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Sample records for underlying mechanisms involved

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

    Science.gov (United States)

    Vidal-Dupiol, Jeremie; Adjeroud, Mehdi; Roger, Emmanuel; Foure, Laurent; Duval, David; Mone, Yves; Ferrier-Pages, Christine; Tambutte, Eric; Tambutte, Sylvie; Zoccola, Didier; Allemand, Denis; Mitta, Guillaume

    2009-08-04

    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. In our experimental procedure, one set of Pocillopora damicornis nubbins was subjected to a gradual increase of water temperature from 28 degrees C to 32 degrees C over 15 days. A second control set kept at constant temperature (28 degrees 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. Under thermal stress

  2. 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

  3. Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms.

    Science.gov (United States)

    Delivanis, Danae A; Gustafson, Michael P; Bornschlegl, Svetlana; Merten, Michele M; Kottschade, Lisa; Withers, Sarah; Dietz, Allan B; Ryder, Mabel

    2017-08-01

    Thyroid immune-related adverse events (irAEs) in patients treated with programmed death receptor-1 (PD-1) blockade are increasingly recognized as one of the most common adverse effects. Our aim was to determine the incidence and examine the potential mechanisms of anti-PD-1-induced thyroid irAEs. Single-center, retrospective cohort study. We studied 93 patients with advanced cancer (ages 24 to 82 years; 60% males) who received at least one infusion of pembrolizumab. Thyroid test results and thyroid imaging modalities were reviewed. Comprehensive 10-color flow cytometry of peripheral blood was performed. Thirteen (14%) thyroid irAEs were observed. Thyroiditis occurred in seven patients (54%), from which four recovered. New onset of hypothyroidism overt/subclinical developed in three patients. Levothyroxine dosing required doubling in three patients with a known history of hypothyroidism. Thyroperoxidase antibodies were positive in the minority of the patients [4/13 (31%)] and diffuse increased 18fludeoxyglucose uptake of the thyroid gland was observed in the majority [7/11 (64%)] of patients. We observed more circulating CD56+CD16+ natural killer (NK) cells and an elevated HLA-DR surface expression in the inflammatory intermediate CD14+CD16+ monocytes in anti-PD-1-treated patients. Thyroid dysfunction is common in cancer patients treated with pembrolizumab. Reversible destructive thyroiditis and overt hypothyroidism are the most common clinical presentations. The mechanism of thyroid destruction appears independent of thyroid autoantibodies and may include T cell, NK cell, and/or monocyte-mediated pathways. Because the thyroid is a frequent target of anti-PD-1 therapies, patients with therapeutically refractory thyroid cancer may be ideal candidates for this treatment. Copyright © 2017 Endocrine Society

  4. 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

  5. Involvement of peripheral III nerve in multiple sclerosis patient: Report of a new case and discussion of the underlying mechanism.

    Science.gov (United States)

    Shor, Natalia; Amador, Maria Del Mar; Dormont, Didier; Lubetzki, Catherine; Bertrand, Anne

    2017-04-01

    Multiple sclerosis (MS) is a chronic disorder that affects the central nervous system myelin. However, a few radiological cases have documented an involvement of peripheral cranial nerves, within the subarachnoid space, in MS patients. We report the case of a 36-year-old female with a history of relapsing-remitting (RR) MS who consulted for a subacute complete paralysis of the right III nerve. Magnetic resonance imaging (MRI) examination showed enhancement and thickening of the cisternal right III nerve, in continuity with a linear, mesencephalic, acute demyelinating lesion. Radiological involvement of the cisternal part of III nerve has been reported only once in MS patients. Radiological involvement of the cisternal part of V nerve occurs more frequently, in almost 3% of MS patients. In both situations, the presence of a central demyelinating lesion, in continuity with the enhancement of the peripheral nerve, suggests that peripheral nerve damage is a secondary process, rather than a primary target of demyelination.

  6. 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.

  7. The mechanisms involved at the cell level

    International Nuclear Information System (INIS)

    Leblanc, G.; Pourcher, Th.; Perron, B.; Guillain, F.; Quemeneur, E.; Fritsch, P.

    2003-01-01

    The mechanisms responsible at the cell level for inducing toxic reactions after contamination are as yet only imperfectly known. Work still needs to be done for both contaminants that have a biological role, such as iodine, and those that do not, such as cadmium, uranium and plutonium. In particular, these mechanisms bring into play, in biological membranes, carriers which are the physiological partners responsible for material exchange with the environment or inside the body. As they lack absolute selectivity, these carriers, which are involved in the assimilation and accumulation of vital mineral elements, also have the ability to transport toxic elements and isotopes. (authors)

  8. Altered DNA methylation: a secondary mechanism involved in carcinogenesis.

    Science.gov (United States)

    Goodman, Jay I; Watson, Rebecca E

    2002-01-01

    This review focuses on the role that DNA methylation plays in the regulation of normal and aberrant gene expression and on how, in a hypothesis-driven fashion, altered DNA methylation may be viewed as a secondary mechanism involved in carcinogenesis. Research aimed at discerning the mechanisms by which chemicals can transform normal cells into frank carcinomas has both theoretical and practical implications. Through an increased understanding of the mechanisms by which chemicals affect the carcinogenic process, we learn more about basic biology while, at the same time, providing the type of information required to make more rational safety assessment decisions concerning their actual potential to cause cancer under particular conditions of exposure. One key question is: does the mechanism of action of the chemical in question involve a secondary mechanism and, if so, what dose may be below its threshold?

  9. 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.

  10. 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.

  11. 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.

  12. Glucan: mechanisms involved in its radioprotective effect

    International Nuclear Information System (INIS)

    Patchen, M.L.; D'Alesandro, M.M.; Brook, I.; Blakely, W.F.; MacVittie, T.J.

    1987-01-01

    It has generally been accepted that most biologically derived agents that are radioprotective in the hemopoietic-syndrome dose range (eg, endotoxin, Bacillus Calmette Guerin, Corynebacterium parvum, etc) exert their beneficial properties by enhancing hemopoietic recovery and hence, by regenerating the host's ability to resist life-threatening opportunistic infections. However, using glucan as a hemopoietic stimulant/radioprotectant, we have demonstrated that host resistance to opportunistic infection is enhanced in these mice even prior to the detection of significant hemopoietic regeneration. This early enhanced resistance to microbial invasion in glucan-treated irradiated mice could be correlated with enhanced and/or prolonged macrophage (but not granulocyte) function. These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free-radical scavenger. Because macrophages have been shown to selectively phagocytize and sequester glucan, the possibility that these specific cells may be protected by virtue of glucan's scavenging ability is also suggested

  13. 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

  14. 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

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

    Science.gov (United States)

    Borges, Juliana Pereira; Lessa, Marcos Adriano

    2015-01-01

    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. PMID:25830711

  16. 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.

  17. Brain mechanisms underlying human communication.

    Science.gov (United States)

    Noordzij, Matthijs L; 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 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.

  18. 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.

  19. A systems biology-based approach to uncovering the molecular mechanisms underlying the effects of dragon's blood tablet in colitis, involving the integration of chemical analysis, ADME prediction, and network pharmacology.

    Directory of Open Access Journals (Sweden)

    Haiyu Xu

    Full Text Available Traditional Chinese medicine (TCM is one of the oldest East Asian medical systems. The present study adopted a systems biology-based approach to provide new insights relating to the active constituents and molecular mechanisms underlying the effects of dragon's blood (DB tablets for the treatment of colitis. This study integrated chemical analysis, prediction of absorption, distribution, metabolism, and excretion (ADME, and network pharmacology. Firstly, a rapid, reliable, and accurate ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was employed to identify 48 components of DB tablets. In silico prediction of the passive absorption of these compounds, based on Caco-2 cell permeability, and their P450 metabolism enabled the identification of 22 potentially absorbed components and 8 metabolites. Finally, networks were constructed to analyze interactions between these DB components/metabolites absorbed and their putative targets, and between the putative DB targets and known therapeutic targets for colitis. This study provided a great opportunity to deepen the understanding of the complex pharmacological mechanisms underlying the effects of DB in colitis treatment.

  20. 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 ...

  1. Peeling mechanism of tomato under infrared heating

    Science.gov (United States)

    Critical behaviors of peeling tomatoes using infrared heat are thermally induced peel loosening and subsequent cracking. However, the mechanism of peel loosening and cracking due to infrared heating remains unclear. This study aimed at investigating the mechanism of peeling tomatoes under infrared h...

  2. 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…

  3. Mechanical properties of cork under contact stresses

    International Nuclear Information System (INIS)

    Parralejo, A. D.; Guiberteau, F.; Fortes, M. A.; Rosa, M. E.

    2001-01-01

    In this work our interest is focussed on the mechanical behaviour of natural cork under contact stresses. Many of the applications of this curious material are related with its mechanical response under such a stress field, however this topic has not been still sufficiently considered in the scientific literature. For this purpose, we proposed the use of Hertzian indentation tests. By using this mythology we have investigated the cork structure influence on the corresponding mechanical properties. Our results reveal a clear mechanical anisotropy effect. Moreover, the elastic modulus corresponding to specific directions have been estimated. Several are the main advantages of this specific test mythology versus traditional uniaxial compression tests, specially simplicity and local character. (Author) 9 refs

  4. Surface Damage Mechanism of Monocrystalline Si Under Mechanical Loading

    Science.gov (United States)

    Zhao, Qingliang; Zhang, Quanli; To, Suet; Guo, Bing

    2017-03-01

    Single-point diamond scratching and nanoindentation on monocrystalline silicon wafer were performed to investigate the surface damage mechanism of Si under the contact loading. The results showed that three typical stages of material removal appeared during dynamic scratching, and a chemical reaction of Si with the diamond indenter and oxygen occurred under the high temperature. In addition, the Raman spectra of the various points in the scratching groove indicated that the Si-I to β-Sn structure (Si-II) and the following β-Sn structure (Si-II) to amorphous Si transformation appeared under the rapid loading/unloading condition of the diamond grit, and the volume change induced by the phase transformation resulted in a critical depth (ductile-brittle transition) of cut (˜60 nm ± 15 nm) much lower than the theoretical calculated results (˜387 nm). Moreover, it also led to abnormal load-displacement curves in the nanoindentation tests, resulting in the appearance of elbow and pop-out effects (˜270 nm at 20 s, 50 mN), which were highly dependent on the loading/unloading conditions. In summary, phase transformation of Si promoted surface deformation and fracture under both static and dynamic mechanical loading.

  5. 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.

  6. 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 <5%. The bubble size is larger than resonance size and smaller than acoustic wavelength. The amplitude of acoustic pressure wave was estimated using the 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.

  7. 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.

  8. Deformation Mechanisms of Gum Metals Under Nanoindentation

    Science.gov (United States)

    Sankaran, Rohini Priya

    defect structures to applied loading, we perform ex-situ nanoindentation. Nanoindentation is a convenient method as the plastic deformation is localized and probes a nominally defect free volume of the material. We subsequently characterize the defect structures in these alloys with both conventional TEM and advanced techniques such as HAADF HRSTEM and nanoprobe diffraction. These advanced techniques allow for a more thorough understanding of the observed deformation features. The main findings from this investigation are as follows. As expected we observe that a non-equilibrium phase, o, is present in the leaner beta-stabilized alloy, ST Ref-1. We do not find any direct evidence of secondary phases in STGM, and we find the beta phase in CWGM, along with lath microstructure with subgrain structure consisting of dislocation cell networks. Upon nanoindentation, we find twinning accompanied by beta nucleation on the twin boundary in ST Ref-1 samples. This result is consistent with previous findings and is reasonable considering the alloy is unstable with respect to beta transformation. We find deformation nanotwinning in cold worked gum metals under nanoindentation, which is initially surprising. We argue that when viewed as a nanocrystalline material, such a deformation mechanism is consistent with previous work, and furthermore, a deformation nanotwinned structure does not preclude an ideal shear mechanism from operating in the alloy. Lastly, we observe continuous lattice rotations in STGM under nanoindentation via nanoprobe diffraction. With this technique, for the first time we can demonstrate that the lattice rotations are truly continuous at the nanoscale. We can quantify this lattice rotation, and find that even though the rotation is large, it may be mediated by a reasonable geometrically necessary dislocation density, and note that similar rotations are typically observed in other materials under nanoindentation. HRSTEM and conventional TEM data confirm the

  9. Underlying causal factors associated with construction worker fatalities involving stepladders

    Directory of Open Access Journals (Sweden)

    Aneurin Thomas James Grant

    2013-03-01

    Full Text Available Stepladders are frequently utilized on construction projects as a means of access to elevation. Stepladder heights commonly range from 4 feet (1.2 m to 14 feet (4.3 m. Since these heights are not extreme, there is a common misperception that stepladder use presents a low risk. On the contrary, extreme care must be exercised to ensure that work on stepladders is performed safely, as described in the conspicuously located recommendations and brightly-colored warnings that adorn virtually all newly-purchased equipment. Despite this, accidents involving stepladders occur on a regular basis.  This study was conducted to better understand the underlying causes of these accidents. The narrative descriptions of 180 stepladder-related fatalities were obtained from the U.S. Occupational Safety and Health Administration and were analyzed to identify the at-risk behaviors that preceded the fatality incidents. The results showed that most of the incidents should have been anticipated and could have been avoided. Unsafe practices such as improper lockout-tagout of electrical equipment, loss of balance, working on a folded stepladder, over-reaching, straddling the ladder, “walking” the ladder, poor footing, and unstable/shifting ladders, among others were identified. Virtually all of these fatalities could have been avoided by adhering to the guidelines posted on the stepladders and by complying with basic safe construction practices. 

  10. Underlying causal factors associated with construction worker fatalities involving stepladders

    Directory of Open Access Journals (Sweden)

    Aneurin Thomas James Grant

    2013-03-01

    Full Text Available Stepladders are frequently utilized on construction projects as a means of access to elevation. Stepladder heights commonly range from 4 feet (1.2 m to 14 feet (4.3 m. Since these heights are not extreme, there is a common misperception that stepladder use presents a low risk. On the contrary, extreme care must be exercised to ensure that work on stepladders is performed safely, as described in the conspicuously located recommendations and brightly-colored warnings that adorn virtually all newly-purchased equipment. Despite this, accidents involving stepladders occur on a regular basis.  This study was conducted to better understand the underlying causes of these accidents. The narrative descriptions of 180 stepladder-related fatalities were obtained from the U.S. Occupational Safety and Health Administration and were analyzed to identify the at-risk behaviors that preceded the fatality incidents. The results showed that most of the incidents should have been anticipated and could have been avoided. Unsafe practices such as improper lockout-tagout of electrical equipment, loss of balance, working on a folded stepladder, over-reaching, straddling the ladder, “walking” the ladder, poor footing, and unstable/shifting ladders, among others were identified. Virtually all of these fatalities could have been avoided by adhering to the guidelines posted on the stepladders and by complying with basic safe construction practices.

  11. 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

  12. 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.

  13. 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.

  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. Investigations into the involvement of NMDA mechanisms in recognition memory.

    Science.gov (United States)

    Warburton, E Clea; Barker, Gareth R I; Brown, Malcom W

    2013-11-01

    This review will focus on evidence showing that NMDA receptor neurotransmission is critical for synaptic plasticity processes within brain regions known to be necessary for the formation of object recognition memories. The aim will be to provide evidence concerning NMDA mechanisms related to recognition memory processes and show that recognition memory for objects, places or associations between objects and places depends on NMDA neurotransmission within the perirhinal cortex, temporal association cortex medial prefrontal cortex and hippocampus. Administration of the NMDA antagonist AP5, selectively into each of these brain regions has revealed that the extent of the involvement NMDA receptors appears dependent on the type of information required to solve the recognition memory task; thus NMDA receptors in the perirhinal cortex are crucial for the encoding of long-term recognition memory for objects, and object-in-place associations, but not for short-term recognition memory or for retrieval. In contrast the hippocampus and medial prefrontal cortex are required for both long-term and short-term recognition memory for places or associations between objects and places, or for recognition memory tasks that have a temporal component. Such studies have therefore confirmed that the multiple brain regions make distinct contributions to recognition memory but in addition that more than one synaptic plasticity process must be involved. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Molecular mechanics of silk nanostructures under varied mechanical loading.

    Science.gov (United States)

    Bratzel, Graham; Buehler, Markus J

    2012-06-01

    Spider dragline silk is a self-assembling tunable protein composite fiber that rivals many engineering fibers in tensile strength, extensibility, and toughness, making it one of the most versatile biocompatible materials and most inviting for synthetic mimicry. While experimental studies have shown that the peptide sequence and molecular structure of silk have a direct influence on the stiffness, toughness, and failure strength of silk, few molecular-level analyses of the nanostructure of silk assemblies, in particular, under variations of genetic sequences have been reported. In this study, atomistic-level structures of wildtype as well as modified MaSp1 protein from the Nephila clavipes spider dragline silk sequences, obtained using an in silico approach based on replica exchange molecular dynamics and explicit water molecular dynamics, are subjected to simulated nanomechanical testing using different force-control loading conditions including stretch, pull-out, and peel. The authors have explored the effects of the poly-alanine length of the N. clavipes MaSp1 peptide sequence and identify differences in nanomechanical loading conditions on the behavior of a unit cell of 15 strands with 840-990 total residues used to represent a cross-linking β-sheet crystal node in the network within a fibril of the dragline silk thread. The specific loading condition used, representing concepts derived from the protein network connectivity at larger scales, have a significant effect on the mechanical behavior. Our analysis incorporates stretching, pull-out, and peel testing to connect biochemical features to mechanical behavior. The method used in this study could find broad applications in de novo design of silk-like tunable materials for an array of applications. Copyright © 2011 Wiley Periodicals, Inc.

  17. 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.

  18. Neural Mechanisms Underlying Risk and Ambiguity Attitudes.

    Science.gov (United States)

    Blankenstein, Neeltje E; Peper, Jiska S; Crone, Eveline A; van Duijvenvoorde, Anna C K

    2017-11-01

    Individual differences in attitudes to risk (a taste for risk, known probabilities) and ambiguity (a tolerance for uncertainty, unknown probabilities) differentially influence risky decision-making. However, it is not well understood whether risk and ambiguity are coded differently within individuals. Here, we tested whether individual differences in risk and ambiguity attitudes were reflected in distinct neural correlates during choice and outcome processing of risky and ambiguous gambles. To these ends, we developed a neuroimaging task in which participants ( n = 50) chose between a sure gain and a gamble, which was either risky or ambiguous, and presented decision outcomes (gains, no gains). From a separate task in which the amount, probability, and ambiguity level were varied, we estimated individuals' risk and ambiguity attitudes. Although there was pronounced neural overlap between risky and ambiguous gambling in a network typically related to decision-making under uncertainty, relatively more risk-seeking attitudes were associated with increased activation in valuation regions of the brain (medial and lateral OFC), whereas relatively more ambiguity-seeking attitudes were related to temporal cortex activation. In addition, although striatum activation was observed during reward processing irrespective of a prior risky or ambiguous gamble, reward processing after an ambiguous gamble resulted in enhanced dorsomedial PFC activation, possibly functioning as a general signal of uncertainty coding. These findings suggest that different neural mechanisms reflect individual differences in risk and ambiguity attitudes and that risk and ambiguity may impact overt risk-taking behavior in different ways.

  19. 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.

  20. 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.

  1. Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

    Science.gov (United States)

    Tonacchera, M; Vitti, P; Agretti, P; Ceccarini, G; Perri, A; Cavaliere, R; Mazzi, B; Naccarato, A G; Viacava, P; Miccoli, P; Pinchera, A; Chiovato, L

    1999-11-01

    The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

  2. 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 ….

  3. Magnetization reversal mechanisms under oblique magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Ntallis, N.; Efthimiadis, K.G., E-mail: kge@auth.gr

    2017-03-01

    In this work finite element micromagnetic simulations were performed in order to study the reversal mechanisms of spherical ferromagnetic particles with uniaxial magnetocrystalline anisotropy, when they are magnetized along an oblique direction with respect to the anisotropy axis. Magnetization loops are taken in different directions of external magnetic field, at different anisotropy constants and particle sizes. In the simulation results, the three reversal mechanisms (coherent, curling and domains) are observed and new phenomena arise due to the action of oblique magnetic fields. Moreover, the dependence of the critical fields with respect to the angle of the external field is presented. - Highlights: • Finite element micromagnetic simulation of the three different reversal mechanisms. • For the curling mechanism, the new phenomenon is the rotation of the vortex. • In the domain reversal mechanism, the formed domain wall is smaller than 180°. • In soft ferromagnetic particles a rearrangement of the magnetic domains is observed.

  4. Underlying mechanism in the water chemistry of nuclear systems

    International Nuclear Information System (INIS)

    Walton, G.N.

    1978-01-01

    The equilibrium between dissolved hydrogen and oxygen in the molecular decomposition of water, and the equilibrium between hydrogen ions and hydroxyl ions in the ionic dissociation of water, both constitute important underlying mechanisms in the corrosion behaviour of water. The two equilibria, and the rates of the reactions involved in water and steam, will be compared and contrasted as a function of temperature, pressure and radiation. The effects of the equilibria on the hydrolysis and solubility of ferrous and ferric ions, and the ions of other metals, will be discussed in relation to the control of conditions in the coolant circuits of nuclear reactors. A third mechanism to discussed is the electrochemical exchange reactions that can contribute to the contamination of circuits. (author)

  5. 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.

  6. Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

    Science.gov (United States)

    Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

    2016-01-01

    Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging. Copyright © 2016. Published by Elsevier Inc.

  7. 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.

  8. Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

    NARCIS (Netherlands)

    Denning, Denise; Roos, Wouter H

    2016-01-01

    The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Biochemical mechanisms of signaling: perspectives in plants under arsenic stress.

    Science.gov (United States)

    Islam, Ejazul; Khan, Muhammad Tahir; Irem, Samra

    2015-04-01

    Plants are the ultimate food source for humans, either directly or indirectly. Being sessile in nature, they are exposed to various biotic and abiotic stresses because of changing climate that adversely effects their growth and development. Contamination of heavy metals is one of the major abiotic stresses because of anthropogenic as well as natural factors which lead to increased toxicity and accumulation in plants. Arsenic is a naturally occurring metalloid toxin present in the earth crust. Due to its presence in terrestrial and aquatic environments, it effects the growth of plants. Plants can tolerate arsenic using several mechanisms like phytochelation, vacuole sequestration and activation of antioxidant defense systems. Several signaling mechanisms have evolved in plants that involve the use of proteins, calcium ions, hormones, reactive oxygen species and nitric oxide as signaling molecules to cope with arsenic toxicity. These mechanisms facilitate plants to survive under metal stress by activating their defense systems. The pathways by which these stress signals are perceived and responded is an unexplored area of research and there are lots of gaps still to be filled. A good understanding of these signaling pathways can help in raising the plants which can perform better in arsenic contaminated soil and water. In order to increase the survival of plants in contaminated areas there is a strong need to identify suitable gene targets that can be modified according to needs of the stakeholders using various biotechnological techniques. This review focuses on the signaling mechanisms of plants grown under arsenic stress and will give an insight of the different sensory systems in plants. Furthermore, it provides the knowledge about several pathways that can be exploited to develop plant cultivars which are resistant to arsenic stress or can reduce its uptake to minimize the risk of arsenic toxicity through food chain thus ensuring food security. Copyright © 2015

  14. 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

  15. 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

  16. V1 mechanisms underlying chromatic contrast detection

    Science.gov (United States)

    Hass, Charles A.

    2013-01-01

    To elucidate the cortical mechanisms of color vision, we recorded from individual primary visual cortex (V1) neurons in macaque monkeys performing a chromatic detection task. Roughly 30% of the neurons that we encountered were unresponsive at the monkeys' psychophysical detection threshold (PT). The other 70% were responsive at threshold but on average, were slightly less sensitive than the monkey. For these neurons, the relationship between neurometric threshold (NT) and PT was consistent across the four isoluminant color directions tested. A corollary of this result is that NTs were roughly four times lower for stimuli that modulated the long- and middle-wavelength sensitive cones out of phase. Nearly one-half of the neurons that responded to chromatic stimuli at the monkeys' detection threshold also responded to high-contrast luminance modulations, suggesting a role for neurons that are jointly tuned to color and luminance in chromatic detection. Analysis of neuronal contrast-response functions and signal-to-noise ratios yielded no evidence for a special set of “cardinal color directions,” for which V1 neurons are particularly sensitive. We conclude that at detection threshold—as shown previously with high-contrast stimuli—V1 neurons are tuned for a diverse set of color directions and do not segregate naturally into red–green and blue–yellow categories. PMID:23446689

  17. 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.

  18. Biological pathways and genetic mechanisms involved in social functioning.

    Science.gov (United States)

    Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G

    2013-08-01

    To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.

  19. 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).

  20. 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.

  1. 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.

  2. 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.

  3. An Analysis of the Dispute Settlement Mechanism under the

    African Journals Online (AJOL)

    user

    This article examines and evaluates the consumer redress mechanism, .... 23 The behaviour or conduct must be prohibited in terms of the Competition Act ...... appropriate orders and provide "sufficient" remedies to avoid the involvement of the.

  4. Molecular mechanisms involved in the production of chromosomal aberrations. I

    International Nuclear Information System (INIS)

    Natarajan, A.T.; Obe, G.

    1978-01-01

    Chinese hamster ovary cells (CHO) were X-irradiated in G2 stage of the cell cycle and immediately treated, in the presence of inactivated Sendai virus, with Neurospora endonuclease (E.C. 3.1.4.), an enzyme which is specific for cleaving single-stranded DNA. With this treatment, the frequencies of all types of chromosome aberrations increased when compared to X-irradiated controls. These results are interpreted as due to the conversion of some of the X-ray induced single-stranded DNA breaks into double-strand breaks by this enzyme. Similar enhancement due to this enzyme was found following treatment with methyl methanesulfonate (MMS) and bleomycin, but not following UV and mitomycin C. Addition of Micrococcus endonuclease and Neurospora endonuclease to the cells did not alter the frequencies of aberrations induced by UV. The introduction of enzymes with specific DNA-repair function offers possibilities to probe into the molecular events involved in the formation of structural chromosome aberrations induced by different classes of physical and chemical mutagens. (Auth.)

  5. The Potential Mechanism of ZFX Involvement in the Cell Growth

    Directory of Open Access Journals (Sweden)

    Mahboube Ganji arjenaki

    2016-04-01

    Full Text Available Background:The zinc-finger X linked (ZFX gene encodes a transcription factor that acts as a regulator of self-renewal of stem cells. Due to the role of ZFX in cell growth, understanding ZFX protein-protein interactions helps to clarify its proper biological functions in signaling pathways. The aim of this study is to define ZFX protein-protein interactions and the role of ZFX in cell growth. Materials and Methods: The PIPs output includes three interacting proteins with ZFX: eukaryotic translation initiation factor 3 subunit I(EIF3I, eukaryotic translation initiation factor 3 subunit G(EIF3G and protein nuclear pore and COPII coat complex component homolog isoform 3 (SEC13L1. Results: As a cargo and transmembrane protein interacting with Sec13,eIF3I and eIF3G, ZFX mediates cargo sorting in COPII vesicles at ER exit sites. While traveling to cis-Golgi, eIF3I is phosphorylated by the mechanistic target of rapamycin (mTOR. Proteins transport by COPI vesicles to the nucleusouter site layer containing SEC13 via the contribution of microtubules. EIF3G and eIF3I interact with coatomer protein complex subunit beta 2 (COPB2 that helps to enclose ZFX in COPI vesicle. ZFX and eIF3G enter nucleolus where activation of transcription from pre rDNA genes occurs. Conclusion:We proposed a model in which ZFX is involved in cell growth by promoting the transcription of rDNA genes.

  6. 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.

  7. Mechanisms involved in alternariol-induced cell cycle arrest

    International Nuclear Information System (INIS)

    Solhaug, A.; Vines, L.L.; Ivanova, L.; Spilsberg, B.; Holme, J.A.; Pestka, J.; Collins, A.; Eriksen, G.S.

    2012-01-01

    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 μM almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 μM) 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 μM 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Crack assessment of pipe under combined thermal and mechanical load

    International Nuclear Information System (INIS)

    Song, Tae Kwang; Kim, Yun Jae

    2009-01-01

    In this paper, J-integral and transient C(t)-integral, which were key parameters in low temperature and high temperature fracture mechanics, under combined thermal and mechanical load were estimated via 3-dimensional finite element analyses. Various type of thermal and mechanical load, material hardening were considered to decrease conservatism in existing solutions. As a results, V-factor and redistribution time for combined thermal and mechanical load were proposed to calculate J-integral and C(t)-integral, respectively.

  13. Clustering mechanism of oxocarboxylic acids involving hydration reaction: Implications for the atmospheric models

    Science.gov (United States)

    Liu, Ling; Kupiainen-Määttä, Oona; Zhang, Haijie; Li, Hao; Zhong, Jie; Kurtén, Theo; Vehkamäki, Hanna; Zhang, Shaowen; Zhang, Yunhong; Ge, Maofa; Zhang, Xiuhui; Li, Zesheng

    2018-06-01

    The formation of atmospheric aerosol particles from condensable gases is a dominant source of particulate matter in the boundary layer, but the mechanism is still ambiguous. During the clustering process, precursors with different reactivities can induce various chemical reactions in addition to the formation of hydrogen bonds. However, the clustering mechanism involving chemical reactions is rarely considered in most of the nucleation process models. Oxocarboxylic acids are common compositions of secondary organic aerosol, but the role of oxocarboxylic acids in secondary organic aerosol formation is still not fully understood. In this paper, glyoxylic acid, the simplest and the most abundant atmospheric oxocarboxylic acid, has been selected as a representative example of oxocarboxylic acids in order to study the clustering mechanism involving hydration reactions using density functional theory combined with the Atmospheric Clusters Dynamic Code. The hydration reaction of glyoxylic acid can occur either in the gas phase or during the clustering process. Under atmospheric conditions, the total conversion ratio of glyoxylic acid to its hydration reaction product (2,2-dihydroxyacetic acid) in both gas phase and clusters can be up to 85%, and the product can further participate in the clustering process. The differences in cluster structures and properties induced by the hydration reaction lead to significant differences in cluster formation rates and pathways at relatively low temperatures.

  14. 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.

  15. All Cues Are Not Created Equal: Obtaining Attitude Persistence under Low-Involvement Conditions.

    OpenAIRE

    Sengupta, Jaideep; Goodstein, Ronald C; Boninger, David S

    1997-01-01

    Attitude persistence research in consumer behavior has been predominantly associated with high- rather than low-involvement processing. Advertising, however, is most often processed as a low-involvement communication. The authors predict that different low-involvement cues lead to different degrees of attitude persistence. Consistent with this prediction, they find that under low-involvement conditions, when both related and unrelated peripheral cues evoke similar initial attitudes, only when...

  16. Underlying mechanisms of improving physical activity behavior after rehabilitation

    NARCIS (Netherlands)

    van der Ploeg, H.P.; Streppel, K.R.; van der Beek, A.J.; van der Woude, L.H.V.; van Harten, W.H.; van Mechelen, W.

