in chicks (passive avoidance learning) and rats (spatial orientation in the Morris water maze and contextual fear conditioning), a role for brain corticosterone action through the glucocorticoid receptor type on the mechanisms of memory consolidation is hypothesized. Evidence is also presented to relate post-training corticosterone levels to the strength of memory storage. Finally, the possible molecular mechanisms that might mediate the influences of glucocorticoids in synaptic plasticity subserving long-term memory formation are considered, mainly by focusing on studies implicating a steroid action through (i) glutamatergic transmission and (ii) cell adhesion molecules. PMID:9920681

  18. Mechanism of crack initiation and crack growth under thermal and mechanical fatigue loading

    International Nuclear Information System (INIS)

    Utz, S.; Soppa, E.; Silcher, H.; Kohler, C.

    2013-01-01

    The present contribution is focused on the experimental investigations and numerical simulations of the deformation behaviour and crack development in the austenitic stainless steel X6CrNiNb18-10 under thermal and mechanical cyclic loading in HCF and LCF regimes. The main objective of this research is the understanding of the basic mechanisms of fatigue damage and the development of simulation methods, which can be applied further in safety evaluations of nuclear power plant components. In this context the modelling of crack initiation and crack growth inside the material structure induced by varying thermal or mechanical loads are of particular interest. The mechanisms of crack initiation depend among other things on the type of loading, microstructure, material properties and temperature. The Nb-stabilized austenitic stainless steel in the solution-annealed condition was chosen for the investigations. Experiments with two kinds of cyclic loading - pure thermal and pure mechanical - were carried out and simulated. The fatigue behaviour of the steel X6CrNiNb18-10 under thermal loading was studied within the framework of the joint research project [4]. Interrupted thermal cyclic tests in the temperature range of 150 C to 300 C combined with non-destructive residual stress measurements (XRD) and various microscopic investigations, e.g. in SEM (Scanning Electron Microscope), were used to study the effects of thermal cyclic loading on the material. This thermal cyclic loading leads to thermal induced stresses and strains. As a result intrusions and extrusions appear inside the grains (at the surface), at which microcracks arise and evolve to a dominant crack. Finally, these microcracks cause a continuous and significant decrease of residual stresses. The fatigue behaviour of the steel X6CrNiNb18-10 under mechanical loading at room temperature was studied within the framework of the research project [5], [8]. With a combination of interrupted LCF tests and EBSD

  19. Mechanism of crack initiation and crack growth under thermal and mechanical fatigue loading

    Energy Technology Data Exchange (ETDEWEB)

    Utz, S.; Soppa, E.; Silcher, H.; Kohler, C. [Stuttgart Univ. (Germany). Materials Testing Inst.

    2013-07-01

    The present contribution is focused on the experimental investigations and numerical simulations of the deformation behaviour and crack development in the austenitic stainless steel X6CrNiNb18-10 under thermal and mechanical cyclic loading in HCF and LCF regimes. The main objective of this research is the understanding of the basic mechanisms of fatigue damage and the development of simulation methods, which can be applied further in safety evaluations of nuclear power plant components. In this context the modelling of crack initiation and crack growth inside the material structure induced by varying thermal or mechanical loads are of particular interest. The mechanisms of crack initiation depend among other things on the type of loading, microstructure, material properties and temperature. The Nb-stabilized austenitic stainless steel in the solution-annealed condition was chosen for the investigations. Experiments with two kinds of cyclic loading - pure thermal and pure mechanical - were carried out and simulated. The fatigue behaviour of the steel X6CrNiNb18-10 under thermal loading was studied within the framework of the joint research project [4]. Interrupted thermal cyclic tests in the temperature range of 150 C to 300 C combined with non-destructive residual stress measurements (XRD) and various microscopic investigations, e.g. in SEM (Scanning Electron Microscope), were used to study the effects of thermal cyclic loading on the material. This thermal cyclic loading leads to thermal induced stresses and strains. As a result intrusions and extrusions appear inside the grains (at the surface), at which microcracks arise and evolve to a dominant crack. Finally, these microcracks cause a continuous and significant decrease of residual stresses. The fatigue behaviour of the steel X6CrNiNb18-10 under mechanical loading at room temperature was studied within the framework of the research project [5], [8]. With a combination of interrupted LCF tests and EBSD

  20. Mechanisms underlying the antihypertensive properties of Urtica dioica.

    Science.gov (United States)

    Qayyum, Rahila; Qamar, Hafiz Misbah-Ud-Din; Khan, Shamim; Salma, Umme; Khan, Taous; Shah, Abdul Jabbar

    2016-09-01

    Urtica dioica has traditionally been used in the management of cardiovascular disorders especially hypertension. The aim of this study was to explore pharmacological base of its use in hypertension. Crude methanolic extract of U. dioica (Ud.Cr) and its fractions (Ud.EtAc, Ud.nHex, Ud.Chl and Ud.Aq) were tested in vivo on normotensive and hypertensive rats under anesthesia for blood pressure lowering effect. In-vitro experiments on rat and rabbit aortae were employed to probe the vasorelaxation mechanism(s). The responses were measured using pressure and force transducers connected to PowerLab Data Acquisition System. Ud.Cr and fractions were found more effective antihypertensive in hypertensive rats than normotensive with remarkable potency exhibited by the ethyl acetate fraction. The effect was same in the presence of atropine. In isolated rat aortic rings, Ud.Cr and all its fractions exhibited L-NAME sensitive endothelium-dependent vasodilator effect and also inhibit K(+) (80 mM)-induced pre-contractions. In isolated rabbit thoracic aortic rings Ud.Cr and its fractions induced relaxation with more potency against K(+) (80 mM) than phenylephrine (1 µM) like verapamil, showing Ud.EtAc fraction the most potent one. Pre-incubation of aortic rings with Ud.Cr and its fractions exhibited Ca(2+) channel blocking activity comparable with verapamil by shifting Ca(2+) concentration response curves to the right. Ud.Cr and its fractions also ablated the intracellular Ca(2+) release by suppressing PE peak formation in Ca(2+) free medium. When tested on basal tension, the crude extract and all fractions were devoid of any vasoconstrictor effect. These data indicate that crude methanolic extract and its fractions possess antihypertensive effect. Identification of NO-mediated vasorelaxation and calcium channel blocking effects explain the antihypertensive potential of U. dioica and provide a potential pharmacological base to its medicinal use in the management of hypertension.

  1. Antioxidant Property of Jobelyn as the Possible Mechanism Underlying

    Directory of Open Access Journals (Sweden)

    Solomon Umukoro

    2013-01-01

    Full Text Available   Introduction: Amnesia or loss of memory is the cardinal hallmark of Alzheimer’s disease (AD, a progressive neurodegenerative disorder associated with ageing process. Although, AD had been discovered over a century ago, drugs which could cure or halt the progression of the disease are yet to see the light of the day. However, there has been a growing interest in the use of phytomedicines with multipronged mechanisms of action that could target various aspects of the pathologies of AD. Jobelyn (JB is a potent antioxidant African polyherbal formulation with active components that have been acclaimed to show neuroprotection. T his investigation was carried out to evaluate whether JB has anti-amnesic and antioxidant activities.   Methods: The alteration of alternation behavior in the Y-maze paradigm was utilized as the test for memory function in mice. The effect of JB on a cetylcholinesterase (AChE activity, malondialdehyde (MDA level and the concentrations of glutathione (GSH in the frontal cortex and hippocampus were assessed in rats as means of providing insight into the mechanism underlying its anti-amnesic activity. The animals were given JB (1, 2.5 or 5mg/kg, i.p. daily for 7 days before the biochemical assays or test for memory functions were carried out.   Results: JB was found to produce a significant increase in the level of alternation behavior compared with the control, suggesting anti-amnesic activity. Also, JB reversed the memory impairment induced by scopolamine, which further indicates anti-amnesic property. Furthermore, JB demonstrated a significant inhibition of MDA formation in the frontal cortex and hippocampus of rats, indicating antioxidant property. In addition, it increased the defense armory of the brain tissues, as it significantly increased the concentrations of GSH in the frontal cortex and hippocampus of rats. However, JB did not demonstrate any inhibitory effect against AChE activity in the frontal cortex and

  2. Bronchopulmonary dysplasia: understanding of the underlying pathological mechanisms

    Directory of Open Access Journals (Sweden)

    Daniela Fanni

    2014-06-01

    better understanding of the underlying pathological mechanisms of BPD might provide insight into development of new therapeutic and preventive strategies.  Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  3. Induction of alternative respiratory pathway involves nitric oxide, hydrogen peroxide and ethylene under salt stress.

    Science.gov (United States)

    Wang, Huahua; Huang, Junjun; Bi, Yurong

    2010-12-01

    Alternative respiratory pathway (AP) plays an important role in plant thermogenesis, fruit ripening and responses to environmental stresses. AP may participate in the adaptation to salt stress since salt stress increased the activity of the AP. Recently, new evidence revealed that ethylene and hydrogen peroxide (H(2)O(2)) are involved in the salt-induced increase of the AP, which plays an important role in salt tolerance in Arabidopsis callus, and ethylene may be acting downstream of H(2)O(2). Recent observations also indicated both ethylene and nitric oxide (NO) act as signaling molecules in responses to salt stress, and ethylene may be a part of the downstream signal molecular in NO action. In this addendum, a hypothetical model for NO function in regulation of H(2)O(2)- and ethylene-mediated induction of AP under salt stress is presented.

  4. A novel mechanism of P-type ATPase autoinhibition involving both termini of the protein

    DEFF Research Database (Denmark)

    Ekberg, Kira; Palmgren, Michael; Veierskov, Bjarke

    2010-01-01

    The activity of many P-type ATPases is found to be regulated by interacting proteins or autoinhibitory elements located in N- or C-terminal extensions. An extended C terminus of fungal and plant P-type plasma membrane H+-ATPases has long been recognized to be part of a regulatory apparatus...... involving an autoinhibitory domain. Here we demonstrate that both the N and the C termini of the plant plasma membrane H+-ATPase are directly involved in controlling the pump activity state and that N-terminal displacements are coupled to secondary modifications taking place at the C-terminal end....... This identifies the first group of P-type ATPases for which both ends of the polypeptide chain constitute regulatory domains, which together contribute to the autoinhibitory apparatus. This suggests an intricate mechanism of cis-regulation with both termini of the protein communicating to obtain the necessary...

  5. Assessment of Mechanisms Involved in Antinociception Produced by the Alkaloid Caulerpine

    Directory of Open Access Journals (Sweden)

    Luiz Henrique Agra Cavalcante-Silva

    2014-09-01

    Full Text Available In previous works we showed that oral administration of caulerpine, a bisindole alkaloid isolated from algae of the genus Caulerpa, produced antinociception when assessed in chemical and thermal models of nociception. In this study, we evaluated the possible mechanism of action of this alkaloid in mice, using the writhing test. The antinociceptive effect of caulerpine was not affected by intraperitoneal (i.p. pretreatment of mice with naloxone, flumazenil, l-arginine or atropine, thus discounting the involvement of the opioid, GABAergic, l-arginine-nitric oxide and (muscarinic cholinergic pathways, respectively. In contrast, i.p. pretreatment with yohimbine, an α2-adrenoceptor antagonist, or tropisetron, a 5-HT3 antagonist, significantly blocked caulerpine-induced antinociception. These results suggest that caulerpine exerts its antinociceptive effect in the writhing test via pathways involving α2-adrenoceptors and 5-HT3 receptors. In summary, this alkaloid could be of interest in the development of new dual-action analgesic drugs.

  6. Absorption of Carotenoids and Mechanisms Involved in Their Health-Related Properties.

    Science.gov (United States)

    Cervantes-Paz, Braulio; Victoria-Campos, Claudia I; Ornelas-Paz, José de Jesús

    Carotenoids participate in the normal metabolism and function of the human body. They are involved in the prevention of several diseases, especially those related to the inflammation syndrome. Their main mechanisms of action are associated to their potent antioxidant activity and capacity to regulate the expression of specific genes and proteins. Recent findings suggest that carotenoid metabolites may explain several processes where the participation of their parent carotenoids was unclear. The health benefits of carotenoids strongly depend on their absorption and transformation during gastrointestinal digestion. The estimation of the 'bioaccessibility' of carotenoids through in vitro models have made possible the evaluation of the effect of a large number of factors on key stages of carotenoid digestion and intestinal absorption. The bioaccessibility of these compounds allows us to have a clear idea of their potential bioavailability, a term that implicitly involves the biological activity of these compounds.

  7. Aspects of Information Architecture involved in process mapping in Military Organizations under the semiotic perspective

    Directory of Open Access Journals (Sweden)

    Mac Amaral Cartaxo

    2016-04-01

    Full Text Available Introduction: The description of the processes to represent the activities in an organization has important call semiotic, It is the flowcharts of uses, management reports and the various forms of representation of the strategies used. The subsequent interpretation of the organization's employees involved in learning tasks and the symbols used to translate the meanings of management practices is essential role for the organization. Objective: The objective of this study was to identify evidence of conceptual and empirical, on aspects of information architecture involved in the mapping process carried out in military organizations under the semiotic perspective. Methodology: The research is characterized as qualitative, case study and the data collection technique was the semi-structured interview, applied to management advisors. Results: The main results indicate that management practices described with the use of pictorial symbols and different layouts have greater impact to explain the relevance of management practices and indicators. Conclusion: With regard to the semiotic appeal, it was found that the impact of a management report is significant due to the use of signs and layout that stimulate further reading by simplifying complex concepts in tables, diagrams summarizing lengthy descriptions.

  8. Biochemical Mechanisms and Microorganisms Involved in Anaerobic Testosterone Metabolism in Estuarine Sediments.

    Science.gov (United States)

    Shih, Chao-Jen; Chen, Yi-Lung; Wang, Chia-Hsiang; Wei, Sean T-S; Lin, I-Ting; Ismail, Wael A; Chiang, Yin-Ru

    2017-01-01

    Current knowledge on the biochemical mechanisms underlying microbial steroid metabolism in anaerobic ecosystems is extremely limited. Sulfate, nitrate, and iron [Fe (III)] are common electron acceptors for anaerobes in estuarine sediments. Here, we investigated anaerobic testosterone metabolism in anaerobic sediments collected from the estuary of Tamsui River, Taiwan. The anaerobic sediment samples were spiked with testosterone (1 mM) and individual electron acceptors (10 mM), including nitrate, Fe 3+ , and sulfate. The analysis of androgen metabolites indicated that testosterone biodegradation under denitrifying conditions proceeds through the 2,3- seco pathway, whereas testosterone biodegradation under iron-reducing conditions may proceed through an unidentified alternative pathway. Metagenomic analysis and PCR-based functional assays suggested that Thauera spp. were the major testosterone degraders in estuarine sediment samples incubated with testosterone and nitrate. Thauera sp. strain GDN1, a testosterone-degrading betaproteobacterium, was isolated from the denitrifying sediment sample. This strain tolerates a broad range of salinity (0-30 ppt). Although testosterone biodegradation did not occur under sulfate-reducing conditions, we observed the anaerobic biotransformation of testosterone to estrogens in some testosterone-spiked sediment samples. This is unprecedented since biotransformation of androgens to estrogens is known to occur only under oxic conditions. Our metagenomic analysis suggested that Clostridium spp. might play a role in this anaerobic biotransformation. These results expand our understanding of microbial metabolism of steroids under strictly anoxic conditions.

  9. Biochemical Mechanisms and Microorganisms Involved in Anaerobic Testosterone Metabolism in Estuarine Sediments

    Directory of Open Access Journals (Sweden)

    Chao-Jen Shih

    2017-08-01

    Full Text Available Current knowledge on the biochemical mechanisms underlying microbial steroid metabolism in anaerobic ecosystems is extremely limited. Sulfate, nitrate, and iron [Fe (III] are common electron acceptors for anaerobes in estuarine sediments. Here, we investigated anaerobic testosterone metabolism in anaerobic sediments collected from the estuary of Tamsui River, Taiwan. The anaerobic sediment samples were spiked with testosterone (1 mM and individual electron acceptors (10 mM, including nitrate, Fe3+, and sulfate. The analysis of androgen metabolites indicated that testosterone biodegradation under denitrifying conditions proceeds through the 2,3-seco pathway, whereas testosterone biodegradation under iron-reducing conditions may proceed through an unidentified alternative pathway. Metagenomic analysis and PCR-based functional assays suggested that Thauera spp. were the major testosterone degraders in estuarine sediment samples incubated with testosterone and nitrate. Thauera sp. strain GDN1, a testosterone-degrading betaproteobacterium, was isolated from the denitrifying sediment sample. This strain tolerates a broad range of salinity (0–30 ppt. Although testosterone biodegradation did not occur under sulfate-reducing conditions, we observed the anaerobic biotransformation of testosterone to estrogens in some testosterone-spiked sediment samples. This is unprecedented since biotransformation of androgens to estrogens is known to occur only under oxic conditions. Our metagenomic analysis suggested that Clostridium spp. might play a role in this anaerobic biotransformation. These results expand our understanding of microbial metabolism of steroids under strictly anoxic conditions.

  10. Mechanisms regulating proteostasis are involved in sympatric speciation of the blind mole rat, Spalax galili.

    Science.gov (United States)

    Rodriguez, Karl A; Li, Kexin; Nevo, Eviatar; Buffenstein, Rochelle

    2016-01-01

    Genome-wide analysis demonstrates extensive genomic adaptive complexes involved in sympatric speciation between blind mole rats (Spalax galili) in abutting populations living in basalt and chalk soils. Among the gene ontology (GO) enrichment, musculature and metabolism stood out in basalt dwellers while nutrition and neurogenetics were highlighted in chalk residents. Measurements of mechanisms regulating protein homeostasis inspired by these GO terms suggest that at the proteomic level there is also a habitat/soil-type driven divergence with the basalt residents exhibiting higher proteasome activity whereas elevated levels of markers of autophagy are evident in the chalk inhabitants.

  11. Alteration mechanisms of UOX spent fuel under water

    International Nuclear Information System (INIS)

    Muzeau, B.

    2008-06-01

    The mechanisms of spent fuel alteration in aqueous media need to be understood on the assumption of a direct disposal of the assemblies in a geological formation or for long duration storage in pool. This work is a contribution to the study of the effects of the alpha and/or beta/gamma radiolysis of water on the oxidation and the dissolution of the UO 2 matrix of UOX spent fuel. The effects of the alpha radiolysis, predominant in geological disposal conditions, were quantified by using samples of UO 2 doped with plutonium. The leaching experiments highlighted two types of control for the matrix alteration according to the alpha activity. The first is based on the radiolytic oxidation of the surface and leads to a continuous release of uranium in solution whereas the second is based on a control by the solubility of uranium. An activity threshold, between 18 MBq.g -1 and 33 MBq.g -1 , was defined in a carbonated water. The value of this threshold is dependent on the experimental conditions and the presence or not of electro-active species such as hydrogen in the system. The effects of the alpha/beta/gamma radiolysis in relation with the storage conditions were also quantified. The experimental data obtained on spent fuel indicate that the alteration rate of the matrix based on the behaviour of tracer elements (caesium and strontium) reached a maximum value of some mg.m -2 .d -1 , even under very oxidizing conditions. The solubility of uranium and the nature of the secondary phases depend however on the extent of the oxidizing conditions. (author)

  12. Unraveling the Molecular Mechanisms Underlying the Nasopharyngeal Bacterial Community Structure

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    Wouter A. A. de Steenhuijsen Piters

    2016-03-01

    Full Text Available The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem—also called “microbiome”—is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections. Recent studies using next-generation sequencing show that S. pneumoniae, as well as other potential pathogens, might be kept at bay by certain commensal bacteria, including Corynebacterium and Dolosigranulum spp. Bomar and colleagues are the first to explore a specific biological mechanism contributing to the antagonistic interaction between Corynebacterium accolens and S. pneumoniae in vitro [L. Bomar, S. D. Brugger, B. H. Yost, S. S. Davies, K. P. Lemon, mBio 7(1:e01725-15, 2016, doi:10.1128/mBio.01725-15]. The authors comprehensively show that C. accolens is capable of hydrolyzing host triacylglycerols into free fatty acids, which display antipneumococcal properties, suggesting that these bacteria might contribute to the containment of pneumococcus. This work exemplifies how molecular epidemiological findings can lay the foundation for mechanistic studies to elucidate the host-microbe and microbial interspecies interactions underlying the bacterial community structure. Next, translation of these results to an in vivo setting seems necessary to unveil the magnitude and importance of the observed effect in its natural, polymicrobial setting.

  13. Cognitive mechanisms underlying instructed choice exploration of small city maps

    Directory of Open Access Journals (Sweden)

    Sofia eSakellaridi

    2015-03-01

    Full Text Available We investigated the cognitive mechanisms underlying the exploration and decision-making in realistic and novel environments. Twelve human subjects were shown small circular U.S. city maps with two locations highlighted on the circumference, as possible choices for a post office (targets. At the beginning of a trial, subjects fixated a spot at the center of the map and ultimately chose one of the two locations. A space syntax analysis of the map paths (from the center to each target revealed that the chosen location was associated with the less convoluted path, as if subjects navigated mentally the paths in an ant’s way, i.e. by staying within street boundaries, and ultimately choosing the target that could be reached from the center in the shortest way, and the fewest turns and intersections. The subjects’ strategy for map exploration and decision making was investigated by monitoring eye position during the task. This revealed a restricted exploration of the map delimited by the location of the two alternative options and the center of the map. Specifically, subjects explored the areas around the two target options by repeatedly looking at them before deciding which one to choose, presumably implementing an evaluation and decision-making process. The ultimate selection of a specific target was significantly associated with the time spent exploring the area around that target. Finally, an analysis of the sequence of eye fixations revealed that subjects tended to look systematically towards the target ultimately chosen even from the beginning of the trial. This finding indicates an early cognitive selection bias for the ensuing decision process.

  14. Epigenetic mechanisms in the development of memory and their involvement in certain neurological diseases.

    Science.gov (United States)

    Rosales-Reynoso, M A; Ochoa-Hernández, A B; Juárez-Vázquez, C I; Barros-Núñez, P

    Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways.

    Science.gov (United States)

    Rajsbaum, Ricardo; García-Sastre, Adolfo

    2013-08-01

    Early innate and cell-intrinsic responses are essential to protect host cells against pathogens. In turn, viruses have developed sophisticated mechanisms to establish productive infections by counteracting host innate immune responses. Increasing evidence indicates that these antiviral factors may have a dual role by directly inhibiting viral replication as well as by sensing and transmitting signals to induce antiviral cytokines. Recent studies have pointed at new, unappreciated mechanisms of viral evasion of host innate protective responses including manipulating the host ubiquitin (Ub) system. Virus-mediated inhibition of antiviral factors by Ub-dependent degradation is emerging as a crucial mechanism for evading the antiviral response. In addition, recent studies have uncovered new mechanisms by which virus-encoded proteins inhibit Ub and Ub-like (Ubl) modification of host proteins involved in innate immune signaling pathways. Here we discuss recent findings and novel strategies that viruses have developed to counteract these early innate antiviral defenses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Plant-insect interactions under bacterial influence: ecological implications and underlying mechanisms.

    Science.gov (United States)

    Sugio, Akiko; Dubreuil, Géraldine; Giron, David; Simon, Jean-Christophe

    2015-02-01

    Plants and insects have been co-existing for more than 400 million years, leading to intimate and complex relationships. Throughout their own evolutionary history, plants and insects have also established intricate and very diverse relationships with microbial associates. Studies in recent years have revealed plant- or insect-associated microbes to be instrumental in plant-insect interactions, with important implications for plant defences and plant utilization by insects. Microbial communities associated with plants are rich in diversity, and their structure greatly differs between below- and above-ground levels. Microbial communities associated with insect herbivores generally present a lower diversity and can reside in different body parts of their hosts including bacteriocytes, haemolymph, gut, and salivary glands. Acquisition of microbial communities by vertical or horizontal transmission and possible genetic exchanges through lateral transfer could strongly impact on the host insect or plant fitness by conferring adaptations to new habitats. Recent developments in sequencing technologies and molecular tools have dramatically enhanced opportunities to characterize the microbial diversity associated with plants and insects and have unveiled some of the mechanisms by which symbionts modulate plant-insect interactions. Here, we focus on the diversity and ecological consequences of bacterial communities associated with plants and herbivorous insects. We also highlight the known mechanisms by which these microbes interfere with plant-insect interactions. Revealing such mechanisms in model systems under controlled environments but also in more natural ecological settings will help us to understand the evolution of complex multitrophic interactions in which plants, herbivorous insects, and micro-organisms are inserted. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions

  17. Arbuscular Mycorrhizal Fungi for the Biocontrol of Plant-Parasitic Nematodes: A Review of the Mechanisms Involved.

    Science.gov (United States)

    Schouteden, Nele; De Waele, Dirk; Panis, Bart; Vos, Christine M

    2015-01-01

    Arbuscular mycorrhizal fungi (AMF) are obligate root symbionts that can protect their host plant against biotic stress factors such as plant-parasitic nematode (PPN) infection. PPN consist of a wide range of species with different life styles that can cause major damage in many important crops worldwide. Various mechanisms have been proposed to play a role in the biocontrol effect of AMF against PPN. This review presents an overview of the different mechanisms that have been proposed, and discusses into more detail the plausibility of their involvement in the biocontrol against PPN specifically. The proposed mechanisms include enhanced plant tolerance, direct competition for nutrients and space, induced systemic resistance (ISR) and altered rhizosphere interactions. Recent studies have emphasized the importance of ISR in biocontrol and are increasingly placing rhizosphere effects on the foreground as well, both of which will be the focal point of this review. Though AMF are not yet widely used in conventional agriculture, recent data help to develop a better insight into the modes of action, which will eventually lead toward future field applications of AMF against PPN. The scientific community has entered an exciting era that provides the tools to actually unravel the underlying molecular mechanisms, making this a timely opportunity for a review of our current knowledge and the challenges ahead.

  18. [Progress of researches on mechanism of acupuncture therapy underlying improvement of acute cerebral hemorrhage].

    Science.gov (United States)

    Wang, Fan; Wang, Hai-qiao; Dong, Gui-rong

    2011-04-01

    In the present paper, the authors review the progress of researches on the mechanism of acupuncture therapy underlying improvement of acute cerebral hemorrhage from experimental studies and research methods. The effects of acupuncture intervention mainly involve (1) lessening inflammatory reactions, (2) reducing impairment of free radicals and excitatory amino acids on cerebral neurons, (3) balancing release of vascular bioactive substances to increase regional cerebral blood flow, and (4) promoting repair and regeneration of the neural tissue, etc. In regard to the research methods, many new biological techniques such as biological molecular approaches, neuro-cellular chemical methods, reverse transcription-polymerase chain reaction (RT-PCR) or quantitative real time-PCR, situ hybridization, western blotting, electron microscope, etc., have been extensively applied to researches on the underlying mechanism of acupuncture therapy for cerebral infarction. In addition, the authors also pointed out that in spite of achieving some bigger progresses in experimental studies, most of the results basically reflect static, isolated and regional changes rather than dynamic and whole body changes. For this reason, more vivo research techniques and noninvasive research methods are highly recommended to be used in the future research on the underlying mechanisms of acupuncture therapy for acute cerebral ischemia.

  19. Cellular and molecular mechanisms involved in the neuroprotective effects of VEGF on motoneurons

    Directory of Open Access Journals (Sweden)

    Jerònia eLladó

    2013-10-01

    Full Text Available Vascular endothelial growth factor (VEGF, originally described as a factor with a regulatory role in vascular growth and development, it is also known for its direct effects on neuronal cells. The discovery in the past decade that transgenic mice expressing reduced levels of VEGF developed late-onset motoneuron pathology, reminiscent of amyotrophic lateral sclerosis (ALS, opened a new field of research on this disease. VEGF has been shown to protect motoneurons from excitotoxic death, which is a relevant mechanism involved in motoneuron degeneration in ALS. Thus, VEGF delays motoneuron degeneration and increases survival in animal models of ALS. VEGF exerts its anti-excitotoxic effects on motoneurons through molecular mechanisms involving the VEGF receptor-2 resulting in the activation of the PI3-K/Akt signaling pathway, upregulation of GluR2 subunit of AMPA receptors, inhibition of p38MAPK and induction of the anti-apoptotic molecule Bcl-2. In addition, VEGF acts on astrocytes to reduce astroglial activation and to induce the release of growth factors. The potential use of VEGF as a therapeutic tool in ALS is counteracted by its vascular effects and by its short effective time frame. More studies are needed to assess the optimal isoform, route of administration and time frame for using VEGF in the treatment of ALS.

  20. Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved

    Directory of Open Access Journals (Sweden)

    M. H. Mohd. Sani

    2012-01-01

    Full Text Available Muntingia calabura L. (family Elaeocarpaceae has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test and thermal (hot plate test models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P<0.05 antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO donor, NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS, methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP pathway, or their combination also caused significant (P<0.05 change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

  1. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats.

    Science.gov (United States)

    Lozano-Cuenca, J; González-Hernández, A; López-Canales, O A; Villagrana-Zesati, J R; Rodríguez-Choreão, J D; Morín-Zaragoza, R; Castillo-Henkel, E F; López-Canales, J S

    2017-08-07

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (Pclobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

  2. Molecular Mechanics: The Method and Its Underlying Philosophy.

    Science.gov (United States)

    Boyd, Donald B.; Lipkowitz, Kenny B.

    1982-01-01

    Molecular mechanics is a nonquantum mechanical method for solving problems concerning molecular geometries and energy. Methodology based on: the principle of combining potential energy functions of all structural features of a particular molecule into a total force field; derivation of basic equations; and use of available computer programs is…

  3. Potential Mechanisms Underlying Centralized Pain and Emerging Therapeutic Interventions

    Directory of Open Access Journals (Sweden)

    Olivia C. Eller-Smith

    2018-02-01

    Full Text Available Centralized pain syndromes are associated with changes within the central nervous system that amplify peripheral input and/or generate the perception of pain in the absence of a noxious stimulus. Examples of idiopathic functional disorders that are often categorized as centralized pain syndromes include fibromyalgia, chronic pelvic pain syndromes, migraine, and temporomandibular disorder. Patients often suffer from widespread pain, associated with more than one specific syndrome, and report fatigue, mood and sleep disturbances, and poor quality of life. The high degree of symptom comorbidity and a lack of definitive underlying etiology make these syndromes notoriously difficult to treat. The main purpose of this review article is to discuss potential mechanisms of centrally-driven pain amplification and how they may contribute to increased comorbidity, poorer pain outcomes, and decreased quality of life in patients diagnosed with centralized pain syndromes, as well as discuss emerging non-pharmacological therapies that improve symptomology associated with these syndromes. Abnormal regulation and output of the hypothalamic-pituitary-adrenal (HPA axis is commonly associated with centralized pain disorders. The HPA axis is the primary stress response system and its activation results in downstream production of cortisol and a dampening of the immune response. Patients with centralized pain syndromes often present with hyper- or hypocortisolism and evidence of altered downstream signaling from the HPA axis including increased Mast cell (MC infiltration and activation, which can lead to sensitization of nearby nociceptive afferents. Increased peripheral input via nociceptor activation can lead to “hyperalgesic priming” and/or “wind-up” and eventually to central sensitization through long term potentiation in the central nervous system. Other evidence of central modifications has been observed through brain imaging studies of functional

  4. [Study on main pharmacodynamics and underlying mechanisms of 999 Ganmaoling].

    Science.gov (United States)

    Xu, Qi-Hua; He, Rong; Peng, Bo; Ye, Zu-Guang; Li, Jian-Rong; Zhang, Yue-Fei; Dai, Zhi

    2016-04-01

    To observe synergistic effects of 999 Ganmaoling (GML) and its Chinese/Western materia medica (CMM and WMM) on pharmacodynamic action and to study underlying mechanisms, their anti-inflammatory, antipyretic effects were compared by assaying the increased capillary permeability induced by glacial acetic acid in mice, ear swelling induced by Xylene in mice, non-specific pleurisy induced by carrageenan in rats, and yeast induced fever in rats. Crystal violet (CV) and microbial activity (XTT) assay were used to evaluate the inhibition of GML and its CMM and WMM on KPN biofilm formation, and scanning electron microscopy (SEM) was applied for observing KPN biofilm morphology changes. The results showed that compared with control group, GML could reduce exudation amount of Evans-Blue and the degree of Ear swelling significantly, and CMM and WMM have no significant effects. The concentration of TNF-α and IL-1β of rat pleural effusion in GML, CMM and WMM group decreased significantly. The concentration of TNF-α, IL-1β and IL-8 in GML group, TNF-α, IL-8 in WMM group and IL-8 in CMM in rats serum decreased significantly. The body temperature in rats decreased significantly in GML and WMM group after 4-8 h of administration. CMM group showed no significant difference in rat body temperature compare with control. Compared with control group, GML (55-13.75 g•L⁻¹) could inhibit KPN biofilm formation and reduce number of viable cells in the KPN biofilm. CMM (45-22.5 g•L⁻¹) and WMM (10 g•L⁻¹) could also inhibit KPN biofilm formation and reduce number of viable cells (P<0.01). Result of SEM also showed that GML (55 g•L⁻¹) and its CMM (45 g•L⁻¹) and WMM (10 g•L⁻¹) could interfere the bacterial arrangement of KPN biofilm and extracellular matrix. GML and its CMM & WMM could inhibit the formation of KPN biofilm, CMM & WMM in GML showed synergism and complementation in inhibit KPN biofilm. Results showed that GML had obvious anti-inflammatory and

  5. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.

    Science.gov (United States)

    Shahin, Mohamed H; Johnson, Julie A

    2016-04-01

    Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. Copyright © 2016. Published by Elsevier Ltd.

  6. Cellular and molecular mechanisms involved in the establishment of HIV-1 latency

    Directory of Open Access Journals (Sweden)

    Donahue Daniel A

    2013-02-01

    Full Text Available Abstract Latently infected cells represent the major barrier to either a sterilizing or a functional HIV-1 cure. Multiple approaches to reactivation and depletion of the latent reservoir have been attempted clinically, but full depletion of this compartment remains a long-term goal. Compared to the mechanisms involved in the maintenance of HIV-1 latency and the pathways leading to viral reactivation, less is known about the establishment of latent infection. This review focuses on how HIV-1 latency is established at the cellular and molecular levels. We first discuss how latent infection can be established following infection of an activated CD4 T-cell that undergoes a transition to a resting memory state and also how direct infection of a resting CD4 T-cell can lead to latency. Various animal, primary cell, and cell line models also provide insights into this process and are discussed with respect to the routes of infection that result in latency. A number of molecular mechanisms that are active at both transcriptional and post-transcriptional levels have been associated with HIV-1 latency. Many, but not all of these, help to drive the establishment of latent infection, and we review the evidence in favor of or against each mechanism specifically with regard to the establishment of latency. We also discuss the role of immediate silent integration of viral DNA versus silencing of initially active infections. Finally, we discuss potential approaches aimed at limiting the establishment of latent infection.

  7. An overview of potential molecular mechanisms involved in VSMC phenotypic modulation.

    Science.gov (United States)

    Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Yan-Qin; Wang, Xu; Pi, Yan; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

    2016-02-01

    The fully differentiated medial vascular smooth muscle cells (VSMCs) of mature vessels keep quiescent and contractile. However, VSMC can exhibit the plasticity in phenotype switching from a differentiated and contractile phenotype to a dedifferentiated state in response to alterations in local environmental cues, which is called phenotypic modulation or switching. Distinguishing from its differentiated state expressing more smooth muscle (SM)-specific/selective proteins, the phenotypic modulation in VSMC is characterized by an increased rate of proliferation, migration, synthesis of extracellular matrix proteins and decreased expression of SM contractile proteins. Although it has been well demonstrated that phenotypic modulation of VSMC contributes to the occurrence and progression of many proliferative vascular diseases, little is known about the details of the molecular mechanisms of VSMC phenotypic modulation. Growing evidence suggests that variety of molecules including microRNAs, cytokines and biochemical factors, membrane receptors, ion channels, cytoskeleton and extracellular matrix play important roles in controlling VSMC phenotype. The focus of the present review is to provide an overview of potential molecular mechanisms involved in VSMC phenotypic modulation in recent years. To clarify VSMC differentiation and phenotypic modulation mechanisms will contribute to producing cell-based therapeutic interventions for aberrant VSMC differentiation-related diseases.

  8. Mechanical response of collagen molecule under hydrostatic compression

    International Nuclear Information System (INIS)

    Saini, Karanvir; Kumar, Navin

    2015-01-01

    Proteins like collagen are the basic building blocks of various body tissues (soft and hard). Collagen molecules find their presence in the skeletal system of the body where they bear mechanical loads from different directions, either individually or along with hydroxy-apatite crystals. Therefore, it is very important to understand the mechanical behavior of the collagen molecule which is subjected to multi-axial state of loading. The estimation of strains of collagen molecule along different directions resulting from the changes in hydrostatic pressure magnitude, can provide us new insights into its mechanical behavior. In the present work, full atomistic simulations have been used to study global (volumetric) as well as local (along different directions) mechanical properties of the hydrated collagen molecule which is subjected to different hydrostatic pressure magnitudes. To estimate the local mechanical properties, the strains of collagen molecule along its longitudinal and transverse directions have been acquired at different hydrostatic pressure magnitudes. In spite of non-homogeneous distribution of atoms within the collagen molecule, the calculated values of local mechanical properties have been found to carry the same order of magnitude along the longitudinal and transverse directions. It has been demonstrated that the values of global mechanical properties like compressibility, bulk modulus, etc. as well as local mechanical properties like linear compressibility, linear elastic modulus, etc. are functions of magnitudes of applied hydrostatic pressures. The mechanical characteristics of collagen molecule based on the atomistic model have also been compared with that of the continuum model in the present work. The comparison showed up orthotropic material behavior for the collagen molecule. The information on collagen molecule provided in the present study can be very helpful in designing the future bio-materials.

