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Sample records for mechanisms underlying protection

  1. Multi-targeted mechanisms underlying the endothelial protective effects of the diabetic-safe sweetener erythritol.

    PubMed

    Boesten, Daniëlle M P H J; Berger, Alvin; de Cock, Peter; Dong, Hua; Hammock, Bruce D; den Hartog, Gertjan J M; Bast, Aalt

    2013-01-01

    Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunction onset in diabetic rats. To unravel mechanisms, other than scavenging of radicals, by which erythritol mediates this protective effect, we evaluated effects of erythritol in endothelial cells exposed to normal (7 mM) and high glucose (30 mM) or diabetic stressors (e.g. SIN-1) using targeted and transcriptomic approaches. This study demonstrates that erythritol (i.e. under non-diabetic conditions) has minimal effects on endothelial cells. However, under hyperglycemic conditions erythritol protected endothelial cells against cell death induced by diabetic stressors (i.e. high glucose and peroxynitrite). Also a number of harmful effects caused by high glucose, e.g. increased nitric oxide release, are reversed. Additionally, total transcriptome analysis indicated that biological processes which are differentially regulated due to high glucose are corrected by erythritol. We conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets. Overall, these data indicate a therapeutically important endothelial protective effect of erythritol under hyperglycemic conditions.

  2. Evolution of the fruit endocarp: molecular mechanisms underlying adaptations in seed protection and dispersal strategies

    PubMed Central

    Dardick, Chris; Callahan, Ann M.

    2014-01-01

    Plant evolution is largely driven by adaptations in seed protection and dispersal strategies that allow diversification into new niches. This is evident by the tremendous variation in flowering and fruiting structures present both across and within different plant lineages. Within a single plant family a staggering variety of fruit types can be found such as fleshy fruits including berries, pomes, and drupes and dry fruit structures like achenes, capsules, and follicles. What are the evolutionary mechanisms that enable such dramatic shifts to occur in a relatively short period of time? This remains a fundamental question of plant biology today. On the surface it seems that these extreme differences in form and function must be the consequence of very different developmental programs that require unique sets of genes. Yet as we begin to decipher the molecular and genetic basis underlying fruit form it is becoming apparent that simple genetic changes in key developmental regulatory genes can have profound anatomical effects. In this review, we discuss recent advances in understanding the molecular mechanisms of fruit endocarp tissue differentiation that have contributed to species diversification within three plant lineages. PMID:25009543

  3. Exploring the host transcriptome for mechanisms underlying protective immunity and resistance to nematode infections in ruminants.

    PubMed

    Li, Robert W; Choudhary, Ratan K; Capuco, Anthony V; Urban, Joseph F

    2012-11-23

    Nematode infections in ruminants are a major impediment to the profitable production of meat and dairy products, especially for small farms. Gastrointestinal parasitism not only negatively impacts weight gain and milk yield, but is also a major cause of mortality in small ruminants. The current parasite control strategy involves heavy use of anthelmintics that has resulted in the emergence of drug-resistant parasite strains. This, in addition to increasing consumer demand for animal products that are free of drug residues has stimulated development of alternative strategies, including selective breeding of parasite resistant ruminants. The development of protective immunity and manifestations of resistance to nematode infections relies upon the precise expression of the host genome that is often confounded by mechanisms simultaneously required to control multiple nematode species as well as ecto- and protozoan parasites, and microbial and viral pathogens. Understanding the molecular mechanisms underlying these processes represents a key step toward development of effective new parasite control strategies. Recent progress in characterizing the transcriptome of both hosts and parasites, utilizing high-throughput microarrays and RNA-seq technology, has led to the recognition of unique interactions and the identification of genes and biological pathways involved in the response to parasitism. Innovative use of the knowledge gained by these technologies should provide a basis for enhancing innate immunity while limiting the polarization of acquired immunity can negatively affect optimal responses to co-infection. Strategies for parasite control that use diet and vaccine/adjuvant combination could be evaluated by monitoring the host transcriptome for induction of appropriate mechanisms for imparting parasite resistance. Knowledge of different mechanisms of host immunity and the critical regulation of parasite development, physiology, and virulence can also selectively

  4. The antioxidant mechanisms underlying the aged garlic extract- and S-allylcysteine-induced protection.

    PubMed

    Colín-González, Ana L; Santana, Ricardo A; Silva-Islas, Carlos A; Chánez-Cárdenas, Maria E; Santamaría, Abel; Maldonado, Perla D

    2012-01-01

    Aged garlic extract (AGE) is an odorless garlic preparation containing S-allylcysteine (SAC) as its most abundant compound. A large number of studies have demonstrated the antioxidant activity of AGE and SAC in both in vivo--in diverse experimental animal models associated to oxidative stress--and in vitro conditions--using several methods to scavenge reactive oxygen species or to induce oxidative damage. Derived from these experiments, the protective effects of AGE and SAC have been associated with the prevention or amelioration of oxidative stress. In this work, we reviewed different antioxidant mechanisms (scavenging of free radicals and prooxidant species, induction of antioxidant enzymes, activation of Nrf2 factor, inhibition of prooxidant enzymes, and chelating effects) involved in the protective actions of AGE and SAC, thereby emphasizing their potential use as therapeutic agents. In addition, we highlight the ability of SAC to activate Nrf2 factor--a master regulator of the cellular redox state. Here, we include original data showing the ability of SAC to activate Nrf2 factor in cerebral cortex. Therefore, we conclude that the therapeutic properties of these molecules comprise cellular and molecular mechanisms at different levels. PMID:22685624

  5. The Antioxidant Mechanisms Underlying the Aged Garlic Extract- and S-Allylcysteine-Induced Protection

    PubMed Central

    Colín-González, Ana L.; Santana, Ricardo A.; Silva-Islas, Carlos A.; Chánez-Cárdenas, Maria E.; Santamaría, Abel; Maldonado, Perla D.

    2012-01-01

    Aged garlic extract (AGE) is an odorless garlic preparation containing S-allylcysteine (SAC) as its most abundant compound. A large number of studies have demonstrated the antioxidant activity of AGE and SAC in both in vivo—in diverse experimental animal models associated to oxidative stress—and in vitro conditions—using several methods to scavenge reactive oxygen species or to induce oxidative damage. Derived from these experiments, the protective effects of AGE and SAC have been associated with the prevention or amelioration of oxidative stress. In this work, we reviewed different antioxidant mechanisms (scavenging of free radicals and prooxidant species, induction of antioxidant enzymes, activation of Nrf2 factor, inhibition of prooxidant enzymes, and chelating effects) involved in the protective actions of AGE and SAC, thereby emphasizing their potential use as therapeutic agents. In addition, we highlight the ability of SAC to activate Nrf2 factor—a master regulator of the cellular redox state. Here, we include original data showing the ability of SAC to activate Nrf2 factor in cerebral cortex. Therefore, we conclude that the therapeutic properties of these molecules comprise cellular and molecular mechanisms at different levels. PMID:22685624

  6. Protective effects of Ndfip1 on MPP(+)-induced apoptosis in MES23.5 cells and its underlying mechanisms.

    PubMed

    Liu, Kai; Xu, Huamin; Xiang, Hengwei; Sun, Peng; Xie, Junxia

    2015-11-01

    Apoptosis has been implicated as one of the important mechanisms involved in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Increasing evidence suggests that Ndfip1 is a neuroprotective protein, and Ndfip1-mediated protein ubiquitination might be a possible survival strategy in neuronal injury. The aim of the present study is to investigate the neuroprotective effect of Ndfip1 on 1-methyl-4-phenylpyridinium (MPP(+))-treated MES23.5 cells and the underlying mechanisms. Results showed that overexpression of Ndfip1 could significantly attenuate MPP(+)-induced cell loss and nuclear condensation. Further experiments demonstrated that Ndfip1 could increase Bcl-2/Bax ratio, suppress cytochrome c release from the mitochondria to cytoplasm and decrease caspase-3 activation induced by MPP(+). These results suggested that Ndfip1 protected MES23.5 cells against MPP(+) by its anti-apoptotic effect. In addition, we found that Ndfip1 overexpression could decrease the protein level of dopamine transporter (DAT). In parallel, proteasome inhibitor MG132 could markedly reverse Ndfip1-induced degradation of DAT. These data suggest that Ndfip1 exerts its inhibitory effect on DAT by modulating DAT degradation, in which ubiquitin-proteasome system activation might be involved. Collectively, our study indicated that the ability to decrease the DAT of Ndfip1 might be one of the mechanisms underlying its protective effect on MPP(+)-induced cell damage in MES23.5 cells. PMID:26300475

  7. Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

    PubMed Central

    Hou, Shuai; Shen, Ping-Ping; Zhao, Ming-Ming; Liu, Xiu-Ping; Xie, Hong-Yan; Deng, Fang; Feng, Jia-Chun

    2016-01-01

    We observed mitochondrial connexin43 (mtCx43) expression under cerebral ischemia-reperfusion (I/R) injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO). Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. MtCx43, p-mtCx43, protein kinase C (PKC), and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX) and diazoxide (DZX) groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD) groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA) reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists. PMID:27164087

  8. The Protective Effects of Salubrinal on the Cartilage and Subchondral Bone of the Temporomandibular Joint under Various Compressive Mechanical Stimulations

    PubMed Central

    Zhang, Caixia; Chen, Sheng; Li, Huang

    2016-01-01

    Excessive mechanical loads on the temporomandibular joint (TMJ) can cause mandibular cartilage degradation and subchondral bone erosion, but the treatment of these conditions remains challenging. Salubrinal, which target eukaryotic translation initiation factor 2 alpha, has been shown to have multiple beneficial effects on skeletal tissue. Here, we examined the effect of a Salubrinal injection on the mandibular cartilage and subchondral bone of the TMJ under various compressive stresses. We conducted in vivo analyses in rat models using various compressive stresses (40 g and 80 g), and we observed time-related degeneration and pathological changes in the cartilage and subchondral bone of the TMJ at days 1, 3 and 7 through histological measurements, subcellular observation, and changes in proliferation and apoptosis. After the Salubrinal injection, the thickness of the cartilage recovered, and the pathological change was alleviated. In the Salubrinal/light (Sal/light) compressive stress group, the drug altered the proliferation and apoptosis of chondrocytes most significantly at day 1. In the Salubrinal/heavy (Sal/heavy) compressive stress group, the drug increased the proliferation of chondrocytes most significantly at day 1 and reduced the apoptosis of chondrocytes most significantly at day 7. Salubrinal also increased the area of the bone trabeculae and suppressed inflammatory responses and pathological change in the subchondral bone of the TMJ. Together, these results indicate that the administration of Salubrinal reduces apoptosis and strengthens the proliferation of chondrocyte to varying degrees at days 1, 3 and 7 under various compressive mechanical stresses, both of which contribute to the recovery of cartilage thickness and the alleviation of pathological change. Salubrinal also suppresses inflammatory responses and pathological change in the subchondral bone of the TMJ. PMID:27196267

  9. The Protective Effects of Salubrinal on the Cartilage and Subchondral Bone of the Temporomandibular Joint under Various Compressive Mechanical Stimulations.

    PubMed

    Wen, Juan; Jiang, Yuanyuan; Zhang, Caixia; Chen, Sheng; Li, Huang

    2016-01-01

    Excessive mechanical loads on the temporomandibular joint (TMJ) can cause mandibular cartilage degradation and subchondral bone erosion, but the treatment of these conditions remains challenging. Salubrinal, which target eukaryotic translation initiation factor 2 alpha, has been shown to have multiple beneficial effects on skeletal tissue. Here, we examined the effect of a Salubrinal injection on the mandibular cartilage and subchondral bone of the TMJ under various compressive stresses. We conducted in vivo analyses in rat models using various compressive stresses (40 g and 80 g), and we observed time-related degeneration and pathological changes in the cartilage and subchondral bone of the TMJ at days 1, 3 and 7 through histological measurements, subcellular observation, and changes in proliferation and apoptosis. After the Salubrinal injection, the thickness of the cartilage recovered, and the pathological change was alleviated. In the Salubrinal/light (Sal/light) compressive stress group, the drug altered the proliferation and apoptosis of chondrocytes most significantly at day 1. In the Salubrinal/heavy (Sal/heavy) compressive stress group, the drug increased the proliferation of chondrocytes most significantly at day 1 and reduced the apoptosis of chondrocytes most significantly at day 7. Salubrinal also increased the area of the bone trabeculae and suppressed inflammatory responses and pathological change in the subchondral bone of the TMJ. Together, these results indicate that the administration of Salubrinal reduces apoptosis and strengthens the proliferation of chondrocyte to varying degrees at days 1, 3 and 7 under various compressive mechanical stresses, both of which contribute to the recovery of cartilage thickness and the alleviation of pathological change. Salubrinal also suppresses inflammatory responses and pathological change in the subchondral bone of the TMJ. PMID:27196267

  10. Protein S-Mycothiolation Functions as Redox-Switch and Thiol Protection Mechanism in Corynebacterium glutamicum Under Hypochlorite Stress

    PubMed Central

    Chi, Bui Khanh; Busche, Tobias; Van Laer, Koen; Bäsell, Katrin; Becher, Dörte; Clermont, Lina; Seibold, Gerd M.; Persicke, Marcus; Kalinowski, Jörn; Messens, Joris

    2014-01-01

    Abstract Aims: Protein S-bacillithiolation was recently discovered as important thiol protection and redox-switch mechanism in response to hypochlorite stress in Firmicutes bacteria. Here we used transcriptomics to analyze the NaOCl stress response in the mycothiol (MSH)-producing Corynebacterium glutamicum. We further applied thiol-redox proteomics and mass spectrometry (MS) to identify protein S-mycothiolation. Results: Transcriptomics revealed the strong upregulation of the disulfide stress σH regulon by NaOCl stress in C. glutamicum, including genes for the anti sigma factor (rshA), the thioredoxin and MSH pathways (trxB1, trxC, cg1375, trxB, mshC, mca, mtr) that maintain the redox balance. We identified 25 S-mycothiolated proteins in NaOCl-treated cells by liquid chromatography–tandem mass spectrometry (LC-MS/MS), including 16 proteins that are reversibly oxidized by NaOCl in the thiol-redox proteome. The S-mycothiolome includes the methionine synthase (MetE), the maltodextrin phosphorylase (MalP), the myoinositol-1-phosphate synthase (Ino1), enzymes for the biosynthesis of nucleotides (GuaB1, GuaB2, PurL, NadC), and thiamine (ThiD), translation proteins (TufA, PheT, RpsF, RplM, RpsM, RpsC), and antioxidant enzymes (Tpx, Gpx, MsrA). We further show that S-mycothiolation of the thiol peroxidase (Tpx) affects its peroxiredoxin activity in vitro that can be restored by mycoredoxin1. LC-MS/MS analysis further identified 8 proteins with S-cysteinylations in the mshC mutant suggesting that cysteine can be used for S-thiolations in the absence of MSH. Innovation and Conclusion: We identified widespread protein S-mycothiolations in the MSH-producing C. glutamicum and demonstrate that S-mycothiolation reversibly affects the peroxidase activity of Tpx. Interestingly, many targets are conserved S-thiolated across bacillithiol- and MSH-producing bacteria, which could become future drug targets in related pathogenic Gram-positives. Antioxid. Redox Signal. 20, 589–605

  11. Direct Functionalization of (Un)protected Tetrahydroisoquinoline and Isochroman under Iron and Copper Catalysis: Two Metals, Two Mechanisms

    PubMed Central

    2011-01-01

    A highly facile, straightforward synthesis of 1-(3-indolyl)-tetrahydroisoquinolines was developed using either simple copper or iron catalysts. N-protected and unprotected tetrahydroisoquinolines (THIQ) could be used as starting materials. Extension of the substrate scope of the pronucleophile from indoles to pyrroles and electron-rich arenes was realized. Additionally, methoxyphenylation is not limited to THIQ but can be carried out on isochroman as well, again employing iron and copper catalysis. PMID:21902275

  12. Integrated investigation of lipidome and related signaling pathways uncovers molecular mechanisms of tetramethylpyrazine and butylidenephthalide protecting endothelial cells under oxidative stress.

    PubMed

    Yang, Jie; Yang, Song; Yuan, Ying-Jin

    2012-06-01

    Tetramethylpyrazine (TMP) and butylidenephthalide (BP) are two bioactive components isolated from Ligusticum chuanxiong Hort and Angelica sinensis, respectively. These two traditional Chinese medicines have been widely used in clinical treatments for vascular disease. The mechanism by which TMP and BP protect endothelial cells (ECs) against oxidative stress remains unknown, as does their effects on the steady state of the lipidome of ECs. Here, we demonstrate that both compounds protect EA.hy926 cells against H(2)O(2) induced injury in a dose-dependent manner. We then apply an integrated analysis of the lipidome and signal transduction pathways to explore the underlying mechanism of their protective effects. We found that TMP elevates the content of several phosphatidylcholine (PC) species, reduces the release of arachidonic acid (AA) and inhibits the phosphorylation of cytosolic phospholipase A(2) (cPLA(2)). Compared to eicosatetraynoic acid (ETYA), a cPLA(2) inhibitor, TMP preferentially increases the content of arachidonoyl PCs. We also show that BP mainly elevates the pool of phosphatidylinositol (PI) species and inhibits the phosphorylation of both phospholipase C(γ) (PLC(γ)) and extracellular signal-regulated kinase 1/2 (ERK1/2). In contrast, specific inhibition of ERK1/2 by PD98059 decreases the cell viability and increases pool of phosphatidylserine (PS). Taken together, these results demonstrate that TMP protects oxidatively stressed ECs through inhibition of cPLA(2) and preferential increase of arachidonoyl PC levels. Conversely, the effects of BP are tied to inhibition of PLC(γ) and an increase in PI levels. The current work suggests that the interaction of the lipidome and phospholipases can serve as a promising therapeutic target in oxidatively stressed ECs. PMID:22506278

  13. State protection under collective damping and diffusion

    SciTech Connect

    Ponte, M. A. de; Mizrahi, S. S.; Moussa, M. H. Y.

    2011-07-15

    In this paper we provide a recipe for state protection in a network of oscillators under collective damping and diffusion. Our strategy is to manipulate the network topology, i.e., the way the oscillators are coupled together, the strength of their couplings, and their natural frequencies, in order to create a relaxation-diffusion-free channel. This protected channel defines a decoherence-free subspace (DFS) for nonzero-temperature reservoirs. Our development also furnishes an alternative approach to build up DFSs that offers two advantages over the conventional method: it enables the derivation of all the network-protected states at once, and also reveals, through the network normal modes, the mechanism behind the emergence of these protected domains.

  14. Singlet Oxygen Production by PSII Under Light Stress: Mechanism, Detection and the Protective role of β-Carotene

    PubMed Central

    Telfer, Alison

    2014-01-01

    In this review, I outline the indirect evidence for the formation of singlet oxygen (1O2) obtained from experiments with the isolated PSII reaction center complex. I also review the methods we used to measure singlet oxygen directly, including luminescence at 1,270 nm, both steady state and time resolved. Other methods we used were histidine-catalyzed molecular oxygen uptake (enabling 1O2 yield measurements), and dye bleaching and difference absorption spectroscopy to identify where quenchers of 1O2 can access this toxic species. We also demonstrated the protective behavior of carotenoids bound within Chl–protein complexes which bring about a substantial amount of 1O2 quenching within the reaction center complex. Finally, I describe how these techniques have been used and expanded in research on photoinhibition and on the role of 1O2 as a signaling molecule in instigating cellular responses to various stress factors. I also discuss the current views on the role of 1O2 as a signaling molecule and the distance it might be able to travel within cells. PMID:24566536

  15. Singlet oxygen production by PSII under light stress: mechanism, detection and the protective role of β-carotene.

    PubMed

    Telfer, Alison

    2014-07-01

    In this review, I outline the indirect evidence for the formation of singlet oxygen ((1)O(2)) obtained from experiments with the isolated PSII reaction center complex. I also review the methods we used to measure singlet oxygen directly, including luminescence at 1,270 nm, both steady state and time resolved. Other methods we used were histidine-catalyzed molecular oxygen uptake (enabling (1)O(2) yield measurements), and dye bleaching and difference absorption spectroscopy to identify where quenchers of (1)O(2) can access this toxic species. We also demonstrated the protective behavior of carotenoids bound within Chl-protein complexes which bring about a substantial amount of (1)O(2) quenching within the reaction center complex. Finally, I describe how these techniques have been used and expanded in research on photoinhibition and on the role of (1)O(2) as a signaling molecule in instigating cellular responses to various stress factors. I also discuss the current views on the role of (1)O(2) as a signaling molecule and the distance it might be able to travel within cells.

  16. Physiological parameters and protective energy dissipation mechanisms expressed in the leaves of two Vitis vinifera L. genotypes under multiple summer stresses.

    PubMed

    Palliotti, Alberto; Tombesi, Sergio; Frioni, Tommaso; Silvestroni, Oriana; Lanari, Vania; D'Onofrio, Claudio; Matarese, Fabiola; Bellincontro, Andrea; Poni, Stefano

    2015-08-01

    Photosynthetic performances and energy dissipation mechanisms were evaluated on the anisohydric cv. Sangiovese and on the isohydric cv. Montepulciano (Vitis vinifera L.) under conditions of multiple summer stresses. Potted vines of both cultivars were maintained at 90% and 40% of maximum water availability from fruit-set to veraison. One week before veraison, at predawn and midday, main gas-exchange and chlorophyll fluorescence parameters, chlorophyll content, xanthophyll pool and cycle and catalase activity were evaluated. Under water deficit and elevated irradiance and temperature, contrary to cv. Montepulciano and despite a significant leaf water potential decrease, Sangiovese's leaves kept their stomata more open and continued to assimilate CO2 while also showing higher water use efficiency. Under these environmental conditions, in comparison with the isohydric cv. Montepulciano, the protective mechanisms of energy dissipation exerted by the anisohydric cv. Sangiovese were: (i) higher stomatal conductance and thermoregulation linked to higher transpiration rate; (ii) greater ability at dissipating more efficiently the excess energy via the xanthophylls cycle activity (thermal dissipation) due to higher VAZ pool and greater increase of de-epoxidation activity. PMID:26310367

  17. The protective effects and underlying mechanism of an anti-oligomeric Aβ42 single-chain variable fragment antibody.

    PubMed

    Zhang, Yuan; Chen, Xu; Liu, Jinyu; Zhang, Yingjiu

    2015-12-01

    Oligomeric Aβ42 aggregates have been identified as one of the major neurotoxic components of Alzheimer's disease (AD). Immunotherapy targeted against these Aβ42 aggregates has been proposed as an appropriate therapeutic approach for the treatment of AD. Here, we report an anti-oligomeric Aβ42 single-chain variable fragment (scFv) antibody, named MO6, obtained from the human antibody library of a healthy donor. ScFv MO6 specifically recognized and bound to the oligomeric Aβ42 (Aβ42 oligomers and immature protofibrils; 18-37 kDa), and reduced their levels mainly by blocking their formation, although scFv MO6 also induced disaggregation of Aβ42 aggregates. More importantly, scFv MO6 ameliorated or attenuated Aβ42-induced cytotoxicity and increased cell viability by up to 33%. Furthermore, scFv MO6 efficiently passed through an in vitro blood-brain barrier (BBB) model with a delivery efficiency of 66% after 60 min post-administration. ScFv MO6 is a monovalent antibody with an affinity constant (KD) of 5.2×10(-6) M for Aβ42 oligomers. Molecular docking simulations of Aβ42 to scFv MO6 revealed that the approach and specific binding of scFv MO6 to oligomeric Aβ42 aggregates was achieved by conformational recognition and directed induction, which resulted in a more dynamic adaptation of Aβ42 to scFv MO6, occurring mainly in the N-terminal (3-4), middle (12-19) and C-terminal (34-42) regions of Aβ42. This binding mode of scFv MO6 to Aβ42 explains its protective effects against oligomeric Aβ42. Our findings may be applied for the design of a smaller antibody specific for Aβ42 oligermers. PMID:26256421

  18. [Growing up under adversity in Germany : Design and methods of a developmental study on risk and protective mechanisms in families with diverse psychosocial risk].

    PubMed

    Zimmermann, Peter; Vierhaus, Marc; Eickhorst, Andreas; Sann, Alexandra; Egger, Carine; Förthner, Judith; Gerlach, Jennifer; Iwanski, Alexandra; Liel, Christoph; Podewski, Fritz; Wyrwich, Sandra; Spangler, Gottfried

    2016-10-01

    Family adversity comprises many risk factors for parents and children. The German early intervention approach Frühe Hilfen aims at providing enduring, effective, and scientifically validated prevention and intervention for effective child protection against those risks. The study on risk and protective mechanisms in the development of families with diverse psychosocial risks aims at identifying those mechanisms that cause and stabilize or moderate and diminish maltreatment and neglect, as well as cognitive, social, and emotional developmental deviations in risk families, specifically in the current German social and child protection system. The study examines the development of competence and early behavior problems in a sample of infants and toddlers and the interaction quality with their caregivers by applying a longitudinal sequential-cohort design. The assessments include developmental tests, systematic observations, and questionnaire data. First results suggest stable risk group membership and moderate stability of single risk factors.

  19. Mechanical properties of thermal protection system materials.

    SciTech Connect

    Hardy, Robert Douglas; Bronowski, David R.; Lee, Moo Yul; Hofer, John H.

    2005-06-01

    An experimental study was conducted to measure the mechanical properties of the Thermal Protection System (TPS) materials used for the Space Shuttle. Three types of TPS materials (LI-900, LI-2200, and FRCI-12) were tested in 'in-plane' and 'out-of-plane' orientations. Four types of quasi-static mechanical tests (uniaxial tension, uniaxial compression, uniaxial strain, and shear) were performed under low (10{sup -4} to 10{sup -3}/s) and intermediate (1 to 10/s) strain rate conditions. In addition, split Hopkinson pressure bar tests were conducted to obtain the strength of the materials under a relatively higher strain rate ({approx}10{sup 2} to 10{sup 3}/s) condition. In general, TPS materials have higher strength and higher Young's modulus when tested in 'in-plane' than in 'through-the-thickness' orientation under compressive (unconfined and confined) and tensile stress conditions. In both stress conditions, the strength of the material increases as the strain rate increases. The rate of increase in LI-900 is relatively small compared to those for the other two TPS materials tested in this study. But, the Young's modulus appears to be insensitive to the different strain rates applied. The FRCI-12 material, designed to replace the heavier LI-2200, showed higher strengths under tensile and shear stress conditions. But, under a compressive stress condition, LI-2200 showed higher strength than FRCI-12. As far as the modulus is concerned, LI-2200 has higher Young's modulus both in compression and in tension. The shear modulus of FRCI-12 and LI-2200 fell in the same range.

  20. [Mechanisms that protect against homocysteine toxicity].

    PubMed

    Zimny, Jarosław

    2008-01-01

    Elevated concentrations of homocysteine (Hcy) in human tissues have been correlated with some diseases, such as cardio-vascular, neurodegenerative, and kidney disorders. Hcy occurs in human blood in several forms. The most reactive is homocysteine thiolactone (HcyTl). It spontaneously homocysteinylates proteins impairing their functions. As has been evidenced recently, organisms developed protective mechanisms against the HcyTl toxicity. The first mechanism discovered was the calcium-dependent enzyme occurring in mammalian sera, known till then as paraoxonase, which hydrolyzes HcyTl to Hcy. Chronologically second mechanism discovered was urinary excretion of HcyTl. The third protective mechanism is the HcyTl hydrolysis catalyzed by intracellular enzyme known as bleomycin hydrolase. This review outlines current knowledge of the Hcy toxicity and of the three aforementioned protective mechanisms, emphasizing the role of bleomycin hydrolase/ homocysteine-thiolactonase. PMID:18610586

  1. Prebiotics: Definition and protective mechanisms.

    PubMed

    Valcheva, Rosica; Dieleman, Levinus A

    2016-02-01

    The increase in chronic metabolic and immunologic disorders in the modern society is linked to major changes in the dietary patterns. These chronic conditions are associated with intestinal microbiota dysbiosis where important groups of carbohydrate fermenting, short-chain fatty acids-producing bacteria are reduced. Dietary prebiotics are defined as a selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health. Application of prebiotics may then restore the gut microbiota diversity and activity. Unlike the previously accepted prebiotics definition, where a limited number of bacterial species are involved in the prebiotic activity, new data from community-wide microbiome analysis demonstrated a broader affect of the prebiotics on the intestinal microbiota. These new findings require a revision of the current definition. In addition, prebiotics may exert immunomodulatory effects through microbiota-independent mechanisms that will require future investigations involving germ-free animal disease models.

  2. Prebiotics: Definition and protective mechanisms.

    PubMed

    Valcheva, Rosica; Dieleman, Levinus A

    2016-02-01

    The increase in chronic metabolic and immunologic disorders in the modern society is linked to major changes in the dietary patterns. These chronic conditions are associated with intestinal microbiota dysbiosis where important groups of carbohydrate fermenting, short-chain fatty acids-producing bacteria are reduced. Dietary prebiotics are defined as a selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health. Application of prebiotics may then restore the gut microbiota diversity and activity. Unlike the previously accepted prebiotics definition, where a limited number of bacterial species are involved in the prebiotic activity, new data from community-wide microbiome analysis demonstrated a broader affect of the prebiotics on the intestinal microbiota. These new findings require a revision of the current definition. In addition, prebiotics may exert immunomodulatory effects through microbiota-independent mechanisms that will require future investigations involving germ-free animal disease models. PMID:27048894

  3. Redox mechanisms of cardiomyocyte mitochondrial protection

    PubMed Central

    Bartz, Raquel R.; Suliman, Hagir B.; Piantadosi, Claude A.

    2015-01-01

    Oxidative and nitrosative stress are primary contributors to the loss of myocardial tissue in insults ranging from ischemia/reperfusion injury from coronary artery disease and heart transplantation to sepsis-induced myocardial dysfunction and drug-induced myocardial damage. This cell damage caused by oxidative and nitrosative stress leads to mitochondrial protein, DNA, and lipid modifications, which inhibits energy production and contractile function, potentially leading to cell necrosis and/or apoptosis. However, cardiomyocytes have evolved an elegant set of redox-sensitive mechanisms that respond to and contain oxidative and nitrosative damage. These responses include the rapid induction of antioxidant enzymes, mitochondrial DNA repair mechanisms, selective mitochondrial autophagy (mitophagy), and mitochondrial biogenesis. Coordinated cytoplasmic to nuclear cell-signaling and mitochondrial transcriptional responses to the presence of elevated cytoplasmic oxidant production, e.g., H2O2, allows nuclear translocation of the Nfe2l2 transcription factor and up-regulation of downstream cytoprotective genes such as heme oxygenase-1 which generates physiologic signals, such as CO that up-regulates Nfe212 gene transcription. Simultaneously, a number of other DNA binding transcription factors are expressed and/or activated under redox control, such as Nuclear Respiratory Factor-1 (NRF-1), and lead to the induction of genes involved in both intracellular and mitochondria-specific repair mechanisms. The same insults, particularly those related to vascular stress and inflammation also produce elevated levels of nitric oxide, which also has mitochondrial protein thiol-protective functions and induces mitochondrial biogenesis through cyclic GMP-dependent and perhaps other pathways. This brief review provides an overview of these pathways and interconnected cardiac repair mechanisms. PMID:26578967

  4. Molecular Mechanisms Underlying Pituitary Pathogenesis.

    PubMed

    Sapochnik, Melanie; Nieto, Leandro Eduardo; Fuertes, Mariana; Arzt, Eduardo

    2016-04-01

    During the last years, progress has been made on the identification of mechanisms involved in anterior pituitary cell transformation and tumorigenesis. Oncogene activation, tumor suppressor gene inactivation, epigenetic changes, and microRNAs deregulation contribute to the initiation of pituitary tumors. Despite the high prevalence of pituitary adenomas, they are mostly benign, indicating that intrinsic mechanisms may regulate pituitary cell expansion. Senescence is characterized by an irreversible cell cycle arrest and represents an important protective mechanism against malignancy. Pituitary tumor transforming gene (PTTG) is an oncogene involved in early stages of pituitary tumor development, and also triggers a senescence response by activating DNA-damage signaling pathway. Cytokines, as well as many other factors, play an important role in pituitary physiology, affecting not only cell proliferation but also hormone secretion. Special interest is focused on interleukin-6 (IL-6) because its dual function of stimulating pituitary tumor cell growth but inhibiting normal pituitary cells proliferation. It has been demonstrated that IL-6 has a key role in promoting and maintenance of the senescence program in tumors. Senescence, triggered by PTTG activation and mediated by IL-6, may be a mechanism for explaining the benign nature of pituitary tumors.