    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

  17. 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

  18. Nonlinear Mechanics of MEMS Rectangular Microplates under Electrostatic Actuation

    KAUST Repository

    Saghir, Shahid

    2016-01-01

    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

  19. Animal behavior models of the mechanisms underlying antipsychotic atypicality.

    NARCIS (Netherlands)

    Geyer, M.A.; Ellenbroek, B.A.

    2003-01-01

    This review describes the animal behavior models that provide insight into the mechanisms underlying the critical differences between the actions of typical vs. atypical antipsychotic drugs. Although many of these models are capable of differentiating between antipsychotic and other psychotropic

  20. Control of a perturbed under-actuated mechanical system

    KAUST Repository

    Zayane, Chadia; Laleg-Kirati, Taous-Meriem; Chemori, Ahmed

    2015-01-01

    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

  1. Mechanisms and neuronal networks involved in reactive and proactive cognitive control of interference in working memory.

    Science.gov (United States)

    Irlbacher, Kerstin; Kraft, Antje; Kehrer, Stefanie; Brandt, Stephan A

    2014-10-01

    Cognitive control can be reactive or proactive in nature. Reactive control mechanisms, which support the resolution of interference, start after its onset. Conversely, proactive control involves the anticipation and prevention of interference prior to its occurrence. The interrelation of both types of cognitive control is currently under debate: Are they mediated by different neuronal networks? Or are there neuronal structures that have the potential to act in a proactive as well as in a reactive manner? This review illustrates the way in which integrating knowledge gathered from behavioral studies, functional imaging, and human electroencephalography proves useful in answering these questions. We focus on studies that investigate interference resolution at the level of working memory representations. In summary, different mechanisms are instrumental in supporting reactive and proactive control. Distinct neuronal networks are involved, though some brain regions, especially pre-SMA, possess functions that are relevant to both control modes. Therefore, activation of these brain areas could be observed in reactive, as well as proactive control, but at different times during information processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Rules and mechanisms governing octahedral tilts in perovskites under pressure

    Science.gov (United States)

    Xiang, H. J.; Guennou, Mael; Íñiguez, Jorge; Kreisel, Jens; Bellaiche, L.

    2017-08-01

    The rotation of octahedra (octahedral tilting) is common in A B O3 perovskites and relevant to many physical phenomena, ranging from electronic and magnetic properties, metal-insulator transitions to improper ferroelectricity. Hydrostatic pressure is an efficient way to tune and control octahedral tiltings. However, the pressure behavior of such tiltings can dramatically differ from one material to another, with the origins of such differences remaining controversial. In this paper, we discover several new mechanisms and formulate a set of simple rules that allow us to understand how pressure affects oxygen octahedral tiltings via the use and analysis of first-principles results for a variety of compounds. Besides the known A -O interactions, we reveal that the interactions between specific B ions and oxygen ions contribute to the tilting instability. We explain the previously reported trend that the derivative of the oxygen octahedral tilting with respect to pressure (dR /dP ) usually decreases with both the tolerance factor and the ionization state of the A ion by illustrating the key role of A -O interactions and their change under pressure. Furthermore, three new mechanisms/rules are discovered, namely that (i) the octahedral rotations in A B O3 perovskites with empty low-lying d states on the B site are greatly enhanced by pressure, in order to lower the electronic kinetic energy; (ii) dR /dP is enhanced when the system possesses weak tilt instabilities, and (iii) for the most common phase exhibited by perovskites—the orthorhombic Pbnm state—the in-phase and antiphase octahedral rotations are not automatically both suppressed or both enhanced by the application of pressure because of a trilinear coupling between these two rotation types and an antipolar mode involving the A ions. We further predict that the polarization associated with the so-called hybrid improper ferroelectricity could be manipulated by hydrostatic pressure by indirectly controlling the

  3. New Insights on Neurobiological Mechanisms underlying Alcohol Addiction

    Science.gov (United States)

    Cui, Changhai; Noronha, Antonio; Morikawa, Hitoshi; Alvarez, Veronica A.; Stuber, Garret D.; Szumlinski, Karen K.; Kash, Thomas L.; Roberto, Marisa; Wilcox, Mark V.

    2012-01-01

    Alcohol dependence/addiction is mediated by complex neural mechanisms that involve multiple brain circuits and neuroadaptive changes in a variety of neurotransmitter and neuropeptide systems. Although recent studies have provided substantial information on the neurobiological mechanisms that drive alcohol drinking behavior, significant challenges remain in understanding how alcohol-induced neuroadaptations occur and how different neurocircuits and pathways cross-talk. This review article highlights recent progress in understanding neural mechanisms of alcohol addiction from the perspectives of the development and maintenance of alcohol dependence. It provides insights on cross talks of different mechanisms and reviews the latest studies on metaplasticity, structural plasticity, interface of reward and stress pathways, and cross-talk of different neural signaling systems involved in binge-like drinking and alcohol dependence. PMID:23159531

  4. 77 FR 54584 - Final Action Under the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH...

    Science.gov (United States)

    2012-09-05

    ... changes. Human gene transfer also raises scientific, medical, social, and ethical considerations that... currently reviewed under Section III-B-1, Experiments Involving the Cloning of Toxin Molecules with LD50 of...

  5. Believing versus interacting: Behavioural and neural mechanisms underlying interpersonal coordination

    DEFF Research Database (Denmark)

    Konvalinka, Ivana; Bauer, Markus; Kilner, James

    When two people engage in a bidirectional interaction with each other, they use both bottom-up sensorimotor mechanisms such as monitoring and adapting to the behaviour of the other, as well as top-down cognitive processes, modulating their beliefs and allowing them to make decisions. Most research...... in joint action has investigated only one of these mechanisms at a time – low-level processes underlying joint coordination, or high-level cognitive mechanisms that give insight into how people think about another. In real interactions, interplay between these two mechanisms modulates how we interact...

  6. Mechanisms underlying reduced fertility in anovular dairy cows.

    Science.gov (United States)

    Santos, J E P; Bisinotto, R S; Ribeiro, E S

    2016-07-01

    Resumption of ovulation after parturition is a coordinated process that involves recoupling of the GH/insulin-like growth factor 1 axis in the liver, increase in follicular development and steroidogenesis, and removal of negative feedback from estradiol in the hypothalamus. Infectious diseases and metabolic disorders associated with extensive negative energy balance during early lactation disrupt this pathway and delay first ovulation postpartum. Extended periods of anovulation postpartum exert long-lasting effects on fertility in dairy cows including the lack of spontaneous estrus, reduced pregnancy per artificial insemination (P/AI), and increased risk of pregnancy loss. Concentrations of progesterone in anovular cows subjected to synchronized programs for AI are insufficient to optimize follicular maturation, oocyte competence, and subsequent fertility to AI. Ovulation of first wave follicles, which develop under low concentrations of progesterone, reduces embryo quality in the first week after fertilization and P/AI in dairy cows. Although the specific mechanisms by which anovulation and low concentrations of progesterone impair oocyte quality have not been defined, studies with persistent follicles support the involvement of premature resumption of meiosis and degradation of maternal RNA. Suboptimal concentrations of progesterone before ovulation also increase the synthesis of PGF2α in response to oxytocin during the subsequent estrous cycle, which explains the greater incidence of short luteal phases after the first AI postpartum in anovular cows compared with estrous cyclic herd mates. It is suggested that increased spontaneous luteolysis early in the estrous cycle is one of the mechanisms that contributes to early embryonic losses in anovular cows. Anovulation also leads to major shifts in gene expression in elongated conceptuses during preimplantation stages of pregnancy. Transcripts involved with control of energy metabolism and DNA repair were

  7. 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.

  8. 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

  9. 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.

  10. Depression and Chronic Liver Diseases: Are There Shared Underlying Mechanisms?

    Directory of Open Access Journals (Sweden)

    Xiaoqin Huang

    2017-05-01

    Full Text Available The occurrence of depression is higher in patients with chronic liver disease (CLD than that in the general population. The mechanism described in previous studies mainly focused on inflammation and stress, which not only exists in CLD, but also emerges in common chronic diseases, leaving the specific mechanism unknown. This review was to summarize the prevalence and risk factors of depression in CLD including chronic hepatitis B, chronic hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease, and to point out the possible underlying mechanism of this potential link. Clarifying the origins of this common comorbidity (depression and CLD may provide more information to understand both diseases.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Mechanical behavior of silicon carbide nanoparticles under uniaxial compression

    Energy Technology Data Exchange (ETDEWEB)

    He, Qiuxiang; Fei, Jing; Tang, Chao; Zhong, Jianxin; Meng, Lijun, E-mail: ljmeng@xtu.edu.cn [Xiangtan University, Hunan Key Laboratory for Micro-Nano Energy Materials and Devices, Faculty of School of Physics and Optoelectronics (China)

    2016-03-15

    The mechanical behavior of SiC nanoparticles under uniaxial compression was investigated using an atomic-level compression simulation technique. The results revealed that the mechanical deformation of SiC nanocrystals is highly dependent on compression orientation, particle size, and temperature. A structural transformation from the original zinc-blende to a rock-salt phase is identified for SiC nanoparticles compressed along the [001] direction at low temperature. However, the rock-salt phase is not observed for SiC nanoparticles compressed along the [110] and [111] directions irrespective of size and temperature. The high-pressure-generated rock-salt phase strongly affects the mechanical behavior of the nanoparticles, including their hardness and deformation process. The hardness of [001]-compressed nanoparticles decreases monotonically as their size increases, different from that of [110] and [111]-compressed nanoparticles, which reaches a maximal value at a critical size and then decreases. Additionally, a temperature-dependent mechanical response was observed for all simulated SiC nanoparticles regardless of compression orientation and size. Interestingly, the hardness of SiC nanocrystals with a diameter of 8 nm compressed in [001]-orientation undergoes a steep decrease at 0.1–200 K and then a gradual decline from 250 to 1500 K. This trend can be attributed to different deformation mechanisms related to phase transformation and dislocations. Our results will be useful for practical applications of SiC nanoparticles under high pressure.

  19. 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)

  20. 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)

  1. 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.

  2. Turing mechanism underlying a branching model for lung morphogenesis.

    Science.gov (United States)

    Xu, Hui; Sun, Mingzhu; Zhao, Xin

    2017-01-01

    The mammalian lung develops through branching morphogenesis. Two primary forms of branching, which occur in order, in the lung have been identified: tip bifurcation and side branching. However, the mechanisms of lung branching morphogenesis remain to be explored. In our previous study, a biological mechanism was presented for lung branching pattern formation through a branching model. Here, we provide a mathematical mechanism underlying the branching patterns. By decoupling the branching model, we demonstrated the existence of Turing instability. We performed Turing instability analysis to reveal the mathematical mechanism of the branching patterns. Our simulation results show that the Turing patterns underlying the branching patterns are spot patterns that exhibit high local morphogen concentration. The high local morphogen concentration induces the growth of branching. Furthermore, we found that the sparse spot patterns underlie the tip bifurcation patterns, while the dense spot patterns underlies the side branching patterns. The dispersion relation analysis shows that the Turing wavelength affects the branching structure. As the wavelength decreases, the spot patterns change from sparse to dense, the rate of tip bifurcation decreases and side branching eventually occurs instead. In the process of transformation, there may exists hybrid branching that mixes tip bifurcation and side branching. Since experimental studies have reported that branching mode switching from side branching to tip bifurcation in the lung is under genetic control, our simulation results suggest that genes control the switch of the branching mode by regulating the Turing wavelength. Our results provide a novel insight into and understanding of the formation of branching patterns in the lung and other biological systems.

  3. Mechanical Behaviour of Bolted Joints Under Impact Rates of Loading

    Science.gov (United States)

    2012-01-01

    M. (1995). Bearing Strength of Autoclave and oven cured kevlar / epoxy laminates under static and dynamic loading. Compostes, 451-456. Kretsis, G...Joints in Glass Fibre/ Epoxy Laminates. Composites, Volume 16. No 2. Kolsky, H. (1949). An Investigation of the Mechanical Properties of Materials at...elongating the pulse width. The responses are read by the strain gages bonded on the incident and transmission bar with Vishay AE-10 epoxy . The gages

  4. 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.

  5. 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.

  6. 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.

  7. Fracture mechanics of hydroxyapatite single crystals under geometric confinement.

    Science.gov (United States)

    Libonati, Flavia; Nair, Arun K; Vergani, Laura; Buehler, Markus J

    2013-04-01

    Geometric confinement to the nanoscale, a concept that refers to the characteristic dimensions of structural features of materials at this length scale, has been shown to control the mechanical behavior of many biological materials or their building blocks, and such effects have also been suggested to play a crucial role in enhancing the strength and toughness of bone. Here we study the effect of geometric confinement on the fracture mechanism of hydroxyapatite (HAP) crystals that form the mineralized phase in bone. We report a series of molecular simulations of HAP crystals with an edge crack on the (001) plane under tensile loading, and we systematically vary the sample height whilst keeping the sample and the crack length constant. We find that by decreasing the sample height the stress concentration at the tip of the crack disappears for samples with a height smaller than 4.15nm, below which the material shows a different failure mode characterized by a more ductile mechanism with much larger failure strains, and the strength approaching that of a flaw-less crystal. This study directly confirms an earlier suggestion of a flaw-tolerant state that appears under geometric confinement and may explain the mechanical stability of the reinforcing HAP platelets in bone. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. 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-...

  9. 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.

  10. Studies on Molecular Mechanisms Underlying Spinocerebellar Ataxia Type 3

    DEFF Research Database (Denmark)

    Kristensen, Line Vildbrad

    . 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...... in protein quality control. In SCA3 patients polyQ expanded ataxin-3 forms intranuclear inclusions in various brain areas, but why the polyQ expansion of ataxin-3 leads to neuronal dysfunction is still not well understood. This thesis describes molecular biological investigations of ataxin-3 biology, aimed...... at furthering our understanding of SCA3 disease mechanisms. In manuscript I, we investigated if post-translational modifications of ataxin-3 were changed by the polyQ expansion. The ubiquitin chain topology and ubiquitination pattern of ataxin-3 were unaltered by the polyQ expansion. In contrast...

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Vascular mechanisms underlying the hypotensive effect of Rumex acetosa.

    Science.gov (United States)

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

    2018-12-01

    Rumex acetosa L. (Polygonaceae) is well known in traditional medicine for its therapeutic efficacy as an antihypertensive. The study investigates antihypertensive potential of crude methanol extract (Ra.Cr) and fractions of Rumex acetosa in normotensive and hypertensive rat models and probes the underlying vascular mechanisms. Ra.Cr and its fractions were tested in vivo on normotensive and hypertensive Sprague-Dawley rats under anaesthesia for blood pressure lowering effect. In vitro experiments on rat and Oryctolagus cuniculus rabbit aortae were employed to probe the underlying vasorelaxant mechanism. In normotensive rats under anaesthesia, Ra.Cr caused fall in MAP (40 mmHg) at 50 mg/kg with % fall of 27.88 ± 4.55. Among the fractions tested, aqueous fraction was more potent at the dose of 50 mg/kg with % fall of 45.63 ± 2.84. In hypertensive rats under similar conditions, extract and fractions showed antihypertensive effect at same doses while aqueous fraction being more potent, exhibited 68.53 ± 4.45% fall in MAP (70 mmHg). In isolated rat aortic rings precontracted with phenylephrine (PE), Ra.Cr and fractions induced endothelium-dependent vasorelaxation, which was partially blocked in presence of l-NAME, indomethacin and atropine. In isolated rabbit aortic rings pre-contracted with PE and K + -(80 mM), Ra.Cr induced vasorelaxation and shifted Ca 2+ concentration-response curves to the right and suppressed PE peak formation, similar to verapamil, in Ca 2+ -free medium. The data indicate that l-NAME and atropine-sensitive endothelial-derived NO and COX enzyme inhibitors and Ca 2+ entry blocking-mediated vasodilator effect of the extract explain its antihypertensive potential.

  16. Proteins involved in flor yeast carbon metabolism under biofilm formation conditions.

    Science.gov (United States)

    Moreno-García, Jaime; García-Martínez, Teresa; Moreno, Juan; Mauricio, Juan Carlos

    2015-04-01

    A lack of sugars during the production of biologically aged wines after fermentation of grape must causes flor yeasts to metabolize other carbon molecules formed during fermentation (ethanol and glycerol, mainly). In this work, a proteome analysis involving OFFGEL fractionation prior to LC/MS detection was used to elucidate the carbon metabolism of a flor yeast strain under biofilm formation conditions (BFC). The results were compared with those obtained under non-biofilm formation conditions (NBFC). Proteins associated to processes such as non-fermentable carbon uptake, the glyoxylate and TCA cycles, cellular respiration and inositol metabolism were detected at higher concentrations under BFC than under the reference conditions (NBFC). This study constitutes the first attempt at identifying the flor yeast proteins responsible for the peculiar sensory profile of biologically aged wines. A better metabolic knowledge of flor yeasts might facilitate the development of effective strategies for improved production of these special wines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Evidence for the involvement of MC4 receptors in the central mechanisms of opioid antinociception

    NARCIS (Netherlands)

    Starowicz, Katarzyna

    2005-01-01

    The data described in this thesis extend general knowledge of the involvement of the MC4 receptor in mechanisms of analgesia. The following aspects outlined below constitute novel information. Firstly, the MC4R localization in the DRG is demonstrated. The MC4 receptor was assumed to exist

  18. 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. ...

  19. 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.

  20. Expected utility violations evolve under status-based selection mechanisms.

    Science.gov (United States)

    Dickson, Eric S

    2008-10-07

    The expected utility theory of decision making under uncertainty, a cornerstone of modern economics, assumes that humans linearly weight "utilities" for different possible outcomes by the probabilities with which these outcomes occur. Despite the theory's intuitive appeal, both from normative and from evolutionary perspectives, many experiments demonstrate systematic, though poorly understood, patterns of deviation from EU predictions. This paper offers a novel theoretical account of such patterns of deviation by demonstrating that EU violations can emerge from evolutionary selection when individual "status" affects inclusive fitness. In humans, battles for resources and social standing involve high-stakes decision making, and assortative mating ensures that status matters for fitness outcomes. The paper therefore proposes grounding the study of decision making under uncertainty in an evolutionary game-theoretic framework.

  1. 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

  2. Mechanisms underlying astringency: introduction to an oral tribology approach

    Science.gov (United States)

    Upadhyay, Rutuja; Brossard, Natalia; Chen, Jianshe

    2016-03-01

    Astringency is one of the predominant factors in the sensory experience of many foods and beverages ranging from wine to nuts. The scientific community is discussing mechanisms that explain this complex phenomenon, since there are no conclusive results which correlate well with sensory astringency. Therefore, the mechanisms and perceptual characteristics of astringency warrant further discussion and investigation. This paper gives a brief introduction of the fundamentals of oral tribology forming a basis of the astringency mechanism. It discusses the current state of the literature on mechanisms underlying astringency describing the existing astringency models. The review discusses the crucial role of saliva and its physiology which contributes significantly in astringency perception in the mouth. It also provides an overview of research concerned with the physiological and psychophysical factors that mediate the perception of this sensation, establishing the ground for future research. Thus, the overall aim of the review is to establish the critical roles of oral friction (thin-film lubrication) in the sensation of astringency and possibly of some other specific sensory features.

  3. Failure Mechanisms of Brittle Rocks under Uniaxial Compression

    Science.gov (United States)

    Liu, Taoying; Cao, Ping

    2017-09-01

    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.

  4. Mechanisms underlying KCNQ1channel cell volume sensitivity

    DEFF Research Database (Denmark)

    Hammami, Sofia

    Cells are constantly exposed to changes in cell volume during cell metabolism, nutrient uptake, cell proliferation, cell migration and salt and water transport. In order to cope with these perturbations, potassium channels in line with chloride channels have been shown to be likely contributors...... to the process of cell volume adjustments. A great diversity of potassium channels being members of either the 6TM, 4 TM or 2 TM K+ channel gene family have been shown to be strictly regulated by small, fast changes in cell volume. However, the precise mechanism underlying the K+ channel sensitivity to cell...... volume alterations is not yet fully understood. The KCNQ1 channel belonging to the voltage gated KCNQ family is considered a precise sensor of volume changes. The goal of this thesis was to elucidate the mechanism that induces cell volume sensitivity. Until now, a number of investigators have implicitly...

  5. 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.

  6. 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

  7. Mechanisms Underlying Mammalian Hybrid Sterility in Two Feline Interspecies Models.

    Science.gov (United States)

    Davis, Brian W; Seabury, Christopher M; Brashear, Wesley A; Li, Gang; Roelke-Parker, Melody; Murphy, William J

    2015-10-01

    The phenomenon of male sterility in interspecies hybrids has been observed for over a century, however, few genes influencing this recurrent phenotype have been identified. Genetic investigations have been primarily limited to a small number of model organisms, thus limiting our understanding of the underlying molecular basis of this well-documented "rule of speciation." We utilized two interspecies hybrid cat breeds in a genome-wide association study employing the Illumina 63 K single-nucleotide polymorphism array. Collectively, we identified eight autosomal genes/gene regions underlying associations with hybrid male sterility (HMS) involved in the function of the blood-testis barrier, gamete structural development, and transcriptional regulation. We also identified several candidate hybrid sterility regions on the X chromosome, with most residing in close proximity to complex duplicated regions. Differential gene expression analyses revealed significant chromosome-wide upregulation of X chromosome transcripts in testes of sterile hybrids, which were enriched for genes involved in chromatin regulation of gene expression. Our expression results parallel those reported in Mus hybrids, supporting the "Large X-Effect" in mammalian HMS and the potential epigenetic basis for this phenomenon. These results support the value of the interspecies feline model as a powerful tool for comparison to rodent models of HMS, demonstrating unique aspects and potential commonalities that underpin mammalian reproductive isolation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. 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.

  9. Behavior of duplex stainless steel casting defects under mechanical loadings

    International Nuclear Information System (INIS)

    Jayet-Gendrot, S.; Gilles, P.

    2000-01-01

    Several components in the primary circuit of pressurized water reactors are made of cast duplex stainless steels. This material contains small casting defects, mainly shrinkage cavities, due to the manufacturing process. In safety analyses, the structural integrity of the components is studied under the most severe assumptions: presence of a large defect, accidental loadings and end-of-life material properties accounting for its thermal aging embrittlement at the service temperature. The casting defects are idealized as semi-circular surface cracks or notches that have envelope dimensions. In order to assess the real severity of the casting defects under mechanical loadings, an experimental program was carried out. It consisted of testing, under both cyclic and monotonic solicitations, three-point bend specimens containing either a natural defect (in the form of a localized cluster of cavities) or a machined notch having the dimensions of the cluster's envelope. The results show that shrinkage cavities are far less harmful than envelope notches thanks to the metal bridges between cavities. Under fatigue loadings, the generalized initiation of a cluster of cavities (defined when the cluster becomes a crack of the same global size) is reached for a number of cycles that is much higher than the one leading to the initiation of a notch. In the case of monotonic loadings, specimens with casting defects offer a very high resistance to ductile tearing. The tests are analyzed in order to develop a method that takes into account the behavior of casting defects in a more realistic fashion than by an envelope crack. Various approaches are investigated, including the search of equivalent defects or of criteria based on continuum mechanics concepts, and compared with literature data. This study shows the conservatism of current safety analyses in modeling casting defects by envelope semi-elliptical cracks and contributes to the development of alternative approaches. (orig.)

  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. Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

    International Nuclear Information System (INIS)

    Amin, Rupesh P.; Hamadeh, Hisham K.; Bushel, Pierre R.; Bennett, Lee; Afshari, Cynthia A.; Paules, Richard S.

    2002-01-01

    Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

  12. Functional brain networks involved in decision-making under certain and uncertain conditions

    Energy Technology Data Exchange (ETDEWEB)

    Farrar, Danielle C.; Moss, Mark B.; Killiany, Ronald J. [Boston University School of Medicine, Department of Anatomy and Neurobiology, Boston, MA (United States); Mian, Asim Z. [Boston University School of Medicine, Department of Radiology, Boston, MA (United States); Budson, Andrew E. [VA Boston Healthcare System, Boston, MA (United States)

    2018-01-15

    The aim of this study was to describe imaging markers of decision-making under uncertain conditions in normal individuals, in order to provide baseline activity to compare to impaired decision-making in pathological states. In this cross-sectional study, 19 healthy subjects ages 18-35 completed a novel decision-making card-matching task using a Phillips T3 Scanner and a 32-channel head coil. Functional data were collected in six functional runs. In one condition of the task, the participant was certain of the rule to apply to match the cards; in the other condition, the participant was uncertain. We performed cluster-based comparison of the two conditions using FSL fMRI Expert Analysis Tool and network-based analysis using MATLAB. The uncertain > certain comparison yielded three clusters - a midline cluster that extended through the midbrain, the thalamus, bilateral prefrontal cortex, the striatum, and bilateral parietal/occipital clusters. The certain > uncertain comparison yielded bilateral clusters in the insula, parietal and temporal lobe, as well as a medial frontal cluster. A larger, more connected functional network was found in the uncertain condition. The involvement of the insula, parietal cortex, temporal cortex, ventromedial prefrontal cortex, and orbitofrontal cortex of the certain condition reinforces the notion that certainty is inherently rewarding. For the uncertain condition, the involvement of the prefrontal cortex, parietal cortex, striatum, thalamus, amygdala, and hippocampal involvement was expected, as these are areas involved in resolving uncertainty and rule updating. The involvement of occipital cortical involvement and midbrain involvement may be attributed to increased visual attention and increased motor control. (orig.)

  13. Functional brain networks involved in decision-making under certain and uncertain conditions

    International Nuclear Information System (INIS)

    Farrar, Danielle C.; Moss, Mark B.; Killiany, Ronald J.; Mian, Asim Z.; Budson, Andrew E.

    2018-01-01

    The aim of this study was to describe imaging markers of decision-making under uncertain conditions in normal individuals, in order to provide baseline activity to compare to impaired decision-making in pathological states. In this cross-sectional study, 19 healthy subjects ages 18-35 completed a novel decision-making card-matching task using a Phillips T3 Scanner and a 32-channel head coil. Functional data were collected in six functional runs. In one condition of the task, the participant was certain of the rule to apply to match the cards; in the other condition, the participant was uncertain. We performed cluster-based comparison of the two conditions using FSL fMRI Expert Analysis Tool and network-based analysis using MATLAB. The uncertain > certain comparison yielded three clusters - a midline cluster that extended through the midbrain, the thalamus, bilateral prefrontal cortex, the striatum, and bilateral parietal/occipital clusters. The certain > uncertain comparison yielded bilateral clusters in the insula, parietal and temporal lobe, as well as a medial frontal cluster. A larger, more connected functional network was found in the uncertain condition. The involvement of the insula, parietal cortex, temporal cortex, ventromedial prefrontal cortex, and orbitofrontal cortex of the certain condition reinforces the notion that certainty is inherently rewarding. For the uncertain condition, the involvement of the prefrontal cortex, parietal cortex, striatum, thalamus, amygdala, and hippocampal involvement was expected, as these are areas involved in resolving uncertainty and rule updating. The involvement of occipital cortical involvement and midbrain involvement may be attributed to increased visual attention and increased motor control. (orig.)

  14. Insights into the Mechanisms Underlying Boron Homeostasis in Plants

    Directory of Open Access Journals (Sweden)

    Akira Yoshinari

    2017-11-01

    Full Text Available Boron is an essential element for plants but is toxic in excess. Therefore, plants must adapt to both limiting and excess boron conditions for normal growth. Boron transport in plants is primarily based on three transport mechanisms across the plasma membrane: passive diffusion of boric acid, facilitated diffusion of boric acid via channels, and export of borate anion via transporters. Under boron -limiting conditions, boric acid channels and borate exporters function in the uptake and translocation of boron to support growth of various plant species. In Arabidopsis thaliana, NIP5;1 and BOR1 are located in the plasma membrane and polarized toward soil and stele, respectively, in various root cells, for efficient transport of boron from the soil to the stele. Importantly, sufficient levels of boron induce downregulation of NIP5;1 and BOR1 through mRNA degradation and proteolysis through endocytosis, respectively. In addition, borate exporters, such as Arabidopsis BOR4 and barley Bot1, function in boron exclusion from tissues and cells under conditions of excess boron. Thus, plants actively regulate intracellular localization and abundance of transport proteins to maintain boron homeostasis. In this review, the physiological roles and regulatory mechanisms of intracellular localization and abundance of boron transport proteins are discussed.

  15. 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.

  16. Behavior of duplex stainless steel casting defects under mechanical loadings

    Energy Technology Data Exchange (ETDEWEB)

    Jayet-Gendrot, S [Electricite de France, 77 - Moret-sur-Loing (France). Dept. of Materials Study; Gilles, P; Migne, C [Societe Franco-Americaine de Constructions Atomiques (FRAMATOME), 92 - Paris-La-Defense (France)

    1997-04-01

    Several components in the primary circuit of pressurized water reactors are made of cast duplex stainless steels. This material contains small casting defects, mainly shrinkage cavities, due to the manufacturing process. In safety analyses, the structural integrity of the components is studied. In order to assess the real severity of the casting defects under mechanical loadings, an experimental program was carried out. It consisted of testing, under both cyclic and monotonic solicitations, three-point bend specimens containing either a natural defect (in the form of a localized cluster of cavities) or a machined notch having the dimensions of the cluster`s envelope. The tests are analyzed in order to develop a method that takes into account the behavior of castings defects in a more realistic fashion than by an envelope crack. Various approaches are investigated, including the search of equivalent defects or of criteria based on continuum mechanics concepts, and compared with literature data. This study shows the conservatism of current safety analyses in modelling casting defects by envelope semi-elliptical cracks and contributes to the development of alternative approaches. (author) 18 refs.

  17. 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.

  18. 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.

  19. The underlying mechanism of action for various medicinal properties of Piper betle (betel).

    Science.gov (United States)

    Haslan, H; Suhaimi, F H; Thent, Zar Chi; Das, S

    2015-01-01

    Piper betle (betel) plant belongs to the Piperaceae family. Piper. betle is widely known for its potent medicinal properties. Various active compounds are present in Piper. betle such as allylpyrocatechol, hydroxychavicol, piperbetol, ethylpiperbetol, piperol A, piperol B, chavibetol, and alkaloids which account for these beneficial medicinal properties. In the present narrative review, we looked into the various active compounds present in the Piper betle and attempted to understand their underlying mechanism of action. Proper understanding of the molecular biology involving the mechanism of action may help in better drug formulation and provide better therapeutic actions in the field of alternative and complementary medicine.