  9. Mechanisms underlying the nociceptive responses induced by platelet-activating factor (PAF) in the rat paw.

    Science.gov (United States)

    Marotta, Denise M; Costa, Robson; Motta, Emerson M; Fernandes, Elizabeth S; Medeiros, Rodrigo; Quintão, Nara L M; Campos, Maria M; Calixto, João B

    2009-04-01

    Platelet-activating factor (PAF) is an inflammatory mediator widely known to exert relevant pathophysiological functions. However, the relevance of PAF in nociception has received much less attention. Herein, we have investigated the mechanisms underlying PAF-induced spontaneous nociception and mechanical hypersensitivity in the rat paw. PAF injection (1- 30 nmol/paw) resulted in a dose-related overt nociception, whilst only the dose of 10 nmol/ paw produced a significant and time-related mechanical hypersensitivity. Local coinjection of PAF antagonist WEB2086 significantly inhibited both spontaneous nociception and mechanical hypersensitivity. Moreover, the coinjection of the natural IL-1beta receptor antagonist (IRA) notably prevented both PAF-induced nociceptive responses, whilst these responses were not altered by anti-TNFalpha coinjection. Interestingly, pretreatment with the ultrapotent vaniloid agonist resiniferotoxin, coinjection of the TRPV1 receptor antagonist SB366791, or mast cell depletion with compound 48/80 markedly prevented PAF-induced spontaneous nociception. Conversely, PAF-elicited mechanical hypersensitivity was strikingly susceptible to distinct antineutrophil-related strategies, namely the antineutrophil antibody, the selectin blocker fucoidin, the chemokine CXCR2 receptor antagonist SB225002, and the C5a receptor antibody anti-CD88. Notably, the same antineutrophil migration strategies significantly prevented the increase of myeloperoxidase activity induced by PAF. The mechanical hypersensitivity caused by PAF was also prevented by the cyclooxygenase inhibitors indomethacin or celecoxib, and by the selective beta(1) adrenergic receptor antagonist atenolol. Collectively, the present results provide consistent evidence indicating that distinct mechanisms are involved in the spontaneous nociception and mechanical hypersensitivity caused by PAF. They also support the concept that selective PAF receptor antagonists might constitute interesting

  10. Oriented scanning is the leading mechanism underlying 5' splice site selection in mammals.

    Directory of Open Access Journals (Sweden)

    Keren Borensztajn

    2006-09-01

    Full Text Available Splice site selection is a key element of pre-mRNA splicing. Although it is known to involve specific recognition of short consensus sequences by the splicing machinery, the mechanisms by which 5' splice sites are accurately identified remain controversial and incompletely resolved. The human F7 gene contains in its seventh intron (IVS7 a 37-bp VNTR minisatellite whose first element spans the exon7-IVS7 boundary. As a consequence, the IVS7 authentic donor splice site is followed by several cryptic splice sites identical in sequence, referred to as 5' pseudo-sites, which normally remain silent. This region, therefore, provides a remarkable model to decipher the mechanism underlying 5' splice site selection in mammals. We previously suggested a model for splice site selection that, in the presence of consecutive splice consensus sequences, would stimulate exclusively the selection of the most upstream 5' splice site, rather than repressing the 3' following pseudo-sites. In the present study, we provide experimental support to this hypothesis by using a mutational approach involving a panel of 50 mutant and wild-type F7 constructs expressed in various cell types. We demonstrate that the F7 IVS7 5' pseudo-sites are functional, but do not compete with the authentic donor splice site. Moreover, we show that the selection of the 5' splice site follows a scanning-type mechanism, precluding competition with other functional 5' pseudo-sites available on immediate sequence context downstream of the activated one. In addition, 5' pseudo-sites with an increased complementarity to U1snRNA up to 91% do not compete with the identified scanning mechanism. Altogether, these findings, which unveil a cell type-independent 5'-3'-oriented scanning process for accurate recognition of the authentic 5' splice site, reconciliate apparently contradictory observations by establishing a hierarchy of competitiveness among the determinants involved in 5' splice site selection.

  11. Mechanical Characterization of Anion Exchange Membranes Under Controlled Environmental Conditions

    Science.gov (United States)

    2015-05-11

    supporting textiles and test the mechanical properties. Even though their films were only 10 microns, the SER fixture was used by applying double stick tape...aramid and stainless steel. The authors conclude that supporting textile has a large impact on mechanical properties due to the difference in...Elongation) are depicted. 2.2 Conductivity Ionic conductivity was measured by electrochemical impedance spectroscopy using a four- electrode in-plane

  12. Features wear nodes mechanization wing aircraft operating under dynamic loads

    Directory of Open Access Journals (Sweden)

    А.М. Хімко

    2009-03-01

    Full Text Available  The conducted researches of titanic alloy ВТ-22 at dynamic loading with cycled sliding and dynamic loading in conditions of rolling with slipping. It is established that roller jamming in the carriage increases wear of rod of mechanization of a wing to twenty times. The optimum covering for strengthening wearied sites and restoration of working surfaces of wing’s mechanization rod is defined.

  13. Peptide Bond Synthesis by a Mechanism Involving an Enzymatic Reaction and a Subsequent Chemical Reaction.

    Science.gov (United States)

    Abe, Tomoko; Hashimoto, Yoshiteru; Zhuang, Ye; Ge, Yin; Kumano, Takuto; Kobayashi, Michihiko

    2016-01-22

    We recently reported that an amide bond is unexpectedly formed by an acyl-CoA synthetase (which catalyzes the formation of a carbon-sulfur bond) when a suitable acid and l-cysteine are used as substrates. DltA, which is homologous to the adenylation domain of nonribosomal peptide synthetase, belongs to the same superfamily of adenylate-forming enzymes, which includes many kinds of enzymes, including the acyl-CoA synthetases. Here, we demonstrate that DltA synthesizes not only N-(d-alanyl)-l-cysteine (a dipeptide) but also various oligopeptides. We propose that this enzyme catalyzes peptide synthesis by the following unprecedented mechanism: (i) the formation of S-acyl-l-cysteine as an intermediate via its "enzymatic activity" and (ii) subsequent "chemical" S → N acyl transfer in the intermediate, resulting in peptide formation. Step ii is identical to the corresponding reaction in native chemical ligation, a method of chemical peptide synthesis, whereas step i is not. To the best of our knowledge, our discovery of this peptide synthesis mechanism involving an enzymatic reaction and a subsequent chemical reaction is the first such one to be reported. This new process yields peptides without the use of a thioesterified fragment, which is required in native chemical ligation. Together with these findings, the same mechanism-dependent formation of N-acyl compounds by other members of the above-mentioned superfamily demonstrated that all members most likely form peptide/amide compounds by using this novel mechanism. Each member enzyme acts on a specific substrate; thus, not only the corresponding peptides but also new types of amide compounds can be formed. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Synthetic oligorotaxanes exert high forces when folding under mechanical load

    Science.gov (United States)

    Sluysmans, Damien; Hubert, Sandrine; Bruns, Carson J.; Zhu, Zhixue; Stoddart, J. Fraser; Duwez, Anne-Sophie

    2018-01-01

    Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems1,2. Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts3-5. Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure6-8. Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

  15. A possible new mechanism involved in non-uniform field breakdown in gaseous dielectrics

    International Nuclear Information System (INIS)

    Pinnaduwage, L.A.; Christophorou, L.G.

    1994-01-01

    The electrical breakdown of gases under uniform field conditions is fairly well understood in terms of the Townsend's breakdown theory. In most cases involving uniform fields, the breakdown voltage can be estimated via this theory using basic electron impact parameters for molecules in their ground electronic states. In contrast, a consistent model of gaseous breakdown under nonuniform fields is not available at present although substantial progress has been made recently. We point out the possibility that electron impact processes involving high-lying electronically-excited states may play a significant role under non-uniform field conditions. Thus, such processes may need to be included in order to obtain a better understanding of non-uniform field breakdown phenomena. The general, breakdown characteristics of highly non-uniform field gaps can be illustrated by that for a point-plane geometry. It has been found that the breakdown voltage for such a gap can be calculated by a simple streamer criterion if the pressure P, is above a critical value, P c ; for P c , the estimated breakdown voltage is found to coincide with the corona inception voltage, with the actual breakdown occurring at a higher voltage, corona discharges occur only for P c . In other words, the presence of corona in the pressure region below P c seems to prevent the breakdown from occurring at the predicted value. This has led to the term ''corona stabilization'' to describe the enhancement in the breakdown voltage for pressures below P c . Non-uniform field breakdown measurements in gases will be discussed. We will discuss the possibility that the ''corona stabilization'' is due to the prevention of avalanche progression by attachment of free electrons to molecules in their high-lying electronically-excited states. Information on electron attachment to electronically-excited states of molecules was not available up until the late 1980's

  16. Adenosine A2Areceptor involves in neuroinflammation-mediated cognitive decline through activating microglia under acute hypobaric hypoxia.

    Science.gov (United States)

    Chen, Peng-Zhi; He, Wen-Juan; Zhu, Zhi-Ru; E, Guo-Ji; Xu, Gang; Chen, De-Wei; Gao, Yu-Qi

    2018-03-06

    Hypobaric hypoxia (HH) at high altitudes leads to a wide range of cognitive impairments which can handicap human normal activities and performances. However, the underlying mechanism is still unclear. Adenosine A 2A receptors (A 2A Rs) of the brain are pivotal to synaptic plasticity and cognition. Besides, insult-induced up-regulation of A 2A R regulates neuroinflammation and therefore induces brain damages in various neuropathological processes. The present study was designed to determine whether A 2A R-mediate neuroinflammation involves in cognitive impairments under acute HH. A 2A R knock-out and wild-type male mice were exposed to a simulated altitude of 8000 m for 7 consecutive days in a hypobaric chamber and simultaneously received behavioral tests including Morris water maze test and open filed test. A 2A R expression, the activation of microglia and the production of TNF-α were evaluated in the hippocampus by immunohistochemistry and ELISA, respectively. Behavioral tests showed that acute HH exposure caused the dysfunction of spatial memory and mood, while genetic inactivation of A 2A R attenuated the impairment of spatial memory but not that of mood. Double-labeled immunofluorescence showed that A 2A Rs were mainly expressed on microglia and up-regulated in the hippocampus of acute HH model mice. Acute HH also induced the accumulation of microglia and increased production of TNF-α in the hippocampus, which could be markedly inhibited by A 2A R inactivation. These findings indicate that microglia-mediated neuroinflammation triggered by A 2A R activation involves in acute HH-induced spatial memory impairment and that A 2A R could be a new target for the pharmacotherapy of cognitive dysfunction at high altitudes. Copyright © 2018. Published by Elsevier B.V.

  17. Early molecular events involved in Pinus pinaster Ait. somatic embryo development under reduced water availability: transcriptomic and proteomic analyses.

    Science.gov (United States)

    Morel, Alexandre; Teyssier, Caroline; Trontin, Jean-François; Eliášová, Kateřina; Pešek, Bedřich; Beaufour, Martine; Morabito, Domenico; Boizot, Nathalie; Le Metté, Claire; Belal-Bessai, Leila; Reymond, Isabelle; Harvengt, Luc; Cadene, Martine; Corbineau, Françoise; Vágner, Martin; Label, Philippe; Lelu-Walter, Marie-Anne

    2014-09-01

    Maritime pine somatic embryos (SEs) require a reduction in water availability (high gellan gum concentration in the maturation medium) to reach the cotyledonary stage. This key switch, reported specifically for pine species, is not yet well understood. To facilitate the use of somatic embryogenesis for mass propagation of conifers, we need a better understanding of embryo development. Comparison of both transcriptome (Illumina RNA sequencing) and proteome [two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis with mass spectrometry (MS) identification] of immature SEs, cultured on either high (9G) or low (4G) gellan gum concentration, was performed, together with analysis of water content, fresh and dry mass, endogenous abscisic acid (ABA; gas chromatography-MS), soluble sugars (high-pressure liquid chromatography), starch and confocal laser microscope observations. This multiscale, integrated analysis was used to unravel early molecular and physiological events involved in SE development. Under unfavorable conditions (4G), the glycolytic pathway was enhanced, possibly in relation to cell proliferation that may be antagonistic to SE development. Under favorable conditions (9G), SEs adapted to culture constraint by activating specific protective pathways, and ABA-mediated molecular and physiological responses promoting embryo development. Our results suggest that on 9G, germin-like protein and ubiquitin-protein ligase could be used as predictive markers of SE development, whereas protein phosphatase 2C could be a biomarker for culture adaptive responses. This is the first characterization of early molecular mechanisms involved in the development of pine SEs following an increase in gellan gum concentration in the maturation medium, and it is also the first report on somatic embryogenesis in conifers combining transcriptomic and proteomic datasets. © 2014 Scandinavian Plant Physiology Society.

  18. On the Path of Election and Martyrdom: Some Psychic Mechanisms Involved in the Anders Behring Breivik's Determination as a Terrorist.

    Science.gov (United States)

    Cotti, Patricia

    2015-08-01

    On 22 July 2011, the Norwegian Anders Behring Breivik carried out two attacks in Oslo that cost the lives of 77 people, injured many others, and plunged the entire Norwegian nation into mourning. When he was arrested, Breivik presented himself as a member of the Knights Templar, whose mission is to defend the Christian Western world. He considers that he has sacrificed himself by his actions for his people and says that he has prepared himself for martyrdom. In analysing Breivik's words and writings, this article attempts to identify the thought mechanisms involved in Breivik's idea of election (megalomania) and martyrology. It highlights the importance of a mechanism of "return to the sender," whereby Breivik returns the reproaches directed at him by an agency of judgment (ego ideal or superegoic object). It emphasizes the existence of a "burning desire" and yearning (Sehnsucht) for this same persecuting superegoic object, an object that Breivik constantly wants to find again, even if in death. Taking into consideration Searles's hypothesis that the sense of being persecuted is a defence against the impossibility of mourning, and also H. Blum's hypothesis that persecutory feelings are indicative of fears of a "regressive loss of object constancy," the different psychic mechanisms and modes of functioning underlying Breivik's terrorist determination are related here to what we know about his affective development and infantile relationships.

  19. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    Energy Technology Data Exchange (ETDEWEB)

    Massi, Paola [Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Via Vanvitelli 32, 20129 Milan (Italy); Valenti, Marta; Solinas, Marta; Parolaro, Daniela, E-mail: daniela.parolaro@uninsubria.it [Department of Structural and Functional Biology, Section of Pharmacology, Center of Neuroscience, University of Insubria, Via A. da Giussano 10, 20152 Busto Arsizio, Varese (Italy)

    2010-05-26

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

  20. [Immune mechanisms involved in the development and eradication of anti-factor VIII alloantibodies in hemophilia].

    Science.gov (United States)

    Ishiguro, Akira

    2011-01-01

    Hemophilia A is an X-linked hereditary bleeding disorder caused by a congenital deficiency in blood coagulation factor VIII (FVIII). Therapy to prevent or treat bleeding is replacement of FVIII. The most significant complication of treatment in patients with hemophilia A is the development of alloantibodies that inhibit FVIII activity, termed inhibitors. In the presence of inhibitors, replacement of the missing clotting factor with FVIII preparations becomes less effective. Once replacement therapy is ineffective, morbidity increases. It remains unsolved to prevent inhibitor formation. The only strategy is long-term administration of a large quantity of FVIII in an attempt to eradicate the inhibitors through immune tolerance. However, little is known about the mechanisms involved in the induction of tolerance. This review will focus on the current understanding of why inhibitors develop and can be eradicated. The development of inhibitors by intravenous infusions of FVIII without adjuvant poses an intriguing challenge to immunologists.

  1. Understanding the neural mechanisms involved in sensory control of voice production.

    Science.gov (United States)

    Parkinson, Amy L; Flagmeier, Sabina G; Manes, Jordan L; Larson, Charles R; Rogers, Bill; Robin, Donald A

    2012-05-15

    Auditory feedback is important for the control of voice fundamental frequency (F0). In the present study we used neuroimaging to identify regions of the brain responsible for sensory control of the voice. We used a pitch-shift paradigm where subjects respond to an alteration, or shift, of voice pitch auditory feedback with a reflexive change in F0. To determine the neural substrates involved in these audio-vocal responses, subjects underwent fMRI scanning while vocalizing with or without pitch-shifted feedback. The comparison of shifted and unshifted vocalization revealed activation bilaterally in the superior temporal gyrus (STG) in response to the pitch shifted feedback. We hypothesize that the STG activity is related to error detection by auditory error cells located in the superior temporal cortex and efference copy mechanisms whereby this region is responsible for the coding of a mismatch between actual and predicted voice F0. Published by Elsevier Inc.

  2. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    International Nuclear Information System (INIS)

    Massi, Paola; Valenti, Marta; Solinas, Marta; Parolaro, Daniela

    2010-01-01

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells

  3. Involvement of the flagellar assembly pathway in Vibrio alginolyticus adhesion under environmental stresses

    Directory of Open Access Journals (Sweden)

    Lu eWang

    2015-08-01

    Full Text Available Adhesion is an important virulence factor of Vibrio alginolyticus. This factor may be affected by environment conditions; however, its molecular mechanism remains unclear. In our previous research, adhesion tender models were obtained by culturing V. alginolyticus under stresses such as Cu2+, Pb2+, Hg2+, and low pH. With high-throughput sequencing and bioinformatics analysis, we found that all of these stress treatments significantly affected the flagellar assembly pathway, which may play an important role in V. alginolyticus adhesion. Therefore, we hypothesized that the environmental stresses of the flagellar assembly pathway may be one way in which environment conditions affect adhesion. To verify our hypothesis, a bioinformatics analysis, QPCR, RNAi, in vitro adhesion assay and motility assay were performed. Our results indicated that 1 the flagellar assembly pathway was sensitive to environmental stresses, 2 the flagellar assembly pathway played an important role in V. alginolyticus adhesion, and 3 motility is not the only way in which the flagellar assembly pathway affects adhesion.

  4. Phenanthrene causes ocular developmental toxicity in zebrafish embryos and the possible mechanisms involved

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Lixing [State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Wang, Chonggang [State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005 (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China); Zhang, Youyu; Wu, Meifang [State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Zuo, Zhenghong, E-mail: zuozhenghong@xmu.edu.cn [State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005 (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China)

    2013-10-15

    Highlights: • Phe exposure caused obvious morphological changes in the retina. • Phe exposure caused apoptosis and reduction of cell proliferation in the retina. • Phe causes ocular toxicity might be via the AhR/Zeb1/Mitf/Pax6 signaling pathway. • AhR is a repressor of Zeb1. -- Abstract: Recent studies show that polycyclic aromatic hydrocarbons (PAHs) may be a candidate cause of developmental defects of the retina, but the mechanism is still unclear. We evaluated the mechanism(s) underlying PAH-induced retinal development defects due to exposure to environmental concentrations of Phenanthrene (Phe) in zebrafish. We found that exposure to environmental concentrations of Phe caused obvious morphological changes, developmental retardation, apoptosis, and reduction of cell proliferation in the retina. Our results indicated that Phe could cause visual system developmental defects. Phe exposure up-regulated aryl hydrocarbon receptor (AhR) and microphthalmia-associated transcription factor (Mtif) expression, and down-regulated zinc finger E-box binding homeobox 1 (Zeb1) and paired box 6 (Pax6). Moreover, we demonstrated that AhR was a repressor of Zeb1. We propose that Phe's ocular toxicity is mediated by up-regulating AhR, which then down-regulates Zeb1, in turn inducing Mitf expression while inhibiting Pax6 expression.

  5. Cellular mechanisms involved in CO(2) and acid signaling in chemosensitive neurons.

    Science.gov (United States)

    Putnam, Robert W; Filosa, Jessica A; Ritucci, Nicola A

    2004-12-01

    An increase in CO(2)/H(+) is a major stimulus for increased ventilation and is sensed by specialized brain stem neurons called central chemosensitive neurons. These neurons appear to be spread among numerous brain stem regions, and neurons from different regions have different levels of chemosensitivity. Early studies implicated changes of pH as playing a role in chemosensitive signaling, most likely by inhibiting a K(+) channel, depolarizing chemosensitive neurons, and thereby increasing their firing rate. Considerable progress has been made over the past decade in understanding the cellular mechanisms of chemosensitive signaling using reduced preparations. Recent evidence has pointed to an important role of changes of intracellular pH in the response of central chemosensitive neurons to increased CO(2)/H(+) levels. The signaling mechanisms for chemosensitivity may also involve changes of extracellular pH, intracellular Ca(2+), gap junctions, oxidative stress, glial cells, bicarbonate, CO(2), and neurotransmitters. The normal target for these signals is generally believed to be a K(+) channel, although it is likely that many K(+) channels as well as Ca(2+) channels are involved as targets of chemosensitive signals. The results of studies of cellular signaling in central chemosensitive neurons are compared with results in other CO(2)- and/or H(+)-sensitive cells, including peripheral chemoreceptors (carotid body glomus cells), invertebrate central chemoreceptors, avian intrapulmonary chemoreceptors, acid-sensitive taste receptor cells on the tongue, and pain-sensitive nociceptors. A multiple factors model is proposed for central chemosensitive neurons in which multiple signals that affect multiple ion channel targets result in the final neuronal response to changes in CO(2)/H(+).

  6. Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

    Science.gov (United States)

    Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

    2016-10-01

    As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Mechanism and kinetics of mineral weathering under acid conditions

    NARCIS (Netherlands)

    Anbeek, C.

    1994-01-01

    This study deals with the relationships between crystal structure, grain diameter, surface morphology and dissolution kinetics for feldspar and quartz under acid conditions.

    Intensively ground samples from large, naturally weathered mineral fragments are frequently used in

  8. Performance of multifilamentary Nb3Sn under mechanical load

    International Nuclear Information System (INIS)

    Easton, D.S.; Schwall, R.E.

    1976-01-01

    The critical current of a commercial multifilamentary Nb 3 Sn conductor has been measured under the application of uniaxial tension at 4.2 K and following bending at room temperature. Significant reductions in J/subc/ are observed under uniaxial loading. Results are presented for a monolithic conductor manufactured by the bronze diffusion technique and for cable conductors formed by the tin-dip technique

  9. Consciousness, unconsciousness and death in the context of slaughter. Part I. Neurobiological mechanisms underlying stunning and killing.

    Science.gov (United States)

    Terlouw, Claudia; Bourguet, Cécile; Deiss, Véronique

    2016-08-01

    This review describes the neurobiological mechanisms that are relevant for the stunning and killing process of animals in the abattoir. The mechanisms underlying the loss of consciousness depend on the technique used: mechanical, electrical or gas stunning. Direct exsanguination (without prior stun) causes also a loss of consciousness before inducing death. The underlying mechanisms may involve cerebral anoxia or ischemia, or the depolarisation, acidification and/or the destruction of brain neurons. These effects may be caused by shock waves, electrical fields, the reduction or arrest of the cerebral blood circulation, increased levels of CO2 or low levels of O2 in the inhaled air, or the mechanical destruction of neurons. The targeted brain structures are the reticular formation, the ascending reticular activating system or thalamus, or the cerebral hemispheres in a general manner. Some of the techniques, when properly used, induce an immediate loss of consciousness; other techniques a progressive loss of consciousness. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Advanced waterflooding in chalk reservoirs: Understanding of underlying mechanisms

    DEFF Research Database (Denmark)

    Zahid, Adeel; Sandersen, Sara Bülow; Stenby, Erling Halfdan

    2011-01-01

    Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recove...... of a microemulsion phase could be the possible reasons for the observed increase in oil recovery with sulfate ions at high temperature in chalk reservoirs besides the mechanism of the rock wettability alteration, which has been reported in most previous studies.......Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recovery...

  11. Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2014-10-01

    There have been considerable advances in uncovering the complex genetic mechanisms that underlie nervous system disease pathogenesis, particularly with the advent of exome and whole genome sequencing techniques. The emerging field of epigenetics is also providing further insights into these mechanisms. Here, we discuss our understanding of the interplay that exists between genetic and epigenetic mechanisms in these disorders, highlighting the nascent field of epigenetic epidemiology-which focuses on analyzing relationships between the epigenome and environmental exposures, development and aging, other health-related phenotypes, and disease states-and next-generation research tools (i.e., those leveraging synthetic and chemical biology and optogenetics) for examining precisely how epigenetic modifications at specific genomic sites affect disease processes.

  12. New developments on the neurobiological and pharmaco-genetic mechanisms underlying internet and videogame addiction.

    Science.gov (United States)

    Weinstein, Aviv; Lejoyeux, Michel

    2015-03-01

    There is emerging evidence that the psychobiological mechanisms underlying behavioral addictions such as internet and videogame addiction resemble those of addiction for substances of abuse. Review of brain imaging, treatment and genetic studies on videogame and internet addiction. Literature search of published articles between 2009 and 2013 in Pubmed using "internet addiction" and "videogame addiction" as the search word. Twenty-nine studies have been selected and evaluated under the criteria of brain imaging, treatment, and genetics. Brain imaging studies of the resting state have shown that long-term internet game playing affected brain regions responsible for reward, impulse control and sensory-motor coordination. Brain activation studies have shown that videogame playing involved changes in reward and loss of control and that gaming pictures have activated regions similarly to those activated by cue-exposure to drugs. Structural studies have shown alterations in the volume of the ventral striatum possible as result of changes in reward. Furthermore, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and that there were faulty inhibitory control and reward mechanisms videogame addicted individuals. Finally, treatment studies using fMRI have shown reduction in craving for videogames and reduced associated brain activity. Videogame playing may be supported by similar neural mechanisms underlying drug abuse. Similar to drug and alcohol abuse, internet addiction results in sub-sensitivity of dopamine reward mechanisms. Given the fact that this research is in its early stage it is premature to conclude that internet addiction is equivalent to substance addictions. © American Academy of Addiction Psychiatry.

  13. A possible new mechanism involved in ferro-cyanide metabolism by plants.

    Science.gov (United States)

    Yu, Xiao-Zhang; Li, Fan; Li, Kun

    2011-09-01

    Ferro-cyanide is one of the commonly found species at cyanide-contaminated soils and groundwater. Unlike botanical metabolism of KCN via the β-cyanoalanine pathway, processes involved in the plant-mediated assimilation of ferro-cyanide are still unclear. The objective of this study was to investigate a possible mechanism involved in uptake and assimilation of ferro-cyanide by plants. Detached roots of plants were exposed to ferro-cyanide in a closed-dark hydroponic system amended with HgCl(2), AgNO(3), LaCl(3), tetraethylammonium chloride (TEACl), or Na(3)VO(4), respectively, at 25 ± 0.5°C for 24 h. Total CN, free CN(-), and dissolved Fe(2+) were analyzed spectrophotometrically. Activity of β-cyanoalanine synthase involved in cyanide assimilation was also assayed using detached roots of plants in vivo. Dissociation of ferro-cyanide [Fe(II)(CN)(6)](-4) to free CN(-) and Fe(2+) in solution was negligible. The applied inhibitors did not show any significant impact on the uptake of ferro-cyanide by soybean (Glycine max L. cv. JD 1) and hybrid willows (Salix matsudana Koidz × alba L.; p > 0.05), but rice (Oryza sativa L. cv. JY 98) was more susceptible to the inhibitors compared with the controls (p ferro-cyanide by soybean, hybrid willows, and maize (Zea mays L. cv. PA 78; p ferro-cyanide was observed compared with the control without any cyanides (p > 0.05), whereas roots exposed to KCN showed a considerable increase in enzyme activity (p ferro-cyanide. Ferro-cyanide is likely metabolized by plants directly through an unknown pathway rather than the β-cyanoalanine pathway.

  14. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    Directory of Open Access Journals (Sweden)

    J. Lozano-Cuenca

    Full Text Available Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10–9–10–5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10–7.5–10–5 M. The present outcome was not modified by 10–6 M atropine (an antagonist of muscarinic acetylcholine receptors, 3.1×10–7 M glibenclamide (an ATP-sensitive K+ channel blocker, 10–3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker, 10–5 M indomethacin (a prostaglandin synthesis inhibitor, 10–5 M clotrimazole (a cytochrome P450 inhibitor or 10–5 M cycloheximide (a general protein synthesis inhibitor. Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05 by 10–5 M L-NAME (a direct inhibitor of nitric oxide synthase, 10–7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase, 10–6 M KT 5823 (an inhibitor of protein kinase G, 10–2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker and 10–7 M apamin plus 10–7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively, and was blocked by 8×10–2 M potassium (a high concentration and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

  15. A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

    Directory of Open Access Journals (Sweden)

    Andrew P. Wojtovich

    2013-03-01

    Full Text Available Opening of BK-type Ca2+ activated K+ channels protects the heart against ischemia-reperfusion (IR injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection.

  16. Propagation of an Aβ Dodecamer Strain Involves a Three-Step Mechanism and a Key Intermediate.

    Science.gov (United States)

    Dean, Dexter N; Rana, Pratip; Campbell, Ryan P; Ghosh, Preetam; Rangachari, Vijayaraghavan

    2018-02-06

    Proteinaceous deposits composed of fibrillar amyloid-β (Aβ) are the primary neuropathological hallmarks in Alzheimer disease (AD) brains. The nucleation-dependent aggregation of Aβ is a stochastic process with frequently observed heterogeneity in aggregate size, structure, and conformation that manifests in fibril polymorphism. Emerging evidence indicates that polymorphic variations in Aβ fibrils contribute to phenotypic diversity and the rate of disease progression in AD. We recently demonstrated that a dodecamer strain derived from synthetic Aβ42 propagates to morphologically distinct fibrils and selectively induces cerebral amyloid angiopathy phenotype in transgenic mice. This report supports the growing contention that stable oligomer strains can influence phenotypic outcomes by faithful propagation of their structures. Although we determined the mechanism of dodecamer propagation on a mesoscopic scale, the molecular details of the microscopic reactions remained unknown. Here, we have dissected and evaluated individually the kinetics of macroscopic phases in aggregation to gain insight into the process of strain propagation. The bulk rates determined experimentally in each phase were used to build an ensemble kinetic simulation model, which confirmed our observation that dodecamer seeds initially grow by monomer addition toward the formation of a key intermediate. This is followed by conversion of the intermediate to fibrils by oligomer elongation and association mechanisms. Overall, this report reveals important insights into the molecular details of oligomer strain propagation involved in AD pathology. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. Protein Machineries Involved in the Attachment of Heme to Cytochrome c: Protein Structures and Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Carlo Travaglini-Allocatelli

    2013-01-01

    Full Text Available Cytochromes c (Cyt c are ubiquitous heme-containing proteins, mainly involved in electron transfer processes, whose structure and functions have been and still are intensely studied. Surprisingly, our understanding of the molecular mechanism whereby the heme group is covalently attached to the apoprotein (apoCyt in the cell is still largely unknown. This posttranslational process, known as Cyt c biogenesis or Cyt c maturation, ensures the stereospecific formation of the thioether bonds between the heme vinyl groups and the cysteine thiols of the apoCyt heme binding motif. To accomplish this task, prokaryotic and eukaryotic cells have evolved distinctive protein machineries composed of different proteins. In this review, the structural and functional properties of the main maturation apparatuses found in gram-negative and gram-positive bacteria and in the mitochondria of eukaryotic cells will be presented, dissecting the Cyt c maturation process into three functional steps: (i heme translocation and delivery, (ii apoCyt thioreductive pathway, and (iii apoCyt chaperoning and heme ligation. Moreover, current hypotheses and open questions about the molecular mechanisms of each of the three steps will be discussed, with special attention to System I, the maturation apparatus found in gram-negative bacteria.

  18. Senescence as a novel mechanism involved in β-adrenergic receptor mediated cardiac hypertrophy

    Science.gov (United States)

    Sun, Rongrong; Zhu, Baoling; Sun, Yan; Shi, Dandan; Chen, Li; Zhang, Youyi; Li, Zijian; Xue, Lixiang

    2017-01-01

    Pathological cardiac hypertrophy used to be elucidated by biomechanical, stretch-sensitive or neurohumoral mechanisms. However, a series of hints have indicated that hypertrophy process simulates senescence program. However, further evidence need to be pursued. To verify this hypothesis and examine whether cardiac senescence is a novel mechanism of hypertrophy induced by isoproterenol, 2-month-old male Sprague Dawley rats were subjected to isoproterenol infusion (0.25mg/kg/day) for 7 days by subcutaneous injection). Key characteristics of senescence (senescence-associated β-galactosidase activity, lipofuscin, expression of cyclin-dependent kinase inhibitors) were examined in cardiac hypertrophy model. Senescence-like phenotype, such as increased senescence-associated β-galactosidase activity, accumulation of lipofuscin and high levels of cyclin-dependent kinase inhibitors (e.g. p16, p19, p21 and p53) was found along the process of cardiac hypertrophy. Cardiac-specific transcription factor GATA4 increased in isoproterenol-treated cardiomyocytes as well. We further found that myocardial hypertrophy could be inhibited by resveratrol, an anti-aging compound, in a dose-dependent manner. Our results showed for the first time that cardiac senescence is involved in the process of pathological cardiac hypertrophy induced by isoproterenol. PMID:28783759

  19. A review of mechanisms underlying anticarcinogenicity by brassica vegetables

    NARCIS (Netherlands)

    Verhoeven, D.T.H.; Verhagen, H.; Goldbohm, R.A.; Brandt, P.A. van den; Poppel, G. van

    1997-01-01

    The mechanisms by which brassica vegetables might decrease the risk of cancer are reviewed in this paper. Brassicas, including all types of cabbages, broccoli, cauliflower and Brussels sprouts, may be protective against cancer due to their relatively high glucosinolate content. Glucosinolates are

  20. Peer influence: neural mechanisms underlying in-group conformity

    NARCIS (Netherlands)

    Stallen, M.; Smidts, A.; Sanfey, A.G.

    2013-01-01

    People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI). Participants completed

  1. Peer influence: Neural mechanisms underlying in-group conformity

    NARCIS (Netherlands)

    M. Stallen (Mirre); A. Smidts (Ale); A.G. Sanfey (Alan)

    2013-01-01

    textabstractPeople often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI).

  2. Survival under stress: molecular mechanisms of metabolic rate ...

    African Journals Online (AJOL)

    Studies in my laboratory are analysing the molecular mechanisms and regulatory events that underlie transitions to and from hypometabolic states In systems including anoxia-tolerant turtles and molluscs, estivating snails and toads, hibernating small mammals, and freeze tolerant frogs and insects. Our newest research ...

  3. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

    Science.gov (United States)

    Campos, Alline Cristina; Moreira, Fabricio Araújo; Gomes, Felipe Villela; Del Bel, Elaine Aparecida; Guimarães, Francisco Silveira

    2012-01-01

    Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound Δ9-tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARγ receptors agonism, intracellular (Ca2+) increase, etc.), on CBD behavioural effects. PMID:23108553

  4. Transcriptome responses involved in artemisinin production in Artemisia annua L. under UV-B radiation.

    Science.gov (United States)

    Pan, Wei Song; Zheng, Li Ping; Tian, Hao; Li, Wan Yi; Wang, Jian Wen

    2014-11-01

    Artemisinin, an endoperoxide sesquiterpene lactone, is an effective antimalarial drug isolated from Artemisia annua L. In this study, a low dose (1.44 kJm(-2)d(-1)) of UV-B radiation (280-320 nm) for short-term (1h per day for 10 days) was applied to A. annua seedlings to stimulate artemisinin production. UV-B treatment not only induced the generation of reactive oxygen species (ROS), enhanced peroxidase activity and endogenous content of abscisic acid (ABA), but stimulated the biosynthesis of artemisinin in the seedlings. Here, transcriptomic changes during UV-B radiation in A. annua were detected using an Agilent GeneChip with 43,692 probe sets. In total, 358 transcripts were identified as differentially expressed under UV-B stress, of which 172 transcripts increased and 186 transcripts decreased in abundance. In terms of biological processes, gene ontology (GO) terms including primary carbohydrate and nitrogen compound metabolic processes were enriched in UV-B-repressed genes. The up-regulated genes were enriched in response to stress, ROS generation, hormone (ethylene, ABA) stimulus and cell cycle control. The expression of key enzymes such as amorpha-4,11-diene synthase (ADS) and cytochrome P450 dependent monooxygenase/hydroxylase (CYP71AV1), and related WRKY transcription factors was up-regulated significantly for artemisinin biosynthesis. This profile of global gene expression patterns during UV-B stress will be valuable for further identification of the enzymes involved in artemisinin biosynthesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Underlying mechanisms of transient luminous events: a review

    Directory of Open Access Journals (Sweden)

    V. V. Surkov

    2012-08-01

    Full Text Available Transient luminous events (TLEs occasionally observed above a strong thunderstorm system have been the subject of a great deal of research during recent years. The main goal of this review is to introduce readers to recent theories of electrodynamics processes associated with TLEs. We examine the simplest versions of these theories in order to make their physics as transparent as possible. The study is begun with the conventional mechanism for air breakdown at stratospheric and mesospheric altitudes. An electron impact ionization and dissociative attachment to neutrals are discussed. A streamer size and mobility of electrons as a function of altitude in the atmosphere are estimated on the basis of similarity law. An alternative mechanism of air breakdown, runaway electron mechanism, is discussed. In this section we focus on a runaway breakdown field, characteristic length to increase avalanche of runaway electrons and on the role played by fast seed electrons in generation of the runaway breakdown. An effect of thunderclouds charge distribution on initiation of blue jets and gigantic jets is examined. A model in which the blue jet is treated as upward-propagating positive leader with a streamer zone/corona on the top is discussed. Sprite models based on streamer-like mechanism of air breakdown in the presence of atmospheric conductivity are reviewed. To analyze conditions for sprite generation, thunderstorm electric field arising just after positive cloud-to-ground stroke is compared with the thresholds for propagation of positively/negatively charged streamers and with runway breakdown. Our own estimate of tendril's length at the bottom of sprite is obtained to demonstrate that the runaway breakdown can trigger the streamer formation. In conclusion we discuss physical mechanisms of VLF (very low frequency and ELF (extremely low frequency phenomena associated with sprites.

  6. Basal ganglia mechanisms underlying precision grip force control.

    Science.gov (United States)

    Prodoehl, Janey; Corcos, Daniel M; Vaillancourt, David E

    2009-06-01

    The classic grasping network has been well studied but thus far the focus has been on cortical regions in the control of grasping. Sub-cortically, specific nuclei of the basal ganglia have been shown to be important in different aspects of precision grip force control but these findings have not been well integrated. In this review, we outline the evidence to support the hypothesis that key basal ganglia nuclei are involved in parameterizing specific properties of precision grip force. We review literature from different areas of human and animal work that converges to build a case for basal ganglia involvement in the control of precision gripping. Following on from literature showing anatomical connectivity between the basal ganglia nuclei and key nodes in the cortical grasping network, we suggest a conceptual framework for how the basal ganglia could function within the grasping network, particularly as it relates to the control of precision grip force.

  7. An easily reversible structural change underlies mechanisms enabling desert crust cyanobacteria to survive desiccation.

    Science.gov (United States)

    Bar-Eyal, Leeat; Eisenberg, Ido; Faust, Adam; Raanan, Hagai; Nevo, Reinat; Rappaport, Fabrice; Krieger-Liszkay, Anja; Sétif, Pierre; Thurotte, Adrien; Reich, Ziv; Kaplan, Aaron; Ohad, Itzhak; Paltiel, Yossi; Keren, Nir

    2015-10-01

    Biological desert sand crusts are the foundation of desert ecosystems, stabilizing the sands and allowing colonization by higher order organisms. The first colonizers of the desert sands are cyanobacteria. Facing the harsh conditions of the desert, these organisms must withstand frequent desiccation-hydration cycles, combined with high light intensities. Here, we characterize structural and functional modifications to the photosynthetic apparatus that enable a cyanobacterium, Leptolyngbya sp., to thrive under these conditions. Using multiple in vivo spectroscopic and imaging techniques, we identified two complementary mechanisms for dissipating absorbed energy in the desiccated state. The first mechanism involves the reorganization of the phycobilisome antenna system, increasing excitonic coupling between antenna components. This provides better energy dissipation in the antenna rather than directed exciton transfer to the reaction center. The second mechanism is driven by constriction of the thylakoid lumen which limits diffusion of plastocyanin to P700. The accumulation of P700(+) not only prevents light-induced charge separation but also efficiently quenches excitation energy. These protection mechanisms employ existing components of the photosynthetic apparatus, forming two distinct functional modes. Small changes in the structure of the thylakoid membranes are sufficient for quenching of all absorbed energy in the desiccated state, protecting the photosynthetic apparatus from photoinhibitory damage. These changes can be easily reversed upon rehydration, returning the system to its high photosynthetic quantum efficiency. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Basal Ganglia Mechanisms Underlying Precision Grip Force Control

    OpenAIRE

    Prodoehl, Janey; Corcos, Daniel M.; Vaillancourt, David E.

    2009-01-01

    The classic grasping network has been well studied but thus far the focus has been on cortical regions in the control of grasping. Sub-cortically, specific nuclei of the basal ganglia have been shown to be important in different aspects of precision grip force control but these findings have not been well integrated. In this review we outline the evidence to support the hypothesis that key basal ganglia nuclei are involved in parameterizing specific properties of precision grip force. We revi...