  5. A quantum protective mechanism in photosynthesis

    NASA Astrophysics Data System (ADS)

    Marais, Adriana; Sinayskiy, Ilya; Petruccione, Francesco; van Grondelle, Rienk

    2015-03-01

    Since the emergence of oxygenic photosynthesis, living systems have developed protective mechanisms against reactive oxygen species. During charge separation in photosynthetic reaction centres, triplet states can react with molecular oxygen generating destructive singlet oxygen. The triplet product yield in bacteria is observed to be reduced by weak magnetic fields. Reaction centres from plants' photosystem II share many features with bacterial reaction centres, including a high-spin iron whose function has remained obscure. To explain observations that the magnetic field effect is reduced by the iron, we propose that its fast-relaxing spin plays a protective role in photosynthesis by generating an effective magnetic field. We consider a simple model of the system, derive an analytical expression for the effective magnetic field and analyse the resulting triplet yield reduction. The protective mechanism is robust for realistic parameter ranges, constituting a clear example of a quantum effect playing a macroscopic role vital for life.

  6. Protective Mechanisms of Flavonoids in Parkinson's Disease

    PubMed Central

    Magalingam, Kasthuri Bai; Radhakrishnan, Ammu Kutty; Haleagrahara, Nagaraja

    2015-01-01

    Parkinson's disease is a chronic, debilitating neurodegenerative movement disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta region in human midbrain. To date, oxidative stress is the well accepted concept in the etiology and progression of Parkinson's disease. Hence, the therapeutic agent is targeted against suppressing and alleviating the oxidative stress-induced cellular damage. Within the past decades, an explosion of research discoveries has reported on the protective mechanisms of flavonoids, which are plant-based polyphenols, in the treatment of neurodegenerative disease using both in vitro and in vivo models. In this paper, we have reviewed the literature on the neuroprotective mechanisms of flavonoids in protecting the dopaminergic neurons hence reducing the symptoms of this movement disorder. The mechanism reviewed includes effect of flavonoids in activation of endogenous antioxidant enzymes, suppressing the lipid peroxidation, inhibition of inflammatory mediators, flavonoids as a mitochondrial target therapy, and modulation of gene expression in neuronal cells. PMID:26576219

  7. Protective immune mechanisms in helminth infection

    PubMed Central

    Anthony, Robert M.; Rutitzky, Laura I.; Urban, Joseph F.; Stadecker, Miguel J.; Gause, William C.

    2008-01-01

    Important insights have recently been gained in our understanding of how host immune responses mediate resistance to parasitic helminths and control associated pathological responses. Although similar cells and cytokines are evoked in response to infection by helminths as diverse as nematodes and schistosomes, the components of the response that mediate protection are dependent on the particular parasite. In this Review, we examine recent findings regarding the mechanisms of protection in helminth infections that have been elucidated in murine models and discuss the implications of these findings in terms of future therapies. PMID:18007680

  8. Protective effects of friedelin isolated from Azima tetracantha Lam. against ethanol-induced gastric ulcer in rats and possible underlying mechanisms.

    PubMed

    Antonisamy, Paulrayer; Duraipandiyan, Veeramuthu; Aravinthan, Adithan; Al-Dhabi, Naif Abdullah; Ignacimuthu, Savarimuthu; Choi, Ki Choon; Kim, Jong-Hoon

    2015-03-01

    The current study was aimed to investigate the gastroprotective effects of friedelin isolated from the hexane extract of leaves of Azima tetracantha. Ethanol-induced gastric ulcer model was used to investigate the gastroprotective effects of friedelin. Antioxidant enzymes, lipid peroxidation, nitric oxide, gastric vascular permeability, pro and anti-inflammatory cytokines and apoptosis level have been investigated. Ethanol caused severe gastric damage and friedelin pretreatment protected against its deleterious role. Antioxidant enzyme activities, anti-inflammatory cytokines, prostaglandin E2 (PGE2), constitutive nitric oxide synthase (cNOS) and mucus weight have been increased significantly. However, the vascular permeability, pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), caspase-3 and apoptosis level have significantly been decreased after friedelin ingestion. The present study has clearly demonstrated the anti-ulcer potential of friedelin, these findings suggested that friedelin could be a new useful natural gastroprotective tool against gastric ulcer.

  9. Quality of Protection Evaluation of Security Mechanisms

    PubMed Central

    Ksiezopolski, Bogdan; Zurek, Tomasz; Mokkas, Michail

    2014-01-01

    Recent research indicates that during the design of teleinformatic system the tradeoff between the systems performance and the system protection should be made. The traditional approach assumes that the best way is to apply the strongest possible security measures. Unfortunately, the overestimation of security measures can lead to the unreasonable increase of system load. This is especially important in multimedia systems where the performance has critical character. In many cases determination of the required level of protection and adjustment of some security measures to these requirements increase system efficiency. Such an approach is achieved by means of the quality of protection models where the security measures are evaluated according to their influence on the system security. In the paper, we propose a model for QoP evaluation of security mechanisms. Owing to this model, one can quantify the influence of particular security mechanisms on ensuring security attributes. The methodology of our model preparation is described and based on it the case study analysis is presented. We support our method by the tool where the models can be defined and QoP evaluation can be performed. Finally, we have modelled TLS cryptographic protocol and presented the QoP security mechanisms evaluation for the selected versions of this protocol. PMID:25136683

  10. Quality of protection evaluation of security mechanisms.

    PubMed

    Ksiezopolski, Bogdan; Zurek, Tomasz; Mokkas, Michail

    2014-01-01

    Recent research indicates that during the design of teleinformatic system the tradeoff between the systems performance and the system protection should be made. The traditional approach assumes that the best way is to apply the strongest possible security measures. Unfortunately, the overestimation of security measures can lead to the unreasonable increase of system load. This is especially important in multimedia systems where the performance has critical character. In many cases determination of the required level of protection and adjustment of some security measures to these requirements increase system efficiency. Such an approach is achieved by means of the quality of protection models where the security measures are evaluated according to their influence on the system security. In the paper, we propose a model for QoP evaluation of security mechanisms. Owing to this model, one can quantify the influence of particular security mechanisms on ensuring security attributes. The methodology of our model preparation is described and based on it the case study analysis is presented. We support our method by the tool where the models can be defined and QoP evaluation can be performed. Finally, we have modelled TLS cryptographic protocol and presented the QoP security mechanisms evaluation for the selected versions of this protocol.

  11. Market mechanisms protect the vulnerable brain

    PubMed Central

    Ramchandran, Kanchna; Nayakankuppam, Dhananjay; Berg, Joyce; Tranel, Daniel

    2011-01-01

    Markets are mechanisms of social exchange, intended to facilitate trading. However, the question remains as to whether markets would help or hurt individuals with decision-makings deficits, as is frequently encountered in the case of cognitive aging. Essential for predicting future gains and losses in monetary and social domains, the striatal nuclei in the brain undergo structural, neurochemical, and functional decline with age. We correlated the efficacy of market mechanisms with dorsal striatal decline in an aging population, by using market based trading in the context of the 2008 U.S Presidential Elections (primary cycle). Impaired decision-makers displayed higher prediction error (difference between their prediction and actual outcome). Lower in vivo caudate volume was also associated with higher prediction error. Importantly, market-based trading protected older adults with lower caudate volume to a greater extent from their own poorly calibrated predictions. Counterintuitive to the traditional public perception of the market as a fickle, risky proposition where vulnerable traders are most surely to be burned, we suggest that market-based mechanisms protect individuals with brain-based decision-making vulnerabilities. PMID:21600226

  12. Exploring the complexity of the mechanism of cathodic protection

    SciTech Connect

    Thompson, N.G.; Lawson, K.M.; Beavers, J.A.

    1994-12-31

    The present understanding of the mechanism of cathodic protection is too simplistic to explain when, why, and under what conditions corrosion is mitigated for a buried pipeline. This paper presents a general framework which attempts to explain why cathodic protection is achieved and what factors are critical in determining the ability of cathodic protection to mitigate corrosion. It is speculated that the changes in the ``near-surface`` environment due to the reduction processes on the cathodically protected steel surface play a significant role in mitigating corrosion and in defining the level of polarization achieved. This is accomplished by contributing a concentration polarization term to the overall level of polarization. Furthermore, the concentration polarization term explains many field related observations not easily explained by activation polarization and mixed potential theory. 32 refs.

  13. Uncovering high-strain rate protection mechanism in nacre.

    PubMed

    Huang, Zaiwang; Li, Haoze; Pan, Zhiliang; Wei, Qiuming; Chao, Yuh J; Li, Xiaodong

    2011-01-01

    Under high-strain-rate compression (strain rate approximately 10(3) s(-1)), nacre (mother-of-pearl) exhibits surprisingly high fracture strength vis-à-vis under quasi-static loading (strain rate 10(-3) s(-1)). Nevertheless, the underlying mechanism responsible for such sharply different behaviors in these two loading modes remains completely unknown. Here we report a new deformation mechanism, adopted by nacre, the best-ever natural armor material, to protect itself against predatory penetrating impacts. It involves the emission of partial dislocations and the onset of deformation twinning that operate in a well-concerted manner to contribute to the increased high-strain-rate fracture strength of nacre. Our findings unveil that Mother Nature delicately uses an ingenious strain-rate-dependent stiffening mechanism with a purpose to fight against foreign attacks. These findings should serve as critical design guidelines for developing engineered body armor materials. PMID:22355664

  14. Uncovering high-strain rate protection mechanism in nacre

    PubMed Central

    Huang, Zaiwang; Li, Haoze; Pan, Zhiliang; Wei, Qiuming; Chao, Yuh J.; Li, Xiaodong

    2011-01-01

    Under high-strain-rate compression (strain rate ∼103 s−1), nacre (mother-of-pearl) exhibits surprisingly high fracture strength vis-à-vis under quasi-static loading (strain rate 10−3 s−1). Nevertheless, the underlying mechanism responsible for such sharply different behaviors in these two loading modes remains completely unknown. Here we report a new deformation mechanism, adopted by nacre, the best-ever natural armor material, to protect itself against predatory penetrating impacts. It involves the emission of partial dislocations and the onset of deformation twinning that operate in a well-concerted manner to contribute to the increased high-strain-rate fracture strength of nacre. Our findings unveil that Mother Nature delicately uses an ingenious strain-rate-dependent stiffening mechanism with a purpose to fight against foreign attacks. These findings should serve as critical design guidelines for developing engineered body armor materials. PMID:22355664

  15. Mechanisms underlying Children's susceptibility to environmental toxicants.

    PubMed Central

    Faustman, E M; Silbernagel, S M; Fenske, R A; Burbacher, T M; Ponce, R A

    2000-01-01

    An important public health challenge has been the need to protect children's health. To accomplish this goal, the scientific community needs scientifically based child-specific risk assessment methods. Critical to their development is the need to understand mechanisms underlying children's sensitivity to environmental toxicants. Risk is defined as the probability of adverse outcome and when applied to environmental risk assessment is usually defined as a function of both toxicity and exposure. To adequately evaluate the potential for enhanced health risks during development, both child-specific factors affecting toxicity and exposure need to be considered. In the first section of this article, example mechanisms of susceptibility relevant for toxicity assessment are identified and discussed. In the second section, examples of exposure factors that help define children's susceptibility are presented. Examples of pesticide research from the newly funded Child Health Center at the University of Washington will be given for illustration. The final section discusses the importance of putting these considerations of children's susceptibility into an overall framework for ascertaining relevancy for human risk assessment. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 PMID:10698720

  16. Mechanisms Underlying Inflammation in Neurodegeneration

    PubMed Central

    Glass, Christopher K.; Saijo, Kaoru; Winner, Beate; Marchetto, Maria Carolina; Gage, Fred H.

    2010-01-01

    Inflammation is associated with many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. In this Review, we discuss inducers, sensors, transducers, and effectors of neuroinflammation that contribute to neuronal dysfunction and death. Although inducers of inflammation may be generated in a disease-specific manner, there is evidence for a remarkable convergence in the mechanisms responsible for the sensing, transduction, and amplification of inflammatory processes that result in the production of neurotoxic mediators. A major unanswered question is whether pharmacological inhibition of inflammation pathways will be able to safely reverse or slow the course of disease. PMID:20303880

  17. [The neural mechanisms underlying swallowing].

    PubMed

    Inoue, Makoto

    2015-02-01

    Swallowing is regarded as the first step in nutrition; it transports food boluses and liquid from the mouth to the stomach and is a defensive response to prevent aspiration. Swallowing movements are produced by a central pattern generator (CPG) located in the lower brainstem. The swallowing CPG includes two main groups of neurons: one is located within the nucleus tractus solitarii and contains the generator neurons involved in triggering, shaping, and timing the sequential or rhythmic swallowing pattern and the other is located in the ventrolateral medulla and contains switching neurons that distribute the swallowing drive to various pools of related motoneurons. Swallowing movements can be triggered by either central inputs or peripheral inputs from pharyngeal and laryngeal regions, but the precise neural mechanisms of the swallowing CPG remain to be fully elucidated. This review discusses the fundamental knowledge of ingestion behaviors, with a focus on swallowing.

  18. Wellhead protection area delineation under uncertainty

    SciTech Connect

    Jacobson, E.; Andricevic, R.; Hultin, T.

    1994-09-01

    A program to protect groundwater resources used for water supply from all potential threats due to contamination was established in the Amendments to the Safe Drinking Water Act (SDWA). Goal of the State Wellhead Protection (WHP) Program is to ``protect wellhead areas within their jurisdiction from contaminants which may have any adverse effect on the health of persons.`` A major component of WHP is the determination of zones around water-supply wells called Wellhead Protection Areas (WHPAs) within which contaminant source assessment and management should be addressed. WHPAs are defined in the SDWA as ``the surface and subsurface area surrounding a water well or wellfield, supplying a public water system, through which contaminants are reasonably likely to move toward and reach such water well or wellfield.`` A total of 14 water-supply wells are currently being used at the Nevada Test Site (NTS). Eleven of the wells are used for potable water supplies and the remaining three wells are used for construction purposes only. Purpose of this study is to estimate WHPAs for each water-supply well at the NTS. Due to the limited information about the hydraulic properties needed for estimating the WHPAS, an approach that considered the uncertainty in the estimates of the hydraulic properties was developed and implemented.

  19. Metacognitive mechanisms underlying lucid dreaming.

    PubMed

    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.

  20. Metacognitive mechanisms underlying lucid dreaming.

    PubMed

    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. PMID:25609624

  1. Mechanical Thrombectomy of Iliocaval Thrombosis Using a Protective Expandable Sheath

    SciTech Connect

    Truong, Tri H.; Spuentrup, Elmar; Staatz, Gundula; Wildberger, Joachim E.; Schmitz-Rode, Thomas; Nolte-Ernsting, Claus C.A.; Guenther, Rolf W.; Haage, Patrick

    2004-09-15

    We report a case of successful percutaneous treatment of a subacute ilio-caval venous thrombosis in a 64-year-old female patient by using a novel combination of a rotatory fragmentation device (percutaneous thrombectomy device: PTD) and large wire basket (temporary Guenther basket filter) under temporary caval filter protection using an expandable sheath. Because the patient had multiple myeloma with increased risk for contrast media-induced renal failure, the therapeutic angiographic procedure was performed without iodinated contrast medium. Non-contrast-enhanced MR venography (high-resolution True FISP) confirmed the effective thrombus removal by the percutaneous mechanical thrombectomy procedure.

  2. Optimal Climate Protection Policies Under Uncertainty

    NASA Astrophysics Data System (ADS)

    Weber, M.; Barth, V.; Hasselmann, K.; Hooss, G.

    A cost-benefit analysis for greenhouse warming based on a globally integrated cou- pled climate-macro economic cost model SIAM2 (Structural Integrated Assessment Model) is used to compute optimal paths of global CO2 emissions. The aim of the model is to minimize the net time-integrated sum of climate damage and mitigation costs (or maximize the economic and social welfare). The climate model is repre- sented by a nonlinear impulse-response model (NICCS) calibrated against a coupled ocean-atmosphere general circulation model and a three-dimensional global carbon cycle model. The latest version of the economic module is based a macro economic growth model, which is designed to capture not only the interactions between cli- mate damages and economic development, but also the conflicting goals of individual firms and society (government). The model includes unemployment, limited fossil fuel resources, endogenous and stochastic exogenous technological development (unpre- dictable labor or fuel efficiency innovations of random impact amplitude at random points in time). One objective of the project is to examine optimal climate protection policies in the presence of uncertainty. A stochastic model is introduced to simulate the development of technology as well as climate change and climate damages. In re- sponse to this (stochastic) prediction, the fiscal policy is adjusted gradually in a series of discrete steps. The stochastic module includes probability-based methods, sensitiv- ity studies and formal szenario analysis.

  3. Agronomic performance of five banana cultivars under protected cultivation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Banana has been grown both in open-field and protected cultivation in Turkey. So far protected cultivation is very popular due to the high yield and quality. The objective of the study was to evaluate agronomic performance of five new banana cultivars under plastic greenhouse. ‘MA 13’, ‘Williams’, ‘...

  4. Legal mechanisms for protecting riparian resource values

    USGS Publications Warehouse

    Lamb, Berton L.; Lord, Eric

    1992-01-01

    Riparian resources include the borders of rivers, lakes, ponds, and potholes. These border areas are very important for a number of reasons, including stream channel maintenance, flood control, aesthetics, erosion control, fish and wildlife habitat, recreation, and water quality maintenance. These diverse functions are not well protected by law or policy. We reviewed law and policies regarding endangered species habitat designation, land use planning, grazing management, water allocation, takings, and federal permits and licenses, along with the roles of federal, state, and local governments. We discuss the politics of implementing these policies, focusing on the difficulties in changing entrenched water and land use practices. Our review indicates a lack of direct attention to riparian ecosystem issues in almost all environmental and land use programs at every level of government. Protection of riparian resource values requires a means to integrate existing programs to focus on riparian zones.

  5. Mechanisms of endospore inactivation under high pressure.

    PubMed

    Reineke, Kai; Mathys, Alexander; Heinz, Volker; Knorr, Dietrich

    2013-06-01

    It is well known that spore germination and inactivation can be achieved within a broad temperature and pressure range. The existing literature, however, reports contradictory results concerning the effectiveness of different pressure-temperature combinations and the underlying inactivation mechanism(s). Much of the published kinetic data are prone to error as a result of unstable process conditions or an incomplete investigation of the entire inactivation pathway. Here, we review this field of research, and also discuss an inactivation mechanism of at least two steps and propose an inactivation model based on current data. Further, spore resistance properties and matrix interactions are linked to spore inactivation effectiveness.

  6. Protecting the Self: Defense Mechanisms in Action

    ERIC Educational Resources Information Center

    Cramer, Phebe

    2006-01-01

    Integrating theory, research, and practical applications, this book provides a comprehensive examination of defense mechanisms and their role in both normal development and psychopathology. The author describes how children and adults mobilize specific kinds of defenses to maintain their psychological equilibrium and preserve self-esteem,…

  7. Cognitive Mechanisms Underlying Second Language Listening Comprehension

    ERIC Educational Resources Information Center

    Hu, Guiling

    2009-01-01

    This dissertation research investigates the cognitive mechanisms underlying second language (L2) listening comprehension. I use three types of sentential contexts, congruent, neutral and incongruent, to look at how L2 learners construct meaning in spoken sentence comprehension. The three types of contexts differ in their context predictability.…

  8. Protective mechanism against cancer found in progeria patient cells

    Cancer.gov

    NCI scientists have studied cells of patients with an extremely rare genetic disease that is characterized by drastic premature aging and discovered a new protective cellular mechanism against cancer. They found that cells from patients with Hutchinson Gi

  9. Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

    PubMed Central

    Olthof, Pim B; Reiniers, Megan J; Dirkes, Marcel C; van Gulik, Thomas M; Heger, Michal; van Golen, Rowan F

    2015-01-01

    Hepatic ischemia/reperfusion (I/R) injury is a side effect of major liver surgery that often cannot be avoided. Prolonged periods of ischemia put a metabolic strain on hepatocytes and limit the tolerable ischemia and preservation times during liver resection and transplantation, respectively. In both surgical settings, temporarily lowering the metabolic demand of the organ by reducing organ temperature effectively counteracts the negative consequences of an ischemic insult. Despite its routine use, the application of liver cooling is predicated on an incomplete understanding of the underlying protective mechanisms, which has limited a uniform and widespread implementation of liver-cooling techniques. This review therefore addresses how hypothermia-induced hypometabolism modulates hepatocyte metabolism during ischemia and thereby reduces hepatic I/R injury. The mechanisms underlying hypothermia-mediated reduction in energy expenditure during ischemia and the attenuation of mitochondrial production of reactive oxygen species during early reperfusion are described. It is further addressed how hypothermia suppresses the sterile hepatic I/R immune response and preserves the metabolic functionality of hepatocytes. Lastly, a summary of the clinical status quo of the use of liver cooling for liver resection and transplantation is provided. PMID:26552060

  10. Mechanisms underlying the portion-size effect.

    PubMed

    Peter Herman, C; Polivy, Janet; Pliner, Patricia; Vartanian, Lenny R

    2015-05-15

    The portion-size effect (PSE) refers to the fact that people eat more when served larger portions. This effect is neither obvious nor artifactual. We examine the prevailing explanations (or underlying mechanisms) that have been offered for the PSE. The dominant candidate mechanism is "appropriateness"; that is, people accept the portion that they are served as being of an appropriate size and eat accordingly. Because people do not necessarily finish the portion that they are served, variations on the basic appropriateness mechanism have been suggested. We also consider some evidence that is inconsistent with an appropriateness explanation, including the appearance of the PSE in children as young as two years of age. We also examine other mechanisms that do not rely on appropriateness norms. Visual food cues may assist in assessing appropriateness but may also drive food intake in a more mindless fashion. Larger portions induce larger bites, which may increase intake by reducing oral exposure time and sensory-specific satiety. We consider further research questions that could help to clarify the mechanisms underlying the PSE. PMID:25802021

  11. Mechanical and electromagnetic induction of protection against oxidative stress.

    PubMed

    Di Carlo, A L; White, N C; Litovitz, T A

    2001-01-01

    Cells and tissues can be protected against a potentially lethal stress by first exposing them to a brief dose of the same or different stress. This "pre-conditioning" phenomenon has been documented in many models of protection against oxidative stress, including ischemia/reperfusion and ultraviolet (UV) light exposure. Stimuli which induce this protective response include heat, chemicals, brief ischemia, and electromagnetic (EM) field exposures. We report here that constant mechanical vibration pre-conditions chick embryos, protecting them during subsequent stress from hypoxia or UV light exposure. Continuously mechanically vibrated embryos (60 Hz, 1 g (32 ft/s2), 20 min) exhibited nearly double the survival (67.5%, P < 0.001) after subsequent hypoxia as compared to non-vibrated controls (37.6%). As a second set of experiments, embryos were vibrated and then exposed to UV light stress. Those embryos that were vibrated prior to UV had nearly double the survival 3 h after UV exposure (66%, P < 0.001) as compared to controls (35%). The degree of protection, however, was dependent on the constancy of the vibration amplitude. When vibration was turned on and off at 1-s intervals throughout exposure, no increase in hypoxia protection was noted. For 50 s on/off vibration intervals, however, hypoxia protection comparable to continuous vibration was obtained. In contrast, random, inconstant mechanical vibration did not induce protection against subsequent UV exposure. These data suggest that to be an effective pre-conditioning agent, mechanical vibration must have a degree of temporally constancy (on/off intervals of greater than 1 s). Further experiments in both models (hypoxia and UV) indicated an interaction between vibration and EM field-induced protection. Vibration-induced hypoxia protection was inhibited by superposition of a random EM noise field (previously shown to inhibit EM field-induced protection). In addition, EM field-induced UV protection was inhibited by

  12. Vision, language and a protective mechanism towards psychosis.

    PubMed

    Leivada, Evelina

    2016-03-23

    The absence of co-occurrence of schizophrenia with congenital/early blindness (CB) has led to the claim that CB confers protection against schizophrenia. It has recently been shown that the protective effects are particularly reinforced in cases of CB of cortical origin, since cases of CB of peripheral origin and schizophrenia in fact exist. The present work shows that the protection extends to psychosis more broadly and describes the brain basis of the protective mechanism and its relation to the language faculty and the language areas of the brain.

  13. MECHANISMS INVOLVED IN MYCORRHIZAL WHEAT PROTECTION AGAINST POWDERY MILDEW.

    PubMed

    Mustafa, G; Tisserant, B; Randoux, B; Fontaine, J; Sahraoui, A Lounes-Hadj; Reignault, Ph

    2014-01-01

    In France, the Ecophyto 2018 national action plan will set out to reduce the use of pesticides by 50% by 2018, if possible. To achieve this goal, the use of arbuscular mycorrhizal (AM) fungi could be a potential alternative method allowing the control of crop diseases. The inoculation by AM fungi has been demonstrated to protect plants against soil-borne pathogens, but little is known about their effectiveness against aerial pathogens, such as the biotrophic fungus Blumeria graminis f.sp. tritici (Bgt) causing wheat (Triticum aestivum) powdery mildew. In the present study, wheat plants were grown in pots, under controlled conditions. Using various phosphorus (P) concentrations, the effectiveness of three AM inocula (Rhizophagus irregularis (Ri), Funneliformis mosseae (Fm)) and Solrize, a mixture of Ri and Fm) in Orvantis wheat cultivar, were tested. After 42 days of culture, mycorrhizal (M) and non-mycorrhizal (NM) wheat plants were infected by Bgt. A satisfactory mycorrhizal rate was obtained with the phosphorus concentration P/5 (P corresponding to the dose used in wheat fields in = 62 mg/L). Our work shows, for the first time, (i) a protective effect of AM inoculation against wheat powdery mildew, reaching up to 73% with Fm inocula, and (ii) its ability to induce a systemic resistance in wheat. Thereafter, we investigated mechanisms involved in this protection. Control plants, M plants, infected plants by Bgt, and M-infected plants were compared at: (i) cytological level, our results revealed that papillae and whole-fluorescent cells presence was induced, conversely fungal haustorium formation in epidermal cells was reduced within M plants leaves (ii) enzymatic level-by assessing defense enzyme activities (lipoxygenase, peroxidase) known as defense markers were measured 24, 48, 72 and 96 hours after infection (hai). The importance of these activities in the defense pathways induced in wheat by AM fungi will be discussed. PMID:26080475

  14. MECHANISMS INVOLVED IN MYCORRHIZAL WHEAT PROTECTION AGAINST POWDERY MILDEW.

    PubMed

    Mustafa, G; Tisserant, B; Randoux, B; Fontaine, J; Sahraoui, A Lounes-Hadj; Reignault, Ph

    2014-01-01

    In France, the Ecophyto 2018 national action plan will set out to reduce the use of pesticides by 50% by 2018, if possible. To achieve this goal, the use of arbuscular mycorrhizal (AM) fungi could be a potential alternative method allowing the control of crop diseases. The inoculation by AM fungi has been demonstrated to protect plants against soil-borne pathogens, but little is known about their effectiveness against aerial pathogens, such as the biotrophic fungus Blumeria graminis f.sp. tritici (Bgt) causing wheat (Triticum aestivum) powdery mildew. In the present study, wheat plants were grown in pots, under controlled conditions. Using various phosphorus (P) concentrations, the effectiveness of three AM inocula (Rhizophagus irregularis (Ri), Funneliformis mosseae (Fm)) and Solrize, a mixture of Ri and Fm) in Orvantis wheat cultivar, were tested. After 42 days of culture, mycorrhizal (M) and non-mycorrhizal (NM) wheat plants were infected by Bgt. A satisfactory mycorrhizal rate was obtained with the phosphorus concentration P/5 (P corresponding to the dose used in wheat fields in = 62 mg/L). Our work shows, for the first time, (i) a protective effect of AM inoculation against wheat powdery mildew, reaching up to 73% with Fm inocula, and (ii) its ability to induce a systemic resistance in wheat. Thereafter, we investigated mechanisms involved in this protection. Control plants, M plants, infected plants by Bgt, and M-infected plants were compared at: (i) cytological level, our results revealed that papillae and whole-fluorescent cells presence was induced, conversely fungal haustorium formation in epidermal cells was reduced within M plants leaves (ii) enzymatic level-by assessing defense enzyme activities (lipoxygenase, peroxidase) known as defense markers were measured 24, 48, 72 and 96 hours after infection (hai). The importance of these activities in the defense pathways induced in wheat by AM fungi will be discussed.

  15. Nutritional protective mechanisms against gut inflammation☆

    PubMed Central

    Viladomiu, Monica; Hontecillas, Raquel; Yuan, Lijuan; Lu, Pinyi; Bassaganya-Riera, Josep

    2013-01-01

    Inflammatory bowel disease (IBD) is a debilitating and widespread immune-mediated illness characterized by excessive inflammatory and effector mucosal responses leading to tissue destruction at the gastrointestinal tract. Interactions among the immune system, the commensal microbiota and the host genotype are thought to underlie the pathogenesis of IBD. However, the precise etiology of IBD remains unknown. Diet-induced changes in the composition of the gut microbiome can modulate the induction of regulatory versus effector immune responses at the gut mucosa and improve health outcomes. Therefore, manipulation of gut microbiota composition and the local production of microbial-derived metabolites by using prebiotics, probiotics and dietary fibers is being explored as a promising avenue of prophylactic and therapeutic intervention against gut inflammation. Prebiotics and fiber carbohydrates are fermented by resident microflora into short chain fatty acids (SCFAs) in the colon. SCFAs then activate peroxisome proliferator-activated receptor (PPAR)γ, a nuclear transcription factor with widely demonstrated anti-inflammatory efficacy in experimental IBD. The activation of PPARγ by naturally ocurring compounds such as conjugated linoleic acid, pomegranate seed oil-derived punicic acid, eleostearic acid and abscisic acid has been explored as nutritional interventions that suppress colitis by directly modulating the host immune response. The aim of this review is to summarize the status of innovative nutritional interventions against gastrointestinal inflammation, their proposed mechanisms of action, preclinical and clinical efficacy as well as bioinformatics and computational modeling approaches that accelerate discovery in nutritional and mucosal immunology research. PMID:23541470

  16. MECHANICS OF CRACK BRIDGING UNDER DYNAMIC LOADS

    SciTech Connect

    N. SRIDHAR; ET AL

    2001-02-01

    A bridging law for fiber reinforced composites under dynamic crack propagation conditions has been derived. Inertial effects in the mechanism of fiber pullout during dynamic propagation of a bridged crack are critically examined for the first time. By reposing simple shear lag models of pullout as problems of dynamic wave propagation, the effect of the frictional coupling between the fibers and the matrix is accounted for in a fairly straightforward way. The solutions yield the time-dependent relationship between the crack opening displacement and the bridging traction. Engineering criteria and the role of material and geometrical parameters for significant inertial effects are identified.

  17. Protein under tension and mechanical unfolding

    NASA Astrophysics Data System (ADS)

    Shen, Tongye; Canino, Larry; Wolynes, Peter G.; McCammon, J. Andrew

    2003-03-01

    The mechanical properties of proteins are important for a wide variety of functions ranging from stabilizing cellular structures to the transduction of signals across the membrane. We examined changes in protein conformation under external force fields by simple theoretical methods and new simulation techniques. The theoretical model solved a Gaussian chain plus native contact residue-level model under approximations. The simulations used the force ensemble replica exchange method and all-atom stochastic dynamics with a generalized Born plus solvent accessible surface as the solvation model. We applied these methods to study the protein spectrin as well as the domains of titin. Both global properties (such as energy and extension) and local roperties (especially, the specific contacts maintained and the secondary structure) are shown as functions of external force.