  20. Hardening and softening mechanisms of pearlitic steel wire under torsion

    International Nuclear Information System (INIS)

    Zhao, Tian-Zhang; Zhang, Shi-Hong; Zhang, Guang-Liang; Song, Hong-Wu; Cheng, Ming

    2014-01-01

    Highlights: • Mechanical behavior of pearlitic steel wire is studied using torsion. • Work hardening results from refinement lamellar pearlitic structure. • Softening results from recovery, shear bands and lamellar fragmentations. • A microstructure based analytical flow stress model is established. - Abstract: The mechanical behaviors and microstructure evolution of pearlitic steel wires under monotonic shear deformation have been investigated by a torsion test and a number of electron microscopy techniques including scanning electron microscopy (SEM) and transmission electron microscopy (TEM), with an aim to reveal the softening and hardening mechanisms of a randomly oriented pearlitic structure during a monotonic stain path. Significantly different from the remarkable strain hardening in cold wire drawing, the strain hardening rate during torsion drops to zero quickly after a short hardening stage. The microstructure observations indicate that the inter-lamellar spacing (ILS) decreases and the dislocations accumulate with strain, which leads to hardening of the material. Meanwhile, when the strain is larger than 0.154, the enhancement of dynamic recovery, shear bands (SBs) and cementite fragmentations results in the softening and balances the strain hardening. A microstructure based analytical flow stress model with considering the influence of ILS on the mean free path of dislocations and the softening caused by SBs and cementite fragmentations, has been established and the predicted flow shear curve meets well with the measured curve in the torsion test

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Feeding Problems and Their Underlying Mechanisms in the Esophageal Atresia–Tracheoesophageal Fistula Patient

    Science.gov (United States)

    Mahoney, Lisa; Rosen, Rachel

    2017-01-01

    Feeding difficulties such as dysphagia, coughing, choking, or vomiting during meals, slow eating, oral aversion, food refusal, and stressful mealtimes are common in children with repaired esophageal atresia (EA) and the reasons for this are often multifactorial. The aim of this review is to describe the possible underlying mechanisms contributing to feeding difficulties in patients with EA and approaches to management. Underlying mechanisms for these feeding difficulties include esophageal dysphagia, oropharyngeal dysphagia and aspiration, and aversions related to prolonged gastrostomy tube feeding. The initial diagnostic evaluation for feeding difficulties in a patient with EA may involve an esophagram, videofluoroscopic imaging or fiberoptic endoscopic evaluation during swallowing, upper endoscopy with biopsies, pH-impedance testing, and/or esophageal motility studies. The main goal of management is to reduce the factors contributing to feeding difficulties and may include reducing esophageal stasis, maximizing reflux therapies, treating underlying lung disease, dilating strictures, and altering feeding methods, routes, or schedules. PMID:28620597

  6. The mechanisms involved at the cell level; Les mecanismes mis en jeu au niveau cellulaire

    Energy Technology Data Exchange (ETDEWEB)

    Leblanc, G.; Pourcher, Th.; Perron, B. [Nice Univ., Dir. des Sciences du Vivant, Dept. de Biologie Joliot-Curie, 06 (France); Guillain, F. [CEA Grenoble, Dir. des Sciences du Vivant, 38 (France); Quemeneur, E. [CEA Marcoule, Dir. des Sciences du Vivant, 30 (France); Fritsch, P. [CEA Bruyeres le Chatel, Dir. des Sciences du Vivant, 91 (France)

    2003-07-01

    The mechanisms responsible at the cell level for inducing toxic reactions after contamination are as yet only imperfectly known. Work still needs to be done for both contaminants that have a biological role, such as iodine, and those that do not, such as cadmium, uranium and plutonium. In particular, these mechanisms bring into play, in biological membranes, carriers which are the physiological partners responsible for material exchange with the environment or inside the body. As they lack absolute selectivity, these carriers, which are involved in the assimilation and accumulation of vital mineral elements, also have the ability to transport toxic elements and isotopes. (authors)

  7. 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.

    2012-01-01

    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. PMID:23564979

  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. 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.

  10. Under-reporting of accidents involving biological material by nursing professionals at a Brazilian emergency hospital.

    Science.gov (United States)

    Facchin, Luiza Tayar; Gir, Elucir; Pazin-Filho, Antonio; Hayashida, Miyeko; da Silva Canini, Silvia Rita Marin

    2013-01-01

    Pathogens can be transmitted to health professionals after contact with biological material. The exact number of infections deriving from these events is still unknown, due to the lack of systematic surveillance data and under-reporting. A cross-sectional study was carried out, involving 451 nursing professionals from a Brazilian tertiary emergency hospital between April and July 2009. Through an active search, cases of under-reporting of occupational accidents with biological material by the nursing team were identified by means of individual interviews. The Institutional Review Board approved the research project. Over half of the professionals (237) had been victims of one or more accidents (425 in total) involving biological material, and 23.76% of the accidents had not been officially reported using an occupational accident report. Among the underreported accidents, 53.47% were percutaneous and 67.33% were bloodborne. The main reason for nonreporting was that the accident had been considered low risk. The under-reporting rate (23.76%) was low in comparison with other studies, but most cases of exposure were high risk.

  11. 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.

  12. 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.

  13. Involvement of translation and transcription processes into neurophysiological mechanisms of long-term memory reconsolidation.

    Science.gov (United States)

    Kozyrev, S A; Nikitin, V P

    2013-03-01

    We studied the involvement of translation and transcription processes into behavioral and neuronal mechanisms of reconsolidation of the long-term memory of the conditioned taste aversion in edible snails. Injection of cycloheximide (an inhibitor of protein synthesis) to the snails in 48 h after training combined with subsequent reminder and presentation of the conditional stimulus resulted in the development of persistent amnesia and depression of the responses of the defensive behavior command neurons LPl1 and RPl1 to the conditional stimulus. Injection of mRNA synthesis inhibitors actinomycin D or DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidasole) in 48 h after conditioning with subsequent reminding procedure produced no effects on memory retention and on the responses of the command neurons to the conditional stimulus. The study suggests that the proteins translated from previously synthesized and stored mRNA were involved in the mechanisms of reconsolidation of the memory responsible for conditioned taste aversion.

  14. 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

  15. Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability

    OpenAIRE

    Wan, Ruiqian; Weigand, Letitia A.; Bateman, Ryan; Griffioen, Kathleen; Mendelowitz, David; Mattson, Mark P.

    2014-01-01

    Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haplo...

  16. 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...... (SK(Ca)) and intermediate (IK(Ca))-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK(Ca) and SK(Ca)3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries......, respectively. In 5-hydroxytryptamine (1 microM)-contracted bronchioles (828 +/- 20 microm, n = 84) and U46619 (0.03 microM)-contracted arteries (720 +/- 24 microm, n = 68), NS309 (0.001-10 microM) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK...

  17. Neural mechanisms underlying human consensus decision-making.

    Science.gov (United States)

    Suzuki, Shinsuke; Adachi, Ryo; Dunne, Simon; Bossaerts, Peter; O'Doherty, John P

    2015-04-22

    Consensus building in a group is a hallmark of animal societies, yet little is known about its underlying computational and neural mechanisms. Here, we applied a computational framework to behavioral and fMRI data from human participants performing a consensus decision-making task with up to five other participants. We found that participants reached consensus decisions through integrating their own preferences with information about the majority group members' prior choices, as well as inferences about how much each option was stuck to by the other people. These distinct decision variables were separately encoded in distinct brain areas-the ventromedial prefrontal cortex, posterior superior temporal sulcus/temporoparietal junction, and intraparietal sulcus-and were integrated in the dorsal anterior cingulate cortex. Our findings provide support for a theoretical account in which collective decisions are made through integrating multiple types of inference about oneself, others, and environments, processed in distinct brain modules. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. 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.

  19. Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation

    Science.gov (United States)

    Chervyakov, Alexander V.; Chernyavsky, Andrey Yu.; Sinitsyn, Dmitry O.; Piradov, Michael A.

    2015-01-01

    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 and long-term depression. 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 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. PMID:26136672

  20. Mechanism underlying the development of unilateral spatial neglect

    International Nuclear Information System (INIS)

    Nishikiori, Etsuko

    1992-01-01

    To test the hypothesis that functional disturbance of the neural network involving the inferior parietal lobule (IPL), anterior cingulate gyrus (ACG), dorsolateral frontal lobe (DLF), and thalamus (TH) as components of the right hemisphere underlies the development of unilateral spatial neglect (USN), cerebral perfusion was measured by 123 I-IMP SPECT in 32 patients with cerebrovascular right brain damage, 20 of whom had USN and 12 of whom did not. In analyzing the SPECT data, RI uptake in the four component regions and cerebellum (serving as a control) were estimated by symmetrically placing 'regions of interest' from both hemispheres on SPECT slices, most suitable for each region. The 'regional to cerebellar ratio' (R/CE ratio) for each component region was calculated and the values were compared. In the USN group, R/CE ratio values for each component region in the right hemisphere were significantly lower than those in the left, whereas in the non-USN group there was no right-left difference. When R/CE ratio values for each component region in the right hemisphere were compared between the USN and non-USN group, those for the IPL, ACG and TH were significantly lower in the USN group; the value for the DLF was also lower in the USN group, although the difference was not significant. Significantly lower values of R/CE for each component region in the right hemisphere were noticed when the regions showed apparent involvement on X-ray CT/MRI. Furthermore, in seven of the USN patients where lesions revealed by CT/MRI did not involve network components, the R/CE ratio values for the components in the right hemisphere were lower than those in the left; the difference was significant for the IPL, ACG and TH, but not for the DLF. It is suggested that functional disturbance of the neural network involving the IPL, ACG, DLF and TH in the right hemisphere might underlie the development of USN. (author)

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. MECHANICAL BEHAVIOR OF PRESTRESSED VISCOELASTIC ADHESIVE AREAS UNDER COMBINING LOADINGS

    Directory of Open Access Journals (Sweden)

    Halil Murat Enginsoy

    2017-12-01

    Full Text Available In this article, mechanical behaviors of adhesive tape VHB 4950 elastomeric material, which is an element of acrylic polymer group and which is in viscoelastic behavior, under different pre-stress conditions and complex forces of different geometric parameters created by combining loadings have been experimentally and numerically investigated. In experimental studies, loading-unloading cyclic tests, one of the different standardized tests for the mechanical characterization of viscoelastic material, have been applied which give the most suitable convergent optimization parameters for the finite element model. Different material models were also investigated by using the data obtained from loading-unloading test results in all numerical models. According to the experimental results, the most suitable material parameters were determined with the Abaqus Parallel Rheological Framework Model (PRF for 4 Yeoh Networks with Bergstrom-Boyce Flow model created in the Mcalibration software for finite element analysis. Subsequently, using these material parameters, finite element analysis was performed as three dimension non-linear viscoelastic with a commercial finite element software Abaqus. The finite element analysis results showed good correlation to the Force (N-Displacement (mm experimental data for maximum load-carrying capacity of structural specimens.

  4. 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.

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

    Science.gov (United States)

    2017-01-01

    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. PMID:28567415

  6. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

  10. 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

  11. 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.

  12. 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

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

    Science.gov (United States)

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

    2015-09-29

    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 disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are

  14. General mechanism involved in subwavelength optics of conducting microstructures: charge-oscillation-induced light emission and interference.

    Science.gov (United States)

    Huang, Xian-Rong; Peng, Ru-Wen

    2010-04-01

    Interactions between light and conducting microstructures or nanostructures can result in a variety of novel phenomena, but their underlying mechanisms have not been completely understood. From calculations of surface charge density waves on conducting gratings and by comparing them with classical surface plasmons, we revealed a general yet concrete picture regarding the coupling of light to free electron oscillation on structured conducting surfaces that can lead to oscillating subwavelength charge patterns (i.e., structured surface plasmons). New wavelets emitted from these light sources then destructively interfere to form evanescent waves. This principle, usually combined with other mechanisms, is mainly a geometrical effect that can be universally involved in light scattering from all periodic and non-periodic structures containing free electrons. This picture may provide clear guidelines for developing conductor-based nano-optical devices.

  15. 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.

  16. 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.

  17. 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.

  18. Longitudinal investigation on learned helplessness tested under negative and positive reinforcement involving stimulus control.

    Science.gov (United States)

    Oliveira, Emileane C; Hunziker, Maria Helena

    2014-07-01

    In this study, we investigated whether (a) animals demonstrating the learned helplessness effect during an escape contingency also show learning deficits under positive reinforcement contingencies involving stimulus control and (b) the exposure to positive reinforcement contingencies eliminates the learned helplessness effect under an escape contingency. Rats were initially exposed to controllable (C), uncontrollable (U) or no (N) shocks. After 24h, they were exposed to 60 escapable shocks delivered in a shuttlebox. In the following phase, we selected from each group the four subjects that presented the most typical group pattern: no escape learning (learned helplessness effect) in Group U and escape learning in Groups C and N. All subjects were then exposed to two phases, the (1) positive reinforcement for lever pressing under a multiple FR/Extinction schedule and (2) a re-test under negative reinforcement (escape). A fourth group (n=4) was exposed only to the positive reinforcement sessions. All subjects showed discrimination learning under multiple schedule. In the escape re-test, the learned helplessness effect was maintained for three of the animals in Group U. These results suggest that the learned helplessness effect did not extend to discriminative behavior that is positively reinforced and that the learned helplessness effect did not revert for most subjects after exposure to positive reinforcement. We discuss some theoretical implications as related to learned helplessness as an effect restricted to aversive contingencies and to the absence of reversion after positive reinforcement. This article is part of a Special Issue entitled: insert SI title. Copyright © 2014. Published by Elsevier B.V.

  19. 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.

  20. Neural Mechanisms of Updating under Reducible and Irreducible Uncertainty.

    Science.gov (United States)

    Kobayashi, Kenji; Hsu, Ming

    2017-07-19

    Adaptive decision making depends on an agent's ability to use environmental signals to reduce uncertainty. However, because of multiple types of uncertainty, agents must take into account not only the extent to which signals violate prior expectations but also whether uncertainty can be reduced in the first place. Here we studied how human brains of both sexes respond to signals under conditions of reducible and irreducible uncertainty. We show behaviorally that subjects' value updating was sensitive to the reducibility of uncertainty, and could be quantitatively characterized by a Bayesian model where agents ignore expectancy violations that do not update beliefs or values. Using fMRI, we found that neural processes underlying belief and value updating were separable from responses to expectancy violation, and that reducibility of uncertainty in value modulated connections from belief-updating regions to value-updating regions. Together, these results provide insights into how agents use knowledge about uncertainty to make better decisions while ignoring mere expectancy violation. SIGNIFICANCE STATEMENT To make good decisions, a person must observe the environment carefully, and use these observations to reduce uncertainty about consequences of actions. Importantly, uncertainty should not be reduced purely based on how surprising the observations are, particularly because in some cases uncertainty is not reducible. Here we show that the human brain indeed reduces uncertainty adaptively by taking into account the nature of uncertainty and ignoring mere surprise. Behaviorally, we show that human subjects reduce uncertainty in a quasioptimal Bayesian manner. Using fMRI, we characterize brain regions that may be involved in uncertainty reduction, as well as the network they constitute, and dissociate them from brain regions that respond to mere surprise. Copyright © 2017 the authors 0270-6474/17/376972-11$15.00/0.

  1. 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.

  2. 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.

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

    Science.gov (United States)

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

    2015-12-30

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. 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

  5. The Mechanical Behaviors of Various Dental Implant Materials under Fatigue

    Directory of Open Access Journals (Sweden)

    Fatma Bayata

    2018-01-01

    Full Text Available The selection of materials has a considerable role on long-term stability of implants. The materials having high resistance to fatigue are required for dental implant applications since these implants are subjected to cyclic loads during chewing. This study evaluates the performance of different types of materials (AISI 316L stainless steel, alumina and its porous state, CoCr alloys, yttrium-stabilized zirconia (YSZ, zirconia-toughened alumina (ZTA, and cp Ti with the nanotubular TiO2 surface by finite element analysis (FEA under real cyclic biting loads and researches the optimum material for implant applications. For the analysis, the implant design generated by our group was utilized. The mechanical behavior and the life of the implant under biting loads were estimated based on the material and surface properties. According to the condition based on ISO 14801, the FEA results showed that the equivalent von Mises stress values were in the range of 226.95 MPa and 239.05 MPa. The penetration analysis was also performed, and the calculated penetration of the models onto the bone structure ranged between 0.0037389 mm and 0.013626 mm. L-605 CoCr alloy-assigned implant model showed the least penetration, while cp Ti with the nanotubular TiO2 surface led to the most one. However, the difference was about 0.01 mm, and it may not be evaluated as a distinct difference. As the final numerical evaluation item, the fatigue life was executed, and the results were achieved in the range of 4 × 105 and 1 × 109 cycles. These results indicated that different materials showed good performance for each evaluation component, but considering the overall mechanical performance and the treatment process (implant adsorption by means of surface properties, cp Ti with the nanotubular TiO2 surface material was evaluated as the suitable one, and it may also be implied that it displayed enough performance in the designed dental implant model.

  6. On the mechanical properties of tooth enamel under spherical indentation.

    Science.gov (United States)

    Chai, Herzl

    2014-11-01

    The mechanical properties of tooth enamel generally exhibit large variations, which reflect its structural and material complexity. Some key properties were evaluated under localized contact, simulating actual functioning conditions. Prominent cusps of extracted human molar teeth were polished down ~0.7 mm below the cusp tip and indented by tungsten carbide balls. The internal damage was assessed after unloading from longitudinal or transverse sections. The ultimate tensile stress (UTS) was determined using a novel bilayer specimen. The damage is characterized by penny-like radial cracks driven by hoop stresses and cylindrical cracks driven along protein-rich interrod materials by shear stresses. Shallow cone cracks typical of homogeneous materials which may cause rapid tooth wear under repeat contact are thus avoided. The mean stress vs. indentation strain curve is highly nonlinear, attributable to plastic shearing of protein between and within enamel rods. This curve is also affected by damage, especially radial cracks, the onset of which depends on ball radius. Several material properties were extracted from the tests, including shear strain at the onset of ring cracks γ(F) (=0.14), UTS (=119 MPa), toughness K(C) (=0.94 MPa m(1/2)), a crack propagation law and a constitutive response determined by trial and error with the aid of a finite-element analysis. These quantities, which are only slightly sensitive to anatomical location within the enamel region tested, facilitate a quantitative assessment of crown failure. Causes for variations in published UTS and K(C) values are discussed. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  7. Failure mechanisms of aluminium foams under compressive loads

    Directory of Open Access Journals (Sweden)

    Sáenz, E.

    2000-08-01

    Full Text Available The purpose of this paper is the investigation of the major failure mechanisms of aluminium foams, which were obtained by powder metallurgy route, under compressive loads. The study was focused on two commonly aluminium alloys AlMg1Si or A 6061 and AlSi12. Due to the fact that the failure mechanisms strongly depend on the density and the macrostructural properties of the material, the mechanical properties always have to be correlated to the structural properties. Therefore, macrostructural investigations were used as a basis to establish the correlation between structural and mechanical properties. This was done with a commercially available image analysis system. The average cell size, the cell size distribution and the cell density (number of cells/area were obtained. In order to evaluate the influence of foaming direction on the cell morphology, some cross sections parallel to the foaming direction were prepared. For the characterization of the mechanical compression properties the compressive or upper yield strength (UYS, the densification strain (eD, the energy absorption (Ea and the efficiency (Eff were obtained. Furthermore, the failure behavior of the samples was in-situ observed with a digital video camera and continuously recorded during the test.

    El objetivo de este estudio es investigar los principales mecanismos de fallo de espumas de aluminio sometidas a cargas de compresión. Las espumas metálicas fueron obtenidas mediante el proceso pulvimetalúrgico, utilizándose como materia prima dos aleaciones comerciales AlMg1Si o A 6061 y AlSi12. Debido a que los mecanismos de fallo en este tipo de materiales depende fuertemente de la densidad y las características macroestructurales del material, en este estudio se busca correlacionar las propiedades mecánicas con estas características. La macroestructura se caracterizó mediante análisis de imagen. El tamaño de celda promedio, la distribución de tamaño y la densidad de

  8. Mechanisms involved in metformin action in the treatment of polycystic ovary syndrome.

    Science.gov (United States)

    Motta, A B

    2009-01-01

    The N, N' dimethyl-biguanide : Metformin is an antidiabetic drug that increases glucose utilization in insulin-sensitive tissues. As Polycystic Ovary Syndrome (PCOS) and diabetes share some altered parameters-such as abnormal glucose: insulin ratio, altered lipidic metabolism and insulin-resistance syndrome- the use of metformin has become increasingly accepted and widespread in the treatment of PCOS. Currently, metformin is used to induce ovulation and during early pregnancy in PCOS patients, however, a complete knowledge of the metformin action has not been achieved yet. This review describes beyond the classical reproductive action of metformin and explores other benefits of the drug. In addition, the present work discusses the molecular mechanisms involved further than the classical pathway that involves the AMP-activated protein kinase.

  9. 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.

  10. 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.

  11. [Underlying Mechanisms and Management of Refractory Gastroesophageal Reflux Disease].

    Science.gov (United States)

    Lee, Kwang Jae

    2015-08-01

    The prevalence of gastroesophageal reflux disease (GERD) in South Korea has increased over the past 10 years. Patients with erosive reflux disease (ERD) shows better response to proton pump inhibitors (PPIs) than those with non-erosive reflux disease (NERD). NERD is a heterogeneous condition, showing pathological gastroesophageal reflux or esophageal hypersensitivity to reflux contents. NERD patients with pathological gastroesophageal reflux or hypersensitivity to acid may respond to PPIs. However, many patients with esophageal hypersensitivity to nonacid or functional heartburn do not respond to PPIs. Therefore, careful history and investigations are required when managing patients with refractory GERD who show poor response to conventional dose PPIs. Combined pH-impedance studies and a PPI diagnostic trial are recommended to reveal underlying mechanisms of refractory symptoms. For those with ongoing reflux-related symptoms, split dose administration, change to long-acting PPIs or PPIs less influenced by CYP2C19 genotypes, increasing dose of PPIs, and the addition of alginate preparations, prokinetics, selective serotonin reuptake inhibitors, or tricyclic antidepressants can be considered. Pain modulators, selective serotonin reuptake inhibitors, or tricyclic antidepressants are more likely to be effective for those with reflux-unrelated symptoms. Surgery or endoscopic per oral fundoplication may be effective in selected patients.

  12. Enabling optimal energy options under the Clean Development Mechanism

    International Nuclear Information System (INIS)

    Gilau, Asmerom M.; Van Buskirk, Robert; Small, Mitchell J.

    2007-01-01

    This paper addresses the cost effectiveness of renewable energy technologies in achieving low abatement costs and promoting sustainable developments under the Clean Development Mechanism (CDM). According to the results of our optimal energy option's analysis, at project scale, compared with a diesel-only energy option, photovoltaic (PV)-diesel (PVDB), wind-diesel (WDB) and PV-wind-diesel (PVWDB) hybrids are very cost-effective energy options. Moreover, energy options with high levels of renewable energy, including 100% renewables, have the lowest net present cost and they are already cost effective without CDM. On the other hand, while the removal of about 87% carbon dioxide emissions could be achieved at negative cost, initial investment could increase by a factor of 40, which is one of the primary barriers hindering wider renewable energy applications in developing countries, among others. Thus, in order to increase developing countries' participation in the carbon market, CDM policy should shift from a purely market-oriented approach to investigating how to facilitate renewable energy projects through barrier removal. Thus, we recommend that further research should focus on how to efficiently remove renewable energy implementation barriers as a means to improve developing countries' participation in meaningful emission reduction while at the same time meeting the needs of sustainable economic development

  13. 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.

  14. Underlying mechanisms and the evolving influence of diet

    DEFF Research Database (Denmark)

    Larsen, Lesli Hingstrup

    2012-01-01

    Obesity is determined by both genetic and environmental factors. Since 2007, 52 genes have been associated with obesity and obesity-related measurements in genome-wide association studies (GWAS), among these the fat and obesity-associated gene (FTO). Despite the success in identifying genes predi...... and the microbiome that can be modified by diet, and by genotype, adding to the complexity of determining the contributors to obesity....... has been shown to attenuate the effect of FTO on obesity. Several studies have examined gene-diet interactions in relation to obesity, but only a few suggestive interactions have been identified. This is most probably due to small effect sizes of the interactions and thereby a demand for large samples...... to increased risk of developing obesity. Recently, the intestinal microbiome, the collected genome of the bacteria, also has been associated with obesity and with specific dietary profiles. The underlying mechanisms determining the susceptibility to obesity do not only include the genome but also the epigenome...

  15. 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.

  16. 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.

  17. 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.

  18. Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

    Science.gov (United States)

    Goldstein, Rita Z.; Volkow, Nora D.

    2005-01-01

    Objective Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. Method An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. Results The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. Conclusions These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward. PMID:12359667

  19. 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.

  20. 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

  1. 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

  2. Arbuscular mycorrhizal fungi for the biocontrol of plant-parasitic nematodes: a review of the mechanisms involved

    Directory of Open Access Journals (Sweden)

    Nele eSchouteden

    2015-11-01

    Full Text Available 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 towards future field applications of AMF against PPN. The scientific community has entered an exciting era that provide 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.

  3. 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.

  4. 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. PMID:26635750

  5. The Neural Mechanisms Underlying Internally and Externally Guided Task Selection

    Science.gov (United States)

    Orr, Joseph M.; Banich, Marie T.

    2013-01-01

    While some prior work suggests that medial prefrontal cortex (MFC) regions mediate freely chosen actions, other work suggests that the lateral frontal pole (LFP) is responsible for control of abstract, internal goals. The present study uses fMRI to determine whether the voluntary selection of a task in pursuit of an overall goal relies on MFC regions or the LFP. To do so, we used a modified voluntary task switching (VTS) paradigm, in which participants choose an individual task to perform on each trial (i.e., a subgoal), under instructions to perform the tasks equally often and in a random order (i.e. the overall goal). In conjunction, we examined patterns of activation in the face of irrelevant, but task-related external stimuli that might nonetheless influence task selection. While there was some evidence that the MFC was involved in voluntary task selection, we found that the LFP and anterior insula (AI) were crucial to task selection in the pursuit of an overall goal. In addition, activation of the LFP and AI increased in the face of environmental stimuli that might serve as an interfering or conflicting external bias on voluntary task choice. These findings suggest that the LFP supports task selection according to abstract, internal goals, and leaves open the possibility that MFC may guide action selection in situations lacking in such top-down biases. As such, the current study represents a critical step towards understanding the neural underpinnings of how tasks are selected voluntarily to enable an overarching goal. PMID:23994316

  6. 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

  7. 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.

  8. 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.

  9. Mechanisms involved in the chemical inhibition of the Eosin-sensitized photooxidation of trypsin

    Energy Technology Data Exchange (ETDEWEB)

    Rizzuto, F.; Spikes, J.D.

    1975-01-01

    A large series of compounds was screened for ability to protect trypsin from eosin-sensitized photodynamic inactivation. Eosin-sensitized photooxidation reactions of this type typically proceed via the triplet state of the dye and often involve singlet state oxygen as the oxidizing entity. In order to determine the mechanisms by which trypsin is protected from photoinactivation, a number of good protective agents (inhibitors) and some non-protective agents were selected for more detailed flash photolysis studies. Good inhibitors such as p-phenylenediamine, n-propyl gallate, serotonin creatinine sulfate and p-toluenediamine competed efficiently with oxygen and with trypsin for reaction with the triplet state of eosin. The inhibitors were shown to quench triplet eosin to the ground state and/or reduce triplet eosin to form the semireduced eosin radical and an oxidized form of the inhibitor. In the latter case, oxidized inhibitor could react by a reverse electron transfer reaction with the semireduced eosin radical to regenerate ground state eosin and the inhibitor. The good inhibitors also competed effectively with trypsin for oxidation by semioxidized eosin, thus giving another possible protective mechanism. Non-inhibitors such as halogen ions and the paramagnetic ions Co/sup + +/, Cu/sup + +/ and Mn/sup + +/ reacted only slowly with triplet and with semioxidized eosin. The primary pathway for the eosin-sensitized photooxidation of trypsin at pH 8.0 involved singlet oxygen, although semioxidized eosin may also participate.

  10. Mechanisms of microstructure formation under the influence of ultrasonic vibrations

    Science.gov (United States)

    Rakita, Milan

    Positive effects of ultrasound on crystallization have been known for almost 90 years. Application of ultrasound has been very successful in many industries, most notably in chemistry, creating a new branch of science - sonochemistry. However, ultrasonication has not found wide commercial application in the solidification processing. The reason for that is the complexity of underlying phenomena and the lack of predicting models which correlate processing parameters with the properties of a product. The purpose of this study is to give some contribution toward better understanding of mechanisms that lead to changes in the solidifying microstructure. It has been found that, under experimental conditions used in this work, cavitation-induced nucleation is the major contributor to the grain refinement. Ultrasonication at minimal supercoolings is expected to give maximal grain refinement. Dendrite fragmentation has not shown to be a significant contributor to the grain refinement. Dendrite fragmentation is maximal if done by bubbles that come in contact with the solidifying phase, or that are created there. Alloys/solutions with long solidification interval, or wide mushy zone, are expected to exhibit more dendrite fragmentation. Bubbles are recognized as a crucial feature in ultrasonication. Their size distribution in the liquid phase prior to ultrasonication dictates the cavitation threshold and intensity of cavitation. For the first time, radiation pressure has been recognized as potentially significant factor in grain refinement. In the experimental setup used in this study, acoustic pressure at the main (driving) frequency is not substantial to cause significant fragmentation, and only dendrites close to the sonotrode were fragmented. However, application of ultrasound with frequencies that are several times higher than the current industrial practice could substantially increase dendrite fragmentation. Appearance of fractional harmonics has also been recognized

  11. The medial prefrontal cortex is involved in spatial memory retrieval under partial-cue conditions.

    Science.gov (United States)

    Jo, Yong Sang; Park, Eun Hye; Kim, Il Hwan; Park, Soon Kwon; Kim, Hyun; Kim, Hyun Taek; Choi, June-Seek

    2007-12-05

    Brain circuits involved in pattern completion, or retrieval of memory from fragmented cues, were investigated. Using different versions of the Morris water maze, we explored the roles of the CA3 subregion of the hippocampus and the medial prefrontal cortex (mPFC) in spatial memory retrieval under various conditions. In a hidden platform task, both CA3 and mPFC lesions disrupted memory retrieval under partial-cue, but not under full-cue, conditions. For a delayed matching-to-place task, CA3 lesions produced a deficit in both forming and recalling spatial working memory regardless of extramaze cue conditions. In contrast, damage to mPFC impaired memory retrieval only when a fraction of cues was available. To corroborate the lesion study, we examined the expression of the immediate early gene c-fos in mPFC and the hippocampus. After training of spatial reference memory in full-cue conditions for 6 d, the same training procedure in the absence of all cues except one increased the number of Fos-immunoreactive cells in mPFC and CA3. Furthermore, mPFC inactivation with muscimol, a GABA agonist, blocked memory retrieval in the degraded-cue environment. However, mPFC-lesioned animals initially trained in a single-cue environment had no difficulty in retrieving spatial memory when the number of cues was increased, demonstrating that contextual change per se did not impair the behavioral performance of the mPFC-lesioned animals. Together, these findings strongly suggest that pattern completion requires interactions between mPFC and the hippocampus, in which mPFC plays significant roles in retrieving spatial information maintained in the hippocampus for efficient navigation.