  9. Neurobiology of consummatory behavior: mechanisms underlying overeating and drug use.

    Science.gov (United States)

    Barson, Jessica R; Morganstern, Irene; Leibowitz, Sarah F

    2012-01-01

    Consummatory behavior is driven by both caloric and emotional need, and a wide variety of animal models have been useful in research on the systems that drive consumption of food and drugs. Models have included selective breeding for a specific trait, manipulation of gene expression, forced or voluntary exposure to a substance, and identification of biomarkers that predict which animals are prone to overconsuming specific substances. This research has elucidated numerous brain areas and neurochemicals that drive consummatory behavior. Although energy homeostasis is primarily mediated by the hypothalamus, reinforcement is more strongly mediated by nuclei outside the hypothalamus, in mesocorticolimbic regions. Orexigenic neurochemicals that control food intake can provide a general signal for promoting caloric intake or a more specific signal for stimulating consumption of a particular macronutrient, fat, carbohydrate, or protein. The neurochemicals involved in controlling fat ingestion--galanin, enkephalin, orexin, melanin-concentrating hormone, and the endocannabinoids--show positive feedback with this macronutrient, as these peptides both increase fat intake and are further stimulated by its intake. This positive association offers some explanation for why foods high in fat are so often overconsumed. Consumption of ethanol, a drug of abuse that also contains calories, is similarly driven by the neurochemical systems involved in fat intake, according to evidence that closely relates fat and ethanol consumption. Further understanding of the systems involved in consummatory behavior will enable the development of effective therapies for the treatment of both overeating and drug abuse.

  10. Neurobiology of Consummatory Behavior: Mechanisms Underlying Overeating and Drug Use

    Science.gov (United States)

    Barson, Jessica R.; Morganstern, Irene; Leibowitz, Sarah F.

    2013-01-01

    Consummatory behavior is driven not just by caloric need but also by emotional need. In the last several decades, a wide variety of models have been used to study the systems that drive food and drug intake. These include selective breeding for a specific trait, manipulation of gene expression, forced or voluntary exposure to a substance, and identification of biomarkers that predict which animals are prone to overconsuming specific substances. From this research, numerous brain areas and neurochemicals have been identified that drive consummatory behavior. While energy homeostasis is primarily mediated by the hypothalamus, reinforcement is more strongly mediated by nuclei outside of the hypothalamus, in mesocorticolimbic regions. Orexigenic neurochemicals that control food intake can provide a general signal for promoting caloric intake or a more specific signal for stimulating consumption of a particular macronutrient, fat, carbohydrate or protein. Those involved in controlling fat ingestion, including galanin, enkephalin, orexin, melanin-concentrating hormone and the endocannabinoids, show positive feedback with this macronutrient, with these peptides both increasing fat intake and being further stimulated by its intake. This positive relationship offers some explanation for why foods high in fat are so often overconsumed. Consumption of ethanol, a drug of abuse that also contains calories, is similarly driven by these neurochemical systems involved in fat intake, consistent with evidence closely relating fat and ethanol consumption. Further understanding of these systems involved in consummatory behavior will allow researchers to develop effective therapies for the treatment of overeating as well as drug abuse. PMID:23520598

  11. Mechanisms underlying social inequality in post-menopausal breast cancer.

    Science.gov (United States)

    Hvidtfeldt, Ulla Arthur

    2014-10-01

    This thesis is based on studies conducted in the period 2010-2014 at Department of Public Health, University of Copenhagen and at Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York. The results are presented in three scientific papers and a synopsis. The main objective of the thesis was to determine mechanisms underlying social inequality (defined by educational level) in postmenopausal breast cancer (BC) by addressing mediating effects through hormone therapy (HT) use, BMI, lifestyle and reproductive factors. The results of previous studies suggest that the higher risk of postmenopausal BC among women of high socioeconomic position (SEP) may be explained by reproductive factors and health behaviors. Women of higher SEP generally have fewer children and give birth at older ages than women of low SEP, and these factors have been found to affect the risk of BC - probably through altered hormone levels. Adverse effects on BC risk have also been documented for modifiable health behaviors that may affect hormone levels, such as alcohol consumption, high BMI, physical inactivity, and HT use. Alcohol consumption and HT use are likewise more common among women of higher SEP. The analyses were based on the Social Inequality in Cancer (SIC) cohort and a subsample of the Women's Health Initiative Observational Study (WHI-OS). The SIC cohort was derived by pooling 6 individual studies from the Copenhagen area including 33,562 women (1,733 BC cases) aged 50-70 years at baseline. The subsample of WHI-OS consisted of two case-cohort studies with measurements of endogenous estradiol (N = 1,601) and insulin (N = 791). Assessment of mediation often relies on comparing multiplicative models with and without the potential mediator. Such approaches provide potentially biased results, because they do not account for mediator-outcome confounding, exposure-dependent mediator-outcome confounding, exposure-mediator interaction and interactions

  12. 8 CFR 1208.31 - Reasonable fear of persecution or torture determinations involving aliens ordered removed under...

    Science.gov (United States)

    2010-01-01

    ...) The immigration judge shall consider only the alien's application for withholding of removal under... deferred. (ii) Appeal of the immigration judge's decision whether removal must be withheld or deferred lies... determinations involving aliens ordered removed under section 238(b) of the Act and aliens whose removal is...

  13. Mechanical response of human female breast skin under uniaxial stretching.

    Science.gov (United States)

    Kumaraswamy, N; Khatam, Hamed; Reece, Gregory P; Fingeret, Michelle C; Markey, Mia K; Ravi-Chandar, Krishnaswamy

    2017-10-01

    Skin is a complex material covering the entire surface of the human body. Studying the mechanical properties of skin to calibrate a constitutive model is of great importance to many applications such as plastic or cosmetic surgery and treatment of skin-based diseases like decubitus ulcers. The main objective of the present study was to identify and calibrate an appropriate material constitutive model for skin and establish certain universal properties that are independent of patient-specific variability. We performed uniaxial tests performed on breast skin specimens freshly harvested during mastectomy. Two different constitutive models - one phenomenological and another microstructurally inspired - were used to interpret the mechanical responses observed in the experiments. Remarkably, we found that the model parameters that characterize dependence on previous maximum stretch (or preconditioning) exhibited specimen-independent universal behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Peer influence: Neural mechanisms underlying in-group conformity

    Directory of Open Access Journals (Sweden)

    Mirre eStallen

    2013-03-01

    Full Text Available People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI. Participants completed a perceptual decision-making task while undergoing fMRI, during which they were exposed to the judgments of both in-group and out-group members. Our data suggest that conformity to the in-group is mediated by both positive affect as well as the cognitive capacity of perspective taking. Examining the processes that drive in-group conformity by utilizing a basic decision-making paradigm combined with neuroimaging methods provides important insights into the potential mechanisms of conformity. These results may provide an integral step in developing more effective campaigns using group conformity as a tool for behavioral change.

  15. Peer influence: neural mechanisms underlying in-group conformity.

    Science.gov (United States)

    Stallen, Mirre; Smidts, Ale; Sanfey, Alan G

    2013-01-01

    People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI). Participants completed a perceptual decision-making task while undergoing fMRI, during which they were exposed to the judgments of both in-group and out-group members. Our data suggest that conformity to the in-group is mediated by both positive affect as well as the cognitive capacity of perspective taking. Examining the processes that drive in-group conformity by utilizing a basic decision-making paradigm combined with neuroimaging methods provides important insights into the potential mechanisms of conformity. These results may provide an integral step in developing more effective campaigns using group conformity as a tool for behavioral change.

  16. Mental imagery in music performance: underlying mechanisms and potential benefits.

    Science.gov (United States)

    Keller, Peter E

    2012-04-01

    This paper examines the role of mental imagery in music performance. Self-reports by musicians, and various other sources of anecdotal evidence, suggest that covert auditory, motor, and/or visual imagery facilitate multiple aspects of music performance. The cognitive and motor mechanisms that underlie such imagery include working memory, action simulation, and internal models. Together these mechanisms support the generation of anticipatory images that enable thorough action planning and movement execution that is characterized by efficiency, temporal precision, and biomechanical economy. In ensemble performance, anticipatory imagery may facilitate interpersonal coordination by enhancing online predictions about others' action timing. Overlap in brain regions subserving auditory imagery and temporal prediction is consistent with this view. It is concluded that individual differences in anticipatory imagery may be a source of variation in expressive performance excellence and the quality of ensemble cohesion. Engaging in effortful musical imagery is therefore justified when artistic perfection is the goal. © 2012 New York Academy of Sciences.

  17. Neural mechanisms underlying context-dependent shifts in risk preferences

    NARCIS (Netherlands)

    Losecaat Vermeer, A.B.; Boksem, M.A.S.; Sanfey, A.G.

    2014-01-01

    Studies of risky decision-making have demonstrated that humans typically prefer risky options after incurring a financial loss, while generally preferring safer options after a monetary gain. Here, we examined the neural processes underlying these inconsistent risk preferences by investigating the

  18. Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons.

    Science.gov (United States)

    Liu, Zi-Long; Wu, Xu; Luo, Yan-Jia; Wang, Lu; Qu, Wei-Min; Li, Shan-Qun; Huang, Zhi-Li

    2016-04-01

    Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (GG) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (HMNs) and the underlying signaling mechanisms have remained elusive. Here, whole-cell patch-clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited HMNs with an inward current under voltage-clamp and a depolarization membrane potential under current-clamp via histamine H1 receptors (H1Rs). The phospholipase C inhibitor U-73122 blocked H1Rs-mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on HMNs were H1R/Gq/11 /phospholipase C/inositol-1,4,5-trisphosphate (IP3). The effects of histamine were also dependent on extracellular Na(+) and intracellular Ca(2+), which took place via activation of Na(+)-Ca(2+) exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on HMNs. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea. We proposed the post-synaptic mechanisms underlying the modulation effect of histamine on hypoglossal motoneuron. Histamine activates the H1Rs via PLC and IP3, increases Ca(2+) releases from intracellular stores, promotes Na(+) influx and Ca(2+) efflux via the NCXs, and then produces an inward current and depolarizes the neurons. Histamine modulates the excitability of HMNs with other neuromodulators, such as noradrenaline, serotonin and orexin. We think that these findings should provide an important new direction for drug development for the treatment of obstructive sleep apnea. © 2016 International Society for Neurochemistry.

  19. Ablation characteristics and reaction mechanism of insulation materials under slag deposition condition

    Science.gov (United States)

    Guan, Yiwen; Li, Jiang; Liu, Yang

    2017-07-01

    Current understanding of the physical and chemical processes involved in the ablation of insulation materials by highly aluminized solid propellants is limited. The study on the heat transfer and ablation principle of ethylene propylene diene monomer (EPDM) materials under slag deposition condition is essential for future design or modification of large solid rocket motors (SRMs) for launch application. In this paper, the alumina liquid flow pattern and the deposition principle in full-scale SRM engines are discussed. The interaction mechanism between the alumina droplets and the wall are analyzed. Then, an experimental method was developed to simulate the insulation material ablation under slag deposition condition. Experimental study was conducted based on a laboratory-scale device. Meanwhile, from the analysis of the cross-sectional morphology and chemical composition of the charring layer after ablation, the reaction mechanism of the charring layer under deposition condition was discussed, and the main reaction equation was derived. The numerical simulation and experimental results show the following. (i) The alumina droplet flow in the deposition section of the laboratory-scale device is similar to that of a full-scale SRM. (ii) The charring layer of the EPDM insulator displays a porous tight/loose structure under high-temperature slag deposition condition. (iii) A seven-step carbothermal reduction in the alumina is derived and established under high-pressure and high-temperature environment in the SRM combustion chamber. (iv) The analysis using thermodynamic software indicates that the reaction of the alumina and charring layer initially forms Al4C3 during the operation. Then, Al element and Al2OC compound are subsequently produced with the reduction in the release of gas CO as well with continuous environmental heating.

  20. [Mechanisms underlying glucocorticoid resistance in chronic rhinosinusitis with nasal polyps].

    Science.gov (United States)

    Zhang, Y Y; Lou, H F; Wang, C S; Zhang, L

    2018-02-07

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease that occurs in the nasal and sinus mucosa, which is a common disease in otorhinolaryngology. At present, CRSwNP can be effectively treated by glucocorticoids (GC). GC binds to GC receptors in the nasal mucosa, affects the expression of inflammatory genes, inhibits the activation and action of eosinophils, T cell-associated inflammatory responses in nasal polyps, as well as tissue remodeling. However, there are some patients fall reponse to GC, so called GC resistance. The study suggests that the possible mechanism of CRSwNP GC resistance is mainly related to GC receptor abnormal, the role of cytokines and transcription factors, such as Th cells and IL-8. In addition, MAPK-related kinases and histone deacetylase in the GC signaling pathway also play important roles in the GC resistance process. This paper reviews the mechanism of GC treatment of CRSwNP, the mechanism of GC resistance and alternative treatment of GC.

  1. The Survival Advantage: Underlying Mechanisms and Extant Limitations

    Directory of Open Access Journals (Sweden)

    Stephanie A. Kazanas

    2015-04-01

    Full Text Available Recently, researchers have begun to investigate the function of memory in our evolutionary history. According to Nairne and colleagues (e.g., Nairne, Pandeirada, and Thompson, 2008; Nairne, Thompson, and Pandeirada, 2007, the best mnemonic strategy for learning lists of unrelated words may be one that addresses the same problems that our Pleistocene ancestors faced: fitness-relevant problems including securing food and water, as well as protecting themselves from predators. Survival processing has been shown to promote better recall and recognition memory than many well-known mnemonic strategies (e.g., pleasantness ratings, imagery, generation, etc.. However, the survival advantage does not extend to all types of stimuli and tasks. The current review presents research that has replicated Nairne et al.'s (2007 original findings, in addition to the research designs that fail to replicate the survival advantage. In other words, there are specific manipulations in which survival processing does not appear to benefit memory any more than other strategies. Potential mechanisms for the survival advantage are described, with an emphasis on those that are the most plausible. These proximate mechanisms outline the memory processes that may contribute to the advantage, although the ultimate mechanism may be the congruity between the survival scenario and Pleistocene problem-solving.

  2. Passive and active response of bacteria under mechanical compression

    Science.gov (United States)

    Garces, Renata; Miller, Samantha; Schmidt, Christoph F.; Byophysics Team; Institute of Medical Sciences Collaboration

    Bacteria display simple but fascinating cellular structures and geometries. Their shapes are the result of the interplay between osmotic pressure and cell wall construction. Typically, bacteria maintain a high difference of osmotic pressure (on the order of 1 atm) to the environment. This pressure difference (turgor pressure) is supported by the cell envelope, a composite of lipid membranes and a rigid cell wall. The response of the cell envelope to mechanical perturbations such as geometrical confinements is important for the cells survival. Another key property of bacteria is the ability to regulate turgor pressure after abrupt changes of external osmotic conditions. This response relies on the activity of mechanosensitive (MS) channels: membrane proteins that release solutes in response to excessive stress in the cell envelope. We here present experimental data on the mechanical response of the cell envelope and on turgor regulation of bacteria subjected to compressive forces. We indent living cells with micron-sized beads attached to the cantilever of an atomic force microscope (AFM). This approach ensures global deformation of the cell. We show that such mechanical loading is sufficient to gate mechanosensitive channels in isosmotic conditions.

  3. NOX Activation by Subunit Interaction and Underlying Mechanisms in Disease.

    Science.gov (United States)

    Rastogi, Radhika; Geng, Xiaokun; Li, Fengwu; Ding, Yuchuan

    2016-01-01

    Nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOX) is an enzyme complex with the sole function of producing superoxide anion and reactive oxygen species (ROS) at the expense of NADPH. Vital to the immune system as well as cellular signaling, NOX is also involved in the pathologies of a wide variety of disease states. Particularly, it is an integral player in many neurological diseases, including stroke, TBI, and neurodegenerative diseases. Pathologically, NOX produces an excessive amount of ROS that exceed the body's antioxidant ability to neutralize them, leading to oxidative stress and aberrant signaling. This prevalence makes it an attractive therapeutic target and as such, NOX inhibitors have been studied and developed to counter NOX's deleterious effects. However, recent studies of NOX have created a better understanding of the NOX complex. Comprised of independent cytosolic subunits, p47- phox , p67- phox , p40- phox and Rac , and membrane subunits, gp91- phox and p22- phox , the NOX complex requires a unique activation process through subunit interaction. Of these subunits, p47- phox plays the most important role in activation, binding and translocating the cytosolic subunits to the membrane and anchoring to p22- phox to organize the complex for NOX activation and function. Moreover, these interactions, particularly that between p47- phox and p22- phox , are dependent on phosphorylation initiated by upstream processes involving protein kinase C (PKC). This review will look at these interactions between subunits and with PKC. It will focus on the interaction involving p47- phox with p22- phox , key in bringing the cytosolic subunits to the membrane. Furthermore, the implication of these interactions as a target for NOX inhibitors such as apocynin will be discussed as a potential avenue for further investigation, in order to develop more specific NOX inhibitors based on the inhibition of NOX assembly and activation.

  4. Activity-Dependent Dendritic Spine Shrinkage and Growth Involve Downregulation of Cofilin via Distinct Mechanisms

    Science.gov (United States)

    Calabrese, Barbara; Saffin, Jean-Michel; Halpain, Shelley

    2014-01-01

    A current model posits that cofilin-dependent actin severing negatively impacts dendritic spine volume. Studies suggested that increased cofilin activity underlies activity-dependent spine shrinkage, and that reduced cofilin activity induces activity-dependent spine growth. We suggest instead that both types of structural plasticity correlate with decreased cofilin activity. However, the mechanism of inhibition determines the outcome for spine morphology. RNAi in rat hippocampal cultures demonstrates that cofilin is essential for normal spine maintenance. Cofilin-F-actin binding and filament barbed-end production decrease during the early phase of activity-dependent spine shrinkage; cofilin concentration also decreases. Inhibition of the cathepsin B/L family of proteases prevents both cofilin loss and spine shrinkage. Conversely, during activity-dependent spine growth, LIM kinase stimulates cofilin phosphorylation, which activates phospholipase D-1 to promote actin polymerization. These results implicate novel molecular mechanisms and prompt a revision of the current model for how cofilin functions in activity-dependent structural plasticity. PMID:24740405

  5. ERK1/2 pathway is involved in renal gluconeogenesis inhibition under conditions of lowered NADPH oxidase activity.

    Science.gov (United States)

    Winiarska, Katarzyna; Jarzyna, Robert; Dzik, Jolanta M; Jagielski, Adam K; Grabowski, Michal; Nowosielska, Agata; Focht, Dorota; Sierakowski, Bartosz

    2015-04-01

    The aim of this study was to elucidate the mechanisms involved in the inhibition of renal gluconeogenesis occurring under conditions of lowered activity of NADPH oxidase (Nox), the enzyme considered to be one of the main sources of reactive oxygen species in kidneys. The in vitro experiments were performed on primary cultures of rat renal proximal tubules, with the use of apocynin, a selective Nox inhibitor, and TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a potent superoxide radical scavenger. In the in vivo experiments, Zucker diabetic fatty (ZDF) rats, a well established model of diabetes type 2, were treated with apocynin solution in drinking water. The main in vitro findings are the following: (1) both apocynin and TEMPOL attenuate the rate of gluconeogenesis, inhibiting the step catalyzed by phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme of the process; (2) in the presence of the above-noted compounds the expression of PEPCK and the phosphorylation of transcription factor CREB and ERK1/2 kinases are lowered; (3) both U0126 (MEK inhibitor) and 3-(2-aminoethyl)-5-((4-ethoxyphenyl)methylene)-2,4-thiazolidinedione (ERK inhibitor) diminish the rate of glucose synthesis via mechanisms similar to those of apocynin and TEMPOL. The observed apocynin in vivo effects include: (1) slight attenuation of hyperglycemia; (2) inhibition of renal gluconeogenesis; (3) a decrease in renal PEPCK activity and content. In view of the results summarized above, it can be concluded that: (1) the lowered activity of the ERK1/2 pathway is of importance for the inhibition of renal gluconeogenesis found under conditions of lowered superoxide radical production by Nox; (2) the mechanism of this phenomenon includes decreased PEPCK expression, resulting from diminished activity of transcription factor CREB; (3) apocynin-evoked inhibition of renal gluconeogenesis contributes to the hypoglycemic action of this compound observed in diabetic animals. Thus, the study has

  6. Viewing Generativity and Social Capital as Underlying Factors of Parent Involvement

    Science.gov (United States)

    Stevens, Sharon; Patel, Nimisha

    2015-01-01

    Parent involvement in education is a multifaceted support that has many well-documented benefits for students of all ages. Parent involvement is also a common expression of generativity as defined in Erik Erikson's theory of psychosocial development. The activities parents engage in during their children's educational pursuits, as well as their…

  7. Hydrocarbon activation under sulfate-reducing and methanogenic conditions proceeds by different mechanisms.

    Science.gov (United States)

    Head, Ian; Gray, Neil; Aitken, Caroline; Sherry, Angela; Jones, Martin; Larter, Stephen

    2010-05-01

    Microbial degradation of alkanes typically involves their conversion to fatty acids which are then catabolised by beta-oxidation. The critical step in this process is activation of the hydrocarbon. Under oxic conditions this is catalyzed by monooxygenase enzymes with the formation of long chain alcohols. In the absence of oxygen alternative alkane activation mechanisms have been observed or proposed. Fumarate addition to alkanes to form alkyl succinates is considered a central process in anaerobic hydrocarbon degradation. Comparative studies of crude oil degradation under sulphate-reducing and methanogenic conditions revealed distinctive patterns of compound class removal and metabolite formation. Alkyl succinates derived from C7 to C26 n-alkanes and branched chain alkanes were found in abundance in sulfate-reducing systems but these were not detected during methanogenic crude oil degradation. Only one other mechanism of alkane activation has been elucidated to date. This involves addition of carbon derived from bicarbonate/CO2 to C-3 of an alkane chain to form a 2-ethylalkane with subsequent removal of the ethyl group leading to the formation of a fatty acid 1 carbon shorter than the original alkane. 2-ethylalkanes have never been detected as metabolites of anaerobic alkane degradation and were not detected in crude oil-degrading methanogenic systems. Due to the range of alkanes present in crude oil it was not possible to infer the generation of C-odd acids from C-even alkanes which is characteristic of the C-3 carboxylation mechanism. Furthermore genes homologous to alkysuccinate synthetases were not detected in the methanogenic hydrocarbon degrading community by pyrosequencing of total DNA extracted from methanogenic enrichments cultures. beta-oxidation genes were detected and intriguingly, alcohol and aldehyde dehydrogenase genes were present. This offers the possibility that alkane activation in the methanogenic system does not proceed via acid metabolites

  8. Phosphorene under strain:electronic, mechanical and piezoelectric responses

    Science.gov (United States)

    Drissi, L. B.; Sadki, S.; Sadki, K.

    2018-01-01

    Structural, electronic, elastic and piezoelectric properties of pure phosphorene under in-plane strain are investigated using first-principles calculations based on density functional theory. The two critical yielding points are determined along armchair and zigzag directions. It is shown that the buckling, the band gap and the charge transfer can be controlled under strains. A semiconductor to metallic transition is observed in metastable region. Polar plots of Young's modulus, Poisson ratio, sound velocities and Debye temperature exhibit evident anisotropic feature of phosphorene and indicate auxetic behavior for some angles θ. Our calculations show also that phosphorene has both in-plane and out-of-plane piezoelectric responses comparable to known 2D materials. The findings of this work reveal the great potential of pure phosphorene in nanomechanical applications.

  9. 29 CFR 1904.9 - Recording criteria for cases involving medical removal under OSHA standards.

    Science.gov (United States)

    2010-07-01

    ... under OSHA standards. 1904.9 Section 1904.9 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL... removal under OSHA standards. (a) Basic requirement. If an employee is medically removed under the medical surveillance requirements of an OSHA standard, you must record the case on the OSHA 300 Log. (b) Implementation...

  10. Electronic, mechanical and dielectric properties of silicane under tensile strain

    Energy Technology Data Exchange (ETDEWEB)

    Jamdagni, Pooja, E-mail: j.poojaa1228@gmail.com; Sharma, Munish; Ahluwalia, P. K. [Physics Department, Himachal Pradesh University, Shimla, Himachal Pradesh, India 171005 (India); Kumar, Ashok [Physics Department, Panjab University, Chandigarh, India, 160014 (India); Thakur, Anil [Physics Department, Govt. Collage Solan, Himachal Pradesh, India,173212 (India)

    2015-05-15

    The electronic, mechanical and dielectric properties of fully hydrogenated silicene i.e. silicane in stable configuration are studied by means of density functional theory based calculations. The band gap of silicane monolayer can be flexibly reduced to zero when subjected to bi-axial tensile strain, leading to semi-conducting to metallic transition, whereas the static dielectric constant for in-plane polarization increases monotonically with increasing strain. Also the EEL function show the red shift in resonance peak with tensile strain. Our results offer useful insight for the application of silicane monolayer in nano-optical and electronics devices.

  11. Electronic, mechanical and dielectric properties of silicane under tensile strain

    International Nuclear Information System (INIS)

    Jamdagni, Pooja; Sharma, Munish; Ahluwalia, P. K.; Kumar, Ashok; Thakur, Anil

    2015-01-01

    The electronic, mechanical and dielectric properties of fully hydrogenated silicene i.e. silicane in stable configuration are studied by means of density functional theory based calculations. The band gap of silicane monolayer can be flexibly reduced to zero when subjected to bi-axial tensile strain, leading to semi-conducting to metallic transition, whereas the static dielectric constant for in-plane polarization increases monotonically with increasing strain. Also the EEL function show the red shift in resonance peak with tensile strain. Our results offer useful insight for the application of silicane monolayer in nano-optical and electronics devices

  12. Mechanisms involved in calcium oxalate endocytosis by Madin-Darby canine kidney cells

    Directory of Open Access Journals (Sweden)

    A.H. Campos

    2000-01-01

    Full Text Available Calcium oxalate (CaOx crystals adhere to and are internalized by tubular renal cells and it seems that this interaction is related (positively or negatively to the appearance of urinary calculi. The present study analyzes a series of mechanisms possibly involved in CaOx uptake by Madin-Darby canine kidney (MDCK cells. CaOx crystals were added to MDCK cell cultures and endocytosis was evaluated by polarized light microscopy. This process was inhibited by an increase in intracellular calcium by means of ionomycin (100 nM; N = 6; 43.9% inhibition; P<0.001 or thapsigargin (1 µM; N = 6; 33.3% inhibition; P<0.005 administration, and via blockade of cytoskeleton assembly by the addition of colchicine (10 µM; N = 8; 46.1% inhibition; P<0.001 or cytochalasin B (10 µM; N = 8; 34.2% inhibition; P<0.001. Furthermore, CaOx uptake was reduced when the activity of protein kinase C was inhibited by staurosporine (10 nM; N = 6; 44% inhibition; P<0.01, or that of cyclo-oxygenase by indomethacin (3 µM; N = 12; 17.2% inhibition; P<0.05; however, the uptake was unaffected by modulation of potassium channel activity with glibenclamide (3 µM; N = 6, tetraethylammonium (1 mM; N = 6 or cromakalim (1 µM; N = 6. Taken together, these data indicate that the process of CaOx internalization by renal tubular cells is similar to the endocytosis reported for other systems. These findings may be relevant to cellular phenomena involved in early stages of the formation of renal stones.

  13. Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.

    Science.gov (United States)

    Srinivasan, Padmanabhan; Kapadia, Rubina; Biswas, Arundhati; Said, Hamid M

    2014-11-01

    Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5'-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na(+) dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms. Copyright © 2014 the American Physiological Society.

  14. Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins

    Directory of Open Access Journals (Sweden)

    Li Junlin

    2013-02-01

    Full Text Available Abstract Neurodevelopmental disorders are classified as diseases that cause abnormal functions of the brain or central nervous system. Children with neurodevelopmental disorders show impaired language and speech abilities, learning and memory damage, and poor motor skills. However, we still know very little about the molecular etiology of these disorders. Recent evidence implicates the bromodomain-containing proteins (BCPs in the initiation and development of neurodevelopmental disorders. BCPs have a particular domain, the bromodomain (Brd, which was originally identified as specifically binding acetyl-lysine residues at the N-terminus of histone proteins in vitro and in vivo. Other domains of BCPs are responsible for binding partner proteins to form regulatory complexes. Once these complexes are assembled, BCPs alter chromosomal states and regulate gene expression. Some BCP complexes bind nucleosomes, are involved in basal transcription regulation, and influence the transcription of many genes. However, most BCPs are involved in targeting. For example, some BCPs function as a recruitment platform or scaffold through their Brds-binding targeting sites. Others are recruited to form a complex to bind the targeting sites of their partners. The regulation mediated by these proteins is especially critical during normal and abnormal development. Mutant BCPs or dysfunctional BCP-containing complexes are implicated in the initiation and development of neurodevelopmental disorders. However, the pathogenic molecular mechanisms are not fully understood. In this review, we focus on the roles of regulatory BCPs associated with neurodevelopmental disorders, including mental retardation, Fragile X syndrome (FRX, Williams syndrome (WS, Rett syndrome and Rubinstein-Taybi syndrome (RTS. A better understanding of the molecular pathogenesis, based upon the roles of BCPs, will lead to screening of targets for the treatment of neurodevelopmental disorders.

  15. Interactive evolution concept for analyzing a rock salt cavern under cyclic thermo-mechanical loading

    Science.gov (United States)

    König, Diethard; Mahmoudi, Elham; Khaledi, Kavan; von Blumenthal, Achim; Schanz, Tom

    2016-04-01

    The excess electricity produced by renewable energy sources available during off-peak periods of consumption can be used e.g. to produce and compress hydrogen or to compress air. Afterwards the pressurized gas is stored in the rock salt cavities. During this process, thermo-mechanical cyclic loading is applied to the rock salt surrounding the cavern. Compared to the operation of conventional storage caverns in rock salt the frequencies of filling and discharging cycles and therefore the thermo-mechanical loading cycles are much higher, e.g. daily or weekly compared to seasonally or yearly. The stress strain behavior of rock salt as well as the deformation behavior and the stability of caverns in rock salt under such loading conditions are unknown. To overcome this, existing experimental studies have to be supplemented by exploring the behavior of rock salt under combined thermo-mechanical cyclic loading. Existing constitutive relations have to be extended to cover degradation of rock salt under thermo-mechanical cyclic loading. At least the complex system of a cavern in rock salt under these loading conditions has to be analyzed by numerical modeling taking into account the uncertainties due to limited access in large depth to investigate material composition and properties. An interactive evolution concept is presented to link the different components of such a study - experimental modeling, constitutive modeling and numerical modeling. A triaxial experimental setup is designed to characterize the cyclic thermo-mechanical behavior of rock salt. The imposed boundary conditions in the experimental setup are assumed to be similar to the stress state obtained from a full-scale numerical simulation. The computational model relies primarily on the governing constitutive model for predicting the behavior of rock salt cavity. Hence, a sophisticated elasto-viscoplastic creep constitutive model is developed to take into account the dilatancy and damage progress, as well as

  16. Modeling of the mechanical behavior of austenitic stainless steels under pure fatigue and fatigue relaxation loadings

    International Nuclear Information System (INIS)

    Hajjaji-Rachdi, Fatima

    2015-01-01

    Austenitic stainless steels are potential candidates for structural components of sodium-cooled fast neutron reactors. Many of these components will be subjected to cyclic loadings including long hold times (1 month) under creep or relaxation at high temperature. These hold times are unattainable experimentally. The aim of the present study is to propose mechanical models which take into account the involved mechanisms and their interactions during such complex loadings. First, an experimental study of the pure fatigue and fatigue-relaxation behavior of 316L(N) at 500 C has been carried out with very long hold times (10 h and 50 h) compared with the ones studied in literature. Tensile tests at 600 C with different applied strain rates have been undertaken in order to study the dynamic strain ageing phenomenon. Before focusing on more complex loadings, the mean field homogenization approach has been used to predict the mechanical behavior of different FCC metals and alloys under low cycle fatigue at room temperature. Both Hill-Hutchinson and Kroener models have been used. Next, a physically-based model based on dislocation densities has been developed and its parameters measured. The model allows predictions in a qualitative agreement with experimental data for tensile loadings. Finally, this model has been enriched to take into account visco-plasticity, dislocation climb and interaction between dislocations and solute atoms, which are influent during creep-fatigue or fatigue relaxation at high temperature. The proposed model uses three adjustable parameters only and allows rather accurate prediction of the behavior of 316L(N) steel under tensile loading and relaxation. (author) [fr

  17. Involvement of metabolites in early defense mechanism of oil palm (Elaeis guineensis Jacq.) against Ganoderma disease.

    Science.gov (United States)

    Nusaibah, S A; Siti Nor Akmar, A; Idris, A S; Sariah, M; Mohamad Pauzi, Z

    2016-12-01

    Understanding the mechanism of interaction between the oil palm and its key pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen leads to a major loss of revenue in leading palm oil producing countries in Southeast Asia. Here in this study, we assess the morphological and biochemical changes in Ganoderma disease infected oil palm seedling roots in both resistant and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were applied as a source of inoculum to artificially infect the roots of resistant and susceptible oil palm progenies. Gas chromatography-mass spectrometry was used to measure an array of plant metabolites in 100 resistant and susceptible oil palm seedling roots treated with pathogenic Ganoderma boninense fungus. Statistical effects, univariate and multivariate analyses were used to identify key-Ganoderma disease associated metabolic agitations in both resistant and susceptible oil palm root tissues. Ganoderma disease related defense shifts were characterized based on (i) increased antifungal activity in crude extracts, (ii) increased lipid levels, beta- and gamma-sitosterol particularly in the resistant progeny, (iii) detection of heterocyclic aromatic organic compounds, benzo [h] quinoline, pyridine, pyrimidine (iv) elevation in antioxidants, alpha- and beta-tocopherol (iv) degraded cortical cell wall layers, possibly resulting from fungal hydrolytic enzyme activity needed for initial penetration. The present study suggested that plant metabolites mainly lipids and heterocyclic aromatic organic metabolites could be potentially involved in early oil palm defense mechanism against G. boninense infection, which may also highlight biomarkers for disease detection, treatment, development of resistant variety and monitoring. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    International Nuclear Information System (INIS)

    Wang, Jun; Cao, Hui; Wang, Hongjie; Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli; Xiang, Ming

    2015-01-01

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4 + CD25 + Foxp3 + regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation

  19. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jun [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Pharmacology, College of Medicine, Wuhan University of Science and Technology, Wuhan (China); Cao, Hui [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Hongjie [Section of Neurobiology, Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL (United States); Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xiang, Ming, E-mail: xiangming@mails.tjmu.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

    2015-06-15

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation.

  20. Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications

    Directory of Open Access Journals (Sweden)

    Ambrish Kumar

    2013-06-01

    Full Text Available Ethanol is the main constituent of alcoholic beverages that exerts toxicity to neuronal development. Ethanol affects synaptogenesis and prevents proper brain development. In humans, synaptogenesis takes place during the third trimester of pregnancy, and in rodents this period corresponds to the initial few weeks of postnatal development. In this period neuronal maturation and differentiation begin and neuronal cells start migrating to their ultimate destinations. Although the neuronal development of all areas of the brain is affected, the cerebellum and cerebellar neurons are more susceptible to the damaging effects of ethanol. Ethanol’s harmful effects include neuronal cell death, impaired differentiation, reduction of neuronal numbers, and weakening of neuronal plasticity. Neuronal development requires many hormones and growth factors such as retinoic acid, nerve growth factors, and cytokines. These factors regulate development and differentiation of neurons by acting through various receptors and their signaling pathways. Ethanol exposure during development impairs neuronal signaling mechanisms mediated by the N-methyl-d-aspartate (NMDA receptors, the retinoic acid receptors, and by growth factors such as brain-derived neurotrophic factor (BDNF, insulin-like growth factor 1 (IGF-I, and basic fibroblast growth factor (bFGF. In combination, these ethanol effects disrupt cellular homeostasis, reduce the survival and migration of neurons, and lead to various developmental defects in the brain. Here we review the signaling mechanisms that are required for proper neuronal development, and how these processes are impaired by ethanol resulting in harmful consequences to brain development.

  1. Brainstem mechanisms underlying the cough reflex and its regulation.

    Science.gov (United States)

    Mutolo, Donatella

    2017-09-01

    Cough is a very important airway protective reflex. Cough-related inputs are conveyed to the caudal nucleus tractus solitarii (cNTS) that projects to the brainstem respiratory network. The latter is reconfigured to generate the cough motor pattern. A high degree of modulation is exerted on second-order neurons and the brainstem respiratory network by sensory inputs and higher brain areas. Two medullary structures proved to have key functions in cough production and to be strategic sites of action for centrally active drugs: the cNTS and the caudal ventral respiratory group (cVRG). Drugs microinjected into these medullary structures caused downregulation or upregulation of the cough reflex. The results suggest that inhibition and disinhibition are prominent regulatory mechanisms of this reflex and that both the cNTS and the cVRG are essential in the generation of the entire cough motor pattern. Studies on the basic neural mechanisms subserving the cough reflex may provide hints for novel therapeutic approaches. Different proposals for further investigations are advanced. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Evaluation of Possible Proximate Mechanisms Underlying the Kinship Theory of Intragenomic Conflict in Social Insects.

    Science.gov (United States)

    Galbraith, David A; Yi, Soojin V; Grozinger, Christina M

    2016-12-01

    Kinship theory provides a universal framework in which to understand the evolution of altruism, but there are many molecular and genetic mechanisms that can generate altruistic behaviors. Interestingly, kinship theory specifically predicts intragenomic conflict between maternally-derived alleles (matrigenes) and paternally-derived alleles (patrigenes) over the generation of altruistic behavior in cases where the interests of the matrigenes and patrigenes are not aligned. Under these conditions, individual differences in selfish versus altruistic behavior are predicted to arise from differential expression of the matrigenes and patrigenes (parent-specific gene expression or PSGE) that regulate selfish versus altruistic behaviors. As one of the leading theories to describe PSGE and genomic imprinting, kinship theory has been used to generate predictions to describe the reproductive division of labor in social insect colonies, which represents an excellent model system to test the hypotheses of kinship theory and examine the underlying mechanisms driving it. Recent studies have confirmed the predicted differences in the influence of matrigenes and patrigenes on reproductive division of labor in social insects, and demonstrated that these differences are associated with differences in PSGE of key genes involved in regulating reproductive physiology, providing further support for kinship theory. However, the mechanisms mediating PSGE in social insects, and how PSGE leads to differences in selfish versus altruistic behavior, remain to be determined. Here, we review the available supporting evidence for three possible epigenetic mechanisms (DNA methylation, piRNAs, and histone modification) that may generate PSGE in social insects, and discuss how these may lead to variation in social behavior. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email

  3. Mechanisms of Prescription Drug Diversion Among Drug-Involved Club- and Street-Based Populations

    Science.gov (United States)

    Inciardi, James A.; Surratt, Hilary L.; Kurtz, Steven P.; Cicero, Theodore J.