  18. Protective Mechanisms of Mitochondria and Heart Function in Diabetes

    PubMed Central

    Tocchetti, Carlo G.; Bhatt, Niraj; Paolocci, Nazareno; Cortassa, Sonia

    2015-01-01

    Abstract Significance: The heart depends on continuous mitochondrial ATP supply and maintained redox balance to properly develop force, particularly under increased workload. During diabetes, however, myocardial energetic-redox balance is perturbed, contributing to the systolic and diastolic dysfunction known as diabetic cardiomyopathy (DC). Critical Issues: How these energetic and redox alterations intertwine to influence the DC progression is still poorly understood. Excessive bioavailability of both glucose and fatty acids (FAs) play a central role, leading, among other effects, to mitochondrial dysfunction. However, where and how this nutrient excess affects mitochondrial and cytoplasmic energetic/redox crossroads remains to be defined in greater detail. Recent Advances: We review how high glucose alters cellular redox balance and affects mitochondrial DNA. Next, we address how lipid excess, either stored in lipid droplets or utilized by mitochondria, affects performance in diabetic hearts by influencing cardiac energetic and redox assets. Finally, we examine how the reciprocal energetic/redox influence between mitochondrial and cytoplasmic compartments shapes myocardial mechanical activity during the course of DC, focusing especially on the glutathione and thioredoxin systems. Future Directions: Protecting mitochondria from losing their ability to generate energy, and to control their own reactive oxygen species emission is essential to prevent the onset and/or to slow down DC progression. We highlight mechanisms enforced by the diabetic heart to counteract glucose/FAs surplus-induced damage, such as lipid storage, enhanced mitochondria-lipid droplet interaction, and upregulation of key antioxidant enzymes. Learning more on the nature and location of mechanisms sheltering mitochondrial functions would certainly help in further optimizing therapies for human DC. Antioxid. Redox Signal. 22, 1563–1586. PMID:25674814

  19. Deformation Mechanisms of Gum Metals Under Nanoindentation

    NASA Astrophysics Data System (ADS)

    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

  20. Integrated production and protection under protected cultivation in the Mediterranean region.

    PubMed

    Hanafi, A; Papasolomontos, A

    1999-09-01

    The article discusses some basic aspects of the integrated production and protection of horticultural crops, basically vegetables (e.g. tomatoes, cucumbers, peppers, eggplants, beans, etc.) and fruit trees (bananas), as well as flowers grown under cover in the Mediterranean region, namely Morocco, Syria, Lebanon, Egypt, Jordan, Tunisia, Cyprus, and Turkey.

  1. Rights to information access under the Data Protection Act.

    PubMed

    Dimond, Bridgit

    A patient has a legal right to access personal information held by health professionals on the basis of statutory provisions, such as the Data Protection Act 1998 and the regulations made under that Act, the Access to Health Reports Act 1988 (which is considered in a later article), and also on the basis of the common law, i.e. judge made or case law. Neither legal rights, however, give the patient an absolute right, but are qualified.

  2. Molecular mechanisms underlying chemical liver injury

    PubMed Central

    Gu, Xinsheng; Manautou, Jose E.

    2013-01-01

    The liver is necessary for survival. Its strategic localisation, blood flow and prominent role in the metabolism of xenobiotics render this organ particularly susceptible to injury by chemicals to which we are ubiquitously exposed. The pathogenesis of most chemical-induced liver injuries is initiated by the metabolic conversion of chemicals into reactive intermediate species, such as electrophilic compounds or free radicals, which can potentially alter the structure and function of cellular macromolecules. Many reactive intermediate species can produce oxidative stress, which can be equally detrimental to the cell. When protective defences are overwhelmed by excess toxicant insult, the effects of reactive intermediate species lead to deregulation of cell signalling pathways and dysfunction of biomolecules, leading to failure of target organelles and eventual cell death. A myriad of genetic factors determine the susceptibility of specific individuals to chemical-induced liver injury. Environmental factors, lifestyle choices and pre-existing pathological conditions also have roles in the pathogenesis of chemical liver injury. Research aimed at elucidating the molecular mechanism of the pathogenesis of chemical-induced liver diseases is fundamental for preventing or devising new modalities of treatment for liver injury by chemicals. PMID:22306029

  3. Deformation Mechanisms of Gum Metals Under Nanoindentation

    NASA Astrophysics Data System (ADS)

    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

  4. Two distinct neural mechanisms underlying indirect reciprocity.

    PubMed

    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.

  5. Two distinct neural mechanisms underlying indirect reciprocity

    PubMed Central

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

    2014-01-01

    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. PMID:24591599

  6. [Clinical significance of gastrointestinal decontamination under protected environment].

    PubMed

    Nagao, T; Yonekura, S; Komatsuda, M; Nozaki, H; Arimori, S; Sawamura, S; Ozawa, A; Sasaki, S

    1991-01-01

    Many infections are caused by the patient's own oro-intestinal microbial flora under a protected environment. Thirty-eight patients with acute leukemia and two patients with blast crisis of chronic myelocytic leukemia were treated under a protected environment with or without prophylactic antibiotics. Antibiotics used for decontamination were vancomycin (V), polymyxin B (P) and nystatin (N). The number of patients in the VPN, PN and the no antibiotic group were 13, 13 and 14, respectively. While the intestinal microbial flora was almost completely eliminated in VPN group, the number of bacteria decreased slightly in PN group. The mean number of pharyngeal and anorectal bacterial species decreased most markedly in the VPN group, but there were no significant differences among the three groups. The number of febrile days was significantly lower in the VPN and PN group than the no antibiotics group with neutrophil counts of less than 100 microliters. The average number of episodes of infection per patient was lowest in VPN group and highest in the no antibiotic group. These data indicate that VPN administration is effective for eliminating intestinal bacterial flora and resultantly protecting endogenous infections.

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

    PubMed

    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. PMID:22020792

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

    PubMed

    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.

  9. Epigenetic mechanisms underlying cardiac degeneration and regeneration*

    PubMed Central

    Chaturvedi, Pankaj; Tyagi, Suresh C.

    2014-01-01

    Epigenetic modifications which are defined by DNA methylation, histone modifications and microRNA mediated gene regulation, have been found to be associated with cardiac dysfunction and cardiac regeneration but the mechanisms are unclear. MicroRNA therapies have been proposed for cardiac regeneration and proliferation of stem cells into cardiomyocytes. Cardiovascular disorders are represented by abnormal methylation of CpG islands and drugs that inhibit DNA methyl transferases such as 5-methyl Aza cytidine are under trials. Histone modifications which include acetylation, methylation, phosphorylation, ADP ribosylation, sumoylation and biotinylation are represented within abnormal phenotypes of cardiac hypertrophy, cardiac development and contractility. MicroRNAs have been used efficiently to epigenetically reprogram fibroblasts into cardiomyocytes. MicroRNAs represent themselves as potential biomarkers for early detection of cardiac disorders which are difficult to diagnose and are captured at later stages. Because microRNAs regulate circadian genes, for example a nocturnin gene of circadian clockwork is regulated by mir122, they have profound role in regulating biological clock and this may explain the high cardiovascular risk during the morning time. This review highlights the role of epigenetics which can be helpful in disease management strategies. PMID:24636549

  10. Molecular Mechanisms Underlying Peritoneal EMT and Fibrosis

    PubMed Central

    Strippoli, Raffaele; Moreno-Vicente, Roberto; Battistelli, Cecilia; Cicchini, Carla; Noce, Valeria; Amicone, Laura; Marchetti, Alessandra; del Pozo, Miguel Angel; Tripodi, Marco

    2016-01-01

    Peritoneal dialysis is a form of renal replacement alternative to the hemodialysis. During this treatment, the peritoneal membrane acts as a permeable barrier for exchange of solutes and water. Continual exposure to dialysis solutions, as well as episodes of peritonitis and hemoperitoneum, can cause acute/chronic inflammation and injury to the peritoneal membrane, which undergoes progressive fibrosis, angiogenesis, and vasculopathy, eventually leading to discontinuation of the peritoneal dialysis. Among the different events controlling this pathological process, epithelial to mesenchymal transition of mesothelial cells plays a main role in the induction of fibrosis and in subsequent functional deterioration of the peritoneal membrane. Here, the main extracellular inducers and cellular players are described. Moreover, signaling pathways acting during this process are elucidated, with emphasis on signals delivered by TGF-β family members and by Toll-like/IL-1β receptors. The understanding of molecular mechanisms underlying fibrosis of the peritoneal membrane has both a basic and a translational relevance, since it may be useful for setup of therapies aimed at counteracting the deterioration as well as restoring the homeostasis of the peritoneal membrane. PMID:26941801

  11. Molecular Mechanisms Underlying Psychological Stress and Cancer.

    PubMed

    Shin, Kyeong Jin; Lee, Yu Jin; Yang, Yong Ryoul; Park, Seorim; Suh, Pann-Ghill; Follo, Matilde Yung; Cocco, Lucio; Ryu, Sung Ho

    2016-01-01

    Psychological stress is an emotion experienced when people are under mental pressure or encounter unexpected problems. Extreme or repetitive stress increases the risk of developing human disease, including cardiovascular disease (CVD), immune diseases, mental disorders, and cancer. Several studies have shown an association between psychological stress and cancer growth and metastasis in animal models and case studies of cancer patients. Stress induces the secretion of stress-related mediators, such as catecholamine, cortisol, and oxytocin, via the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis or the sympathetic nervous system (SNS). These stress-related hormones and neurotransmitters adversely affect stress-induced tumor progression and cancer therapy. Catecholamine is the primary factor that influences tumor progression. It can regulate diverse cellular signaling pathways through adrenergic receptors (ADRs), which are expressed by several types of cancer cells. Activated ADRs enhance the proliferation and invasion abilities of cancer cells, alter cell activity in the tumor microenvironment, and regulate the interaction between cancer and its microenvironment to promote tumor progression. Additionally, other stress mediators, such as glucocorticoids and oxytocin, and their cognate receptors are involved in stress-induced cancer growth and metastasis. Here, we will review how each receptor-mediated signal cascade contributes to tumor initiation and progression and discuss how we can use these molecular mechanisms for cancer therapy.

  12. Mechanical stability of trees under static loads.

    PubMed

    Peltola, Heli M

    2006-10-01

    Wind affects the structure and functioning of a forest ecosystem continuously and may cause significant economic loss in managed forests by reducing the yield of recoverable timber, increasing the cost of unscheduled thinning and clear-cuttings, and creating problems in forestry planning. Furthermore, broken and uprooted trees within the forest are subject to insect attack and may provide a suitable breeding substrate, endangering the remaining trees. Therefore, an improved understanding of the processes behind the occurrence of wind-induced damage is of interest to many forest ecologists, but may also help managers of forest resources to make appropriate management decisions related to risk management. Using fundamental physics, empirical experiments, and mechanistic model-based approaches in interaction, we can study the susceptibility of tree stands to wind damage as affected by the wind and site and tree/stand characteristics and management. Such studies are not possible based on statistical approaches alone, which are not able to define the causal links between tree parameters and susceptibility to wind damage. The aim of this paper is to review the recent work done related to tree-pulling and wind tunnel experiments and mechanistic modeling approaches to increase our understanding of the mechanical stability of trees under static loading.

  13. Memory repression: brain mechanisms underlying dissociative amnesia.

    PubMed

    Kikuchi, Hirokazu; Fujii, Toshikatsu; Abe, Nobuhito; Suzuki, Maki; Takagi, Masahito; Mugikura, Shunji; Takahashi, Shoki; Mori, Etsuro

    2010-03-01

    Dissociative amnesia usually follows a stressful event and cannot be attributable to explicit brain damage. It is thought to reflect a reversible deficit in memory retrieval probably due to memory repression. However, the neural mechanisms underlying this condition are not clear. We used fMRI to investigate neural activity associated with memory retrieval in two patients with dissociative amnesia. For each patient, three categories of face photographs and three categories of people's names corresponding to the photographs were prepared: those of "recognizable" high school friends who were acquainted with and recognizable to the patients, those of "unrecognizable" colleagues who were actually acquainted with but unrecognizable to the patients due to their memory impairments, and "control" distracters who were unacquainted with the patients. During fMRI, the patients were visually presented with these stimuli and asked to indicate whether they were personally acquainted with them. In the comparison of the unrecognizable condition with the recognizable condition, we found increased activity in the pFC and decreased activity in the hippocampus in both patients. After treatment for retrograde amnesia, the altered pattern of brain activation disappeared in one patient whose retrograde memories were recovered, whereas it remained unchanged in the other patient whose retrograde memories were not recovered. Our findings provide direct evidence that memory repression in dissociative amnesia is associated with an altered pattern of neural activity, and they suggest the possibility that the pFC has an important role in inhibiting the activity of the hippocampus in memory repression.

  14. Managing protected areas under climate change: challenges and priorities.

    PubMed

    Rannow, Sven; Macgregor, Nicholas A; Albrecht, Juliane; Crick, Humphrey Q P; Förster, Michael; Heiland, Stefan; Janauer, Georg; Morecroft, Mike D; Neubert, Marco; Sarbu, Anca; Sienkiewicz, Jadwiga

    2014-10-01

    The implementation of adaptation actions in local conservation management is a new and complex task with multiple facets, influenced by factors differing from site to site. A transdisciplinary perspective is therefore required to identify and implement effective solutions. To address this, the International Conference on Managing Protected Areas under Climate Change brought together international scientists, conservation managers, and decision-makers to discuss current experiences with local adaptation of conservation management. This paper summarizes the main issues for implementing adaptation that emerged from the conference. These include a series of conclusions and recommendations on monitoring, sensitivity assessment, current and future management practices, and legal and policy aspects. A range of spatial and temporal scales must be considered in the implementation of climate-adapted management. The adaptation process must be area-specific and consider the ecosystem and the social and economic conditions within and beyond protected area boundaries. However, a strategic overview is also needed: management at each site should be informed by conservation priorities and likely impacts of climate change at regional or even wider scales. Acting across these levels will be a long and continuous process, requiring coordination with actors outside the "traditional" conservation sector. To achieve this, a range of research, communication, and policy/legal actions is required. We identify a series of important actions that need to be taken at different scales to enable managers of protected sites to adapt successfully to a changing climate.

  15. Managing Protected Areas Under Climate Change: Challenges and Priorities

    NASA Astrophysics Data System (ADS)

    Rannow, Sven; Macgregor, Nicholas A.; Albrecht, Juliane; Crick, Humphrey Q. P.; Förster, Michael; Heiland, Stefan; Janauer, Georg; Morecroft, Mike D.; Neubert, Marco; Sarbu, Anca; Sienkiewicz, Jadwiga

    2014-10-01

    The implementation of adaptation actions in local conservation management is a new and complex task with multiple facets, influenced by factors differing from site to site. A transdisciplinary perspective is therefore required to identify and implement effective solutions. To address this, the International Conference on Managing Protected Areas under Climate Change brought together international scientists, conservation managers, and decision-makers to discuss current experiences with local adaptation of conservation management. This paper summarizes the main issues for implementing adaptation that emerged from the conference. These include a series of conclusions and recommendations on monitoring, sensitivity assessment, current and future management practices, and legal and policy aspects. A range of spatial and temporal scales must be considered in the implementation of climate-adapted management. The adaptation process must be area-specific and consider the ecosystem and the social and economic conditions within and beyond protected area boundaries. However, a strategic overview is also needed: management at each site should be informed by conservation priorities and likely impacts of climate change at regional or even wider scales. Acting across these levels will be a long and continuous process, requiring coordination with actors outside the "traditional" conservation sector. To achieve this, a range of research, communication, and policy/legal actions is required. We identify a series of important actions that need to be taken at different scales to enable managers of protected sites to adapt successfully to a changing climate.

  16. Managing protected areas under climate change: challenges and priorities.

    PubMed

    Rannow, Sven; Macgregor, Nicholas A; Albrecht, Juliane; Crick, Humphrey Q P; Förster, Michael; Heiland, Stefan; Janauer, Georg; Morecroft, Mike D; Neubert, Marco; Sarbu, Anca; Sienkiewicz, Jadwiga

    2014-10-01

    The implementation of adaptation actions in local conservation management is a new and complex task with multiple facets, influenced by factors differing from site to site. A transdisciplinary perspective is therefore required to identify and implement effective solutions. To address this, the International Conference on Managing Protected Areas under Climate Change brought together international scientists, conservation managers, and decision-makers to discuss current experiences with local adaptation of conservation management. This paper summarizes the main issues for implementing adaptation that emerged from the conference. These include a series of conclusions and recommendations on monitoring, sensitivity assessment, current and future management practices, and legal and policy aspects. A range of spatial and temporal scales must be considered in the implementation of climate-adapted management. The adaptation process must be area-specific and consider the ecosystem and the social and economic conditions within and beyond protected area boundaries. However, a strategic overview is also needed: management at each site should be informed by conservation priorities and likely impacts of climate change at regional or even wider scales. Acting across these levels will be a long and continuous process, requiring coordination with actors outside the "traditional" conservation sector. To achieve this, a range of research, communication, and policy/legal actions is required. We identify a series of important actions that need to be taken at different scales to enable managers of protected sites to adapt successfully to a changing climate. PMID:24722848

  17. A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis

    PubMed Central

    Marcoux, Julien; Mangione, P Patrizia; Porcari, Riccardo; Degiacomi, Matteo T; Verona, Guglielmo; Taylor, Graham W; Giorgetti, Sofia; Raimondi, Sara; Sanglier-Cianférani, Sarah; Benesch, Justin LP; Cecconi, Ciro; Naqvi, Mohsin M; Gillmore, Julian D; Hawkins, Philip N; Stoppini, Monica; Robinson, Carol V; Pepys, Mark B; Bellotti, Vittorio

    2015-01-01

    The mechanisms underlying transthyretin-related amyloidosis in vivo remain unclear. The abundance of the 49–127 transthyretin fragment in ex vivo deposits suggests that a proteolytic cleavage has a crucial role in destabilizing the tetramer and releasing the highly amyloidogenic 49–127 truncated protomer. Here, we investigate the mechanism of cleavage and release of the 49–127 fragment from the prototypic S52P variant, and we show that the proteolysis/fibrillogenesis pathway is common to several amyloidogenic variants of transthyretin and requires the action of biomechanical forces provided by the shear stress of physiological fluid flow. Crucially, the non-amyloidogenic and protective T119M variant is neither cleaved nor generates fibrils under these conditions. We propose that a mechano-enzymatic mechanism mediates transthyretin amyloid fibrillogenesis in vivo. This may be particularly important in the heart where shear stress is greatest; indeed, the 49–127 transthyretin fragment is particularly abundant in cardiac amyloid. Finally, we show that existing transthyretin stabilizers, including tafamidis, inhibit proteolysis-mediated transthyretin fibrillogenesis with different efficiency in different variants; however, inhibition is complete only when both binding sites are occupied. PMID:26286619

  18. A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis.

    PubMed

    Marcoux, Julien; Mangione, P Patrizia; Porcari, Riccardo; Degiacomi, Matteo T; Verona, Guglielmo; Taylor, Graham W; Giorgetti, Sofia; Raimondi, Sara; Sanglier-Cianférani, Sarah; Benesch, Justin L P; Cecconi, Ciro; Naqvi, Mohsin M; Gillmore, Julian D; Hawkins, Philip N; Stoppini, Monica; Robinson, Carol V; Pepys, Mark B; Bellotti, Vittorio

    2015-10-01

    The mechanisms underlying transthyretin-related amyloidosis in vivo remain unclear. The abundance of the 49-127 transthyretin fragment in ex vivo deposits suggests that a proteolytic cleavage has a crucial role in destabilizing the tetramer and releasing the highly amyloidogenic 49-127 truncated protomer. Here, we investigate the mechanism of cleavage and release of the 49-127 fragment from the prototypic S52P variant, and we show that the proteolysis/fibrillogenesis pathway is common to several amyloidogenic variants of transthyretin and requires the action of biomechanical forces provided by the shear stress of physiological fluid flow. Crucially, the non-amyloidogenic and protective T119M variant is neither cleaved nor generates fibrils under these conditions. We propose that a mechano-enzymatic mechanism mediates transthyretin amyloid fibrillogenesis in vivo. This may be particularly important in the heart where shear stress is greatest; indeed, the 49-127 transthyretin fragment is particularly abundant in cardiac amyloid. Finally, we show that existing transthyretin stabilizers, including tafamidis, inhibit proteolysis-mediated transthyretin fibrillogenesis with different efficiency in different variants; however, inhibition is complete only when both binding sites are occupied. PMID:26286619

  19. Mechanical protection of DLC films on fused silica slides

    NASA Technical Reports Server (NTRS)

    Nir, D.

    1985-01-01

    Measurements were made with a new test for improved quantitative estimation of the mechanical protection of thin films on optical materials. The mechanical damage was induced by a sand blasting system using spherical glass beads. Development of the surface damage was measured by the changes in the specular transmission and reflection, and by inspection using a surface profilometer and a scanning electron microscope. The changes in the transmittance versus the duration of sand blasting was measured for uncoated fused silica slides and coated ones. It was determined that the diamond like carbon films double the useful optical lifetime of the fused silica. Theoretical expressions were developed to describe the stages in surface deterioration. Conclusions were obtained for the SiO2 surface mechanism and for the film removal mechanism.

  20. Signaling mechanisms underlying metamorphic transitions in animals.

    PubMed

    Heyland, Andreas; Moroz, Leonid L

    2006-12-01

    Metamorphosis in many animal groups involves a radical transition from a larval to a juvenile/adult body plan and the challenge of orchestrating 2 overlapping developmental programs simultaneously, that is, larval development and juvenile development. Metamorphic competence directly precedes this radical change in morphology and can be best described as the developmental potential of a larva to undergo the radical transition in response to internal or external signals. Several studies have employed genomic approaches (for example, microarrays or subtractive hybridization methods) to gain insights into the complexity of changes in gene expression associated with metamorphic transitions. Availability of this technology for an increasing number of organisms from diverse taxonomic groups expands the scope of species for which we can gain detailed understanding of the genetic and epigenetic architecture underlying metamorphosis. Here, we review metamorphosis in insects, amphibians, and several marine invertebrate species including the sea hare Aplysia californica and summarize mechanisms underlying the transition. We conclude that all metamorphoses share at least 4 components: (1) the differentiation of juvenile/adult structures, (2) the degeneration of larval structures, (3) metamorphic competence, and (4) change in habitat. While transcription levels detected by microarray or other molecular methods can vary significantly, some similarities can be observed. For example, transcripts related to stress response, immunity, and apoptosis are associated with metamorphosis in all investigated phyla. It also appears that signaling mediated by hormones and by nitric oxide can contribute to these stress-related responses and that these molecules can act as regulators of metamorphic transitions. This might indicate either that all of these distantly related organisms inherited the same basic regulatory machinery that was employed by their most recent common ancestor (RCA) in

  1. Heliox Improves Carbon Dioxide Removal during Lung Protective Mechanical Ventilation.

    PubMed

    Beurskens, Charlotte J; Brevoord, Daniel; Lagrand, Wim K; van den Bergh, Walter M; Vroom, Margreeth B; Preckel, Benedikt; Horn, Janneke; Juffermans, Nicole P

    2014-01-01

    Introduction. Helium is a noble gas with low density and increased carbon dioxide (CO2) diffusion capacity. This allows lower driving pressures in mechanical ventilation and increased CO2 diffusion. We hypothesized that heliox facilitates ventilation in patients during lung-protective mechanical ventilation using low tidal volumes. Methods. This is an observational cohort substudy of a single arm intervention study. Twenty-four ICU patients were included, who were admitted after a cardiac arrest and mechanically ventilated for 3 hours with heliox (50% helium; 50% oxygen). A fixed protective ventilation protocol (6 mL/kg) was used, with prospective observation for changes in lung mechanics and gas exchange. Statistics was by Bonferroni post-hoc correction with statistical significance set at P < 0.017. Results. During heliox ventilation, respiratory rate decreased (25 ± 4 versus 23 ± 5 breaths min(-1), P = 0.010). Minute volume ventilation showed a trend to decrease compared to baseline (11.1 ± 1.9 versus 9.9 ± 2.1 L min(-1), P = 0.026), while reducing PaCO2 levels (5.0 ± 0.6 versus 4.5 ± 0.6 kPa, P = 0.011) and peak pressures (21.1 ± 3.3 versus 19.8 ± 3.2 cm H2O, P = 0.024). Conclusions. Heliox improved CO2 elimination while allowing reduced minute volume ventilation in adult patients during protective mechanical ventilation.

  2. Protective effect of Klebsiella bacteria on lawn grasses under conditions of soil salinization

    NASA Astrophysics Data System (ADS)

    Emtsev, V. T.; Sokolova, A. Ya.; Selitskaya, O. V.

    2010-07-01

    The protective effect of the inoculation of lawn grasses grown under conditions of soil salinization with bacteria of the Klebsiella genus ( K. planticola and K. pneumoniae) was demonstrated. It was found that K. pneumoniae improves the plant growth under conditions of a high concentration of sodium chloride. It was also shown that the inoculation of lawn grasses with these bacteria optimizes the morphophysiological parameters of the plants and increases the number of mitoses in the apical parts of the roots, which leads to a less significant decrease in the mitotic index under the impact of salinization. The capacity of K. planticola to penetrate into the plants may favor the activation of protective mechanisms improving the immunological status of the plants and, hence, their tolerance to salinization.

  3. A possible mechanism in DHEA-mediated protection against osteoarthritis.

    PubMed

    Li, Wei-Jun; Tang, Lu-Ping; Xiong, Yan; Chen, Wei-Ping; Zhou, Xin-Die; Ding, Qian-Hai; Wu, Li-Dong

    2014-11-01

    Dehydroepiandrosterone (DHEA) and its ester form, DHEA-S, are the most abundant steroids in human plasma. Our previous studies showed that DHEA protects against osteoarthritis (OA). The aim of this paper was to explore the possible mechanisms that underlie DHEA-mediated protection against OA. We tested the expression of β-catenin, it was increased significantly in OA. Rabbit cartilage was treated with various concentrations of DHEA in both IL-1β-induced rabbit chondrocytes and in rabbit cartilage from the anterior cruciate ligament transaction-induced OA model. We found DHEA decreased the expression of β-catenin. Then we further activated Wnt/β-catenin signaling by β-catenin transfection and inactivated it by the inhibitor Dickkopf1 in chondrocytes to reveal its role in the pathogenesis of OA. It turns out the protective effect of DHEA was significantly decreased when Wnt/β-catenin signaling was activated, while inactivating Wnt/β-catenin signaling enhanced the effects of DHEA. Therefore, we hypothesize that DHEA probably exerted its chondroprotective effect by regulating Wnt/β-catenin signaling. Our findings demonstrate the critical role of Wnt/β-catenin signaling in DHEA-mediated protection against OA. PMID:25065588

  4. Protective mechanisms of the common fibular nerve in and around the fibular tunnel: a new concept.

    PubMed

    El Gharbawy, Ramadan M; Skandalakis, Lee J; Skandalakis, John E

    2009-09-01

    The most frequent site at which the common fibular nerve is affected by compression, trauma, traction, masses, and surgery is within and around the fibular tunnel. The aim of this study was to determine whether there were protective mechanisms at this site that guard against compression of the nerve. Twenty-six lower limbs of 13 preserved adult cadavers (11 males and two females) were used. Proximal to the entrance of the tunnel, three anatomical configurations seemed to afford the required protection for the nerve: reinforcement of the deep fascia; tethering of the common fibular nerve to both the tendon of the biceps femoris and the reinforced fascia; and the particular arrangement of the deep fascia, fibular head, and soleus and gastrocnemius muscles. At the entrance of the tunnel, contraction of the first segment of fibularis longus muscle could afford the required protection. In the tunnel, contraction of the second and third segments of fibularis longus muscle could guard against compression of the nerve. The tough fascia on the surface of fibularis longus muscle and the fascial band within it, which have long been accused of compression of the nerve, may actually be elements of the protective mechanisms. We conclude that there are innate, anatomical protective mechanisms which should be taken into consideration when decompressing the common fibular nerve. To preserve these mechanisms whenever possible, the technique should be planned and varied according to the underlying etiology.

  5. Radiation-induced Cochlea hair cell death: mechanisms and protection.

    PubMed

    Tan, Pei-Xin; Du, Sha-Sha; Ren, Chen; Yao, Qi-Wei; Yuan, Ya-Wei

    2013-01-01

    Cochlea hair cell death is regarded to be responsible for the radiation-induced sensorineural hearing loss (SNHL), which is one of the principal complications of radiotherapy (RT) for head and neck cancers. In this mini- review, we focus on the current progresses trying to unravel mechanisms of radiation-induced hair cell death and find out possible protection. P53, reactive oxygen species (ROS) and c-Jun N-terminal kinase (JNK) pathways have been proposed as pivotal in the processes leading to radiation hair cell death. Potential protectants, such as amifostine, N-acetylcysteine (NAC) and epicatechin (EC) , are claimed to be effective at reducing radiation- inducedhair cell death. The RT dosage, selection and application of concurrent chemotherapy should be pre- examined in order to minimize the damage to cochlea hair cells.

  6. [Progress on cardiovascular protections and mechanism research of puerarin].

    PubMed

    Wei, Shu-yong

    2015-06-01

    Puerarin is one of the most important effective components of Pueraria lobata which exhibited classic estrogen-like biological activities and had remarkable cardiovascular protections in vivo and in vitro experiments. These protections of puerarin are mainly exhibited on improving the myocardial cells membrane potential and arrhythmia based on effecting the Na+, K+ , and Ca2+ channels,resisting myocardial fibrosis damage, diastolic effect on blood vessels, promoting angiogenesis, resisting calcification and atherosclerosis, improving blood flow, antiplatelet aggregation, reducing lipid and resisting diabetes. The main mechanisms are to improve the membrane potential and reduce cardiovascular damage caused by inflammation, oxidative stress and apoptosis, and the main regulated signal pathways are the PI3K/Akt, the NF-kappa B and the caspases. PMID:26591509

  7. Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism

    PubMed Central

    Wang, Tingting; Lin, Huajuan; Tu, Qian; Liu, Jingjing; Li, Xican

    2016-01-01

    Purpose: The paper tries to assess the protective effect of fisetin against •OH-induced DNA damage, then to investigate the possible mechanism. Methods: The protective effect was evaluated based on the content of malondialdehyde (MDA). The possible mechanism was analyzed using various antioxidant methods in vitro, including •OH scavenging (deoxyribose degradation), •O2- scavenging (pyrogallol autoxidation), DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays. Results: Fisetin increased dose-dependently its protective percentages against •OH-induced DNA damage (IC50 value =1535.00±29.60 µM). It also increased its radical-scavenging percentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in •OH scavenging, •O2- scavenging, DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays, were 47.41±4.50 µM, 34.05±0.87 µM, 9.69±0.53 µM, 2.43±0.14 µM, and 1.49±0.16 µM, respectively. Conclusion: Fisetin can effectively protect DNA against •OH-induced oxidative damage possibly via reactive oxygen species (ROS) scavenging approach, which is assumed to be hydrogen atom (H•) and/or single electron (e) donation (HAT/SET) pathways. In the HAT pathway, the 3’,4’-dihydroxyl moiety in B ring of fisetin is thought to play an important role, because it can be ultimately oxidized to a stable ortho-benzoquinone form. PMID:27478791

  8. 19 CFR 206.66 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... business information under administrative protective order. 206.66 Section 206.66 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO GLOBAL... certain confidential business information under administrative protective order. In an investigation...

  9. Parallel mechanisms suppress cochlear bone remodeling to protect hearing.

    PubMed

    Jáuregui, Emmanuel J; Akil, Omar; Acevedo, Claire; Hall-Glenn, Faith; Tsai, Betty S; Bale, Hrishikesh A; Liebenberg, Ellen; Humphrey, Mary Beth; Ritchie, Robert O; Lustig, Lawrence R; Alliston, Tamara

    2016-08-01

    Bone remodeling, a combination of bone resorption and formation, requires precise regulation of cellular and molecular signaling to maintain proper bone quality. Whereas osteoblasts deposit and osteoclasts resorb bone matrix, osteocytes both dynamically resorb and replace perilacunar bone matrix. Osteocytes secrete proteases like matrix metalloproteinase-13 (MMP13) to maintain the material quality of bone matrix through perilacunar remodeling (PLR). Deregulated bone remodeling impairs bone quality and can compromise hearing since the auditory transduction mechanism is within bone. Understanding the mechanisms regulating cochlear bone provides unique ways to assess bone quality independent of other aspects that contribute to bone mechanical behavior. Cochlear bone is singular in its regulation of remodeling by expressing high levels of osteoprotegerin. Since cochlear bone expresses a key PLR enzyme, MMP13, we examined whether cochlear bone relies on, or is protected from, osteocyte-mediated PLR to maintain hearing and bone quality using a mouse model lacking MMP13 (MMP13(-/-)). We investigated the canalicular network, collagen organization, lacunar volume via micro-computed tomography, and dynamic histomorphometry. Despite finding defects in these hallmarks of PLR in MMP13(-/-) long bones, cochlear bone revealed no differences in these markers, nor hearing loss as measured by auditory brainstem response (ABR) or distortion product oto-acoustic emissions (DPOAEs), between wild type and MMP13(-/-) mice. Dynamic histomorphometry revealed abundant PLR by tibial osteocytes, but near absence in cochlear bone. Cochlear suppression of PLR corresponds to repression of several key PLR genes in the cochlea relative to long bones. These data suggest that cochlear bone uniquely maintains bone quality and hearing independent of MMP13-mediated osteocytic PLR. Furthermore, the cochlea employs parallel mechanisms to inhibit remodeling by osteoclasts and osteoblasts, and by

  10. Mechanical Testing of Carbon Based Woven Thermal Protection Materials

    NASA Technical Reports Server (NTRS)

    Pham, John; Agrawal, Parul; Arnold, James O.; Peterson, Keith; Venkatapathy, Ethiraj

    2013-01-01

    Three Dimensional Woven thermal protection system (TPS) materials are one of the enabling technologies for mechanically deployable hypersonic decelerator systems. These materials have been shown capable of serving a dual purpose as TPS and as structural load bearing members during entry and descent operations. In order to ensure successful structural performance, it is important to characterize the mechanical properties of these materials prior to and post exposure to entry-like heating conditions. This research focuses on the changes in load bearing capacity of woven TPS materials after being subjected to arcjet simulations of entry heating. Preliminary testing of arcjet tested materials [1] has shown a mechanical degradation. However, their residual strength is significantly more than the requirements for a mission to Venus [2]. A systematic investigation at the macro and microstructural scales is reported here to explore the potential causes of this degradation. The effects of heating on the sizing (an epoxy resin coating used to reduce friction and wear during fiber handling) are discussed as one of the possible causes for the decrease in mechanical properties. This investigation also provides valuable guidelines for margin policies for future mechanically deployable entry systems.