  12. Polymer Composite Rebars under Moisture and Mechanical Loading

    Science.gov (United States)

    Adam, Mohamed Ibrahim

    structural GFRP composites will, through their design life, be exposed to a range of hygrothermal and other environmental conditions. This study aims to investigate the durability of glass fiber reinforced vinyl ester rebars exposed to moisture at different temperatures and under mechanical loading. Rebars of 10 mm, 13 mm, and 16 mm diameter were immersed in deionized water until saturation for 220 days at three different temperatures 30°C, 70°C, and 100°C. The rebars were examined as-received and following exposure to moisture by scanning electron microscopy and CT scan for possible microvoids and for modes of failures after being tested in both compression as well as non-tested specimens. Diffusion parameters were calculated and the accelerated hygrothermal effect on the compressive strength, modulus, and porosity was investigated. Significant decrease in compressive modulus and a much less degree of degradation in strength was observed. Three modes of failure were noted: splitting, fiber microbuckling, and fiber kinking. Presence of microvoids on both as-received and exposed to moisture specimens was evident. Despite this degradation due to hygrothermal exposure, GFRP rebars were able to maintain their strength. This can be regarded as an edge in their performance compared to steel. However this advantage may not hold with prolonged exposure. It was also noted that the specimens exposed to moisture and temperature exhibited an increase in microvoids of approximately 33% and new distribution of microvoids sizes was recorded. The degradation of the mechanical properties of the GFRP rebars was attributed to the hygrothermal effect that was facilitated by the presence of microvoids which allow moisture to diffuse. Presence and growth of Microvoids due to exposure to moisture and temperature was deemed the primary reason causing the degradation of GFRP rebars. Presence of microvoids needs to be addressed in order to enhance the durability and performance of GFRP rebar.

  13. 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.

  14. Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

    Science.gov (United States)

    Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

    2012-08-01

    Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

  15. 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)

  16. Involvement of rho-gtpases in fibroblast adhesion and fibronectine fibrillogenesis under stretch

    Science.gov (United States)

    Guignandon, A.; Lambert, C.; Rattner, A.; Servotte, S.; Lapiere, C.; Nusgens, B.; Vico, L.

    The Rho family small GTPases play a crucial role in mediating cellular adaptation to mechanical stimulation (MS), and possibly to microgravity (μg), through effects on the cytoskeleton and cell adhesion which is, in turn, mainly regulated by fibronectin fibrillogenesis (FnF). It remains unclear how mechanical stimulation is transduced to the Rho signaling pathways and how it impacts on fibronectin (fbn) fibrillogenesis (FnF). μg (2 days, mission STS-095) led to de-adhesion of fibroblasts and modification of the underlying extracellular matrix. To determine whether GTPases modulated FnF, we generated stable cell lines expressing high level of activated RhoA and Rac1 (QL) as compared to wild type (WI26-WT). After MS application [8% deformation, 1Hz, 15 min., 3 times/day for 1-2 days], we quantified focal adhesion (vinculin, paxillin, FAKY397), f-actin stress fibers (Sf) and FnF with home-developed softwares. We reported that after MS, Sf are more rapidly (30min) formed under the nucleus in Wi26-WT (+100%) and Rac1 (+200%) than in RhoA (+20%). Vinculin & paxillin were only restricted to the cell edge in static conditions and homogeneously distributed after MS in WT and Rac1. The relative area of contacts (vinculin & paxillin) was more dramatically enhanced by MS in Rac1 (+80%) than in WT (+40%) and RhoA (+25%) indicating that new focal contacts are formed under MS and supported the presence of Sf. MS Activation of FAK (FAKY397) was clear in WT and Rac1 and reduced in RhoA. FnF was restricted to cell-cell contacts zone without any change in the relative area of fbn after a 2-days MS. However we found more numerous spots of fbn at the cell center in Rac1 as compared with RhoA & WT suggesting that these fibrillar contacts will grow upon maturation and modulate FnF. The results indicate that MS induces formation of Sf and focal adhesions and enhances FF. RhoA has been shown to induce the formation of Sf and focal adhesions, and Rac1 activation decreases Rho activity in

  17. Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.

    Directory of Open Access Journals (Sweden)

    Tamas Kiss

    Full Text Available Pulmonary arterial hypertension (PH is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt pathway and nuclear factor (NF-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP-1, interleukin (IL-1α, lipopolysaccharide induced CXC chemokine (LIX, monokine induced by gamma interferon (MIG, macrophage inflammatory protein (MIP-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.

  18. 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.

  19. 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

  20. Design options for cooperation mechanisms under the new European renewable energy directive

    International Nuclear Information System (INIS)

    Klessmann, Corinna; Lamers, Patrick; Ragwitz, Mario; Resch, Gustav

    2010-01-01

    In June 2009, a new EU directive on the promotion of renewable energy sources (RES) entered into effect. The directive 2009/28/EC, provides for three cooperation mechanisms that will allow member states to achieve their national RES target in cooperation with other member states: statistical transfer, joint projects, and joint support schemes. This article analyses the pros and cons of the three mechanisms and explores design options for their implementation through strategic and economic questions: How to counterbalance the major drawbacks of each mechanism? How to reflect a balance of costs and benefits between the involved member states? The analysis identifies a number of design options that respond to these questions, e.g. long term contracts to ensure sufficient flexibility for statistical transfers, a coordinated, standardised joint project approach to increase transparency in the European market, and a stepwise harmonisation of joint support schemes that is based on a cost-effective accounting approach. One conclusion is that the three cooperation mechanisms are closely interlinked. One can consider their relation to be a gradual transition from member state cooperation under fully closed national support systems in case of statistical transfers, to cooperation under fully open national support systems in a joint support scheme.

  1. [Neural mechanism underlying autistic savant and acquired savant syndrome].

    Science.gov (United States)

    Takahata, Keisuke; Kato, Motoichiro

    2008-07-01

    , especially that of the prefrontal cortex and the posterior regions of the brain. (3) Autistic models, including those based on weak central coherence theory (Frith, 1989), that focus on how savant skills emerge from an autistic brain. Based on recent neuroimaging studies of ASD, Just et al. (2004) suggested the underconnectivity theory, which emphasizes the disruption of long-range connectivity and the relative intact or even more enhanced local connectivity in the autistic brain. All the models listed above have certain advantages and shortcomings. At the end of this review, we propose another integrative model of savant syndrome. In this model, we predict an altered balance of local/global connectivity patterns that contribute to an altered functional segregation/integration ratio. In particular, we emphasize the crucial role played by the disruption of global connectivity in a parallel distributed cortical network, which might result in impairment in integrated cognitive processing, such as impairment in executive function and social cognition. On the other hand, the reduced inter-regional collaboration could lead to a disinhibitory enhancement of neural activity and connectivity in local cortical regions. In addition, enhanced connectivity in the local brain regions is partly due to the abnormal organization of the cortical network as a result of developmental and pathological states. This enhanced local connectivity results in the specialization and facilitation of low-level cognitive processing. The disruption of connectivity between the prefrontal cortex and other regions is considered to be a particularly important factor because the prefrontal region shows the most influential inhibitory control on other cortical areas. We propose that these neural mechanisms as the underlying causes for the emergence of savant ability in ASD and FTD patients.

  2. Neural Mechanisms Underlying Cross-Modal Phonetic Encoding.

    Science.gov (United States)

    Shahin, Antoine J; Backer, Kristina C; Rosenblum, Lawrence D; Kerlin, Jess R

    2018-02-14

    Audiovisual (AV) integration is essential for speech comprehension, especially in adverse listening situations. Divergent, but not mutually exclusive, theories have been proposed to explain the neural mechanisms underlying AV integration. One theory advocates that this process occurs via interactions between the auditory and visual cortices, as opposed to fusion of AV percepts in a multisensory integrator. Building upon this idea, we proposed that AV integration in spoken language reflects visually induced weighting of phonetic representations at the auditory cortex. EEG was recorded while male and female human subjects watched and listened to videos of a speaker uttering consonant vowel (CV) syllables /ba/ and /fa/, presented in Auditory-only, AV congruent or incongruent contexts. Subjects reported whether they heard /ba/ or /fa/. We hypothesized that vision alters phonetic encoding by dynamically weighting which phonetic representation in the auditory cortex is strengthened or weakened. That is, when subjects are presented with visual /fa/ and acoustic /ba/ and hear /fa/ ( illusion-fa ), the visual input strengthens the weighting of the phone /f/ representation. When subjects are presented with visual /ba/ and acoustic /fa/ and hear /ba/ ( illusion-ba ), the visual input weakens the weighting of the phone /f/ representation. Indeed, we found an enlarged N1 auditory evoked potential when subjects perceived illusion-ba , and a reduced N1 when they perceived illusion-fa , mirroring the N1 behavior for /ba/ and /fa/ in Auditory-only settings. These effects were especially pronounced in individuals with more robust illusory perception. These findings provide evidence that visual speech modifies phonetic encoding at the auditory cortex. SIGNIFICANCE STATEMENT The current study presents evidence that audiovisual integration in spoken language occurs when one modality (vision) acts on representations of a second modality (audition). Using the McGurk illusion, we show

  3. 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.

  4. 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 [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.

  5. 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

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

    Directory of Open Access Journals (Sweden)

    Paola Massi

    2010-05-01

    Full Text Available 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.

  7. Hippocampal NMDA receptors are involved in rats' spontaneous object recognition only under high memory load condition.

    Science.gov (United States)

    Sugita, Manami; Yamada, Kazuo; Iguchi, Natsumi; Ichitani, Yukio

    2015-10-22

    The possible involvement of hippocampal N-methyl-D-aspartate (NMDA) receptors in spontaneous object recognition was investigated in rats under different memory load conditions. We first estimated rats' object memory span using 3-5 objects in "Different Objects Task (DOT)" in order to confirm the highest memory load condition in object recognition memory. Rats were allowed to explore a field in which 3 (3-DOT), 4 (4-DOT), or 5 (5-DOT) different objects were presented. After a delay period, they were placed again in the same field in which one of the sample objects was replaced by another object, and their object exploration behavior was analyzed. Rats could differentiate the novel object from the familiar ones in 3-DOT and 4-DOT but not in 5-DOT, suggesting that rats' object memory span was about 4. Then, we examined the effects of hippocampal AP5 infusion on performance in both 2-DOT (2 different objects were used) and 4-DOT. The drug treatment before the sample phase impaired performance only in 4-DOT. These results suggest that hippocampal NMDA receptors play a critical role in spontaneous object recognition only when the memory load is high. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Huang, Lixing; Wang, Chonggang; Zhang, Youyu; Wu, Meifang; Zuo, Zhenghong

    2013-01-01

    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

  9. Sonic hedgehog promotes neurite outgrowth of cortical neurons under oxidative stress: Involving of mitochondria and energy metabolism.

    Science.gov (United States)

    He, Weiliang; Cui, Lili; Zhang, Cong; Zhang, Xiangjian; He, Junna; Xie, Yanzhao; Chen, Yanxia

    2017-01-01

    Oxidative stress has been demonstrated to be involved in the etiology of several neurobiological disorders. Sonic hedgehog (Shh), a secreted glycoprotein factor, has been implicated in promoting several aspects of brain remodeling process. Mitochondria may play an important role in controlling fundamental processes in neuroplasticity. However, little evidence is available about the effect and the potential mechanism of Shh on neurite outgrowth in primary cortical neurons under oxidative stress. Here, we revealed that Shh treatment significantly increased the viability of cortical neurons in a dose-dependent manner, which was damaged by hydrogen peroxide (H 2 O 2 ). Shh alleviated the apoptosis rate of H 2 O 2 -induced neurons. Shh also increased neuritogenesis injuried by H 2 O 2 in primary cortical neurons. Moreover, Shh reduced the generation of reactive oxygen species (ROS), increased the activities of SOD and and decreased the productions of MDA. In addition, Shh protected mitochondrial functions, elevated the cellular ATP levels and amelioratesd the impairment of mitochondrial complex II activities of cortical neurons induced by H 2 O 2 . In conclusion, all these results suggest that Shh acts as a prosurvival factor playing an essential role to neurite outgrowth of cortical neuron under H 2 O 2 -induced oxidative stress, possibly through counteracting ROS release and preventing mitochondrial dysfunction and ATP as well as mitochondrial complex II activities against oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Physiological and Molecular Mechanism of Nitric Oxide (NO Involved in Bermudagrass Response to Cold Stress.

    Directory of Open Access Journals (Sweden)

    Jibiao Fan

    Full Text Available Bermudagrass is widely utilized in parks, lawns, and golf courses. However, cold is a key factor limiting resource use in bermudagrass. Therefore, it is meaningful to study the mechanism of bermudagrass response to cold. Nitric oxide (NO is a crucial signal molecule with multiple biological functions. Thus, the objective of this study was to investigate whether NO play roles in bermudagrass response to cold. Sodium nitroprusside (SNP was used as NO donor, while 2-phenyl-4,4,5,5-tetramentylimidazoline-l-oxyl-3-xide (PTIO plus NG-nitro-L-arginine methyl ester (L-NAME were applied as NO inhibitor. Wild bermudagrass was subjected to 4 °C in a growth chamber under different treatments (Control, SNP, PTIO + L-NAME. The results indicated lower levels of malondialdehyde (MDA content and electrolyte leakage (EL, higher value for chlorophyll content, superoxide dismutase (SOD and peroxidase (POD activities after SNP treatment than that of PTIO plus L-NAME treatments under cold stress. Analysis of Chlorophyll (Chl a fluorescence transient displayed that the OJIP transient curve was higher after treatment with SNP than that of treated with PTIO plus L-NAME under cold stress. The values of photosynthetic fluorescence parameters were higher after treatment with SNP than that of treated with PTIO plus L-NAME under cold stress. Expression of cold-responsive genes was altered under cold stress after treated with SNP or PTIO plus L-NAME. In summary, our findings indicated that, as an important strategy to protect bermudagrass against cold stress, NO could maintain the stability of cell membrane, up-regulate the antioxidant enzymes activities, recover process of photosystem II (PSII and induce the expression of cold-responsive genes.

  11. 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.

  12. Mechanical response of collagen molecule under hydrostatic compression.

    Science.gov (United States)

    Saini, Karanvir; Kumar, Navin

    2015-04-01

    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. Copyright © 2015 Elsevier B.V. All rights

  13. Mechanical response of collagen molecule under hydrostatic compression

    Energy Technology Data Exchange (ETDEWEB)

    Saini, Karanvir, E-mail: karans@iitrpr.ac.in; Kumar, Navin

    2015-04-01

    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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Involvement of adrenergic and serotonergic nervous mechanisms in allethrin-induced tremors in mice.

    Science.gov (United States)

    Nishimura, M; Obana, N; Yagasaki, O; Yanagiya, I

    1984-05-01

    Oral or intravenous administration of allethrin, a synthetic derivative of the pirethrin-based insecticides, produces neurotoxic symptoms consisting of mild salivation, hyperexcitability, tremors and convulsions which result in death. Intracerebroventricular injection of allethrin to mouse at about one-nineth the dose of intravenous administration, produced qualitatively identical but less prominent symptoms, indicating that at least some of the symptoms may be originated in the central nervous system. To investigate the mechanism of action of the compound, we studied the ability of agents which alter neurotransmission to prevent or potentiate the effect of convulsive doses of technical grade (15.5% cis, 84.5% trans) allethrin. Intraperitoneal pretreatment with drugs which block noradrenergic receptors or norepinephrine synthesis, such as pentobarbital, chlorpromazine, phentolamine, phenoxybenzamine and reserpine, depressed the tremor induced by allethrin. The inhibitory effect of reserpine was reversed by phenylephrine. Both the serotonergic blocker, methysergide, and the serotonin depletor, rho-chlorphenylalanine, potentiated the effect of allethrin. The potentiating effect of methysergide was antagonized by 5-hydroxytryptamine. However, intracerebroventricular administration of methysergide was ineffective in potentiating the effect of allethrin. alpha 2- and beta-adrenoceptor blockers, muscarinic antagonists, GABA mimenergics and morphine had no effect. These results suggest that allethrin produces its neurotoxic responses in mice by acting on the brain and spinal levels. Furthermore, adrenergic excitatory and serotonergic inhibitory mechanisms may be involved in the neural pathway through which the allethrin-induced tremor is evoked.

  20. Poroelastic Mechanical Effects of Hemicelluloses on Cellulosic Hydrogels under Compression

    Science.gov (United States)

    Lopez-Sanchez, Patricia; Cersosimo, Julie; Wang, Dongjie; Flanagan, Bernadine; Stokes, Jason R.; Gidley, Michael J.

    2015-01-01

    Hemicelluloses exhibit a range of interactions with cellulose, the mechanical consequences of which in plant cell walls are incompletely understood. We report the mechanical properties of cell wall analogues based on cellulose hydrogels to elucidate the contribution of xyloglucan or arabinoxylan as examples of two hemicelluloses displaying different interactions with cellulose. We subjected the hydrogels to mechanical pressures to emulate the compressive stresses experienced by cell walls in planta. Our results revealed that the presence of either hemicellulose increased the resistance to compression at fast strain rates. However, at slow strain rates, only xyloglucan increased composite strength. This behaviour could be explained considering the microstructure and the flow of water through the composites confirming their poroelastic nature. In contrast, small deformation oscillatory rheology showed that only xyloglucan decreased the elastic moduli. These results provide evidence for contrasting roles of different hemicelluloses in plant cell wall mechanics and man-made cellulose-based composite materials. PMID:25794048

  1. Fracture behavior and deformation mechanisms under fast neutron irradiation

    International Nuclear Information System (INIS)

    Boutard, J.L.; Dupouy, J.M.

    1980-09-01

    We have established the out-of-pile and in-pile deformation mechanism maps of a 316 stainless steel irradiated in a fast reactor. The knowledge of the dominating deformation mechanism either in post irradiation creep experiments or during the in-pile steady state operating conditions allows to rationalize the apparent discrepancy between the very low out-of-pile ductility and the rather high plastic diametral strains which are obtained in the fast reactor environment without fracture

  2. 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.

  3. 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.

  4. Some mechanisms involved in the radiosensitization of E. coli B/r by paracetamol

    Energy Technology Data Exchange (ETDEWEB)

    Shenoy, M A; Gopalakrishna, K [Bhabha Atomic Research Centre, Bombay (India). Biology and Agriculture Div.

    1977-06-01

    Paracetamol, a widely-used analgesic and antipyretic drug, sensitized E.coli B/r to /sup 60/Co gamma rays under hypoxic conditions. Part of the sensitizing effect has been shown to be due to an electron adduct of the drug. Paracetamol inhibited both post-irradiation DNA and protein syntheses. The targets involved in the inhibition of post-irradiation DNA synthesis have been shown to be different in the presence of the sensitizer. Increased DNA degradation after irradiation was also observed when E.coli B/r were irradiated in the presence of the drug. The presence of paracetamol during hypoxic irradiation of E.coli B/r resulted in the enhancement of DNA single-strand scissions with no apparent effect on their rejoining.

  5. Some mechanisms involved in the radiosensitization of E.coli B/r by paracetamol

    International Nuclear Information System (INIS)

    Shenoy, M.A.; Gopalakrishna, K.

    1977-01-01

    Paracetamol, a widely-used analgesic and antipyretic drug, sensitized E.coli B/r to 60 Co gamma-rays under hypoxic conditions. Part of the sensitizing effect has been shown to be due to an electron adduct of the drug. Paracetamol inhibited both post-irradiation DNA and protein syntheses. The targets involved in the inhibition of post-irradiation DNA synthesis have been shown to be different in the presence of the sensitizer. Increased DNA degradation after irradiation was also observed when E.coli B/r were irradiated in the presence of the drug. The presence of paracetamol during hypoxic irradiation of E.coli B/r resulted in the enhancement of DNA single-strand scissions with no apparent effect on their rejoining. (author)

  6. Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth.

    Science.gov (United States)

    Commandeur, Arno E; Styer, Aaron K; Teixeira, Jose M

    2015-01-01

    Uterine leiomyomas (fibroids) are highly prevalent benign smooth muscle tumors of the uterus. In the USA, the lifetime risk for women developing uterine leiomyomas is estimated as up to 75%. Except for hysterectomy, most therapies or treatments often provide only partial or temporary relief and are not successful in every patient. There is a clear racial disparity in the disease; African-American women are estimated to be three times more likely to develop uterine leiomyomas and generally develop more severe symptoms. There is also familial clustering between first-degree relatives and twins, and multiple inherited syndromes in which fibroid development occurs. Leiomyomas have been described as clonal and hormonally regulated, but despite the healthcare burden imposed by the disease, the etiology of uterine leiomyomas remains largely unknown. The mechanisms involved in their growth are also essentially unknown, which has contributed to the slow progress in development of effective treatment options. A comprehensive PubMed search for and critical assessment of articles related to the epidemiological, biological and genetic clues for uterine leiomyoma development was performed. The individual functions of some of the best candidate genes are explained to provide more insight into their biological function and to interconnect and organize genes and pathways in one overarching figure that represents the current state of knowledge about uterine leiomyoma development and growth. In this review, the widely recognized roles of estrogen and progesterone in uterine leiomyoma pathobiology on the basis of clinical and experimental data are presented. This is followed by fundamental aspects and concepts including the possible cellular origin of uterine fibroids. The central themes in the subsequent parts are cytogenetic aberrations in leiomyomas and the racial/ethnic disparities in uterine fibroid biology. Then, the attributes of various in vitro and in vivo, human syndrome

  7. Neural mechanisms underlying cognitive control of men with lifelong antisocial behavior.

    Science.gov (United States)

    Schiffer, Boris; Pawliczek, Christina; Mu Ller, Bernhard; Forsting, Michael; Gizewski, Elke; Leygraf, Norbert; Hodgins, Sheilagh

    2014-04-30

    Results of meta-analyses suggested subtle deficits in cognitive control among antisocial individuals. Because almost all studies focused on children with conduct problems or adult psychopaths, however, little is known about cognitive control mechanisms among the majority of persistent violent offenders who present an antisocial personality disorder (ASPD). The present study aimed to determine whether offenders with ASPD, relative to non-offenders, display dysfunction in the neural mechanisms underlying cognitive control and to assess the extent to which these dysfunctions are associated with psychopathic traits and trait impulsivity. Participants comprised 21 violent offenders and 23 non-offenders who underwent event-related functional magnetic resonance imaging while performing a non-verbal Stroop task. The offenders, relative to the non-offenders, exhibited reduced response time interference and a different pattern of conflict- and error-related activity in brain areas involved in cognitive control, attention, language, and emotion processing, that is, the anterior cingulate, dorsolateral prefrontal, superior temporal and postcentral cortices, putamen, thalamus, and amygdala. Moreover, between-group differences in behavioural and neural responses revealed associations with core features of psychopathy and attentional impulsivity. Thus, the results of the present study confirmed the hypothesis that offenders with ASPD display alterations in the neural mechanisms underlying cognitive control and that those alterations relate, at least in part, to personality characteristics. Copyright © 2014. Published by Elsevier Ireland Ltd.

  8. 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

  9. 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...

  10. 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

  11. Anticonvulsants Teratogenic Mechanism Involves Alteration of Bioelectrically-controlled Processes in the Embryo. A hypothesis

    Science.gov (United States)

    Hernández-Díaz, Sonia; Levin, Michael

    2014-01-01

    Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations is controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. If our theory were correct, development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs. PMID:24815983

  12. Mechanisms involved in growth inhibition induced by clofibrate in hepatoma cells

    International Nuclear Information System (INIS)

    Muzio, Giuliana; Maggiora, Marina; Trombetta, Antonella; Martinasso, Germana; Reffo, Patrizia; Colombatto, Sebastiano; Canuto, Rosa Angela

    2003-01-01

    Low concentrations of some peroxisome proliferators have been found to decrease apoptosis in rat liver cells, whereas higher but pharmacological concentrations have been found to inhibit cell proliferation or to induce apoptosis in human and rat hepatoma cells. The highly deviated JM2 rat hepatoma cell line was used to examine the mechanisms underlying the inhibitory effect on cell proliferation. Clofibrate chiefly inhibited cell proliferation in these cells. Parallel to the decrease in cell proliferation there was an increase of peroxisome proliferator activated receptor (PPAR) gamma and of protein phosphatase 2A, whose importance was confirmed, respectively, by using antisense oliginucleotides (AS-ODN) or okadaic acid. The increase of protein phosphatase 2A induced by PPARgamma caused a decrease of MAPK, an intracellular signaling transduction pathway, as shown by evaluation of Erk1,2 and c-myc. In light of these results, clofibrate, like conventional synthetic ligands of PPARgamma, may be regarded as a possible prototype anti-tumour drug

  13. 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.

  14. 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

  15. Mechanical behaviour of adhesive joint under tensile and shear loading

    NARCIS (Netherlands)

    Jiang, X.; Kolstein, M.H.; Bijlaard, F.S.K.

    2013-01-01

    Due to various advantages of Fibre-Reinforced Polymer (FRP) decks, the FRP to steel composite bridge system is being increasingly used in new bridge structures as well as rehabilitation projects for old bridges. This paper focuses on the mechanical behaviours and failure modes of the

  16. Wire bond degradation under thermo- and pure mechanical loading

    DEFF Research Database (Denmark)

    Pedersen, Kristian Bonderup; Nielsen, Dennis Achton; Czerny, Bernhard

    2017-01-01

    This paper presents a fundamental study on degradation of heavy Al bond wires typically used in high power modules. Customized samples are designed to only consist of Al bond wires on standard Si diodes. These samples are subjected to pure mechanical and passive thermal cycling to investigate...

  17. Transcriptome profiling reveals regulatory mechanisms underlying Corolla Senescence in Petunia

    Science.gov (United States)

    Genetic regulatory mechanisms that govern petal natural senescence in petunia is complicated and unclear. To identify key genes and pathways that regulate the process, we initiated a transcriptome analysis in petunia petals at four developmental time points, including petal opening without anthesis ...

  18. 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 ...

  19. 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.

  20. 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.

  1. 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…

  2. 29 CFR 1904.9 - Recording criteria for cases involving medical removal under OSHA standards.

    Science.gov (United States)

    2010-07-01

    ... surveillance requirements of an OSHA standard, you must record the case on the OSHA 300 Log. (b) Implementation—(1) How do I classify medical removal cases on the OSHA 300 Log? You must enter each medical removal case on the OSHA 300 Log as either a case involving days away from work or a case involving restricted...

  3. QTL analysis of frost damage in pea suggests different mechanisms involved in frost tolerance.

    Science.gov (United States)

    Klein, Anthony; Houtin, Hervé; Rond, Céline; Marget, Pascal; Jacquin, Françoise; Boucherot, Karen; Huart, Myriam; Rivière, Nathalie; Boutet, Gilles; Lejeune-Hénaut, Isabelle; Burstin, Judith

    2014-06-01

    Avoidance mechanisms and intrinsic resistance are complementary strategies to improve winter frost tolerance and yield potential in field pea. The development of the winter pea crop represents a major challenge to expand plant protein production in temperate areas. Breeding winter cultivars requires the combination of freezing tolerance as well as high seed productivity and quality. In this context, we investigated the genetic determinism of winter frost tolerance and assessed its genetic relationship with yield and developmental traits. Using a newly identified source of frost resistance, we developed a population of recombinant inbred lines and evaluated it in six environments in Dijon and Clermont-Ferrand between 2005 and 2010. We developed a genetic map comprising 679 markers distributed over seven linkage groups and covering 947.1 cM. One hundred sixty-one quantitative trait loci (QTL) explaining 9-71 % of the phenotypic variation were detected across the six environments for all traits measured. Two clusters of QTL mapped on the linkage groups III and one cluster on LGVI reveal the genetic links between phenology, morphology, yield-related traits and frost tolerance in winter pea. QTL clusters on LGIII highlighted major developmental gene loci (Hr and Le) and the QTL cluster on LGVI explained up to 71 % of the winter frost damage variation. This suggests that a specific architecture and flowering ideotype defines frost tolerance in winter pea. However, two consistent frost tolerance QTL on LGV were independent of phenology and morphology traits, showing that different protective mechanisms are involved in frost tolerance. Finally, these results suggest that frost tolerance can be bred independently to seed productivity and quality.

  4. 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

  5. Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.

    Science.gov (United States)

    Zhang, Ruowen; Wu, Jiahui; Ferrandon, Sylvain; Glowacki, Katie J; Houghton, Janet A

    2016-12-06

    The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Pore closure in zeolitic imidazolate frameworks under mechanical pressure.

    Science.gov (United States)

    Henke, Sebastian; Wharmby, Michael T; Kieslich, Gregor; Hante, Inke; Schneemann, Andreas; Wu, Yue; Daisenberger, Dominik; Cheetham, Anthony K

    2018-02-14

    We investigate the pressure-dependent mechanical behaviour of the zeolitic imidazolate framework ZIF-4 (M(im) 2 ; M 2+ = Co 2+ or Zn 2+ , im - = imidazolate) with high pressure, synchrotron powder X-ray diffraction and mercury intrusion measurements. A displacive phase transition from a highly compressible open pore ( op ) phase with continuous porosity (space group Pbca , bulk modulus ∼1.4 GPa) to a closed pore ( cp ) phase with inaccessible porosity (space group P 2 1 / c , bulk modulus ∼3.3-4.9 GPa) is triggered by the application of mechanical pressure. Over the course of the transitions, both ZIF-4 materials contract by about 20% in volume. However, the threshold pressure, the reversibility and the immediate repeatability of the phase transition depend on the metal cation. ZIF-4(Zn) undergoes the op-cp phase transition at a hydrostatic mechanical pressure of only 28 MPa, while ZIF-4(Co) requires about 50 MPa to initiate the transition. Interestingly, ZIF-4(Co) fully returns to the op phase after decompression, whereas ZIF-4(Zn) remains in the cp phase after pressure release and requires subsequent heating to switch back to the op phase. These variations in high pressure behaviour can be rationalised on the basis of the different electron configurations of the respective M 2+ ions (3d 10 for Zn 2+ and 3d 7 for Co 2+ ). Our results present the first examples of op-cp phase transitions ( i.e. breathing transitions) of ZIFs driven by mechanical pressure and suggest potential applications of these functional materials as shock absorbers, nanodampers, or in mechanocalorics.

  12. Underlying mechanisms of transient luminous events: a review

    OpenAIRE

    V. V. Surkov; M. Hayakawa

    2012-01-01

    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...

  13. Mechanical Characterization of Femoral Cartilage Under Unicompartimental Osteoarthritis

    OpenAIRE

    Vidal-Lesso, A.; Ledesma-Orozco, E.; Daza-Benítez, L.; Lesso-Arroyo, R.

    2014-01-01

    The aim of this study was to determine the mechanical properties and thickness of articular cartilage in the unaffected femoral regions in cases of unicompartimental osteoarthritis on the knees. The specimens were tested using a 3mm plane-ended cylindrical indenter and a displacement of 0.5mm was applied at specific points in seven femoral knee cartilages with unicompartimental osteoarthritis. The thickness, stiffness, elastic modulus, shear modulus and bulk modulus were obtained. These prope...