    2010-01-01

    Objective Prescription drug diversion involves the unlawful channeling of regulated pharmaceuticals from legal sources to the illicit marketplace, and can occur along all points in the drug delivery process, from the original manufacturing site to the wholesale distributor, the physician's office, the retail pharmacy, or the patient. However, empirical data on diversion are limited. Method In an attempt to develop a better understanding of how specific drug-using populations are diverting prescription opioids and other medications, or obtaining controlled drugs that have already been diverted, qualitative interviews and focus group data were collected on four separate populations of prescription drug abusers in Miami, Florida—club drug users, street-based illicit drug users, methadone maintenance patients, and HIV positive individuals who abuse and/or divert drugs. Results Sources of abused prescription drugs cited by focus group participants were extremely diverse, including their physicians and pharmacists; parents and relatives; “doctor shopping”; leftover supplies following an illness or injury; personal visits to Mexico, South America and the Caribbean; prescriptions intended for the treatment of mental illness; direct sales on the street and in nightclubs; pharmacy and hospital theft; through friends or acquaintances; under-the-door apartment flyers advertising telephone numbers to call; and “stealing from grandma's medicine cabinet.” Conclusion While doctor shoppers, physicians and the Internet receive much of the attention regarding diversion, the data reported in this paper suggest that there are numerous active street markets involving patients, Medicaid recipients and pharmacies as well. In addition, there are other data which suggest that the contributions of residential burglaries, pharmacy robberies and thefts, and “sneak thefts” to the diversion problem may be understated. PMID:17305688

  4. Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

    Science.gov (United States)

    Wang, Yanan; Qin, Qing-Hua

    2010-03-01

    The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological-mechanical therapies to treat bone loss diseases such as osteoporosis.

  5. Mechanisms Underlying the Risk to Develop Drug Addiction, Insights From Studies in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Julia Ryvkin

    2018-04-01

    Full Text Available The ability to adapt to environmental changes is an essential feature of biological systems, achieved in animals by a coordinated crosstalk between neuronal and hormonal programs that allow rapid and integrated organismal responses. Reward systems play a key role in mediating this adaptation by reinforcing behaviors that enhance immediate survival, such as eating or drinking, or those that ensure long-term survival, such as sexual behavior or caring for offspring. Drugs of abuse co-opt neuronal and molecular pathways that mediate natural rewards, which under certain circumstances can lead to addiction. Many factors can contribute to the transition from drug use to drug addiction, highlighting the need to discover mechanisms underlying the progression from initial drug use to drug addiction. Since similar responses to natural and drug rewards are present in very different animals, it is likely that the central systems that process reward stimuli originated early in evolution, and that common ancient biological principles and genes are involved in these processes. Thus, the neurobiology of natural and drug rewards can be studied using simpler model organisms that have their systems stripped of some of the immense complexity that exists in mammalian brains. In this paper we review studies in Drosophila melanogaster that model different aspects of natural and drug rewards, with an emphasis on how motivational states shape the value of the rewarding experience, as an entry point to understanding the mechanisms that contribute to the vulnerability of drug addiction.

  6. Molecular mechanisms underlying cardiac antihypertrophic and antifibrotic effects of natriuretic peptides.

    Science.gov (United States)

    Calvieri, Camilla; Rubattu, Speranza; Volpe, Massimo

    2012-01-01

    Natriuretic peptides (NPs) exert well-characterized protective effects on the cardiovascular system, such as vasorelaxation, natri- and diuresis, increase of endothelial permeability, and inhibition of renin-angiotensin-aldosterone system. It has been reported that they also possess antihypertrophic and antifibrotic properties and contribute actively to cardiac remodeling. As a consequence, they are involved in several aspects of cardiovascular diseases. Antihypertrophic and antifibrotic actions of NPs appear to be mediated by specific signaling pathways within a more complex cellular network. Elucidation of the molecular mechanisms underlying the effects of NPs on cardiac remodeling represents an important research objective in order to gain more insights on the complex network leading to cardiac hypertrophy, ventricular dysfunction, and transition to heart failure, and in the attempt to develop novel therapeutic agents. The aim of the present article is to review well-characterized molecular mechanisms underlying the antihypertrophic and antifibrotic effects of NPs in the heart that appear to be mainly mediated by guanylyl cyclase type A receptor. In particular, we discuss the calcineurin/NFAT, the sodium exchanger NHE-1, and the TGFβ1/Smad signaling pathways. The role of guanylyl cyclase type B receptor, along with the emerging functional significance of natriuretic peptide receptor type C as mediators of CNP antihypertrophic and antifibrotic actions in the heart are also considered.

  7. Mechanisms Underlying Profibrotic Epithelial Phenotype and Epithelial-Mesenchymal Crosstalk

    DEFF Research Database (Denmark)

    Bialik, Janne Folke

    , their roles in epithelial reprogramming are unclear. The aim of this thesis was to elucidate (i) the mechanism of TGFβ-induced TAZ expression in kidney fibrosis, (ii) the roles of MRTF and TAZ in PEP, (iii) how MRTF and TAZ regulate the oxidative state of the epithelium, and (iv) if the ensuing ROS production...... and TAZ prevented this, linking the cytoskeleton to the oxidative state of the cell. In Paper II TGFβ-induced increase in TAZ expression was investigated. Using pharmacological inhibition we show that non-canonical signaling via p38 and its downstream target MK2 mediates this upregulation. Furthermore......, MRTF regulates TAZ expression in a translocation-independent manner. Pharmacological inhibition of Nox4, a known activator of p38, resulted in decreased TAZ, suggesting a feedback loop in which Nox4 regulates TAZ and MRTF, which in turn regulates Nox4. In Paper III we investigated cytokine expression...

  8. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2012-02-01

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  9. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2011-03-17

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  10. Molecular mechanisms underlying the development of hepatocellular carcinoma.

    Science.gov (United States)

    Bergsland, E K

    2001-10-01

    Hepatocellular carcinoma (HCC) is a disease that is extremely difficult to manage and is markedly increasing in incidence. Malignant transformation generally occurs in the setting of liver dysfunction related to a number of different diseases, including viral hepatitis, alcoholic liver disease, and aflatoxin exposure. Short of surgical or ablative approaches, no standard therapy exists for HCC and the prognosis is poor. Perhaps our best hope is that further elucidation of the specific molecular features underlying the disease will translate into innovative, and potentially disease-specific strategies to manage this difficult cancer. Exposure to aflatoxin is associated with a specific mutation in the tumor-suppressor gene p53. The exact molecular events underlying hepatocarcinogenesis in the setting of viral infection have yet to be elucidated, although there is evidence to suggest that virus-encoded proteins contribute to malignant transformation. Both hepatitis B X antigen and hepatitis C core protein appear to interact with a variety of cellular proteins leading to alterations in signal transduction and transcriptional activity. These events presumably cooperate to facilitate malignant progression by promoting extended hepatocyte survival, evasion of the immune response, and acquisition of mutations through genomic instability. Copyright 2001 by W.B. Saunders Company.

  11. Neural mechanisms underlying neurooptometric rehabilitation following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hudac CM

    2012-01-01

    Full Text Available Caitlin M Hudac1, Srinivas Kota1, James L Nedrow2, Dennis L Molfese1,31Department of Psychology, University of Nebraska-Lincoln, 2Oculi Vision Rehabilitation, 3Center for Brain, Biology, and Behavior, University of Nebraska-Lincoln, Lincoln, NEAbstract: Mild to severe traumatic brain injuries have lasting effects on everyday functioning. Issues relating to sensory problems are often overlooked or not addressed until well after the onset of the injury. In particular, vision problems related to ambient vision and the magnocellular pathway often result in posttrauma vision syndrome or visual midline shift syndrome. Symptoms from these syndromes are not restricted to the visual domain. Patients commonly experience proprioceptive, kinesthetic, vestibular, cognitive, and language problems. Neurooptometric rehabilitation often entails the use of corrective lenses, prisms, and binasal occlusion to accommodate the unstable magnocellular system. However, little is known regarding the neural mechanisms engaged during neurooptometric rehabilitation, nor how these mechanisms impact other domains. Event-related potentials from noninvasive electrophysiological recordings can be used to assess rehabilitation progress in patients. In this case report, high-density visual event-related potentials were recorded from one patient with posttrauma vision syndrome and secondary visual midline shift syndrome during a pattern reversal task, both with and without prisms. Results indicate that two factors occurring during the end portion of the P148 component (168–256 milliseconds poststimulus onset map onto two separate neural systems that were engaged with and without neurooptometric rehabilitation. Without prisms, neural sources within somatosensory, language, and executive brain regions engage inefficient magnocellular system processing. However, when corrective prisms were worn, primary visual areas were appropriately engaged. The impact of using early

  12. Mechanical characterization of stomach tissue under uniaxial tensile action.

    Science.gov (United States)

    Jia, Z G; Li, W; Zhou, Z R

    2015-02-26

    In this article, the tensile properties of gastric wall were investigated by using biomechanical test and theoretical analysis. The samples of porcine stomach strips from smaller and greater curvature of the stomach were cut in longitudinal and circumferential direction, respectively. The loading-unloading, stress relaxation, strain creep, tensile fracture tests were performed at mucosa-submucosa, serosa-muscle and intact layer, respectively. Results showed that the biomechanical properties of the porcine stomach depended on the layers, orientations and locations of the gastric wall and presented typical viscoelastic, nonlinear and anisotropic mechanical properties. During loading-unloading test, the stress of serosa-muscle layer in the longitudinal direction was 15-20% more than that in the circumferential direction at 12% stretch ratio, while it could reach about 40% for the intact layer and 50% for the mucosa-submucosa layer. The results of stress relaxation and strain creep showed that the variation degree was obviously faster in the circumferential direction than that in the longitudinal direction, and the ultimate residual values were also different for the different layers, orientations and locations. In the process of fracture test, the serosa-muscle layer fractured firstly followed by the mucosa-submucosa layer when the intact layer was tested, the longitudinal strips firstly began to fracture and the required stress value was about twice as much as that in the circumferential strips. The anisotropy and heterogeneity of mechanical characterization of the porcine stomach were related to its complicated geometry, structure and functions. The results would help us to understand the biomechanics of soft organ tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Mechanisms underlying probucol-induced hERG-channel deficiency

    Directory of Open Access Journals (Sweden)

    Shi YQ

    2015-07-01

    Full Text Available Yuan-Qi Shi,1,* Cai-Chuan Yan,1,* Xiao Zhang,1 Meng Yan,1 Li-Rong Liu,1 Huai-Ze Geng,1 Lin Lv,1 Bao-Xin Li1,21Department of Pharmacology, Harbin Medical University, 2State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workAbstract: The hERG gene encodes the pore-forming α-subunit of the rapidly activating delayed rectifier potassium channel (IKr, which is important for cardiac repolarization. Reduction of IhERG due to genetic mutations or drug interferences causes long QT syndrome, leading to life-threatening cardiac arrhythmias (torsades de pointes or sudden death. Probucol is a cholesterol-lowering drug that could reduce hERG current by decreasing plasma membrane hERG protein expression and eventually cause long QT syndrome. Here, we investigated the mechanisms of probucol effects on IhERG and hERG-channel expression. Our data demonstrated that probucol reduces SGK1 expression, known as SGK isoform, in a concentration-dependent manner, resulting in downregulation of phosphorylated E3 ubiquitin ligase Nedd4-2 expression, but not the total level of Nedd4-2. As a result, the hERG protein reduces, due to the enhanced ubiquitination level. On the contrary, carbachol could enhance the phosphorylation level of Nedd4-2 as an alternative to SGK1, and thus rescue the ubiquitin-mediated degradation of hERG channels caused by probucol. These discoveries provide a novel mechanism of probucol-induced hERG-channel deficiency, and imply that carbachol or its analog may serve as potential therapeutic compounds for the handling of probucol cardiotoxicity.Keywords: long QT, hERG potassium channels, probucol, SGK1, Nedd4-2

  14. Study of Possible Mechanisms Involved in the Inhibitory Effects of Coumarin Derivatives on Neutrophil Activity

    Science.gov (United States)

    Drábiková, Katarína; Perečko, Tomáš; Nosál', Radomír; Harmatha, Juraj; Šmidrkal, Jan; Jančinová, Viera

    2013-01-01

    To specify the site of action of the synthetic coumarin derivatives 7-hydroxy-3-(4′-hydroxyphenyl) coumarin (HHC) and 7-hydroxy-3-(4′-hydroxyphenyl) dihydrocoumarin (HHDC), we evaluated their effects on extra- and intracellular reactive oxygen species (ROS) formation in phorbol-myristate-13-acetate (PMA) stimulated human neutrophils. We studied also the effects of HHC and HHDC on possible molecular mechanisms which participate in the activation of NADPH oxidase, that is, on PKC activity, on phosphorylation of some PKC isoforms (α, βII, and δ), and on phosphorylation of the NADPH oxidase subunit p40phox. Without affecting cytotoxicity, both coumarines tested were effective inhibitors/scavengers of ROS produced by neutrophils on extracellular level. HHC markedly diminished oxidant production and also, intracellularly, decreased PKC activity and partly phosphorylation of PKCα, βII. On the other hand, we did not observe any effect of coumarin derivatives on phosphorylation of PKCδ and on phosphorylation of the NADPH oxidase subunit p40phox, which were suggested to be involved in the PMA-dependent intracellular activation process. In agreement with our previous findings, we assume that the different molecular structures of HHC and HHDC with their different physicochemical and free radical scavenging characteristics are responsible for their diverse effects on the parameters tested. PMID:24349608

  15. Mechanisms and secondary factors involved in the induction of radiation transformation in vitro

    International Nuclear Information System (INIS)

    Little, J.B.

    1983-01-01

    The long term of this research program was to gain information concerning the mechanisms that determine the carcinogenic effects of ionizing radiation, particularly high LET radiation exposure. The experimental approach involves parallel studies of the induction of malignant transformation in BALB/3T3 cells and of specific gene mutations in human lymphoblastoid cells. Emphasis was on the biologic effects of internally incorporated Auger electron emitting radionuclides and the initiation of studies to determine the effects of low dose-rate neutron exposure. Auger electron irradiation sever as a model for high LET-type radiation effects and as an experimental tool for studying the effects of radiation at specific sites within the cell. Auger-emitting radiosotopes are commonly used in clinical nuclear medicine, rendering them a potential hazard to human populations. We examined the influence of cellular localization of Auger-emitting radionuclides and the spectrum of energy distribution in DNA on their mutagenic, cytogenetic, and transformational effects. The effects of 125 I (an energetic beta emitter) were compared. We studied the induction of cytogenetic changes by 125 I exposure of the cell membrane, as well as its potential to promote (enhance) transformation initiated by low dose external x-ray exposure. We will investigate the Relative Biological Effectiveness for mutagenesis and transformation of low doses of fast neutrons delivered continuously at variable low dose-rates. 34 refs., 1 tab

  16. Involvement of Sodium Nitroprusside (SNP in the Mechanism That Delays Stem Bending of Different Gerbera Cultivars

    Directory of Open Access Journals (Sweden)

    Aung H. Naing

    2017-11-01

    Full Text Available Longevity of cut flowers of many gerbera cultivars (Gerbera jamesonii is typically short because of stem bending; hence, stem bending that occurs during the early vase life period is a major problem in gerbera. Here, we investigated the effects of sodium nitroprusside (SNP on the delay of stem bending in the gerbera cultivars, Alliance, Rosalin, and Bintang, by examining relative fresh weight, bacterial density in the vase solution, transcriptional analysis of a lignin biosynthesis gene, antioxidant activity, and xylem blockage. All three gerbera cultivars responded to SNP by delaying stem bending, compared to the controls; however, the responses were dose- and cultivar-dependent. Among the treatments, SNP at 20 mg L-1 was the best to delay stem bending in Alliance, while dosages of 10 and 5 mg L-1 were the best for Rosalin and Bintang, respectively. However, stem bending in Alliance and Rosalin was faster than in Bintang, indicating a discrepancy influenced by genotype. According to our analysis of the role of SNP in the delay of stem bending, the results revealed that SNP treatment inhibited bacterial growth and xylem blockage, enhanced expression levels of a lignin biosynthesis gene, and maintained antioxidant activities. Therefore, it is suggested that the cause of stem bending is associated with the above-mentioned parameters and SNP is involved in the mechanism that delays stem bending in the different gerbera cultivars.

  17. Mechanisms involved in alleviation of intestinal inflammation by bifidobacterium breve soluble factors.

    Directory of Open Access Journals (Sweden)

    Elise Heuvelin

    Full Text Available OBJECTIVES: Soluble factors released by Bifidobacterium breve C50 (Bb alleviate the secretion of pro-inflammatory cytokines by immune cells, but their effect on intestinal epithelium remains elusive. To decipher the mechanisms accounting for the cross-talk between bacteria/soluble factors and intestinal epithelium, we measured the capacity of the bacteria, its conditioned medium (Bb-CM and other Gram(+ commensal bacteria to dampen inflammatory chemokine secretion. METHODS: TNFalpha-induced chemokine (CXCL8 secretion and alteration of NF-kappaB and AP-1 signalling pathways by Bb were studied by EMSA, confocal microscopy and western blotting. Anti-inflammatory capacity was also tested in vivo in a model of TNBS-induced colitis in mice. RESULTS: Bb and Bb-CM, but not other commensal bacteria, induced a time and dose-dependent inhibition of CXCL8 secretion by epithelial cells driven by both AP-1 and NF-kappaB transcription pathways and implying decreased phosphorylation of p38-MAPK and IkappaB-alpha molecules. In TNBS-induced colitis in mice, Bb-CM decreased the colitis score and inflammatory cytokine expression, an effect reproduced by dendritic cell conditioning with Bb-CM. CONCLUSIONS: Bb and secreted soluble factors contribute positively to intestinal homeostasis by attenuating chemokine production. The results indicate that Bb down regulate inflammation at the epithelial level by inhibiting phosphorylations involved in inflammatory processes and by protective conditioning of dendritic cells.

  18. FINANCING MECHANISMS FOR INVESTMENT PROJECTS IN THE AGRICULTURAL SECTOR OF UKRAINE'S ECONOMY INVOLVING ANGEL INVESTORS

    Directory of Open Access Journals (Sweden)

    T. Nagachevska

    2014-06-01

    Full Text Available The challenges connected with attracting foreign investments into the agricultural sector of the Ukrainian economy as well as diversification of forms of international investments are actual due to the immediate needs of realization of innovative development, technological upgrading and strengthening of agricultural sector attractiveness on the world market. Current situation and problems connected with attracting foreign investments into the agricultural sector of the Ukrainian economy are revealed. It is detected that level of attracting foreign investments into the agricultural sector of Ukraine and into AIC together don't meet the needs of its innovative potential. The following factors of agricultural sector attractiveness have been considered: high soil fertility and favorable weather conditions for growing crops; export capacity; high yield of the Ukrainian farming companies; undervalued assets and low level of capitalization of agricultural companies; attractive tax regime for agricultural producers. It is recommended that agricultural producers should indicate these factors in investment proposals and projects that they present to potential international investors. State investment policy in the agricultural sector is viewed to consolidate the resource base and the sources of investment have been determined. Suggestions to expand the financing mechanisms for investment projects in the agricultural sector involving angel investors have been justified. Economic feasibility of attracting foreign investments for financing of innovation activity of farming companies has been revealed. The key requirements and main stages of investments of angel investment association have been described.

  19. Modulation of MicroRNAs by Phytochemicals in Cancer: Underlying Mechanisms and Translational Significance

    Science.gov (United States)

    Srivastava, Sanjeev K.; Arora, Sumit; Averett, Courey; Singh, Ajay P.

    2015-01-01

    MicroRNAs (miRNAs) are small, endogenous noncoding RNAs that regulate a variety of biological processes such as differentiation, development, and survival. Recent studies suggest that miRNAs are dysregulated in cancer and play critical roles in cancer initiation, progression, and chemoresistance. Therefore, exploitation of miRNAs as targets for cancer prevention and therapy could be a promising approach. Extensive evidence suggests that many naturally occurring phytochemicals regulate the expression of numerous miRNAs involved in the pathobiology of cancer. Therefore, an understanding of the regulation of miRNAs by phytochemicals in cancer, their underlying molecular mechanisms, and functional consequences on tumor pathophysiology may be useful in formulating novel strategies to combat this devastating disease. These aspects are discussed in this review paper with an objective of highlighting the significance of these observations from the translational standpoint. PMID:25853141

  20. Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report

    International Nuclear Information System (INIS)

    Bull, R.J.; Miller, J.H.; Sasser, L.B.; Schultz, I.R.; Thrall, B.D.

    1998-01-01

    'The objective of this project is to develop critical data for changing risk-based clean-up standards for trichloroethylene (TCE). The project is organized around two interrelated tasks: Task 1 addresses the tumorigenic and dosimetry issues for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work had suggested that TCA was primarily responsible for TCE-induced liver tumors, but several, more mechanistic observations suggest that DCA may play a prominent role. This task is aimed at determining the basis for the selection hypothesis and seeks to prove that this mode of action is responsible for TCE-induced tumors. This project will supply the basic dose-response data from which low-dose extrapolations would be made. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation model. As of May of 1998, this research has identified two plausible modes of action by which TCE produces liver tumors in mice. These modes of action do not require the compounds to be mutagenic. The bulk of the experimental evidence suggests that neither TCE nor the two hepatocarcinogenic metabolites of TCE are mutagenic. The results from the colony formation assay clearly establish that both of these metabolites cause colony growth from initiated cells that occur spontaneously in the liver of B 6 C 3 F 1 mice, although the phenotypes of the colonies differ in the same manner as tumors differ, in vivo. In the case of DCA, a second mechanism may occur at a lower dose involving the release of insulin. This observation is timely as it was recently reported that occupational exposures to trichloroethylene results in 2 to 4-fold

  1. Herb pair Danggui-Honghua: mechanisms underlying blood stasis syndrome by system pharmacology approach

    Science.gov (United States)

    Yue, Shi-Jun; Xin, Lan-Ting; Fan, Ya-Chu; Li, Shu-Jiao; Tang, Yu-Ping; Duan, Jin-Ao; Guan, Hua-Shi; Wang, Chang-Yun

    2017-01-01

    Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as HMOX1, NOS2, NOS3, HIF1A and PTGS2 were mainly involved in TNF signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway and neurotrophin signaling pathway. The contribution index of every active ingredient also indicated six compounds, including hydroxysafflor yellow A, safflor yellow A, safflor yellow B, Z-ligustilide, ferulic acid, and Z-butylidenephthalide, as the principal components of this herb pair. These results successfully explained the polypharmcological mechanisms underlying the efficiency of Danggui-Honghua for BSS treatment, and also probed into the potential novel therapeutic strategies for BSS in TCM.

  2. Mechanisms underlying post-inflammatory hyperpigmentation: lessons from solar lentigo.

    Science.gov (United States)

    Cardinali, G; Kovacs, D; Picardo, M

    2012-12-01

    Hyperpigmentation of the skin is a common dermatologic condition in all skin types but most prominent in brown-skinned population. In skin of color any inflammation or injury can be accompanied by alterations in pigmentation (hyper/hypo-pigmentation). Postinflammatory hyperpigmentation (PIH) can be observed in many skin conditions including acne, eczema, and contact dermatitis. In the control of skin pigmentation, parallel to the cross-talk between keratinocytes and melanocytes, increasing evidence has underlined the crucial role exerted by the interactions between mesenchymal and epithelial cells through the release of fibroblast-derived growth factors. Among these factors, the keratinocyte growth factor (KGF), alone or in combination with interleukin-1α, induces melanin deposition in vitro and hyperpigmented lesions in vivo. Furthermore, a moderate increase of KGF and a high induction of its receptor have been shown in solar lentigo lesions, suggesting the involvement of this growth factor in the onset of the hyperpigmented spots. Several studies highlight the possible contribution of the fibroblast-derived melanogenic growth factors to the hyperpigmentated lesions, in the context of the mesenchymal - epithelial interactions modulating melanocyte functions. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  3. [Mechanisms underlying post-inflammatory hyperpigmentation: lessons from solar lentigo].

    Science.gov (United States)

    Cardinali, G; Kovacs, D; Picardo, M

    2012-11-01

    Hyperpigmentation of the skin is a common dermatologic condition in all skin types but most prominent in brown-skinned population. In skin of color any inflammation or injury can be accompanied by alterations in pigmentation (hyper/hypo-pigmentation). Postinflammatory hyperpigmentation (PIH) can be observed in many skin conditions including acne, eczema, and contact dermatitis. In the control of skin pigmentation, parallel to the cross-talk between keratinocytes and melanocytes, increasing evidence has underlined the crucial role exerted by the interactions between mesenchymal and epithelial cells through the release of fibroblast-derived growth factors. Among these factors, the keratinocyte growth factor (KGF), alone or in combination with interleukin-1α, induces melanin deposition in vitro and hyperpigmented lesions in vivo. Furthermore, a moderate increase of KGF and a high induction of its receptor have been shown in solar lentigo lesions, suggesting the involvement of this growth factor in the onset of the hyperpigmented spots. Several studies highlight the possible contribution of the fibroblast-derived melanogenic growth factors to the hyperpigmentated lesions, in the context of the mesenchymal - epithelial interactions modulating melanocyte functions. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. Mechanisms of microstructural changes of fuel under irradiation

    International Nuclear Information System (INIS)

    Garcia, P.; Carlot, G.; Dorado, B.; Maillard, S.; Sabathier, C.; Martin, G.; Oh, J.Y.; Welland, M.J.

    2015-01-01

    Nuclear fuels are subjected to high levels of radiation damage mainly due to the slowing of fission fragments, which results in substantial modifications of the initial fuel microstructure. Microstructure changes alter practically all engineering fuel properties such as atomic transport or thermomechanical properties so understanding these changes is essential to predicting the performance of fuel elements. Also, with increasing burn-up, the fuel drifts away from its initial composition as the fission process produces new chemical elements. Because nuclear fuels operate at high temperature and usually under high-temperature gradients, damage annealing, foreign atom or defect clustering and migration occur on multiple time and length scales, which make long-term predictions difficult. The end result is a fuel microstructure which may show extensive differences on the scale of a single fuel pellet. The main challenge we are faced with is, therefore, to identify the phenomena occurring on the atom scale that are liable to have macroscopic effects that will determine the microstructure changes and ultimately the life-span of a fuel element. One step towards meeting this challenge is to develop and apply experimental or modelling methods capable of connecting events that occur over very short length and timescales to changes in the fuel microstructure over engineering length and timescales. In the first part of this chapter, we provide an overview of some of the more important microstructure modifications observed in nuclear fuels. The emphasis is placed on oxide fuels because of the extensive amount of data available in relation to these materials under neutron or ion irradiation. When possible and relevant, the specifics of other types of fuels such as metallic or carbide fuels are alluded to. Throughout this chapter but more specifically in the latter part, we attempt to give examples of how modelling and experimentation at various scales can provide us with

  5. Separable mechanisms underlying global feature-based attention.

    Science.gov (United States)

    Bondarenko, Rowena; Boehler, Carsten N; Stoppel, Christian M; Heinze, Hans-Jochen; Schoenfeld, Mircea A; Hopf, Jens-Max

    2012-10-31

    Feature-based attention is known to operate in a spatially global manner, in that the selection of attended features is not bound to the spatial focus of attention. Here we used electromagnetic recordings in human observers to characterize the spatiotemporal signature of such global selection of an orientation feature. Observers performed a simple orientation-discrimination task while ignoring task-irrelevant orientation probes outside the focus of attention. We observed that global feature-based selection, indexed by the brain response to unattended orientation probes, is composed of separable functional components. One such component reflects global selection based on the similarity of the probe with task-relevant orientation values ("template matching"), which is followed by a component reflecting selection based on the similarity of the probe with the orientation value under discrimination in the focus of attention ("discrimination matching"). Importantly, template matching occurs at ∼150 ms after stimulus onset, ∼80 ms before the onset of discrimination matching. Moreover, source activity underlying template matching and discrimination matching was found to originate from ventral extrastriate cortex, with the former being generated in more anterolateral and the latter in more posteromedial parts, suggesting template matching to occur in visual cortex higher up in the visual processing hierarchy than discrimination matching. We take these observations to indicate that the population-level signature of global feature-based selection reflects a sequence of hierarchically ordered operations in extrastriate visual cortex, in which the selection based on task relevance has temporal priority over the selection based on the sensory similarity between input representations.

  6. Catecholamine biosynthesis pathway potentially involved in banana defense mechanisms to crown rot disease.

    Science.gov (United States)

    Lassois, L; De Clerck, C; Frettinger, P; De Lapeyre De Bellaire, L; Lepoivre, P; Haïssam Jijakli, M

    2011-01-01

    Variations in Cavendish bananas susceptibility to crown rot disease have been observed (Lassois et al., 2010a), but the molecular mechanisms underlying these quantitative host-pathogen relationships were still unknown. The present study was designed to compare gene expression between bananas (Musa acuminata, AAA, 'Grande-Naine') showing a high post-harvest susceptibility (S+) and bananas showing a low post-harvest susceptibility (S-) to crown rot disease. This comparison was performed between crowns (S+ and S-) collected one hour before standardized artificial inoculations with Colletotrichum musae. Fruit susceptibility was evaluated through lesion size on the crown 13 days later. Gene expression comparisons were performed with the cDNA-AFLP technique (Lassois et al., 2009). This revealed that a gene showing a strong homology with a dopamine-beta-monooxygenase (DoH) is differently expressed between S+ and S (Lassois et al., 2011). Furthermore, semi-quantitative real-time RT-PCR analyses between S+ and S- were applied to confirm the differential expression results for DoH obtained by cDNA-AFLP. Two biological replicates were tested. These semi-quantitative analyses were performed not only on tissues collected one hour before C. musae inoculation but also on crown tissues collected 13 days after inoculation. The real-time RT-PCR confirmed that DoH was upregulated in the S tissues collected at harvest, just before C. musae inoculation. This gene was also highly upregulated in the S- tissues collected 13 days after crown inoculation. Similar results were obtained for both biological replicates. Our results suggest that catecholamine's could play a role in banana defense mechanisms to crown rot disease.

  7. Study of the physical mechanisms involved in the femtosecond laser optical breakdown of dielectric materials

    International Nuclear Information System (INIS)

    Mouskeftaras, Alexandros

    2013-01-01

    We have carried out detailed time resolved experimental studies of the mechanism of electron excitation-relaxation, when an ultrashort (60 fs -1 ps) laser (UV and IR) pulse interacts with a wide band gap dielectric material. The studies cover a range of different dielectric materials and the investigated regimes span from nondestructive ionization of the material at the low power end (∼TW/cm 2 ) to ablative domain at a higher laser power (∼10 TW/cm 2 ). This gives fundamental insight into the understanding of the laser damaging process taking place under our irradiation conditions. The usage of time-resolved spectral interferometry technique allows to directly measure the electron density of the irradiated material under different excitation conditions and hence leads to quantification of the process. The measurements, carried out at the optical breakdown threshold utilizing different pulse durations, raise questions regarding the usage of critical excitation density as a universal ablation criterion. A new criterion related to the exchanged energy is proposed. Additionally, the use of an experimental setup implementing a double pump pulse allows the identification of different excitation mechanisms taking place at time scales of the order of the pulse duration used. Electronic avalanche is observed in some materials (SiO 2 , NaCl) while this is not the case for others (Al 2 O 3 , MgO). These differences are discussed in detail. Next, we measure the energy spectrum of excited electrons with a complementary technique: the photoemission spectroscopy. These results allow us on one hand to show a crossed effect between the two 'pump' pulses and on the other hand to measure electron relaxation characteristic times, as a function of their kinetic energy. Finally, a morphological study of craters resulting from ablation in the case of a single pulse has been carried out for different irradiation parameters: number of shots, energy and pulse duration. This work has

  8. Mechanisms underlying the formation of induced pluripotent stem cells

    Science.gov (United States)

    González, Federico; Huangfu, Danwei

    2015-01-01

    Human pluripotent stem cells (hPSCs) offer unique opportunities for studying human biology, modeling diseases and for therapeutic applications. The simplest approach so far to generate human PSCs lines is through reprogramming of somatic cells from an individual by defined factors, referred to simply as reprogramming. Reprogramming circumvents the ethical issues associated with human embryonic stem cells (hESCs) and nuclear transfer hESCs (nt-hESCs), and the resulting induced pluripotent stem cells (hiPSCs) retain the same basic genetic makeup as the somatic cell used for reprogramming. Since the first report of iPSCs by Takahashi and Yamanaka, the molecular mechanisms of reprogramming have been extensively investigated. A better mechanistic understanding of reprogramming is fundamental not only to iPSC biology and improving the quality of iPSCs for therapeutic use, but also to our understanding of the molecular basis of cell identity, pluripotency and plasticity. Here we summarize the genetic, epigenetic and cellular events during reprogramming, and the roles of various factors identified thus far in the reprogramming process. PMID:26383234

  9. The neural sociometer: brain mechanisms underlying state self-esteem.

    Science.gov (United States)

    Eisenberger, Naomi I; Inagaki, Tristen K; Muscatell, Keely A; Byrne Haltom, Kate E; Leary, Mark R

    2011-11-01

    On the basis of the importance of social connection for survival, humans may have evolved a "sociometer"-a mechanism that translates perceptions of rejection or acceptance into state self-esteem. Here, we explored the neural underpinnings of the sociometer by examining whether neural regions responsive to rejection or acceptance were associated with state self-esteem. Participants underwent fMRI while viewing feedback words ("interesting," "boring") ostensibly chosen by another individual (confederate) to describe the participant's previously recorded interview. Participants rated their state self-esteem in response to each feedback word. Results demonstrated that greater activity in rejection-related neural regions (dorsal ACC, anterior insula) and mentalizing regions was associated with lower-state self-esteem. Additionally, participants whose self-esteem decreased from prescan to postscan versus those whose self-esteem did not showed greater medial prefrontal cortical activity, previously associated with self-referential processing, in response to negative feedback. Together, the results inform our understanding of the origin and nature of our feelings about ourselves.

  10. Adhesive wear mechanism under combined electric diamond grinding

    Directory of Open Access Journals (Sweden)

    Popov Vyacheslav

    2017-01-01

    Full Text Available The article provides a scientific substantiation of loading of metal-bond diamond grinding wheels and describes the mechanism of contact interaction (interlocking of wheels with tool steel as well as its general properties having an influence on combined electric diamond grinding efficiency. The study concluded that a loaded layer can be formed in a few stages different by nature. It is known, that one of the causes of grinding degradation is a continuous loading of active grits (abrasive grinding tool by workpiece chips. It all affects the diamond grinding wheels efficiency and grinding ability with a result in increase of tool pressure, contact temperature and wheels specific removal rate. Science has partially identified some various methods to minimize grinding wheel loading, however, as to loading of metal-bond diamond grinding wheels the search is still in progress. Therefore, research people have to state, that in spite of the fact that the wheels made of cubic boron nitride are of little use as applied to ceramic, ultrahard, hard-alloyed hard-to-machine and nano-materials of the time, but manufactures have to apply cubic boron nitride wheels wherein diamond ones preferable.

  11. Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms.

    Science.gov (United States)

    Hernández, Antonio F; Menéndez, Pablo

    2016-03-29

    Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides) include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs) in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations) may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation). Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events.

  12. Assessing mechanical vulnerability in water distribution networks under multiple failures

    Science.gov (United States)

    Berardi, Luigi; Ugarelli, Rita; Røstum, Jon; Giustolisi, Orazio

    2014-03-01

    Understanding mechanical vulnerability of water distribution networks (WDN) is of direct relevance for water utilities since it entails two different purposes. On the one hand, it might support the identification of severe failure scenarios due to external causes (e.g., natural or intentional events) which result into the most critical consequences on WDN supply capacity. On the other hand, it aims at figure out the WDN portions which are more prone to be affected by asset disruptions. The complexity of such analysis stems from the number of possible scenarios with single and multiple simultaneous shutdowns of asset elements leading to modifications of network topology and insufficient water supply to customers. In this work, the search for the most disruptive combinations of multiple asset failure events is formulated and solved as a multiobjective optimization problem. The higher vulnerability failure scenarios are detected as those causing the lower supplied demand due to the lower number of simultaneous failures. The automatic detection of WDN topology, subsequent to the detachments of failed elements, is combined with pressure-driven analysis. The methodology is demonstrated on a real water distribution network. Results show that, besides the failures causing the detachment of reservoirs, tanks, or pumps, there are other different topological modifications which may cause severe WDN service disruptions. Such information is of direct relevance to support planning asset enhancement works and improve the preparedness to extreme events.

  13. Obstructive sleep apnea and dyslipidemia: evidence and underlying mechanism.

    Science.gov (United States)

    Adedayo, Ajibola Monsur; Olafiranye, Oladipupo; Smith, David; Hill, Alethea; Zizi, Ferdinand; Brown, Clinton; Jean-Louis, Girardin

    2014-03-01

    Over the past half century, evidence has been accumulating on the emergence of obstructive sleep apnea (OSA), the most prevalent sleep-disordered breathing, as a major risk factor for cardiovascular disease. A significant body of research has been focused on elucidating the complex interplay between OSA and cardiovascular risk factors, including dyslipidemia, obesity, hypertension, and diabetes mellitus that portend increased morbidity and mortality in susceptible individuals. Although a clear causal relationship of OSA and dyslipidemia is yet to be demonstrated, there is increasing evidence that chronic intermittent hypoxia, a major component of OSA, is independently associated and possibly the root cause of the dyslipidemia via the generation of stearoyl-coenzyme A desaturase-1 and reactive oxygen species, peroxidation of lipids, and sympathetic system dysfunction. The aim of this review is to highlight the relationship between OSA and dyslipidemia in the development of atherosclerosis and present the pathophysiologic mechanisms linking its association to clinical disease. Issues relating to epidemiology, confounding factors, significant gaps in research and future directions are also discussed.