  11. Changes in Benefits of Flood Protection Standard under Climate Change

    NASA Astrophysics Data System (ADS)

    Lim, W. H.; Koirala, S.; Yamazaki, D.; Hirabayashi, Y.; Kanae, S.

    2014-12-01

    Understanding potential risk of river flooding under future climate scenarios might be helpful for developing risk management strategies (including mitigation, adaptation). Such analyses are typically performed at the macro scales (e.g., regional, global) where the climate model output could support (e.g., Hirabayashi et al., 2013, Arnell and Gosling, 2014). To understand the potential benefits of infrastructure upgrading as part of climate adaptation strategies, it is also informative to understand the potential impact of different flood protection standards (in terms of return periods) on global river flooding under climate change. In this study, we use a baseline period (forced by observed hydroclimate conditions) and CMIP5 model output (historic and future periods) to drive a global river routing model called CaMa-Flood (Yamazaki et al., 2011) and simulate the river water depth at a spatial resolution of 15 min x 15 min. From the simulated results of baseline period, we use the annual maxima river water depth to fit the Gumbel distribution and prepare the return period-flood risk relationship (involving population and GDP). From the simulated results of CMIP5 model, we also used the annual maxima river water depth to obtain the Gumbel distribution and then estimate the exceedance probability (historic and future periods). We apply the return period-flood risk relationship (above) to the exceedance probability and evaluate the potential risk of river flooding and changes in the benefits of flood protection standard (e.g., 100-year flood of the baseline period) from the past into the future (represented by the representative concentration pathways). In this presentation, we show our preliminary results. References: Arnell, N.W, Gosling, S., N., 2014. The impact of climate change on river flood risk at the global scale. Climatic Change 122: 127-140, doi: 10.1007/s10584-014-1084-5. Hirabayashi et al., 2013. Global flood risk under climate change. Nature Climate

  12. The Mechanism Underlying Inhibition of Saccadic Return

    ERIC Educational Resources Information Center

    Ludwig, Casimir J. H.; Farrell, Simon; Ellis, Lucy A.; Gilchrist, Iain D.

    2009-01-01

    Human observers take longer to re-direct gaze to a previously fixated location. Although there has been some exploration of the characteristics of inhibition of saccadic return (ISR), the exact mechanisms by which ISR operates are currently unknown. In the framework of accumulation models of response times, in which evidence is integrated over…

  13. Mechanisms underlying an ability to behave ethically.

    PubMed

    Pfaff, Donald W; Kavaliers, Martin; Choleris, Elena

    2008-05-01

    Cognitive neuroscientists have anticipated the union of neural and behavioral science with ethics (Gazzaniga 2005). The identification of an ethical rule--the dictum that we should treat others in the manner in which we would like to be treated--apparently widespread among human societies suggests a dependence on fundamental human brain mechanisms. Now, studies of neural and molecular mechanisms that underlie the feeling of fear suggest how this form of ethical behavior is produced. Counterintuitively, a new theory presented here states that it is actually a loss of social information that leads to sharing others' fears with our own, thus allowing us to treat others as we would like to be treated. Adding to that hypothetical mechanism is the well-studied predilection toward affiliative behaviors. Thus, even as Chomsky hypothesizes that humans are predisposed to utter grammatical sentences, we propose that humans are 'wired for reciprocity'. However, these two neural forces supporting ethical behavior do not explain individual or collective violence. At any given moment, the ability to produce behavior that obeys this ethical rule is proposed to depend on a balance between mechanisms for prosocial and antisocial behaviors. That balance results not only from genetic influences on temperament but also from environmental effects particularly during critical neonatal and pubertal periods.

  14. Salvianolic acids: small compounds with multiple mechanisms for cardiovascular protection

    PubMed Central

    2011-01-01

    Salvianolic acids are the most abundant water-soluble compounds extracted from Radix Salvia miltiorrhiza (Danshen). In China, Danshen has been wildly used to treat cardiovascular diseases for hundreds of years. Salvianolic acids, especially salvianolic acid A (Sal A) and salvianolic acid B (Sal B), have been found to have potent anti-oxidative capabilities due to their polyphenolic structure. Recently, intracellular signaling pathways regulated by salvianolic acids in vascular endothelial cells, aortic smooth muscle cells, as well as cardiomyocytes, have been investigated both in vitro and in vivo upon various cardiovascular insults. It is discovered that the cardiovascular protection of salvianolic acids is not only because salvianolic acids act as reactive oxygen species scavengers, but also due to the reduction of leukocyte-endothelial adherence, inhibition of inflammation and metalloproteinases expression from aortic smooth muscle cells, and indirect regulation of immune function. Competitive binding of salvianolic acids to target proteins to interrupt protein-protein interactions has also been found to be a mechanism of cardiovascular protection by salvianolic acids. In this article, we review a variety of studies focusing on the above mentioned mechanisms. Besides, the target proteins of salvianolic acids are also described. These results of recent advances have shed new light to the development of novel therapeutic strategies for salvianolic acids to treat cardiovascular diseases. PMID:21569331

  15. Mechanism of protection by metallothionein against acetaminophen hepatotoxicity

    SciTech Connect

    Saito, Chieko; Yan, H.-M.; Artigues, Antonio; Villar, Maria T.; Farhood, Anwar; Jaeschke, Hartmut

    2010-01-15

    Acetaminophen (APAP) overdose is the most frequent cause of drug-induced liver failure in the US. Metallothionein (MT) expression attenuates APAP-induced liver injury. However, the mechanism of this protection remains incompletely understood. To address this issue, C57BL/6 mice were treated with 100 mumol/kg ZnCl{sub 2} for 3 days to induce MT. Twenty-four hours after the last dose of zinc, the animals received 300 mg/kg APAP. Liver injury (plasma ALT activities, area of necrosis), DNA fragmentation, peroxynitrite formation (nitrotyrosine staining), MT expression, hepatic glutathione (GSH), and glutathione disulfide (GSSG) levels were determined after 6 h. APAP alone caused severe liver injury with oxidant stress (increased GSSG levels), peroxynitrite formation, and DNA fragmentation, all of which were attenuated by zinc-induced MT expression. In contrast, MT knockout mice were not protected by zinc. Hydrogen peroxide-induced cell injury in primary hepatocytes was dependent only on the intracellular GSH levels but not on MT expression. Thus, the protective effect of MT in vivo was not due to the direct scavenging of reactive oxygen species. Zinc treatment had no effect on the early GSH depletion kinetics after APAP administration, which is an indicator of the metabolic activation of APAP to its reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). However, MT was able to effectively trap NAPQI by covalent binding. We conclude that MT scavenges some of the excess NAPQI after GSH depletion and prevents covalent binding to cellular proteins, which is the trigger for the propagation of the cell injury mechanisms through mitochondrial dysfunction and nuclear DNA damage.

  16. Cellular and molecular mechanisms underlying presynapse formation

    PubMed Central

    Chia, Poh Hui; Li, Pengpeng

    2013-01-01

    Synapse formation is a highly regulated process that requires the coordination of many cell biological events. Decades of research have identified a long list of molecular components involved in assembling a functioning synapse. Yet how the various steps, from transporting synaptic components to adhering synaptic partners and assembling the synaptic structure, are regulated and precisely executed during development and maintenance is still unclear. With the improvement of imaging and molecular tools, recent work in vertebrate and invertebrate systems has provided important insight into various aspects of presynaptic development, maintenance, and trans-synaptic signals, thereby increasing our understanding of how extrinsic organizers and intracellular mechanisms contribute to presynapse formation. PMID:24127213

  17. Mechanical stability of trees under dynamic loads.

    PubMed

    James, Kenneth R; Haritos, Nicholas; Ades, Peter K

    2006-10-01

    Tree stability in windstorms and tree failure are important issues in urban areas where there can be risks of damage to people and property and in forests where wind damage causes economic loss. Current methods of managing trees, including pruning and assessment of mechanical strength, are mainly based on visual assessment or the experience of people such as trained arborists. Only limited data are available to assess tree strength and stability in winds, and most recent methods have used a static approach to estimate loads. Recent research on the measurement of dynamic wind loads and the effect on tree stability is giving a better understanding of how different trees cope with winds. Dynamic loads have been measured on trees with different canopy shapes and branch structures including a palm (Washingtonia robusta), a slender Italian cypress (Cupressus sempervirens) and trees with many branches and broad canopies including hoop pine (Araucaria cunninghamii) and two species of eucalypt (Eucalyptus grandis, E. teretecornus). Results indicate that sway is not a harmonic, but is very complex due to the dynamic interaction of branches. A new dynamic model of a tree is described, incorporating the dynamic structural properties of the trunk and branches. The branch mass contributes a dynamic damping, termed mass damping, which acts to reduce dangerous harmonic sway motion of the trunk and so minimizes loads and increases the mechanical stability of the tree. The results from 12 months of monitoring sway motion and wind loading forces are presented and discussed.

  18. Mechanisms Underlying Early Medieval Droughts in Mesoamerica

    NASA Astrophysics Data System (ADS)

    Bhattacharya, T.; Chiang, J. C. H.

    2015-12-01

    Multidecadal drought during the early Medieval Climate Anomaly (MCA, 800-1200 CE) in Mesoamerica has been implicated in the demise of many pre-Columbian societies, including the Maya. The mechanisms behind these droughts, however, are poorly understood. Researchers most often interpret these records as tracking the mean position of the ITCZ, with a southward shifted ITCZ resulting in Mesoamerican drought. This is puzzling, however, because our dynamical understanding of the ITCZ and its role in interhemispheric heat transport would suggest a more northward shifted ITCZ during the MCA. Here, we evaluate two hypotheses to reconcile existing proxies and dynamics. First, we assess whether evidence for dry conditions during the MCA is robust across multiple Mesoamerican proxy records, focusing on the influence of radiometric dating uncertainty on estimates of drought timing. Second, we use control simulations of CCSM4 and HadCM3, as well as a broader synthesis of oceanic and terrestrial proxies, to explore the mechanisms responsible for long-term drought in Mesoamerica. Ultimately, we suggest that a temporary slowdown of the AMOC, either internally or externally forced, combined with local and regional land surface feedbacks can explain these droughts in Mesoamerica.

  19. 49 CFR 236.304 - Mechanical locking or same protection effected by circuits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Mechanical locking or same protection effected by..., AND APPLIANCES Interlocking Standards § 236.304 Mechanical locking or same protection effected by circuits. Mechanical locking, or the same protection effected by means of circuits, shall be provided....

  20. 49 CFR 236.304 - Mechanical locking or same protection effected by circuits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Mechanical locking or same protection effected by..., AND APPLIANCES Interlocking Standards § 236.304 Mechanical locking or same protection effected by circuits. Mechanical locking, or the same protection effected by means of circuits, shall be provided....

  1. 49 CFR 236.304 - Mechanical locking or same protection effected by circuits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Mechanical locking or same protection effected by..., AND APPLIANCES Interlocking Standards § 236.304 Mechanical locking or same protection effected by circuits. Mechanical locking, or the same protection effected by means of circuits, shall be provided....

  2. 49 CFR 236.304 - Mechanical locking or same protection effected by circuits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Mechanical locking or same protection effected by..., AND APPLIANCES Interlocking Standards § 236.304 Mechanical locking or same protection effected by circuits. Mechanical locking, or the same protection effected by means of circuits, shall be provided....

  3. 49 CFR 236.304 - Mechanical locking or same protection effected by circuits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Mechanical locking or same protection effected by..., AND APPLIANCES Interlocking Standards § 236.304 Mechanical locking or same protection effected by circuits. Mechanical locking, or the same protection effected by means of circuits, shall be provided....

  4. Environmental genotoxicity: Probing the underlying mechanisms

    SciTech Connect

    Shugart, L.; Theodorakis, C.

    1993-12-31

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

  5. Neural mechanisms underlying the evolvability of behaviour

    PubMed Central

    Katz, Paul S.

    2011-01-01

    The complexity of nervous systems alters the evolvability of behaviour. Complex nervous systems are phylogenetically constrained; nevertheless particular species-specific behaviours have repeatedly evolved, suggesting a predisposition towards those behaviours. Independently evolved behaviours in animals that share a common neural architecture are generally produced by homologous neural structures, homologous neural pathways and even in the case of some invertebrates, homologous identified neurons. Such parallel evolution has been documented in the chromatic sensitivity of visual systems, motor behaviours and complex social behaviours such as pair-bonding. The appearance of homoplasious behaviours produced by homologous neural substrates suggests that there might be features of these nervous systems that favoured the repeated evolution of particular behaviours. Neuromodulation may be one such feature because it allows anatomically defined neural circuitry to be re-purposed. The developmental, genetic and physiological mechanisms that contribute to nervous system complexity may also bias the evolution of behaviour, thereby affecting the evolvability of species-specific behaviour. PMID:21690127

  6. Duodenal mucosal protection by bicarbonate secretion and its mechanisms.

    PubMed

    Konturek, S J; Konturek, P C; Pawlik, T; Sliwowski, Z; Ochmański, W; Hahn, E G

    2004-07-01

    Proximal portion of duodenum is exposed to intermittent pulses of gastric H(+) discharged by the stomach. This review summarizes the mechanisms of duodenal mucosal integrity, mainly the role of mucus-alkaline secretion and the mucous barrier protecting surface epithelium against gastric H(+). The mucous barrier protects the leaky duodenal epithelium against each pulse of gastric H(+), which penetrates this barrier and diffuses into duodenocytes, but fails to damage them due to; a) an enhanced expression of cyclooxygenase-1 (COX-1), with release of protective prostaglandins (PG) and of nitric oxide (NO) synthase (NOS) with, however, production of NO, stimulating duodenal HCO(3)(-) secretion and b) the release of several neurotransmitters also stimulating HCO(3)(-) secretion such as vasoactive intestinal peptide (VIP), pituitary adenylate-cyclase activating polypeptide (PACAP), acetylcholine, melatonin, leptin and ghrelin released by enteric nerves and mucosal cells. At the apical duodenocyte membrane at least two HCO(3)(-)/Cl(-) anion exchangers operate in response to luminal H(+) to provide adequate extrusion of HCO(3)(-) into duodenal lumen. In the basolateral portion of duodenocyte membrane, both non-electrogenic (NBC) and electrogenic (NBC(n)) Na(+) HCO(3)(-) cotransporters are activated by the exposure to duodenal acidification, causing inward movement of HCO(3)(-) from extracellular fluid to duodenocytes. There are also at least three Na(+)/H(+) (NHE1-3) amiloride-sensitive exchangers, eliminating H(+)which diffused into these cells. The Helicobacter pylori (Hp) infection and gastric metaplasia in the duodenum with bacterium inoculating metaplastic mucosa and inhibiting HCO(3)(-) secretion by its endogenous inhibitor, asymmetric dimethyl arginine (ADMA), may result in duodenal ulcerogenesis. PMID:15608357

  7. [Elucidation of mechanisms underlying docosahexaenoic acid-induced antinociception].

    PubMed

    Nishinaka, Takashi; Matsumoto, Kengo; Nakamoto, Kazuo; Anbo, Akihiro; Mankura, Mitsumasa; Koyama, Yutaka; Tokuyama, Shogo

    2013-01-01

    Docosahexaenoic acid (DHA), a predominant of n-3 polyunsaturated fatty acids (n-3 PUFA), has numerous beneficial physiological effects, including neuroprotection and cardiovascular protection. Recently, a possible involvement of n-3 PUFA in pain control has gathered considerable attention because numerous studies have reported a regulatory role of n-3 PUFAs. However, the mechanisms underlying how DHA exerts antinociceptive effect remain unknown. Here, we performed elucidation of mechanisms underlying DHA-induced antinociception. DHA administration dose-dependently exerted an antinociceptive effect. This effect was abolished by pretreated with the β-funaltrexamine (β-FNA), a μ-opioid receptor antagonist, and the nartrindole (NTI), a δ-opioid receptor antagonist, but not by the nor-binaltorphimine (nor-BNI), a κ-opioid receptor antagonist. In the radioligand binding assay, DHA itself did not have the affinity for μ-, δ- and κ- opioid receptor. Furthermore, the pretreatment of anti β-endorphin antiserum inhibited DHA-induced antinociception. The plasma levels of β-endorphin increased 30 min after DHA administration. The β-endorphin immunoreactivity in the brain increased at 30 min after DHA treatment. Expression of GPR40 protein was widely observed in the brain as well as the spinal cord. The intracerebroventricular but not intrathecal injection of DHA and GW9508, a GPR40/GPR120 agonist, significantly reduced formalin-induced pain behavior. The β-endorphin immunoreactivity in the brain increased at 10 and 20 min after intracerebroventricular injection of DHA and GW9508. These findings suggest that DHA-induced antinociception via β-endorphin release may be mediated through GPR40 signaling in the supraspinal area. PMID:23649389

  8. Acetaminophen hepatotoxicity: studies on the mechanism of cysteamine protection

    SciTech Connect

    Miller, M.G.; Jollow, D.J.

    1986-03-30

    Inhibition of the cytochrome P-450-dependent formation of the acetaminophen-reactive metabolite was investigated as a possible mechanism for cysteamine protection against acetaminophen hepatotoxicity. Studies in isolated hamster hepatocytes indicated that cysteamine competitively inhibited the cytochrome P-450 enzyme system as represented by formation of the acetaminophen-glutathione conjugate. However, cysteamine was not a potent inhibitor of glutathione conjugate formation (Ki = 1.17 mM). Cysteamine also weakly inhibited the glucuronidation of acetaminophen (Ki = 2.44 mM). In vivo studies were in agreement with the results obtained in isolated hepatocytes; cysteamine moderately inhibited both glucuronidation and the cytochrome P-450-dependent formation of acetaminophen mercapturate. The overall elimination rate constant (beta) for acetaminophen was correspondingly decreased. Since cysteamine decreased both beta and the apparent rate constant for mercapturate formation (K'MA), the proportion of the dose of acetaminophen which is converted to the toxic metabolite (K'MA/beta) was not significantly decreased in the presence of cysteamine. Apparently, cysteamine does inhibit the cytochrome P-450-dependent formation of the acetaminophen-reactive metabolite, but this effect is not sufficient to explain antidotal protection.

  9. [Alcohol and cardiovascular system: mechanisms of the protective effects].

    PubMed

    Schlienger, J L

    2001-11-01

    Moderate and regularly alcohol consumption reduces death rate from coronary heart disease and thrombotic stroke. This beneficial correlation observed with several alcoholic beverages seems to be mainly due to an ethanol effect. However the particular role of microconstituants contained in red wine must be considered. The mechanism of the putative protective effect of alcohol intake is mediated through the elevation of HDL cholesterol and through the aintioxydative effect of polyphenolic compounds. In addition, alcohol acts favourably on platelets agregation, fibrinolysis and several other coagulation parameters. Despite these explanations are yet speculative and there is no causal relation between alcohol and reduced coronary death, epidemiological data are consistent with the belief that daily consumption of one or two glasses of an alcoholic beverage has salutary effect on health.

  10. V1 mechanisms underlying chromatic contrast detection

    PubMed Central

    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

  11. Changes of trabecular bone under control of biologically mechanical mechanism

    NASA Astrophysics Data System (ADS)

    Wang, C.; Zhang, C. Q.; Dong, X.; Wu, H.

    2008-10-01

    In this study, a biological process of bone remodeling was considered as a closed loop feedback control system, which enables bone to optimize and renew itself over a lifetime. A novel idea of combining strain-adaptive and damage-induced remodeling algorithms at Basic Multicellular Unit (BMU) level was introduced. In order to make the outcomes get closer to clinical observation, the stochastic occurrence of microdamage was involved and a hypothesis that remodeling activation probability is related to the value of damage rate was assumed. Integrated with Finite Element Analysis (FEA), the changes of trabecular bone in morphology and material properties were simulated in the course of five years. The results suggest that deterioration and anisotropy of trabecluar bone are inevitable with natural aging, and that compression rather than tension can be applied to strengthen the ability of resistance to fracture. This investigation helps to gain more insight the mechanism of bone loss and identify improved treatment and prevention for osteoporosis or stress fracture.

  12. [Neural Mechanisms Underlying the Face Inversion Effect].

    PubMed

    Sugase-Miyamoto, Yasuko; Matsumoto, Narihisa; Kawano, Kenji

    2015-10-01

    The ability to recognize faces is reduced with a picture-plane inversion of the faces, known as the face inversion effect. It has been reported that the configuration of facial features, for example, the distance between the eyes and mouth, becomes less perceptible when the face is inverted. In macaque monkeys, designated cortical areas, i.e., face patches, where face images are processed, have been found in the temporal visual cortex along the ventral visual pathway. Neurons in the anterior face patch (anterior part of the inferior temporal cortex) are known to encode view-invariant identity information. Thus, the anterior face patch is believed to be the final processing stage in the face patch system. A recent study showed that the face-inversion decreases the amount of the information about facial identity and facial expression conveyed by neurons, though it did not affect the information about the global category of the stimulus images (monkey versus human versus shape). The anterior face patch may, therefore, serve as the neural basis underlying the face inversion effect. PMID:26450075

  13. Light-Induced Ambient Degradation of Few-Layer Black Phosphorus: Mechanism and Protection.

    PubMed

    Zhou, Qionghua; Chen, Qian; Tong, Yilong; Wang, Jinlan

    2016-09-12

    The environmental instability of single- or few-layer black phosphorus (BP) has become a major hurdle for BP-based devices. The degradation mechanism remains unclear and finding ways to protect BP from degradation is still highly challenging. Based on ab initio electronic structure calculations and molecular dynamics simulations, a three-step picture on the ambient degradation of BP is provided: generation of superoxide under light, dissociation of the superoxide, and eventual breakdown under the action of water. The well-matched band gap and band-edge positions for the redox potential accelerates the degradation of thinner BP. Furthermore, it was found that the formation of P-O-P bonds can greatly stabilize the BP framework. A possible protection strategy using a fully oxidized BP layer as the native capping is thus proposed. Such a fully oxidization layer can resist corrosion from water and leave the BP underneath intact with simultaneous high hole mobility. PMID:27529543

  14. Light-Induced Ambient Degradation of Few-Layer Black Phosphorus: Mechanism and Protection.

    PubMed

    Zhou, Qionghua; Chen, Qian; Tong, Yilong; Wang, Jinlan

    2016-09-12

    The environmental instability of single- or few-layer black phosphorus (BP) has become a major hurdle for BP-based devices. The degradation mechanism remains unclear and finding ways to protect BP from degradation is still highly challenging. Based on ab initio electronic structure calculations and molecular dynamics simulations, a three-step picture on the ambient degradation of BP is provided: generation of superoxide under light, dissociation of the superoxide, and eventual breakdown under the action of water. The well-matched band gap and band-edge positions for the redox potential accelerates the degradation of thinner BP. Furthermore, it was found that the formation of P-O-P bonds can greatly stabilize the BP framework. A possible protection strategy using a fully oxidized BP layer as the native capping is thus proposed. Such a fully oxidization layer can resist corrosion from water and leave the BP underneath intact with simultaneous high hole mobility.

  15. Protecting quantum entanglement and nonlocality for tripartite states under decoherence

    NASA Astrophysics Data System (ADS)

    Zhang, Rui; Yin, Yu Hao; Ma, Wen Chao; Ye, Liu

    2016-06-01

    Quantum entanglement and nonlocality will suffer inevitable harm from decoherence environment. Based on GHZ state, we study the harm of the generalized amplitude damping (GAD) operation and the protection by the single local filtering (SLF) operation in this paper. We verify that the SLF functions to depress the loss of entanglement and nonlocality from GAD. This conclusion will guide us to select the best method to protect the GHZ state from GAD decoherence.

  16. Protective mechanism of quercetin on acute myocardial infarction in rats.

    PubMed

    Li, B; Yang, M; Liu, J W; Yin, G T

    2016-03-11

    To investigate the protective mechanism of quercetin on acute myocardial infarction (AMI) rats, an AMI rat model was established by ligating the left coronary anterior descending branch. The rats were randomly divided into the model group and low- and high-dose quercetin groups. The control group comprised sham-operated rats. The rats in the low- and high-dose quercetin groups were administered 100 and 400 mg/kg quercetin, respectively, by gavage. The rats in the control and model groups were administered isometric normal saline once daily for one week. The mRNA and protein levels of TNF-α and IL-1β in the myocardial tissue of rats were detected in each group by real time polymerase chain reaction and enzyme-linked immunosorbent assay. Malondialdehyde (MDA) content in the myocardial tissue and superoxide dismutase (SOD) and catalase (CAT) activities were detected using a colorimetric method. The level of apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. Compared with those in the control group, the mRNA and protein levels of TNF-α, IL-1β and MDA content in the model, low-, and high-dose groups significantly increased. SOD and CAT activities decreased significantly. The cell apoptosis index increased significantly  (P < 0.05). Compared with those in the model group, the mRNA and protein levels of TNF-α and IL-1β and MDA content in myocardial tissue of rats in the low-dose and high-dose groups decreased significantly. SOD and CAT activities increased significantly. The cell apoptosis index significantly reduced (P < 0.05). In conclusion, quercetin has significant anti-inflammatory, antioxidant, and anti-apoptotic effects on AMI rats and can effectively protect against myocardium damage.

  17. Mechanical cytoprotection: A review of cytoskeleton-protection approaches for cells.

    PubMed

    Gefen, Amit; Weihs, Daphne

    2016-05-24

    We review a class of cutting-edge approaches for cytoprotection of cells exposed to assaults such as sustained deformations, chemotherapy, radiotherapy, or ischemia. These approaches will enhance cell survival by mechanically protecting the structure and dynamics of the actin cytoskeleton (CSK). Cortical actin provides structural support to the plasma membrane (PM), protecting its integrity. Consequently, assaults can fragment the actin cortex leading to local, mechanical failure of the PM and poration of the cell. This disrupts normal trafficking of biomolecules across the PM, leading to loss of homeostasis and eventually, to cell death and tissue necrosis. Two different approaches to cytoskeletal protection are covered in this review paper. The first is to supply energy-related molecules to maintain and enhance the energy-consuming dynamics of the actin CSK. The second is to stabilize newly formed actin CSK directly¸ for example through cross-linking or reinforcement at PM anchoring sites. Research in this area is clearly still in its infancy. Very few studies have gone beyond characterizing the effects of induced damage to the actin CSK (and subsequent PM collapse). Recent work, focusing instead on sustaining the actin under non-physiological or pathophysiological conditions, has shown great promise. Such cytoskeletal-protection may find medical applications in preventing or minimizing tissue damage when tissues are unhealthy or at risk, or in enhancing cell performance under stress. Here, we condense the relevant cell biology and biomechanics background, assess candidate cytoskeletal protective agents, and review published works that have shown potential for medical benefit in experimental model systems. PMID:26549762

  18. The mechanisms of protection of antioxidants on Nostoc sphaeroides against UV-B radiation

    NASA Astrophysics Data System (ADS)

    Wang, G. H.

    UV radiation is one of space harmful factor for earth organisms in space exploration In the present work we studied on the role of antioxidant system in Nostoc sphaeroides K u tz Cyanobacteria and the effects of exogenous antioxidant molecules on its photosynthetic rate under UV-B radiation It was found that UV-B radiation decreased the photosynthetic activity of cyanobacterium but promoted the activity of antioxidant system to protect photosystem II PSII and exogenous antioxidant sodium nitroprusside SNP N-acetylcysteine NAC had an obvious protection on PSII activity under UV-B radiation The activity of SOD Superoxide Dismutase EC 1 15 1 1 CAT Catalase EC 1 11 1 6 POD Peroxidase EC 1 11 1 7 and content of MDA and ASC were improved by 0 5mM and 1mM SNP but 0 1mM SNP decreased the activity of antioxide system Exogenous NAC addition decreased the activity of SOD POD CAT and the content MDA and ASC but exogenous NAC addition increased the content of GSH The results suggested that exogenous SNP and NAC may protect algae by different mechanisms in which SNP maybe play double roles as sources of reactive free radicals or ROS scavengers in formation of algae s protection of PSII under UV-B radiation while NAC does function as antioxidant reagent or precursor of glutathione which could protect PSII directly from UV-B radiation Keyword antioxidant system exogenous or endogenous antioxidant Nostoc sphaeroides photosynthesis UV-B radiation

  19. Adaptive forest management for drinking water protection under climate change

    NASA Astrophysics Data System (ADS)

    Koeck, R.; Hochbichler, E.

    2012-04-01

    Drinking water resources drawn from forested catchment areas are prominent for providing water supply on our planet. Despite the fact that source waters stemming from forested watersheds have generally lower water quality problems than those stemming from agriculturally used watersheds, it has to be guaranteed that the forest stands meet high standards regarding their water protection functionality. For fulfilling these, forest management concepts have to be applied, which are adaptive regarding the specific forest site conditions and also regarding climate change scenarios. In the past century forest management in the alpine area of Austria was mainly based on the cultivation of Norway spruce, by the way neglecting specific forest site conditions, what caused in many cases highly vulnerable mono-species forest stands. The GIS based forest hydrotope model (FoHyM) provides a framework for forest management, which defines the most crucial parameters in a spatial explicit form. FoHyM stratifies the spacious drinking water protection catchments into forest hydrotopes, being operational units for forest management. The primary information layer of FoHyM is the potential natural forest community, which reflects the specific forest site conditions regarding geology, soil types, elevation above sea level, exposition and inclination adequately and hence defines the specific forest hydrotopes. For each forest hydrotope, the adequate tree species composition and forest stand structure for drinking water protection functionality was deduced, based on the plant-sociological information base provided by FoHyM. The most important overall purpose for the related elaboration of adaptive forest management concepts and measures was the improvement of forest stand stability, which can be seen as the crucial parameter for drinking water protection. Only stable forest stands can protect the fragile soil and humus layers and hence prevent erosion process which could endanger the water

  20. Plant protection under conditions of radioactive contamination of agricultural lands

    SciTech Connect

    Filipas, A.S.; Oulianenko, L.N.; Pimenov, E.P.

    1995-12-31

    Increasing influence of anthropogenic contaminants as well as substantiated risk of the action of ionizing radiation on agroecosystems suggest the necessity of studying both the state of separate components of cenosis and search for methods on retention of ecosystem stability as a whole. In this case it should be taken into account that by retention of resistance of living organisms to the action of stress agents not only genetically conditioned potential but induction of protective reactions at the expense of ecogene action is of deciding significance as well. Protection of agricultural plants on the territories subjected to radioactive contamination resulting from the ChNPP accident brings attention of research works to a series of problems, the main one being the minimization of pesticide use by the total ecologization of technological processes, in plant growing. But an ordinary discontinuance of conducting protective chemical measures leads to growth in the number of harmful organisms in crop sowings and as a consequence an increase of crop loss and decrease of its quality. It is possible to solve this problem by introduction of measures increasing the resistance of agricultural plants to the action of unfavorable factors of environment. Application of biologically active substances (BAS) of natural and synthetic nature for incrustation of seeds fits into these methods. For the territories with increased content of radionuclides and especially by their rehabilitation the methods of preventive treatments directed to retarding the development of harmful organisms in crop sowings and excluding subsequent technological operations on chemical protection of sowings takes on special significance as it is directly connected with the problem of radiation burden on workers of agroindustrial complex.