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Towards a Better Understanding of the Molecular Mechanisms Involved in Sunlight-Induced Melanoma

    Directory of Open Access Journals (Sweden)

    Williams Mandy

    2005-01-01

    Full Text Available Although much less prevalent than its nonmelanoma skin cancer counterparts, cutaneous malignant melanoma (CMM is the most lethal human skin cancer. Epidemiological and biological studies have established a strong link between lifetime exposure to ultraviolet (UV light, particularly sunburn in childhood, and the development of melanoma. However, the specific molecular targets of this environmental carcinogen are not known. Data obtained from genetic and molecular studies over the last few years have identified the INK4a/ARF locus as the “gatekeeper” melanoma suppressor, encoding two tumour suppressor proteins in human, p16 INK4a and p14 ARF . Recent developments in molecular biotechnology and research using laboratory animals have made a significant gene breakthrough identifying the components of the p16 INK4a /Rb pathway as the principal and rate-limiting targets of UV radiation actions in melanoma formation. This review summarizes the current knowledge of the molecular mechanisms involved in melanoma development and its relationship to sunlight UV radiation.

  19. 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.

  20. Interfacial Mechanics Analysis of a Brittle Coating–Ductile Substrate System Involved in Thermoelastic Contact

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    2017-02-01

    Full Text Available In this paper, interfacial stress analysis for a brittle coating/ductile substrate system, which is involved in a sliding contact with a rigid ball, is presented. By combining interface mechanics theory and the image point method, stress and displacement responses within a coated material for normal load, tangential load, and thermal load are obtained; further, the Green’s functions are established. The effects of coating thickness, friction coefficient, and a coating’s thermoelastic properties on the interfacial shear stress, τxz, and transverse stress, σxx, distributions are discussed in detail. A phenomenon, where interfacial shear stress tends to be relieved by frictional heating, is found in the case of a coating material’s thermal expansion coefficient being less than a substrate material’s thermal expansion coefficient. Additionally, numerical results show that distribution of interfacial stress can be altered and, therefore, interfacial damage can be modified by adjusting a coating’s structural parameters and thermoelastic properties.

  1. 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.

  2. Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

    Science.gov (United States)

    Guzman, David Calderón; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; de la Cruz, Diego Zamora; Soto, Monica Punzo

    2017-01-01

    Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

  3. Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms : Involvement of JNK and ERK MAP kinases

    NARCIS (Netherlands)

    Conde de la Rosa, L; Schoemaker, MH; Vrenken, TE; Buist-Homan, M; Havinga, R; Jansen, PLM; Moshage, H

    Background/Aims: In liver diseases, reactive oxygen species (ROS) are involved in cell death and liver injury, but the mechanisms are not completely elucidated. To elucidate the mechanisms of hepatocyte cell death induced by the ROS superoxide anions and hydrogen peroxide, primary cultures of

  4. Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms: involvement of JNK and ERK MAP kinases

    NARCIS (Netherlands)

    Conde de la Rosa, Laura; Schoemaker, Marieke H.; Vrenken, Titia E.; Buist-Homan, Manon; Havinga, Rick; Jansen, Peter L. M.; Moshage, Han

    2006-01-01

    BACKGROUND/AIMS: In liver diseases, reactive oxygen species (ROS) are involved in cell death and liver injury, but the mechanisms are not completely elucidated. To elucidate the mechanisms of hepatocyte cell death induced by the ROS superoxide anions and hydrogen peroxide, primary cultures of

  5. 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

  6. 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.

  7. Corrosion mechanisms of spent fuel under oxidizing conditions

    International Nuclear Information System (INIS)

    Finn, P.A.; Finch, R.; Buck, E.; Bates, J.

    1997-01-01

    The release of 99 Tc can be used as a reliable marker for the extent of spent oxide fuel reaction under unsaturated high-drip-rate conditions at 90 degrees C. Evidence from leachate data and from scanning and transmission electron microscopy (SEM and TEM) examination of reacted fuel samples is presented for radionuclide release, potential reaction pathways, and the formation of alteration products. In the ATM-103 fuel, 0.03 of the total inventory of 99 Tc is released in 3.7 years under unsaturated and oxidizing conditions. Two reaction pathways that have been identified from SEM are (1) through-grain dissolution with subsequent formation of uranyl alteration products, and (2) grain-boundary dissolution. The major alteration product identified by x-ray diffraction (XRD) and SEM, is Na-boltwoodite, Na[(UO 2 )(SiO 3 OH)]lg-bullet H 2 O, which is formed from sodium and silicon in the water leachant

  8. Performance of multifilamentary Nb3Sn under mechanical load

    International Nuclear Information System (INIS)

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

    1976-11-01

    The critical current density of commercial multifilamentary Nb 3 Sn conductor has been measured during the application of uniaxial tension at 4.2 0 K and after bending at room temperature. Significant reductions in the critical current density J/sub c/ occurred 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. 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

  10. Self-DNA inhibitory effects: Underlying mechanisms and ecological implications.

    Science.gov (United States)

    Cartenì, Fabrizio; Bonanomi, Giuliano; Giannino, Francesco; Incerti, Guido; Vincenot, Christian Ernest; Chiusano, Maria Luisa; Mazzoleni, Stefano

    2016-01-01

    DNA is usually known as the molecule that carries the instructions necessary for cell functioning and genetic inheritance. A recent discovery reported a new functional role for extracellular DNA. After fragmentation, either by natural or artificial decomposition, small DNA molecules (between ∼50 and ∼2000 bp) exert a species specific inhibitory effect on individuals of the same species. Evidence shows that such effect occurs for a wide range of organisms, suggesting a general biological process. In this paper we explore the possible molecular mechanisms behind those findings and discuss the ecological implications, specifically those related to plant species coexistence.

  11. 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

  12. 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.

  13. 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

  14. Modeling of glycerol-3-phosphate transporter suggests a potential 'tilt' mechanism involved in its function.

    Science.gov (United States)

    Tsigelny, Igor F; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K

    2008-10-01

    "rocker switch" may apply to certain MFS transporters, intermediate "tilted" states may exist under certain circumstances or as transitional structures. Although wet lab experimental confirmation is required, our results suggest that transport mechanisms in this transporter family should probably not be assumed to be conserved simply based on standard structural homology considerations. Furthermore, steered molecular dynamics elucidating energetic interactions of ligands with amino acid residues in an appropriately modeled transporter may have predictive value in understanding the impact of mutations and/or polymorphisms on transporter function.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress.

    Directory of Open Access Journals (Sweden)

    Olivier Girard

    Full Text Available Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C and CON (25°C conditions.Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting.Mean skin (37.2±0.7 vs. 32.7±0.8°C; P<0.001 and core (38.9±0.2 vs. 38.8±0.3°C; P<0.05 temperatures, together with thermal comfort (P<0.001 were higher following repeated sprinting in HOT vs. CON. Step frequency and vertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both P<0.001 and contact time (+3.2±2.4%; P<0.01 higher in HOT for the mean of sets 1-3 compared to CON. Running distance per sprint decreased from set 1 to 3 (-7.0±6.4%; P<0.001, with a tendency for shorter distance covered in HOT vs. CON (-2.7±3.4%; P = 0.06. Mean vertical (-2.6±5.5%; P<0.01, horizontal (-9.1±4.4%; P<0.001 and resultant ground reaction forces (-3.0±2.8%; P<0.01 along with vertical stiffness (-12.9±2.3%; P<0.001 and leg stiffness (-8.4±2.7%; P<0.01 decreased from set 1 to 3, independently of conditions. Propulsive power decreased from set 1 to 3 (-16.9±2.4%; P<0.001, with lower propulsive power values in set 2 (-6.6%; P<0.05 in HOT vs. CON. No changes in constant-velocity running patterns occurred between conditions, or from pre-to-post repeated-sprint exercise.Thermal strain alters step frequency and vertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations.

  20. Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress

    Science.gov (United States)

    Brocherie, Franck; Morin, Jean-Benoit; Racinais, Sébastien; Millet, Grégoire P.; Périard, Julien D.

    2017-01-01

    Purpose Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C) and CON (25°C) conditions. Methods Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting. Results Mean skin (37.2±0.7 vs. 32.7±0.8°C; P<0.001) and core (38.9±0.2 vs. 38.8±0.3°C; P<0.05) temperatures, together with thermal comfort (P<0.001) were higher following repeated sprinting in HOT vs. CON. Step frequency and vertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both P<0.001) and contact time (+3.2±2.4%; P<0.01) higher in HOT for the mean of sets 1–3 compared to CON. Running distance per sprint decreased from set 1 to 3 (-7.0±6.4%; P<0.001), with a tendency for shorter distance covered in HOT vs. CON (-2.7±3.4%; P = 0.06). Mean vertical (-2.6±5.5%; P<0.01), horizontal (-9.1±4.4%; P<0.001) and resultant ground reaction forces (-3.0±2.8%; P<0.01) along with vertical stiffness (-12.9±2.3%; P<0.001) and leg stiffness (-8.4±2.7%; P<0.01) decreased from set 1 to 3, independently of conditions. Propulsive power decreased from set 1 to 3 (-16.9±2.4%; P<0.001), with lower propulsive power values in set 2 (-6.6%; P<0.05) in HOT vs. CON. No changes in constant-velocity running patterns occurred between conditions, or from pre-to-post repeated-sprint exercise. Conclusions Thermal strain alters step frequency and vertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations. PMID:28146582

  1. 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

  2. Functional methods underlying classical mechanics, relativity and quantum theory

    International Nuclear Information System (INIS)

    Kryukov, A

    2013-01-01

    The paper investigates the physical content of a recently proposed mathematical framework that unifies the standard formalisms of classical mechanics, relativity and quantum theory. In the framework states of a classical particle are identified with Dirac delta functions. The classical space is ''made'' of these functions and becomes a submanifold in a Hilbert space of states of the particle. The resulting embedding of the classical space into the space of states is highly non-trivial and accounts for numerous deep relations between classical and quantum physics and relativity. One of the most striking results is the proof that the normal probability distribution of position of a macroscopic particle (equivalently, position of the corresponding delta state within the classical space submanifold) yields the Born rule for transitions between arbitrary quantum states.

  3. 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.

  4. 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.

  5. Ecological mechanisms underlying arthropod species diversity in grasslands.

    Science.gov (United States)

    Joern, Anthony; Laws, Angela N

    2013-01-01

    Arthropods are an important component of grassland systems, contributing significantly to biodiversity and ecosystem structure and function. Climate, fire, and grazing by large herbivores are important drivers in grasslands worldwide. Arthropod responses to these drivers are highly variable and clear patterns are difficult to find, but responses are largely indirect with respect to changes in resources, species interactions, habitat structure, and habitat heterogeneity resulting from interactions among fire, grazing, and climate. Here, we review these ecological mechanisms influencing grassland arthropod diversity. We summarize hypotheses describing species diversity at local and regional scales and then discuss specific factors that may affect arthropod diversity in grassland systems. These factors include direct and indirect effects of grazing, fire, and climate, species interactions, above- and belowground interactions, and landscape-level effects.

  6. 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.

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

    Science.gov (United States)

    Ryvkin, Julia; Bentzur, Assa; Zer-Krispil, Shir; Shohat-Ophir, Galit

    2018-01-01

    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.

  8. 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.

  9. Uranium dioxide sintering Kinetics and mechanisms under controlled oxygen potentials

    International Nuclear Information System (INIS)

    Freitas, C.T. de.

    1980-06-01

    The initial, intermediate, and final sintering stages of uranium dioxide were investigated as a function of stoichiometry and temperature by following the kinetics of the sintering reaction. Stoichiometry was controlled by means of the oxygen potential of the sintering atmosphere, which was measured continuously by solid-state oxygen sensors. Included in the kinetic study were microspheres originated from UO 2 gels and UO 2 pellets produced by isostatic pressing ceramic grade powders. The microspheres sintering behavior was examined using hot-stage microscopy and a specially designed high-temperature, controlled atmosphere furnace. This same furnace was employed as part of an optical dilatometer, which was utilized in the UO 2 pellet sintering investigations. For controlling the deviations from stoichiometry during heat treatment, the oxygen partial pressure in the sintering atmosphere was varied by passing the gas through a Cu-Ti-Cu oxygen trap. The trap temperature determined the oxygen partial pressure of the outflowing mixture. Dry hydrogen was also used in some of the UO sub(2+x) sintering experiments. The determination of diametrial shrinkages and sintering indices was made utilizing high-speed microcinematography and ultra-microbalance techniques. It was observed that the oxygen potential has a substantial influence on the kinetics of the three sintering stages. The control of the sintering atmosphere oxygen partial pressure led to very fast densification of UO sub(2+x). Values in the interval 95.0 to 99.5% of theoretical density were reached in less than one minute. Uranium volume diffusion is the dominant mechanism in the initial and intermediate sintering stages. For the final stage, uranium grain boundary diffusion was found to be the main sintering mechanism. (Author) [pt

  10. 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

  11. Pathological mechanisms underlying single large‐scale mitochondrial DNA deletions

    Science.gov (United States)

    Rocha, Mariana C.; Rosa, Hannah S.; Grady, John P.; Blakely, Emma L.; He, Langping; Romain, Nadine; Haller, Ronald G.; Newman, Jane; McFarland, Robert; Ng, Yi Shiau; Gorman, Grainne S.; Schaefer, Andrew M.; Tuppen, Helen A.; Taylor, Robert W.

    2018-01-01

    Objective Single, large‐scale deletions in mitochondrial DNA (mtDNA) are a common cause of mitochondrial disease. This study aimed to investigate the relationship between the genetic defect and molecular phenotype to improve understanding of pathogenic mechanisms associated with single, large‐scale mtDNA deletions in skeletal muscle. Methods We investigated 23 muscle biopsies taken from adult patients (6 males/17 females with a mean age of 43 years) with characterized single, large‐scale mtDNA deletions. Mitochondrial respiratory chain deficiency in skeletal muscle biopsies was quantified by immunoreactivity levels for complex I and complex IV proteins. Single muscle fibers with varying degrees of deficiency were selected from 6 patient biopsies for determination of mtDNA deletion level and copy number by quantitative polymerase chain reaction. Results We have defined 3 “classes” of single, large‐scale deletion with distinct patterns of mitochondrial deficiency, determined by the size and location of the deletion. Single fiber analyses showed that fibers with greater respiratory chain deficiency harbored higher levels of mtDNA deletion with an increase in total mtDNA copy number. For the first time, we have demonstrated that threshold levels for complex I and complex IV deficiency differ based on deletion class. Interpretation Combining genetic and immunofluorescent assays, we conclude that thresholds for complex I and complex IV deficiency are modulated by the deletion of complex‐specific protein‐encoding genes. Furthermore, removal of mt‐tRNA genes impacts specific complexes only at high deletion levels, when complex‐specific protein‐encoding genes remain. These novel findings provide valuable insight into the pathogenic mechanisms associated with these mutations. Ann Neurol 2018;83:115–130 PMID:29283441

  12. Mechanism and kinetics of parathion degradation under ultrasonic irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yao Juanjuan, E-mail: yao_juanjuan@yahoo.cn [State Key laboratory of Pollution Control and Resources Reuse, Tongji University, Shanghai, 200092 (China); Gao Naiyun; Li Cong; Li Lei; Xu Bin [State Key laboratory of Pollution Control and Resources Reuse, Tongji University, Shanghai, 200092 (China)

    2010-03-15

    The parathion degradation under ultrasonic irradiation in aqueous solution was investigated. The results indicate that at the conditions in question, degradation rate of parathion decreased with increasing initial concentration and decreasing power. The optimal frequency for parathion degradation was 600 kHz. The free radical reactions predominate in the sonochemical degradation of parathion and the reaction zones are predominately at the bubble interface and, to a much lesser extent, in bulk solution. The gas/liquid interfacial regions are the real effective reaction sites for sonochemical degradation of parathion. The reaction can be well described as a gas/liquid heterogeneous reaction which obeys a kinetic model based on Langmuir-Hinshelwood model. The main pathways of parathion degradation by ultrasonic irradiation were also proposed by qualitative and quantitative analysis of organic and inorganic byproducts. It is indicated that the N{sub 2} in air takes part in the parathion degradation through the formation of {center_dot}NO{sub 2} under ultrasonic irradiation. Parathion is decomposed into paraoxon and 4-nitrophenol in the first step via two different pathways, respectively, which is in agreement with the theoretical molecular orbital (MO) calculations.

  13. 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)

  14. Mechanisms Involved in Guiding the Preference for Fat Emulsion Differ Depending on the Concentration.

    Science.gov (United States)

    Sakamoto, Kazuhiro; Matsumura, Shigenobu; Okafuji, Yoko; Eguchi, Ai; Lee, Shinhye; Adachi, Shin-ichi; Fujitani, Mina; Tsuzuki, Satoshi; Inoue, Kazuo; Fushiki, Tohru

    2015-01-01

    High-fat foods tend to be palatable and can cause addiction in mice via a reinforcing effect. However, mice showed preference for low fat concentrations that do not elicit a reinforcing effect in a two-bottle choice test with water as the alternative. This behavior indicates the possibility that the mechanism underlying fat palatability may differ depending on the dietary fat content. To address this issue, we examined the influences of the opioid system and olfactory and gustatory transductions on the intake and reinforcing effects of various concentrations of a dietary fat emulsion (Intralipid). We found that the intake and reinforcing effects of fat emulsion were reduced by the administration of an opioid receptor antagonist (naltrexone). Furthermore, the action of naltrexone was only observed at higher concentrations of fat emulsion. The intake and the reinforcing effects of fat emulsion were also reduced by olfactory and glossopharyngeal nerve transections (designated ONX and GLX, respectively). In contrast to naltrexone, the effects of ONX and GLX were mainly observed at lower concentrations of fat emulsion. These results imply that the opioid system seems to have a greater role in determining the palatability of high-fat foods unlike the contribution of olfactory and glossopharyngeal nerves.

  15. 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

  16. NEUROBIOLOGICAL AND PSYCHOPATHOLOGICAL MECHANISMS UNDERLYING ADDICTION-LIKE BEHAVIORS: AN OVERVIEW AND THEMATIC SYNTHESIS.

    Directory of Open Access Journals (Sweden)

    Loredana Scala

    2017-08-01

    Full Text Available The term dependency is increasingly being used also to explain symptoms resulting from the repetition of a behavior or legalized and socially accepted activities that do not involve substance assumption. These activities, although considered normal habits of daily life can become real addictions that may affect and disrupt socio-relational and working functioning. Growing evidence suggests to consider behavioral addictions similar to drug dependence for their common symptoms, the high frequency of poly-dependence conditions, and the correlation in risk (impulsivity, sensation seeking, early exposure, familiarity and protective (parental control, adequate metacognitive skills factors. The aim of this paper is to describe addiction in its general aspects, highlighting the underlying neurobiological and psychopathological mechanisms.

  17. Protein metabolism in marine animals: the underlying mechanism of growth.

    Science.gov (United States)

    Fraser, Keiron P P; Rogers, Alex D

    2007-01-01

    Growth is a fundamental process within all marine organisms. In soft tissues, growth is primarily achieved by the synthesis and retention of proteins as protein growth. The protein pool (all the protein within the organism) is highly dynamic, with proteins constantly entering the pool via protein synthesis or being removed from the pool via protein degradation. Any net change in the size of the protein pool, positive or negative, is termed protein growth. The three inter-related processes of protein synthesis, degradation and growth are together termed protein metabolism. Measurement of protein metabolism is vital in helping us understand how biotic and abiotic factors affect growth and growth efficiency in marine animals. Recently, the developing fields of transcriptomics and proteomics have started to offer us a means of greatly increasing our knowledge of the underlying molecular control of protein metabolism. Transcriptomics may also allow us to detect subtle changes in gene expression associated with protein synthesis and degradation, which cannot be detected using classical methods. A large literature exists on protein metabolism in animals; however, this chapter concentrates on what we know of marine ectotherms; data from non-marine ectotherms and endotherms are only discussed when the data are of particular relevance. We first consider the techniques available to measure protein metabolism, their problems and what validation is required. Protein metabolism in marine organisms is highly sensitive to a wide variety of factors, including temperature, pollution, seasonality, nutrition, developmental stage, genetics, sexual maturation and moulting. We examine how these abiotic and biotic factors affect protein metabolism at the level of whole-animal (adult and larval), tissue and cellular protein metabolism. Available gene expression data, which help us understand the underlying control of protein metabolism, are also discussed. As protein metabolism appears to

  18. Uncovering the neural mechanisms underlying learning from tests.

    Directory of Open Access Journals (Sweden)

    Xiaonan L Liu

    Full Text Available People learn better when re-study opportunities are replaced with tests. While researchers have begun to speculate on why testing is superior to study, few studies have directly examined the neural underpinnings of this effect. In this fMRI study, participants engaged in a study phase to learn arbitrary word pairs, followed by a cued recall test (recall second half of pair when cued with first word of pair, re-study of each pair, and finally another cycle of cued recall tests. Brain activation patterns during the first test (recall of the studied pairs predicts performance on the second test. Importantly, while subsequent memory analyses of encoding trials also predict later accuracy, the brain regions involved in predicting later memory success are more extensive for activity during retrieval (testing than during encoding (study. Those additional regions that predict subsequent memory based on their activation at test but not at encoding may be key to understanding the basis of the testing effect.

  19. Neural mechanisms underlying motivation of mental versus physical effort.

    Directory of Open Access Journals (Sweden)

    Liane Schmidt

    2012-02-01

    Full Text Available Mental and physical efforts, such as paying attention and lifting weights, have been shown to involve different brain systems. These cognitive and motor systems, respectively, include cortical networks (prefronto-parietal and precentral regions as well as subregions of the dorsal basal ganglia (caudate and putamen. Both systems appeared sensitive to incentive motivation: their activity increases when we work for higher rewards. Another brain system, including the ventral prefrontal cortex and the ventral basal ganglia, has been implicated in encoding expected rewards. How this motivational system drives the cognitive and motor systems remains poorly understood. More specifically, it is unclear whether cognitive and motor systems can be driven by a common motivational center or if they are driven by distinct, dedicated motivational modules. To address this issue, we used functional MRI to scan healthy participants while performing a task in which incentive motivation, cognitive, and motor demands were varied independently. We reasoned that a common motivational node should (1 represent the reward expected from effort exertion, (2 correlate with the performance attained, and (3 switch effective connectivity between cognitive and motor regions depending on task demand. The ventral striatum fulfilled all three criteria and therefore qualified as a common motivational node capable of driving both cognitive and motor regions of the dorsal striatum. Thus, we suggest that the interaction between a common motivational system and the different task-specific systems underpinning behavioral performance might occur within the basal ganglia.

  20. 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...

  1. 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

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

    OpenAIRE

    Tambutte Sylvie; Tambutte Eric; Ferrier-Pages Christine; Mone Yves; Duval David; Foure Laurent; Roger Emmanuel; Adjeroud Mehdi; Vidal-Dupiol Jeremie; Zoccola Didier; Allemand Denis; Mitta Guillaume

    2009-01-01

    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 unde...

  3. 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

  4. Thin circular cylinder under axisymmetrical thermal and mechanical loading

    International Nuclear Information System (INIS)

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

    1977-01-01

    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 ratchetting occurs is reduced when compared with the domain predicted by the Bree diagram. To investigate the effect of material hardening the authors verify Halphen's Theorem which states that a structure made of material with kinematic hardening behavior and constant properties with temperature will always shake down to a periodic behavior. (Auth.)

  5. 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.

  6. Neurobiological mechanisms underlying the blocking effect in aversive learning.

    Science.gov (United States)

    Eippert, Falk; Gamer, Matthias; Büchel, Christian

    2012-09-19

    Current theories of classical conditioning assume that learning depends on the predictive relationship between events, not just on their temporal contiguity. Here we employ the classic experiment substantiating this reasoning-the blocking paradigm-in combination with functional magnetic resonance imaging (fMRI) to investigate whether human amygdala responses in aversive learning conform to these assumptions. In accordance with blocking, we demonstrate that significantly stronger behavioral and amygdala responses are evoked by conditioned stimuli that are predictive of the unconditioned stimulus than by conditioned stimuli that have received the same pairing with the unconditioned stimulus, yet have no predictive value. When studying the development of this effect, we not only observed that it was related to the strength of previous conditioned responses, but also that predictive compared with nonpredictive conditioned stimuli received more overt attention, as measured by fMRI-concurrent eye tracking, and that this went along with enhanced amygdala responses. We furthermore observed that prefrontal regions play a role in the development of the blocking effect: ventromedial prefrontal cortex (subgenual anterior cingulate) only exhibited responses when conditioned stimuli had to be established as nonpredictive for an outcome, whereas dorsolateral prefrontal cortex also showed responses when conditioned stimuli had to be established as predictive. Most importantly, dorsolateral prefrontal cortex connectivity to amygdala flexibly switched between positive and negative coupling, depending on the requirements posed by predictive relationships. Together, our findings highlight the role of predictive value in explaining amygdala responses and identify mechanisms that shape these responses in human fear conditioning.

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

    Directory of Open Access Journals (Sweden)

    Antonio F. Hernández

    2016-03-01

    Full Text Available 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.

  8. Coordination of frontline defense mechanisms under severe oxidative stress.

    Science.gov (United States)

    Kaur, Amardeep; Van, Phu T; Busch, Courtney R; Robinson, Courtney K; Pan, Min; Pang, Wyming Lee; Reiss, David J; DiRuggiero, Jocelyne; Baliga, Nitin S

    2010-07-01

    Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations--this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of gamma rays.

  9. 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.

  10. RISK FACTORS FOR PANCREATIC CANCER: UNDERLYING MECHANISMS AND POTENTIAL TARGETS

    Directory of Open Access Journals (Sweden)

    Thomas eKolodecik

    2014-01-01

    Full Text Available Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcription factor NF-kB are important mechanisms that induce acute pancreatitis. Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogneic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16 can ultimately lead to development of pancreatic cancer. Summary:Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Mechanical Model for Dynamic Behavior of Concrete Under Impact Loading

    Science.gov (United States)

    Sun, Yuanxiang

    Concrete is a geo-material which is used substantively in the civil building and military safeguard. One coupled model of damage and plasticity to describe the complex behavior of concrete subjected to impact loading is proposed in this research work. The concrete is assumed as homogeneous continuum with pre-existing micro-cracks and micro-voids. Damage to concrete is caused due to micro-crack nucleation, growth and coalescence, and defined as the probability of fracture at a given crack density. It induces a decrease of strength and stiffness of concrete. Compaction of concrete is physically a collapse of the material voids. It produces the plastic strain in the concrete and, at the same time, an increase of the bulk modulus. In terms of crack growth model, micro-cracks are activated, and begin to propagate gradually. When crack density reaches a critical value, concrete takes place the smashing destroy. The model parameters for mortar are determined using plate impact experiment with uni-axial strain state. Comparison with the test results shows that the proposed model can give consistent prediction of the impact behavior of concrete. The proposed model may be used to design and analysis of concrete structures under impact and shock loading. This work is supported by State Key Laboratory of Explosion science and Technology, Beijing Institute of Technology (YBKT14-02).

  16. The effects of divided attention on encoding processes under incidental and intentional learning instructions: underlying mechanisms?

    Science.gov (United States)

    Naveh-Benjamin, Moshe; Guez, Jonathan; Hara, Yoko; Brubaker, Matthew S; Lowenschuss-Erlich, Iris

    2014-01-01

    Divided attention (DA) at encoding has been shown to significantly disrupt later memory for the studied information. However, what type of processing gets disrupted during DA remains unresolved. In this study, we assessed the degree to which strategic effortful processes are affected under DA by comparing the effects of DA at encoding under intentional and pure incidental learning instructions. In three experiments, participants studied list of words or word pairs under either full or divided attention. Results of three experiments, which used different methodologies, converged to show that the effects of DA at encoding reduce memory performance to the same degree under incidental and intentional learning. Secondary task performance indicated that encoding under intentional learning instructions was more effortful than under incidental learning instructions. In addition, the results indicated enhanced attention to the initial appearance of the words under both types of learning instructions. Results are interpreted to imply that other processes, rather than only strategic effortful ones, might be affected by DA at encoding.

  17. Particle behavior and char burnout mechanisms under pressurized combustion conditions

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, C.M.; Spliethoff, H.; Hein, K.R.G.

    1999-07-01

    Combined cycle systems with coal-fired gas turbines promise highest cycle efficiencies for this fuel. Pressurized pulverized coal combustion, in particular, yields high cycle efficiencies due to the high flue gas temperatures possible. The main problem, however, is to ensure a flue gas clean enough to meet the high gas turbine standards with a dirty fuel like coal. On the one hand, a profound knowledge of the basic chemical and physical processes during fuel conversion under elevated pressures is required whereas on the other hand suitable hot gas cleaning systems need to be developed. The objective of this work was to provide experimental data to enable a detailed description of pressurized coal combustion processes. A series of experiments were performed with two German hvb coals, Ensdorf and Goettelborn, and one German brown coal, Garzweiler, using a semi-technical scale pressurized entrained flow reactor. The parameters varied in the experiments were pressure, gas temperature and bulk gas oxygen concentration. A two-color pyrometer was used for in-situ determination of particle surface temperatures and particle sizes. Flue gas composition was measured and solid residue samples taken and subsequently analyzed. The char burnout reaction rates were determinated varying the parameters pressure, gas temperature and initial oxygen concentration. Variation of residence time was achieved by taking the samples at different points along the reaction zone. The most influential parameters on char burnout reaction rates were found to be oxygen partial pressure and fuel volatile content. With increasing pressure the burn-out reactions are accelerated and are mostly controlled by product desorption and pore diffusion being the limiting processes. The char burnout process is enhanced by a higher fuel volatile content.

  18. 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.

  19. 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.

  20. Mechanisms Involved in the Association between Periodontitis and Complications in Pregnancy

    Science.gov (United States)

    Zi, Marcela Yang Hui; Longo, Priscila Larcher; Bueno-Silva, Bruno; Mayer, Marcia Pinto Alves

    2015-01-01

    The association between periodontitis and some of the problems with pregnancy such as premature delivery, low weight at birth, and preeclampsia (PE) 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 some of these problems with pregnancy 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 that 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 PE 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. PMID:25688342

  1. 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

  2. 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.

  3. 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.

  4. Mechanisms underlying electrical and mechanical responses of the bovine retractor penis to inhibitory nerve stimulation and to an inhibitory extract.

    Science.gov (United States)

    Byrne, N. G.; Muir, T. C.

    1985-01-01

    concluded that the inhibitory response to nerve stimulation and extract in the BRP may involve several ionic species. However, unlike that in gastrointestinal muscles the NANC response in the BRP is accompanied by an increased membrane resistance and does not primarily involve K+. The underlying mechanisms for the inhibitory response to both NANC nerve stimulation and inhibitory extract appear to be similar, compatible with the view that the latter may contain the inhibitory transmitter released from these nerves in this tissue. PMID:4027462

  5. Corticonic models of brain mechanisms underlying cognition and intelligence

    Science.gov (United States)

    Farhat, Nabil H.

    underlying intelligence and other higher level brain functions.

  6. A chromatin modifying enzyme, SDG8, is involved in morphological, gene expression, and epigenetic responses to mechanical stimulation

    OpenAIRE

    Cazzonelli, Christopher I.; Nisar, Nazia; Roberts, Andrea C.; Murray, Kevin D.; Borevitz, Justin O.; Pogson, Barry J.