  14. Potassium channel and NKCC cotransporter involvement in ocular refractive control mechanisms.

    Directory of Open Access Journals (Sweden)

    Sheila G Crewther

    Full Text Available Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/-10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5 mM Ba(2+ and 10(-5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba(2+ but significant change only for negative lens defocus with bumetanide (Rx(SAL(-10D = -8.6 +/- .9 D; Rx(Ba2+(-10D = -2.9 +/- .9 D; Rx(Bum(-10D = -2.9 +/- .9 D; Rx(SAL(+10D = +8.2 +/- .9 D; Rx(Ba2+(+10D = +2.8 +/- 1.3 D; Rx(Bum(+10D = +8.0 +/- .7 D. Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba(2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a

  15. Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels

    Science.gov (United States)

    Hristov, Kiril L.; Parajuli, Shankar P.; Provence, Aaron

    2016-01-01

    In addition to improving sexual function, testosterone has been reported to have beneficial effects in ameliorating lower urinary tract symptoms by increasing bladder capacity and compliance, while decreasing bladder pressure. However, the cellular mechanisms by which testosterone regulates detrusor smooth muscle (DSM) excitability have not been elucidated. Here, we used amphotericin-B perforated whole cell patch-clamp and single channel recordings on inside-out excised membrane patches to investigate the regulatory role of testosterone in guinea pig DSM excitability. Testosterone (100 nM) significantly increased the depolarization-induced whole cell outward currents in DSM cells. The selective pharmacological inhibition of the large-conductance voltage- and Ca2+-activated K+ (BK) channels with paxilline (1 μM) completely abolished this stimulatory effect of testosterone, suggesting a mechanism involving BK channels. At a holding potential of −20 mV, DSM cells exhibited transient BK currents (TBKCs). Testosterone (100 nM) significantly increased TBKC activity in DSM cells. In current-clamp mode, testosterone (100 nM) significantly hyperpolarized the DSM cell resting membrane potential and increased spontaneous transient hyperpolarizations. Testosterone (100 nM) rapidly increased the single BK channel open probability in inside-out excised membrane patches from DSM cells, clearly suggesting a direct BK channel activation via a nongenomic mechanism. Live-cell Ca2+ imaging showed that testosterone (100 nM) caused a decrease in global intracellular Ca2+ concentration, consistent with testosterone-induced membrane hyperpolarization. In conclusion, the data provide compelling mechanistic evidence that under physiological conditions, testosterone at nanomolar concentrations directly activates BK channels in DSM cells, independent from genomic testosterone receptors, and thus regulates DSM excitability. PMID:27605581

  16. Effects and mechanisms of 3α,5α,-THP on emotion, motivation, and reward functions involving pregnane xenobiotic receptor

    Directory of Open Access Journals (Sweden)

    Cheryl A Frye

    2012-01-01

    Full Text Available Progestogens [progesterone (P4 and its products] play fundamental roles in the development and/or function of the central nervous system during pregnancy. We, and others, have investigated the role of pregnane neurosteroids for a plethora of functional effects beyond their pro-gestational processes. Emerging findings regarding the effects, mechanisms, and sources of neurosteroids have challenged traditional dogma about steroid action. How the P4 metabolite and neurosteroid, 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP, influences cellular functions and behavioral processes involved in emotion/affect, motivation, and reward, is the focus of the present review. To further understand these processes, we have utilized an animal model assessing the effects, mechanisms, and sources of 3α,5α-THP. In the ventral tegmental area (VTA, 3α,5α-THP has actions to facilitate affective, and motivated, social behaviors through non-traditional targets, such as GABA, glutamate, and dopamine receptors. 3α,5α-THP levels in the midbrain VTA both facilitate, and/or are enhanced by, affective and social behavior. The pregnane xenobiotic receptor (PXR mediates the production of, and/or metabolism to, various neurobiological factors. PXR is localized to the midbrain VTA of rats. The role of PXR to influence 3α,5α-THP production from central biosynthesis, and/or metabolism of peripheral P4, in the VTA, as well as its role to facilitate, or be increased by, affective/social behaviors is under investigation. Investigating novel behavioral functions of 3α,5α-THP extends our knowledge of the neurobiology of progestogens, relevant for affective/social behaviors, and their connections to systems that regulate affect and motivated processes, such as those important for stress regulation and neuropsychiatric disorders (anxiety, depression, schizophrenia, drug dependence. Thus, further understanding of 3α,5α-THP’s role and mechanisms to enhance affective and motivated

  17. Molecular Mechanisms Underlying Origin and Diversification of the Angiosperm Flower

    Science.gov (United States)

    Theissen, Guenter; Melzer, Rainer

    2007-01-01

    Background Understanding the mode and mechanisms of the evolution of the angiosperm flower is a long-standing and central problem of evolutionary biology and botany. It has essentially remained unsolved, however. In contrast, considerable progress has recently been made in our understanding of the genetic basis of flower development in some extant model species. The knowledge that accumulated this way has been pulled together in two major hypotheses, termed the ‘ABC model’ and the ‘floral quartet model’. These models explain how the identity of the different types of floral organs is specified during flower development by homeotic selector genes encoding transcription factors. Scope We intend to explain how the ‘ABC model’ and the ‘floral quartet model’ are now guiding investigations that help to understand the origin and diversification of the angiosperm flower. Conclusions Investigation of orthologues of class B and class C floral homeotic genes in gymnosperms suggest that bisexuality was one of the first innovations during the origin of the flower. The transition from dimer to tetramer formation of floral homeotic proteins after establishment of class E proteins may have increased cooperativity of DNA binding of the transcription factors controlling reproductive growth. That way, we hypothesize, better ‘developmental switches’ originated that facilitated the early evolution of the flower. Expression studies of ABC genes in basally diverging angiosperm lineages, monocots and basal eudicots suggest that the ‘classical’ ABC system known from core eudicots originated from a more fuzzy system with fading borders of gene expression and gradual transitions in organ identity, by sharpening of ABC gene expression domains and organ borders. Shifting boundaries of ABC gene expression may have contributed to the diversification of the angiosperm flower many times independently, as may have changes in interactions between ABC genes and their target

  18. Enhancement of sleep slow waves: underlying mechanisms and practical consequences.

    Directory of Open Access Journals (Sweden)

    Michele eBellesi

    2014-10-01

    Full Text Available Even modest sleep restriction, especially the loss of sleep slow wave activity, is invariably associated with slower EEG activity during wake, the occurrence of local sleep in an otherwise awake brain, and impaired performance due to cognitive and memory deficits. Recent studies not only confirm the beneficial role of sleep in memory consolidation, but also point to a specific role for sleep slow waves. Thus, the implementation of methods to enhance sleep slow waves without unwanted arousals or lightening of sleep could have significant practical implications. Here we first review the evidence that it is possible to enhance sleep slow waves in humans using transcranial direct-current stimulation and transcranial magnetic stimulation. Since these methods are currently impractical and their safety is questionable, especially for chronic long-term exposure, we then discuss novel data suggesting that it is possible to enhance slow waves using sensory stimuli. We consider the physiology of the K-complex, a peripheral evoked slow wave, and show that, among different sensory modalities, acoustic stimulation is the most effective in increasing the magnitude of slow waves, likely through the activation of non-lemniscal ascending pathways to the thalamo-cortical system. In addition, we discuss how intensity and frequency of the acoustic stimuli, as well as exact timing and pattern of stimulation, affect sleep enhancement. Finally, we discuss automated algorithms that read the EEG and, in real-time, adjust the stimulation parameters in a closed-loop manner to obtain an increase in sleep slow waves and avoid undesirable arousals. In conclusion, while discussing the mechanisms that underlie the generation of sleep slow waves, we review the converging evidence showing that acoustic stimulation is safe and represents an ideal tool for slow wave sleep enhancement.

  19. Thin circular cylinder under axisymmetrical thermal and mechanical loading

    International Nuclear Information System (INIS)

    Arnaudeau, F.; Zarka, J.; Gerij, J.

    1977-01-01

    To assess structural integrity of components subjected to cyclic thermal loadings one must look at thermal ratchetting as a possible failure mode. Considering a thin circular cylinder subjected to constant internal pressure and cyclically varying thermal gradient through the thickness Bree, J. Strain Analysis 2 (1967) No.3, obtained a diagram that serves as a foundation for many design rules (e.g.: ASME code). The upper part of the french LMFBR main vessel is subjected to an axisymmetrical axial thermal loading and an axial load (own weight). Operation of the reactor leads to cyclic variations of the axial thermal loading. The question that arises is whether or not the Bree diagram is realistic for such loading conditions. A special purpose computer code (Ratch) was developed to analyse a thin circular cylinder subjected to axisymmetrical mechanical and thermal loadings. The Mendelson's approach of this problem is followed. Classical Kirchoff-Love hypothesis of thin shells is used and a state of plane stress is assumed. Space integrations are performed by Gaussian quadrature in the axial direction and by Simpson's one third rule throughout the thickness. Thermoelastic-plastic constitutive equations are solved with an implicit scheme (Nguyen). Thermovisco-plastic constitutive equations are solved with an explicit time integration scheme (Treanor's algorithm especially fitted). A Bree type diagram is obtained for an axial step of temperature which varies cyclically and a sustained constant axial load. The material behavior is assumed perfectly plastic and creep effect is not considered. Results show that the domain where no ratchetting occurs is reduced when compared with the domain predicted by the Bree diagram

  20. Compression under a mechanical counter pressure space suit glove

    Science.gov (United States)

    Waldie, James M A.; Tanaka, Kunihiko; Tourbier, Dietmar; Webb, Paul; Jarvis, Christine W.; Hargens, Alan R.

    2002-01-01

    Background: Current gas-pressurized space suits are bulky stiff shells severely limiting astronaut function and capability. A mechanical counter pressure (MCP) space suit in the form of a tight elastic garment could dramatically improve extravehicular activity (EVA) dexterity, but also be advantageous in safety, cost, mass and volume. The purpose of this study was to verify that a prototype MCP glove exerts the design compression of 200 mmHg, a pressure similar to the current NASA EVA suit. Methods: Seven male subjects donned a pressure measurement array and MCP glove on the right hand, which was placed into a partial vacuum chamber. Average compression was recorded on the palm, the bottom of the middle finger, the top of the middle finger and the dorsum of the hand at pressures of 760 (ambient), 660 and 580 mmHg. The vacuum chamber was used to simulate the pressure difference between the low breathing pressure of the current NASA space suits (approximately 200 mmHg) and an unprotected hand in space. Results: At ambient conditions, the MCP glove compressed the dorsum of the hand at 203.5 +/- 22.7 mmHg, the bottom of the middle finger at 179.4 +/- 16.0 mmHg, and the top of the middle finger at 183.8 +/- 22.6 mmHg. The palm compression was significantly lower (59.6 +/- 18.8 mmHg, pglove compression with the chamber pressure reductions. Conclusions: The MCP glove compressed the dorsum of the hand and middle finger at the design pressure.

  1. Study of the Genes and Mechanism Involved in the Radioadaptive Response

    Science.gov (United States)

    Dasgupta, Pushan R.

    2009-01-01

    The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor

  2. The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity

    DEFF Research Database (Denmark)

    Gordillo, M.; Vega, H.; Trainer, A.H.

    2008-01-01

    Roberts syndrome/SC phocomelia (RBS) is an autosomal recessive disorder with growth retardation, craniofacial abnormalities and limb reduction. Cellular alterations in RBS include lack of cohesion at the heterochromatic regions around centromeres and the long arm of the Y chromosome, reduced growth...... and nonsense mutations associated with decreased levels of mRNA and absence of protein. We found decreased proliferation capacity in RBS cell lines associated with cell death, but not with increased cell cycle duration, which could be a factor in the development of phocomelia and cleft palate in RBS...

  3. The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity

    NARCIS (Netherlands)

    Gordillo, Miriam; Vega, Hugo; Trainer, Alison H.; Hou, Fajian; Sakai, Norio; Luque, Ricardo; Kayserili, Hülya; Basaran, Seher; Skovby, Flemming; Hennekam, Raoul C. M.; Uzielli, Maria L. Giovannucci; Schnur, Rhonda E.; Manouvrier, Sylvie; Chang, Susan; Blair, Edward; Hurst, Jane A.; Forzano, Francesca; Meins, Moritz; Simola, Kalle O. J.; Raas-Rothschild, Annick; Schultz, Roger A.; McDaniel, Lisa D.; Ozono, Keiichi; Inui, Koji; Zou, Hui; Jabs, Ethylin Wang

    2008-01-01

    Roberts syndrome/SC phocomelia (RBS) is an autosomal recessive disorder with growth retardation, craniofacial abnormalities and limb reduction. Cellular alterations in RBS include lack of cohesion at the heterochromatic regions around centromeres and the long arm of the Y chromosome, reduced growth

  4. The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity

    DEFF Research Database (Denmark)

    Gordillo, M.; Vega, H.; Trainer, A.H.

    2008-01-01

    Roberts syndrome/SC phocomelia (RBS) is an autosomal recessive disorder with growth retardation, craniofacial abnormalities and limb reduction. Cellular alterations in RBS include lack of cohesion at the heterochromatic regions around centromeres and the long arm of the Y chromosome, reduced grow...

  5. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?

    Directory of Open Access Journals (Sweden)

    Sagai Masaru

    2011-12-01

    moderate oxidative stress. Recently these concepts have become widely accepted. The versatility of ozone in treating vascular and degenerative diseases as well as skin lesions, hernial disc and primary root carious lesions in children is emphasized. Further researches able to elucidate whether the mechanisms of action of ozone therapy involve nuclear transcription factors, such as Nrf2, NFAT, AP-1, and HIF-1α are warranted.

  6. Studies of the mechanisms involved in the laser surface hardening process of aluminum base alloys

    International Nuclear Information System (INIS)

    Silva, Luciana Ventavele da

    2011-01-01

    The Al-Si alloys are widely used in industry to replace the steel and gray cast iron in high-tech sectors. The commercial importance of these alloys is mainly due to its low weight, excellent wear (abrasion) and corrosion resistance, high resistance at elevated temperatures, low coefficient of thermal expansion and lesser fuel consumption that provide considerable reduction of emission of pollutants. In this work, Al-Si alloy used in the automotive industry to manufacture pistons of internal combustion engines, was undergone to surface treatments using LASER remelting (Nd:YAG, λ = 1.06 μm, pulsed mode). The LASER enables various energy concentrations with accurate transfer to the material without physical contact. The intense energy transfer causes the occurrence of structural changes in the superficial layer of the material. Experiments with single pulses and trails were conducted under various conditions of LASER processing in order to analyze microstructural changes resulting from treatments and their effects on the hardness. For the characterization of hardened layer was utilized the following techniques: optical microscopy, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), x-ray mapping, Vickers microhardness and maximum roughness tests. The high cooling rate caused a change in the alloy structure due to the refinement of the primary eutectic silicon particles, resulting in increase of the mechanical properties (hardness) of the Al-Si alloy. (author)

  7. Neural mechanisms underlying cognitive inflexibility in Parkinson's disease.

    Science.gov (United States)

    Lange, Florian; Seer, Caroline; Loens, Sebastian; Wegner, Florian; Schrader, Christoph; Dressler, Dirk; Dengler, Reinhard; Kopp, Bruno

    2016-12-01

    Cognitive inflexibility is a hallmark of executive dysfunction in Parkinson's disease (PD). This deficit consistently manifests itself in a PD-related increase in the number of perseverative errors committed on the Wisconsin Card Sorting Test (WCST). However, the neural processes underlying perseverative WCST performance in PD are still largely unknown. The present study is the first to investigate the event-related potential (ERP) correlates of cognitive inflexibility on the WCST in PD patients. Thirty-two PD patients and 35 matched control participants completed a computerized version of the WCST while the electroencephalogram (EEG) was recorded. Behavioral results revealed the expected increase in perseverative errors in patients with PD. ERP analysis focused on two established indicators of executive processes: the fronto-central P3a as an index of attentional orienting and the sustained parietal positivity (SPP) as an index of set-shifting processes. In comparison to controls, P3a amplitudes were significantly attenuated in PD patients. Regression analysis further revealed that P3a and SPP amplitudes interactively contributed to the prediction of perseverative errors in PD patients: The number of perseverative errors was only increased when both ERP amplitudes were attenuated. Notably, the two ERP markers of executive processes accounted for more than 40% of the variance in perseverative errors in PD patients. We conclude that cognitive inflexibility in PD occurs when the neural bases of multiple executive processes are affected by the pathophysiology of PD. The combined measurement of P3a and SPP might yield an electrophysiological marker of cognitive inflexibility in PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Design principles and developmental mechanisms underlying retinal mosaics.

    Science.gov (United States)

    Reese, Benjamin E; Keeley, Patrick W

    2015-08-01

    Most structures within the central nervous system (CNS) are composed of different types of neuron that vary in both number and morphology, but relatively little is known about the interplay between these two features, i.e. about the population dynamics of a given cell type. How such arrays of neurons are distributed within a structure, and how they differentiate their dendrites relative to each other, are issues that have recently drawn attention in the invertebrate nervous system, where the genetic and molecular underpinnings of these organizing principles are being revealed in exquisite detail. The retina is one of the few locations where these principles have been extensively studied in the vertebrate CNS, indeed, where the design principles of 'mosaic regularity' and 'uniformity of coverage' were first explicitly defined, quantified, and related to each other. Recent studies have revealed a number of genes that influence the formation of these histotypical features in the retina, including homologues of those invertebrate genes, although close inspection reveals that they do not always mediate comparable developmental processes nor elucidate fundamental design principles. The present review considers just how pervasive these features of 'mosaic regularity' and 'uniform dendritic coverage' are within the mammalian retina, discussing the means by which such features can be assessed in the mature and developing nervous system and examining the limitations associated with those assessments. We then address the extent to which these two design principles co-exist within different populations of neurons, and how they are achieved during development. Finally, we consider the neural phenotypes obtained in mutant nervous systems, to address whether a prospective gene of interest underlies those very design principles. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  9. Mechanism of attenuation of leptin signaling under chronic ligand stimulation

    Directory of Open Access Journals (Sweden)

    Bamberg-Lemper Simone

    2010-01-01

    Full Text Available Abstract Background Leptin is an adipocyte-derived hormone that acts via its hypothalamic receptor (LEPRb to regulate energy balance. A downstream effect essential for the weight-regulatory action of leptin is the phosphorylation and activation of the latent transcription factor STAT3 by LEPRb-associated Janus kinases (JAKs. Obesity is typically associated with chronically elevated leptin levels and a decreased ability of LEPRb to activate intracellular signal transduction pathways (leptin resistance. Here we have studied the roles of the intracellular tyrosine residues in the negative feedback regulation of LEPRb-signaling under chronic leptin stimulation. Results Mutational analysis showed that the presence of either Tyr985 and Tyr1077 in the intracellular domain of LEPRb was sufficient for the attenuation of STAT3 phosphorylation, whereas mutation of both tyrosines rendered LEPRb resistant to feedback regulation. Overexpression and RNA interference-mediated downregulation of suppressor of cytokine signaling 3 (SOCS3 revealed that both Tyr985 and Tyr1077 were capable of supporting the negative modulatory effect of SOCS3 in reporter gene assays. In contrast, the inhibitory effect of SOCS1 was enhanced by the presence of Tyr985 but not Tyr1077. Finally, the reduction of the STAT-phosphorylating activity of the LEPRb complex after 2 h of leptin stimulation was not accompanied by the dephosphorylation or degradation of LEPRb or the receptor-associated JAK molecule, but depended on Tyr985 and/or Tyr1077. Conclusions Both Tyr985 and Tyr1077 contribute to the negative regulation of LEPRb signaling. The inhibitory effects of SOCS1 and SOCS3 differ in the dependence on the tyrosine residues in the intracellular domain of LEPRb.

  10. Photodegradation kinetics, products and mechanism of timolol under simulated sunlight

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yong, E-mail: ychen@hust.edu.cn [School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Liang, Qi; Zhou, Danna [College of Material Science and Chemical Engineering, China University of Geosciences, Wuhan 430074 (China); Wang, Zongping, E-mail: zongpingw@hust.edu.cn [School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Tao, Tao [School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Zuo, Yuegang [Department of Chemistry and Biochemistry, University of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, MA 02747 (United States)

    2013-05-15

    Highlights: ► The indirect degradation of timolol is first investigated in fulvic acid solution. ► {sup 3}FA{sup *} and {sup 1}O{sub 2} accounted for the degradation of timolol in the aerated FA solutions. ► The presence of halides inhibited the degradation in the order of Cl{sup −} < Br{sup −} < I{sup −}. ► The role of I{sup −} in the degradation was first found to be concentration-dependent. ► The photoproducts of timolol were identified by LC-DAD/ESI-MS/MS analysis. -- Abstract: The photodegradation of β-blocker timolol in fulvic acid (FA) solution was investigated under simulated sunlight. The triplet excited state of FA ({sup 3}FA{sup *}) and singlet oxygen ({sup 1}O{sub 2}) were the main reactive species responsible for the degradation of timolol in the aerated FA solutions. Both dissolved oxygen and iodide ions (I{sup −}) are the efficient quenchers of {sup 3}FA{sup *}. The photodegradation was drastically accelerated after removing the dissolved oxygen. The presence of I{sup −} inhibited the photosensitized degradation of timolol in the deoxygenated FA solutions, whereas the role of I{sup −} in the reaction was concentration-dependent in the aerated solutions. The other halide ions such as chloride (Cl{sup −}) and bromide (Br{sup −}) exhibited less effect on the photodegradation of timolol in both aerated and deoxygenated solutions. By LC-DAD/ESI-MS/MS analysis, the photoproducts of timolol in both aerated and deoxygenated FA solutions were identified. Electron transfer interaction occurred between {sup 3}FA{sup *} and amine moiety of timolol, leading to the cleavage of C–O bond in the side chain and oxidation of the hexatomic ring. These findings suggest the photosensitized degradation was a significant pathway for the elimination of timolol in natural waters.

  11. Involvement of immunologic mechanisms in a guinea pig model of western red cedar asthma.

    Science.gov (United States)

    Salari, H; Howard, S; Chan, H; Dryden, P; Chan-Yeung, M

    1994-05-01

    Western red cedar asthma is the most common form of occupational asthma in the Pacific Northwest. Plicatic acid (PA) is the chemical component of Western red cedar that causes asthma. The role of immunologic processes involved in the PA-induced asthmatic reaction has not been established. To characterize the mechanisms of PA-induced asthmatic reaction, guinea pigs were sensitized to PA through biweekly injection of PA-ovalbumin conjugate with aluminum hydroxide as an adjuvant for a period of 6 months. Specific IgG1 antibodies to PA were detected in the blood 3 months after sensitization of animals. The level of specific IgG1 antibodies to ovalbumin after 6 months was about two times the level of specific IgG1 to PA. At 6 months, tracheal tissue from PA-ovalbumin-sensitized guinea pigs contracted after exposure to either PA or ovalbumin in vitro. The degree of contraction induced by PA was two to three times less than the contraction induced by ovalbumin. PA caused histamine, prostaglandin D2, and leukotriene D4 release from both lung mast cells and blood basophils. The amount of histamine and eicosanoids released by PA was also two to three times less than the amount of mediators released by ovalbumin. When the trachea of normal guinea pigs was passively sensitized with serum from PA-ovalbumin-sensitized guinea pigs, it contracted in response to PA or ovalbumin in an organ bath. When the serum of PA-ovalbumin-sensitized guinea pigs was depleted of immunoglobulins and then used for passive sensitization of normal trachea, no contraction was observed when challenged with PA, suggesting that IgG1 antibodies mediate the tracheal reaction to PA.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Signaling pathways and cell mechanics involved in wound closure by epithelial cell sheets.

    Science.gov (United States)

    Fenteany, G; Janmey, P A; Stossel, T P

    2000-07-13

    Sheets of cells move together as a unit during wound healing and embryonic tissue movements, such as those occurring during gastrulation and neurulation. We have used epithelial wound closure as a model system for such movements and examined the mechanisms of closure and the importance of the Rho family of Ras-related small GTPases in this process. Wounds induced in Madin-Darby canine kidney (MDCK) epithelial cell monolayers close by Rac- and phosphoinositide-dependent cell crawling, with formation of lamellipodia at the wound margin, and not by contraction of a perimarginal actomyosin purse-string. Although Rho-dependent actin bundles usually form at the margin, neither Rho activity nor formation of these structures is required for wound closure to occur at a normal rate. Cdc42 activity is also not required for closure. Inhibition of Rho or Cdc42 results, however, in statistically significant decreases in the regularity of wound closure, as determined by the ratio of wound margin perimeter over the remaining denuded area at different times. The Rac-dependent force generation for closure is distributed over several rows of cells from the wound margin, as inhibition of motility in the first row of cells alone does not inhibit closure and can be compensated for by generation of motile force in cells behind the margin. Furthermore, we observed high levels of Rac-dependent actin assembly in the first few rows of cells from the wound margin. Wounds in MDCK cell sheets do not close by purse-string contraction but by a crawling behavior involving Rac, phosphoinositides and active movement of multiple rows of cells. This finding suggests a new distributed mode of signaling and movement that, nevertheless, resembles individual cell motility. Although Rho and Cdc42 activities are not required for closure, they have a role in determining the regularity of closure.

  13. Study of the mechanisms involved in the laser superficial hardening process of metallic alloys

    International Nuclear Information System (INIS)

    Silva, Edmara Marques Rodrigues da

    2001-01-01

    The laser superficial hardening process of a ferrous alloy (gray cast iron) and of an aluminum-silicon alloy was investigated in this work. These metallic alloys are used in the automobile industry for manufacturing cylinders and pistons, respectively. By application of individual pulses and single tracks, the involved mechanisms during the processing were studied. Variables such as energy density, power density, temporal width, beam diameter on the sample surface, atmosphere of the processing region, overlapping and scanning velocity. The hardened surface was characterized by optical and scanning electronic microscopy, dispersive energy microanalysis, X-ray mapping, X-ray diffraction, and measurements of roughness and Vickers microhardness. Depending on the processing parameters, it is possible to obtain different microstructures. The affected area of gray cast iron, can be hardened by remelting or transformation hardening (total or partial) if the reached temperature is higher or not that of melting temperature. Laser treatment originated new structures such as retained austenite, martensite and, occasionally, eutectic of cellular dendritic structure. Aluminum-silicon alloy does not have phase transformation in solid state, it can be hardened only by remelting. The increase of hardness is a function of the precipitation hardening process, which makes the silicon particles smaller and more disperse in the matrix. Maximal values of microhardness (700-1000 HV) were reached with the laser treatment in gray cast iron samples. The initial microhardness is of 242 HV. For aluminum-silicon alloy, the laser remelting increases the initial microhardness of 128 HV to the range of 160-320 HV. The found results give a new perspective for using the CLA/IPEN's laser in the heat treatment area. Besides providing a higher absorptivity to the materials, compared with the CO 2 laser, and optical fiber access, the superficial hardening with Nd:YAG laser, depending on the level of

  14. Achyranthes aspera Attenuates epilepsy in experimental animals: possible involvement of GABAergic mechanism.

    Science.gov (United States)

    Viswanatha, Gollapalle Lakshminarayanashastry; Venkataranganna, Marikunte V; Prasad, Nunna Bheema Lingeswara; Godavarthi, Ashok

    2017-06-01

    The present study was aimed to examine the possible anticonvulsant property of aerial parts of Achyranthes aspera using various experimental models of epilepsy in mice. Petroleum ether extract of aerial parts of A. aspera (PeAA), methanolic eAA (MeAA) and aqueous eAA (AeAA) was initially evaluated against six-hertz seizure model in mice, based on the outcomes the effective extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ) models in mice. In addition, the potent extract was evaluated against the PTZ model by co-administering with flumazenil (FMZ), and also evaluated for its effect on GABA levels in brain and NMDA-induced lethality in mice. Furthermore, the probable locomotor deficit-inducing property of the extract was evaluated by actophotometer test in mice. In results, only MeAA showed protection against six-hertz-induced seizures in mice, based on these outcomes only MeAA was evaluated in MES and PTZ models. Notably, the MeAA (200, 400 and 800 mg/kg) has offered mild and dose dependent protection against MES and PTZ-induced seizures in mice. Alongside, the MeAA (400 mg/kg) showed a significant increase in GABA levels in the brain compared to control, and in line with these findings the anti-PTZ effect of MeAA (400 mg/kg, p.o.) was blocked when co-administered with flumazenil (5 mg/kg, i.p.). However, the MeAA has not shown significant protection against NMDA-induced mortality and also did not cause significant change in locomotor activity compared to before treatment. These findings suggest that MeAA possess mild anticonvulsant activity and the outcomes further confirmed the involvement of GABAergic mechanism behind the anticonvulsant activity of MeAA.

  15. Mechanisms involved in the selective transfer of long chain polyunsaturted fatty acids to the fetus

    Directory of Open Access Journals (Sweden)

    Alfonso eGil-Sánchez

    2011-09-01

    Full Text Available The concentration of long chain polyunsaturated fatty acid (LCPUFA in the fetal brain increases dramatically from the third trimester until 18 months of life. Several studies have shown an association between the percentage of maternal plasma docosahexaenoic acid (DHA during gestation and development of the cognitive functions in the neonate. Since only very low levels of LCPUFA are synthesized in the fetus and placenta, their primary source for the fetus is that of maternal origin. Both in vitro and human in vivo studies using labelled fatty acids have shown the preferential transfer of LCPUFA from the placenta to the fetus compared with other fatty acids, although the mechanisms involved are still uncertain. The placenta takes up circulating maternal non-esterified fatty acids (NEFA and fatty acids released mainly by maternal lipoprotein lipase and endothelial lipase. These NEFA may enter the cell by passive diffusion or by means of membrane carrier proteins. Once in the cytosol, NEFA bind to cytosolic fatty acid-binding proteins for transfer to the fetal circulation or can be oxidized within the trophoblasts and even re-esterified and stored in lipid droplets (LD. Although trophoblast cells are not specialized in lipid storage, LCPUFA may up-regulate peroxisome proliferator activated receptor-γ (PPARγ and hence the gene expression of fatty acid transport carriers, fatty acid acyl-CoA synthetases and adipophilin or other enzymes related with lipolysis, modifying their rate of placental transfer and metabolization. The placental transfer of LCPUFA during pregnancy seems to be a key factor in the neurological development of the fetus. Increased knowledge on the factors that modify placental transfer of fatty acids would contribute to our understanding of this complex process.

  16. Mechanism of phytohormone involvement in feedback regulation of cotton leaf senescence induced by potassium deficiency.

    Science.gov (United States)

    Wang, Ye; Li, Bo; Du, Mingwei; Eneji, A Egrinya; Wang, Baomin; Duan, Liusheng; Li, Zhaohu; Tian, Xiaoli

    2012-10-01

    To elucidate the phytohormonal basis of the feedback regulation of leaf senescence induced by potassium (K) deficiency in cotton (Gossypium hirsutum L.), two cultivars contrasting in sensitivity to K deficiency were self- and reciprocally grafted hypocotyl-to-hypocotyl, using standard grafting (one scion grafted onto one rootstock), Y grafting (two scions grafted onto one rootstock), and inverted Y grafting (one scion grafted onto two rootstocks) at the seedling stage. K deficiency (0.03mM for standard and Y grafting, and 0.01mM for inverted Y grafting) increased the root abscisic acid (ABA) concentration by 1.6- to 3.1-fold and xylem ABA delivery rates by 1.8- to 4.6-fold. The K deficiency also decreased the delivery rates of xylem cytokinins [CKs; including the zeatin riboside (ZR) and isopentenyl adenosine (iPA) type] by 29-65% and leaf CK concentration by 16-57%. The leaf ABA concentration and xylem ABA deliveries were consistently greater in CCRI41 (more sensitive to K deficiency) than in SCRC22 (less sensitive to K deficiency) scions under K deficiency, and ZR- and iPA-type levels were consistently lower in the former than in the latter, irrespective of rootstock cultivar or grafting type, indicating that cotton shoot influences the levels of ABA and CKs in leaves and xylem sap. Because the scions had little influence on phytohormone levels in the roots (rootstocks) of all three types of grafts and rootstock xylem sap (collected below the graft union) of Y and inverted Y grafts, it appears that the site for basipetal feedback signal(s) involved in the regulation of xylem phytohormones is the hypocotyl of cotton seedlings. Also, the target of this feedback signal(s) is more likely to be the changes in xylem phytohormones within tissues of the hypocotyl rather than the export of phytohormones from the roots.

  17. Vacuolar Sequestration of Paraquat Is Involved in the Resistance Mechanism in Lolium perenne L. spp. multiflorum

    Science.gov (United States)

    Brunharo, Caio A. C. G.; Hanson, Bradley D.

    2017-01-01

    Lolium perenne L. spp. multiflorum (Lam.) Husnot (LOLMU) is a winter annual weed, common to row crops, orchards and roadsides. Glyphosate-resistant populations of LOLMU are widespread in California. In many situations, growers have switched to paraquat or other postemergence herbicides to manage glyphosate-resistant LOLMU populations. Recently, poor control of LOLMU with paraquat was reported in a prune orchard in California where paraquat has been used several times. We hypothesize that the low efficacy observed is due to the selection of a paraquat-resistant biotype of LOLMU. Greenhouse dose-response experiments conducted with a susceptible (S) and the putative paraquat-resistant biotype (PRHC) confirmed paraquat resistance in PRHC. Herbicide absorption studies indicated that paraquat is absorbed faster in S than PRHC, although the maximum absorption estimates were similar for the two biotypes. Conversely, translocation of 14C-paraquat under light-manipulated conditions was restricted to the treated leaf of PRHC, whereas herbicide translocation out of the treated leaf was nearly 20 times greater in S. To determine whether paraquat was active within the plant cells, the photosynthetic performance was assessed after paraquat application using the parameter maximum quantum yield of photosystem II (Fv/Fm). Paraquat reaches the chloroplasts of PRHC, since there was a transitory inhibition of photosynthetic activity in PRHC leaves. However, PRHC Fv/Fm recovered to initial levels by 48 h after paraquat treatment. No paraquat metabolites were found, indicating that resistance is not due to paraquat degradation. LOLMU leaf segments were exposed to paraquat following pretreatments with inhibitors of plasma membrane- and tonoplast-localized transporter systems to selectively block paraquat intracellular movement. Subsequent evaluation of membrane integrity indicated that pre-exposure to putrescine resulted in the resistant biotype responding to paraquat similarly to S

  18. The mechanisms of low nitrogen induced weakened photosynthesis in summer maize (Zea mays L.) under field conditions.

    Science.gov (United States)

    Wei, Shanshan; Wang, Xiangyu; Shi, Deyang; Li, Yanhong; Zhang, Jiwang; Liu, Peng; Zhao, Bin; Dong, Shuting

    2016-08-01

    Soil nitrogen (N) shortage is a problem which affects many developing nations. Crops grown with low soil N levels show a marked decrease in the rate of photosynthesis and this deficiency reduces crop yield significantly. Therefore, developing a better understanding of the mechanisms by which low N levels cause decreased photosynthesis is crucial for maize agriculture. To better understand this process, we assessed the responses of photosynthesis traits and enzymatic activities in the summer maize cultivar Denghai 618 under field conditions with and without the use of N fertilisers. We measured photosynthesis parameters, and compared proteome compositions to identify the mechanisms of physiological and biochemical adaptations to N deficiency in maize. We observed that parameters that indicated the rate of photosynthesis decreased significantly under N deficiency, and this response was associated with leaf senescence. Moreover, we identified 37 proteins involved in leaf photosynthesis, and found that N deficiency significantly affected light-dependent and light-independent reactions in maize leaf photosynthesis. Although further analysis is required to fully elucidate the roles of these proteins in the response to N deficiency, our study identified candidate proteins which may be involved in the regulatory mechanisms involved in reduced photosynthesis under low N conditions in maize. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Associative and sensorimotor learning for parenting involves mirror neurons under the influence of oxytocin.

    Science.gov (United States)

    Ho, S Shaun; Macdonald, Adam; Swain, James E

    2014-04-01

    Mirror neuron-based associative learning may be understood according to associative learning theories, in addition to sensorimotor learning theories. This is important for a comprehensive understanding of the role of mirror neurons and related hormone modulators, such as oxytocin, in complex social interactions such as among parent-infant dyads and in examples of mirror neuron function that involve abnormal motor systems such as depression.

  20. Associative and sensorimotor learning for parenting involves mirror neurons under the influence of oxytocin

    OpenAIRE

    Ho, S. Shaun; MacDonald, Adam; Swain, James E.

    2014-01-01

    Mirror neuron–based associative learning may be understood according to associative learning theories, in addition to sensorimotor learning theories. This is important for a comprehensive understanding of the role of mirror neurons and related hormone modulators, such as oxytocin, in complex social interactions such as among parent–infant dyads and in examples of mirror neuron function that involve abnormal motor systems such as depression.

  1. Finding candidate genes under positive selection in Non-model species: examples of genes involved in host specialization in pathogens.

    Science.gov (United States)

    Aguileta, G; Lengelle, J; Marthey, S; Chiapello, H; Rodolphe, F; Gendrault, A; Yockteng, R; Vercken, E; Devier, B; Fontaine, M C; Wincker, P; Dossat, C; Cruaud, C; Couloux, A; Giraud, T

    2010-01-01

    Numerous genes in diverse organisms have been shown to be under positive selection, especially genes involved in reproduction, adaptation to contrasting environments, hybrid inviability, and host-pathogen interactions. Looking for genes under positive selection in pathogens has been a priority in efforts to investigate coevolution dynamics and to develop vaccines or drugs. To elucidate the functions involved in host specialization, here we aimed at identifying candidate sequences that could have evolved under positive selection among closely related pathogens specialized on different hosts. For this goal, we sequenced c. 17,000-32,000 ESTs from each of four Microbotryum species, which are fungal pathogens responsible for anther smut disease on host plants in the Caryophyllaceae. Forty-two of the 372 predicted orthologous genes showed significant signal of positive selection, which represents a good number of candidate genes for further investigation. Sequencing 16 of these genes in 9 additional Microbotryum species confirmed that they have indeed been rapidly evolving in the pathogen species specialized on different hosts. The genes showing significant signals of positive selection were putatively involved in nutrient uptake from the host, secondary metabolite synthesis and secretion, respiration under stressful conditions and stress response, hyphal growth and differentiation, and regulation of expression by other genes. Many of these genes had transmembrane domains and may therefore also be involved in pathogen recognition by the host. Our approach thus revealed fruitful and should be feasible for many non-model organisms for which candidate genes for diversifying selection are needed.

  2. Under-Represented College Students and Extracurricular Involvement: The Effects of Various Student Organizations on Academic Performance

    Science.gov (United States)

    Baker, Christina N.

    2008-01-01

    Several studies indicate that students who are involved in extracurricular activities during college are more academically successful than are those who are not; however, most studies do not distinguish between different types of activities nor do they adequately consider the unique experiences of under-represented college students. Drawing on…

  3. Mechanisms involved in the association between periodontitis and complications in pregnancy.

    Directory of Open Access Journals (Sweden)

    Marcela eYang

    2015-01-01

    Full Text Available The association between periodontitis and gestation complications such as premature delivery, low weight at birth and preeclampsia has been suggested. Nevertheless, epidemiological data have shown contradictory data, mainly due to differences in clinical parameters of periodontitis assessment. Furthermore, differences in microbial composition and immune response between aggressive and chronic periodontitis are not addressed by these epidemiological studies. We aimed to review the current data on the association between gestation complications and periodontitis, and the mechanisms underlying this association. Shifts in the microbial composition of the subgingival biofilm may occur during pregnancy, leading to a potentially more hazardous microbial community. Pregnancy is characterized by physiological immune tolerance. However, the infection leads to a shift in maternal immune response to a pathogenic pro-inflammatory response, with production of inflammatory cytokines and toxic products. In women with periodontitis, the infected periodontal tissues may act as reservoirs of bacteria and their products which can disseminate to the fetus-placenta unit. In severe periodontitis patients, the infection agents and their products are able to activate inflammatory signaling pathways locally and in extra-oral sites, including the placenta-fetal unit, which may not only induce preterm labor, but also lead to preeclampsia and restrict intrauterine growth. Despite these evidences, the effectiveness of periodontal treatment in preventing gestational complications was still not established since it may be influenced by several factors such as severity of disease, composition of microbial community, treatment strategy, and period of treatment throughout pregnancy. This lack of scientific evidence does not exclude the need to control infection and inflammation in periodontitis patients during pregnancy, and treatment protocols should be validated.

  4. Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms

    Science.gov (United States)

    Bishayee, Anupam; Bhatia, Deepak; Thoppil, Roslin J.; Darvesh, Altaf S.; Nevo, Eviatar; Lansky, Ephraim P.

    2011-01-01

    Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC. Pomegranate, an ancient fruit, is gaining tremendous attention due to its powerful antioxidant properties. Here, we examined mechanism-based chemopreventive potential of a pomegranate emulsion (PE) against dietary carcinogen diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis that mimics human HCC. PE treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC. Both doses of PE significantly attenuated the number and area of γ-glutamyl transpeptidase-positive hepatic foci compared with the DENA control. PE also attenuated DENA-induced hepatic lipid peroxidation and protein oxidation. Mechanistic studies revealed that PE elevated gene expression of an array of hepatic antioxidant and carcinogen detoxifying enzymes in DENA-exposed animals. PE elevated protein and messenger RNA expression of the hepatic nuclear factor E2-related factor 2 (Nrf2). Our results provide substantial evidence, for the first time, that pomegranate constituents afford chemoprevention of hepatocarcinogenesis possibly through potent antioxidant activity achieved by upregulation of several housekeeping genes under the control of Nrf2 without toxicity. The outcome of this study strongly supports the development of pomegranate-derived products in the prevention and treatment of human HCC, which remains a devastating disease. PMID:21389260

  5. Formation of conical fractures in sedimentary basins: Experiments involving pore fluids and implications for sandstone intrusion mechanisms

    Science.gov (United States)

    Mourgues, R.; Bureau, D.; Bodet, L.; Gay, A.; Gressier, J. B.