  1. Biochemical and immunological mechanisms by which sickle cell trait protects against malaria.

    PubMed

    Gong, Lauren; Parikh, Sunil; Rosenthal, Philip J; Greenhouse, Bryan

    2013-01-01

    Sickle cell trait (HbAS) is the best-characterized genetic polymorphism known to protect against falciparum malaria. Although the protective effect of HbAS against malaria is well known, the mechanism(s) of protection remain unclear. A number of biochemical and immune-mediated mechanisms have been proposed, and it is likely that multiple complex mechanisms are responsible for the observed protection. Increased evidence for an immune component of protection as well as novel mechanisms, such as enhanced tolerance to disease mediated by HO-1 and reduced parasitic growth due to translocation of host micro-RNA into the parasite, have recently been described. A better understanding of relevant mechanisms will provide valuable insight into the host-parasite relationship, including the role of the host immune system in protection against malaria. PMID:24025776

  2. The Challenge of Characterizing Operations in the Mechanisms Underlying Behavior

    ERIC Educational Resources Information Center

    Bechtel, William

    2005-01-01

    Neuroscience and cognitive science seek to explain behavioral regularities in terms of underlying mechanisms. An important element of a mechanistic explanation is a characterization of the operations of the parts of the mechanism. The challenge in characterizing such operations is illustrated by an example from the history of physiological…

  3. 28 CFR 200.1 - Eligibility for Protection under the Convention Against Torture.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Eligibility for Protection under the Convention Against Torture. 200.1 Section 200.1 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) ALIEN TERRORIST REMOVAL PROCEDURES § 200.1 Eligibility for Protection under the Convention...

  4. 28 CFR 200.1 - Eligibility for Protection under the Convention Against Torture.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Eligibility for Protection under the Convention Against Torture. 200.1 Section 200.1 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) ALIEN TERRORIST REMOVAL PROCEDURES § 200.1 Eligibility for Protection under the Convention...

  5. 28 CFR 200.1 - Eligibility for Protection under the Convention Against Torture.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Eligibility for Protection under the Convention Against Torture. 200.1 Section 200.1 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) ALIEN TERRORIST REMOVAL PROCEDURES § 200.1 Eligibility for Protection under the Convention...

  6. 28 CFR 200.1 - Eligibility for Protection under the Convention Against Torture.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Eligibility for Protection under the Convention Against Torture. 200.1 Section 200.1 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) ALIEN TERRORIST REMOVAL PROCEDURES § 200.1 Eligibility for Protection under the Convention...

  7. 28 CFR 200.1 - Eligibility for Protection under the Convention Against Torture.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Eligibility for Protection under the Convention Against Torture. 200.1 Section 200.1 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) ALIEN TERRORIST REMOVAL PROCEDURES § 200.1 Eligibility for Protection under the Convention...

  8. 75 FR 66385 - Protecting Tenants at Foreclosure Act: Guidance on Notification Responsibilities Under the Act...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-28

    ... URBAN DEVELOPMENT Protecting Tenants at Foreclosure Act: Guidance on Notification Responsibilities Under the Act With Respect to Occupied Conveyance AGENCY: Office of the Assistant Secretary for Housing... existing tenants under the Protecting Tenants at Foreclosure Act of 2009 (PTFA). FHA's existing...

  9. The Intricate Interplay between Mechanisms Underlying Aging and Cancer.

    PubMed

    Piano, Amanda; Titorenko, Vladimir I

    2015-02-01

    Age is the major risk factor in the incidence of cancer, a hyperplastic disease associated with aging. Here, we discuss the complex interplay between mechanisms underlying aging and cancer as a reciprocal relationship. This relationship progresses with organismal age, follows the history of cell proliferation and senescence, is driven by common or antagonistic causes underlying aging and cancer in an age-dependent fashion, and is maintained via age-related convergent and divergent mechanisms. We summarize our knowledge of these mechanisms, outline the most important unanswered questions and suggest directions for future research.

  10. Mechanisms of Nattokinase in protection of cerebral ischemia.

    PubMed

    Ji, Hongrui; Yu, Liang; Liu, Keyu; Yu, Zhigang; Zhang, Qian; Zou, Fengjuan; Liu, Bo

    2014-12-15

    In vivo, the level of cyclic Adenosine Monophosphate (cAMP) and the pathway of the Janus Kinase1/Signal Transducers and Activators of Transcription1 (JAK1/STAT1) were studied. In vitro, the Ca(2+) mobilization in human platelet stimulated by thrombin was observed. In addition, vasomotion of vascular smooth muscle was measured by adding KCl or norepinephrine(NE) under the Ca(2+) contained bath solutions. The effect induced by NE in the presence of N-nitro-L-arginine methyl ester (L-NAME) or indometacin (Indo) was also detected. At last, the levels of tissue plasminogen activator (t-PA) and Plasminogen activator inhibitor-1 (PAI-1) in cultured supernatans in Human umbilical vein endothelial cells (Huvecs) were measured by means of ELISA kit. Results showed that Nattokinase (NK) significantly increased the cAMP level, activated the signal passage of JAK1/STAT1 in injured part and inhibited remarkably the rise of platelet intracellular Ca(2+) ([Ca(2+)]i) in human platelet. Furthermore, NK relaxed rat thoracic aortic artery in the dose-dependent manner and in the endothelium dependent manner and its effect could be attenuated by L-NAME. Also, the secretion of t-PA and PAI-1 were reduced stimulated by Adr on Huvecs. These data indicated that the neuroprotective effect of NK was associated with its antiplatelet activity by elevating cAMP level and attenuating the calcium release from calcium stores; with its anti-apoptotic effect through the activation of JAK1/STAT1 pathway; with its relaxing vascular smooth muscle by promoting synthesis and release of NO, reducing ROC calcium ion influx and with its protection on endothelial cells through increasing fibrinolytic activity and facilitating spontaneous thrombolysis.

  11. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM)-Mediated Protection of Ischemic Brain

    PubMed Central

    Lin, Chi-Hsin; Wang, Chen-Hsuan; Hsu, Shih-Lan; Liao, Li-Ya; Lin, Ting-An; Hsueh, Chi-Mei

    2016-01-01

    The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation. PMID:26745377

  12. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM)-Mediated Protection of Ischemic Brain.

    PubMed

    Lin, Chi-Hsin; Wang, Chen-Hsuan; Hsu, Shih-Lan; Liao, Li-Ya; Lin, Ting-An; Hsueh, Chi-Mei

    2016-01-01

    The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation. PMID:26745377

  13. Formation mechanism of the graphite-rich protective layer in blast furnace hearths

    NASA Astrophysics Data System (ADS)

    Jiao, Ke-xin; Zhang, Jian-liang; Liu, Zheng-jian; Liu, Feng; Liang, Li-sheng

    2016-01-01

    A long campaign life of blast furnaces is heavily linked to the existence of a protective layer in their hearths. In this work, we conducted dissection studies and investigated damage in blast furnace hearths to estimate the formation mechanism of the protective layer. The results illustrate that a significant amount of graphite phase was trapped within the hearth protective layer. Furthermore, on the basis of the thermodynamic and kinetic calculations of the graphite precipitation process, a precipitation potential index related to the formation of the graphite-rich protective layer was proposed to characterize the formation ability of this layer. We determined that, under normal operating conditions, the precipitation of graphite phase from hot metal was thermodynamically possible. Among elements that exist in hot metal, C, Si, and P favor graphite precipitation, whereas Mn and Cr inhibit this process. Moreover, at the same hot-face temperature, an increase of carbon concentration in hot metal can shorten the precipitation time. Finally, the results suggest that measures such as reducing the hot-face temperature and increasing the degree of carbon saturation in hot metal are critically important to improve the precipitation potential index.

  14. Hydrogen Assisted Crack in Dissimilar Metal Welds for Subsea Service under Cathodic Protection

    NASA Astrophysics Data System (ADS)

    Bourgeois, Desmond

    Dissimilar metal welds (DMWs) are routinely used in the oil and gas industries for structural joining of high strength steels in order to eliminate the need for post weld heat treatment (PWHT) after field welding. There have been reported catastrophic failures in these DMWs, particularly the AISI 8630 steel - Alloy 625 DMW combination, during subsea service while under cathodic protection (CP). This is due to local embrittlement that occurs in susceptible microstructures that are present at the weld fusion boundary region. This type of cracking is known as hydrogen assisted cracking (HAC) and it is influenced by base/filler metal combination, and welding and PWHT procedures. DMWs of two material combinations (8630 steel -- Alloy 625 and F22 steel -- Alloy 625), produced with two welding procedures (BS1 and BS3) in as welded and PWHT conditions were investigated in this study. The main objectives included: 1) evaluation of the effect of materials composition, welding and PWHT procedures on the gradients of composition, microstructure, and properties in the dissimilar transition region and on the susceptibility to HAC; 2) investigation of the influence of microstructure on the HAC failure mechanism and identification of microstructural constituents acting as crack nucleation and propagation sites; 3) assessment of the applicability of two-step PWHT to improve the resistance to HAC in DMWs; 4) establishment of non-failure criterion for the delayed hydrogen cracking test (DHCT) that is applicable for qualification of DMWs for subsea service under cathodic protection (CP).

  15. Modeling of fracture of protective concrete structures under impact loads

    NASA Astrophysics Data System (ADS)

    Radchenko, P. A.; Batuev, S. P.; Radchenko, A. V.; Plevkov, V. S.

    2015-10-01

    This paper presents results of numerical simulation of interaction between a Boeing 747-400 aircraft and the protective shell of a nuclear power plant. The shell is presented as a complex multilayered cellular structure consisting of layers of concrete and fiber concrete bonded with steel trusses. Numerical simulation was performed three-dimensionally using the original algorithm and software taking into account algorithms for building grids of complex geometric objects and parallel computations. Dynamics of the stress-strain state and fracture of the structure were studied. Destruction is described using a two-stage model that allows taking into account anisotropy of elastic and strength properties of concrete and fiber concrete. It is shown that wave processes initiate destruction of the cellular shell structure; cells start to destruct in an unloading wave originating after the compression wave arrival at free cell surfaces.

  16. Modeling of fracture of protective concrete structures under impact loads

    SciTech Connect

    Radchenko, P. A. Batuev, S. P.; Radchenko, A. V.; Plevkov, V. S.

    2015-10-27

    This paper presents results of numerical simulation of interaction between a Boeing 747-400 aircraft and the protective shell of a nuclear power plant. The shell is presented as a complex multilayered cellular structure consisting of layers of concrete and fiber concrete bonded with steel trusses. Numerical simulation was performed three-dimensionally using the original algorithm and software taking into account algorithms for building grids of complex geometric objects and parallel computations. Dynamics of the stress-strain state and fracture of the structure were studied. Destruction is described using a two-stage model that allows taking into account anisotropy of elastic and strength properties of concrete and fiber concrete. It is shown that wave processes initiate destruction of the cellular shell structure; cells start to destruct in an unloading wave originating after the compression wave arrival at free cell surfaces.

  17. [Secondary traumatization while under care of child protective services].

    PubMed

    Schmitt, A

    1999-01-01

    Quality management is in everybody's mouth. Actually there is only few evaluation research in child protection, and almost no evaluated practice. The paper takes a perspective of "errors", not of "effectiveness". It roughly assesses the frequency of secondary traumas maltreated children experience when they are in care of the helping system. Examples and statistics from the "Vienna Child Protection Center" are used. The client's risk of experiencing a secondary trauma is about 1:3. In about 10% of all cases, the traumas are important and enduring; they range from psychotic episode to massive suicidality and long-lasting feelings of guilt and anxiety. Comparatively, the risk of being traumatized by psychotherapy is about 1:6. Psychotherapy leads to important and positive changes in about one third of all clients; similar effectiveness is attributed to those helping maltreated children. Causes of secondary traumas are: Helpers act too quickly in the heat of affect; they lack specialized knowledge (e.g. self-experience, crisis management); they seldom consult with neutral experts; they have few insight in the effects of their ideological and ethical back-ground; they deal with clients in a distrust enhancing way. On the structural level, I discuss sensationalism and scandalism of massmedia; bureaucratic procedures and their slowness, unaccessibility, inconsistency and indifference to the single case; policy of damage control when errors of the helping system become public; parallelism of decreasing financial/personal support and increasing numbers of customers; badly organized practice in criminal justice. The paper ends by demanding (more) quality circles and supervision. PMID:10500408

  18. Mechanisms of radio-protection by catecholamines in the hamster /Mesocricetus auratus/

    NASA Technical Reports Server (NTRS)

    Prewitt, R. L.; Musacchia, X. J.

    1975-01-01

    Experiments were conducted on normal and splenectomized male and female hamsters between 2 and 3 months old subjected to a whole-body exposure of 1000 or 2000 rads in a Co-60 source with a view toward evaluating their radio-protection by norepinephrine, isoproterenol, and phenylephrine. Vasoconstriction hypoxia mechanism of radio-protection is examined along with the hypothesis that isoproterenol protects by hypercalcemia-induced cell proliferation. Radiation experiment results are found to be consistent with the hypothesis that stimulation of alpha receptors results in radio-protection through a tissue hypoxia mechanism. Beta agonists seem to protect by a hypotensive-hypoxia mechanism. The catecholamines protect against the hematopoietic syndrome, but show no evidence of protection against the gastrointestinal syndrome.

  19. Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile.

    PubMed

    Xia, Kang; Zhan, Haifei; Hu, De'an; Gu, Yuantong

    2016-01-01

    The excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft.

  20. Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile

    PubMed Central

    Xia, Kang; Zhan, Haifei; Hu, De’an; Gu, Yuantong

    2016-01-01

    The excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft. PMID:27618989

  1. Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile

    NASA Astrophysics Data System (ADS)

    Xia, Kang; Zhan, Haifei; Hu, De’An; Gu, Yuantong

    2016-09-01

    The excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft.

  2. Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile.

    PubMed

    Xia, Kang; Zhan, Haifei; Hu, De'an; Gu, Yuantong

    2016-01-01

    The excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft. PMID:27618989

  3. Common Practice Lightning Strike Protection Characterization Technique to Quantify Damage Mechanisms on Composite Substrates

    NASA Technical Reports Server (NTRS)

    Szatkowski, George N.; Dudley, Kenneth L.; Koppen, Sandra V.; Ely, Jay J.; Nguyen, Truong X.; Ticatch, Larry A.; Mielnik, John J.; Mcneill, Patrick A.

    2013-01-01

    To support FAA certification airworthiness standards, composite substrates are subjected to lightning direct-effect electrical waveforms to determine performance characteristics of the lightning strike protection (LSP) conductive layers used to protect composite substrates. Test results collected from independent LSP studies are often incomparable due to variability in test procedures & applied practices at different organizations, which impairs performance correlations between different LSP data sets. Under a NASA supported contract, The Boeing Company developed technical procedures and documentation as guidance in order to facilitate a test method for conducting universal common practice lightning strike protection test procedures. The procedures obtain conformity in future lightning strike protection evaluations to allow meaningful performance correlations across data sets. This universal common practice guidance provides the manufacturing specifications to fabricate carbon fiber reinforced plastic (CFRP) test panels, including finish, grounding configuration, and acceptable methods for pretest nondestructive inspection (NDI) and posttest destructive inspection. The test operations guidance elaborates on the provisions contained in SAE ARP5416 to address inconsistencies in the generation of damage protection performance data, so as to provide for maximum achievable correlation across capable lab facilities. In addition, the guidance details a direct effects test bed design to aid in quantification of the multi-physical phenomena surrounding a lightning direct attachment supporting validation data requirements for the development of predictive computational modeling. The lightning test bed is designed to accommodate a repeatable installation procedure to secure the test panel and eliminate test installation uncertainty. It also facilitates a means to capture the electrical waveform parameters in 2 dimensions, along with the mechanical displacement and thermal

  4. Mechanical annealing under low-amplitude cyclic loading in micropillars

    NASA Astrophysics Data System (ADS)

    Cui, Yi-nan; Liu, Zhan-li; Wang, Zhang-jie; Zhuang, Zhuo

    2016-04-01

    Mechanical annealing has been demonstrated to be an effective method for decreasing the overall dislocation density in submicron single crystal. However, simultaneously significant shape change always unexpectedly happens under extremely high monotonic loading to drive the pre-existing dislocations out of the free surfaces. In the present work, through in situ TEM experiments it is found that cyclic loading with low stress amplitude can drive most dislocations out of the submicron sample with virtually little change of the shape. The underlying dislocation mechanism is revealed by carrying out discrete dislocation dynamic (DDD) simulations. The simulation results indicate that the dislocation density decreases within cycles, while the accumulated plastic strain is small. By comparing the evolution of dislocation junction under monotonic, cyclic and relaxation deformation, the cumulative irreversible slip is found to be the key factor of promoting junction destruction and dislocation annihilation at free surface under low-amplitude cyclic loading condition. By introducing this mechanics into dislocation density evolution equations, the critical conditions for mechanical annealing under cyclic and monotonic loadings are discussed. Low-amplitude cyclic loading which strengthens the single crystal without seriously disturbing the structure has the potential applications in the manufacture of defect-free nano-devices.

  5. The protective effects of temporary immunity under imposed infection pressure.

    PubMed

    Swart, A N; Tomasi, M; Kretzschmar, M; Havelaar, A H; Diekmann, O

    2012-03-01

    The aim of this paper is to show in explicit detail that, due to the effects of waning and boosting of immunity, an increasing force of infection does not necessarily lead to an increase in the incidence of disease. Under certain conditions, a decrease of the force of infection may in fact lead to an increase of the incidence of disease. Thus we confirm and reinforce the conclusions from Águas et al. (2006), concerning pertussis. We do so, however, in the context of Campylobacter infections in humans deriving from animal reservoirs. For such an externally 'driven' epidemic we can ignore the transmission feedback cycle and treat the force of infection as a parameter. As this parameter is, to a certain extent, under public health control, our findings constitute an important warning: reducing exposure may not necessarily lead to a reduction in the occurrence of clinical illness. In a second part of the paper we relate the model parameters to the available data concerning campylobacteriosis.

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

    PubMed

    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.

  7. Fostering Resilience: Protective Agents, Resources, and Mechanisms for Adolescent Refugees’ Psychosocial Well-Being

    PubMed Central

    Weine, Stevan Merrill; Ware, Norma; Hakizimana, Leonce; Tugenberg, Toni; Currie, Madeleine; Dahnweih, Gonwo; Wagner, Maureen; Polutnik, Chloe; Wulu, Jacqueline

    2014-01-01

    Background Adolescent refugees face many challenges but also have the potential to become resilient. The purpose of this study was to identify and characterize the protective agents, resources, and mechanisms that promote their psychosocial well-being. Methods Participants included a purposively sampled group of 73 Burundian and Liberian refugee adolescents and their families who had recently resettled in Boston and Chicago. The adolescents, families, and their service providers participated in a two-year longitudinal study using ethnographic methods and grounded theory analysis with Atlas/ti software. A grounded theory model was developed which describes those persons or entities who act to protect adolescents (Protective Agents), their capacities for doing so (Protective Resources), and how they do it (Protective Mechanisms). Protective agents are the individuals, groups, organizations, and systems that can contribute either directly or indirectly to promoting adolescent refugees’ psychosocial well-being. Protective resources are the family and community capacities that can promote psychosocial well-being in adolescent refugees. Protective mechanisms are the processes fostering adolescent refugees’ competencies and behaviors that can promote their psychosocial well-being. Results Eight family and community capacities were identified that appeared to promote psychosocial well-being in the adolescent refugees. These included 1) finances for necessities; 2) English proficiency; 3) social support networks; 4) engaged parenting; 5) family cohesion; 6) cultural adherence and guidance; 7) educational support; and 8) faith and religious involvement. Nine protective mechanisms identified were identified and grouped into three categories: 1) Relational (supporting, connecting, belonging); 2) Informational (informing, preparing), and; 3) Developmental (defending, promoting, adapting). Conclusions To further promote the psychosocial well-being of adolescent refugees

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

    SciTech Connect

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

    2014-05-15

    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.

  9. Mechanical Isolation of Highly Stable Antimonene under Ambient Conditions.

    PubMed

    Ares, Pablo; Aguilar-Galindo, Fernando; Rodríguez-San-Miguel, David; Aldave, Diego A; Díaz-Tendero, Sergio; Alcamí, Manuel; Martín, Fernando; Gómez-Herrero, Julio; Zamora, Félix

    2016-08-01

    Antimonene fabricated by mechanical exfoliation is highly stable under atmospheric conditions over periods of months and even when immersed in water. Density functional theory confirms the experiments and predicts an electronic gap of ≈1 eV. These results highlight the use of antimonene for optoelectronics applications. PMID:27272099

  10. Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

    ERIC Educational Resources Information Center

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

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

  11. 77 FR 5241 - No FEAR Act Notice; Notice of Rights and Protections Available Under the Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ... PROTECTION No FEAR Act Notice; Notice of Rights and Protections Available Under the Federal... Antidiscrimination and Retaliation Act (No FEAR Act), as implemented by Office of Personnel Management (OPM... Employee Antidiscrimination and Retaliation Act of 2002 (No FEAR Act), Public Law 107-174, 116 Stat. 566...

  12. Protective effects of geniposide against Tripterygium glycosides (TG)-induced liver injury and its mechanisms.

    PubMed

    Wang, Junming; Miao, Mingsan; Qu, Lingbo; Cui, Ying; Zhang, Yueyue

    2016-02-01

    Tripterygium glycosides (TG) are commonly used for basic medicine in curing rheumatoid arthritis but with a high incidence of liver injury. Geniposide (GP) has broad and diverse bioactivities, but until now it is still unknown whether GP can protect against TG-induced liver injury. This study, for the first time, observed the possible protection of GP against TG-induced liver injury in mice and its mechanisms underlying. Oral administration of TG (270 mg/kg) induced significant elevation in the levels of serum alanine / aspartate transaminase (ALT/AST), hepatic malondialdehyde (MDA) and pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) (all P < 0.01). On the other hand, remarkably decreased biomarkers, including hepatic glutathione (GSH) level, activities of glutathione transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), and anti-inflammatory cytokine interleukin (IL)-10, were observed following TG exposure (all P < 0.01). Nevertheless, all of these phenotypes were evidently reversed by pre-administration of GP for 7 continuous days. Further analysis showed that the mRNA expression of hepatic growth factor-beta1 (TGF-β1), one of tissue repair and regeneration cytokines, was enhanced by GP. Taken together, the current research suggests that GP protects against TG-induced liver injury in mice probably involved during attenuating oxidative stress and inflammation, and promoting tissue repair and regeneration.

  13. Protective effects of Ginkgo biloba leaf polysaccharide on nonalcoholic fatty liver disease and its mechanisms.

    PubMed

    Yan, Zhengui; Fan, Ruifeng; Yin, Shaojie; Zhao, Xiaona; Liu, Jianzhu; Li, Liuhui; Zhang, Wenqi; Ge, Lijiang

    2015-09-01

    A water-soluble polysaccharide fraction extracted from the leaf of Ginkgo biloba was named GBLP. The protective effect of GBLP on nonalcoholic fatty liver disease (NAFLD) was observed and underlying mechanism was explored. Wistar male rats were randomly divided into five groups, namely, normal control group, model control group and GBLP groups (100, 200 and 400 mg/kg/d). A rat model of NAFLD was established in male Wistar rats by feeding with high-fat diet (HFD) for 8 weeks. On day 57, the intragastric administration of GBLP started once daily for 4 weeks. The results showed that GBLP supplementation significantly and dose-dependently lowered the weight gain of body, liver index and serum lipid parameters in HFD-fed rat. Meanwhile, GBLP attenuated HFD-induced liver injury through reducing hepatic steatosis, TG accumulation, serum ALT, AST and ALP levels. GBLP had a positive effect on obesity-associated insulin resistance (IR) via reducing serum glucose and insulin levels. Furthermore, GBLP enhanced the activities of antioxidant enzymes and reduced MDA levels in serum and liver. These results indicate that GBLP can play a certain protective role against HFD-induced NAFLD, and the protective effects may be associated with attenuating IR, preserving liver function, enhancing antioxidant defense system, and reducing lipid peroxidation.

  14. Corrosion protection mechanism of polyaniline blended organic coating on steel

    SciTech Connect

    Sathiyanarayanan, S.; Jeyaram, R.; Muthukrishnan, S.; Venkatachari, G.

    2009-07-01

    Epoxy-coal tar coatings are widely used to protect steel structures exposed to marine atmosphere due to their good barrier property. However, the presence of micropores and microcracks formed during the coating formation leads to failure of the coating due to permeation of corrosive ions. In recent years, it has been established that the coatings containing polyaniline (PANI) is able to protect pinholes and defects due to its passivating ability. Hence, a study has been made on the effect of polyaniline content (1 and 3%) in epoxy-coal tar coating on the corrosion protection of steel in 3% NaCl solution by electrochemical impedance spectroscopy (EIS) studies. Both phosphate- and chloride-doped polyanilines were prepared by a chemical oxidative polymerization method. From EIS studies, it has been found that the resistance value of the coatings containing 1 and 3% phosphate-doped polyaniline and 3% chloride-doped polyaniline pigmented coatings are similar to 10{sup 9} {Omega} cm{sup 2} even after 90 days exposure to NaCl solution, which are two orders high in comparison to that of conventional coal tar epoxy coatings. Besides, the conducting state of polyaniline has been found to be decreased after exposure to NaCl solution due to redox property of PANI. X-ray photoelectron spectroscopy studies have shown that polyaniline forms a complex layer with iron beneath the coating along with iron oxide.

  15. Hydrogen Induced Stress Cracking of Materials Under Cathodic Protection

    NASA Astrophysics Data System (ADS)

    LaCoursiere, Marissa P.

    Hydrogen embrittlement of AISI 4340, InconelRTM 718, Alloy 686 and Alloy 59 was studied using slow strain rate tests of both smooth and notched cylindrical specimens. Two heat treatments of the AISI 4340 material were used as a standard for two levels of yield strength: 1479 MPa, and 1140 MPa. A subset of the 1140 MPa AISI 4340 material also underwent plasma nitriding. The InconelRTM 718 material was hardened following AMS 5663M to obtain a yield strength of 1091 MPa. The Alloy 686 material was obtained in the Grade 3 condition with a minimum yield strength of 1034 MPa. The Alloy 59 material was obtained with a cold worked condition similar to the Alloy 686 and with a minimum yield strength of 1034 MPa. Ninety-nine specimens were tested, including smooth cylindrical tensile test specimens and smooth and notched cylindrical slow strain rate tensile tests specimens. Testing included specimens that had been precharged with hydrogen in 3.5% NaCl at 50°C for 2 weeks (AISI 4340), 4 weeks (InconelRTM 718, Alloy 686, Alloy 59) and 16 weeks (InconelRTM 718, Alloy 686, Alloy 59) using a potentiostat to deliver a cathodic potential of -1100 mV vs. SCE. The strain rate over the gauge section for the smooth specimens and in the notch root for the notched specimens was 1 x 10-6 /s. It was found that the AISI 4340 was highly embrittled in simulated ocean water when compared to the nickel based superalloys. The higher strength AISI 4340 showed much more embrittlement, as expected. Testing of the AISI 4340 at both 20°C and 4°C showed that the temperature had no effect on the hydrogen embrittlement response. The InconelRTM 718 was highly embrittled when precharged, although it only showed low levels of embrittlement when unprecharged. Both the Alloy 686 and Alloy 59 showed minimal embrittlement in all conditions. Therefore, for the materials examined, the use of Alloy 686 and Alloy 59 for components in salt water environments when under a cathodic potential of -1100 mV vs. SCE is

  16. Dynamic performance of dissipative dielectric elastomers under alternating mechanical load

    NASA Astrophysics Data System (ADS)

    Zhang, Junshi; Chen, Hualing; Sheng, Junjie; Liu, Lei; Wang, Yongquan; Jia, Shuhai

    2014-07-01

    This paper presents a theoretical study about the effect of dissipation on the dynamic performance of a dielectric elastomer membrane subject to a combination of mechanical load and voltage. The thermodynamic dissipative model is given and the equation of motion is deduced by a free energy method. It is found that when the applied mechanical load and voltage are static, the membrane may reach a state of equilibrium after the viscoelastic relaxation. When the voltage is static but the mechanical load is sinusoidal, the membrane will resonate at multiple frequencies. The study result indicates that the viscoelasticity can reduce the natural frequency and increase the mean stretch of the dielectric elastomer. After the power source is cut off, the effect of current leakage on dynamic performance under alternating mechanical load is that the natural frequency increases and the mean stretch reduces.

  17. Linkages of plant–soil feedbacks and underlying invasion mechanisms

    PubMed Central

    Inderjit; Cahill, James F.

    2015-01-01

    Soil microbial communities and processes have repeatedly been shown to impact plant community assembly and population growth. Soil-driven effects may be particularly pronounced with the introduction of plants to non-native ranges, as introduced plants are not typically accompanied by transference of local soil communities. Here we describe how the mechanisms by which soil community processes influence plant growth overlap with several known and well-described mechanisms of plant invasion. Critically, a given soil community process may either facilitate or limit invasion, depending upon local conditions and the specific mechanisms of soil processes involved. Additionally, as soil communities typically consist of species with short generation times, the net consequences of plant–soil feedbacks for invasion trajectories are likely to change over time, as ecological and evolutionary adjustments occur. Here we provide an overview of the ecological linkages of plant–soil feedbacks and underlying mechanisms of invasion. PMID:25784668

  18. The Protection of Salidroside of the Heart against Acute Exhaustive Injury and Molecular Mechanism in Rat

    PubMed Central

    Wang, Yunru; Xu, Peng; Wang, Yang; Liu, Haiyan; Zhou, Yuwen; Cao, Xuebin

    2013-01-01

    Objective. To investigate the protection of salidroside of the heart against acute exhaustive injury and its mechanism of antioxidative stress and MAPKs signal transduction. Method. Adult male SD rats were divided into four groups randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD were determined by ELISA method, and the phosphorylation degrees of ERK and p38 MAPK were assayed by Western blotting. Cardiac function of isolated rat heart ischemia/reperfusion was detected by Langendorff technique. Results. Salidroside reduced the myocardium ultrastructure injury caused by exhaustive swimming, decreased the contents of CK, CK-MB, and LDH, improved the LVDP, ±LV dp/dtmax under the basic condition, reduced the content of MDA and the phosphorylation degree of p38 MAPK, and increased the content of SOD and the phosphorylation degree of ERK in acute exhaustive rats. Conclusion. Salidroside has the protection of the heart against acute exhaustive injury. The cardioprotection is mainly mediated by antioxidative stress and MAPKs signal transduction through reducing the content of MDA, increasing the content of SOD, and increasing p-ERK and decreasing p-p38 protein expressions in rat myocardium, which might be the mechanisms of the cardioprotective effect of salidroside. PMID:24454984

  19. Protective mechanisms of green tea polyphenols in skin.

    PubMed

    OyetakinWhite, Patricia; Tribout, Heather; Baron, Elma

    2012-01-01

    Skin is frequently exposed to a variety of environmental, chemical, and genotoxic agents that contribute to disease and carcinogenesis. Ultraviolet light (UVR) is the main external stress that leads to immunosuppression, oxidative stress, premature aging, and tumor formation. Scientists and health professionals emphasize the importance of prevention strategies to circumvent such unfavorable outcomes. Plant polyphenols are a promising approach to disease prevention and treatment. Green tea is an abundant source of plant polyphenols that exhibit significant antioxidant, chemopreventive, and immunomodulatory effects in protecting the skin. PMID:22792414

  20. Would protecting tropical forest fragments provide carbon and biodiversity cobenefits under REDD+?

    PubMed

    Magnago, Luiz Fernando S; Magrach, Ainhoa; Laurance, William F; Martins, Sebastião V; Meira-Neto, João Augusto A; Simonelli, Marcelo; Edwards, David P

    2015-09-01

    Tropical forests store vast amounts of carbon and are the most biodiverse terrestrial habitats, yet they are being converted and degraded at alarming rates. Given global shortfalls in the budgets required to prevent carbon and biodiversity loss, we need to seek solutions that simultaneously address both issues. Of particular interest are carbon-based payments under the Reducing Emissions from Deforestation and Forest Degradation (REDD+) mechanism to also conserve biodiversity at no additional cost. One potential is for REDD+ to protect forest fragments, especially within biomes where contiguous forest cover has diminished dramatically, but we require empirical tests of the strength of any carbon and biodiversity cobenefits in such fragmented systems. Using the globally threatened Atlantic Forest landscape, we measured above-ground carbon stocks within forest fragments spanning 13 to 23 442 ha in area and with different degrees of isolation. We related these stocks to tree community structure and to the richness and abundance of endemic and IUCN Red-listed species. We found that increasing fragment size has a positive relationship with above-ground carbon stock and with abundance of IUCN Red-listed species and tree community structure. We also found negative relationships between distance from large forest block and tree community structure, endemic species richness and abundance, and IUCN Red-listed species abundance. These resulted in positive congruence between carbon stocks and Red-listed species, and the abundance and richness of endemic species, demonstrating vital cobenefits. As such, protecting forest fragments in hotspots of biodiversity, particularly larger fragments and those closest to sources, offers important carbon and biodiversity cobenefits. More generally, our results suggest that macroscale models of cobenefits under REDD+ have likely overlooked key benefits at small scales, indicating the necessity to apply models that include finer

  1. Would protecting tropical forest fragments provide carbon and biodiversity cobenefits under REDD+?

    PubMed

    Magnago, Luiz Fernando S; Magrach, Ainhoa; Laurance, William F; Martins, Sebastião V; Meira-Neto, João Augusto A; Simonelli, Marcelo; Edwards, David P

    2015-09-01

    Tropical forests store vast amounts of carbon and are the most biodiverse terrestrial habitats, yet they are being converted and degraded at alarming rates. Given global shortfalls in the budgets required to prevent carbon and biodiversity loss, we need to seek solutions that simultaneously address both issues. Of particular interest are carbon-based payments under the Reducing Emissions from Deforestation and Forest Degradation (REDD+) mechanism to also conserve biodiversity at no additional cost. One potential is for REDD+ to protect forest fragments, especially within biomes where contiguous forest cover has diminished dramatically, but we require empirical tests of the strength of any carbon and biodiversity cobenefits in such fragmented systems. Using the globally threatened Atlantic Forest landscape, we measured above-ground carbon stocks within forest fragments spanning 13 to 23 442 ha in area and with different degrees of isolation. We related these stocks to tree community structure and to the richness and abundance of endemic and IUCN Red-listed species. We found that increasing fragment size has a positive relationship with above-ground carbon stock and with abundance of IUCN Red-listed species and tree community structure. We also found negative relationships between distance from large forest block and tree community structure, endemic species richness and abundance, and IUCN Red-listed species abundance. These resulted in positive congruence between carbon stocks and Red-listed species, and the abundance and richness of endemic species, demonstrating vital cobenefits. As such, protecting forest fragments in hotspots of biodiversity, particularly larger fragments and those closest to sources, offers important carbon and biodiversity cobenefits. More generally, our results suggest that macroscale models of cobenefits under REDD+ have likely overlooked key benefits at small scales, indicating the necessity to apply models that include finer

  2. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy.