    2014-01-01

    Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzym...

  7. 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

  8. Failure mechanism of coated biomaterials under high impact-sliding contact stresses

    Science.gov (United States)

    Chen, Ying

    This study uses a newly developed testing method--- inclined cyclic impact-sliding test to investigate the failure behaviors of different types of biomaterials, (SS316L, Ti6Al4V and CoCr) coated by different coatings (TiN, DLC and PEO), under extremely high dynamic contact stress conditions. This test method can simulate the combined impact and sliding/rolling loading conditions, which is very practical in many aspects of commercial usages. During the tests, fatigue cracking, chipping, peeling and material transferring were observed in damaged area. This research is mainly focused on the failure behaviors of load-bearing materials which cyclic impacting and sliding are always involved. This purpose was accomplished in the three stages: First, impact-sliding test was carried out on TiN coated unhardened M2. It was found that soft substrate can cause early failure of coating due to the considerable plastic deformation in the substrate. In this case, stronger substrate is required to support coating better when tested under high contact stresses. Second, PEO coated Ti-6Al-4V was tested under pure sliding and impact-sliding wear conditions. PEO coating was found not strong enough to afford the high contact pressure under cyclic impact-sliding wear test due to its porous surface structure. However, the wear performance of PEO coating was enhanced due to the sub-stoichiometric oxide. To sum up, for load-bearing biomedical implants involved in high impacting movement, PEO coating may not be a promising surface protection. Third, the dense, smooth PVD/CVD bio-inert coatings were reconsidered. DLC and TiN coatings, combined by different substrates together with different interface materials were tested under the cyclic impact-sliding test using a set of proper loading. The results show that to choose a proper combination of coating, interface and substrate based on their mechanical properties is of great importance under the test condition. Hard substrates provide support

  9. Electroencephalogram oscillations support the involvement of task-unrelated thoughts in the mechanism of boredom: A pilot study.

    Science.gov (United States)

    Miyauchi, Eri; Kawasaki, Masahiro

    2018-06-11

    Boredom is a universal experience; however, the neural mechanisms underlying the phenomenon remain unclear. Previous research suggests that boredom is related to attentional failure and derives a possible explanation for the cognitive processes of boredom as a product of appraisals made about task-unrelated thoughts. There are little published data regarding proposed processes from neuroscientific perspectives. Therefore, the authors aimed to examine whether cognitive processes of boredom with task-unrelated thoughts followed by appraisals of them can be explained by examining oscillatory correlates. Electroencephalography was used to measure changes in neural oscillatory activity during subjective experiences of boredom or dislike in healthy subjects. Using this approach, temporal information of brain activity particular to the boredom experience was acquired. Additionally, the Adult Attention-Deficit Hyperactivity Disorder Self-Report Scale was used to evaluate the effects of attentional deficits in the neural processing of boredom. Tonic increase in theta and transient increases in alpha activity were exhibited before the key press response for experiencing boredom; however, only tonic increases in theta amplitudes were boredom specific. The results of this pilot study suggest that the boredom experience is possibly associated with cognitive processes involved in task-unrelated thoughts, followed by their appraisals to be bored, mediated by alpha and theta activity. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin.

    Science.gov (United States)

    Ouadah-Boussouf, Nafia; Babin, Patrick J

    2016-03-01

    One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin

    Energy Technology Data Exchange (ETDEWEB)

    Ouadah-Boussouf, Nafia; Babin, Patrick J., E-mail: p.babin@gpp.u-bordeaux1.fr

    2016-03-01

    One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. - Highlights: • The environmental contaminant tributyltin (TBT) may promote obesity development. • TBT may induce adipocyte hypertrophy through a PPARγ independent mechanism. • RXR/RXR and RXR/LXR dimers are potential in vivo effectors of TBT in zebrafish.

  12. Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin

    International Nuclear Information System (INIS)

    Ouadah-Boussouf, Nafia; Babin, Patrick J.

    2016-01-01

    One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. - Highlights: • The environmental contaminant tributyltin (TBT) may promote obesity development. • TBT may induce adipocyte hypertrophy through a PPARγ independent mechanism. • RXR/RXR and RXR/LXR dimers are potential in vivo effectors of TBT in zebrafish.

  13. 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.

  14. 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 ...

  15. Failure of the integrated circuits involving complementary MOS transistors under thermal and ionizing radiation stresses

    International Nuclear Information System (INIS)

    Sarrabayrouse, G.; Rossel, P.; Buxo, J.; Vialaret, G.

    Some criteria for reliability and sorting of complementary MOS transistor integrated circuits are proposed, that take account for special environmental stresses near plane reactors or nuclear reactor cores. An analysis of the damaging causes for these circuits at high and low temperatures is proposed, results obtained on the evolution of these devices under irradiation and irradiation behaviors are discussed. The whole set of experiments has been carried out on CD 4007 AD(K) circuits [fr

  16. Chromic-P32 phosphate treatment of implanted pancreatic carcinoma: mechanism involved.

    Science.gov (United States)

    Liu, Lu; Feng, Guo-Sheng; Gao, Hong; Tong, Guan-Sheng; Wang, Yu; Gao, Wen; Huang, Ying; Li, Cheng

    2005-04-14

    To study the effects of chromic-P32 phosphate (32P colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism. Ninety-eight tumor bearing nude mice were killed at different time points after the injection of 32P colloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32P colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Bax-related gene expression were observed too. The half-life of effective medication is 13 d after injection of 32P colloids to the tumor stroma, in 1-6 groups, the tumor cell necrosis rates were 20%, 45%, 65%, 70%, 95% and 4%, respectively (F = 4.14-105.36, Pscabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group. The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM in animals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiation-induced apoptosis, the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. 32P colloids intra-tumor injection having prominent anticancer effectiveness may reveal the ability of promoting cell differentiation. The low dose 32P colloids may induce human pancreatic carcinoma Pc-3 implanted tumor cell apoptosis; Apo2.7, caspase-3

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. Rice LTG1 is involved in adaptive growth and fitness under low ambient temperature.

    Science.gov (United States)

    Lu, Guangwen; Wu, Fu-Qing; Wu, Weixun; Wang, Hong-Jun; Zheng, Xiao-Ming; Zhang, Yunhui; Chen, Xiuling; Zhou, Kunneng; Jin, Mingna; Cheng, Zhijun; Li, Xueyong; Jiang, Ling; Wang, Haiyang; Wan, Jianmin

    2014-05-01

    Low temperature (LT) is one of the most prevalent factors limiting the productivity and geographical distribution of rice (Oryza sativa L.). Although significant progress has been made in elucidating the effect of LT on seed germination and reproductive development in rice, the genetic component affecting vegetative growth under LT remains poorly understood. Here, we report that rice cultivars harboring the dominant LTG1 (Low Temperature Growth 1) allele are more tolerant to LT (15-25°C, a temperature range prevalent in high-altitude, temperate zones and high-latitude areas), than those with the ltg1 allele. Using a map-based cloning strategy, we show that LTG1 encodes a casein kinase I. A functional nucleotide polymorphism was identified in the coding region of LTG1, causing a single amino acid substitution (I357K) that is associated with the growth rate, heading date and yield of rice plants grown at LT. We present evidence that LTG1 affects rice growth at LT via an auxin-dependent process(es). Furthermore, phylogenetic analysis of this locus suggests that the ltg1 haplotype arose before the domestication of rice in tropical climates. Together, our data demonstrate that LTG1 plays an important role in the adaptive growth and fitness of rice cultivars under conditions of low ambient temperature. © 2014 The Authors. The Plant Journal © 2014 John Wiley & Sons Ltd.

  4. A Mechanism for Land-Atmosphere Feedback Involving Planetary Wave Structures

    Science.gov (United States)

    Koster, Randal D.; Chang, Yehui; Schubert, Siegfried D.

    2014-01-01

    While the ability of land surface conditions to influence the atmosphere has been demonstrated in various modeling and observational studies, the precise mechanisms by which land-atmosphere feedback occurs are still largely unknown particularly the mechanisms that allow land moisture state in one region to affect atmospheric conditions in another. Such remote impacts are examined here in the context of atmospheric general circulation model (AGCM) simulations, leading to the identification of one potential mechanism: the phase-locking and amplification of a planetary wave through the imposition of a spatial pattern of soil moisture at the land surface. This mechanism, shown here to be relevant in the AGCM, apparently also operates in nature, as suggested by supporting evidence found in reanalysis data.

  5. 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 ...

  6. 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.

  7. Biophysical modeling of in vitro and in vivo processes underlying regulated photoprotective mechanism in cyanobacteria.

    Science.gov (United States)

    Shirshin, Evgeny A; Nikonova, Elena E; Kuzminov, Fedor I; Sluchanko, Nikolai N; Elanskaya, Irina V; Gorbunov, Maxim Y; Fadeev, Victor V; Friedrich, Thomas; Maksimov, Eugene G

    2017-09-01

    Non-photochemical quenching (NPQ) is a mechanism responsible for high light tolerance in photosynthetic organisms. In cyanobacteria, NPQ is realized by the interplay between light-harvesting complexes, phycobilisomes (PBs), a light sensor and effector of NPQ, the photoactive orange carotenoid protein (OCP), and the fluorescence recovery protein (FRP). Here, we introduced a biophysical model, which takes into account the whole spectrum of interactions between PBs, OCP, and FRP and describes the experimental PBs fluorescence kinetics, unraveling interaction rate constants between the components involved and their relative concentrations in the cell. We took benefit from the possibility to reconstruct the photoprotection mechanism and its parts in vitro, where most of the parameters could be varied, to develop the model and then applied it to describe the NPQ kinetics in the Synechocystis sp. PCC 6803 mutant lacking photosystems. Our analyses revealed  that while an excess of the OCP over PBs is required to obtain substantial PBs fluorescence quenching in vitro, in vivo the OCP/PBs ratio is less than unity, due to higher local concentration of PBs, which was estimated as ~10 -5 M, compared to in vitro experiments. The analysis of PBs fluorescence recovery on the basis of the generalized model of enzymatic catalysis resulted in determination of the FRP concentration in vivo close to 10% of the OCP concentration. Finally, the possible role of the FRP oligomeric state alteration in the kinetics of PBs fluorescence was shown. This paper provides the most comprehensive model of the OCP-induced PBs fluorescence quenching to date and the results are important for better understanding of the regulatory molecular mechanisms underlying NPQ in cyanobacteria.

  8. 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......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......) can be employed as a highly useful tool to characterize the inhibitory mechanism of specific antagonist antibodies. Two inhibitory antibodies against uPAR, mAb R3 and mAb R5, were shown to exhibit competitive and non-competitive inhibition, respectively, of ligand binding to the receptor. The former...

  9. Dro1, a major QTL involved in deep rooting of rice under upland field conditions.

    Science.gov (United States)

    Uga, Yusaku; Okuno, Kazutoshi; Yano, Masahiro

    2011-05-01

    Developing a deep root system is an important strategy for avoiding drought stress in rice. Using the 'basket' method, the ratio of deep rooting (RDR; the proportion of total roots that elongated through the basket bottom) was calculated to evaluate deep rooting. A new major quantitative trait locus (QTL) controlling RDR was detected on chromosome 9 by using 117 recombinant inbred lines (RILs) derived from a cross between the lowland cultivar IR64, with shallow rooting, and the upland cultivar Kinandang Patong (KP), with deep rooting. This QTL explained 66.6% of the total phenotypic variance in RDR in the RILs. A BC(2)F(3) line homozygous for the KP allele of the QTL had an RDR of 40.4%, compared with 2.6% for the homozygous IR64 allele. Fine mapping of this QTL was undertaken using eight BC(2)F(3) recombinant lines. The RDR QTL Dro1 (Deeper rooting 1) was mapped between the markers RM24393 and RM7424, which delimit a 608.4 kb interval in the reference cultivar Nipponbare. To clarify the influence of Dro1 in an upland field, the root distribution in different soil layers was quantified by means of core sampling. A line homozygous for the KP allele of Dro1 (Dro1-KP) and IR64 did not differ in root dry weight in the shallow soil layers (0-25 cm), but root dry weight of Dro1-KP in deep soil layers (25-50 cm) was significantly greater than that of IR64, suggesting that Dro1 plays a crucial role in increased deep rooting under upland field conditions.

  10. 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

  11. Understanding the molecular mechanisms involved in the interfacial self-healing of supramolecular rubbers

    NARCIS (Netherlands)

    Bose, R.K.; Garcia Espallargas, S.J.; Van der Zwaag, S.

    2013-01-01

    Supramolecular rubbers based on 2-aminoethylimidazolidone and fatty acids with epoxy crosslinks have been shown to self-heal via multiple hydrogen bonding sites. In this work, several tools are used to investigate the molecular mechanisms taking place at the interface to understand cohesive healing

  12. Nitric oxide is involved in the down-regulation of sost expression induced by mechanical loading

    NARCIS (Netherlands)

    Delgado-Calle, J.; Riancho, J.A.; Klein-Nulend, J.

    2014-01-01

    Mechanical stimulation reduces sclerostin expression in rodents. However, few data are available about the effect of physical stimuli in human systems. Recently we observed that the demethylating agent AzadC induces SOST expression in bone cells. This allowed us in this study to explore the effect

  13. "Coding" and "Decoding": hypothesis for the regulatory mechanism involved in heparan sulfate biosynthesis.

    Science.gov (United States)

    Zhang, Xu; Wang, Fengshan; Sheng, Juzheng

    2016-06-16

    Heparan sulfate (HS) is widely distributed in mammalian tissues in the form of HS proteoglycans, which play essential roles in various physiological and pathological processes. In contrast to the template-guided processes involved in the synthesis of DNA and proteins, HS biosynthesis is not believed to involve a template. However, it appears that the final structure of HS chains was strictly regulated. Herein, we report research based hypothesis that two major steps, namely "coding" and "decoding" steps, are involved in the biosynthesis of HS, which strictly regulate its chemical structure and biological activity. The "coding" process in this context is based on the distribution of sulfate moieties on the amino groups of the glucosamine residues in the HS chains. The sulfation of these amine groups is catalyzed by N-deacetylase/N-sulfotransferase, which has four isozymes. The composition and distribution of sulfate groups and iduronic acid residues on the glycan chains of HS are determined by several other modification enzymes, which can recognize these coding sequences (i.e., the "decoding" process). The degree and pattern of the sulfation and epimerization in the HS chains determines the extent of their interactions with several different protein factors, which further influences their biological activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 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

  15. Imitation in Newborn Infants: Exploring the Range of Gestures Imitated and the Underlying Mechanisms.

    Science.gov (United States)

    Meltzoff, Andrew N.; Moore, M. Keith

    1989-01-01

    Evaluated psychological mechanisms underlying imitation of facial actions in 40 newborn infants. Results showed imitation of head movement and a tongue-protrusion gesture. Subjects imitated from memory after displays had stopped. (RJC)

  16. Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis

    NARCIS (Netherlands)

    Beijers, R.; Buitelaar, J.K.; Weerth, C. de

    2014-01-01

    Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the possible mechanisms underlying these relations is limited. In the present paper, we review the most often

  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. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

    Science.gov (United States)

    Borges, Cibele S; Missassi, Gabriela; Pacini, Enio S A; Kiguti, Luiz Ricardo A; Sanabria, Marciana; Silva, Raquel F; Banzato, Thais P; Perobelli, Juliana E; Pupo, André S; Kempinas, Wilma G

    2013-01-01

    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-norepinephrine reuptake inhibitors

  19. 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

  20. M-type thioredoxins are involved in the xanthophyll cycle and proton motive force to alter NPQ under low-light conditions in Arabidopsis.

    Science.gov (United States)

    Da, Qingen; Sun, Ting; Wang, Menglong; Jin, Honglei; Li, Mengshu; Feng, Dongru; Wang, Jinfa; Wang, Hong-Bin; Liu, Bing

    2018-02-01

    M-type thioredoxins are required to regulate zeaxanthin epoxidase activity and to maintain the steady-state level of the proton motive force, thereby influencing NPQ properties under low-light conditions in Arabidopsis. Non-photochemical quenching (NPQ) helps protect photosynthetic organisms from photooxidative damage via the non-radiative dissipation of energy as heat. Energy-dependent quenching (qE) is a major constituent of NPQ. However, the mechanism underlying the regulation of qE is not well understood. In this study, we demonstrate that the m-type thioredoxins TRX-m1, TRX-m2, and TRX-m4 (TRX-ms) interact with the xanthophyll cycle enzyme zeaxanthin epoxidase (ZE) and are required for maintaining the redox-dependent stabilization of ZE by regulating its intermolecular disulfide bridges. Reduced ZE activity and accumulated zeaxanthin levels were observed under TRX-ms deficiency. Furthermore, concurrent deficiency of TRX-ms resulted in a significant increase in proton motive force (pmf) and acidification of the thylakoid lumen under low irradiance, perhaps due to the significantly reduced ATP synthase activity under TRX-ms deficiency. The increased pmf, combined with acidification of the thylakoid lumen and the accumulation of zeaxanthin, ultimately contribute to the elevated stable qE in VIGS-TRX-m2m4/m1 plants under low-light conditions. Taken together, these results indicate that TRX-ms are involved in regulating NPQ-dependent photoprotection in Arabidopsis.

  1. 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...to stress fracture risk. In particular, in Study 1, we will perform advanced skeletal imaging along with gait-assessments in subjects with history of

  2. Metabotropic Glutamate Receptor 7 Modulates the Rewarding Effects of Cocaine in Rats: Involvement of a Ventral Pallidal GABAergic Mechanism

    Science.gov (United States)

    Li, Xia; Li, Jie; Peng, Xiao-Qing; Spiller, Krista; Gardner, Eliot L; Xi, Zheng-Xiong

    2013-01-01

    The metabotropic glutamate receptor 7 (mGluR7) has received much attention as a potential target for the treatment of epilepsy, major depression, and anxiety. In this study, we investigated the possible involvement of mGluR7 in cocaine reward in animal models of drug addiction. Pretreatment with the selective mGluR7 allosteric agonist N,N’-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082; 1-20 mg/kg, i.p.) dose-dependently inhibited cocaine-induced enhancement of electrical brain-stimulation reward and intravenous cocaine self-administration under both fixed-ratio and progressive-ratio reinforcement conditions, but failed to alter either basal or cocaine-enhanced locomotion or oral sucrose self-administration, suggesting a specific inhibition of cocaine reward. Microinjections of AMN082 (1–5 μg/μl per side) into the nucleus accumbens (NAc) or ventral pallidum (VP), but not dorsal striatum, also inhibited cocaine self-administration in a dose-dependent manner. Intra-NAc or intra-VP co-administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP, 5 μg/μl per side), a selective mGluR7 allosteric antagonist, significantly blocked AMN082’s action, suggesting an effect mediated by mGluR7 in these brain regions. In vivo microdialysis demonstrated that cocaine (10 mg/kg, i.p.) priming significantly elevated extracellular DA in the NAc or VP, while decreasing extracellular GABA in VP (but not in NAc). AMN082 pretreatment selectively blocked cocaine-induced changes in extracellular GABA, but not in DA, in both naive rats and cocaine self-administration rats. These data suggest: (1) mGluR7 is critically involved in cocaine’s acute reinforcement; (2) GABA-, but not DA-, dependent mechanisms in the ventral striatopallidal pathway appear to underlie AMN082’s actions; and (3) AMN082 or other mGluR7-selective agonists may be useful in the treatment of cocaine addiction. PMID:19158667

  3. Study of mechanism involved in synthesis of graphene oxide and reduced graphene oxide from graphene nanoplatelets

    Science.gov (United States)

    Sharma, Bhasha; Shekhar, Shashank; Malik, Parul; Jain, Purnima

    2018-06-01

    Graphene, a wonder material has inspired quest among researchers due to its numerous applications and exceptional properties. This paper highlights the mechanism and chemistry behind the fabrication of graphene oxide by using phosphoric acid. Chemical functionalization is of prime importance which avoids agglomeration of nanoparticles to attain inherent properties. As non-homogeneous dispersion limits its utilization due to interfacial interactions which restrict reactive sites to produce intercalated network. Thus, chemically functionalized graphene leads to stable dispersion and enhances thermal, mechanical and electrical properties of the resultant polymer composite materials. Solubility of graphene in aqueous solution is the major issue because graphene is hydrophobic, to rectify this oxygen containing hydrophilic groups must be introduced to make it compatible and this can be attained by covalent functionalization. Among all nanofiller GO has shown average particle size i.e. 95 nm and highest surface charge density. The characteristic changes were estimated using Raman spectra.

  4. 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.

  5. 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.

  6. Central and peripheral mechanisms underlying gastric distention inhibitory reflex responses in hypercapnic-acidotic rats.

    Science.gov (United States)

    Tjen-A-Looi, Stephanie C; Hsiao, An-Fu; Longhurst, John C

    2011-03-01

    We have observed that in chloralose-anesthetized animals, gastric distension (GD) typically increases blood pressure (BP) under normoxic normocapnic conditions. However, we recently noted repeatable decreases in BP and heart rate (HR) in hypercapnic-acidotic rats in response to GD. The neural pathways, central processing, and autonomic effector mechanisms involved in this cardiovascular reflex response are unknown. We hypothesized that GD-induced decrease in BP and HR reflex responses are mediated during both withdrawal of sympathetic tone and increased parasympathetic activity, involving the rostral (rVLM) and caudal ventrolateral medulla (cVLM) and the nucleus ambiguus (NA). Rats anesthetized with ketamine and xylazine or α-chloralose were ventilated and monitored for HR and BP changes. The extent of cardiovascular inhibition was related to the extent of hypercapnia and acidosis. Repeated GD with both anesthetics induced consistent falls in BP and HR. The hemodynamic inhibitory response was reduced after blockade of the celiac ganglia or the intraabdominal vagal nerves with lidocaine, suggesting that the decreased BP and HR responses were mediated by both sympathetic and parasympathetic afferents. Blockade of the NA decreased the bradycardia response. Microinjection of kainic acid into the cVLM reduced the inhibitory BP response, whereas depolarization blockade of the rVLM decreased both BP and HR inhibitory responses. Blockade of GABA(A) receptors in the rVLM also reduced the BP and HR reflex responses. Atropine methyl bromide completely blocked the reflex bradycardia, and atenolol blocked the negative chronotropic response. Finally, α(1)-adrenergic blockade with prazosin reversed the depressor. Thus, in the setting of hypercapnic-acidosis, a sympathoinhibitory cardiovascular response is mediated, in part, by splanchnic nerves and is processed through the rVLM and cVLM. Additionally, a vagal excitatory reflex, which involves the NA, facilitates the GD

  7. 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

  8. Mechanisms for closing bores and releasably securing articles within the bores under longitudinal load

    International Nuclear Information System (INIS)

    Klahn, F.C.; Nolan, J.H.; Wills, C.

    1979-01-01

    This invention relates to mechanisms for closing bores of tubular passages and for releasably securing articles within the bores under longitudinal load. The system includes an axially movable latch, an actuator and locking devices. Embodiments of the invention can be used as closure mechanisms for tubular irradiation surveillance specimen assembly holders used in nuclear reactors. (UK)

  9. Mechanisms for closing bores and releasably securing articles within the bores under longitudinal load

    International Nuclear Information System (INIS)

    Kalen, D.D.; Mitchem, J.W.

    1979-01-01

    This invention relates to mechanisms for closing bores of tubular passages and for releasably securing articles within the bores under longitudinal load. The system includes an axially movable actuator and a latch which engages the tubular opening. Embodiments of the invention can be used as closure mechanisms for tubular irradiation surveillance specimen assembly holders used in nuclear reactors. (UK)

  10. Molecular Mechanisms Underlying the Epileptogenesis and Seizure Progression in Tuberous Sclerosis Complex 1 Deficient Mouse Models

    Science.gov (United States)

    2016-10-01

    dysregulation in epileptogenesis in the developing brain? 2) What are the molecular mechanisms downstream of mTOR hyperactivation that trigger epileptogenesis...underlying epilepsy. Hopefully, a knowledge of these mechanisms will aid in a rational development of therapies. KEYWORDS Tuberous Sclerosis, Epilepsy

  11. AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration.

    Directory of Open Access Journals (Sweden)

    Kazuki Tajima

    Full Text Available The precise role of AMP-activated protein kinase (AMPK, a target of metformin, in pancreatic β cells remains controversial, even though metformin was recently shown to enhance the expression of incretin receptors (GLP-1 and GIP receptors in pancreatic β cells. In this study, we investigated the effect of AMPK in the regulation of incretin receptors expression in pancreatic islets. The phosphorylation of AMPK in the mouse islets was decreased by increasing glucose concentrations. We showed the expression of incretin receptors in bell-shaped response to glucose. Expression of the incretin receptors in the isolated islets showed higher levels under a medium glucose concentration (11.1 mM than that under a low glucose concentration (2.8 mM, but was suppressed under a high glucose concentration (22.2 mM. Both treatment with an AMPK inhibitor and DN-AMPK expression produced a significant increase of the incretin receptors expression under a low glucose concentration. By contrast, in hyperglycemic db/db islets, the enhancing effect of the AMPK inhibitor on the expression of incretin receptors was diminished under a low glucose concentration. Taken together, AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration.

  12. Friction Stir Weld Failure Mechanisms in Aluminum-Armor Structures Under Ballistic Impact Loading Conditions

    Science.gov (United States)

    2013-01-01

    REPORT Friction Stir Weld Failure Mechanisms in Aluminum-Armor Structures Under Ballistic Impact Loading Conditions 14. ABSTRACT 16. SECURITY...properties and of the attendant ballistic-impact failure mechanisms in prototypical friction stir welding (FSW) joints found in armor structures made of high...mechanisms, friction stir welding M. Grujicic, B. Pandurangan, A. Arakere, C-F. Yen, B. A. Cheeseman Clemson University Office of Sponsored Programs 300

  13. Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms.

    Science.gov (United States)

    Kloosterman, Wigard P; Tavakoli-Yaraki, Masoumeh; van Roosmalen, Markus J; van Binsbergen, Ellen; Renkens, Ivo; Duran, Karen; Ballarati, Lucia; Vergult, Sarah; Giardino, Daniela; Hansson, Kerstin; Ruivenkamp, Claudia A L; Jager, Myrthe; van Haeringen, Arie; Ippel, Elly F; Haaf, Thomas; Passarge, Eberhard; Hochstenbach, Ron; Menten, Björn; Larizza, Lidia; Guryev, Victor; Poot, Martin; Cuppen, Edwin

    2012-06-28

    Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Mechanisms involved in the intestinal digestion and absorption of dietary vitamin A.

    Science.gov (United States)

    Harrison, E H; Hussain, M M

    2001-05-01

    Dietary retinyl esters are hydrolyzed in the intestine by the pancreatic enzyme, pancreatic triglyceride lipase (PTL), and intestinal brush border enzyme, phospholipase B. Recent work on the carboxylester lipase (CEL) knockout mouse suggests that CEL may not be involved in dietary retinyl ester digestion. The possible roles of the pancreatic lipase-related proteins (PLRP) 1 and 2 and other enzymes require further investigation. Unesterified retinol is taken up by the enterocytes, perhaps involving both diffusion and protein-mediated facilitated transport. Once in the cell, retinol is complexed with cellular retinol-binding protein type 2 (CRBP2) and the complex serves as a substrate for reesterification of the retinol by the enzyme lecithin:retinol acyltransferase (LRAT). Retinol not bound to CRBP2 is esterified by acyl-CoA acyltransferase (ARAT). The retinyl esters are incorporated into chylomicrons, intestinal lipoproteins that transport other dietary lipids such as triglycerides, phospholipids, and cholesterol. Chylomicrons containing newly absorbed retinyl esters are then secreted into the lymph.

  15. Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

    Science.gov (United States)

    Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

    2010-01-01

    Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

  16. Involvement of three mechanisms in the alteration of cytokine responses by sodium methyldithiocarbamate

    International Nuclear Information System (INIS)

    Pruett, Stephen B.; Fan, Ruping; Zheng, Qiang

    2006-01-01

    Sodium methyldithiocarbamate (SMD) is the third most abundantly used conventional pesticide in the U.S. We recently reported that it alters the induction of cytokine production mediated though Toll-like receptor (TLR) 4 at relevant dosages in mice. Its chemical properties and evidence from the literature suggest thee potential mechanisms of action for this compound. It could either act as a free radical scavenger (by means of its free S - group) or promote oxidation by breaking down to form methylisothiocyanate, which can deplete glutathione. It is a potent copper chelator and may affect the availability of copper to a number of copper-dependent enzymes (including some signaling molecules). SMD induces a classical neuroendocrine stress response characterized by elevated serum corticosterone concentrations, which could affect cytokine production. Although each of these mechanisms could potentially contribute to altered cytokine responses, direct evidence is lacking. The present study was conducted to obtain such evidence. The role of redox balance was investigated by pretreating mice with N-acetyl cysteine (NAC), which increases cellular glutathione concentrations, before administration of SMD. NAC exacerbated the SMD-induced suppression of IL-12 and the SMD-induced enhancement of IL-10 in the serum. The role of copper chelation was investigated by comparing the effects of SMD with an equimolar dose to SMD that was administered in the form of a copper chelation complex. Addition of copper significantly decreased the action of SMD on IL-12 production but not on IL-10 production. The role of the stress response was investigated by pretreating mice with antagonists of corticosterone and catecholamines. This treatment partially prevented the action of SMD on IL-10 and IL-12 in the peritoneal fluid. The results suggest that all of the proposed mechanisms have some role in the alteration of cytokine production by SMD

  17. 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....... 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...

  18. 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.

  19. Insights into the energetics and mechanism underlying the interaction of tetraethylammonium bromide with proteins

    International Nuclear Information System (INIS)

    Banerjee, Tuhina; Kishore, Nand

    2008-01-01

    Calorimetry has been employed to investigate the quantitative energetic aspects and mechanism underlying protein-tetraethylammonium bromide (TEAB) interactions. Differential scanning calorimetry and UV-Visible spectroscopy have been used to study the thermal unfolding of three proteins of different structure and function (bovine serum albumin, α-lactalbumin, and bovine pancreatic ribonuclease A). The mode of interaction has been studied by using isothermal titration calorimetry, which demonstrates the absence of appreciable specific binding of TEAB to the protein. This suggests the involvement of solvent mediated effects and, possibly weak non-specific binding. The thermal unfolding transitions were found to be calorimetrically reversible for α-lactalbumin and bovine pancreatic ribonuclease A and partially reversible in the case of bovine serum albumin. The results indicate protein destabilization promoted by the TEAB interaction. The preferential interaction parameters of TEAB with α-lactalbumin and ribonuclease A confirm that an increased interaction of the hydrophobic groups of the TEAB with that of the protein upon denaturation is responsible for the reduced thermal stability of the protein. The decrease in the thermal stability of proteins in the presence of TEAB is well supported by a red shift in the intrinsic fluorescence of these proteins leading to conformational change thereby shifting the native ↔ denatured equilibrium towards right. The forces responsible for the thermal denaturation of the proteins of different structure and function in the presence of TEAB are discussed

  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. 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.