    2012-01-01

    a flat cone. We make use of a P.I.V. (Particle Imaging Velocimetry) technique to analyse plastic deformation, showing that these inclined fractures are opened in mixed modes. Close to the surface, they change into steep shear bands where fluids can infiltrate. The final morphology of the fracture network is very similar to the common tripartite architecture of various injection complexes, indicating that different mechanisms may be involved in the formation of dykes. Feeder dykes under the sill zones may open as tensile fractures, while overlying dykes may be guided by the deformation induced by the growth of sills. These deformation conditions may also favour the formation of fluid escape structures and pockmarks.

  6. Liability for Sexual Harassment Involving Students under Federal Civil Rights Law.

    Science.gov (United States)

    Beckham, Joseph

    1995-01-01

    Discusses school district liability for sexual harassment under two provisions of federal law that are typically invoked as alternative bases for liability for sexual harassment: Title IX of the Education Amendments of 1972 and Section 1983 of the Civil Rights Act of 1964. (78 footnotes) (MLF)

  7. 77 FR 54584 - Final Action Under the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH...

    Science.gov (United States)

    2012-09-05

    ..., researchers in gene and cell therapy, and microbiologists. In addition, a day-long public discussion of the... changes. Human gene transfer also raises scientific, medical, social, and ethical considerations that... replicate does not raise significant biosafety concerns that warrant oversight under the NIH Guidelines...

  8. Mechanisms involved in the psychological distress of Black Caribbeans in the United States

    Science.gov (United States)

    Govia, Ishtar O.

    The mental health of ethnic minorities in the United States is of urgent concern. The accelerated growth of groups of ethnic minorities and immigrants in the United States and the stressors to which they are exposed, implores academic researchers to investigate more deeply health disparities and the factors that exacerbate or minimize such inequalities. This dissertation attended to that concern. It used data from the National Survey of American Life (NSAL), the first survey with a national representative sample of Black Caribbeans, to explore mechanisms that involved in the psychological distress of Black Caribbeans in the United States. In a series of three studies, the dissertation investigated the role and consequence of (1) chronic discrimination, immigration factors, and closeness to ethnic and racial groups; (2) personal control and social support; and (3) family relations and social roles in the psychological distress of Black Caribbeans. Study 1 examined how the associations between discrimination and psychological distress were buffered or exacerbated by closeness to ethnic group and closeness to racial group. It also examined how these associations differed depending on immigration factors. Results indicated that the buffering or exacerbating effect of ethnic and racial group closeness varied according to the type of discrimination (subtle or severe) and were more pronounced among those born in the United States. Using the stress process framework, Study 2 tested moderation and mediation models of the effects of social support and personal control in the association between discrimination and distress. Results from a series of analyses on 579 respondents suggested that personal control served as a mediator in this relationship and that emotional support exerted a direct distress deterring function. Study 3 investigated sex differences in the associations between social roles, intergenerational family relationship perceptions and distress. Results

  9. Protective effects of bellidifolin in hypoxia-induced in pheochromocytoma cells (PC12) and underlying mechanisms.

    Science.gov (United States)

    Zhao, Zhi-Ying; Gao, Yang-Yang; Gao, Li; Zhang, Ming; Wang, He; Zhang, Chun-Hong

    2017-01-01

    Bellidifolin, a xanthone compound derived from plants of Gentiana species, is known to exert a variety of pharmacological activities including anti-oxidation, anti-inflammatory and antitumor actions as well as a protective effect on cerebral ischemic nerve injury. The aim of this study was to examine the protective effects of bellidifolin on nerve injury produced by hypoxia and possible underlying mechanisms using pheochromocytoma cells (PC12). Data showed that the viability of PC12 cells subjected to hypoxia resulted in a significant decrease; however; pretreatment with certain concentrations of bellidifolin (20 or 40 μmol/L) prior to hypoxia significantly increased the survival rate. The results of immunohistochemical staining analysis revealed that there were no marked alterations in the expression of pERK protein between all bellidifolin groups while the expression of p-p38MAPK protein was significantly enhanced by hypoxia. Pretreatment with different concentrations of bellidifolin followed by hypoxia significantly decreased the expression of p-p38MAPK protein. The results of western blot analysis showed that hypoxia induced the expression of the MAPK signaling pathway downstream of the key apoptosis factor caspase-3. Compared to hypoxia, the expression of caspase-3 in the presence of belliidifolin was significantly lower. Data suggest that bellidifolin may contribute to the protective effects associated with nerve injury initiated by hypoxia by mechanisms related to inhibition of cell apoptosis independent of the ERK pathway, but may involve blockade of p38MAPK signaling pathway activation and downstream caspase-3 expression.

  10. Mechanisms Underlying the Antidepressant Response of Acupuncture via PKA/CREB Signaling Pathway.

    Science.gov (United States)

    Jiang, Huili; Zhang, Xuhui; Wang, Yu; Zhang, Huimin; Li, Jing; Yang, Xinjing; Zhao, Bingcong; Zhang, Chuntao; Yu, Miao; Xu, Mingmin; Yu, Qiuyun; Liang, Xingchen; Li, Xiang; Shi, Peng; Bao, Tuya

    2017-01-01

    Protein kinase A (PKA)/cAMP response element-binding (CREB) protein signaling pathway, contributing to impaired neurogenesis parallel to depressive-like behaviors, has been identified as the crucial factor involved in the antidepressant response of acupuncture. However, the molecular mechanisms associated with antidepressant response of acupuncture, neurogenesis, and depressive-like behaviors ameliorating remain unexplored. The objective was to identify the mechanisms underlying the antidepressant response of acupuncture through PKA signaling pathway in depression rats by employing the PKA signaling pathway inhibitor H89 in in vivo experiments. Our results indicated that the expression of hippocampal PKA- α and p-CREB was significantly downregulated by chronic unpredicted mild stress (CUMS) procedures. Importantly, acupuncture reversed the downregulation of PKA- α and p-CREB. The expression of PKA- α was upregulated by fluoxetine, but not p-CREB. No significant difference was found between Acu and FLX groups on the expression of PKA- α and p-CREB. Interestingly, H89 inhibited the effects of acupuncture or fluoxetine on upregulating the expression of p-CREB, but not PKA- α . There was no significant difference in expression of CREB among the groups. Conclusively, our findings further support the hypothesis that acupuncture could ameliorate depressive-like behaviors by regulating PKA/CREB signaling pathway, which might be mainly mediated by regulating the phosphorylation level of CREB.

  11. Frequency of cerebral infarction secondary to head injury and the underlying mechanisms: CT study

    International Nuclear Information System (INIS)

    Fernande-Fresno, L.; Manzanares, R.; Caniego, J.L.; Velasco, M.; Parra, M.L.; Monasterio, F.

    1997-01-01

    To study the frequency of and possible mechanisms producing severe head injury (HI) by serial CT studies. We reviewed brain CT results in 154 HI patients examined over the past 31 months. All of them were hospitalized in the Intensive Care Unit (ICU) presenting coma with Glosgow Coma Scale scores of 9 or under. A first CT scan was performed when the patients arrived in the emergency room and at a least one more was carried out over the following 1 to 6 days. Sixteen of the 154 patients presented ischemic areas of low attenuation in a territory of defined vascular distribution that did not exist in the CT done at admission; the majority of them also had extensive extraaxial or intraaxial hematomas causing a considerable mass effect and cerebral displacement inducing different types of herniation. The vascular territories involved were anterior cerebral artery in five cases, middle cerebral artery in two, posterior cerebral artery in seven lenticulostriate arteries in six, anterior choroidal artery in five, perforating thalamus in six, recurrent artery in one case and superior cerebellar artery in another. In our series, there was a high prevalence (10.4%) of infarcts associated with severe HI; the most common etiopathogenic mechanisms are cerebral displacement accompanied by compression and vessel strain. (Author) 13 refs

  12. Improvement of Learning and Memory Induced by Cordyceps Polypeptide Treatment and the Underlying Mechanism

    Directory of Open Access Journals (Sweden)

    Guangxin Yuan

    2018-01-01

    Full Text Available Our previous research revealed that Cordyceps militaris can improve the learning and memory, and although the main active ingredient should be its polypeptide complexes, the underlying mechanism of its activity remains poorly understood. In this study, we explored the mechanisms by which Cordyceps militaris improves learning and memory in a mouse model. Mice were given scopolamine hydrobromide intraperitoneally to establish a mouse model of learning and memory impairment. The effects of Cordyceps polypeptide in this model were tested using the Morris water maze test; serum superoxide dismutase activity; serum malondialdehyde levels; activities of acetyl cholinesterase, Na+-k+-ATPase, and nitric oxide synthase; and gamma aminobutyric acid and glutamate contents in brain tissue. Moreover, differentially expressed genes and the related cellular signaling pathways were screened using an mRNA expression profile chip. The results showed that the genes Pik3r5, Il-1β, and Slc18a2 were involved in the effects of Cordyceps polypeptide on the nervous system of these mice. Our findings suggest that Cordyceps polypeptide may improve learning and memory in the scopolamine-induced mouse model of learning and memory impairment by scavenging oxygen free radicals, preventing oxidative damage, and protecting the nervous system.

  13. Fracture mechanics in new designed power module under thermo-mechanical loads

    Directory of Open Access Journals (Sweden)

    Durand Camille

    2014-06-01

    Full Text Available Thermo-mechanically induced failure is a major reliability issue in the microelectronic industry. On this account, a new type of Assembly Interconnected Technology used to connect MOSFETs in power modules has been developed. The reliability is increased by using a copper clip soldered on the top side of the chip, avoiding the use of aluminium wire bonds, often responsible for the failure of the device. Thus the new designed MOSFET package does not follow the same failure mechanisms as standard modules. Thermal and power cycling tests were performed on these new packages and resulting failures were analyzed. Thermo-mechanical simulations including cracks in the aluminium metallization and intermetallics (IMC were performed using Finite Element Analysis in order to better understand crack propagation and module behaviour.

  14. Deciphering the molecular mechanisms underlying sea urchin reversible adhesion: A quantitative proteomics approach.

    Science.gov (United States)

    Lebesgue, Nicolas; da Costa, Gonçalo; Ribeiro, Raquel Mesquita; Ribeiro-Silva, Cristina; Martins, Gabriel G; Matranga, Valeria; Scholten, Arjen; Cordeiro, Carlos; Heck, Albert J R; Santos, Romana

    2016-04-14

    Marine bioadhesives have unmatched performances in wet environments, being an inspiration for biomedical applications. In sea urchins specialized adhesive organs, tube feet, mediate reversible adhesion, being composed by a disc, producing adhesive and de-adhesive secretions, and a motile stem. After tube foot detachment, the secreted adhesive remains bound to the substratum as a footprint. Sea urchin adhesive is composed by proteins and sugars, but so far only one protein, Nectin, was shown to be over-expressed as a transcript in tube feet discs, suggesting its involvement in sea urchin adhesion. Here we use high-resolution quantitative mass-spectrometry to perform the first study combining the analysis of the differential proteome of an adhesive organ, with the proteome of its secreted adhesive. This strategy allowed us to identify 163 highly over-expressed disc proteins, specifically involved in sea urchin reversible adhesion; to find that 70% of the secreted adhesive components fall within five protein groups, involved in exocytosis and microbial protection; and to provide evidences that Nectin is not only highly expressed in tube feet discs but is an actual component of the adhesive. These results give an unprecedented insight into the molecular mechanisms underlying sea urchin adhesion, and opening new doors to develop wet-reliable, reversible, and ecological biomimetic adhesives. Sea urchins attach strongly but in a reversible manner to substratum, being a valuable source of inspiration for industrial and biomedical applications. Yet, the molecular mechanisms governing reversible adhesion are still poorly studied delaying the engineering of biomimetic adhesives. We used the latest mass spectrometry techniques to analyze the differential proteome of an adhesive organ and the proteome of its secreted adhesive, allowing us to uncover the key players in sea urchin reversible adhesion. We demonstrate, that Nectin, a protein previously pointed out as potentially

  15. Ethylene and nitric oxide are involved in maintaining ion homeostasis in Arabidopsis callus under salt stress.

    Science.gov (United States)

    Wang, Huahua; Liang, Xiaolei; Wan, Qi; Wang, Xiaomin; Bi, Yurong

    2009-07-01

    In the present study, the role of ethylene in nitric oxide (NO)-mediated protection by modulating ion homeostasis in Arabidopsis callus under salt stress was investigated. Results showed that the ethylene-insensitive mutant etr1-3 was more sensitive to salt stress than the wild type (WT). Under 100 mM NaCl, etr1-3 callus displayed a greater electrolyte leakage and Na(+)/K(+) ratio but a lower plasma membrane (PM) H(+)-ATPase activity compared to WT callus. Application of exogenous 1-aminocyclopropane-1-carboxylic acid (ACC, an ethylene precursor) or sodium nitroprusside (SNP, a NO donor) alleviated NaCl-induced injury by maintaining a lower Na(+)/K(+) ratio and an increased PM H(+)-ATPase activity in WT callus but not in etr1-3 callus. The SNP actions in NaCl stress were attenuated by a specific NO scavenger or an ethylene biosynthesis inhibitor in WT callus. Under 100 mM NaCl, the NO accumulation and ethylene emission appeared at early time, and NO production greatly stimulated ethylene emission in WT callus. In addition, ethylene induced the expression of PM H(+)-ATPase genes under salt stress. The recovery experiment showed that NaCl-induced injury was reversible, as signaled by the similar recovery of Na(+)/K(+) ratio and PM H(+)-ATPase activity in WT callus. Taken together, the results indicate that ethylene and NO cooperate in stimulating PM H(+)-ATPase activity to modulate ion homeostasis for salt tolerance, and ethylene may be a part of the downstream signal molecular in NO action.

  16. A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-α

    Directory of Open Access Journals (Sweden)

    Dickinson Bryony A

    2009-06-01

    Full Text Available Abstract Background Long-term depression (LTD in the hippocampus can be induced by activation of different types of G-protein coupled receptors, in particular metabotropic glutamate receptors (mGluRs and muscarinic acethycholine receptors (mAChRs. Since mGluRs and mAChRs activate the same G-proteins and isoforms of phospholipase C (PLC, it would be expected that these two forms of LTD utilise the same molecular mechanisms. However, we find a distinct mechanism of LTD involving GRIP and liprin-α. Results Whilst both forms of LTD require activation of tyrosine phosphatases and involve internalisation of AMPARs, they use different molecular interactions. Specifically, mAChR-LTD, but not mGluR-LTD, is blocked by peptides that inhibit the binding of GRIP to the AMPA receptor subunit GluA2 and the binding of GRIP to liprin-α. Thus, different receptors that utilise the same G-proteins can regulate AMPAR trafficking and synaptic efficacy via distinct molecular mechanisms. Conclusion Our results suggest that mAChR-LTD selectively involves interactions between GRIP and liprin-α. These data indicate a novel mechanism of synaptic plasticity in which activation of M1 receptors results in AMPAR endocytosis, via a mechanism involving interactions between GluA2, GRIP and liprin-α.

  17. Transcriptional Regulation of Aluminum-Tolerance Genes in Higher Plants: Clarifying the Underlying Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Abhijit A. Daspute

    2017-08-01

    Full Text Available Aluminum (Al rhizotoxicity is one of the major environmental stresses that decrease global food production. Clarifying the molecular mechanisms underlying Al tolerance may contribute to the breeding of Al-tolerant crops. Recent studies identified various Al-tolerance genes. The expression of these genes is inducible by Al. Studies of the major Arabidopsis thaliana Al-tolerance gene, ARABIDOPSIS THALIANA ALUMINUM-ACTIVATED MALATE TRANSPORTER 1 (AtALMT1, which encodes an Al-activated malate transporter, revealed that the Al-inducible expression is regulated by a SENSITIVE TO PROTON RHIXOTOXICITY 1 (STOP1 zinc-finger transcription factor. This system, which involves STOP1 and organic acid transporters, is conserved in diverse plant species. The expression of AtALMT1 is also upregulated by several phytohormones and hydrogen peroxide, suggesting there is crosstalk among the signals involved in the transcriptional regulation of AtALMT1. Additionally, phytohormones and reactive oxygen species (ROS activate various transcriptional responses, including the expression of genes related to increased Al tolerance or the suppression of root growth under Al stress conditions. For example, Al suppressed root growth due to abnormal accumulation of auxin and cytokinin. It activates transcription of TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1 and other phytohormone responsive genes in distal transition zone, which causes suppression of root elongation. On the other hand, overexpression of Al inducible genes for ROS-detoxifying enzymes such as GLUTATHIONE–S-TRANSFERASE, PEROXIDASE, SUPEROXIDE DISMUTASE enhances Al resistance in several plant species. We herein summarize the complex transcriptional regulation of an Al-inducible genes affected by STOP1, phytohormones, and ROS.

  18. Mechanisms involved in the evasion of the host defence by Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Kharazmi, A

    1991-01-01

    Pseudomonas aeruginosa, an extracellular opportunistic pathogen, utilizes two major mechanisms to evade the host defence system. One of these mechanisms is the production of a large number of extracellular products, such as proteases, toxins, and lipases. The two proteases, alkaline protease and ...

  19. Ethylene promotes germination of Arabidopsis seed under salinity by decreasing reactive oxygen species: evidence for the involvement of nitric oxide simulated by sodium nitroprusside.

    Science.gov (United States)

    Lin, Yingchao; Yang, Lei; Paul, Matthew; Zu, Yuangang; Tang, Zhonghua

    2013-12-01

    Both ethylene and nitric oxide (NO) are involved in modulating seed germination in adverse environments. However, the mechanisms by which they interact and affect germination have not been explained. In this study, the relationship between ethylene and NO during germination of Arabidopsis seed under salinity was analysed. Application of exogenous 1-aminocyclopropane-1-carboxylate (ACC, a precursor of ethylene biosynthesis) or sodium nitroprusside (SNP, an NO donor) largely overcame the inhibition of germination induced by salinity. The effects of ACC and SNP were decreased by 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO), a specific NO scavenger, or by aminoisobutyric acid (AIB), an inhibitor of ethylene biosynthesis, indicating that ethylene and NO interact during germination under salinity. Further, we demonstrated that ACC increased NO production and that SNP greatly induced the expression of the ACS2 gene involved in ethylene synthesis in Arabidopsis seeds germinating under salinity stress, suggesting that each substance influences the production of the other. Application of exogenous ACC increased germination under oxidative stress induced by hydrogen peroxide (H2O2) while SNP had a much smaller effect on wild-type Arabidopsis (Col-0) and no effect on the ethylene insensitive mutant (ein3-1) seeds, respectively. This shows that NO increased germination under salinity indirectly through H2O2 acting via the ethylene pathway. The endogenous concentration of H2O2 was increased by salinity in germinating seeds but was decreased by exogenous ACC, which stimulated germination ultimately. To explain all these results and the regulation of germination of Arabidopsis seed under salinity we propose a model involving ethylene, NO and H2O2 interaction. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  20. Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

    Science.gov (United States)

    Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

    factors and are expressed during development, we hypothesized they may play a role newt tail regenerative morphogenesis under altered g-levels. Specifically there is increasing evidence for HSPs expression changes as a result of hyper-and microgravity. HSPs are also expressed throughout regeneration, rather than just after surgery. To test this hypothesis we performed heat shock on intact and regenerating newts and collected tail tissues. In these experiments we observed that some tails had uplifted tips while others mimicked hook-like regenerates at 1g or 2g. These findings suggest that heat shock, and HSPs induction, may be involved in the mechanism responsible for gravity effects on morphogenesis, or at least interact with them. Current work underway is focused on analyzing the expression of mRNA and localization of proteins for two members of the group, Hsp70 and Hsp90. In summary, we developed and characterized a new practical animal model in which gravity mechanostimulation at 1g, versus unloading in aquaria, causes prominent effects on newt tail regenerative morphogenesis. This model can be achieved without the use of a centrifuge, significantly simplifying its research applications. Initial results using this model suggest that induction of HSPs may be involved in gravity regulation of newt tail regenerative morphogenesis. Further research based on this simple model may help to unravel mechanisms of gravity influence relevant not only to newt tail regeneration, but also to a broad range of other biological processes in amphibian models.

  1. miR-126 Is Involved in Vascular Remodeling under Laminar Shear Stress

    Directory of Open Access Journals (Sweden)

    Ana Mondadori dos Santos

    2015-01-01

    Full Text Available Morphology and changes in gene expression of vascular endothelium are mainly due to shear stress and inflammation. Cell phenotype modulation has been clearly demonstrated to be controlled by small noncoding micro-RNAs (miRNAs. This study focused on the effect of laminar shear stress (LSS on human endothelial cells (HUVECs, with an emphasis on the role of miRNA-126 (miR-126. Exposure of HUVECs in vitro to LSS modified the shape of HUVECs and concomitantly regulated the expression of miR-126, vascular cell adhesion molecule 1 (VCAM-1, and syndecan-4 (SDC-4. A significant upregulation of miR-126 during long-term exposure to flow was shown. Interestingly, LSS enhanced SDC-4 expression on the HUVEC membranes. Overexpression of miR-126 in HUVECs decreased the levels of targets stromal cell-derived factor-1 SDF-1/CXCL12 and VCAM-1 but increased the expression of RGS16, CXCR4, and SDC-4. No significant difference in terms of cell proliferation and apoptosis was observed between scramble, anti-miR-126, and pre-miR-126 transfected HUVECs. In Apo-E KO/CKD mice aortas expressing a high level of miR-126, SDC-4 was concomitantly increased. In conclusion, our results suggest that miR-126 (i is overexpressed by long-term LSS, (ii has a role in up- and downregulation of genes involved in atherosclerosis, and (iii affects SDC-4 expression.

  2. Differential sulphur assimilation mechanism regulates response of Arabidopsis thaliana natural variation towards arsenic stress under limiting sulphur condition.

    Science.gov (United States)

    Khare, Ria; Kumar, Smita; Shukla, Tapsi; Ranjan, Avriti; Trivedi, Prabodh Kumar

    2017-09-05

    Arsenic (As) is a ubiquitous element, which imposes threat to crops productivity and human health through contaminated food chain. As a part of detoxification mechanism, As is chelated and sequestered into the vacuoles via sulphur containing compounds glutathione (GSH) and phytochelatins (PCs). Under limiting sulphur (LS) conditions, exposure of As leads to enhanced toxic effects in plants. Therefore, it is a prerequisite to understand molecular mechanisms involved in As stress response under sulphur deficiency conditions in plants. In recent years, natural variation has been utilized to explore the genetic determinants linked to plant development and stress response. In this study, natural variation in Arabidopsis has been utilized to understand the molecular mechanisms underlying LS and As(III) stress response. Analysis of different accession of Arabidopsis led to the identification of Koz2-2 and Ri-0 as the most tolerant and sensitive accessions, respectively, towards As(III) and LS+As(III) stress. Biochemical analysis and expression profiling of the genes responsible for sulphur transport and assimilation as well as metal detoxification and accumulation revealed significantly enhanced sulphur assimilation mechanism in Koz2-2 as compared to Ri-0. Analyses suggest that genetic variation regulates differential response of accessions towards As(III) under LS condition. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Swarming mechanisms in the yellow fever mosquito: aggregation pheromones involved in the mating behavior of Aedes aegypti

    Science.gov (United States)

    Mosquitoes of various species mate in swarms comprised of tens to thousands flying males. Yet little information is known about mosquito swarming mechanism. Discovering chemical cues involved in mosquito biology leads to better adaptation of disease control interventions. In this study, we aimed ...

  4. Interactivity effects in social media marketing on brand engagement: an investigation of underlying mechanisms

    NARCIS (Netherlands)

    Antheunis, M.L.; van Noort, G.; Eisend, M.; Langner, T.

    2011-01-01

    Although, SNS advertising spending increases, research on SNS campaigning is still underexposed. First, this study aims to investigate the effect of SNS campaign interactivity on the receivers brand engagement, taking four underlying mechanisms into account (brand identification, campaign

  5. Molecular mechanism for the involvement of nuclear receptor FXR in HBV-associated hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yong-dong Niu

    2011-08-01

    Full Text Available Farnesoid X receptor (FXR, also termed nuclear receptor NR1H4 is critically involved in the regulation of nascent bile formation and bile acid enterohepatic circulation. FXR and bile acids have been shown to play roles in liver regeneration and inflammatory responses. There is increasing evidence suggesting that FXR and the FXR signaling pathway are involved in the pathophysiology of a wide range of liver diseases, such as viral hepatitis, cirrhosis, and hepatocellular carcinoma (HCC. Here we discuss the latest discoveries of FXR functions with relevance to bile acid metabolism and HBV-associated HCC. More specifically, the goal of this review is to discuss the roles of FXR and bile acids in regulating HBV replication and how disregulation of the FXR-bile acid signaling pathway is involved in HBV-associated hepatocarcinogenesis.

  6. micro-mechanical experimental investigation and modelling of strain and damage of argillaceous rocks under combined hydric and mechanical loads

    International Nuclear Information System (INIS)

    Wang, L.

    2012-01-01

    The hydro-mechanical behavior of argillaceous rocks, which are possible host rocks for underground radioactive nuclear waste storage, is investigated by means of micro-mechanical experimental investigations and modellings. Strain fields at the micrometric scale of the composite structure of this rock, are measured by the combination of environmental scanning electron microscopy, in situ testing and digital image correlation technique. The evolution of argillaceous rocks under pure hydric loading is first investigated. The strain field is strongly heterogeneous and manifests anisotropy. The observed nonlinear deformation at high relative humidity (RH) is related not only to damage, but also to the nonlinear swelling of the clay mineral itself, controlled by different local mechanisms depending on RH. Irreversible deformations are observed during hydric cycles, as well as a network of microcracks located in the bulk of the clay matrix and/or at the inclusion-matrix interface. Second, the local deformation field of the material under combined hydric and mechanical loadings is quantified. Three types of deformation bands are evidenced under mechanical loading, either normal to stress direction (compaction), parallel (microcracking) or inclined (shear). Moreover, they are strongly controlled by the water content of the material: shear bands are in particular prone to appear at high RH states. In view of understanding the mechanical interactions a local scale, the material is modeled as a composite made of non-swelling elastic inclusions embedded in an elastic swelling clay matrix. The internal stress field induced by swelling strain incompatibilities between inclusions and matrix, as well as the overall deformation, is numerically computed at equilibrium but also during the transient stage associated with a moisture gradient. An analytical micro-mechanical model based on Eshelby's solution is proposed. In addition, 2D finite element computations are performed. Results

  7. Activated spinal astrocytes are involved in the maintenance of chronic widespread mechanical hyperalgesia after cast immobilization

    Science.gov (United States)

    2014-01-01

    Background In the present study, we examined spinal glial cell activation as a central nervous system mechanism of widespread mechanical hyperalgesia in rats that experienced chronic post-cast pain (CPCP) 2 weeks after cast immobilization. Activated spinal microglia and astrocytes were investigated immunohistologically in lumbar and coccygeal spinal cord segments 1 day, 5 weeks, and 13 weeks following cast removal. Results In the lumbar cord, astrocytes were activated after microglia. Astrocytes also were activated after microglia in the coccygeal cord, but with a delay that was longer than that observed in the lumbar cord. This activation pattern paralleled the observation that mechanical hyperalgesia occurred in the hindleg or the hindpaw before the tail. The activating transcription factor 3 (ATF3) immune response in dorsal root ganglia (DRG) on the last day of cast immobilization suggested that nerve damage might not occur in CPCP rats. The neural activation assessed by the phosphorylated extracellular signal-regulated kinase (pERK) immune response in DRG arose 1 day after cast removal. In addition, L-α-aminoadipate (L-α-AA), an inhibitor of astrocyte activation administered intrathecally 5 weeks after cast removal, inhibited mechanical hyperalgesia in several body parts including the lower leg skin and muscles bilaterally, hindpaws, and tail. Conclusions These findings suggest that activation of lumbar cord astrocytes is an important factor in widespread mechanical hyperalgesia in CPCP. PMID:24456903

  8. Microbial Mechanisms Underlying Acidity-induced Reduction in Soil Respiration Under Nitrogen Fertilization

    Science.gov (United States)

    Niu, S.; Li, Y.

    2016-12-01

    Terrestrial ecosystems are receiving increasing amounts of reactive nitrogen (N) due to anthropogenic activities, which largely changes soil respiration and its feedback to climate change. N enrichment can not only increase N availability but also induce soil acidification, both may affect soil microbial activity and root growth with a consequent impact on soil respiration. However, it remains unclear whether elevated N availability or soil acidity has greater impact on soil respiration (Rs). We conducted a manipulative experiment to simulate N enrichment (10 g m-2 yr-1 NH4NO3) and soil acidity (0.552 mol H+ m-2 yr-1 sulfuric acid) and studied their effects on Rs and its components in a temperate forest. Our results showed that soil pH was reduced by 0.2 under N addition or acid addition treatment. Acid addition significantly decreased autotrophic respiration (Ra) and heterotrophic respiration (Rh) by 21.5% and 22.7% in 2014, 34.8% and 21.9% in 2015, respectively, resulting in a reduction of Rs by 22.2% in 2014 and 26.1% in 2015. Nitrogen enrichment reduced Ra, Rh, Rs by 21.9%, 16.2%, 18.6% in 2014 and 22.1%, 5.9%, 11.7% in 2015, respectively. The reductions of Rs and its components were attributable to decrease of fine root biomass, microbial biomass, and cellulose degrading enzymes. N addition did not change microbial community but acid addition increased both fungal and arbuscular mycorrhiza fungi PLFAs, and N plus acid addition significantly enhanced fungal to bacterial ratio. All the hydrolase enzymes were reduced more by soil acidity (43-50%) than nitrogen addition (30-39%). Structural equation model showed that soil acidity played more important role than N availability in reducing soil respiration mainly by changing microbial extracellular enzymes. We therefore suggest that N deposition induced indirect effect of soil acidification on microbial properties is critical and should be taken into account to better understand and predict ecosystem C cycling in

  9. Cognitive mechanisms underlying disorganization of thought in a genetic syndrome (47,XXY)

    NARCIS (Netherlands)

    Van Rijn, Sophie; Aleman, Andre; De Sonneville, Leo; Swaab, Hanna

    Because of the risk for development of psychopathology such as psychotic symptoms, it has been suggested that studying men with the XXY karyotype may help in the search for underlying cognitive, neural and genetic mechanisms. The aim of this study was to identify cognitive mechanisms that may

  10. STATIC AND DYNAMIC ANALYSIS UNDER MECHANICAL AND THERMAL LOADS OF THE DOUBLE SCARA ROBOT

    Directory of Open Access Journals (Sweden)

    Iosif TEMPEA

    2016-05-01

    Full Text Available The paper presents a synthesis of the Double SCARA Robot modelling, leading to an optimal solution, from workspace point of view, as well as precision and stability of the endeffector in performing the planned trajectory. For the design of the final mechanism CATIA software has been used, as well as NASTRAN/PATRAN software, for the mechanism analysis under mechanical and thermal loads.

  11. The effects of different size gold nanoparticles on mechanical properties of vascular smooth muscle cells under mechanical stretching

    Science.gov (United States)

    Kieu, Tri Minh

    Nanotechnology is an emerging and promising frontier for medicine and biomedical research due to its potential for applications such as drug delivery, imaging enhancement, and cancer treatment. While these materials may possess significant possibilities, the effects of these particles in the body and how the particles affect the cells is not fully understood. In this study, vascular smooth muscle cells (VSMCs) will be exposed to 5 and 20 nm diameter citrate AuNPs under mechanical conditions. The cytotoxicity properties of these particles will be investigated using LDH and MTT assays. Atomic force microscopy will be used to study how the size of the nanoparticles affect the mechanical properties of the VSMCs. Immunofluorescence staining for alpha actin will also be performed to enhance understanding of the phenotypic shift. The LDH and MTT cytotoxicity assay results demonstrated that neither 5 nor 20 nm diameter nanoparticles are cytotoxic to the cells. However, the mechanical properties and cell morphology of the VSMCs was altered. Under static conditions, both AuNP treatments decreased the mechanical properties of the cells. The size of the nanoparticles had a softening effect on elastic modulus of the cell and sign of a synthetic phenotype was observed. The VSMCs subjected to mechanical stretching exhibited higher elastic modulus compared to the static experimental groups. Again, both AuNPs treatments decreased the mechanical properties of the cells and signs of more synthetic phenotype was seen. However, the size of the nanoparticles did not have any influence on cell's elastic modulus unlike the static treated cells. The mechanical testing condition provided a better look at how these particles would affect the cells in vivo. While the nanoparticles are not cytotoxic to the VSMCs, they are altering the mechanical properties and phenotype of the cell.

  12. Up-date on neuro-immune mechanisms involved in allergic and non-allergic rhinitis

    NARCIS (Netherlands)

    van Gerven, L.; Boeckxstaens, G.; Hellings, P.

    2012-01-01

    Non-allergic rhinitis (NAR) is a common disorder, which can be defined as chronic nasal inflammation, independent of systemic IgE-mediated mechanisms. Symptoms of NAR patients mimic those of allergic rhinitis (AR) patients. However, AR patients can easily be diagnosed with skin prick test or

  13. Different mechanisms are involved in the antibody mediated inhibition of ligand binding to the urokinase receptor

    DEFF Research Database (Denmark)

    List, K; Høyer-Hansen, G; Rønne, E

    1999-01-01

    Certain monoclonal antibodies are capable of inhibiting the biological binding reactions of their target proteins. At the molecular level, this type of effect may be brought about by completely different mechanisms, such as competition for common binding determinants, steric hindrance or interfer...

  14. Neural mechanisms underlying migrating motor complex formation in mouse isolated colon

    Science.gov (United States)

    Brierley, Stuart M; Nichols, Kim; Grasby, Dallas J; Waterman, Sally A

    2001-01-01

    Little is known about the intrinsic enteric reflex pathways associated with migrating motor complex (MMC) formation. Acetylcholine (ACh) mediates the rapid component of the MMC, however a non-cholinergic component also exists. The present study investigated the possible role of endogenous tachykinins (TKs) in the formation of colonic MMCs and the relative roles of excitatory and inhibitory pathways.MMCs were recorded from the circular muscle at four sites (proximal, proximal-mid, mid-distal and distal) along the mouse colon using force transducers.The tachykinin (NK1 and NK2) receptor antagonists SR-140 333 (250 nM) and SR-48 968 (250 nM) reduced the amplitude of MMCs at all recording sites, preferentially abolishing the long duration contraction. Residual MMCs were abolished by the subsequent addition of atropine (1 μM).The neuronal nitric oxide synthase inhibitor, Nωnitro-L-arginine (L-NOARG, 100 μM), increased MMC amplitude in the distal region, whilst reducing the amplitude in the proximal region. In preparations where MMCs did not migrate to the distal colon, addition of L-NOARG resulted in the formation of MMCs. Subsequent addition of apamin (250 nM) or suramin (100 μM) further increased MMC amplitude in the distal region, whilst suramin increased MMC amplitude in the mid-distal region. Apamin but not suramin reduced MMC amplitude in the proximal region. Subsequent addition of SR-140 333 and SR-48 968 reduced MMC amplitude at all sites. Residual MMCs were abolished by atropine (1 μM).In conclusion, TKs, ACh, nitric oxide (NO) and ATP are involved in the neural mechanisms underlying the formation of MMCs in the mouse colon. Tachykinins mediate the long duration component of the MMC via NK1 and NK2 receptors. Inhibitory pathways may be involved in determining whether MMCs are formed. PMID:11159701

  15. [Biological effects of arsenic and diseases: The mechanisms involved in arsenic-induced carcinogenesis].

    Science.gov (United States)

    Suzuki, Takehiro; Takumi, Shota; Okamura, Kazuyuki; Nohara, Keiko

    2016-07-01

    Chronic arsenic exposure is associated with many diseases, including cancers. Our study using in vivo assay in gpt-delta transgenic mice showed that arsenic particularly induces G : C to T : A transversions, a mutation type induced through oxidative-stress-induced 8-OHdG formation. Gestational arsenic exposure of C3H mice was reported to increase hepatic tumor incidence. We showed that gestational arsenic exposure increased hepatic tumors having activated oncogene Ha-ras by C to A mutation. We also showed that DNA methylation status of Fosb region is implicated in tumor augmentation by gestational arsenic exposure. We further showed that long-term arsenic exposure induces premature senescence. Recent studies reported that senescence is involved in not only tumor suppression, but also tumorgenesis. All these effects of arsenic might be involved in arsenic-induced carcinogenesis.

  16. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    DEFF Research Database (Denmark)

    Wong, Mei Mei Jaslyn Elizabeth; Midtgaard, Søren Roi; Gysel, Kira

    2015-01-01

    LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multi......LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement...... solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers...

  17. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

    Directory of Open Access Journals (Sweden)

    Cibele S Borges

    Full Text Available Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin

  18. Study of the effects of dietary polyunsaturated fatty acids: Molecular mechanisms involved intestinal inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Knoch, B.; Barnett, M. P. G.; Roy, N. C.; McNabb, W. C.

    2009-07-01

    The use of omics techniques in combination with model systems and molecular tools allows to understand how foods and food components act on metabolic pathways to regulate transcriptional processes. Polyunsaturated fatty acids have distinctive nutritional and metabolic effects because they give rise to lipid mediated products and affect the expression of various genes involved in intestinal inflammation. The present review focuses on the molecular effects of dietary polyunsaturated fatty acids on intestinal inflammation. (Author) 74 refs.

  19. VIGS for dissecting mechanisms involved in the symbiotic interaction of microbes with plants

    DEFF Research Database (Denmark)

    Grønlund, Mette

    2015-01-01

    Virus-induced gene silencing (VIGS) is an alternative reverse genetics tool for silencing of genes in some plants which are difficult to transform. The pea early browning virus (PEBV) has been developed as a VIGS vector and used in pea for functional analysis of several genes. Here, a PEBV-VIGS p......-VIGS protocol is described which is suitable for reverse genetics studies in pea for genes involved in the symbiosis with arbuscular mycorrhizal fungi and Rhizobium....

  20. Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

    Science.gov (United States)

    Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

    2017-10-01

    Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

  1. Mechanisms underlying reductant-induced reactive oxygen species formation by anticancer copper(II) compounds.

    Science.gov (United States)

    Kowol, Christian R; Heffeter, Petra; Miklos, Walter; Gille, Lars; Trondl, Robert; Cappellacci, Loredana; Berger, Walter; Keppler, Bernhard K

    2012-03-01

    Intracellular generation of reactive oxygen species (ROS) via thiol-mediated reduction of copper(II) to copper(I) has been assumed as the major mechanism underlying the anticancer activity of copper(II) complexes. The aim of this study was to compare the anticancer potential of copper(II) complexes of Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone; currently in phase II clinical trials) and its terminally dimethylated derivative with that of 2-formylpyridine thiosemicarbazone and that of 2,2'-bipyridyl-6-carbothioamide. Experiments on generation of oxidative stress and the influence of biologically relevant reductants (glutathione, ascorbic acid) on the anticancer activity of the copper complexes revealed that reductant-dependent redox cycling occurred mainly outside the cells, leading to generation and dismutation of superoxide radicals resulting in cytotoxic amounts of H(2)O(2). However, without extracellular reductants only weak intracellular ROS generation was observed at IC(50) levels, suggesting that cellular thiols are not involved in copper-complex-induced oxidative stress. Taken together, thiol-induced intracellular ROS generation might contribute to the anticancer activity of copper thiosemicarbazone complexes but is not the determining factor.