    PubMed

    Yang, Lili; Rozenfeld, Raphael; Wu, Defeng; Devi, Lakshmi A; Zhang, Zhenfeng; Cederbaum, Arthur

    2014-03-01

    Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis. We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis. Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway. Cannabidiol per se can increase autophagy both in CYP2E1-expressing HepG2 cells and in mouse liver. Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol. In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy.

  3. A review of complementary mechanisms which protect the developing marsupial pouch young.

    PubMed

    Edwards, M J; Hinds, L A; Deane, E M; Deakin, J E

    2012-06-01

    Marsupials are born without a functioning adaptive immune system, into a non-sterile environment where they continue to develop. This review examines the extent of exposure of pouch young to microorganisms and describes the protective mechanisms that are complementary to adaptive immunity in the developing young. Complementary protective mechanisms include the role of the innate immune system and maternal protection strategies, such as immune compounds in milk, prenatal transfer of immunoglobulins, antimicrobial compounds secreted in the pouch, and chemical or mechanical cleaning of the pouch and pouch young.

  4. Investigation of defect nucleation in titanium under mechanical loading

    SciTech Connect

    Zolnikov, Konstantin P. Kryzhevich, Dmitrij S.; Korchuganov, Aleksandr V.; Psakhie, Sergey G.

    2014-11-14

    The paper undertakes a study of plastic deformation in a titanium crystallite under mechanical loading (uniaxial tension and indentation) in terms of atomic mechanisms of its generation and development. The molecular dynamics method with many-body interatomic potentials is employed. It is shown that there is a threshold strain, at which a crystal reveals the generation of local structural transformations associated with changes in atomic configurations of the first and second coordination spheres. The onset of plastic deformation in a crystallite is accompanied by a stepwise decrease in potential energy. The effect of free surfaces and grain boundaries on the generation of local structural transformations in a titanium crystallite is investigated.

  5. Nanomaterial-modulated autophagy: underlying mechanisms and functional consequences.

    PubMed

    Zheng, Wei; Wei, Min; Li, Song; Le, Weidong

    2016-06-01

    Autophagy is an essential lysosome-dependent process that controls the quality of the cytoplasm and maintains cellular homeostasis, and dysfunction of this protein degradation system is correlated with various disorders. A growing body of evidence suggests that nanomaterials (NMs) have autophagy-modulating effects, thus predicting a valuable and promising application potential of NMs in the diagnosis and treatment of autophagy-related diseases. NMs exhibit unique physical, chemical and biofunctional properties, which may endow NMs with capabilities to modulate autophagy via various mechanisms. The present review highlights the impacts of various NMs on autophagy and their functional consequences. The possible underlying mechanisms for NM-modulated autophagy are also discussed.

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

    PubMed

    Juslin, Patrik N; Västfjäll, Daniel

    2008-10-01

    Research indicates that people value music primarily because of the emotions it evokes. Yet, the notion of musical emotions remains controversial, and researchers have so far been unable to offer a satisfactory account of such emotions. We argue that the study of musical emotions has suffered from a neglect of underlying mechanisms. Specifically, researchers have studied musical emotions without regard to how they were evoked, or have assumed that the emotions must be based on the "default" mechanism for emotion induction, a cognitive appraisal. Here, we present a novel theoretical framework featuring six additional mechanisms through which music listening may induce emotions: (1) brain stem reflexes, (2) evaluative conditioning, (3) emotional contagion, (4) visual imagery, (5) episodic memory, and (6) musical expectancy. We propose that these mechanisms differ regarding such characteristics as their information focus, ontogenetic development, key brain regions, cultural impact, induction speed, degree of volitional influence, modularity, and dependence on musical structure. By synthesizing theory and findings from different domains, we are able to provide the first set of hypotheses that can help researchers to distinguish among the mechanisms. We show that failure to control for the underlying mechanism may lead to inconsistent or non-interpretable findings. Thus, we argue that the new framework may guide future research and help to resolve previous disagreements in the field. We conclude that music evokes emotions through mechanisms that are not unique to music, and that the study of musical emotions could benefit the emotion field as a whole by providing novel paradigms for emotion induction. PMID:18826699

  7. Experimental Analysis of the Mechanism of Hearing under Water

    PubMed Central

    Chordekar, Shai; Kishon-Rabin, Liat; Kriksunov, Leonid; Adelman, Cahtia; Sohmer, Haim

    2015-01-01

    The mechanism of human hearing under water is debated. Some suggest it is by air conduction (AC), others by bone conduction (BC), and others by a combination of AC and BC. A clinical bone vibrator applied to soft tissue sites on the head, neck, and thorax also elicits hearing by a mechanism called soft tissue conduction (STC) or nonosseous BC. The present study was designed to test whether underwater hearing at low intensities is by AC or by osseous BC based on bone vibrations or by nonosseous BC (STC). Thresholds of normal hearing participants to bone vibrator stimulation with their forehead in air were recorded and again when forehead and bone vibrator were under water. A vibrometer detected vibrations of a dry human skull in all similar conditions (in air and under water) but not when water was the intermediary between the sound source and the skull forehead. Therefore, the intensities required to induce vibrations of the dry skull in water were significantly higher than the underwater hearing thresholds of the participants, under conditions when hearing by AC and osseous BC is not likely. The results support the hypothesis that hearing under water at low sound intensities may be attributed to nonosseous BC (STC). PMID:26770975

  8. Experimental Analysis of the Mechanism of Hearing under Water.

    PubMed

    Chordekar, Shai; Kishon-Rabin, Liat; Kriksunov, Leonid; Adelman, Cahtia; Sohmer, Haim

    2015-01-01

    The mechanism of human hearing under water is debated. Some suggest it is by air conduction (AC), others by bone conduction (BC), and others by a combination of AC and BC. A clinical bone vibrator applied to soft tissue sites on the head, neck, and thorax also elicits hearing by a mechanism called soft tissue conduction (STC) or nonosseous BC. The present study was designed to test whether underwater hearing at low intensities is by AC or by osseous BC based on bone vibrations or by nonosseous BC (STC). Thresholds of normal hearing participants to bone vibrator stimulation with their forehead in air were recorded and again when forehead and bone vibrator were under water. A vibrometer detected vibrations of a dry human skull in all similar conditions (in air and under water) but not when water was the intermediary between the sound source and the skull forehead. Therefore, the intensities required to induce vibrations of the dry skull in water were significantly higher than the underwater hearing thresholds of the participants, under conditions when hearing by AC and osseous BC is not likely. The results support the hypothesis that hearing under water at low sound intensities may be attributed to nonosseous BC (STC).

  9. Protective effects of mangiferin on cerebral ischemia-reperfusion injury and its mechanisms.

    PubMed

    Yang, Zhang; Weian, Chen; Susu, Huang; Hanmin, Wang

    2016-01-15

    The aim of our study was to investigate the protective properties of mangiferin, a natural glucosyl xanthone found in both mango and papaya on the cerebral ischemia-reperfusion injury and the underlying mechanism. Wistar male rats were subjected to middle cerebral artery occlusion for 2h followed by 24h of reperfusion. Mangiferin (25, 50, and 100mg/kg, ig) or 0.5% carboxymethyl cellulose sodium was administered three times before ischemia and once at 2h after the onset of ischemia. Neurological score, infarct volume, and brain water content, some oxidative stress markers and inflammatory cytokines were evaluated after 24h of reperfusion. Treatment with mangiferin significantly ameliorated neurologic deficit, infarct volume and brain water content after cerebral ischemia reperfusion. Mangiferin also reduced the content of malondialdehyde (MDA), IL-1β and TNF-α, and up-regulated the activities of superoxide dismutase (SOD), glutathione (GSH) and IL-10 levels in the brain tissue of rats with the cerebral ischemia-reperfusion injury. Moreover, mangiferin up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream anti-oxidant protein heme oxygenase-1 (HO-1). The results indicate that mangiferin can play a certain protective role in the cerebral ischemia-reperfusion injury, and the protective effect of mangiferin may be related to the improvement on the antioxidant capacity of brain tissue and the inhibition of overproduction of inflammatory cytokines. The mechanisms are associated with enhancing the oxidant defense systems via the activation of Nrf2/HO-1 pathway. PMID:26656757

  10. Damage Evolution On Mechanical Parts Under Cyclic Loading

    NASA Astrophysics Data System (ADS)

    Lestriez, P.; Bogard, F.; Shan, J. L.; Guo, Y. Q.

    2007-05-01

    This paper presents a fatigue damage model, based on the continuum damage mechanics and general thermodynamic theory, proposed by Lemaitre and Chaboche, for rolling bearings under very numerous loading cycles. A flow surface of fatigue using the Sines criterion is adopted. The coupling between the hardening plasticity and damage effects is considered in the constitutive equations. An explicit algorithm of weak coupling leads to a calculation very fast. This fatigue damage model is implemented into Abaqus/Explicit using a Vumat user's subroutine. Moreover, the damage variable in function of time is transformed into a function of number of cycles. An algorithm of cycle jump, with a criterion for choosing the number increment of cycles, is proposed, which allows to largely reduce the CPU time. The present damage simulation allows to determine the lifetime of mechanical parts under cyclic loading.

  11. Autophagy: A protective mechanism in response to stress and inflammation

    PubMed Central

    Heymann, Dominique

    2006-01-01

    Autophagy is one of the intracellular systems responsible of protein trafficking (degradation/recycling) in eukaryotic cells. Whereas this ubiquitous process contributes to the cytosolic homeostasis, its deregulation is often associated to various pathologies (neurodegenerative diseases, cancer, pathologies with altered inflammatory response, etc.). The present paper gives an overview of autophagy, especially in inflammation, including mechanisms, regulation, functions and future therapies. PMID:16729721

  12. Mechanisms of saccharide protection against epigallocatechin-3-gallate deterioration in aqueous solutions.

    PubMed

    Shpigelman, Avi; Zisapel, Adi; Cohen, Yifat; Livney, Yoav D

    2013-08-15

    We investigated the mechanisms of the protection conferred by sugars to epigallocatechin-3-gallate (EGCG) against deterioration. Additionally, we present a rapid method for evaluating the deterioration rate of EGCG using absorbance spectroscopy. We found that various sugars provided different levels of protection at identical weight percentage, and the combination of sugars and β-lactoglobulin nanocomplexes provided greater protection for EGCG than each protective component alone. We suggest that the concentration-dependent protection by sugars resulted from a combination of mechanisms, including: (1) reduced aqueous O2 solubility, (2) scavenging of reactive oxygen species, and (3) chelation of traces of transition metal ions, which is suggested to be the main reason for the differences among the sugars. The observed protective effect of sugars can be easily applied by the industry in proper selection of sugars for enrichment of syrups or concentrates with EGCG and for the preparation of enriched beverages and foods for health promotion. PMID:23561215

  13. Blast mines: physics, injury mechanisms and vehicle protection.

    PubMed

    Ramasamy, A; Hill, A M; Hepper, A E; Bull, A M J; Clasper, J C

    2009-12-01

    Since World War II, more vehicles have been lost to land mines than all other threats combined. Anti-vehicular (AV) mines are capable of disabling a heavy vehicle, or completely destroying a lighter vehicle. The most common form of AV mine is the blast mine, which uses a large amount of explosive to directly damage the target. In a conventional military setting, landmines are used as a defensive force-multiplier and to restrict the movements of the opposing force. They are relatively cheap to purchase and easy to acquire, hence landmines are also potent weapons in the insurgents' armamentarium. The stand-offnature of its design has allowed insurgents to cause significant injuries to security forces in current conflicts with little personal risk. As a result, AV mines and improvised explosive devices (IEDs) have become the most common cause of death and injury to Coalition and local security forces operating in Iraq and Afghanistan. Detonation of an AV mine causes an explosive, exothermic reaction which results in the formation of a shockwave followed by a rapid expansion of gases. The shockwave is mainly reflected by the soillair interface and fractures the soil cap overthe mine. The detonation products then vent through the voids in the soil, resulting in a hollow inverse cone which consists of the detonation gases surrounded by the soil ejecta. It is the combination of the detonation products and soil ejecta that interact with the target vehicle and cause injury to the vehicle occupants. A number of different strategies are required to mitigate the blast effects of an explosion. Primary blast effects can be reduced by increasing the standoff distance between the seat of the explosion and the crew compartment. Enhancement of armour on the base of the vehicle, as well as improvements in personal protection can prevent penetration of fragments. Mitigating tertiary effects can be achieved by altering the vehicle geometry and structure, increasing vehicle mass, as

  14. Blast mines: physics, injury mechanisms and vehicle protection.

    PubMed

    Ramasamy, A; Hill, A M; Hepper, A E; Bull, A M J; Clasper, J C

    2009-12-01

    Since World War II, more vehicles have been lost to land mines than all other threats combined. Anti-vehicular (AV) mines are capable of disabling a heavy vehicle, or completely destroying a lighter vehicle. The most common form of AV mine is the blast mine, which uses a large amount of explosive to directly damage the target. In a conventional military setting, landmines are used as a defensive force-multiplier and to restrict the movements of the opposing force. They are relatively cheap to purchase and easy to acquire, hence landmines are also potent weapons in the insurgents' armamentarium. The stand-offnature of its design has allowed insurgents to cause significant injuries to security forces in current conflicts with little personal risk. As a result, AV mines and improvised explosive devices (IEDs) have become the most common cause of death and injury to Coalition and local security forces operating in Iraq and Afghanistan. Detonation of an AV mine causes an explosive, exothermic reaction which results in the formation of a shockwave followed by a rapid expansion of gases. The shockwave is mainly reflected by the soillair interface and fractures the soil cap overthe mine. The detonation products then vent through the voids in the soil, resulting in a hollow inverse cone which consists of the detonation gases surrounded by the soil ejecta. It is the combination of the detonation products and soil ejecta that interact with the target vehicle and cause injury to the vehicle occupants. A number of different strategies are required to mitigate the blast effects of an explosion. Primary blast effects can be reduced by increasing the standoff distance between the seat of the explosion and the crew compartment. Enhancement of armour on the base of the vehicle, as well as improvements in personal protection can prevent penetration of fragments. Mitigating tertiary effects can be achieved by altering the vehicle geometry and structure, increasing vehicle mass, as

  15. Liuweiwuling tablets protect against acetaminophen hepatotoxicity: What is the protective mechanism?

    PubMed Central

    Du, Kuo; Jaeschke, Hartmut

    2016-01-01

    Study of the effects of natural products, including traditional Chinese Medicines, on acetaminophen hepatotoxicity has gained considerable popularity in recent years, and some of them showed positive results and even promising therapeutic potentials. A recent report suggested that Liuweiwuling tablets protect against acetaminophen hepatotoxicity and promote liver regeneration in a rodent model through alleviating the inflammatory response. However, several concerns exist regarding the limitations of the experimental design and interpretation of the data presented in this manuscript. PMID:27004010

  16. Liuweiwuling tablets protect against acetaminophen hepatotoxicity: What is the protective mechanism?

    PubMed

    Du, Kuo; Jaeschke, Hartmut

    2016-03-21

    Study of the effects of natural products, including traditional Chinese Medicines, on acetaminophen hepatotoxicity has gained considerable popularity in recent years, and some of them showed positive results and even promising therapeutic potentials. A recent report suggested that Liuweiwuling tablets protect against acetaminophen hepatotoxicity and promote liver regeneration in a rodent model through alleviating the inflammatory response. However, several concerns exist regarding the limitations of the experimental design and interpretation of the data presented in this manuscript.

  17. Analysis of internal crack healing mechanism under rolling deformation.

    PubMed

    Gao, Haitao; Ai, Zhengrong; Yu, Hailiang; Wu, Hongyan; Liu, Xianghua

    2014-01-01

    A new experimental method, called the 'hole filling method', is proposed to simulate the healing of internal cracks in rolled workpieces. Based on the experimental results, the evolution in the microstructure, in terms of diffusion, nucleation and recrystallisation were used to analyze the crack healing mechanism. We also validated the phenomenon of segmented healing. Internal crack healing involves plastic deformation, heat transfer and an increase in the free energy introduced by the cracks. It is proposed that internal cracks heal better under high plastic deformation followed by slow cooling after rolling. Crack healing is controlled by diffusion of atoms from the matrix to the crack surface, and also by the nucleation and growth of ferrite grain on the crack surface. The diffusion mechanism is used to explain the source of material needed for crack healing. The recrystallisation mechanism is used to explain grain nucleation and growth, accompanied by atomic migration to the crack surface.

  18. Acetaminophen hepatotoxicity and sterile inflammation: The mechanism of protection of Chlorogenic acid.

    PubMed

    Jaeschke, Hartmut

    2016-01-01

    Acetaminophen hepatotoxicity is characterized by extensive necrotic cell death and a sterile inflammatory response. A recent report suggested that a therapeutic intervention with chlorogenic acid, a dietary polyphenolic compound, protects against acetaminophen-induced liver injury by inhibiting the inflammatory injury. The purpose of this letter is to discuss a number of reasons why the protective mechanism of chlorogenic acid against acetaminophen hepatotoxicity does not involve an anti-inflammatory effect and provides an alternative explanation for the observed protection. PMID:26363200

  19. Acetaminophen hepatotoxicity and sterile inflammation: The mechanism of protection of Chlorogenic acid.

    PubMed

    Jaeschke, Hartmut

    2016-01-01

    Acetaminophen hepatotoxicity is characterized by extensive necrotic cell death and a sterile inflammatory response. A recent report suggested that a therapeutic intervention with chlorogenic acid, a dietary polyphenolic compound, protects against acetaminophen-induced liver injury by inhibiting the inflammatory injury. The purpose of this letter is to discuss a number of reasons why the protective mechanism of chlorogenic acid against acetaminophen hepatotoxicity does not involve an anti-inflammatory effect and provides an alternative explanation for the observed protection.

  20. Through what mechanisms do protected areas affect environmental and social outcomes?

    PubMed Central

    Ferraro, Paul J.; Hanauer, Merlin M.

    2015-01-01

    To develop effective protected area policies, scholars and practitioners must better understand the mechanisms through which protected areas affect social and environmental outcomes. With strong evidence about mechanisms, the key elements of success can be strengthened, and the key elements of failure can be eliminated or repaired. Unfortunately, empirical evidence about these mechanisms is limited, and little guidance for quantifying them exists. This essay assesses what mechanisms have been hypothesized, what empirical evidence exists for their relative contributions and what advances have been made in the past decade for estimating mechanism causal effects from non-experimental data. The essay concludes with a proposed agenda for building an evidence base about protected area mechanisms. PMID:26460122

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

    PubMed

    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. PMID:23500480

  2. The survival advantage: Underlying mechanisms and extant limitations.

    PubMed

    Kazanas, Stephanie A; Altarriba, Jeanette

    2015-01-01

    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. PMID:25947360

  3. Optical tests of a space mechanism under an adverse environment: GAIA secondary mirror mechanism under vaccum and thermal controlled conditions

    NASA Astrophysics Data System (ADS)

    Ramos Zapata, Gonzalo; Sánchez Rodríguez, Antonio; Belenguer Dávila, Tomás; Urgoiti, Eduardo; Ramírez Quintana, Argiñe

    2007-09-01

    In this work, the optical evaluation of a mechanism for space applications under vacuum and temperature controlled conditions at the facilities of the Space Instrumentation Laboratory (LINES) of the Aerospace Technical Nacional Institute of Spain (INTA) is reported. The mechanism was developed by the Spanish company SENER to fulfill the high performance requirements from ESA technology preparatory program for GAIA Astrometric Mission; in particular, a five degrees of freedom (dof), three translations and two rotations positioning mechanism for the secondary mirror of the GAIA instrument. Both interferometric tests and autocollimator measurements have been combined in order to extract the information about the accuracy of the mechanism movements as well as their repeatability under adverse environmental conditions: vacuum and thermal controlled conditions, up to a 10 -6mbar and 100K. The scope of this paper will cover the measurements concept selection, the presentation of verification activities, the results of such dedicated optical measurements, the correlation with the mechanical models and a brief description of the design process followed to meet the test requirements.

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

    PubMed

    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. PMID:27498423

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

    PubMed

    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.

  6. Oxidant conditioning protects cartilage from mechanically induced damage.

    PubMed

    Ramakrishnan, Prem; Hecht, Benjamin A; Pedersen, Douglas R; Lavery, Matthew R; Maynard, Jerry; Buckwalter, Joseph A; Martin, James A

    2010-07-01

    Articular cartilage degeneration in osteoarthritis has been linked to abnormal mechanical stresses that are known to cause chondrocyte apoptosis and metabolic derangement in in vitro models. Evidence implicating oxidative damage as the immediate cause of these harmful effects suggests that the antioxidant defenses of chondrocytes might influence their tolerance for mechanical injury. Based on evidence that antioxidant defenses in many cell types are stimulated by moderate oxidant exposure, we hypothesized that oxidant preconditioning would reduce acute chondrocyte death and proteoglycan depletion in cartilage explants after exposure to abnormal mechanical stresses. Porcine cartilage explants were treated every 48 h with tert-butyl hydrogen peroxide (tBHP) at nonlethal concentrations (25, 100, 250, and 500 microM) for a varying number of times (one, two, or four) prior to a bout of unconfined axial compression (5 MPa, 1 Hz, 1800 cycles). When compared with untreated controls, tBHP had significant positive effects on post-compression viability, lactate production, and proteoglycan losses. Overall, the most effective regime was 100 microM tBHP applied four times. RNA analysis revealed significant effects of 100 microM tBHP on gene expression. Catalase, hypoxia-inducible factor-1alpha (HIF-1alpha), and glyceraldehyde 6-phosphate dehydrogenase (GAPDH) were significantly increased relative to untreated controls in explants treated four times with 100 microM tBHP, a regime that also resulted in a significant decrease in matrix metalloproteinase-3 (MMP-3) expression. These findings demonstrate that repeated exposure of cartilage to sublethal concentrations of peroxide can moderate the acute effects of mechanical stress, a conclusion supported by evidence of peroxide-induced changes in gene expression that could render chondrocytes more resistant to oxidative damage. PMID:20058262

  7. Nuclear Technology. Course 30: Mechanical Inspection. Module 30-6, Protective Coating Inspection.

    ERIC Educational Resources Information Center

    Espy, John

    This sixth in a series of eight modules for a course titled Mechanical Inspection describes the duties of the nuclear quality assurance/quality control technician that are associated with protective coatings, and the national standards that govern the selection, application, and inspection of protective coatings for the reactor containment…

  8. Pharmacological mechanisms underlying gastroprotective activities of the fractions obtained from Polygonum minus in Sprague Dawley rats.

    PubMed

    Qader, Suhailah Wasman; Abdulla, Mahmood Ameen; Chua, Lee Suan; Sirat, Hasnah Mohd; Hamdan, Salehhuddin

    2012-01-01

    The leaves of Polygonum minus were fractionated using an eluting solvent to evaluate the pharmacological mechanisms underlying the anti-ulcerogenic activity of P. minus. Different P. minus fractions were obtained and evaluated for their ulcer preventing capabilities using the ethanol induction method. In this study, Sprague Dawley rats weighing 150-200 g were used. Different parameters were estimated to identify the active fraction underlying the mechanism of the gastroprotective action of P. minus: the gastric mucus barrier, as well as superoxide dismutase, total hexosamine, and prostaglandin synthesis. Amongst the five fractions from the ethanolic extract of P. minus, the ethyl acetate:methanol 1:1 v/v fraction (F2) significantly (p < 0.005) exhibited better inhibition of ulcer lesions in a dose-dependent manner. In addition, rats pre-treated with F2 showed a significant elevation in superoxide dismutase (SOD), hexosamine and PGE2 levels in the stomach wall mucosa in a dose-dependent matter. Based on these results, the ethyl acetate:methanol 1:1 v/v fraction was considered to be the best fraction for mucous protection in the ethanol induction model. The mechanisms underlying this protection were attributed to the synthesis of antioxidants and PGE2. PMID:22408403

  9. An epigenetic signal encoded protection mechanism is activated by graphene oxide to inhibit its induced reproductive toxicity in Caenorhabditis elegans.

    PubMed

    Zhao, Yunli; Wu, Qiuli; Wang, Dayong

    2016-02-01

    Although many studies have suggested the adverse effects of engineered nanomaterials (ENMs), the self-protection mechanisms for organisms against ENMs toxicity are still largely unclear. Using Caenorhabditis elegans as an in vivo assay system, our results suggest the toxicity of graphene oxide in reducing reproductive capacity by inducing damage on gonad development. The observed reproductive toxicity of GO on gonad development was due to the combinational effect of germline apoptosis and cell cycle arrest, and DNA damage activation might act as an inducer for this combinational effect. For the underlying molecular mechanism of reproductive toxicity of GO, we raised a signaling cascade of HUS-1/CLK-2-CEP-1-EGL-1-CED-4-CED-3 to explain the roles of core apoptosis signaling pathway and DNA damage checkpoints. Moreover, we identified a miRNA regulation mechanism activated by GO to suppress its induced reproductive toxicity. A mir-360 regulation mechanism was activated by GO to suppress its induced DNA damage-apoptosis signaling cascade through affecting component of CEP-1. Our identified epigenetic signal encoded protection mechanism activated by GO suggests a novel self-protection mechanism for organisms against the ENMs toxicity.

  10. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    NASA Astrophysics Data System (ADS)

    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

  11. Open consent, biobanking and data protection law: can open consent be 'informed' under the forthcoming data protection regulation?

    PubMed

    Hallinan, Dara; Friedewald, Michael

    2015-01-01

    This article focuses on whether a certain form of consent used by biobanks--open consent--is compatible with the Proposed Data Protection Regulation. In an open consent procedure, the biobank requests consent once from the data subject for all future research uses of genetic material and data. However, as biobanks process personal data, they must comply with data protection law. Data protection law is currently undergoing reform. The Proposed Data Protection Regulation is the culmination of this reform and, if voted into law, will constitute a new legal framework for biobanking. The Regulation puts strict conditions on consent--in particular relating to information which must be given to the data subject. It seems clear that open consent cannot meet these requirements. 4 categories of information cannot be provided with adequate specificity: purpose, recipient, possible third country transfers, data collected. However, whilst open consent cannot meet the formal requirements laid out by the Regulation, this is not to say that these requirements are substantially undebateable. Two arguments could be put forward suggesting the applicable consent requirements should be rethought. First, from policy documents regarding the drafting process, it seems that the informational requirements in the Regulation are so strict in order to protect the data subject from risks inherent in the use of the consent mechanism in a certain context--exemplified by the online context. There are substantial differences between this context and the biobanking context. Arguably, a consent transaction in the biobanking does not present the same type of risk to the data subject. If the risks are different, then perhaps there are also grounds for a reconsideration of consent requirements? Second, an argument can be made that the legislator drafted the Regulation based on certain assumptions as to the nature of 'data'. The authors argue that these assumptions are difficult to apply to genetic data

  12. Open consent, biobanking and data protection law: can open consent be 'informed' under the forthcoming data protection regulation?

    PubMed

    Hallinan, Dara; Friedewald, Michael

    2015-01-01

    This article focuses on whether a certain form of consent used by biobanks--open consent--is compatible with the Proposed Data Protection Regulation. In an open consent procedure, the biobank requests consent once from the data subject for all future research uses of genetic material and data. However, as biobanks process personal data, they must comply with data protection law. Data protection law is currently undergoing reform. The Proposed Data Protection Regulation is the culmination of this reform and, if voted into law, will constitute a new legal framework for biobanking. The Regulation puts strict conditions on consent--in particular relating to information which must be given to the data subject. It seems clear that open consent cannot meet these requirements. 4 categories of information cannot be provided with adequate specificity: purpose, recipient, possible third country transfers, data collected. However, whilst open consent cannot meet the formal requirements laid out by the Regulation, this is not to say that these requirements are substantially undebateable. Two arguments could be put forward suggesting the applicable consent requirements should be rethought. First, from policy documents regarding the drafting process, it seems that the informational requirements in the Regulation are so strict in order to protect the data subject from risks inherent in the use of the consent mechanism in a certain context--exemplified by the online context. There are substantial differences between this context and the biobanking context. Arguably, a consent transaction in the biobanking does not present the same type of risk to the data subject. If the risks are different, then perhaps there are also grounds for a reconsideration of consent requirements? Second, an argument can be made that the legislator drafted the Regulation based on certain assumptions as to the nature of 'data'. The authors argue that these assumptions are difficult to apply to genetic data

  13. Tests of a protective shell passive release mechanism for hypersonic wind-tunnel models

    NASA Technical Reports Server (NTRS)

    Puster, R. L.; Dunn, J. E.

    1979-01-01

    A protective shell mechanism for wind tunnel models was developed and tested. The mechanism is passive in operation, reliable, and imposes no new structural design changes for wind tunnel models. Methods of predicting the release time and the measured loads associated with the release of the shell are given. The mechanism was tested in a series of wind tunnel tests to validate the removal process and measure the pressure loads on the model. The protective shell can be used for wind tunnel models that require a step input of heating and loading such as a thin skin heat transfer model. The mechanism may have other potential applications.

  14. Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase.