  2. Mechanisms Involved in Secondary Cardiac Dysfunction in Animal Models of Trauma and Hemorrhagic Shock.

    Science.gov (United States)

    Wilson, Nick M; Wall, Johanna; Naganathar, Veena; Brohi, Karim; De'Ath, Henry D

    2017-10-01

    Clinical evidence reveals the existence of a trauma-induced secondary cardiac injury (TISCI) that is associated with poor patient outcomes. The mechanisms leading to TISCI in injured patients are uncertain. Conversely, animal models of trauma hemorrhage have repeatedly demonstrated significant cardiac dysfunction following injury, and highlighted mechanisms through which this might occur. The aim of this review was to provide an overview of the animal studies describing TISCI and its pathophysiology.Basic science models of trauma show evidence of innate immune system activation via Toll-like receptors, the exact protagonists of which remain unclear. Shortly following trauma and hemorrhage, cardiomyocytes upregulate gene regulatory protein and inflammatory molecule expression including nuclear factor kappa beta, tumor necrosis factor alpha, and interleukin-6. This is associated with expression of membrane bound adhesion molecules and chemokines leading to marked myocardial leukocyte infiltration. This cell activation and infiltration is linked to a rise in enzymes that cause oxidative and nitrative stress and subsequent protein misfolding within cardiomyocytes. Such protein damage may lead to reduced contractility and myocyte apoptosis. Other molecules have been identified as cardioprotective following injury. These include p38 mitogen-activated protein kinases and heat shock proteins.The balance between increasing damaging mediators and a reduction in cardio-protective molecules appears to define myocardial function following trauma. Exogenous therapeutics have been trialled in rodents with promising abilities to favorably alter this balance, and subsequently lead to improved cardiac function.

  3. 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.

  4. 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.

  5. Application of microscopy methods to the understanding of mechanisms involved in ilmenite reduction by hydrogen

    International Nuclear Information System (INIS)

    De Vries, M.; Grey, I.; Fitzgerald, J.

    2003-01-01

    Full text: Titania pigment is one of the major drivers of the mineral sands industry with production of over 4 million tpa in 2002 for paints, plastics, paper and ceramics applications. The main feedstock for titania pigment production is ilmenite, FeTiO 3 . It is used either directly or after it has been upgraded to a higher titania content. The major commercial upgrading processes are electro smelting (titania slag) or high temperature char reduction followed by iron removal (synthetic rutile SR). Future ilmenite upgrading processes are likely to use low temperature hydrogen reduction according to reaction, followed by aeration of the metallic iron and acid leaching to produce a high grade SR (Nicholson et al, 2000). The commercial application of such a process requires a detailed knowledge of the kinetics of reaction. FeTiO 3 + H 2 = Fe(m) + TiO 2 + H 2 O. The kinetics of ilmenite reduction has been studied at CSIRO Minerals using a specially designed thermogravimetric apparatus built around a Cahn pressurised symmetrical beam balance. The kinetics have been measured as a function of different operating parameters such as temperature, gas velocity and pressure. The parameters were set so as to minimise mass transport effects and increase chemical reaction control and to ensure the reduction kinetics are outside the gas starvation region. Small samples were used that had been sintered at close to melting point to form large grains with low unconnected porosity. High flow rates of reactant gas were also used. The application of a range of microscopy techniques to the reduced samples at various stages of reaction conversion has been critical to the development of an understanding of the reaction mechanisms. From analysis of TEM, IFESEM and optical microscopy results it appears that initially, chemical reaction is rate controlling at the surface and as the reaction proceeds topochemically inwards then diffusion mechanisms increase their control. Reaction proceeds

  6. Global Combustion Mechanisms for Use in CFD Modeling under Oxy-Fuel Conditions

    DEFF Research Database (Denmark)

    Andersen, Jimmy; Rasmussen, Christian Lund; Giselsson, Trine

    2009-01-01

    Two global multistep schemes, the two-step mechanism of Westbrook and Dryer (WD) and the four-step mechanism of Jones and Lindstedt (JL), have been refined for oxy-fuel conditions. Reference calculations were conducted with a detailed chemical kinetic mechanism, validated for oxy-fuel combustion...... conditions. In the modification approach, the initiating reactions involving hydrocarbon and oxygen were retained, while modifying the H-2-CO-CO2 reactions in order to improve prediction of major species concentrations. The main attention has been to capture the trend and level of CO predicted...... by the detailed mechanism as well as the correct equilibrium concentration. A CFD analysis of a propane oxy-fuel flame has been performed using both the original and modified mechanisms. Compared to the original schemes, the modified WD mechanism improved the prediction of the temperature field and of CO...

  7. THE TRANSFORMATIONAL PROCESSES INVOLVING MOTOR SKILLS THAT OCCUR UNDER THE INFLUENCE OF BASIC PRELIMINARY TRAINING IN YOUNG HANDBALL PLAYERS

    Directory of Open Access Journals (Sweden)

    Markovic Sasa

    2011-06-01

    Full Text Available The population from which we extracted a sample of 76 subjects consisted of elementary school students in Kursumlija, all male, aged 12-13, who were divided into a sub-sample consisting of 38 young handball players who took part in the training sessions of a school of handball and another sub-sample consisting of 38 non-athletes, who only took part in their regular physical education classes. The aim of the research was to determine the transformation processes involving motor skills, which occur under the influence of basic preliminary training in young handball players. The subject matter of the study was to examine whether a statistically significant increase in the level of motor skills would occur under the influence of physical exercise as part of basic preliminary training in the final as compared to the initial state. Six motor tests which define the dimensions of explosive and repetitive strength were used. The results of the research indicate that significant transformational processes involving the motor skills of young handball players occurred in the final as compared to the initial measuring, under the influence of basic preliminary training.

  8. Opioidergic mechanisms are not involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

    Science.gov (United States)

    Stepanovic-Petrovic, Radica M; Tomic, M A; Vuckovic, S M; Ugresic, N D; Prostran, M S; Boskovic, B

    2007-04-01

    The mechanisms of the analgesic action of carbamazepine and oxcarbazepine, in particular the role of opioid receptors, have not been established precisely. The systemic effects of naloxone, an opioid receptor antagonist, on the antihyperalgesic effects of carbamazepine and oxcarbazepine were examined in the model of inflammatory hyperalgesia induced by the intraplantar (i.pl.) administration of concanavaline A (Con A, 0.8 mg/paw) into the rat hind paw. Naloxone (3 mg/kg; i.p.) did not alter the antihyperalgesic effects of either carbamazepine or oxcarbazepine. These results indicate that the opioid system of pain modulation does not play a significant role in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

  9. 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.

  10. Intrauterine infection/inflammation during pregnancy and offspring brain damages: Possible mechanisms involved

    Directory of Open Access Journals (Sweden)

    Golan Hava

    2004-04-01

    Full Text Available Abstract Intrauterine infection is considered as one of the major maternal insults during pregnancy. Intrauterine infection during pregnancy could lead to brain damage of the developmental fetus and offspring. Effects on the fetal, newborn, and adult central nervous system (CNS may include signs of neurological problems, developmental abnormalities and delays, and intellectual deficits. However, the mechanisms or pathophysiology that leads to permanent brain damage during development are complex and not fully understood. This damage may affect morphogenic and behavioral phenotypes of the developed offspring, and that mice brain damage could be mediated through a final common pathway, which includes over-stimulation of excitatory amino acid receptor, over-production of vascularization/angiogenesis, pro-inflammatory cytokines, neurotrophic factors and apoptotic-inducing factors.

  11. 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

    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...... the role of calcium and ROCK in contraction evoked by activation of the thromboxane receptors. Rat intracavernous penile arteries were mounted for isometric tension and intracellular calcium ([Ca2+]i) recording and corpus cavernosum for measurements of MYPT1 phosphorylation. In penile arteries, U46619...

  12. 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.

  13. 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.

  14. Molecular mechanisms involved in adaptive responses to radiation, UV light, and heat

    International Nuclear Information System (INIS)

    Takahashi, Akihisa; Ohnishi, Takeo

    2009-01-01

    Viable organisms recognize and respond to environmental changes or stresses. When these environmental changes and their responses by organisms are extreme, they can limit viability. However, organisms can adapt to these different stresses by utilizing different possible responses via signal transduction pathways when the stress is not lethal. In particular, prior mild stresses can provide some aid to prepare organisms for subsequent more severe stresses. These adjustments or adaptations for future stresses have been called adaptive responses. These responses are present in bacteria, plants and animals. The following review covers recent research which can help describe or postulate possible mechanisms which may be active in producing adaptive responses to radiation, ultraviolet light, and heat. (author)

  15. Effects of high fluoride intake on child mental work capacity: preliminary investigation into the mechanisms involved

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.; Li, X.J.; Wei, S.Q. [Child & Adolescent Hygiene Teaching Research Station, Chengdu (China)

    2008-10-15

    A study was carried out on 157 children, age 12-13, from a coal-burning fluorosis endemic area together with an experiment looking into the effect of high fluoride intake in animals. The results showed that early, prolonged high fluoride intake causes a decrease in a child's mental work capacity and that prolonged high uptake of fluoride causes a child's levels of hair zinc to drop. A multifactoral correlative analysis demonstrated a direct correlation between hair zinc and mental work capacity. The decrease of 5-hydroxyindoleacetic acid and the increase of norepinephrine in animal brains exposed to high levels of fluoride suggest a possible mechanism for mental work capacity deficits in children. However, further research is necessary.

  16. 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.

  17. Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway.

    Science.gov (United States)

    Ha, Ae Wha; Kim, Woo Kyoung

    2017-06-01

    Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin F2α (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly ( P concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly ( P antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

  18. 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.

  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. PMID:26309232

  20. Mechanical and tribological behaviour of molten salt processed self-lubricated aluminium composite under different treatments

    Science.gov (United States)

    Kannan, C.; Ramanujam, R.

    2018-05-01

    The aim of this research work is to evaluate the mechanical and tribological behaviour of Al 7075 based self-lubricated hybrid nanocomposite under different treated conditions viz. as-cast, T6 and deep cryo treated. In order to overcome the drawbacks associated with conventional stir casting, a combinational approach that consists of molten salt processing, ultrasonic assistance and optimized mechanical stirring is adopted in this study to fabricate the nanocomposite. The mechanical characterisation tests carried out on this nanocomposite reveals an improvement of about 39% in hardness and 22% in ultimate tensile strength possible under T6 condition. Under specific conditions, the wear rate can be reduced to the extent of about 63% through the usage of self-lubricated hybrid nanocomposite under T6 condition.

  1. 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.

  2. Oxidative stress in the pathophysiology of metabolic syndrome: which mechanisms are involved?

    Directory of Open Access Journals (Sweden)

    Thalia M. T. Avelar

    2015-08-01

    Full Text Available ABSTRACTMetabolic syndrome (MS is a combination of cardiometabolic risk factors, including obesity, hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension. Several studies report that oxidative condition caused by overproduction of reactive oxygen species (ROS plays an important role in the development of MS. Our body has natural antioxidant system to reduce oxidative stress, which consists of numerous endogenous and exogenous components and antioxidants enzymes that are able to inactivate ROS. The main antioxidant defense enzymes that contribute to reduce oxidative stress are superoxide dismutase (SOD, catalase (CAT and gluthatione peroxidase (GPx. The high-density lipoprotein cholesterol (HDL-c is also associated with oxidative stress because it presents antioxidant and anti-inflammatory properties. HDL-c antioxidant activity may be attributed at least in part, to serum paraoxonase 1 (PON1 activity. Furthermore, derivatives of reactive oxygen metabolites (d-ROMs also stand out as acting in cardiovascular disease and diabetes, by the imbalance in ROS production, and close relationship with inflammation. Recent reports have indicated the gamma-glutamyl transferase (GGT as a promising biomarker for diagnosis of MS, because it is related to oxidative stress, since it plays an important role in the metabolism of extracellular glutathione. Based on this, several studies have searched for better markers for oxidative stress involved in development of MS.

  3. 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

  4. Involvement of Reactive Oxygen Species and Mitochondrial Proteins in Biophoton Emission in Roots of Soybean Plants under Flooding Stress.

    Science.gov (United States)

    Kamal, Abu Hena Mostafa; Komatsu, Setsuko

    2015-05-01

    To understand the mechanism of biophoton emission, ROS and mitochondrial proteins were analyzed in soybean plants under flooding stress. Enzyme activity and biophoton emission were increased in the flooding stress samples when assayed in reaction mixes specific for antioxidant enzymes and reactive oxygen species; although the level of the hydroxyl radicals was increased at day 4 (2 days of flooding) compared to nonflooding at day 4, the emission of biophotons did not change. Mitochondria were isolated and purified from the roots of soybean plants grown under flooding stress by using a Percoll gradient, and proteins were analyzed by a gel-free proteomic technique. Out of the 98 mitochondrial proteins that significantly changed abundance under flooding stress, 47 increased and 51 decreased at day 4. The mitochondrial enzymes fumarase, glutathione-S-transferase, and aldehyde dehydrogenase increased at day 4 in protein abundance and enzyme activity. Enzyme activity and biophoton emission decreased at day 4 by the assay of lipoxygenase under stress. Aconitase, acyl CoA oxidase, succinate dehydrogenase, and NADH ubiquinone dehydrogenase were up-regulated at the transcription level. These results indicate that oxidation and peroxide scavenging might lead to biophoton emission and oxidative damage in the roots of soybean plants under flooding stress.

  5. 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.

  6. On the dynamic mechanical property and deformation mechanism of as-extruded Mg-Sn-Ca alloys under tension

    International Nuclear Information System (INIS)

    Huang, Qiuyan; Pan, Hucheng; Tang, Aitao; Ren, Yuping; Song, Bo; Qin, Gaowu; Zhang, Mingxing; Pan, Fusheng

    2016-01-01

    To further understand the deformation mechanism of magnesium alloys and expand their applications under dynamic conditions, the newly developed Mg-2Sn-1Ca alloy (TX21) is selected as the representative sample and tested under wide loading rate ranging from quasi-static to dynamic level (10"−"3–500/s). Both ultimate tensile strength and elongation of the as-extruded TX21 alloys increase with strain rate. Although twinning is accompanied due to the enhanced activity at higher strain rate, the preferential activation of dislocations is readily clarified and confirmed as the dominant deformation modes. Active interactions of pyramidal dislocations result in the higher strain hardening ability and could be correlated to the obviously positive strain-rate sensitivity for mechanical properties. Moreover, it is observed that the larger grain size and higher content of solute atoms dissolved in matrix would lead to the more active dislocations and twinning formations. The present results would provide insight into further understanding the deformation mechanism under dynamic rate loading and designing Mg alloy suitable for impact conditions.

  7. On the dynamic mechanical property and deformation mechanism of as-extruded Mg-Sn-Ca alloys under tension

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Qiuyan [National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China); Pan, Hucheng [Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China); Tang, Aitao, E-mail: tat@cqu.edu.cn [National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China); Ren, Yuping [Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China); Song, Bo [Faculty of Materials and Energy, Southwest University, Chongqing 400715 (China); Qin, Gaowu, E-mail: qingw@smm.neu.edu.cn [Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China); Zhang, Mingxing [School of Mechanical and Mining Engineering, University of Queensland, St Lucia, QLD 4072 (Australia); Pan, Fusheng [National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China)

    2016-05-10

    To further understand the deformation mechanism of magnesium alloys and expand their applications under dynamic conditions, the newly developed Mg-2Sn-1Ca alloy (TX21) is selected as the representative sample and tested under wide loading rate ranging from quasi-static to dynamic level (10{sup −3}–500/s). Both ultimate tensile strength and elongation of the as-extruded TX21 alloys increase with strain rate. Although twinning is accompanied due to the enhanced activity at higher strain rate, the preferential activation of dislocations is readily clarified and confirmed as the dominant deformation modes. Active interactions of pyramidal dislocations result in the higher strain hardening ability and could be correlated to the obviously positive strain-rate sensitivity for mechanical properties. Moreover, it is observed that the larger grain size and higher content of solute atoms dissolved in matrix would lead to the more active dislocations and twinning formations. The present results would provide insight into further understanding the deformation mechanism under dynamic rate loading and designing Mg alloy suitable for impact conditions.

  8. 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.

  9. 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.

  10. Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis.

    Science.gov (United States)

    Silvestre, Marilene Chaves; Sato, Maria Notomi; Reis, Vitor Manoel Silva Dos

    2018-03-01

    Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation.

  11. Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis*

    Science.gov (United States)

    Silvestre, Marilene Chaves; Sato, Maria Notomi; dos Reis, Vitor Manoel Silva

    2018-01-01

    Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation. PMID:29723367

  12. 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.

  13. 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.

  14. Survival in amyotrophic lateral sclerosis with home mechanical ventilation: the impact of systematic respiratory assessment and bulbar involvement.

    Science.gov (United States)

    Farrero, Eva; Prats, Enric; Povedano, Mónica; Martinez-Matos, J Antonio; Manresa, Frederic; Escarrabill, Joan

    2005-06-01

    To analyze (1) the impact of a protocol of early respiratory evaluation of the indications for home mechanical ventilation (HMV) in patients with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and of bulbar involvement on the survival of patients receiving noninvasive ventilation (NIV). Retrospective study in a tertiary care referral center. HMV was indicated in 86 patients with ALS, with 22 patients (25%) presenting with intolerance to treatment associated with bulbar involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to initiating the protocol (group A) and in the remaining 49 patients after protocol initiation (group B). In group A, the majority of patients began treatment with HMV during an acute episode requiring ICU admission (p = 0.001) and tracheal ventilation (p = 0.025), with a lower percentage of patients beginning HMV treatment without respiratory insufficiency (p = 0.013). No significant differences in survival rates were found between groups A and B among patients treated with NIV. Greater survival was observed in group B (p = 0.03) when patients with bulbar involvement were excluded (96%). Patients without bulbar involvement at the start of therapy with NIV presented a significantly better survival rate (p = 0.03). Multivariate analysis showed bulbar involvement to be an independent prognostic factor for survival (relative risk, 1.6; 95% confidence interval, 1.01 to 2.54; p = 0.04). No significant differences in survival were observed between patients with bulbar involvement following treatment with NIV and those with intolerance, except for the subgroup of patients who began NIV treatment with hypercapnia (p = 0.0002). Early systematic respiratory evaluation in patients with ALS is necessary to improve the results of HMV. Further studies are required to confirm the benefits of NIV treatment in patients with bulbar involvement, especially in the early stages.

  15. 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.

  16. Molecular mechanisms of drug resistance and tumor promotion involving mammalian ribonucleotide reductase

    Energy Technology Data Exchange (ETDEWEB)

    Choy, B.B.K.

    1991-01-01

    Mammalian ribonucleotide reductase is a highly regulated, rate-limiting activity responsible for converting ribonucleoside diphosphates to the deoxyribonucleotide precursors of DNA. The enzyme consists of two nonidentical proteins called M1 and M2, both of which are required for activity. Hydroxyurea is an antitumor agent which inhibits ribonucleotide reductase by interacting with the M2 component specifically at a unique tyrosyl free radical. Studies were conducted on a series of drug resistant mouse cell lines, selected by a step-wise procedure for increasing levels of resistance to the cytotoxic effects of hydroxyurea. Each successive drug selection step leading to the isolation of highly resistant cells was accompanied by stable elevations in cellular resistance and ribonucleotide reductase activity. The drug resistant cell lines exhibited gene amplification of the M2 gene, elevated M2 mRNA, and M2 protein. In addition to M2 gene amplification, posttranscriptional modulation also occurred during the drug selection. Studies of the biosynthesis rates with exogenously added iron suggest a role for iron in regulating the level of M2 protein when cells are cultured in the presence of hydroxyurea. The hydroxyurea-inactivated ribonucleotide reductase protein M2 has a destabilized iron centre, which readily releases iron. Altered expression of ferritin appears to be required for the development of hydroxyurea resistance in nammalian cells. The results show an interesting relationship between the expressions of ribonucleotide reductase and ferritin. The phorbol ester tumor promoter, TPA, is also able to alter the expression of M2. TPA was able to induce M2 mRNA levels transiently up to 18-fold within 1/2 hour. This rapid and large elevation of ribonucleotide reductase suggests that the enzyme may play a role in tumor promotion. Studies of the M2 promoter region were undertaken to better understand the mechanism of TPA induction of M2.

  17. Mechanisms involved in reproductive damage caused by gossypol in rats and protective effects of vitamin E

    Directory of Open Access Journals (Sweden)

    Andréia T Santana

    2015-01-01

    Full Text Available BACKGROUND: Gossypol is a chemical present in the seeds of cotton plants (Gossypium sp. that reduces fertility in farm animals. Vitamin E is an antioxidant and may help to protect cells and tissues against the deleterious effects of free radicals. The aim of this study was to evaluate the mechanisms of reproductive toxicity of gossypol in rats and the protective effects of vitamin E. Forty Wistar rats were used, divided into four experimental groups (n = 10: DMSO/ saline + corn oil; DMSO/saline + vitamin E; gossypol + corn oil; and gossypol + vitamin E. RESULTS: Fertility was significantly reduced in male rats treated with gossypol in that a significant decrease in epididy-mal sperm count was observed (P 0.05. The levels of reduced glutathione and pyridine nucleotides in testis homogen-ate were significantly reduced by gossypol (P < 0.05 and P < 0.01, respectively and this reduction was accompanied by increased levels of oxidized glutathione (P < 0.05. Vitamin E showed a preventive effect on the changes in the levels of these substances. Gossypol significantly increased the levels of malondialdehyde (P < 0.01, a lipid peroxida-tion indicator, whereas treatment with vitamin E inhibited the action of the gossypol. Vitamin E prevented a decrease in mitochondrial ATP induced by gossypol (P < 0.05. CONCLUSIONS: This study suggests that the reproductive dysfunction caused by gossypol may be related to oxidative stress and mitochondrial bioenergetic damage and that treatment with vitamin E can prevent the infertility caused by the toxin.

  18. 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.

  19. Involvement of Hookworm Co-Infection in the Pathogenesis and Progression of Podoconiosis: Possible Immunological Mechanism

    Directory of Open Access Journals (Sweden)

    Damilare O. Famakinde

    2018-03-01

    Full Text Available Podoconiosis is an endemic, non-infectious, geochemical and non-filarial inflammatory cause of tropical elephantiasis. The immunology of podoconiosis is not yet expressly understood. In spite of this, co-infection and co-morbidity with the infectious, soil-transmitted hookworm disease that causes iron deficiency anemia has been found to be predominant among affected individuals living in co-endemic settings, thus creating a more complex immunological interplay that still has not been investigated. Although deworming and iron-rich nutrient supplementation have been suggested in podoconiosis patients living under resource-poor conditions, and it is thought that hookworm infection may help to suppress inflammatory responses, the undisputed link that exists between a non-infectious and an infectious disease may create a scenario whereby during a co-infection, treatment of one exacerbates the other disease condition or is dampened by the debilitation caused by the other. In this paper, we elaborate on the immunopathogenesis of podoconiosis and examine the possible immunological dynamics of hookworm co-infection in the immunopathology of podoconiosis, with a view toward improved management of the disease that will facilitate its feasible elimination.

  20. 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.

  1. 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

  2. Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation.

    Science.gov (United States)

    Fujita, Masahide; Andoh, Tsugunobu; Saiki, Ikuo; Kuraishi, Yasushi

    2008-02-01

    We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but not the ET(B)-receptor antagonist BQ-788 (1 and 3 nmol/site), inhibited mechanical allodynia in mice with grown melanoma. In naive mice, an intraplantar injection of tumor extract (1 and 3 mg/site), which was prepared from the grown melanoma in the paw, produced mechanical allodynia, which was inhibited by BQ-123 and BQ-788 at doses of 3 and 10 nmol/site. An intraplantar injection of ET-1 (1 and 10 pmol/site) elicited licking behavior, which was increased in the melanoma-bearing hind paw. BQ-123 (3 and 10 nmol/site) inhibited licking induced by ET-1 (10 pmol/site). The level of mRNA of ET(A), but not ET(B), receptor, was significantly increased in the dorsal root ganglia on the inoculated side. Cultured B16-BL6 cells contained ET, and the melanoma mass increased the concentration of ET as it grew bigger. These results suggest that ET-1 and ET(A) receptor are at least partly involved in the induction of pain induced by melanoma cell inoculation.

  3. Progressive damage analysis of carbon/epoxy laminates under couple laser and mechanical loading

    Directory of Open Access Journals (Sweden)

    Wanlei Liu

    Full Text Available A multiscale model based bridge theory is proposed for the progressive damage analysis of carbon/epoxy laminates under couple laser and mechanical loading. The ablation model is adopted to calculate ablation temperature changing and ablation surface degradation. The polynomial strengthening model of matrix is used to improve bridging model for reducing parameter input. Stiffness degradation methods of bridging model are also improved in order to analyze the stress redistribution more accurately when the damage occurs. Thermal-mechanical analyses of the composite plate are performed using the ABAQUS/Explicit program with the developed model implemented in the VUMAT. The simulation results show that this model can be used to proclaim the mesoscale damage mechanism of composite laminates under coupled loading. Keywords: Laser irradiation, Multiscale analysis, Bridge model, Thermal-mechanical

  4. 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.

  5. PHYSIOLOGICAL QUALITY OF SOYBEAN SEEDS UNDER MECHANICAL INJURIES CAUSED BY COMBINES

    OpenAIRE

    FÁBIO PALCZEWSKI PACHECO; LÚCIA HELENA PEREIRA NÓBREGA; GISLAINE PICOLLO DE LIMA; MÁRCIA SANTORUM; WALTER BOLLER; LORIVAN FORMIGHIERI

    2015-01-01

    The mechanical harvesting causes injuries on seeds and may affect their quality. Different threshing mechanisms and their adjustments may also affect the intensity of impacts that machines cause on seeds. So, this study aimed at diagnosing and evaluating the effect of two combines: the first one with a threshing system of axial flow and the other one with a threshing system of tangential flow, under adjustments of concave opening (10 mm, 30 mm and 10 mm for a combine with axial ...

  6. Uncovering the underlying physical mechanisms of biological systems via quantification of landscape and flux

    International Nuclear Information System (INIS)

    Xu Li; Chu Xiakun; Yan Zhiqiang; Zheng Xiliang; Zhang Kun; Zhang Feng; Yan Han; Wu Wei; Wang Jin

    2016-01-01

    In this review, we explore the physical mechanisms of biological processes such as protein folding and recognition, ligand binding, and systems biology, including cell cycle, stem cell, cancer, evolution, ecology, and neural networks. Our approach is based on the landscape and flux theory for nonequilibrium dynamical systems. This theory provides a unifying principle and foundation for investigating the underlying mechanisms and physical quantification of biological systems. (topical review)

  7. Investigation on the interaction of catalase with sodium lauryl sulfonate and the underlying mechanisms.

    Science.gov (United States)

    Wang, Jing; Jia, Rui; Wang, Jiaxi; Sun, Zhiqiang; Wu, Zitao; Liu, Rutao; Zong, Wansong

    2018-02-01

    As a classic type of anionic surfactants, sodium lauryl sulfonate (SLS) might change the structure and function of antioxidant enzyme catalase (CAT) through their direct interactions. However, the underlying molecular mechanism is still unknown. This study investigated the direct interaction of SLS with CAT molecule and the underlying mechanisms using multi-spectroscopic methods, isothermal titration calorimetry, and molecular docking studies. No obvious effects were observed on CAT structure and activity under low SLS concentration exposure. The particle size of CAT molecule decreased and CAT activity was slightly inhibited under high SLS concentration exposure. SLS prefers to bind to the interface of CAT mainly via van der Waals' forces and hydrogen bonds. Subsequently, SLS interacts with the amino acid residues around the heme groups of CAT via hydrophobic interactions and might inhibit CAT activity. © 2017 Wiley Periodicals, Inc.

  8. A Neural Circuit Mechanism for the Involvements of Dopamine in Effort-Related Choices: Decay of Learned Values, Secondary Effects of Depletion, and Calculation of Temporal Difference Error

    Science.gov (United States)

    2018-01-01

    Abstract Dopamine has been suggested to be crucially involved in effort-related choices. Key findings are that dopamine depletion (i) changed preference for a high-cost, large-reward option to a low-cost, small-reward option, (ii) but not when the large-reward option was also low-cost or the small-reward option gave no reward, (iii) while increasing the latency in all the cases but only transiently, and (iv) that antagonism of either dopamine D1 or D2 receptors also specifically impaired selection of the high-cost, large-reward option. The underlying neural circuit mechanisms remain unclear. Here we show that findings i–iii can be explained by the dopaminergic representation of temporal-difference reward-prediction error (TD-RPE), whose mechanisms have now become clarified, if (1) the synaptic strengths storing the values of actions mildly decay in time and (2) the obtained-reward-representing excitatory input to dopamine neurons increases after dopamine depletion. The former is potentially caused by background neural activity–induced weak synaptic plasticity, and the latter is assumed to occur through post-depletion increase of neural activity in the pedunculopontine nucleus, where neurons representing obtained reward exist and presumably send excitatory projections to dopamine neurons. We further show that finding iv, which is nontrivial given the suggested distinct functions of the D1 and D2 corticostriatal pathways, can also be explained if we additionally assume a proposed mechanism of TD-RPE calculation, in which the D1 and D2 pathways encode the values of actions with a temporal difference. These results suggest a possible circuit mechanism for the involvements of dopamine in effort-related choices and, simultaneously, provide implications for the mechanisms of TD-RPE calculation. PMID:29468191

  9. Single turnover studies of oxidative halophenol dehalogenation by horseradish peroxidase reveal a mechanism involving two consecutive one electron steps: toward a functional halophenol bioremediation catalyst.

    Science.gov (United States)

    Sumithran, Suganya; Sono, Masanori; Raner, Gregory M; Dawson, John H

    2012-12-01

    Horseradish peroxidase (HRP) catalyzes the oxidative para-dechlorination of the environmental pollutant/carcinogen 2,4,6-trichlorophenol (2,4,6-TCP). A possible mechanism for this reaction is a direct oxygen atom transfer from HRP compound I (HRP I) to trichlorophenol to generate 2,6-dichloro 1,4-benzoquinone, a two-electron transfer process. An alternative mechanism involves two consecutive one-electron transfer steps in which HRP I is reduced to compound II (HRP II) and then to the ferric enzyme as first proposed by Wiese et al. [F.W. Wiese, H.C. Chang, R.V. Lloyd, J.P. Freeman, V.M. Samokyszyn, Arch. Environ. Contam. Toxicol. 34 (1998) 217-222]. To probe the mechanism of oxidative halophenol dehalogenation, the reactions between 2,4,6-TCP and HRP compounds I or II have been investigated under single turnover conditions (i.e., without excess H(2)O(2)) using rapid scan stopped-flow spectroscopy. Addition of 2,4,6-TCP to HRP I leads rapidly to HRP II and then more slowly to the ferric resting state, consistent with a mechanism involving two consecutive one-electron oxidations of the substrate via a phenoxy radical intermediate. HRP II can also directly dechlorinate 2,4,6-TCP as judged by rapid scan stopped-flow and mass spectrometry. This observation is particularly significant since HRP II can only carry out one-electron oxidations. A more detailed understanding of the mechanism of oxidative halophenol dehalogenation will facilitate the use of HRP as a halophenol bioremediation catalyst. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation

    DEFF Research Database (Denmark)

    Leucci, E; Cocco, M; Onnis, A

    2008-01-01

    at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split-signal as well as a dual-fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify...... whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level. Several studies have reported their involvement in cancer...