  2. Molecular mechanisms underlying monosynaptic sensory-motor circuit development in the spinal cord.

    Science.gov (United States)

    Imai, Fumiyasu; Yoshida, Yutaka

    2018-04-01

    Motor behaviors are precisely controlled by the integration of sensory and motor systems in the central nervous system (CNS). Proprioceptive sensory neurons, key components of the sensory system, are located in the dorsal root ganglia and project axons both centrally to the spinal cord and peripherally to muscles and tendons, communicating peripheral information about the body to the CNS. Changes in muscle length detected by muscle spindles, and tension variations in tendons conveyed by Golgi tendon organs, are communicated to the CNS through group Ia /II, and Ib proprioceptive sensory afferents, respectively. Group Ib proprioceptive sensory neurons connect with motor neurons indirectly through spinal interneurons, whereas group Ia/II axons form both direct (monosynaptic) and indirect connections with motor neurons. Although monosynaptic sensory-motor circuits between spindle proprioceptive sensory neurons and motor neurons have been extensively studied since 1950s, the molecular mechanisms underlying their formation and upkeep have only recently begun to be understood. We will discuss our current understanding of the molecular foundation of monosynaptic circuit development and maintenance involving proprioceptive sensory neurons and motor neurons in the mammalian spinal cord. Developmental Dynamics 247:581-587, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Circulatory mechanisms underlying adaptive increases in thermogenic capacity in high-altitude deer mice.

    Science.gov (United States)

    Tate, Kevin B; Ivy, Catherine M; Velotta, Jonathan P; Storz, Jay F; McClelland, Grant B; Cheviron, Zachary A; Scott, Graham R

    2017-10-15

    We examined the circulatory mechanisms underlying adaptive increases in thermogenic capacity in deer mice ( Peromyscus maniculatus ) native to the cold hypoxic environment at high altitudes. Deer mice from high- and low-altitude populations were born and raised in captivity to adulthood, and then acclimated to normoxia or hypobaric hypoxia (simulating hypoxia at ∼4300 m). Thermogenic capacity [maximal O 2 consumption ( V̇ O 2 ,max ), during cold exposure] was measured in hypoxia, along with arterial O 2 saturation ( S a O 2 ) and heart rate ( f H ). Hypoxia acclimation increased V̇ O 2 ,max by a greater magnitude in highlanders than in lowlanders. Highlanders also had higher S a O 2  and extracted more O 2 from the blood per heartbeat (O 2 pulse= V̇ O 2 ,max / f H ). Hypoxia acclimation increased f H , O 2 pulse and capillary density in the left ventricle of the heart. Our results suggest that adaptive increases in thermogenic capacity involve integrated functional changes across the O 2 cascade that augment O 2 circulation and extraction from the blood. © 2017. Published by The Company of Biologists Ltd.

  4. Mechanisms underlying cognitive conspicuity in the detection of cyclists by car drivers.

    Science.gov (United States)

    Rogé, Joceline; Ndiaye, Daniel; Aillerie, Isabelle; Aillerie, Stéphane; Navarro, Jordan; Vienne, Fabrice

    2017-07-01

    The aim of this study was to evaluate the visibility of cyclists for motorists in a simulated car driving task. In several cases involving collisions between cars and cyclists, car drivers failed to detect the latter in time to avoid collision because of their low conspicuity. 2 groups of motorists (29.2 years old), including 12 cyclist-motorists and 13 non-cyclist-motorists, performed a vulnerable road user detection task in a car-driving simulator. They had to detect cyclists and pedestrians in an urban setting and evaluate the realism of the cyclists, the traffic, the city, the infrastructure, the car driven and the situations. Cyclists appeared in critical situations derived from previous accounts given by injured cyclists and from cyclists' observations in real-life situations. Cyclist's levels of visibility for car drivers were either high or low in these situations according to the cyclists. Realism scores were similar and high in both groups. Cyclist-motorists had fewer collisions with cyclists and detected cyclists at a greater distance in all situations, irrespective of cyclist visibility. Several mechanisms underlying the cognitive conspicuity of cyclists for car drivers were considered. The attentional selection of a cyclist in the road environment during car driving depends on top-down processing. We consider the practical implications of these results for the safety of vulnerable road users and future directions of research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Intermittent vibration protects aged muscle from mechanical and oxidative damage under prolonged compression.

    Science.gov (United States)

    Wong, Sing Wan; Cheung, Brian Chun Ho; Pang, Bruce Tak Keung; Kwong, Ateline; Chung, Anna; Lee, Kenneth Ka Ho; Mak, Arthur Fut Tak

    2017-04-11

    Deep tissue pressure ulcers, a serious clinical challenge originating in the muscle layer, are hardly detectable at the beginning. The challenge apparently occurs in aged subjects more frequently. As the ulcer propagates to the skin surface, it becomes very difficult to manage and can lead to fatal complications. Preventive measures are thus highly desirable. Although the complex pathological mechanisms have not been fully understood, prolonged and excessive physical challenges and oxidative stress are believed to be involved in the ulcer development. Previous reports have demonstrated that oxidative stress could compromise the mechanical properties of muscle cells, making them easier to be damaged when physical challenges are introduced. In this study, we used senescence accelerated (SAMP8) mice and its control breed (SAMR1) to examine the protective effects of intermittent vibration on aged and control muscle tissues during prolonged epidermal compression under 100mmHg for 6h. Results showed that an application of 35Hz, 0.25g intermittent vibration during compression decreased the compression-induced muscle breakdown in SAMP8 mice, as indicated histologically in terms of number of interstitial nuclei. The fact that no significant difference in muscle damage could be established in the corresponding groups in SAMR1 mice suggests that SAMR1 mice could better accommodate the compression insult than SAMP8 mice. Compression-induced oxidative damage was successfully curbed using intermittent vibration in SAMP8 mice, as indicated by 8-OHdG. A possible explanation is that the anti-oxidative defense could be maintained with intermittent vibration during compression. This was supported by the expression level of PGC-1-alpha, catalase, Gpx-1 and SOD1. Our data suggested intermittent vibration could serve as a preventive measure for deep tissue ulcer, particularly in aged subjects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Developmental Exposure to Pesticides Alters Motor Activity and Coordination in Rats: Sex Differences and Underlying Mechanisms.

    Science.gov (United States)

    Gómez-Giménez, B; Felipo, V; Cabrera-Pastor, A; Agustí, A; Hernández-Rabaza, V; Llansola, M

    2018-02-01

    It has been proposed that developmental exposure to pesticides contributes to increasing prevalence of neurodevelopmental disorders in children, such as attention deficit with hyperactivity (ADHD) and to alterations in coordination skills. However, the mechanisms involved in these alterations remain unclear. We analyzed the effects on spontaneous motor activity and motor coordination of developmental exposure to a representative pesticide of each one of the four main chemical families: organophosphates (chlorpyrifos), carbamates (carbaryl), organochlorines (endosulfan), and pyrethroids (cypermethrin). Pesticides were administered once a day orally, in a sweet jelly, from gestational day 7 to post natal day 21. Spontaneous motor activity was assessed by an actimeter and motor coordination using the rotarod, when rats were adults. The effects were analyzed separately in males and females. Extracellular GABA in cerebellum and NMDA receptor subunits in hippocampus were assessed as possible underlying mechanisms of motor alterations. Motor coordination was impaired by developmental exposure to endosulfan, cypermethrin, and chlorpyrifos in females but not in males. The effect of endosulfan and cypermethrin would be due to increased extracellular GABA in cerebellum, which remains unaltered in male rats. Chlorpyrifos increased motor activity in males and females. Cypermethrin decreased motor activity mainly in males. In male rats, but not in females, expression of the NR2B subunit of NMDA receptor in hippocampus correlated with motor activity. These results show sex-specific effects of different pesticides on motor activity and coordination, associated with neurotransmission alterations. These data contribute to better understand the relationship between developmental exposure to the main pesticide families and motor disorders in children.

  7. Mechanisms underlying food-drug interactions: inhibition of intestinal metabolism and transport.

    Science.gov (United States)

    Won, Christina S; Oberlies, Nicholas H; Paine, Mary F

    2012-11-01

    Food-drug interaction studies are critical to evaluate appropriate dosing, timing, and formulation of new drug candidates. These interactions often reflect prandial-associated changes in the extent and/or rate of systemic drug exposure. Physiologic and physicochemical mechanisms underlying food effects on drug disposition are well-characterized. However, biochemical mechanisms involving drug metabolizing enzymes and transport proteins remain underexplored. Several plant-derived beverages have been shown to modulate enzymes and transporters in the intestine, leading to altered pharmacokinetic (PK) and potentially negative pharmacodynamic (PD) outcomes. Commonly consumed fruit juices, teas, and alcoholic drinks contain phytochemicals that inhibit intestinal cytochrome P450 and phase II conjugation enzymes, as well as uptake and efflux transport proteins. Whereas myriad phytochemicals have been shown to inhibit these processes in vitro, translation to the clinic has been deemed insignificant or undetermined. An overlooked prerequisite for elucidating food effects on drug PK is thorough knowledge of causative bioactive ingredients. Substantial variability in bioactive ingredient composition and activity of a given dietary substance poses a challenge in conducting robust food-drug interaction studies. This confounding factor can be addressed by identifying and characterizing specific components, which could be used as marker compounds to improve clinical trial design and quantitatively predict food effects. Interpretation and integration of data from in vitro, in vivo, and in silico studies require collaborative expertise from multiple disciplines, from botany to clinical pharmacology (i.e., plant to patient). Development of more systematic methods and guidelines is needed to address the general lack of information on examining drug-dietary substance interactions prospectively. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Comparison of mechanical and thermodynamic properties of fcc and bcc titanium under high pressure

    Science.gov (United States)

    Zhang, Yongmei; Zhao, Yuhong; Hou, Hua; Wen, Zhiqin; Duan, Meiling

    2018-02-01

    The mechanical and thermodynamic properties of fcc and bcc Ti have been discussed based on the first-principles calculation combined with the quasi-harmonic Debye model. We find that the bulk modulus B, shear modulus G, Young’s modulus E of fcc Ti are larger, while Poisson’s ratio σ is smaller than that of bcc Ti under the same pressure, which indicates the better mechanical performance of fcc Ti compared with bcc Ti. The values of B/G and σ indicate that mechanically stable fcc structure is much less ductile than the bcc structure, while mechanically metastable fcc structure has better ductility than stable bcc structure under high pressure. The normalized volume, isothermal bulk modulus, heat capacity, volume thermal expansion coefficient and Debye temperature under pressure and temperature for fcc and bcc Ti are predicted.

  9. Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease.

    Science.gov (United States)

    Grover, Harpreet Singh; Luthra, Shailly

    2013-05-01

    Both diabetes and periodontitis are chronic diseases. Diabetes has many adverse effects on the periodontium, and conversely periodontitis may have deleterious effects further aggravating the condition in diabetics. The potential common pathophysiologic pathways include those associated with inflammation, altered host responses, altered tissue homeostasis, and insulin resistance. This review examines the relationship that exists between periodontal diseases and diabetes mellitus with a focus on potential common pathophysiologic mechanisms.

  10. MECHANISMS INVOLVED IN THE ASSOCIATION BETWEEN PERIDONTAL DISEASES AND CARDIOVASCULAR DISEASE

    OpenAIRE

    Teles, Ricardo; Wang, Cun-Yu

    2011-01-01

    It is now well accepted that besides the cholesterol associated mechanisms of atherogenesis, inflammation plays a crucial role in all stages of the development of the atherosclerotic lesion. This “inflammation hypothesis” raises the possibility that, through systemic elevations of pro-inflammatory cytokines, periodontal diseases might also contribute to systemic inflammation and, therefore, to atherogenesis. In fact, there is evidence that periodontal diseases are associated with higher syste...

  11. A new bacterial staining method involving Gram stain with theoretical considerations of the staining mechanism.

    Science.gov (United States)

    Noda, Y; Tôei, K

    1992-01-01

    In order to investigate the mechanism of Gram staining of bacteria, tests with anionic dyes followed by treatment with cationic octyltrimethylammonium (OTMA) were carried out. The study revealed that tetrabromophenolphthalein ethylester (TBPE) gave the most reliable staining of Gram-negative bacteria with negative staining of Gram-positive bacteria. Tests on many species of bacteria showed that TBPE positive bacteria were Gram-negative and vice versa, without exception.

  12. Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease

    Science.gov (United States)

    Grover, Harpreet Singh; Luthra, Shailly

    2013-01-01

    Both diabetes and periodontitis are chronic diseases. Diabetes has many adverse effects on the periodontium, and conversely periodontitis may have deleterious effects further aggravating the condition in diabetics. The potential common pathophysiologic pathways include those associated with inflammation, altered host responses, altered tissue homeostasis, and insulin resistance. This review examines the relationship that exists between periodontal diseases and diabetes mellitus with a focus on potential common pathophysiologic mechanisms. PMID:24049328

  13. Involvement of Arabidopsis Prolyl 4 Hydroxylases in Hypoxia, Anoxia and Mechanical Wounding

    OpenAIRE

    Vlad, Florina; Spano, Thodhoraq; Vlad, Daniela; Daher, Firas Bou; Ouelhadj, Akli; Fragkostefanakis, Sotirios; Kalaitzis, Panagiotis

    2007-01-01

    Arabidopsis prolyl 4 hydroxylases (P4Hs) catalyze an important post-translational modification in plants, though the only information on their patterns of expression is solely based on Arabidopsis microarray analysis data. In addition, the expression patterns of plants P4Hs in response to hypoxia, anoxia and other abiotic stresses such as mechanical wounding have never been studied extensively, despite their central role in hypoxic response of several other organisms through the regulation of...

  14. Involvement of glucokinase translocation in the mechanism by which resorcinol inhibits glycolysis in hepatocytes.

    OpenAIRE

    Agius, L

    1997-01-01

    Proglycosyn and resorcinol stimulate glycogen synthesis and inhibit glycolysis in hepatocytes. The former effect is attributed to inactivation of phosphorylase mediated by glucuronidated metabolites. This study investigated the mechanism by which resorcinol inhibits glycolysis. Resorcinol (150 microM) inhibited glycolysis in hepatocytes incubated with glucose (15-35 mM) but not with dihydroxyacetone (10 mM). The inhibition of glycolysis at elevated glucose concentration was associated with in...

  15. Involvement of epigenetic mechanisms in the development of posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Tomaž Zupanc

    2012-03-01

    victims with no childhood abuse were found. It was suggested that changes in glucocorticoid system are mediated by tissue-specific changes in gene expression. Recent studies suggest that epigenetic mechanisms may play an important role in the interplay between stress exposure and genetic vulnerability. Conclusions: Integrating epigenetics into a model that permits prior experience to have a central role in determining individual differences is also consistent with a developmental perspective of PTSD vulnerability.

  16. Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease

    Directory of Open Access Journals (Sweden)

    Harpreet Singh Grover

    2013-01-01

    Full Text Available Both diabetes and periodontitis are chronic diseases. Diabetes has many adverse effects on the periodontium, and conversely periodontitis may have deleterious effects further aggravating the condition in diabetics. The potential common pathophysiologic pathways include those associated with inflammation, altered host responses, altered tissue homeostasis, and insulin resistance. This review examines the relationship that exists between periodontal diseases and diabetes mellitus with a focus on potential common pathophysiologic mechanisms.

  17. Mechanisms involved in the association between periodontal diseases and cardiovascular disease.

    Science.gov (United States)

    Teles, R; Wang, C-Y

    2011-07-01

    It is now well accepted that besides the cholesterol associated mechanisms of atherogenesis, inflammation plays a crucial role in all stages of the development of the atherosclerotic lesion. This 'inflammation hypothesis' raises the possibility that through systemic elevations of pro-inflammatory cytokines, periodontal diseases might also contribute to systemic inflammation and, therefore, to atherogenesis. In fact, there is evidence that periodontal diseases are associated with higher systemic levels of high-sensitivity C-reactive protein and a low grade systemic inflammation. This phenomenon has been explained based on mechanisms associated with either the infectious or the inflammatory nature of periodontal diseases. The purposes of this article were to review (1) the evidence suggesting a role for oral bacterial species, particularly periodontal pathogens, in atherogenesis; (2) the potential mechanisms explaining an etiological role for oral bacteria in atherosclerosis; (3) the evidence suggesting that periodontal infections are accompanied by a heightened state of systemic inflammation; (4) the potential sources of systemic inflammatory biomarkers associated with periodontal diseases; and (5) the effects of periodontal therapy on systemic inflammatory biomarkers and cardiovascular risk. © 2011 John Wiley & Sons A/S.

  18. Different mechanisms are involved in the antibody mediated inhibition of ligand binding to the urokinase receptor

    DEFF Research Database (Denmark)

    List, K; Høyer-Hansen, G; Rønne, E

    1999-01-01

    or interference with conformational properties of the receptor critical for ligand binding. This distinction is central when employing the antibodies as tools in the elucidation of the structure-function relationship of the protein in question. We have studied the effect of monoclonal antibodies against......PA/uPAR complex. The continuous recording of binding and dissociation, obtained in BIA, is central in characterizing these phenomena. The identification of a non-competitive inhibitory mechanism against this receptor reveals the presence of a determinant which influences the binding properties of a remote site...

  19. A novel mechanism involved in the coupling of mitochondrial biogenesis to oxidative phosphorylation

    Directory of Open Access Journals (Sweden)

    Jelena Ostojić

    2014-01-01

    Full Text Available Mitochondria are essential organelles that are central to a multitude of cellular processes, including oxidative phosphorylation (OXPHOS, which produces most of the ATP in animal cells. Thus it is important to understand not only the mechanisms and biogenesis of this energy production machinery but also how it is regulated in both physiological and pathological contexts. A recent study by Ostojić et al. [Cell Metabolism (2013 18, 567-577] has uncovered a regulatory loop by which the biogenesis of a major enzyme of the OXPHOS pathway, the respiratory complex III, is coupled to the energy producing activity of the mitochondria.

  20. The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamicpituitary- adrenal axis activity in female rats

    OpenAIRE

    Švob Štrac, Dubravka; Muck-Šeler, Dorotea

    2012-01-01

    Aim To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity. Methods Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α2-adrenoreceptor agonist), yohimbine (α2-adrenoreceptor antagonist), alpha-methylp- tyrosine (α-MPT, an inhibitor of ca...

  1. Swarming Mechanisms in the Yellow Fever Mosquito: Aggregation Pheromones are Involved in the Mating Behavior of Aedes aegypti

    Science.gov (United States)

    2014-12-01

    Vol. 39, no. 2 Journal of Vector Ecology 347 Swarming mechanisms in the yellow fever mosquito: aggregation pheromones are involved in the mating...Downes 1966, Provost and Haeger 1967), Aedes albopictus (Nijhot and Craig 1971), Culiseta inornata (Kliewer et al. 1966, Lang and Foster 1976), and some...aegypti Linnaeus is one of the most medically important mosquitoes as the main vector of dengue, chikungunya, and yellow fever viruses, in addition to its

  2. Identification and Characterization of the Phage Gene sav, Involved in Sensitivity to the Lactococcal Abortive Infection Mechanism AbiV

    DEFF Research Database (Denmark)

    Haaber, Jakob Brandt Borup; Rousseau, G. M.; Hammer, Karin

    2009-01-01

    Lactococcus lactis phage mutants that are insensitive to the recently characterized abortive infection mechanism AbiV were isolated and analyzed in an effort to elucidate factors involved in the sensitivity to AbiV. Whole-genome sequencing of the phage mutants p2.1 and p2.2 revealed mutations...... effect. Conserved, evolutionarily related regions in SaV polypeptides of different phage groups are likely to be responsible for the AbiV-sensitive phenotype and the toxicity....

  3. Mechanical behaviour and microstructural evolution of alloy 800H under biaxial cyclic loading

    International Nuclear Information System (INIS)

    Dolabella Portella, P.; Feng Jiao; Oesterle, W.; Ziebs, J.

    1999-01-01

    The mechanical behaviour of alloy 800H under biaxial cyclic loading was investigated at room temperature and at 800 C. The low-cycle fatigue experiments were carried out using tubular specimens under axial and torsional loading with constant total equivalent strain amplitude following either proportional or nonproportional loading paths. The cyclic hardening observed under nonproportional loading was clearly higher than that under proportional loading. The extra hardening due to the nonproportional loading path was more pronounced at room temperature. The evolution of the dislocation structure was characterized by transmission electron microscopy of specimens after interrupted fatigue tests. The changes in the dislocation structure and the precipitation phenomena are in accordance with the observed mechanical behaviour of the specimens. Twinning was observed in very few grains of some specimens and does not influence the extra hardening under nonproportional loading, martensite was not detected in any specimen. (orig.)

  4. Mechanism of Anti-glioblastoma Effect of Temzolomide Involved in ROS-Mediated SIRT 1 Pathway

    Directory of Open Access Journals (Sweden)

    Yuan Jiang

    2014-03-01

    Full Text Available Objective: To explore the new molecular mechanism of anti-tumor effect of temzolomide (TMZon glioblastoma cell strain. Methods: MTT methods and Hoechst 33342 staining method were applied to determine the effect of TMZ on the proliferation and apoptosis of glioblastoma cell strains U251 and SHG44, while flow cytometry was used to detect the impact of TMZ on cellular cycles. Additionally, DCFH-DA probe was adopted to test intracellular reactive oxygen species (ROS level while Real-time PCR and Western blot tests were applied to determine the influence of TMZ on SIRT1 expression. Results: TMZ in different concentrations added into glioblastoma cell strain for 72 h could concentration-dependently inhibit the proliferation of glioblastoma cells, 100 μmol/L of which could also block cells in phase G2/M and improve cellular apoptosis. In addition, TMZ could evidently increase intracellular ROS level so as to activate SIRT1. Conclusion: The mechanism of anti-tumor effect of TMZ on glioblastoma may be associated with ROS-induced SIRT1 pathway, providing theoretical basis for the clinical efficacy of TMZ.

  5. Intersections of pathways involving biotin and iron relative to therapeutic mechanisms for progressive multiple sclerosis.

    Science.gov (United States)

    Heidker, Rebecca M; Emerson, Mitchell R; LeVine, Steven M

    2016-12-01

    While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression. We suggest one reason that a greater percentage of patients with MS didn't respond to biotin therapy is the inaccessibility or lack of other nutrients, such as iron. In addition to biotin, iron (or heme) is necessary for energy production, biosynthesis of cholesterol and lipids, and for some protective mechanisms. Both biotin and iron are required for myelination during development, and by inference, remyelination. However, iron can also play a role in the pathology of MS. Increased deposition of iron can occur in some CNS structures possibly promoting oxidative damage while low iron levels can occur in other areas. Thus, the potential, detrimental effects of iron need to be considered together with the need for iron to support metabolic demands associated with repair and/or protective processes. We propose the optimal utilization of iron may be necessary to maximize the beneficial effects of biotin. This review will examine the interactions between biotin and iron in pathways that may have therapeutic or pathogenic implications for MS.

  6. Possible Mechanisms Involved in Attenuation of Lipopolysaccharide-Induced Memory Deficits by Methyl Jasmonate in Mice.

    Science.gov (United States)

    Eduviere, Anthony Taghogho; Umukoro, Solomon; Adeoluwa, Olusegun A; Omogbiya, Itivere Adrian; Aluko, Oritoke Modupe

    2016-12-01

    This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.

  7. Sensitizing Children to the Social and Emotional Mechanisms involved in Racism: a program evaluation

    Directory of Open Access Journals (Sweden)

    Sofia Triliva

    2014-11-01

    Full Text Available This paper describes and discusses the results of an intervention aiming to sensitize children to the social and emotional processes involved in racism. The intervention was applied and evaluated in 10 Greek elementary schools. The goals and the intervention methods of the program modules are briefly outlined and the results of the program evaluation are elaborated and discussed. Two-hundred students participated in the program and 180 took part in the pre-and-post-testing which assessed their ability to identify emotions associated with prejudice, discrimination and stereotypical thinking; to understand similarities and differences between people; and to develop perspective taking and empathic skills in relation to diverse others. Results indicate gains in all three areas of assessment although the increased ability to identify similarities between people can also be attributed to age/grade effects. The implications of the findings are discussed with regard to antiracism intervention methods and evaluation strategies.

  8. Oriented scanning is the leading mechanism underlying 5' splice site selection in mammals

    NARCIS (Netherlands)

    Borensztajn, Keren; Sobrier, Marie-Laure; Duquesnoy, Philippe; Fischer, Anne-Marie; Tapon-Bretaudière, Jacqueline; Amselem, Serge

    2006-01-01

    Splice site selection is a key element of pre-mRNA splicing. Although it is known to involve specific recognition of short consensus sequences by the splicing machinery, the mechanisms by which 5' splice sites are accurately identified remain controversial and incompletely resolved. The human F7

  9. INSTRUMENTS AND METHODS OF INVESTIGATION: Physical mechanisms underlying the selective removal of atoms

    Science.gov (United States)

    Gurovich, Boris A.; Prikhod'ko, Kirill E.

    2009-02-01

    This paper reviews the current understanding of the selective removal of atoms (SRA), a technique that uses ion irradiation to controllably change the chemical composition and properties of polyatomic materials. The main effects involved and the possible mechanisms that govern the process are discussed. It is shown that SRA holds great promise for manufacturing functional nanoelements.

  10. Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats

    Science.gov (United States)

    Zhang, Xiao-Yang; Yu, Lei; Zhuang, Qian-Xing; Peng, Shi-Yu; Zhu, Jing-Ning; Wang, Jian-Jun

    2013-01-01

    Background and Purpose Anti-histaminergic drugs have been widely used in the clinical treatment of vestibular disorders and most studies concentrate on their presynaptic actions. The present study investigated the postsynaptic effect of histamine on medial vestibular nucleus (MVN) neurons and the underlying mechanisms. Experimental Approach Histamine-induced postsynaptic actions on MVN neurons and the corresponding receptor and ionic mechanisms were detected by whole-cell patch-clamp recordings on rat brain slices. The distribution of postsynaptic histamine H1, H2 and H4 receptors was mapped by double and single immunostaining. Furthermore, the expression of mRNAs for H1, H2 and H4 receptors and for subtypes of Na+–Ca2+ exchangers (NCXs) and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels was assessed by quantitative real-time RT-PCR. Key Results A marked postsynaptic excitatory effect, co-mediated by histamine H1 and H2 receptors, was involved in the histamine-induced depolarization of MVN neurons. Postsynaptic H1 and H2 rather than H4 receptors were co-localized in the same MVN neurons. NCXs contributed to the inward current mediated by H1 receptors, whereas HCN channels were responsible for excitation induced by activation of H2 receptors. Moreover, NCX1 and NCX3 rather than NCX2, and HCN1 rather than HCN2-4 mRNAs, were abundantly expressed in MVN. Conclusion and Implications NCXs coupled to H1 receptors and HCN channels linked to H2 receptors co-mediate the strong postsynaptic excitatory action of histamine on MVN neurons. These results highlight an active role of postsynaptic mechanisms in the modulation by central histaminergic systems of vestibular functions and suggest potential targets for clinical treatment of vestibular disorders. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 PMID:23713466

  11. RNA sequencing of Populus x canadensis roots identifies key molecular mechanisms underlying physiological adaption to excess zinc.

    Directory of Open Access Journals (Sweden)

    Andrea Ariani

    Full Text Available Populus x canadensis clone I-214 exhibits a general indicator phenotype in response to excess Zn, and a higher metal uptake in roots than in shoots with a reduced translocation to aerial parts under hydroponic conditions. This physiological adaptation seems mainly regulated by roots, although the molecular mechanisms that underlie these processes are still poorly understood. Here, differential expression analysis using RNA-sequencing technology was used to identify the molecular mechanisms involved in the response to excess Zn in root. In order to maximize specificity of detection of differentially expressed (DE genes, we consider the intersection of genes identified by three distinct statistical approaches (61 up- and 19 down-regulated and validate them by RT-qPCR, yielding an agreement of 93% between the two experimental techniques. Gene Ontology (GO terms related to oxidation-reduction processes, transport and cellular iron ion homeostasis were enriched among DE genes, highlighting the importance of metal homeostasis in adaptation to excess Zn by P. x canadensis clone I-214. We identified the up-regulation of two Populus metal transporters (ZIP2 and NRAMP1 probably involved in metal uptake, and the down-regulation of a NAS4 gene involved in metal translocation. We identified also four Fe-homeostasis transcription factors (two bHLH38 genes, FIT and BTS that were differentially expressed, probably for reducing Zn-induced Fe-deficiency. In particular, we suggest that the down-regulation of FIT transcription factor could be a mechanism to cope with Zn-induced Fe-deficiency in Populus. These results provide insight into the molecular mechanisms involved in adaption to excess Zn in Populus spp., but could also constitute a starting point for the identification and characterization of molecular markers or biotechnological targets for possible improvement of phytoremediation performances of poplar trees.

  12. An investigation of the mechanism underlying teacher aggression : Testing I3 theory and the General Aggression Model

    NARCIS (Netherlands)

    Montuoro, Paul; Mainhard, Tim

    2017-01-01

    Background: Considerable research has investigated the deleterious effects of teachers responding aggressively to students who misbehave, but the mechanism underlying this dysfunctional behaviour remains unknown. Aims: This study investigated whether the mechanism underlying teacher aggression

  13. Tensile mechanical behavior of hollow and filled carbon nanotubes under tension or combined tension-torsion

    Science.gov (United States)

    Jeong, Byeong-Woo; Lim, Jang-Keun; Sinnott, Susan B.

    2007-01-01

    The tensile mechanical behavior of hollow and filled single-walled carbon nanotubes under tension or combined tension-torsion is examined using classical molecular dynamics simulations. These simulations indicate that the tensile strength under combined tension-torsion can be increased by filling the carbon nanotubes, and the amount of this increase depends on the kind of filling material. They also predict that the tensile strength under combined tension-torsion decreases linearly under applied torsion. The tensile strength can be modified by adjusting the system temperature and through chemical functionalization to the carbon nanotube walls.

  14. Calcium ion involvement in growth inhibition of mechanically stressed soybean (Glycine max) seedlings

    Science.gov (United States)

    Jones, R. S.; Mitchell, C. A.

    1989-01-01

    A 40-50% reduction in soybean [Glycine max (L.) Merr. cv. Century 84] hypocotyl elongation occurred 24 h after application of mechanical stress. Exogenous Ca2+ at 10 mM inhibited growth by 28% if applied with the Ca2+ ionophore A23187 to the zone of maximum hypocotyl elongation. La3+ was even more inhibitory than Ca2+, especially above 5 mM. Treatment with ethyleneglycol-bis-(beta-aminoethylether)-N, N, N', N'-tetraacetic acid (EGTA) alone had no effect on growth of non-stressed seedlings at the concentrations used but negated stress-induced growth reduction by 36% at 4 mM when compared to non-treated, stressed controls. Treatment with EDTA was ineffective in negating stress-induced growth inhibition. Calmodulin antagonists calmidazolium, chlorpromazine, and 48/80 also negated stress-induced growth reduction by 23, 50, and 35%, respectively.

  15. Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system.

    Science.gov (United States)

    Kibria, Golam; Hatakeyama, Hiroto; Harashima, Hideyoshi

    2014-01-01

    Multidrug resistance (MDR), the principal mechanism by which many cancers develop resistance to chemotherapy, is one of the major obstacles to the successful clinical treatment of various types of cancer. Several key regulators are responsible for mediating MDR, a process that renders chemotherapeutic drugs ineffective in the internal organelles of target cells. A nanoparticulate drug delivery system (DDS) is a potentially promising tool for circumventing such MDR, which can be achieved by targeting tumor cells themselves or tumor endothelial cells that support the survival of MDR cancer cells. The present article discusses key factors that are responsible for MDR in cancer cells, with a specific focus on the application of DDS to overcome MDR via the use of chemotherapy or macromolecules.

  16. Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Alline C. Campos

    2017-05-01

    Full Text Available Beneficial effects of cannabidiol (CBD have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. The mechanisms responsible for these effects, however, are still poorly understood. Similar to clinical antidepressant or atypical antipsychotic drugs, recent findings clearly indicate that CBD, either acutely or repeatedly administered, induces plastic changes. For example, CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress and prevents microglia activation and the decrease in the number of parvalbumin-positive GABA neurons in a pharmacological model of schizophrenia. More recently, it was found that CBD modulates cell fate regulatory pathways such as autophagy and others critical pathways for neuronal survival in neurodegenerative experimental models, suggesting the potential benefit of CBD treatment for psychiatric/cognitive symptoms associated with neurodegeneration. These changes and their possible association with CBD beneficial effects in psychiatric disorders are reviewed here.

  17. Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

    Science.gov (United States)

    Gaut, Carrie; Sugaya, Kiminobu

    2015-01-01

    Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

  18. Mechanisms Involved in Thromboxane A2-induced Vasoconstriction of Rat Intracavernous Small Penile Arteries

    DEFF Research Database (Denmark)

    Grann, Martin; Comerma Steffensen, Simon Gabriel; Arcanjo, Daniel Dias Rufino

    2015-01-01

    by activation of thromboxane receptors concentration-dependently increased calcium and contraction. U46619-induced calcium influx was blocked by nifedipine, a blocker of L-type calcium channels, and by 2-aminoethoxydiphenyl borate, a blocker of transient receptor potential (TRP) channels. Inhibitors of ROCK, Y...... relaxation in rat mesenteric arteries. Our findings suggest that U46619 contraction depends on Ca2+ influx through L-type and TRP channels, and ROCKdependent mechanisms in penile arteries. Inhibition of the ROCK pathway is a potential approach for the treatment of erectile dysfunction associated......Diabetes is associated with erectile dysfunction and with hypercontractility in erectile tissue and this is in part ascribed to increased formation of thromboxane. Rho kinase (ROCK) is a key regulator of calcium sensitization and contraction in vascular smooth muscle. This study investigated...

  19. Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women.

    Science.gov (United States)

    Ma, Yidan; Zhao, Guang; Tu, Shen; Zheng, Yong

    2015-01-01

    A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females) in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed.

  20. Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women.

    Directory of Open Access Journals (Sweden)

    Yidan Ma

    Full Text Available A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed.

  1. Involvement of glucokinase translocation in the mechanism by which resorcinol inhibits glycolysis in hepatocytes.

    Science.gov (United States)

    Agius, L

    1997-01-01

    Proglycosyn and resorcinol stimulate glycogen synthesis and inhibit glycolysis in hepatocytes. The former effect is attributed to inactivation of phosphorylase mediated by glucuronidated metabolites. This study investigated the mechanism by which resorcinol inhibits glycolysis. Resorcinol (150 microM) inhibited glycolysis in hepatocytes incubated with glucose (15-35 mM) but not with dihydroxyacetone (10 mM). The inhibition of glycolysis at elevated glucose concentration was associated with inhibition of glucose-induced dissociation of glucokinase and aldolase. The resorcinol concentration that caused half-maximal inhibition (20-43 microM) increased with increasing glucose concentration (15-35 mM). Resorcinol inhibited the translocation of glucokinase and the stimulation of detritiation of [2-3H]glucose and [3-3H]glucose caused by sorbitol (10-200 microM), but it potentiated the stimulation of glycogen synthesis. The inhibition of glycolysis by resorcinol could not be accounted for by diversion of substrate to glycogen. The glucose 6-phosphate content correlated with the free glucokinase activity. Resorcinol counteracted the increase in glucose 6-phosphate and fructose 2,6-bisphosphate caused by elevated glucose concentration or by sorbitol. The suppression of glucose 6-phosphate at high glucose concentration (15-35 mM) could be explained by the low activity of free glucokinase. However, the suppression at 5 mM glucose was due in part to an independent mechanism. The effect of resorcinol on glucokinase translocation was partly counteracted by galactosamine, which suppresses UDP-glucose and inhibits glucuronide formation, and was mimicked by phenol and p-nitrophenol but not by p-nitrophenylglucuronide. It is concluded that resorcinol inhibits glycolysis at elevated glucose concentration or when stimulated by sorbitol through increased glucokinase binding. The results indicate a link between glucuronidation and glucokinase translocation. PMID:9271087

  2. Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women

    Science.gov (United States)

    Ma, Yidan; Zhao, Guang; Tu, Shen; Zheng, Yong

    2015-01-01

    A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females) in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed. PMID:26309232

  3. Involvement of Glycogen Synthase Kinase-3 in the Mechanisms of Conditioned Food Aversion Memory Reconsolidation.

    Science.gov (United States)

    Nikitin, V P; Solntseva, S V; Kozyrev, S A

    2017-02-01

    Experiments were performed on the snails trained in conditioned food aversion for 3 days. Injection of TDZD-8 (glycogen synthase kinase-3 inhibitor, 2 mg/kg) in combination with reminder (presentation of a conditioned food stimulus) led to memory impairment developing 3 days after inhibitor/reminder exposure and followed by spontaneous recovery in 10 days. Injections of TDZD-8 in a dose of 4 or 20 mg/kg before reminder were shown to cause amnesia that persisted for more than 10 days. Memory recovery during repeated training was observed at the earlier period than after initial training. The impairment of memory reconsolidation by TDZD-8 after training of snails for 1 day was less pronounced than under standard training conditions (3 days). The effect of a glycogen synthase kinase-3 inhibitor during memory reconsolidation is probably followed by impairment of memory retrieval and/or partial loss, which can be compensated spontaneously or after repeated training.

  4. Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids☆

    Science.gov (United States)

    Harrison, Earl H.

    2012-01-01

    Vitamin A is an essential nutrient for humans and is converted to the visual chromophore, 11-cis-retinal, and to the hormone, retinoic acid. Vitamin A in animal-derived foods is found as long chain acyl esters of retinol and these are digested to free fatty acids and retinol before uptake by the intestinal mucosal cell. The retinol is then reesterified to retinyl esters for incorporation into chlylomicrons and absorbed via the lymphatics or effluxed into the portal circulation facilitated by the lipid transporter, ABCA1. Provitamin A carotenoids such as β-carotene are found in plant-derived foods. These and other carotenoids are transported into the mucosal cell by scavenger receptor class B type I (SR-BI). Provitamin A carotenoids are partly converted to retinol by oxygenase and reductase enzymes and the retinol so produced is available for absorption via the two pathways described above. The efficiency of vitamin A and carotenoid intestinal absorption is determined by the regulation of a number of proteins involved in the process. Polymorphisms in genes for these proteins lead to individual variability in the metabolism and transport of vitamin A and carotenoids. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism. PMID:21718801

  5. Epigenetic mechanisms involved in the effects of stress exposure: focus on 5-hydroxymethylcytosine.

    Science.gov (United States)

    Hack, Laura M; Dick, Alec L W; Provençal, Nadine

    2016-08-01

    5-hydroxymethylcytosine (5hmC) is a recently re-discovered transient intermediate in the active demethylation pathway that also appears to play an independent role in modulating gene function. Epigenetic marks, particularly 5-methylcytosine, have been widely studied in relation to stress-related disorders given the long-lasting effect that stress has on these marks. 5hmC is a good candidate for involvement in the etiology of these disorders given its elevated concentration in mammalian neurons, its dynamic regulation during development of the central nervous system, and its high variability among individuals. Although we are unaware of any studies published to date examining 5 hmC profiles in human subjects who have developed a psychiatric disorder after a life stressor, there is emerging evidence from the animal literature that 5hmC profiles are altered in the context of fear-conditioning paradigms and stress exposure, suggesting a possible role for 5hmC in the biological underpinnings of stress-related disorders. In this review, the authors examine the available approaches for profiling 5hmC and describe their advantages and disadvantages as well as discuss the studies published thus far investigating 5hmC in the context of fear-related learning and stress exposure in animals. The authors also highlight the global versus locus-specific regulation of 5hmC in these studies. Finally, the limitations of the current studies and their implications are discussed.