    PubMed

    Zimny, Jaroslaw; Sikora, Marta; Guranowski, Andrzej; Jakubowski, Hieronim

    2006-08-11

    Homocysteine (Hcy) editing by methionyl-tRNA synthetase results in the formation of Hcy-thiolactone and initiates a pathway that has been implicated in human disease. In addition to being cleared from the circulation by urinary excretion, Hcy-thiolactone is detoxified by the serum Hcy-thiolactonase/paraoxonase carried on high density lipoprotein. Whether Hcy-thiolactone is detoxified inside cells was unknown. Here we show that Hcy-thiolactone is hydrolyzed by an intracellular enzyme, which we have purified to homogeneity from human placenta and identified by proteomic analyses as human bleomycin hydrolase (hBLH). We have also purified an Hcy-thiolactonase from the yeast Saccharomyces cerevisiae and identified it as yeast bleomycin hydrolase (yBLH). BLH belongs to a family of evolutionarily conserved cysteine aminopeptidases, and its only known biologically relevant function was deamidation of the anticancer drug bleomycin. Recombinant hBLH or yBLH, expressed in Escherichia coli, exhibits Hcy-thiolactonase activity similar to that of the native enzymes. Active site mutations, C73A for hBLH and H369A for yBLH, inactivate Hcy-thiolactonase activities. Yeast blh1 mutants are deficient in Hcy-thiolactonase activity in vitro and in vivo, produce more Hcy-thiolactone, and exhibit greater sensitivity to Hcy toxicity than wild type yeast cells. Our data suggest that BLH protects cells against Hcy toxicity by hydrolyzing intracellular Hcy-thiolactone. PMID:16769724

  15. Mitochondria-controlled signaling mechanisms of brain protection in hypoxia.

    PubMed

    Lukyanova, Ludmila D; Kirova, Yulia I

    2015-01-01

    The article is focused on the role of the cell bioenergetic apparatus, mitochondria, involved in development of immediate and delayed molecular mechanisms for adaptation to hypoxic stress in brain cortex. Hypoxia induces reprogramming of respiratory chain function and switching from oxidation of NAD-related substrates (complex I) to succinate oxidation (complex II). Transient, reversible, compensatory activation of respiratory chain complex II is a major mechanism of immediate adaptation to hypoxia necessary for (1) succinate-related energy synthesis in the conditions of oxygen deficiency and formation of urgent resistance in the body; (2) succinate-related stabilization of HIF-1α and initiation of its transcriptional activity related with formation of long-term adaptation; (3) succinate-related activation of the succinate-specific receptor, GPR91. This mechanism participates in at least four critical regulatory functions: (1) sensor function related with changes in kinetic properties of complex I and complex II in response to a gradual decrease in ambient oxygen concentration; this function is designed for selection of the most efficient pathway for energy substrate oxidation in hypoxia; (2) compensatory function focused on formation of immediate adaptive responses to hypoxia and hypoxic resistance of the body; (3) transcriptional function focused on activated synthesis of HIF-1 and the genes providing long-term adaptation to low pO2; (4) receptor function, which reflects participation of mitochondria in the intercellular signaling system via the succinate-dependent receptor, GPR91. In all cases, the desired result is achieved by activation of the succinate-dependent oxidation pathway, which allows considering succinate as a signaling molecule. Patterns of mitochondria-controlled activation of GPR-91- and HIF-1-dependent reaction were considered, and a possibility of their participation in cellular-intercellular-systemic interactions in hypoxia and adaptation was

  16. Mitochondria-controlled signaling mechanisms of brain protection in hypoxia

    PubMed Central

    Lukyanova, Ludmila D.; Kirova, Yulia I.

    2015-01-01

    The article is focused on the role of the cell bioenergetic apparatus, mitochondria, involved in development of immediate and delayed molecular mechanisms for adaptation to hypoxic stress in brain cortex. Hypoxia induces reprogramming of respiratory chain function and switching from oxidation of NAD-related substrates (complex I) to succinate oxidation (complex II). Transient, reversible, compensatory activation of respiratory chain complex II is a major mechanism of immediate adaptation to hypoxia necessary for (1) succinate-related energy synthesis in the conditions of oxygen deficiency and formation of urgent resistance in the body; (2) succinate-related stabilization of HIF-1α and initiation of its transcriptional activity related with formation of long-term adaptation; (3) succinate-related activation of the succinate-specific receptor, GPR91. This mechanism participates in at least four critical regulatory functions: (1) sensor function related with changes in kinetic properties of complex I and complex II in response to a gradual decrease in ambient oxygen concentration; this function is designed for selection of the most efficient pathway for energy substrate oxidation in hypoxia; (2) compensatory function focused on formation of immediate adaptive responses to hypoxia and hypoxic resistance of the body; (3) transcriptional function focused on activated synthesis of HIF-1 and the genes providing long-term adaptation to low pO2; (4) receptor function, which reflects participation of mitochondria in the intercellular signaling system via the succinate-dependent receptor, GPR91. In all cases, the desired result is achieved by activation of the succinate-dependent oxidation pathway, which allows considering succinate as a signaling molecule. Patterns of mitochondria-controlled activation of GPR-91- and HIF-1-dependent reaction were considered, and a possibility of their participation in cellular-intercellular-systemic interactions in hypoxia and adaptation was

  17. Neural circuitry and plasticity mechanisms underlying delay eyeblink conditioning

    PubMed Central

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of parallel fiber synapses on Purkinje cells and long-term potentiation of mossy fiber synapses on neurons in the anterior interpositus nucleus. Conditioned stimulus and unconditioned stimulus inputs arise from the pontine nuclei and inferior olive, respectively, converging in the cerebellar cortex and deep nuclei. Projections from subcortical sensory nuclei to the pontine nuclei that are necessary for eyeblink conditioning are beginning to be identified, and recent studies indicate that there are dynamic interactions between sensory thalamic nuclei and the cerebellum during eyeblink conditioning. Cerebellar output is projected to the magnocellular red nucleus and then to the motor nuclei that generate the blink response(s). Tremendous progress has been made toward determining the neural mechanisms of delay eyeblink conditioning but there are still significant gaps in our understanding of the necessary neural circuitry and plasticity mechanisms underlying cerebellar learning. PMID:21969489

  18. Underlying mechanisms in size control of uniform nanoparticles.

    PubMed

    Sugimoto, Tadao

    2007-05-01

    Insights are given into underlying mechanisms for size control of uniform nanoparticles in liquid phases. At the outset, instead of the classical nucleation theories, which are hardly applicable to the size control of uniform particles, a fundamental equation for the nucleation of monodisperse particles, derived for their size control on the basis of the LaMer model, is introduced. This equation was derived on three assumptions: (1) There is a mass balance between the supply rate of solute and its consumption rate for nucleation and growth of the generated nuclei; (2) The supply rate of solute is independent of the subsequent precipitation events; (3) The nucleation rate is controlled only by the growth of the preformed nuclei at a fixed supply rate of solute. Thus, this nucleation theory is applicable to a system in which the precursor solute is supplied by slow irreversible generation in a closed system or by continuous feed from outside in an open system. However, it is inapplicable even if only one of these three assumptions is not fulfilled. Examples of applicable and inapplicable systems are listed, and finally discussion is focused on the underlying mechanisms of size control in some unique processes chosen from them, such as hydrolysis-induced precipitation of AgCl nanoparticles, double-jet precipitation of AgCl nanoparticles in a reverse micelle system to resolve the mechanism of particle formation in general reverse micelle systems, and a gel-sol process for the formation of nanoparticles of anatase TiO2.

  19. Peptide Formation Mechanism on Montmorillonite Under Thermal Conditions

    NASA Astrophysics Data System (ADS)

    Fuchida, Shigeshi; Masuda, Harue; Shinoda, Keiji

    2014-02-01

    The oligomerization of amino acids is an essential process in the chemical evolution of proteins, which are precursors to life on Earth. Although some researchers have observed peptide formation on clay mineral surfaces, the mechanism of peptide bond formation on the clay mineral surface has not been clarified. In this study, the thermal behavior of glycine (Gly) adsorbed on montmorillonite was observed during heating experiments conducted at 150 °C for 336 h under dry, wet, and dry-wet conditions to clarify the mechanism. Approximately 13.9 % of the Gly monomers became peptides on montmorillonite under dry conditions, with diketopiperazine (cyclic dimer) being the main product. On the other hand, peptides were not synthesized in the absence of montmorillonite. Results of IR analysis showed that the Gly monomer was mainly adsorbed via hydrogen bonding between the positively charged amino groups and negatively charged surface sites (i.e., Lewis base sites) on the montmorillonite surface, indicating that the Lewis base site acts as a catalyst for peptide formation. In contrast, peptides were not detected on montmorillonite heated under wet conditions, since excess water shifted the equilibrium towards hydrolysis of the peptides. The presence of water is likely to control thermodynamic peptide production, and clay minerals, especially those with electrophilic defect sites, seem to act as a kinetic catalyst for the peptide formation reaction.

  20. Behaviorally Induced Camouflage: A New Mechanism of Avian Egg Protection.

    PubMed

    Mayani-Parás, Fernando; Kilner, Rebecca M; Stoddard, Mary Caswell; Rodríguez, Cristina; Drummond, Hugh

    2015-10-01

    When animals potentially occupy diverse microhabitats, how can camouflage be achieved? Here we combine descriptive and experimental methods to uncover a novel form of phenotypic plasticity in the camouflage of bird eggs that may be present in other avian taxa. Soil from the bare substrate adheres to the blue-footed booby's (Sula nebouxii's) pale eggs, which parents manipulate both under and on top of their webs. Analysis of digital images confirmed that dirtiness increases progressively during the first 16 days of the incubation period, making eggs more similar to the nest substrate. Observations of 3,668 single-egg clutches showed that the probability of egg loss declines progressively over the same time frame and then remains low for the rest of the 41-day incubation period. An experiment showed that when chicken eggs are soiled and exposed in artificial booby nests, they are less likely to be taken by Heermann's gulls (Larus heermanni) than clean eggs. PMID:26655580

  1. Behaviorally Induced Camouflage: A New Mechanism of Avian Egg Protection.

    PubMed

    Mayani-Parás, Fernando; Kilner, Rebecca M; Stoddard, Mary Caswell; Rodríguez, Cristina; Drummond, Hugh

    2015-10-01

    When animals potentially occupy diverse microhabitats, how can camouflage be achieved? Here we combine descriptive and experimental methods to uncover a novel form of phenotypic plasticity in the camouflage of bird eggs that may be present in other avian taxa. Soil from the bare substrate adheres to the blue-footed booby's (Sula nebouxii's) pale eggs, which parents manipulate both under and on top of their webs. Analysis of digital images confirmed that dirtiness increases progressively during the first 16 days of the incubation period, making eggs more similar to the nest substrate. Observations of 3,668 single-egg clutches showed that the probability of egg loss declines progressively over the same time frame and then remains low for the rest of the 41-day incubation period. An experiment showed that when chicken eggs are soiled and exposed in artificial booby nests, they are less likely to be taken by Heermann's gulls (Larus heermanni) than clean eggs.

  2. Physical mechanisms underlying the strain-rate-dependent mechanical behavior of kangaroo shoulder cartilage

    NASA Astrophysics Data System (ADS)

    Thibbotuwawa, Namal; Oloyede, Adekunle; Li, Tong; Singh, Sanjleena; Senadeera, Wijitha; Gu, YuanTong

    2015-09-01

    Due to anatomical and biomechanical similarities to human shoulder, kangaroo was chosen as a model to study shoulder cartilage. Comprehensive enzymatic degradation and indentation tests were applied on kangaroo shoulder cartilage to study mechanisms underlying its strain-rate-dependent mechanical behavior. We report that superficial collagen plays a more significant role than proteoglycans in facilitating strain-rate-dependent behavior of the kangaroo shoulder cartilage. By comparing the mechanical properties of degraded and normal cartilages, it was noted that proteoglycan and collagen degradation significantly compromised strain-rate-dependent mechanical behavior of the cartilage. Superficial collagen contributed equally to the tissue behavior at all strain-rates. This is different to the studies reported on knee cartilage and confirms the importance of superficial collagen on shoulder cartilage mechanical behavior. A porohyperelastic numerical model also indicated that collagen disruption would lead to faster damage of the shoulder cartilage than when proteoglycans are depleted.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  5. The mechanisms of cachexia underlying muscle dysfunction in COPD.

    PubMed

    Remels, A H V; Gosker, H R; Langen, R C J; Schols, A M W J

    2013-05-01

    Pulmonary cachexia is a prevalent, debilitating, and well-recognized feature of COPD associated with increased mortality and loss of peripheral and respiratory muscle function. The exact cause and underlying mechanisms of cachexia in COPD are still poorly understood. Increasing evidence, however, shows that pathological changes in intracellular mechanisms of muscle mass maintenance (i.e., protein turnover and myonuclear turnover) are likely involved. Potential factors triggering alterations in these mechanisms in COPD include oxidative stress, myostatin, and inflammation. In addition to muscle wasting, peripheral muscle in COPD is characterized by a fiber-type shift toward a more type II, glycolytic phenotype and an impaired oxidative capacity (collectively referred to as an impaired oxidative phenotype). Atrophied diaphragm muscle in COPD, however, displays an enhanced oxidative phenotype. Interestingly, intrinsic abnormalities in (lower limb) peripheral muscle seem more pronounced in either cachectic patients or weight loss-susceptible emphysema patients, suggesting that muscle wasting and intrinsic changes in peripheral muscle's oxidative phenotype are somehow intertwined. In this manuscript, we will review alterations in mechanisms of muscle mass maintenance in COPD and discuss the involvement of oxidative stress, inflammation, and myostatin as potential triggers of cachexia. Moreover, we postulate that an impaired muscle oxidative phenotype in COPD can accelerate the process of cachexia, as it renders muscle in COPD less energy efficient, thereby contributing to an energy deficit and weight loss when not dietary compensated. Furthermore, loss of peripheral muscle oxidative phenotype may increase the muscle's susceptibility to inflammation- and oxidative stress-induced muscle damage and wasting.

  6. Alcohol and cardiovascular disease: still unresolved underlying mechanisms.

    PubMed

    Carnevale, Roberto; Nocella, Cristina

    2012-01-01

    Alcoholic (ethanol-containing) beverages are consumed by most societies in the world. Low-to-moderate levels of ethanol consumption have been shown to reduce the risk of cardiovascular diseases and atherosclerosis. The decreased risk is likely due to alcohol's favorable pleiotropic effects on lipids, adhesion molecules, platelet activation and oxidative stress. However, there is also an abundance of clinical, experimental and epidemiological evidence showing that chronic high-dose ethanol consumption increases mortality, cardiovascular complications and also the progression of atherosclerosis. This last phenomenon appears to be due to the metabolism of ethanol, that leads to the formation of acetaldehyde, which is oxidized to acetate, leading to the generation of reactive oxygen species (ROS) and a toxic effect of ethanol on the formation of the atherosclerosis plaque. We will here briefly review the mechanisms through which high intakes of ethanol induce the formation of atherosclerotic plaque, focusing on increased oxidative stress as the main underlying mechanism.

  7. The molecular basis of mechanisms underlying polarization vision

    PubMed Central

    Roberts, Nicholas W.; Porter, Megan L.; Cronin, Thomas W.

    2011-01-01

    The underlying mechanisms of polarization sensitivity (PS) have long remained elusive. For rhabdomeric photoreceptors, questions remain over the high levels of PS measured experimentally. In ciliary photoreceptors, and specifically cones, little direct evidence supports any type of mechanism. In order to promote a greater interest in these fundamental aspects of polarization vision, we examined a varied collection of studies linking membrane biochemistry, protein–protein interactions, molecular ordering and membrane phase behaviour. While initially these studies may seem unrelated to polarization vision, a common narrative emerges. A surprising amount of evidence exists demonstrating the importance of protein–protein interactions in both rhabdomeric and ciliary photoreceptors, indicating the possible long-range ordering of the opsin protein for increased PS. Moreover, we extend this direction by considering how such protein paracrystalline organization arises in all cell types from controlled membrane phase behaviour and propose a universal pathway for PS to occur in both rhabdomeric and cone photoreceptors. PMID:21282166

  8. Protective Mechanisms for Depression among Racial/Ethnic Minority Youth: Empirical Findings, Issues, and Recommendations.

    PubMed

    Scott, Sarah M; Wallander, Jan L; Cameron, Linda

    2015-12-01

    We (1) review empirical studies that report findings regarding putative protective mechanisms when exposed to risk of depression in African American and Hispanic adolescents; (2) identify key protective mechanisms for different risk contexts that garner empirical support; (3) synthesize the mechanisms identified as protective against depression among racial/ethnic minority adolescents; and (4) discuss improved methods for advancing understanding of resilience against depression in minority youth. The studies were selected from PsycINFO searches that met the following inclusion criteria: participants between 12 and 21 years of age, inclusions of racial/ethnic minority members, examining protection through an interaction with a risk factor, and outcome measures of depression, depressed mood, or depressive symptomatology. We found 39 eligible studies; 13 of which included multiple racial/ethnic groups. The following were supported as protective mechanisms, at least preliminarily, for at least one racial/ethnic group and in at least one risk context: employment, extracurricular activities, father-adolescent closeness, familism, maternal support, attending predominately minority schools, neighborhood composition, non-parent support, parental inductive reasoning, religiosity, self-esteem, social activities, and positive early teacher relationships. To investigate protective mechanisms more comprehensively and accurately across individual, social, and community levels of influence, we recommend incorporating multilevel modeling or multilevel growth curve analyses and large diverse samples. PMID:26374228

  9. Protective Mechanisms for Depression among Racial/Ethnic Minority Youth: Empirical Findings, Issues, and Recommendations.

    PubMed

    Scott, Sarah M; Wallander, Jan L; Cameron, Linda

    2015-12-01

    We (1) review empirical studies that report findings regarding putative protective mechanisms when exposed to risk of depression in African American and Hispanic adolescents; (2) identify key protective mechanisms for different risk contexts that garner empirical support; (3) synthesize the mechanisms identified as protective against depression among racial/ethnic minority adolescents; and (4) discuss improved methods for advancing understanding of resilience against depression in minority youth. The studies were selected from PsycINFO searches that met the following inclusion criteria: participants between 12 and 21 years of age, inclusions of racial/ethnic minority members, examining protection through an interaction with a risk factor, and outcome measures of depression, depressed mood, or depressive symptomatology. We found 39 eligible studies; 13 of which included multiple racial/ethnic groups. The following were supported as protective mechanisms, at least preliminarily, for at least one racial/ethnic group and in at least one risk context: employment, extracurricular activities, father-adolescent closeness, familism, maternal support, attending predominately minority schools, neighborhood composition, non-parent support, parental inductive reasoning, religiosity, self-esteem, social activities, and positive early teacher relationships. To investigate protective mechanisms more comprehensively and accurately across individual, social, and community levels of influence, we recommend incorporating multilevel modeling or multilevel growth curve analyses and large diverse samples.

  10. Mitochondrial protection and anti-aging activity of Astragalus polysaccharides and their potential mechanism.

    PubMed

    Li, Xing-Tai; Zhang, Ya-Kui; Kuang, Hai-Xue; Jin, Feng-Xin; Liu, De-Wen; Gao, Ming-Bo; Liu, Ze; Xin, Xiao-Juan

    2012-01-01

    The current study was performed to investigate mitochondrial protection and anti-aging activity of Astragalus polysaccharides (APS) and the potential underlying mechanism. Lipid peroxidation of liver and brain mitochondria was induced by Fe(2+)-Vit C in vitro. Thiobarbituric acid (TBA) colorimetry was used to measure the content of thiobarbituric acid reactive substances (TBARS). Mouse liver mitochondrial permeability transition (PT) was induced by calcium overload in vitro and spectrophotometry was used to measure it. The scavenging activities of APS on superoxide anion (O(2) (•-)) and hydroxyl radical (•OH), which were produced by reduced nicotinamide adenine dinucleotide (NADH)-N-Methylphenazonium methyl sulfate (PMS) and hydrogen peroxide (H(2)O(2))-Fe(2+) system respectively, were measured by 4-nitrobluetetrazolium chloride (NBT) reduction and Fenton reaction colorimetry respectively. The Na(2)S(2)O(3) titration method was used to measure the scavenging activities of APS on H(2)O(2). APS could inhibit TBARS production, protect mitochondria from PT, and scavenge O(2) (•-), •OH and H(2)O(2) significantly in a concentration-dependent manner respectively. The back of the neck of mice was injected subcutaneously with D-galactose to induce aging at a dose of 100 mg/kg/d for seven weeks. Moreover, the activities of catalase (CAT), surperoxide dismutase (SOD) and glutathione peroxidase (GPx) and anti-hydroxyl radical which were assayed by using commercial monitoring kits were increased significantly in vivo by APS. According to this research, APS protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting mitochondrial PT and increasing the activities of antioxidases. Therefore, APS has the effect of promoting health. PMID:22408421

  11. Mitochondrial Protection and Anti-aging Activity of Astragalus Polysaccharides and Their Potential Mechanism

    PubMed Central

    Li, Xing-Tai; Zhang, Ya-Kui; Kuang, Hai-Xue; Jin, Feng-Xin; Liu, De-Wen; Gao, Ming-Bo; Liu, Ze; Xin, Xiao-Juan

    2012-01-01

    The current study was performed to investigate mitochondrial protection and anti-aging activity of Astragalus polysaccharides (APS) and the potential underlying mechanism. Lipid peroxidation of liver and brain mitochondria was induced by Fe2+–Vit C in vitro. Thiobarbituric acid (TBA) colorimetry was used to measure the content of thiobarbituric acid reactive substances (TBARS). Mouse liver mitochondrial permeability transition (PT) was induced by calcium overload in vitro and spectrophotometry was used to measure it. The scavenging activities of APS on superoxide anion (O2•−) and hydroxyl radical (•OH), which were produced by reduced nicotinamide adenine dinucleotide (NADH)—N-Methylphenazonium methyl sulfate (PMS) and hydrogen peroxide (H2O2)–Fe2+ system respectively, were measured by 4-nitrobluetetrazolium chloride (NBT) reduction and Fenton reaction colorimetry respectively. The Na2S2O3 titration method was used to measure the scavenging activities of APS on H2O2. APS could inhibit TBARS production, protect mitochondria from PT, and scavenge O2•−, •OH and H2O2 significantly in a concentration-dependent manner respectively. The back of the neck of mice was injected subcutaneously with D-galactose to induce aging at a dose of 100 mg/kg/d for seven weeks. Moreover, the activities of catalase (CAT), surperoxide dismutase (SOD) and glutathione peroxidase (GPx) and anti-hydroxyl radical which were assayed by using commercial monitoring kits were increased significantly in vivo by APS. According to this research, APS protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting mitochondrial PT and increasing the activities of antioxidases. Therefore, APS has the effect of promoting health. PMID:22408421

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

    PubMed

    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.

  13. Study of mechanical properties of nanomaterials under high pressure

    NASA Astrophysics Data System (ADS)

    Sharma, Jyoti; Kaur, Namrat; Srivastava, A. K.

    2015-08-01

    In the present work, the study of physical properties and behaviour of nanomaterials i.e. n-γ- Al2O3and n-Si3C4 under high pressure is done. For this purpose Murnaghan equation of state is used. The applicability of Murnaghan equation of state is fully tested by calculating mechanical properties of nano materials i.e. volume compression (V/Vo), bulk modulus (KT) and relative isothermal compression coefficient (α(P)/α0) at different pressures. The present calculated values of compression curve for the cited nanomaterials come out to be in reasonable good agreement with the available experimental data.

  14. [Underlying mechanisms of the heavy metal tolerance of mycorrhizal fungi].

    PubMed

    Chen, Bao-Dong; Sun, Yu-Qing; Zhang, Xin; Wu, Song-Lin

    2015-03-01

    Mycorrhizal fungi are ubiquitous in natural ecosystems and can form symbiotic associations with the majority of terrestrial plants. They can be detected even in heavy metal-contaminated soils, while some fungal strains show strong heavy metal tolerance and could potentially be used in bioremediation of contaminated soils. We reviewed current research progresses in the underlying mechanisms of heavy metal tolerance of mycorrhizal fungi, with focuses on habitat selection, physiological adaptation and functional genes. Future research perspectives were proposed to promote the basic research and development of mycorrhizal technology for remediation of heavy metal-contaminated soils.

  15. Effect of Trehalose on a Phospholipid Membrane under Mechanical Stress

    PubMed Central

    Pereira, Cristina S.; Hünenberger, Philippe H.

    2008-01-01

    Explicit solvent molecular dynamics simulations were used to investigate at atomic resolution the effect of trehalose on a hydrated phospholipid bilayer under mechanical stress (stretching forces imposed in the form of negative lateral pressure). Simulations were performed in the absence or presence of trehalose at 325 K, and with different values for negative lateral pressure. In the concentration regime (2 molal) and range of lateral pressures (1 to −250 bar) investigated, trehalose was found to interact directly with the membrane, partially replacing water molecules in the formation of hydrogen bonds with the lipid headgroups. Similar to previous findings in the context of thermal stress, the number, degree of bridging, and reaching depth of these hydrogen bonds increased with the magnitude of perturbation. However, at the concentration considered, trehalose was not sufficient to preserve the integrity of the membrane structure and to prevent its extreme elongation (and possible disruption) under the effect of stretching forces. PMID:18599628

  16. Ribonuclease 4 protects neuron degeneration by promoting angiogenesis, neurogenesis, and neuronal survival under stress

    PubMed Central

    Li, Shuping; Sheng, Jinghao; Hu, Jamie K.; Yu, Wenhao; Kishikawa, Hiroko; Hu, Miaofen G.; Shima, Kaori; Wu, David; Xu, Zhengping; Xin, Winnie; Sims, Katherine B.; Landers, John E.; Brown, Robert H.; Hu, Guo-fu

    2012-01-01

    Altered RNA processing is an underlying mechanism of amyotrophic lateral sclerosis (ALS). Missense mutations in a number of genes involved in RNA function and metabolisms are associated with ALS. Among these genes is angiogenin (ANG), the fifth member of the vertebrate-specific, secreted ribonuclease superfamily. ANG is an angiogenic ribonuclease, and both its angiogenic and ribonucleolytic activities are important for motor neuron health. Ribonuclease 4 (RNASE4), the fourth member of this superfamily, shares the same promoters with ANG and is co-expressed with ANG. However, the biological role of RNASE4 is unknown. To determine whether RNASE4 is involved in ALS pathogenesis, we sequenced the coding region of RNASE4 in ALS and control subjects and characterized the angiogenic, neurogenic, and neuroprotective activities of RNASE4 protein. We identified an allelic association of SNP rs3748338 with ALS and demonstrated that RNASE4 protein is able to induce angiogenesis in in vitro, ex vivo, and in vivo assays. RNASE4 also induces neural differentiation of P19 mouse embryonal carcinoma cells and mouse embryonic stem (ES) cells. Moreover, RNASE4 not only stimulates the formation of neurofilaments from mouse embryonic cortical neurons, but also protects hypothermia-induced degeneration. Importantly, systemic treatment with RNASE4 protein slowed weight loss and enhanced neuromuscular function of SOD1G93A mice. PMID:23143660

  17. The reduced effectiveness of protected areas under climate change threatens Atlantic forest tiger moths.

    PubMed

    Ferro, Viviane G; Lemes, Priscila; Melo, Adriano S; Loyola, Rafael

    2014-01-01

    Climate change leads to species' range shifts, which may end up reducing the effectiveness of protected areas. These deleterious changes in biodiversity may become amplified if they include functionally important species, such as herbivores or pollinators. We evaluated how effective protected areas in the Brazilian Atlantic Forest are in maintaining the diversity of tiger moths (Arctiinae) under climate change. Specifically, we assessed whether protected areas will gain or lose species under climate change and mapped their locations in the Atlantic Forest, in order to assess potential spatial patterns of protected areas that will gain or lose species richness. Comparisons were completed using modeled species occurrence data based on the current and projected climate in 2080. We also built a null model for random allocation of protected areas to identify where reductions in species richness will be more severe than expected. We employed several modern techniques for modeling species' distributions and summarized results using ensembles of models. Our models indicate areas of high species richness in the central and southern regions of the Atlantic Forest both for now and the future. However, we estimate that in 2080 these regions should become climatically unsuitable, decreasing the species' distribution area. Around 4% of species were predicted to become extinct, some of them being endemic to the biome. Estimates of species turnover from current to future climate tended to be high, but these findings are dependent on modeling methods. Our most important results show that only a few protected areas in the southern region of the biome would gain species. Protected areas in semideciduous forests in the western region of the biome would lose more species than expected by the null model employed. Hence, current protected areas are worse off, than just randomly selected areas, at protecting species in the future. PMID:25229422

  18. The reduced effectiveness of protected areas under climate change threatens Atlantic forest tiger moths.

    PubMed

    Ferro, Viviane G; Lemes, Priscila; Melo, Adriano S; Loyola, Rafael

    2014-01-01

    Climate change leads to species' range shifts, which may end up reducing the effectiveness of protected areas. These deleterious changes in biodiversity may become amplified if they include functionally important species, such as herbivores or pollinators. We evaluated how effective protected areas in the Brazilian Atlantic Forest are in maintaining the diversity of tiger moths (Arctiinae) under climate change. Specifically, we assessed whether protected areas will gain or lose species under climate change and mapped their locations in the Atlantic Forest, in order to assess potential spatial patterns of protected areas that will gain or lose species richness. Comparisons were completed using modeled species occurrence data based on the current and projected climate in 2080. We also built a null model for random allocation of protected areas to identify where reductions in species richness will be more severe than expected. We employed several modern techniques for modeling species' distributions and summarized results using ensembles of models. Our models indicate areas of high species richness in the central and southern regions of the Atlantic Forest both for now and the future. However, we estimate that in 2080 these regions should become climatically unsuitable, decreasing the species' distribution area. Around 4% of species were predicted to become extinct, some of them being endemic to the biome. Estimates of species turnover from current to future climate tended to be high, but these findings are dependent on modeling methods. Our most important results show that only a few protected areas in the southern region of the biome would gain species. Protected areas in semideciduous forests in the western region of the biome would lose more species than expected by the null model employed. Hence, current protected areas are worse off, than just randomly selected areas, at protecting species in the future.

  19. Current models broadly neglect specific needs of biodiversity conservation in protected areas under climate change

    PubMed Central

    2011-01-01

    Background Protected areas are the most common and important instrument for the conservation of biological diversity and are called for under the United Nations' Convention on Biological Diversity. Growing human population densities, intensified land-use, invasive species and increasing habitat fragmentation threaten ecosystems worldwide and protected areas are often the only refuge for endangered species. Climate change is posing an additional threat that may also impact ecosystems currently under protection. Therefore, it is of crucial importance to include the potential impact of climate change when designing future nature conservation strategies and implementing protected area management. This approach would go beyond reactive crisis management and, by necessity, would include anticipatory risk assessments. One avenue for doing so is being provided by simulation models that take advantage of the increase in computing capacity and performance that has occurred over the last two decades. Here we review the literature to determine the state-of-the-art in modeling terrestrial protected areas under climate change, with the aim of evaluating and detecting trends and gaps in the current approaches being employed, as well as to provide a useful overview and guidelines for future research. Results Most studies apply statistical, bioclimatic envelope models and focus primarily on plant species as compared to other taxa. Very few studies utilize a mechanistic, process-based approach and none examine biotic interactions like predation and competition. Important factors like land-use, habitat fragmentation, invasion and dispersal are rarely incorporated, restricting the informative value of the resulting predictions considerably. Conclusion The general impression that emerges is that biodiversity conservation in protected areas could benefit from the application of modern modeling approaches to a greater extent than is currently reflected in the scientific literature. It is

  20. Investigating the mechanism(s) underlying switching between states in bipolar disorder.

    PubMed

    Young, Jared W; Dulcis, Davide

    2015-07-15

    Bipolar disorder (BD) is a unique disorder that transcends domains of function since the same patient can exhibit depression or mania, states with polar opposite mood symptoms. During depression, people feel helplessness, reduced energy, and risk aversion, while with mania behaviors include grandiosity, increased energy, less sleep, and risk preference. The neural mechanism(s) underlying each state are gaining clarity, with catecholaminergic disruption seen during mania, and cholinergic dysfunction during depression. The fact that the same patient cycles/switches between these states is the defining characteristic of BD however. Of greater importance therefore, is the mechanism(s) underlying cycling from one state - and its associated neural changes - to another, considered the 'holy grail' of BD research. Herein, we review studies investigating triggers that induce switching to these states. By identifying such triggers, researchers can study neural mechanisms underlying each state and importantly how such mechanistic changes can occur in the same subject. Current animal models of this switch are also discussed, from submissive- and dominant-behaviors to kindling effects. Focus however, is placed on how seasonal changes can induce manic and depressive states in BD sufferers. Importantly, changing photoperiod lengths can induce local switches in neurotransmitter expression in normal animals, from increased catecholaminergic expression during periods of high activity, to increased somatostatin and corticotrophin releasing factor during periods of low activity. Identifying susceptibilities to this switch would enable the development of targeted animal models. From animal models, targeted treatments could be developed and tested that would minimize the likelihood of switching.