  11. Study of the Chemical Mechanism Involved in the Formation of Tungstite in Benzyl Alcohol by the Advanced QEXAFS Technique

    DEFF Research Database (Denmark)

    Olliges‐Stadler, Inga; Stötzel, Jan; Koziej, Dorota

    2012-01-01

    Insight into the complex chemical mechanism for the formation of tungstite nanoparticles obtained by the reaction of tungsten hexachloride with benzyl alcohol is presented herein. The organic and inorganic species involved in the formation of the nanoparticles were studied by time‐dependent gas......‐scanning extended X‐ray absorption fine structure spectroscopy enabled the time‐dependent evolution of the starting compound, the intermediates and the product to be monitored over the full reaction period. The reaction starts with fast chlorine substitution and partial reduction during the dissolution...

  12. The progestin etonogestrel enhances the respiratory response to metabolic acidosis in newborn rats. Evidence for a mechanism involving supramedullary structures.

    Science.gov (United States)

    Loiseau, Camille; Osinski, Diane; Joubert, Fanny; Straus, Christian; Similowski, Thomas; Bodineau, Laurence

    2014-05-01

    Central congenital hypoventilation syndrome is a neuro-respiratory disease characterized by the dysfunction of the CO2/H(+) chemosensitive neurons of the retrotrapezoid nucleus/parafacial respiratory group. A recovery of CO2/H(+) chemosensitivity has been observed in some central congenital hypoventilation syndrome patients coincidental with contraceptive treatment by a potent progestin, desogestrel (Straus et al., 2010). The mechanisms of this progestin effect remain unknown, although structures of medulla oblongata, midbrain or diencephalon are known to be targets for progesterone. In the present study, on ex vivo preparations of central nervous system of newborn rats, we show that acute exposure to etonogestrel (active metabolite of desogestrel) enhanced the increased respiratory frequency induced by metabolic acidosis via a mechanism involving supramedullary structures located in pontine, mesencephalic or diencephalic regions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. 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...

  14. Crack formation and crack propagation under multiaxial mechanical and thermal stresses. Proceedings

    International Nuclear Information System (INIS)

    1993-01-01

    The 25th meeting of the DV Fracture Group was held on 16/17 February 1993 at Karlsruhe Technical University. The main topic, ''Crack formation and crack propagation under multiaxial mechanical and thermal stresses'', was discussed by five invited papers (by K.J. Miller, D. Loehe, H.A. Richard, W. Brocks, A. Brueckner-Foit) and 23 short papers. The other 21 papers were devoted to various domains of fracture mechanics, with emphasis on elastoplastic fracture mechanics. (orig./MM) [de

  15. “Intensity-Response” Effects of Electroacupuncture on Gastric Motility and Its Underlying Peripheral Neural Mechanism

    Directory of Open Access Journals (Sweden)

    Yang-Shuai Su

    2013-01-01

    Full Text Available The aim of this study was to explore the “intensity-response” relationship between EAS and the effect of gastric motility of rats and its underlying peripheral neural mechanism by employing ASIC3 knockout (ASIC3−/−, TRPV1 knockout (TRPV1−/−, and C57BL/6 mice. For adult male Sprague-Dawley (n=18 rats, the intensities of EAS were 0.5, 1, 3, 5, 7, and 9 mA, respectively. For mice (n=8 in each group, only 1 mA was used, by which C fiber of the mice can be activated. Gastric antrum motility was measured by intrapyloric balloon. Gastric motility was facilitated by EAS at ST36 and inhibited by EAS at CV12. The half maximal facilitation intensity of EAS at ST36 was 2.1–2.3 mA, and the half maximal inhibitory intensity of EAS at CV12 was 2.8 mA. In comparison with C57BL/6 mice, the facilitatory effect of ST36 and inhibitive effect of CV12 in ASIC3−/− mice decreased, but the difference was not statistically significant (P>0.05. However, these effects in TRPV1−/− mice decreased significantly (P<0.001. The results indicated that there existed an “intensity-response” relationship between EAS and the effect of gastric motility. TRPV1 receptor was involved in the regulation of gastric motility of EAS.

  16. Ultrastructural changes of cell walls under intense mechanical treatment of selective plant raw material

    International Nuclear Information System (INIS)

    Bychkov, Aleksey L.; Ryabchikova, E.I.; Korolev, K.G.; Lomovsky, O.I.

    2012-01-01

    Structural changes of cell walls under intense mechanical treatment of corn straw and oil-palm fibers were studied by electron and light microscopy. Differences in the character of destruction of plant biomass were revealed, and the dependence of destruction mechanisms on the structure of cell walls and lignin content was demonstrated. We suggest that the high reactivity of the particles of corn straw (about 18% of lignin) after intense mechanical treatment is related to disordering of cell walls and an increase of the surface area, while in the case of oil palm (10% of lignin) the major contribution into an increase in the reactivity is made by an increase of surface area. -- Highlights: ► Structure of cell walls determines the processes of plant materials' destruction. ► Ultrastructure of highly lignified materials strongly disordering by mechanical action. ► Ultrastructure of low-lignified materials is not disordering by mechanical action.

  17. Thermodynamics of diffusion under pressure and stress: Relation to point defect mechanisms

    International Nuclear Information System (INIS)

    Aziz, M.J.

    1997-01-01

    A thermodynamic formalism is developed for illuminating the predominant point defect mechanism of self- and impurity diffusion in silicon and is used to provide a rigorous basis for point defect-based interpretation of diffusion experiments in biaxially strained epitaxial layers in the Si endash Ge system. A specific combination of the hydrostatic and biaxial stress dependences of the diffusivity is ±1 times the atomic volume, depending upon whether the predominant mechanism involves vacancies or interstitials. Experimental results for Sb diffusion in biaxially strained Si endash Ge films and ab initio calculations of the activation volume for Sb diffusion by a vacancy mechanism are in quantitative agreement with no free parameters. Key parameters are identified that must be measured or calculated for a quantitative test of interstitial-based mechanisms. copyright 1997 American Institute of Physics

  18. Meiotic restitution mechanisms involved in the formation of 2n pollen in Agave tequilana Weber and Agave angustifolia Haw.

    Science.gov (United States)

    Gómez-Rodríguez, Víctor Manuel; Rodríguez-Garay, Benjamín; Barba-Gonzalez, Rodrigo

    2012-01-01

    A cytological analysis of the microsporogenesis was carried out in the Agave tequilana and A. angustifolia species. Several abnormalities such as chromosomal bridges, lagging chromosomes, micronuclei, monads, dyads and triads were found. The morphological analysis of the pollen, together with the above-mentioned 2n microspores, allowed us to confirm the presence of 2n pollen as well as its frequency. In both A. tequilana and A. angustifolia two different mechanisms were observed: the first mechanism, a failure in the cytokinesis in meiosis II caused the formation of dyads with two 2n cells and triads containing two n cells and one 2n cell; the second mechanism, involves an abnormal spindle, which caused the formation of triads with two n cells and one 2n cell. Likewise, the presence of monads was detected in both species, these, might be caused by a failure of the cytokinesis in both meiotic divisions. This is the first report about the presence of a Second Division Restitution mechanism (SDR) which causes the formation of 2n pollen in the genus Agave. The genetic implications of the presence of 2n pollen in the genus Agave are discussed.

  19. Mechanisms Underlying Serotonergic Excitation of Callosal Projection Neurons in the Mouse Medial Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Emily K. Stephens

    2018-01-01

    Full Text Available Serotonin (5-HT selectively excites subpopulations of pyramidal neurons in the neocortex via activation of 5-HT2A (2A receptors coupled to Gq subtype G-protein alpha subunits. Gq-mediated excitatory responses have been attributed primarily to suppression of potassium conductances, including those mediated by KV7 potassium channels (i.e., the M-current, or activation of non-specific cation conductances that underlie calcium-dependent afterdepolarizations (ADPs. However, 2A-dependent excitation of cortical neurons has not been extensively studied, and no consensus exists regarding the underlying ionic effector(s involved. In layer 5 of the mouse medial prefrontal cortex, we tested potential mechanisms of serotonergic excitation in commissural/callosal (COM projection neurons, a subpopulation of pyramidal neurons that exhibits 2A-dependent excitation in response to 5-HT. In baseline conditions, 5-HT enhanced the rate of action potential generation in COM neurons experiencing suprathreshold somatic current injection. This serotonergic excitation was occluded by activation of muscarinic acetylcholine (ACh receptors, confirming that 5-HT acts via the same Gq-signaling cascades engaged by ACh. Like ACh, 5-HT promoted the generation of calcium-dependent ADPs following spike trains. However, calcium was not necessary for serotonergic excitation, as responses to 5-HT were enhanced (by >100%, rather than reduced, by chelation of intracellular calcium with 10 mM BAPTA. This suggests intracellular calcium negatively regulates additional ionic conductances gated by 2A receptors. Removal of extracellular calcium had no effect when intracellular calcium signaling was intact, but suppressed 5-HT response amplitudes, by about 50%, when BAPTA was included in patch pipettes. This suggests that 2A excitation involves activation of a non-specific cation conductance that is both calcium-sensitive and calcium-permeable. M-current suppression was found to be a third

  20. Aquaporin-mediated increase in root hydraulic conductance is involved in silicon-induced improved root water uptake under osmotic stress in Sorghum bicolor L.

    Science.gov (United States)

    Liu, Peng; Yin, Lina; Deng, Xiping; Wang, Shiwen; Tanaka, Kiyoshi; Zhang, Suiqi

    2014-09-01

    The fact that silicon application alleviates water deficit stress has been widely reported, but the underlying mechanism remains unclear. Here the effects of silicon on water uptake and transport of sorghum seedlings (Sorghum bicolor L.) growing under polyethylene glycol-simulated osmotic stress in hydroponic culture and water deficit stress in sand culture were investigated. Osmotic stress dramatically decreased dry weight, photosynthetic rate, transpiration rate, stomatal conductance, and leaf water content, but silicon application reduced these stress-induced decreases. Although silicon application had no effect on stem water transport capacity, whole-plant hydraulic conductance (Kplant) and root hydraulic conductance (Lp) were higher in silicon-treated seedlings than in those without silicon treatment under osmotic stress. Furthermore, the extent of changes in transpiration rate was similar to the changes in Kplant and Lp. The contribution of aquaporin to Lp was characterized using the aquaporin inhibitor mercury. Under osmotic stress, the exogenous application of HgCl2 decreased the transpiration rates of seedlings with and without silicon to the same level; after recovery induced by dithiothreitol (DTT), however, the transpiration rate was higher in silicon-treated seedlings than in untreated seedlings. In addition, transcription levels of several root aquaporin genes were increased by silicon application under osmotic stress. These results indicate that the silicon-induced up-regulation of aquaporin, which was thought to increase Lp, was involved in improving root water uptake under osmotic stress. This study also suggests that silicon plays a modulating role in improving plant resistance to osmotic stress in addition to its role as a mere physical barrier. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  1. Global transcriptomic profiling of aspen trees under elevated [CO2] to identify potential molecular mechanisms responsible for enhanced radial growth.

    Science.gov (United States)

    Wei, Hairong; Gou, Jiqing; Yordanov, Yordan; Zhang, Huaxin; Thakur, Ramesh; Jones, Wendy; Burton, Andrew

    2013-03-01

    Aspen (Populus tremuloides) trees growing under elevated [CO(2)] at a free-air CO(2) enrichment (FACE) site produced significantly more biomass than control trees. We investigated the molecular mechanisms underlying the observed increase in biomass by producing transcriptomic profiles of the vascular cambium zone (VCZ) and leaves, and then performed a comparative study to identify significantly changed genes and pathways after 12 years exposure to elevated [CO(2)]. In leaves, elevated [CO(2)] enhanced expression of genes related to Calvin cycle activity and linked pathways. In the VCZ, the pathways involved in cell growth, cell division, hormone metabolism, and secondary cell wall formation were altered while auxin conjugation, ABA synthesis, and cytokinin glucosylation and degradation were inhibited. Similarly, the genes involved in hemicellulose and pectin biosynthesis were enhanced, but some genes that catalyze important steps in lignin biosynthesis pathway were inhibited. Evidence from systemic analysis supported the functioning of multiple molecular mechanisms that underpin the enhanced radial growth in response to elevated [CO(2)].

  2. Presentation of an approach for the analysis of the mechanical response of propellant under a large spectrum of loadings: numerical and mechanical issues

    Science.gov (United States)

    Fanget, Alain

    2009-06-01

    Many authors claim that to understand the response of a propellant, specifically under quasi static and dynamic loading, the mesostructural morphology and the mechanical behaviour of each of its components have to be known. However the scale of the mechanical description of the behaviour of a propellant is relative to its heterogeneities and the wavelength of loading. The shorter it is, the more important the topological description of the material is. In our problems, involving the safety of energetic materials, the propellant can be subjected to a large spectrum of loadings. This presentation is divided into five parts. The first part describes the processes used to extract the information about the morphology of the meso-structure of the material and presents some results. The results, the difficulties and the perspectives for this part will be recalled. The second part determines the physical processes involved at this scale from experimental results. Taking into account the knowledge of the morphology, two ways have been chosen to describe the response of the material. One concerns the quasi static loading, the object of the third part, in which we show how we use the mesoscopic scale as a base of development to build constitutive models. The fourth part presents for low but dynamic loading the comparison between numerical analysis and experiments.

  3. Nitric oxide is involved in light-specific responses of tomato during germination under normal and osmotic stress conditions.

    Science.gov (United States)

    Piterková, Jana; Luhová, Lenka; Hofman, Jakub; Turecková, Veronika; Novák, Ondrej; Petrivalsky, Marek; Fellner, Martin

    2012-09-01

    Nitric oxide (NO) is involved in the signalling and regulation of plant growth and development and responses to biotic and abiotic stresses. The photoperiod-sensitive mutant 7B-1 in tomato (Solanum lycopersicum) showing abscisic acid (ABA) overproduction and blue light (BL)-specific tolerance to osmotic stress represents a valuable model to study the interaction between light, hormones and stress signalling. The role of NO as a regulator of seed germination and ABA-dependent responses to osmotic stress was explored in wild-type and 7B-1 tomato under white light (WL) and BL. Germination data were obtained from the incubation of seeds on germinating media of different composition. Histochemical analysis of NO production in germinating seeds was performed by fluorescence microscopy using a cell-permeable NO probe, and endogenous ABA was analysed by mass spectrometry. The NO donor S-nitrosoglutathione stimulated seed germination, whereas the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) had an inhibitory effect. Under WL in both genotypes, PTIO strongly suppressed germination stimulated by fluridone, an ABA inhibitor. The stimulatory effect of the NO donor was also observed under osmotic stress for 7B-1 seeds under WL and BL. Seed germination inhibited by osmotic stress was restored by fluridone under WL, but less so under BL, in both genotypes. This effect of fluridone was further modulated by the NO donor and NO scavenger, but only to a minor extent. Fluorescence microscopy using the cell-permeable NO probe DAF-FM DA (4-amino-5-methylamino-2',7'-difluorofluorescein diacetate) revealed a higher level of NO in stressed 7B-1 compared with wild-type seeds. As well as defective BL signalling, the differential NO-dependent responses of the 7B-1 mutant are probably associated with its high endogenous ABA concentration and related impact on hormonal cross-talk in germinating seeds. These data confirm that light-controlled seed germination and

  4. Calcium and Calmodulin Are Involved in Nitric Oxide-Induced Adventitious Rooting of Cucumber under Simulated Osmotic Stress.

    Science.gov (United States)

    Niu, Lijuan; Yu, Jian; Liao, Weibiao; Yu, Jihua; Zhang, Meiling; Dawuda, Mohammed M

    2017-01-01

    Osmotic stress is a major form of abiotic stress that adversely affects growth and development of plants and subsequently reduces yield and quality of crops. In this study, the effect of nitric oxide (NO) and calcium (Ca 2+ ) on the process of adventitious rooting in cucumber ( Cucumis sativus L.) under simulated osmotic stress was investigated. The results revealed that the effect of exogenous NO and Ca 2+ in promoting the development of adventitious roots in cucumber seedlings under simulated osmotic stress was dose-dependent, with a maximal biological response at 10 μM NO donor nitroprusside (SNP) or 200 μM Ca 2+ . The application of Ca 2+ chelators or channel inhibitors and calmodulin (CaM) antagonists significantly reversed NO-induced adventitious rooting, implying that endogenous Ca 2+ /CaM might be involved in NO-induced adventitious rooting under osmotic stress. Moreover, intracellular Ca amount was also increased by NO in cucumber hypocotyls during the development of adventitious roots under osmotic stress. This increase of endogenous Ca 2+ was inhibited by NO specific scavenger 2-(4-carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO), nitrate reductase inhibitors tungstate (Na 2 WO 4 ) and sodium azide (NaN 3 ) . This gives an indication that Ca 2+ might be a downstream signaling molecule in the adventitious root development by NO under osmotic condition. The results also show that NO or Ca 2+ play a positive role in improving plant water status and photosynthetic system by increasing chlorophyll content and photochemical activity in leaves. Furthermore, NO and Ca 2+ treatment might alleviate the negative effects of osmotic stress by decreasing membrane damage and reactive oxygen species (ROS) production by enhancing the activities of superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX). Therefore, Ca 2+ /CaM may act as a downstream signaling molecule in NO-induced development of adventitious root

  5. Insecticide Resistance and Metabolic Mechanisms Involved in Larval and Adult Stages of Aedes aegypti Insecticide-Resistant Reference Strains from Cuba.

    Science.gov (United States)

    Bisset, Juan Andrés; Rodríguez, María Magdalena; French, Leydis; Severson, David W; Gutiérrez, Gladys; Hurtado, Daymi; Fuentes, Ilario

    2014-12-01

    Studies were conducted to compare levels of insecticide resistance and to determine the metabolic resistance mechanisms in larval and adult stages of Aedes aegypti from Cuba. Three insecticide-resistant reference strains of Ae. aegypti from Cuba were examined. These strains were derived from a Santiago de Cuba strain isolated in 1997; it was previously subjected to a strong selection for resistance to temephos (SAN-F6), deltamethrin (SAN-F12), and propoxur (SAN-F13) and routinely maintained in the laboratory under selection pressure up to the present time, when the study was carried out. In addition, an insecticide-susceptible strain was used for comparison. The insecticide resistance in larvae and adults was determined using standard World Health Organization methodologies. Insecticide resistance mechanisms were determined by biochemical assays. The esterases (α EST and β EST) and mixed function oxidase (MFO) activities were significantly higher in adults than in the larvae of the three resistant strains studied. The association of resistance level with the biochemical mechanism for each insecticide was established for each stage. The observed differences between larval and adult stages of Ae. aegypti in their levels of insecticide resistance and the biochemical mechanisms involved should be included as part of monitoring and surveillance activities in Ae. aegypti vector control programs.

  6. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  7. Asymmetric migration of human keratinocytes under mechanical stretch and cocultured fibroblasts in a wound repair model.

    Directory of Open Access Journals (Sweden)

    Dongyuan Lü

    Full Text Available Keratinocyte migration during re-epithelization is crucial in wound healing under biochemical and biomechanical microenvironment. However, little is known about the underlying mechanisms whereby mechanical tension and cocultured fibroblasts or keratinocytes modulate the migration of keratinocytes or fibroblasts. Here we applied a tensile device together with a modified transwell assay to determine the lateral and transmembrane migration dynamics of human HaCaT keratinocytes or HF fibroblasts. A novel pattern of asymmetric migration was observed for keratinocytes when they were cocultured with non-contact fibroblasts, i.e., the accumulative distance of HaCaT cells was significantly higher when moving away from HF cells or migrating from down to up cross the membrane than that when moving close to HF cells or when migrating from up to down, whereas HF migration was symmetric. This asymmetric migration was mainly regulated by EGF derived from fibroblasts, but not transforming growth factor α or β1 production. Mechanical stretch subjected to fibroblasts fostered keratinocyte asymmetric migration by increasing EGF secretion, while no role of mechanical stretch was found for EGF secretion by keratinocytes. These results provided a new insight into understanding the regulating mechanisms of two- or three-dimensional migration of keratinocytes or fibroblasts along or across dermis and epidermis under biomechanical microenvironment.

  8. Nonlinear Dynamic Analysis of Telescopic Mechanism for Truss Structure Bridge Inspection Vehicle Under Pedestrian Excitation

    Directory of Open Access Journals (Sweden)

    Wenwen Sui

    Full Text Available Abstract Nonlinear dynamic analysis of an axially moving telescopic mechanism for truss structure bridge inspection vehicle under pedestrian excitation is carried out. A biomechanically inspired inverted-pendulum model is utilized to simplify the pedestrian. The nonlinear equations of motion for the beam-pedestrian system are derived using the Hamilton's principle. The equations are transformed into two ordinary differential equations by applying the Galerkin's method at the first two orders. The solutions to the equations are acquired by using the Newmark-β method associated with the Newton-Raphson method. The time-dependent feature of the eigenfunctions for the two beams are taken into consideration in the solutions. Accordingly, the equations of motion for a simplified system, in which the pedestrian is regarded as moving cart, are given. In the numerical examples, dynamic responses of the telescopic mechanism in eight conditions of different beam-telescoping and pedestrian-moving directions are simulated. Comparisons between the vibrations of the beams under pedestrian excitation and corresponding moving cart are carried out to investigate the influence of the pedestrian excitation on the telescopic mechanism. The results show that the displacement of the telescopic mechanism under pedestrian excitation is smaller than that under moving cart especially when the pedestrian approaches the beams end. Additionally, compared with moving cart, the pedestrian excitation can effectively strengthen the vibration when the beam extension is small or when the pedestrian is close to the beams end.

  9. Unraveling the mechanisms underlying postural instability in Parkinson's disease using dynamic posturography

    NARCIS (Netherlands)

    Nonnekes, J.H.; Kam, D. de; Geurts, A.C.; Weerdesteijn, V.G.M.; Bloem, B.R.

    2013-01-01

    Postural instability, one of the cardinal symptoms of Parkinson's disease (PD), has devastating consequences for affected patients. Better strategies to prevent falls are needed, but this calls for an improved understanding of the complex mechanisms underlying postural instability. We must also

  10. Mechanisms underlying the associations of maternal age with adverse perinatal outcomes

    DEFF Research Database (Denmark)

    Lawlor, Debbie A; Mortensen, Laust; Andersen, Anne-Marie Nybo

    2011-01-01

    The mechanisms underlying the association between maternal age (both young and older maternal age) and adverse perinatal outcomes are unclear. Methods We examined the association of maternal age at first birth with preterm birth (<37 weeks gestation) and small for gestational age (SGA) in a cohor...

  11. The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

    Science.gov (United States)

    Cheng, Ying; Shao, Can; Lathrop, Quinn N.

    2016-01-01

    Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

  12. Biological mechanisms underlying the role of physical fitness in health and resilience

    OpenAIRE

    Silverman, Marni N.; Deuster, Patricia A.

    2014-01-01

    Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appear...

  13. Chemotherapeutics-resistance "arms" race: An update on mechanisms involved in resistance limiting EGFR inhibitors in lung cancer.

    Science.gov (United States)

    Singh, Pankaj Kumar; Silakari, Om

    2017-10-01

    Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc., in the development of tolerance towards the EGFR TKI's, along with other commonly known mechanisms, such as amplification of signalling pathways such as, c-MET, Erbb2, AXL, additional acquired secondary mutations (PIK3CA, BRAF), or phenotypic transformation (small cell or epithelial to mesenchymal transitions). Interestingly, a recent study showed development of resistance via another point mutation, C797S, in case of tumors which were previously resistant and were administered agents capable of overcoming T790M gatekeeper mutation based resistance. Thus, raising serious concern over the direction of drug development involving tyrosine kinases such as EGFR. Current approaches focussing on development of third generation inhibitors, dual inhibitors or inhibitors of HSP90 have shown significant activity but do not answer the long term question of resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved.

    Science.gov (United States)

    Bonfiglio, Juan José; Inda, Carolina; Refojo, Damián; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

    2011-01-01

    Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright © 2011 S. Karger AG, Basel.

  15. Mechanisms involved in the p62-73 idiopeptide-modulated delay of lupus nephritis in SNF(1) mice.

    Science.gov (United States)

    Nyland, J F; Stoll, M L; Jiang, F; Feng, F; Gavalchin, J

    2012-12-01

    The F(1) progeny of the (SWR × NZB) cross develop a lupus-like disease with high serum titers of autoantibodies, and increased frequency and severity of immune complex-mediated glomerulonephritis in females. In previous work, we found that an idiotypic peptide corresponding to aa62-73 (p62-73) of the heavy chain variable region of autoantibody 540 (Id(LN)F(1)) induced the proliferation of p62-73 idiotype-reactive T cell clones. Further, monthly immunization of pre-nephritic SNF(1) female mice with p62-73 resulted in decreased nephritis and prolonged life spans. Here we show that this treatment modulated proliferative responses to Id(LN)F(1) antigen, including a reduction in the population of idiopeptide-presenting antigen-presenting cells (APCs), as early as two weeks after immunization (10 weeks of age). Th1-type cytokine production was increased at 12 weeks of age. The incidence and severity of nephritis was reduced by 14 weeks compared to controls. Clinical indicators of nephritis, specifically histological evidence of glomerulonephritis and urine protein levels, were reduced by 20 weeks. Together these data suggest that events involved in the mechanism(s) whereby p62-73 immunization delayed nephritis occurred early after immunization, and involved modulation of APCs, B and T cell populations.

  16. Mechanical behavior of glass/epoxy composite laminate with varying amount of MWCNTs under different loadings

    Science.gov (United States)

    Singh, K. K.; Rawat, Prashant

    2018-05-01

    This paper investigates the mechanical response of three phased (glass/MWCNTs/epoxy) composite laminate under three different loadings. Flexural strength, short beam strength and low-velocity impact (LVI) testing are performed to find an optimum doping percentage value for maximum enhancement in mechanical properties. In this work, MWCNTs were used as secondary reinforcement for three-phased composite plate. MWCNT doping was done in a range of 0–4 wt% of the thermosetting matrix system. Symmetrical design eight layered glass/epoxy laminate with zero bending extension coupling laminate was fabricated using a hybrid method i.e. hand lay-up technique followed by vacuum bagging method. Ranging analysis of MWCNT mixing highlighted the enhancement in flexural, short beam strength and improvement in damage tolerance under LVI loading. While at higher doping wt%, agglomeration of MWCNTs are observed. Results of mechanical testing proposed an optimized doping value for maximum strength and damage resistance of the laminate.

  17. Intercomparison of chemical mechanisms for air quality policy formulation and assessment under North American conditions.

    Science.gov (United States)

    Derwent, Richard

    2017-07-01

    The intercomparison of seven chemical mechanisms for their suitability for air quality policy formulation and assessment is described. Box modeling techniques were employed using 44 sets of background environmental conditions covering North America to constrain the chemical development of the longer lived species. The selected mechanisms were modified to enable an unbiased assessment of the adequacy of the parameterizations of photochemical ozone production from volatile organic compound (VOC) oxidation in the presence of NO x . Photochemical ozone production rates responded differently to 30% NO x and VOC reductions with the different mechanisms, despite the striking similarities between the base-case ozone production rates. The 30% reductions in NO x and VOCs also produced changes in OH. The responses in OH to 30% reductions in NO x and VOCs appeared to be more sensitive to mechanism choice, compared with the responses in the photochemical ozone production rates. Although 30% NO x reductions generally led to decreases in OH, 30% reductions in VOCs led to increases in OH, irrespective of mechanism choice and background environmental conditions. The different mechanisms therefore gave different OH responses to NO x and VOC reductions and so would give different responses in terms of changes in the fate and behavior of air toxics, acidification and eutrophication, and fine particle formation compared with others, in response to ozone control strategies. Policymakers need to understand that there are likely to be inherent differences in the responses to ozone control strategies between different mechanisms, depending on background environmental conditions and the extents of NO x and VOC reductions under consideration. The purpose of this paper is to compare predicted ozone responses to NO x and VOC reductions with seven chemical mechanisms under North American conditions. The good agreement found between the tested mechanisms should provide some support for their

  18. Efficacy of a group-based multimedia HIV prevention intervention for drug-involved women under community supervision: project WORTH.

    Science.gov (United States)

    El-Bassel, Nabila; Gilbert, Louisa; Goddard-Eckrich, Dawn; Chang, Mingway; Wu, Elwin; Hunt, Tim; Epperson, Matt; Shaw, Stacey A; Rowe, Jessica; Almonte, Maria; Witte, Susan

    2014-01-01

    This study is designed to address the need for evidence-based HIV/STI prevention approaches for drug-involved women under criminal justice community supervision. We tested the efficacy of a group-based traditional and multimedia HIV/STI prevention intervention (Project WORTH: Women on the Road to Health) among drug-involved women under community supervision. We randomized 306 women recruited from community supervision settings to receive either: (1) a four-session traditional group-based HIV/STI prevention intervention (traditional WORTH); (2) a four-session multimedia group-based HIV/STI prevention intervention that covered the same content as traditional WORTH but was delivered in a computerized format; or (3) a four-session group-based Wellness Promotion intervention that served as an attention control condition. The study examined whether the traditional or multimedia WORTH intervention was more efficacious in reducing risks when compared to Wellness Promotion; and whether multimedia WORTH was more efficacious in reducing risks when compared to traditional WORTH. Primary outcomes were assessed over the 12-month post-intervention period and included the number of unprotected sex acts, the proportion of protected sex acts, and consistent condom use. At baseline, 77% of participants reported unprotected vaginal or anal sex (n = 237) and 63% (n = 194) had multiple sex partners. Women assigned to traditional or multimedia WORTH were significantly more likely than women assigned to the control condition to report an increase in the proportion of protected sex acts (β = 0.10; 95% CI = 0.02-0.18) and a decrease in the number of unprotected sex acts (IRR = 0.72; 95% CI = 0.57-0.90). The promising effects of traditional and multimedia WORTH on increasing condom use and high participation rates suggest that WORTH may be scaled up to redress the concentrated epidemics of HIV/STIs among drug-involved women in the criminal justice system. Clinical

  19. Mechanical Behavior of Shale Rock under Uniaxial Cyclic Loading and Unloading Condition

    Directory of Open Access Journals (Sweden)

    Baoyun Zhao

    2018-01-01

    Full Text Available In order to investigate the mechanical behavior of shale rock under cyclic loading and unloading condition, two kinds of incremental cyclic loading tests were conducted. Based on the result of the short-term uniaxial incremental cyclic loading test, the permanent residual strain, modulus, and damage evolution were analyzed firstly. Results showed that the relationship between the residual strains and the cycle number can be expressed by an exponential function. The deformation modulus E50 and elastic modulus ES first increased and then decreased with the peak