  6. Evolutionary mechanisms involved in the virulence of infectious salmon anaemia virus (ISAV), a piscine orthomyxovirus

    International Nuclear Information System (INIS)

    Markussen, Turhan; Jonassen, Christine Monceyron; Numanovic, Sanela; Braaen, Stine; Hjortaas, Monika; Nilsen, Hanne; Mjaaland, Siri

    2008-01-01

    Infectious salmon anaemia virus (ISAV) is an orthomyxovirus causing a multisystemic, emerging disease in Atlantic salmon. Here we present, for the first time, detailed sequence analyses of the full-genome sequence of a presumed avirulent isolate displaying a full-length hemagglutinin-esterase (HE) gene (HPR0), and compare this with full-genome sequences of 11 Norwegian ISAV isolates from clinically diseased fish. These analyses revealed the presence of a virulence marker right upstream of the putative cleavage site R 267 in the fusion (F) protein, suggesting a Q 266 → L 266 substitution to be a prerequisite for virulence. To gain virulence in isolates lacking this substitution, a sequence insertion near the cleavage site seems to be required. This strongly suggests the involvement of a protease recognition pattern at the cleavage site of the fusion protein as a determinant of virulence, as seen in highly pathogenic influenza A virus H5 or H7 and the paramyxovirus Newcastle disease virus

  7. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Jaslyn E. M. M. [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Midtgaard, Søren Roi [University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark); Gysel, Kira [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Thygesen, Mikkel B.; Sørensen, Kasper K.; Jensen, Knud J. [University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Stougaard, Jens; Thirup, Søren; Blaise, Mickaël, E-mail: mickael.blaise@cpbs.cnrs.fr [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)

    2015-03-01

    The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

  8. How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

    Science.gov (United States)

    Truini, Andrea; Cruccu, Giorgio

    2016-02-01

    Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

  9. Visualization of hot spot formation in energetic materials under periodic mechanical excitation using phosphor thermography

    Science.gov (United States)

    Casey, Alex; Fenoglio, Gabriel; Detrinidad, Humberto

    2017-06-01

    Under mechanical excitation, energy is known to localize within an energetic material resulting in `hot spot' formation. While many formation mechanisms have been proposed, additional insight to heat generation mechanisms, the effect of binder/crystal interfaces, and predication capabilities can be gained by quantifying the initiation and growth of the hot spots. Phosphor thermography is a well established temperature sensing technique wherein an object's temperature is obtained by collecting the temperature dependent luminescence of an optically excited phosphor. Herein, the phosphor thermography technique has been applied to Dow Corning Sylgard® 184/octahydro 1,3,5,7 tetranitro 1,3,5,7 tetrazocine (HMX) composite materials under mechanical excitation in order to visualize the evolution of the temperature field, and thus hot spot formation, within the binder. Funded by AFOSR. Supported by the Department of Defense (DoD) through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program.

  10. A Cross-Cultural Approach to Psychological Mechanisms Underlying Emotional Reactions to Music

    OpenAIRE

    Barradas, Gonçalo

    2017-01-01

    Music plays a crucial role in everyday life by enabling listeners to seek individual emotional experiences. To explain why such emotions occur, we must understand the underlying process that mediates between surface-level features of the music and aroused emotions. This thesis aimed to investigate how musical emotions are mediated by psychological mechanisms from a cross-cultural perspective. Study I manipulated four mechanisms by selecting ecologically valid pieces of music that featured inf...

  11. Potential markers and metabolic processes involved in the mechanism of radiation-induced heart injury.

    Science.gov (United States)

    Slezak, Jan; Kura, Branislav; Babal, Pavel; Barancik, Miroslav; Ferko, Miroslav; Frimmel, Karel; Kalocayova, Barbora; Kukreja, Rakesh C; Lazou, Antigone; Mezesova, Lucia; Okruhlicova, Ludmila; Ravingerova, Tanya; Singal, Pawan K; Szeiffova Bacova, Barbara; Viczenczova, Csilla; Vrbjar, Norbert; Tribulova, Narcis

    2017-10-01

    Irradiation of normal tissues leads to acute increase in reactive oxygen/nitrogen species that serve as intra- and inter-cellular signaling to alter cell and tissue function. In the case of chest irradiation, it can affect the heart, blood vessels, and lungs, with consequent tissue remodelation and adverse side effects and symptoms. This complex process is orchestrated by a large number of interacting molecular signals, including cytokines, chemokines, and growth factors. Inflammation, endothelial cell dysfunction, thrombogenesis, organ dysfunction, and ultimate failing of the heart occur as a pathological entity - "radiation-induced heart disease" (RIHD) that is major source of morbidity and mortality. The purpose of this review is to bring insights into the basic mechanisms of RIHD that may lead to the identification of targets for intervention in the radiotherapy side effect. Studies of authors also provide knowledge about how to select targeted drugs or biological molecules to modify the progression of radiation damage in the heart. New prospective studies are needed to validate that assessed factors and changes are useful as early markers of cardiac damage.

  12. Auxin-induced growth of Avena coleoptiles involves two mechanisms with different pH optima

    Science.gov (United States)

    Cleland, R. E.

    1992-01-01

    Although rapid auxin-induced growth of coleoptile sections can persist for at least 18 hours, acid-induced growth lasts for a much shorter period of time. Three theories have been proposed to explain this difference in persistence. To distinguish between these theories, the pH dependence for auxin-induced growth of oat (Avena sativa L.) coleoptiles has been determined early and late in the elongation process. Coleoptile sections from which the outer epidermis was removed to facilitate buffer entry were incubated, with or without 10 micromolar indoleacetic acid, in 20 millimolar buffers at pH 4.5 to 7.0 to maintain a fixed wall pH. During the first 1 to 2 hours after addition of auxin, elongation occurs by acid-induced extension (i.e. the pH optimum is Auxin causes no additional elongation because the buffers prevent further changes in wall pH. After 60 to 90 minutes, a second mechanism of auxin-induced growth, whose pH optimum is 5.5 to 6.0, predominates. It is proposed that rapid growth responses to changes in auxin concentration are mediated by auxin-induced changes in wall pH, whereas the prolonged, steady-state growth rate is controlled by a second, auxin-mediated process whose pH optimum is less acidic.

  13. Flavonoids Active Against Osteosarcoma: A Review of the Molecular Mechanisms Involved.

    Science.gov (United States)

    Liu, Hui; Gao, Yutong; Dong, Yonghui; Cheng, Peng; Chen, Anmin; Huang, Hui

    2017-01-01

    Osteosarcoma is the most frequent primitive malignant bone tumor affecting adolescents and young adults worldwide. The tumor exhibits aggressive growth in the primary site and readily metastasizes to other organs. There has been no significant improvement in the 5-year survival rate since the 1970s and the figure remains at 60-70%. In addition, the side effects of chemotherapeutic drugs and resistance to chemotherapy compromise the effects of treatment for osteosarcoma. In recent years, the development of flavonoids drugs inhibiting carcinogenesis is attracting great interest in the scientific community. Flavonoids are one kind of polyphenolic compounds widely found in vegetables and fruits. Moreover, flavonoids have become popular compounds, exhibiting comprehensive antitumor activities, while being safe and inexpensive. Here, the literature on the benefits afforded by flavonoids in terms of osteosarcoma treatment is reviewed and certain flavonoids and their effects on osteosarcoma are discussed. These compounds can perturb the cell cycle, induce apoptosis, inhibit tumor cell invasion and metastasis, potentiate the actions of chemotherapeutic agents, trigger autophagy, and stimulate antitumor activity in vivo. In summary, we highlight the currently well-accepted flavonoid compounds and detail the molecular mechanisms by which flavonoids may treat osteosarcoma, and thus the flavonoids exhibit great promise as anti-osteosarcoma agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Auxin-induced growth of Avena coleoptiles involves two mechanisms with different pH optima

    Science.gov (United States)

    Cleland, R. E.

    1992-01-01

    Although rapid auxin-induced growth of coleoptile sections can persist for at least 18 hours, acid-induced growth lasts for a much shorter period of time. Three theories have been proposed to explain this difference in persistence. To distinguish between these theories, the pH dependence for auxin-induced growth of oat (Avena sativa L.) coleoptiles has been determined early and late in the elongation process. Coleoptile sections from which the outer epidermis was removed to facilitate buffer entry were incubated, with or without 10 micromolar indoleacetic acid, in 20 millimolar buffers at pH 4.5 to 7.0 to maintain a fixed wall pH. During the first 1 to 2 hours after addition of auxin, elongation occurs by acid-induced extension (i.e. the pH optimum is <5 and the elongation varies inversely with the solution pH). Auxin causes no additional elongation because the buffers prevent further changes in wall pH. After 60 to 90 minutes, a second mechanism of auxin-induced growth, whose pH optimum is 5.5 to 6.0, predominates. It is proposed that rapid growth responses to changes in auxin concentration are mediated by auxin-induced changes in wall pH, whereas the prolonged, steady-state growth rate is controlled by a second, auxin-mediated process whose pH optimum is less acidic.

  15. Chemical Compounds and Mechanisms Involved in the Formation and Stabilization of Foam in Sparkling Wines.

    Science.gov (United States)

    Kemp, Belinda; Condé, Bruna; Jégou, Sandrine; Howell, Kate; Vasserot, Yann; Marchal, Richard

    2018-02-08

    The visual properties of sparkling wine including foam and bubbles are an indicator of sparkling wine quality. Foam properties, particularly foam height (FH) and foam stability (TS), are significantly influenced by the chemical composition of the wine. This review investigates our current knowledge of specific chemical compounds and, the mechanisms by which they influence the foam properties of sparkling wines. Grape and yeast proteins, amino acids, polysaccharides, phenolic compounds, organic acids, fatty acids, ethanol and sugar are examined with respect to their contribution to foam characteristics in sparkling wines made with the traditional, transfer, and charmat and carbonation methods. Contradictory results have been identified that appear to be due to the analytical methods used to measure and quantify compounds and foam. Biopolymer complexes are discussed and absent knowledge with regards to thaumatin-like proteins (TLPs), polysaccharides, amino acids, oak-derived phenolic compounds and organic acids are identified. Future research is also likely to concentrate on visual analysis of sparkling wines by in-depth imaging analysis and specific sensory analysis techniques.

  16. Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

    Directory of Open Access Journals (Sweden)

    M.P. da Silva

    2014-02-01

    Full Text Available Physiological evidence indicates that the supraoptic nucleus (SON is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1 the intrinsic membrane properties of the MNCs themselves and 2 synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON.

  17. Modeling the mechanism involved during the sorption of methylene blue onto fly ash.

    Science.gov (United States)

    Kumar, K Vasanth; Ramamurthi, V; Sivanesan, S

    2005-04-01

    Batch sorption experiments were carried out to remove methylene blue from its aqueous solutions using fly ash as an adsorbent. Operating variables studied were initial dye concentration, fly ash mass, pH, and contact time. Maximum color removal was observed at a basic pH of 8. Equilibrium data were represented well by a Langmuir isotherm equation with a monolayer sorption capacity of 5.718 mg/g. Sorption data were fitted to both Lagergren first-order and pseudo-second-order kinetic models and the data were found to follow pseudo-second-order kinetics. Rate constants at different initial concentrations were estimated. The process mechanism was found to be complex, consisting of both surface adsorption and pore diffusion. The effective diffusion parameter D(i) values were estimated at different initial concentrations and the average value was determined to be 2.063 x 10(-9)cm2/s. Analysis of sorption data using a Boyd plot confirms the particle diffusion as the rate-limiting step for the dye concentration ranges studied in the present investigation (20 to 60 mg/L).

  18. Adaptation of grapevine flowers to cold involves different mechanisms depending on stress intensity.

    Directory of Open Access Journals (Sweden)

    Mélodie Sawicki

    Full Text Available Grapevine flower development and fruit set are influenced by cold nights in the vineyard. To investigate the impact of cold stress on carbon metabolism in the inflorescence, we exposed the inflorescences of fruiting cuttings to chilling and freezing temperatures overnight and measured fluctuations in photosynthesis and sugar content. Whatever the temperature, after the stress treatment photosynthesis was modified in the inflorescence, but the nature of the alteration depended on the intensity of the cold stress. At 4°C, photosynthesis in the inflorescence was impaired through non-stomatal limitations, whereas at 0°C it was affected through stomatal limitations. A freezing night (-3°C severely deregulated photosynthesis in the inflorescence, acting primarily on photosystem II. Cold nights also induced accumulation of sugars. Soluble carbohydrates increased in inflorescences exposed to -3°C, 0°C and 4°C, but starch accumulated only in inflorescences of plants treated at 0 and -3°C. These results suggest that inflorescences are able to cope with cold temperatures by adapting their carbohydrate metabolism using mechanisms that are differentially induced according to stress intensity.

  19. Magnetic Resonance investigation into the mechanisms involved in the development of high-altitude cerebral edema.

    Science.gov (United States)

    Sagoo, Ravjit S; Hutchinson, Charles E; Wright, Alex; Handford, Charles; Parsons, Helen; Sherwood, Victoria; Wayte, Sarah; Nagaraja, Sanjoy; Ng'Andwe, Eddie; Wilson, Mark H; Imray, Christopher He

    2017-01-01

    Rapid ascent to high altitude commonly results in acute mountain sickness, and on occasion potentially fatal high-altitude cerebral edema. The exact pathophysiological mechanisms behind these syndromes remain to be determined. We report a study in which 12 subjects were exposed to a FiO 2  = 0.12 for 22 h and underwent serial magnetic resonance imaging sequences to enable measurement of middle cerebral artery velocity, flow and diameter, and brain parenchymal, cerebrospinal fluid and cerebral venous volumes. Ten subjects completed 22 h and most developed symptoms of acute mountain sickness (mean Lake Louise Score 5.4; p Cerebral oxygen delivery was maintained by an increase in middle cerebral artery velocity and diameter (first 6 h). There appeared to be venocompression at the level of the small, deep cerebral veins (116 cm 3 at 2 h to 97 cm 3 at 22 h; p cerebral oxygen delivery was maintained by increased arterial inflow and this preceded the development of cerebral edema. Venous outflow restriction appeared to play a contributory role in the formation of cerebral edema, a novel feature that has not been observed previously. © The Author(s) 2016.

  20. Predictive Mechanisms Are Not Involved the Same Way during Human-Human vs. Human-Machine Interactions: A Review.

    Science.gov (United States)

    Sahaï, Aïsha; Pacherie, Elisabeth; Grynszpan, Ouriel; Berberian, Bruno

    2017-01-01

    Nowadays, interactions with others do not only involve human peers but also automated systems. Many studies suggest that the motor predictive systems that are engaged during action execution are also involved during joint actions with peers and during other human generated action observation. Indeed, the comparator model hypothesis suggests that the comparison between a predicted state and an estimated real state enables motor control, and by a similar functioning, understanding and anticipating observed actions. Such a mechanism allows making predictions about an ongoing action, and is essential to action regulation, especially during joint actions with peers. Interestingly, the same comparison process has been shown to be involved in the construction of an individual's sense of agency, both for self-generated and observed other human generated actions. However, the implication of such predictive mechanisms during interactions with machines is not consensual, probably due to the high heterogeneousness of the automata used in the experimentations, from very simplistic devices to full humanoid robots. The discrepancies that are observed during human/machine interactions could arise from the absence of action/observation matching abilities when interacting with traditional low-level automata. Consistently, the difficulties to build a joint agency with this kind of machines could stem from the same problem. In this context, we aim to review the studies investigating predictive mechanisms during social interactions with humans and with automated artificial systems. We will start by presenting human data that show the involvement of predictions in action control and in the sense of agency during social interactions. Thereafter, we will confront this literature with data from the robotic field. Finally, we will address the upcoming issues in the field of robotics related to automated systems aimed at acting as collaborative agents.

  1. Predictive Mechanisms Are Not Involved the Same Way during Human-Human vs. Human-Machine Interactions: A Review

    Directory of Open Access Journals (Sweden)

    Aïsha Sahaï

    2017-10-01

    Full Text Available Nowadays, interactions with others do not only involve human peers but also automated systems. Many studies suggest that the motor predictive systems that are engaged during action execution are also involved during joint actions with peers and during other human generated action observation. Indeed, the comparator model hypothesis suggests that the comparison between a predicted state and an estimated real state enables motor control, and by a similar functioning, understanding and anticipating observed actions. Such a mechanism allows making predictions about an ongoing action, and is essential to action regulation, especially during joint actions with peers. Interestingly, the same comparison process has been shown to be involved in the construction of an individual's sense of agency, both for self-generated and observed other human generated actions. However, the implication of such predictive mechanisms during interactions with machines is not consensual, probably due to the high heterogeneousness of the automata used in the experimentations, from very simplistic devices to full humanoid robots. The discrepancies that are observed during human/machine interactions could arise from the absence of action/observation matching abilities when interacting with traditional low-level automata. Consistently, the difficulties to build a joint agency with this kind of machines could stem from the same problem. In this context, we aim to review the studies investigating predictive mechanisms during social interactions with humans and with automated artificial systems. We will start by presenting human data that show the involvement of predictions in action control and in the sense of agency during social interactions. Thereafter, we will confront this literature with data from the robotic field. Finally, we will address the upcoming issues in the field of robotics related to automated systems aimed at acting as collaborative agents.

  2. Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology.

    Science.gov (United States)

    Amemiya, Takahiro; Honma, Masashi; Kariya, Yoshiaki; Ghosh, Samik; Kitano, Hiroaki; Kurachi, Yoshihisa; Fujita, Ken-Ichi; Sasaki, Yasutsuna; Homma, Yukio; Abernethy, Darrel R; Kume, Haruki; Suzuki, Hiroshi

    2015-01-01

    Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions.

  3. Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2 leading to cell depolarization and calcium influx

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Bechmann, Louise Ellegaard; Hartmann, Bolette

    2015-01-01

    Neurotensin (NT) is a neurohormone produced in the central nervous system and in the gut epithelium by the enteroendocrine N cell. NT may play a role in appetite regulation and may have potential in obesity treatment. Glucose ingestion stimulates NT secretion in healthy young humans......, but the mechanisms involved are not well understood. Here, we show that rats express NT in the gut and that glucose gavage stimulates secretion similarly to oral glucose in humans. Therefore, we conducted experiments on isolated perfused rat small intestine with a view to characterize the cellular pathways...... of secretion. Luminal glucose (20% wt/vol) stimulated secretion but vascular glucose (5, 10, or 15 mmol/l) was without effect. The underlying mechanisms depend on membrane depolarization and calcium influx, since the voltage-gated calcium channel inhibitor nifedipine and the KATP channel opener diazoxide...

  4. Clinical--imaging aspects of young permanent teeth traumas and the ethiopatogenic mechanisms involved.

    Science.gov (United States)

    Nemţoi, A; Dănila, I; Lăduncă, Oana; Petcu, Ana; Bamboi, Ana; Haba, Danisia

    2013-01-01

    Dental trauma occurring to children and teenagers all over the world represents a serious issue in Public Health. This present study wants to investigate the etiology and the environment in which the dental trauma occurs and also wants to establish a connection between dental trauma and social-economic status. The study was made to collect information about dental trauma on human subjects involving 372 children and teenagers, both female and male, between 8 and 20 years of age. The data obtained from the clinical and radiological exams for each patient have been registered in a special conceived register, which represented a stage of the study. The frequency of dental trauma varied from 62.1% for males to 37.9% for women. Most of them have suffered from dental trauma between the age of 14 and 16 (30.1%), and a few between 18 and 20 years (2.2%). Dental trauma has occurred most frequently in school, during sports lessons, followed by those in public places like the street (23.1%), from which 17.1% have been associated with bicycle accidents, 3.5% with scooter accidents and 2.5% with car accidents. Children and teenagers who live in areas with a low social economic level have been the fewest to seek medical attention due to difficult access to medical services. Overall, this study wanted to present the importance of knowing the frequency of dental trauma in children and teenagers and to point out the need of promoting medical education to parents regarding the means they can use to reduce the risk factors associated with dental trauma.

  5. Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0652 TITLE: Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity PRINCIPAL INVESTIGATOR...5a. CONTRACT NUMBER W81XWH-16-1-0652 Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity 5b. GRANT NUMBER W81XWH...Email addresses: mbouxsei@bidmc.harvard.edu; scaksa@mgh.harvard.edu; serudolph@mgh.harvard.edu ; kpopp@mgh.harvard.edu E-Mail: 5f. WORK UNIT NUMBER 7

  6. Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced mechanical allodynia in rats

    Directory of Open Access Journals (Sweden)

    Yano Takahisa

    2011-01-01

    Full Text Available Abstract Background Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA receptors in oxaliplatin-induced mechanical allodynia in rats. Results Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week caused mechanical allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol and memantine (1 μmol, NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t. and ifenprodil (50 mg/kg, p.o. significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase but not on Day 5 (early phase. Moreover, we examined the involvement of nitric oxide synthase (NOS as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981. Conclusion These results indicated that spinal NR2B-containing NMDA receptors are involved in the oxaliplatin-induced mechanical allodynia.

  7. Comparative proteomics of peanut gynophore development under dark and mechanical stimulation.

    Science.gov (United States)

    Sun, Yong; Wang, Qingguo; Li, Zhen; Hou, Lei; Dai, Shaojun; Liu, Wei

    2013-12-06

    Peanut (Arachis hypogaea. L) is an important leguminous crop and source of proteins and lipids. It has attracted widespread attention of researchers due to its unique growth habit of geocarpy, which is regulated by geotropism, negative phototropism, and haptotropism. However, the protein expression pattern and molecular regulatory mechanism underlying the physiological processes of peanut remain unknown. In this study, the peanut gynophores under five treatment conditions were used for proteomic analysis, including aerial growth of the gynophores, the gynophores penetrated into the soil, as well as aerial growth of the gynophores under mechanical stimulation, dark, and mechanical stimulation combined with dark. The analysis of protein abundances in peanut gynophores under these conditions were conducted using comparative proteomic approaches. A total of 27 differentially expressed proteins were identified and further classified into nine biological functional groups of stress and defense, carbohydrate and energy metabolism, metabolism, photosynthesis, cell structure, signaling, transcription, protein folding and degradation, and function unknown. By searching gene functions against peanut database, 10 genes with similar annotations were selected as corresponding changed proteins, and their variation trends in gynophores under such growth conditions were further verified using quantitative real-time PCR. Overall, the investigation will benefit to enrich our understanding of the internal mechanisms of peanut gynophore development and lay a foundation for breeding and improving crop varieties and qualities.

  8. Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control.

    Science.gov (United States)

    Reis, Janine; Swayne, Orlando B; Vandermeeren, Yves; Camus, Mickael; Dimyan, Michael A; Harris-Love, Michelle; Perez, Monica A; Ragert, Patrick; Rothwell, John C; Cohen, Leonardo G

    2008-01-15

    Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.

  9. Cholinergic and dopaminergic mechanisms involved in the recovery of circadian anticipation by aniracetam in aged rats.

    Science.gov (United States)

    Tanaka, Yushiro; Kurasawa, Mitsue; Nakamura, Kazuo

    2002-05-01

    We have reported that repeated administration of aniracetam (100 mg/kg p.o.) for 7 consecutive days recovers mealtime-associated circadian anticipatory behavior diminished in aged rats. The present study examines the mode of action underlying the restoration by aniracetam with various types of receptor antagonists. Coadministration of scopolamine (0.1 mg/kg i.p.) or haloperidol (0.1 mg/kg i.p.) for the last 3 days significantly reduced the restorative effects of aniracetam without affecting the timed feeding-induced anticipatory behavior by each receptor antagonist itself. The other receptor antagonists, mecamylamine (3 mg/kg i.p.), 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX, 1 microg/rat i.c.v.) had no effect on either the basal or aniracetam-elicited circadian anticipation. In contrast, ketanserin (1 mg/kg i.p.) itself recovered the diminished anticipatory behavior as aniracetam did, but it did not alter the restorative effects of aniracetam. Among the receptor antagonists tested, NBQX reduced appetite and haloperidol induced circadian hypoactivity. These results suggest that the food-entrainable circadian oscillations or the temporal regulatory system of behavior is modulated by cholinergic, dopaminergic and serotonergic systems. Furthermore, aniracetam may restore the aging-diminished behavioral anticipation by activating muscarinic acetylcholine (ACh) and/or dopamine (DA) D2 receptors through the enhanced release of ACh and/or DA in the brain.

  10. A chemokine self-presentation mechanism involving formation of endothelial surface microstructures.

    Science.gov (United States)

    Whittall, Catherine; Kehoe, Oksana; King, Sophie; Rot, Antal; Patterson, Angela; Middleton, Jim

    2013-02-15

    Endothelial surface microstructures have been described previously under inflammatory conditions; however, they remain ill-characterized. In this study, CXCL8, an inflammatory chemokine, was shown to induce the formation of filopodia-like protrusions on endothelial cells; the same effects were observed with CXCL10 and CCL5. Chemokines stimulated filopodia formation by both microvascular (from bone marrow and skin) and macrovascular (from human umbilical vein) endothelial cells. Use of blocking Abs and degradative enzymes demonstrated that CXCL8-stimulated filopodia formation was mediated by CXCR1 and CXCR2, Duffy Ag/receptor for chemokines, heparan sulfate (HS), and syndecans. HS was present on filopodial protrusions appearing as a meshwork on the cell surface, which colocalized with CXCL8, and this glycosaminoglycan was 2,6-O- and 3-O-sulfated. Transmission electron microscopy revealed that CXCL8-stimulated filopodial and microvilli-like protrusions that interacted with leukocytes before transendothelial migration and removal of HS reduced this migration. iTRAQ mass spectrometry showed that changes in the levels of cytoskeletal, signaling, and extracellular matrix proteins were associated with CXCL8-stimulated filopodia/microvilli formation; these included tropomyosin, fascin, and Rab7. This study suggests that chemokines stimulate endothelial filopodia and microvilli formation, leading to their presentation to leukocytes and leukocyte transendothelial migration.

  11. Cytolytic mechanisms involved in non-MHC-restricted cytotoxicity in Chediak-Higashi syndrome

    Science.gov (United States)

    Nakazawa, T; Agematsu, K; Yasui, K; Onodera, T; Inoue, R; Kaneko, H; Kondo, N; Yamamoto, M; Kayagaki, N; Yagita, H; Okumura, K; Komiyama, A

    1999-01-01

    To determine the mechanisms responsible for the impaired lymphocyte-mediated cytotoxicity in Chediak-Higashi syndrome (CHS), we investigated the killing ability of peripheral blood lymphocytes (PBL) from three patients with CHS using several kinds of target cells that were sensitive to perforin, Fas ligand (FasL), and/or tumour necrosis factor-alpha (TNF-α). Freshly isolated CHS PBL did not kill K562 target cells, killing of which by normal PBL was perforin-dependent, as demonstrated by complete inhibition by concanamycin A (CMA), an inhibitor of perforin-based cytotoxicity. In contrast, the CHS PBL exhibited substantial cytotoxicity against Jurkat cells, which was only partially inhibited by CMA treatment but not by the addition of neutralizing anti-FasL or anti-TNF-α antibodies. IL-2-activated CHS PBL exhibited substantial levels of cytotoxicity against K562 and Jurkat cells, the levels being 74% and 83% of the respective normal control values, respectively. CMA treatment showed that while the cytotoxicity of IL-2-activated CHS PBL against K562 was largely dependent on perforin, that against Jurkat was largely not. IL-2-activated CHS PBL expressed FasL mRNA, and killed Fas transfectants. These findings indicate that CHS PBL have an ability to kill some target cells via a perforin-mediated pathway, especially when they are activated by IL-2. It was also demonstrated that CHS PBL can exert cytotoxicity against certain target cells by utilizing FasL and an undefined effector molecule other than perforin, FasL, or TNF-α. PMID:10540167

  12. Use of Lentinan To Control Sharp Eyespot of Wheat, and the Mechanism Involved.

    Science.gov (United States)

    Zhang, Zhongxiao; Wang, Hongyan; Wang, Kaiyun; Jiang, Lili; Wang, Dong

    2017-12-20

    Lentinan (LNT), a complex polysaccharide with a β-(1→3)-linked backbone of d-glucose residues, has been reported to inhibit plant diseases. Our objective was to explore the efficacy and action mechanism of LNT used as a seed dressing to control sharp eyespot of wheat. Seed dressing promoted wheat growth. At control germination rates of 50%, 8 g of LNT/100 kg of seeds of the Jimai 22, Shannong 23, and Luyuan 502 cultivars significantly increased seed germination to 54%, 52%, and 51%, respectively. Seven days after emergence, the heights and root activity of wheat treated with LNT were significantly greater than those of controls. These effects were dose-dependent. At this time, the plant heights of Jimai 22, Shannong 23, and Luyuan 502 cultivars were 9.52, 8.52, and 10.52 cm, respectively, significantly higher than that of the controls. LNT prevented the development of wheat sharp eyespot. In the highly susceptible Jimai 22 cultivar, sharp eyespot development was reduced by 33.7%, 31.9%, and 30.4% at 7, 14, and 21 days after germination. LNT somewhat increased phenylalanine ammonia-lyase, peroxidase, and superoxide dismutase activity; reduced the malondialdehyde content; increased chlorophyll a and b levels; and enhanced the root vigor of wheat. These effects peaked 7 days after germination. LNT increased transcription of the genes encoding alternative oxidase (AOX) and β-1,3-glucanase (GLU), the salicylic acid signaling pathway-related gene NbPR1a, and the sharp eyespot resistance-related gene RS33. A significant dose-effect relationship was evident in terms of AOX transcription; we thus speculate that AOX may be the target gene.

  13. Endocannabinoids are Involved in Male Vertebrate Reproduction: Regulatory Mechanisms at Central and Gonadal Level

    Science.gov (United States)

    Bovolin, Patrizia; Cottone, Erika; Pomatto, Valentina; Fasano, Silvia; Pierantoni, Riccardo; Cobellis, Gilda; Meccariello, Rosaria

    2014-01-01

    Endocannabinoids (eCBs) are natural lipids regulating a large array of physiological functions and behaviors in vertebrates. The eCB system is highly conserved in evolution and comprises several specific receptors (type-1 and type-2 cannabinoid receptors), their endogenous ligands (e.g., anandamide and 2-arachidonoylglycerol), and a number of biosynthetic and degradative enzymes. In the last few years, eCBs have been described as critical signals in the control of male and female reproduction at multiple levels: centrally, by targeting hypothalamic gonadotropin-releasing-hormone-secreting neurons and pituitary, and locally, with direct effects on the gonads. These functions are supported by the extensive localization of cannabinoid receptors and eCB metabolic enzymes at different levels of the hypothalamic–pituitary–gonadal axis in mammals, as well as bonyfish and amphibians. In vivo and in vitro studies indicate that eCBs centrally regulate gonadal functions by modulating the gonadotropin-releasing hormone–gonadotropin–steroid network through direct and indirect mechanisms. Several proofs of local eCB regulation have been found in the testis and male genital tracts, since eCBs control Sertoli and Leydig cells activity, germ cell progression, as well as the acquisition of sperm functions. A comparative approach usually is a key step in the study of physiological events leading to the building of a general model. Thus, in this review, we summarize the action of eCBs at different levels of the male reproductive axis, with special emphasis, where appropriate, on data from non-mammalian vertebrates. PMID:24782832

  14. The mechanism involved in the loss of PTEN expression in NSCLC tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gang; Zhao, Jingfeng; Peng, Xianjing [Department of Radiology, Xiangya Hospital, Central South University, Changsha 410008 (China); Liang, Jian; Deng, Xin [Ruikang Hospital, Guangxi University of Traditional Chinese Medicine, Nanning 530003 (China); Chen, Yuxiang, E-mail: chenyx008@yahoo.cn [Department of Radiology, Xiangya Hospital, Central South University, Changsha 410008 (China); School of Biological Science and Technology, Central South University, Changsha 410008 (China)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Radiation stimulates PTEN reexpression in NSCLC independent of p53 activation. Black-Right-Pointing-Pointer PTEN reexpression is mediated by miR-29b overexpression. Black-Right-Pointing-Pointer miR-29b regulates Dnmts expression in NSCLC tumor cells. Black-Right-Pointing-Pointer Target therapy could be established by overexpressing miR-29b expression. -- Abstract: Loss of PTEN expression is observed in most non-small cell lung cancers (NSCLC). However, the mechanism by which PTEN expression is regulated in NSCLC has not been fully elucidated. In this study, we investigated the role of DNA methyltransferases (Dnmts), microRNA-29b (miR-29b), and anti-miR-29b inhibitor in PTEN promoter methylation and PTEN gene expression in H358 NSCLC cells in vitro and in vivo. PTEN mRNA was measured by RT-PCR. PTEN and Dnmts protein levels were measured by Western blot. miR-29b expression was detected by Northern blot. A xenograft H358 tumor mouse model was established by subcutaneously inoculating H358 cells into the right hind limbs of nude mice. We found that radiation induced cell apoptosis and hypomethylation in PTEN promoter, PTEN and miR-29b expression, and downregulation of Dnmt1, 3a and 3b expression in H358 tumor cells. The effect of radiation on gene expression and apoptosis was blocked by anti-miR-29b inhibitor. In the xenograft H358 tumor model, anti-miR-29b inhibitor reversed radiation-induced tumor growth delay, PTEN reexpression and downregulation of Dnmts expression. Our study suggested that miR-29b is an upstream molecule of PTEN. miR-29b regulates PTEN gene expression through downregulating Dnmts expression and subsequently induces hypomethylation in PTEN promoter. Targeting therapy could be established in NSCLC by upregulating miR-29b expression.

  15. The mechanism involved in the loss of PTEN expression in NSCLC tumor cells

    International Nuclear Information System (INIS)

    Li, Gang; Zhao, Jingfeng; Peng, Xianjing; Liang, Jian; Deng, Xin; Chen, Yuxiang

    2012-01-01

    Highlights: ► Radiation stimulates PTEN reexpression in NSCLC independent of p53 activation. ► PTEN reexpression is mediated by miR-29b overexpression. ► miR-29b regulates Dnmts expression in NSCLC tumor cells. ► Target therapy could be established by overexpressing miR-29b expression. -- Abstract: Loss of PTEN expression is observed in most non-small cell lung cancers (NSCLC). However, the mechanism by which PTEN expression is regulated in NSCLC has not been fully elucidated. In this study, we investigated the role of DNA methyltransferases (Dnmts), microRNA-29b (miR-29b), and anti-miR-29b inhibitor in PTEN promoter methylation and PTEN gene expression in H358 NSCLC cells in vitro and in vivo. PTEN mRNA was measured by RT-PCR. PTEN and Dnmts protein levels were measured by Western blot. miR-29b expression was detected by Northern blot. A xenograft H358 tumor mouse model was established by subcutaneously inoculating H358 cells into the right hind limbs of nude mice. We found that radiation induced cell apoptosis and hypomethylation in PTEN promoter, PTEN and miR-29b expression, and downregulation of Dnmt1, 3a and 3b expression in H358 tumor cells. The effect of radiation on gene expression and apoptosis was blocked by anti-miR-29b inhibitor. In the xenograft H358 tumor model, anti-miR-29b inhibitor reversed radiation-induced tumor growth delay, PTEN reexpression and downregulation of Dnmts expression. Our study suggested that miR-29b is an upstream molecule of PTEN. miR-29b regulates PTEN gene expression through downregulating Dnmts expression and subsequently induces hypomethylation in PTEN promoter. Targeting therapy could be established in NSCLC by upregulating miR-29b expression.

  16. Anorexic response to rapamycin does not appear to involve a central mechanism.

    Science.gov (United States)

    Toklu, Hale Z; Bruce, Erin B; Sakarya, Yasemin; Carter, Christy S; Morgan, Drake; Matheny, Michael K; Kirichenko, Nataliya; Scarpace, Philip J; Tümer, Nihal

    2016-09-01

    The authors have previously demonstrated that a low and intermittent peripheral dose of rapamycin (1 mg/kg three times/week) to rats inhibited mTORC1 signalling, but avoided the hyperlipidemia and diabetes-like syndrome associated with higher doses of rapamycin. The dosing regimen reduced food intake, body weight, adiposity, serum leptin and triglycerides. mTORC1 signalling was inhibited in both liver and hypothalamus, suggesting some of the actions, in particular the decrease in food intake, may be the results of a central mechanism. To test this hypothesis, rapamycin (30 μg/day for 4 weeks) was infused into 23-25-month-old F344xBN rats by intracerebroventricular (icv) mini pumps. Our results demonstrated that central infusion did not alter food intake or body weight, although there was a tendency for a decrease in body weight towards the end of the study. mTORC1 signalling, evidenced by decreased phosphorylation of S6 protein at end of 4 weeks, was not activated in liver, hypothalamus or hindbrain. Fat and lean mass, sum of white adipose tissues, brown adipose tissue, serum glucose, insulin and leptin levels remained unchanged. Thus, these data suggest that the anorexic and body weight responses evident with peripheral rapamycin are not the result of direct central action. The tendency for decreased body weight towards the end of study, suggests that there is either a slow transport of centrally administered rapamycin into the periphery, or that there is delayed action of rapamycin at sites in the brain. © 2016 John Wiley & Sons Australia, Ltd.

  17. Model test study of evaporation mechanism of sand under constant atmospheric condition

    OpenAIRE

    CUI, Yu Jun; DING, Wenqi; SONG, Weikang

    2014-01-01

    The evaporation mechanism of Fontainebleau sand using a large-scale model chamber is studied. First, the evaporation test on a layer of water above sand surface is performed under various atmospheric conditions, validating the performance of the chamber and the calculation method of actual evaporation rate by comparing the calculated and measured cumulative evaporations. Second,the evaporation test on sand without water layer is conducted under constant atmospheric condition. Both the evoluti...

  18. Mechanical behavior of confined self-compacting reinforced concrete circular columns under concentric axial loading

    OpenAIRE

    Khairallah, Fouad

    2013-01-01

    While there is abundant research information on ordinary confined concrete, there are little data on the behavior of Self-Compacting Concrete (SCC) under such condition. Due to higher shrinkage and lower coarse aggregate content of SCC compared to that of Normal Concrete (NC), its composite performance under confined conditions needs more investigation. This paper has been devoted to investigate and compare the mechanical behavior of confined concrete circular columns cast with SCC and NC und...

  19. Automatic polarographic elucidation of electrode mechanisms by means of a knowledge-based system, part 3: Mechanisms ECE, EE and mechanisms involving adsorption

    NARCIS (Netherlands)

    Palys, M.J.; Palys, M.J.; Bos, M.; van der Linden, W.E.

    1993-01-01

    The previously described expert system has been extended: rules allowing the elucidation of a larger number of mechanisms have been added and automatic control of additional experimental parameters such as concentration and composition of the solution in the cell and the electrode size has been made

  20. Gastroduodenal resistance and neural mechanisms involved in saline flow decrease elicited by acute blood volume expansion in anesthetized rats

    Directory of Open Access Journals (Sweden)

    Graça J.R.V.

    1997-01-01

    Full Text Available We have previously demonstrated that blood volume (BV expansion decreases saline flow through the gastroduodenal (GD segment in anesthetized rats (Xavier-Neto J, dos Santos AA & Rola FH (1990 Gut, 31: 1006-1010. The present study attempts to identify the site(s of resistance and neural mechanisms involved in this phenomenon. Male Wistar rats (N = 97, 200-300 g were surgically manipulated to create four gut cir