  1. Autophagy protects end plate chondrocytes from intermittent cyclic mechanical tension induced calcification.

    PubMed

    Xu, Hong-guang; Yu, Yun-fei; Zheng, Quan; Zhang, Wei; Wang, Chuang-dong; Zhao, Xiao-yn; Tong, Wen-xue; Wang, Hong; Liu, Ping; Zhang, Xiao-ling

    2014-09-01

    Calcification of end plate chondrocytes is a major cause of intervertebral disc (IVD) degeneration. However, the underlying molecular mechanism of end plate chondrocyte calcification is still unclear. The aim of this study was to clarify whether autophagy in end plate chondrocytes could protect the calcification of end plate chondrocytes. Previous studies showed that intermittent cyclic mechanical tension (ICMT) contributes to the calcification of end plate chondrocytes in vitro. While autophagy serves as a cell survival mechanism, the relationship of autophagy and induced end plate chondrocyte calcification by mechanical tension in vitro is unknown. Thus, we investigated autophagy, the expression of the autophagy genes, Beclin-1 and LC3, and rat end plate chondrocyte calcification by ICMT. The viability of end plate chondrocytes was examined using the LIVE/DEAD viability/cytotoxicity kit. The reverse transcription-polymerase chain reaction and western blotting were used to detect the expression of Beclin-1; LC3; type I, II and X collagen; aggrecan; and Sox-9 genes. Immunofluorescent and fluorescent microscopy showed decreased autophagy in the 10- and 20-day groups loaded with ICMT. Additionally, Alizarin red and alkaline phosphatase staining detected the palpable calcification of end plate chondrocytes after ICMT treatment. We found that increased autophagy induced by short-term ICMT treatment was accompanied by an insignificant calcification of end plate chondrocytes. To the contrary, the suppressive autophagy inhibited by long-term ICMT was accompanied by a more significant calcification. The process of calcification induced by ICMT was partially resisted by increased autophagy activity induced by rapamycin, implicating that autophagy may prevent end plate chondrocyte calcification.

  2. Efficiency of five chemical protective clothing materials against nano and submicron aerosols when submitted to mechanical deformations.

    PubMed

    Ben Salah, Mehdi; Hallé, Stéphane; Tuduri, Ludovic

    2016-01-01

    Due to their potential toxicity, the use of nanoparticles in the workplace is a growing concern. Some studies indicate that nanoparticles can penetrate the skin and lead to adverse health effects. Since chemical protective clothing is the last barrier to protect the skin, this study aims to better understand nanoparticle penetration behaviour in dermal protective clothing under mechanical deformation. For this purpose, five of the most common types of fabrics used in protective clothing, one woven and four nonwoven, were chosen and submitted to different simulated exposure conditions. They were tested against polydispersed NaCl aerosols having an electrical-mobility diameter between 14 and 400 nm. A bench-scale exposure setup and a sampling protocol was developed to measure the level of penetration of the aerosols through the material samples of disposable coveralls and lab coat, while subjecting them to mechanical deformations to simulate the conditions of usage in the workplace. Particle size distribution of the aerosol was determined upstream and downstream using a scanning mobility particle sizer (SMPS). The measured efficiencies demonstrated that the performances of nonwoven materials were similar. Three nonwovens had efficiencies above 99%, while the woven fabric was by far, the least effective. Moreover, the results established that mechanical deformations, as simulated for this study, did not have a significant effect on the fabrics' efficiencies.

  3. Triplet-triplet energy transfer and protection mechanisms against singlet oxygen in photosynthesis

    NASA Astrophysics Data System (ADS)

    Kihara, Shigeharu

    In photosynthesis, (bacterio)chlorophylls ((B)Chl) play a crucial role in light harvesting and electron transport. (B)Chls, however, are known to be potentially dangerous due to the formation of the triplet excited state which forms the singlet oxygen (1O2*) when exposed to the sunlight. Singlet oxygen is highly reactive and all modern organisms incorporate special protective mechanisms to minimize the oxidative damage. One of the conventional photoprotective mechanisms used by photosynthetic organisms is by the nearby carotenoids quenching the excess energy and releasing it by heat. In this dissertation, two major aspects of this process are studied. First, based on experimental data and model calculations, the oxygen content in a functioning oxygenic photosynthetic oxygen cell was determined. These organisms perform water splitting and as a result significant amount of oxygen can be formed within the organism itself. It was found, that contrary to some published estimates, the excess oxygen concentration generated within an individual cell is extremely low -- 0.025 ... 0.25 microM, i.e. about 103-104 times lower than the oxygen concentration in air saturated water. Such low concentrations imply that the first oxygenic photosynthetic cells that evolved in oxygen-free atmosphere of the Earth ~2.8 billion years ago might have invented the water splitting machinery (photosystem II) without the need for special oxygen-protective mechanisms, and the latter mechanisms could have evolved in the next 500 million years during slow rise of oxygen in the atmosphere. This result also suggests that proteins within photosynthetic membranes are not exposed to significant O2 levels and thus can be studied in vitro under the usual O2 levels. Second, the fate of triplet excited states in the Fenna Matthew Olson (FMO) pigment-protein complex is studied by means of time-resolved nanosecond spectroscopy and exciton model simulations. For the first time, the properties of several

  4. Shared neural mechanisms underlying social warmth and physical warmth.

    PubMed

    Inagaki, Tristen K; Eisenberger, Naomi I

    2013-11-01

    Many of people's closest bonds grow out of socially warm exchanges and the warm feelings associated with being socially connected. Indeed, the neurobiological mechanisms underlying thermoregulation may be shared by those that regulate social warmth, the experience of feeling connected to other people. To test this possibility, we placed participants in a functional MRI scanner and asked them to (a) read socially warm and neutral messages from friends and family and (b) hold warm and neutral-temperature objects (a warm pack and a ball, respectively). Findings showed an overlap between physical and social warmth: Participants felt warmer after reading the positive (compared with neutral) messages and more connected after holding the warm pack (compared with the ball). In addition, neural activity during social warmth overlapped with neural activity during physical warmth in the ventral striatum and middle insula, but neural activity did not overlap during another pleasant task (soft touch). Together, these results suggest that a common neural mechanism underlies physical and social warmth. PMID:24048423

  5. About the role and underlying mechanisms of cofactors in anaphylaxis.

    PubMed

    Wölbing, F; Fischer, J; Köberle, M; Kaesler, S; Biedermann, T

    2013-09-01

    Anaphylaxis is the systemic and most severe presentation of type I allergy. A number of conditions were identified that modulate the onset of anaphylaxis such as co- or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. Next to physical exercise or alcohol consumption, co-administration of nonsteroidal anti-inflammatory drugs (NSAID) or concomitant infectious diseases are well-documented cofactors of anaphylaxis. Registries for anaphylaxis document a role for cofactors in about 30% of anaphylactic reactions. Some disease entities such as 'wheat-dependent exercise-induced anaphylaxis' (WDEIA) are explicitly characterized by elicitation of anaphylaxis only in the presence of at least one such cofactor. Using WDEIA as a model disease, studies demonstrated that exercise increases skin prick test reactivity to and bioavailability of the allergen. Additional data indicate that alcohol consumption and NSAID administration display similar effects. Modulation of the cellular activation threshold is another mechanism underlying cofactor-induced anaphylaxis, most likely also functional when infectious diseases orchestrate elicitation of anaphylaxis. Cofactors are increasingly accepted to play a fundamental role in eliciting anaphylaxis. Consequently, to improve patient management modalities, a better understanding of the underlying mechanisms is warranted. This review aims to update clinicians and clinical scientists on recent developments.

  6. Mechanisms underlying the antidepressant response and treatment resistance

    PubMed Central

    Levinstein, Marjorie R.; Samuels, Benjamin A.

    2014-01-01

    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. PMID:25018708

  7. Shared neural mechanisms underlying social warmth and physical warmth.

    PubMed

    Inagaki, Tristen K; Eisenberger, Naomi I

    2013-11-01

    Many of people's closest bonds grow out of socially warm exchanges and the warm feelings associated with being socially connected. Indeed, the neurobiological mechanisms underlying thermoregulation may be shared by those that regulate social warmth, the experience of feeling connected to other people. To test this possibility, we placed participants in a functional MRI scanner and asked them to (a) read socially warm and neutral messages from friends and family and (b) hold warm and neutral-temperature objects (a warm pack and a ball, respectively). Findings showed an overlap between physical and social warmth: Participants felt warmer after reading the positive (compared with neutral) messages and more connected after holding the warm pack (compared with the ball). In addition, neural activity during social warmth overlapped with neural activity during physical warmth in the ventral striatum and middle insula, but neural activity did not overlap during another pleasant task (soft touch). Together, these results suggest that a common neural mechanism underlies physical and social warmth.

  8. Mechanical response of brain tissue under blast loading.

    PubMed

    Laksari, Kaveh; Sadeghipour, Keyanoush; Darvish, Kurosh

    2014-04-01

    In this study, a framework for understanding the propagation of stress waves in brain tissue under blast loading has been developed. It was shown that tissue nonlinearity and rate dependence are the key parameters in predicting the mechanical behavior under such loadings, as they determine whether traveling waves could become steeper and eventually evolve into shock discontinuities. To investigate this phenomenon, in the present study, brain tissue has been characterized as a quasi-linear viscoelastic (QLV) material and a nonlinear constitutive model has been developed for the tissue that spans from medium loading rates up to blast rates. It was shown that development of shock waves is possible inside the head in response to high rate compressive pressure waves. Finally, it was argued that injury to the nervous tissue at the microstructural level could be partly attributed to the high stress gradients with high rates generated at the shock front and this was proposed as a mechanism of injury in brain tissue. PMID:24457112

  9. Continuous damage parameter calculation under thermo-mechanical random loading

    PubMed Central

    Nagode, Marko

    2014-01-01

    The paper presents a method on how the mean stress effect on fatigue damage can be taken into account under an arbitrary low cycle thermo-mechanical loading. From known stress, elastoplastic strain and temperature histories the cycle amplitudes and cycle mean values are extracted and the damage parameter is computed. In contrast to the existing methods the proposed method enables continuous damage parameter computation without the need of waiting for the cycles to close. The limitations of the standardized damage parameters are thus surpassed. The damage parameters derived initially for closed and isothermal cycles assuming that the elastoplastic stress–strain response follows the Masing and memory rules can now be used to take the mean stress effect into account under an arbitrary low cycle thermo-mechanical loading. The method includes:•stress and elastoplastic strain history transformation into the corresponding amplitude and mean values;•stress and elastoplastic strain amplitude and mean value transformation into the damage parameter amplitude history;•damage parameter amplitude history transformation into the damage parameter history. PMID:26150939

  10. Cell Mechanisms of Bone Tissue Loss Under Space Flight Conditions

    NASA Astrophysics Data System (ADS)

    Rodionova, Natalia

    Investigations on the space biosatellites has shown that the bone skeleton is one of the most im-portant targets of the effect space flight factors on the organism. Bone tissue cells were studied by electron microscopy in biosamples of rats' long bones flown on the board american station "SLS-2" and in experiments with modelling of microgravity ("tail suspension" method) with using autoradiography. The analysis of data permits to suppose that the processes of remod-eling in bone tissue at microgravity include the following succession of cell-to-cell interactions. Osteocytes as mechanosensory cells are first who respond to a changing "mechanical field". The next stage is intensification of osteolytic processes in osteocytes, leading to a volume en-largement of the osteocytic lacunae and removal of the "excess bone". Then mechanical signals have been transmitted through a system of canals and processes of the osteocytic syncitium to certain superficial bone zones and are perceived by osteoblasts and bone-lining cells (superficial osteocytes), as well as by the bone-marrow stromal cells. The sensitivity of stromal cells, pre-osteoblasts and osteoblasts, under microgravity was shown in a number of works. As a response to microgravity, the system of stromal cells -preosteoblasts -osteoblasts displays retardation of proliferation, differentiation and specific functions of osteogenetic cells. This is supported by the 3H-thymidine studies of the dynamics of differentiation of osteogenetic cells in remodeling zones. But unloading is not adequate and in part of the osteocytes are apoptotic changes as shown by our electron microscopic investigations. An osteocytic apoptosis can play the role in attraction the osteoclasts and in regulation of bone remodeling. The apoptotic bodies with a liquid flow through a system of canals are transferred to the bone surface, where they fulfil the role of haemoattractants for monocytes come here and form osteoclasts. The osteoclasts destroy

  11. Amyloid Beta: Multiple Mechanisms of Toxicity and Only Some Protective Effects?

    PubMed Central

    Colín-Barenque, Laura

    2014-01-01

    Amyloid beta (Aβ) is a peptide of 39–43 amino acids found in large amounts and forming deposits in the brain tissue of patients with Alzheimer's disease (AD). For this reason, it has been implicated in the pathophysiology of damage observed in this type of dementia. However, the role of Aβ in the pathophysiology of AD is not yet precisely understood. Aβ has been experimentally shown to have a wide range of toxic mechanisms in vivo and in vitro, such as excitotoxicity, mitochondrial alterations, synaptic dysfunction, altered calcium homeostasis, oxidative stress, and so forth. In contrast, Aβ has also shown some interesting neuroprotective and physiological properties under certain experimental conditions, suggesting that both physiological and pathological roles of Aβ may depend on several factors. In this paper, we reviewed both toxic and protective mechanisms of Aβ to further explore what their potential roles could be in the pathophysiology of AD. The complete understanding of such apparently opposed effects will also be an important guide for the therapeutic efforts coming in the future. PMID:24683437

  12. Amyloid beta: multiple mechanisms of toxicity and only some protective effects?

    PubMed

    Carrillo-Mora, Paul; Luna, Rogelio; Colín-Barenque, Laura

    2014-01-01

    Amyloid beta (Aβ) is a peptide of 39-43 amino acids found in large amounts and forming deposits in the brain tissue of patients with Alzheimer's disease (AD). For this reason, it has been implicated in the pathophysiology of damage observed in this type of dementia. However, the role of Aβ in the pathophysiology of AD is not yet precisely understood. Aβ has been experimentally shown to have a wide range of toxic mechanisms in vivo and in vitro, such as excitotoxicity, mitochondrial alterations, synaptic dysfunction, altered calcium homeostasis, oxidative stress, and so forth. In contrast, Aβ has also shown some interesting neuroprotective and physiological properties under certain experimental conditions, suggesting that both physiological and pathological roles of Aβ may depend on several factors. In this paper, we reviewed both toxic and protective mechanisms of Aβ to further explore what their potential roles could be in the pathophysiology of AD. The complete understanding of such apparently opposed effects will also be an important guide for the therapeutic efforts coming in the future.

  13. Structure and mechanical behaviors of protective armored pangolin scales and effects of hydration and orientation.

    PubMed

    Liu, Z Q; Jiao, D; Weng, Z Y; Zhang, Z F

    2016-03-01

    As natural flexible dermal armor, pangolin scales provide effective protection against predatory threats and possess other notable properties such as anti-adhesion and wear-resistance. In this study, the structure, mechanical properties, deformation and damage behaviors of pangolin scales were systematically investigated with the effects of hydration and orientation evaluated. The scales are divided into three macro-layers constituted by overlapping keratin tiles with distinct lamellar arrangements which are further composed of lower-ordered lamellae. Both hardness and strength are significantly decreased by hydration; while the plasticity is markedly improved concomitantly, and as such, the mechanical damages are mitigated. The tensile strength invariably approximates to one third of hardness in value. The tensile deformation is dominated by lamellae stretching and pulling out under wet condition, which is distinct from the trans-lamellar fracture in dry samples. The compressive behaviors are featured by pronounced plasticity in both dry and wet scales; and notable strain-hardening capacity is introduced by hydration, especially along the thickness direction wherein kinking occurs. Inter-lamellar cracking is effectively alleviated in wet samples compared with the dry ones and both of them deform by macroscopic buckling. This study may help stimulate possible inspiration for the design of high-performance synthetic armor materials by mimicking pangolin scales. PMID:26703230

  14. Structure and mechanical behaviors of protective armored pangolin scales and effects of hydration and orientation.

    PubMed

    Liu, Z Q; Jiao, D; Weng, Z Y; Zhang, Z F

    2016-03-01

    As natural flexible dermal armor, pangolin scales provide effective protection against predatory threats and possess other notable properties such as anti-adhesion and wear-resistance. In this study, the structure, mechanical properties, deformation and damage behaviors of pangolin scales were systematically investigated with the effects of hydration and orientation evaluated. The scales are divided into three macro-layers constituted by overlapping keratin tiles with distinct lamellar arrangements which are further composed of lower-ordered lamellae. Both hardness and strength are significantly decreased by hydration; while the plasticity is markedly improved concomitantly, and as such, the mechanical damages are mitigated. The tensile strength invariably approximates to one third of hardness in value. The tensile deformation is dominated by lamellae stretching and pulling out under wet condition, which is distinct from the trans-lamellar fracture in dry samples. The compressive behaviors are featured by pronounced plasticity in both dry and wet scales; and notable strain-hardening capacity is introduced by hydration, especially along the thickness direction wherein kinking occurs. Inter-lamellar cracking is effectively alleviated in wet samples compared with the dry ones and both of them deform by macroscopic buckling. This study may help stimulate possible inspiration for the design of high-performance synthetic armor materials by mimicking pangolin scales.

  15. CCL7 is a protective factor secreted by mechanically loaded osteocytes.

    PubMed

    Kitase, Y; Lee, S; Gluhak-Heinrich, J; Johnson, M L; Harris, S E; Bonewald, L F

    2014-11-01

    In a search for factors up-regulated by mechanical strain in osteocytes, we discovered that chemokine (C-C motif) ligand 7 (CCL7), a chemotactic myokine, was highly expressed in MLO-Y4 osteocyte-like cells. Although MLO-Y4 cells secrete potent chemotactic factors for osteoclast precursors, CCL7 was not responsible for this activity. CCL7 was increased in osteocytes in response to tooth movement in vivo. Since mechanical loading plays a crucial role in maintaining osteocyte viability, CCL7 was tested for protective activity and found to be protective against cell death induced by dexamethasone and etoposide. CCL7 specific antibody partially, but in combination with indomethacin, completely abrogated the protective effects of fluid flow shear stress against dexamethasone-induced cell death. CCL7 activated the β-catenin pathway through phosphorylation of glycogen synthase kinase 3 (GSK-3), suggesting that this pathway is responsible for the observed protective effects. A related cytokine, CCL2, also produced by MLO-Y4 cells but not regulated by mechanical loading, proved to be more potent and protected against cell death induced by not only dexamethasone, but also by Tumor Necrosis Factor α (TNFα). Whereas osteocytes may produce CCL2 in constitutively low levels, a major function of mechanically induced CCL7 may be to selectively protect osteocytes in an autocrine manner against glucocorticoid-induced cell death.

  16. Septal flash and septal rebound stretch have different underlying mechanisms.

    PubMed

    Walmsley, John; Huntjens, Peter R; Prinzen, Frits W; Delhaas, Tammo; Lumens, Joost

    2016-02-01

    Abnormal left-right motion of the interventricular septum in early systole, known as septal flash (SF), is frequently observed in patients with left bundle branch block (LBBB). Transseptal pressure gradient and early active septal contraction have been proposed as explanations for SF. Similarities in timing (early systole) and location (septum) suggest that SF may be related to septal systolic rebound stretch (SRSsept). We aimed to clarify the mechanisms generating SF and SRSsept. The CircAdapt computer model was used to isolate the effects of timing of activation of the left ventricular free wall (LVFW), right ventricular free wall (RVFW), and septum on SF and SRSsept. LVFW and septal activation times were varied by ±80 ms relative to RVFW activation time. M-mode-derived wall motions and septal strains were computed and used to quantify SF and SRSsept, respectively. SF depended on early activation of the RVFW relative to the LVFW. SF and SRSsept occurred in LBBB-like simulations and against a rising transseptal pressure gradient. When the septum was activated before both LVFW and RVFW, no SF occurred despite the presence of SRSsept. Computer simulations therefore indicate that SF and SRSsept have different underlying mechanisms, even though both can occur in LBBB. The mechanism of leftward motion during SF is early RVFW contraction pulling on and straightening the septum when unopposed by the LVFW. SRSsept is caused by late LVFW contraction following early contraction of the septum. Changes in transseptal pressure gradient are not the main cause of SF in LBBB.

  17. Piezoelectric compliant mechanism energy harvesters under large base excitations

    NASA Astrophysics Data System (ADS)

    Ma, Xiaokun; Trolier-McKinstry, Susan; Rahn, Christopher D.

    2016-09-01

    A piezoelectric compliant mechanism (PCM) energy harvester is designed, modeled, and analyzed that consists of a polyvinylidene diflouoride, PVDF unimorph clamped at its base and attached to a compliant mechanism at its tip. The compliant hinge stiffness is carefully tuned to approach a low frequency first mode with an efficient (nearly quadratic) shape that provides a uniform strain distribution. A nonlinear model of the PCM energy harvester under large base excitation is derived to determine the maximum power that can be generated by the device. Experiments with a fabricated PCM energy harvester prototype show that the compliant mechanism introduces a stiffening effect and a much wider bandwidth than a benchmark proof mass cantilever design. The PCM bridge structure self-limits the displacement and maximum strain at large excitations compared with the proof mass cantilever, improving the device robustness. The PCM outperforms the cantilever in both average power and power-strain sensitivity at high accelerations due to the PCM axial stretching effect and its more uniform strain distribution.

  18. Molecular mechanisms underlying the onset of degenerative aortic valve disease.

    PubMed

    Hakuno, Daihiko; Kimura, Naritaka; Yoshioka, Masatoyo; Fukuda, Keiichi

    2009-01-01

    Morbidity from degenerative aortic valve disease is increasing worldwide, concomitant with the ageing of the general population and the habitual consumption of diets high in calories and cholesterol. Immunohistologic studies have suggested that the molecular mechanism occurring in the degenerate aortic valve resembles that of atherosclerosis, prompting the testing of HMG CoA reductase inhibitors (statins) for the prevention of progression of native and bioprosthetic aortic valve degeneration. However, the effects of these therapies remain controversial. Although the molecular mechanisms underlying the onset of aortic valve degeneration are largely unknown, research in this area is advancing rapidly. The signaling components involved in embryonic valvulogenesis, such as Wnt, TGF-beta(1), BMP, and Notch, are also involved in the onset of aortic valve degeneration. Furthermore, investigations into extracellular matrix remodeling, angiogenesis, and osteogenesis in the aortic valve have been reported. Having noted avascularity of normal cardiac valves, we recently identified chondromodulin-I (chm-I) as a crucial anti-angiogenic factor. The expression of chm-I is restricted to cardiac valves from late embryogenesis to adulthood in the mouse, rat, and human. In human degenerate atherosclerotic valves, the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases and angiogenesis is observed in the area of chm-I downregulation. Gene targeting of chm-I resulted in VEGF expression, angiogenesis, and calcification in the aortic valves of aged mice, and aortic stenosis is detected by echocardiography, indicating that chm-I is a crucial factor for maintaining normal cardiac valvular function by preventing angiogenesis. The present review focuses on the animal models of aortic valve degeneration and recent studies on the molecular mechanisms underlying the onset of degenerative aortic valve disease. PMID:18766323

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

    PubMed Central

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

    2016-01-01

    Objective To assess the effects of manual hyperinflation, performed with a manual resuscitator with and without the positive end-expiratory pressure valve, on the respiratory function of preterm newborns under mechanical ventilation. Methods Cross-sectional study of hemodynamically stable preterm newborns with gestational age of less than 32 weeks, under mechanical ventilation and dependent on it at 28 days of life. Manual hyperinflation was applied randomly, alternating the use or not of the positive end-expiratory pressure valve, followed by tracheal aspiration for ending the maneuver. For nominal data, the two-tailed Wilcoxon test was applied at the 5% significance level and 80% power. Results Twenty-eight preterm newborns, with an average birth weight of 1,005.71 ± 372.16g, an average gestational age of 28.90 ± 1.79 weeks, an average corrected age of 33.26 ± 1.78 weeks, and an average mechanical ventilation time of 29.5 (15 - 53) days, were studied. Increases in inspiratory and expiratory volumes occurred between time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in both the maneuver with the valve (p = 0.001 and p = 0.009) and without the valve (p = 0.026 and p = 0.001), respectively. There was also an increase in expiratory resistance between time-points A5 and C1 (p = 0.044). Conclusion Lung volumes increased when performing the maneuver with and without the valve, with a significant difference in the first minute after aspiration. There was a significant difference in expiratory resistance between the time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in the first minute after aspiration within each maneuver. PMID:27737427

  20. Protection from psychosocial risks at work under the European Convention on Human Rights: is it possible?

    PubMed

    Sychenko, Elena

    2016-09-01

    This paper argues the possibility of establishing common principles of protection from psychosocial risks (PSR) on the basis of the legal positions of the European Court of Human Rights (the Court) expressed in recent cases on degrading treatment and occupational health. The author focuses on the positive obligations of the States to ensure the protection of the right for life and of the right to respect for private life. The prohibition of degrading treatment in relations between private persons is also considered as relevant to the issue of the protection from PSR. Analyzing the Court's case law (judgments of the Court) we substantiate the possibility of claiming protection from PSR under the European Convention on Human Rights, namely, articles 2, 3 and 6, 8. PMID:27064417

  1. Protection from psychosocial risks at work under the European Convention on Human Rights: is it possible?

    PubMed

    Sychenko, Elena

    2016-09-01

    This paper argues the possibility of establishing common principles of protection from psychosocial risks (PSR) on the basis of the legal positions of the European Court of Human Rights (the Court) expressed in recent cases on degrading treatment and occupational health. The author focuses on the positive obligations of the States to ensure the protection of the right for life and of the right to respect for private life. The prohibition of degrading treatment in relations between private persons is also considered as relevant to the issue of the protection from PSR. Analyzing the Court's case law (judgments of the Court) we substantiate the possibility of claiming protection from PSR under the European Convention on Human Rights, namely, articles 2, 3 and 6, 8.

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

    PubMed

    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.

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

    SciTech Connect

    Nguyen, Trung Dung; Gu, YuanTong

    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.

  4. Bactericidal mechanisms of Au@TNBs under visible light irradiation.

    PubMed

    Guo, Lingqiao; Shan, Chao; Liang, Jialiang; Ni, Jinren; Tong, Meiping

    2015-04-01

    Au@TNBs nanocomposites were synthesized by depositing Au nanoparticles onto the surfaces of TiO2 nanobelts (TNBs). The disinfection activities of Au@TNBs on model cell type, Gram-negative Escherichia coli (E. coli), were examined under visible light irradiation conditions. Au@TNBs exhibited stronger bactericidal properties toward E. coli than those of TNBs and Au NPs under visible light irradiation. The bactericidal mechanisms of Au@TNBs under light conditions were explored, specifically, the specific active species controlling the inactivation of bacteria were determined. Active species (H2O2, diffusing ∙OH, ∙O2-, 1O2, and e-) generated by Au@TNBs were found to play important roles on the inactivation of bacteria. Moreover, the concentrations of H2O2, ·OH, ·O2-, and 1O2 generated in the antimicrobial system were estimated. Without the presence of active species, the direct contact of Au@TNBs with bacterial cells was found to have no bactericidal effect. The reusability of Au@TNBs were also determined. Au@TNBs exhibited strong antibacterial activity toward E. coli even in five consecutively reused cycles. This study indicated that the fabricated Au@TNBs could be potentially utilized to inactivate bacteria in water.

  5. 77 FR 56860 - Notice of Proposed Settlement Agreement Under the Park System Resource Protection Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-14

    ... DREAMS regarding claims for response costs and damages ] under the Park System Resource Protection Act, 16 U.S.C. 19jj. The United States' claims arise from the grounding of the vessel COCKTAIL AND DREAMS... DREAMS, DJ No. 90-5-1-1-10656. The proposed settlement agreement may be examined at the Dry...

  6. 19 CFR 206.17 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Investigations Relating to Global Safeguard Actions § 206.17 Limited disclosure of certain confidential business... business information under administrative protective order. 206.17 Section 206.17 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO...

  7. 19 CFR 206.47 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... business information under administrative protective order. 206.47 Section 206.47 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO GLOBAL... Investigations for Relief From Market Disruption § 206.47 Limited disclosure of certain confidential...

  8. 19 CFR 206.47 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 3 2013-04-01 2013-04-01 false Limited disclosure of certain confidential business information under administrative protective order. 206.47 Section 206.47 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO...

  9. 19 CFR 206.37 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 3 2014-04-01 2014-04-01 false Limited disclosure of certain confidential business information under administrative protective order. 206.37 Section 206.37 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO...

  10. 19 CFR 206.66 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 3 2013-04-01 2013-04-01 false Limited disclosure of certain confidential business information under administrative protective order. 206.66 Section 206.66 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO...

  11. 19 CFR 206.37 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 3 2013-04-01 2013-04-01 false Limited disclosure of certain confidential business information under administrative protective order. 206.37 Section 206.37 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO...

  12. 19 CFR 206.47 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 3 2011-04-01 2011-04-01 false Limited disclosure of certain confidential business information under administrative protective order. 206.47 Section 206.47 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO...

  13. 19 CFR 206.66 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 3 2011-04-01 2011-04-01 false Limited disclosure of certain confidential business information under administrative protective order. 206.66 Section 206.66 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO...

  14. 19 CFR 206.47 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 3 2014-04-01 2014-04-01 false Limited disclosure of certain confidential business information under administrative protective order. 206.47 Section 206.47 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO...

  15. 19 CFR 206.66 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 3 2014-04-01 2014-04-01 false Limited disclosure of certain confidential business information under administrative protective order. 206.66 Section 206.66 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO...

  16. 77 FR 47095 - Notice of Proposed Settlement Agreement Under the Park System Resource Protection Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-07

    ... Smith regarding claims for response costs and damages under the Park System Resource Protection Act, 16 U.S.C. 19jj. The United States' claims arise from the grounding of the vessel F.G. Walton Smith in... Agreement. Comments should be addressed to the Assistant Attorney General, Environment and Natural...

  17. 76 FR 39150 - Determination Under Section 107(a) of the William Wilberforce Trafficking Victims Protection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-05

    ... to Congress and published in the Federal Register. Dated: June 15, 2011. Hillary Rodham Clinton... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Determination Under Section 107(a) of the William Wilberforce Trafficking Victims Protection Reauthorization...

  18. 78 FR 13101 - No FEAR Act Notice; Notice of Rights and Protections Available Under Federal Antidiscrimination...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... OVERSIGHT BOARD No FEAR Act Notice; Notice of Rights and Protections Available Under Federal... FEAR Act. The Act requires that federal agencies provide notice to their employees, former employees.... 1214(f). Nothing in the No FEAR Act alters existing laws or permits an agency to take...

  19. Protective Response Mechanisms to Heat Stress in Interaction with High [CO2] Conditions in Coffea spp.

    PubMed

    Martins, Madlles Q; Rodrigues, Weverton P; Fortunato, Ana S; Leitão, António E; Rodrigues, Ana P; Pais, Isabel P; Martins, Lima D; Silva, Maria J; Reboredo, Fernando H; Partelli, Fábio L; Campostrini, Eliemar; Tomaz, Marcelo A; Scotti-Campos, Paula; Ribeiro-Barros, Ana I; Lidon, Fernando J C; DaMatta, Fábio M; Ramalho, José C

    2016-01-01

    Modeling studies have predicted that coffee crop will be endangered by future global warming, but recent reports highlighted that high [CO2] can mitigate heat impacts on coffee. This work aimed at identifying heat protective mechanisms promoted by CO2 in Coffea arabica (cv. Icatu and IPR108) and Coffea canephora cv. Conilon CL153. Plants were grown at 25/20°C (day/night), under 380 or 700 μL CO2 L(-1), and then gradually submitted to 31/25, 37/30, and 42/34°C. Relevant heat tolerance up to 37/30°C for both [CO2] and all coffee genotypes was observed, likely supported by the maintenance or increase of the pools of several protective molecules (neoxanthin, lutein, carotenes, α-tocopherol, HSP70, raffinose), activities of antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), catalase (CAT), and the upregulated expression of some genes (ELIP, Chaperonin 20). However, at 42/34°C a tolerance threshold was reached, mostly in the 380-plants and Icatu. Adjustments in raffinose, lutein, β-carotene, α-tocopherol and HSP70 pools, and the upregulated expression of genes related to protective (ELIPS, HSP70, Chape 20, and 60) and antioxidant (CAT, CuSOD2, APX Cyt, APX Chl) proteins were largely driven by temperature. However, enhanced [CO2] maintained higher activities of GR (Icatu) and CAT (Icatu and IPR108), kept (or even increased) the Cu,Zn-SOD, APX, and CAT activities, and promoted a greater upregulation of those enzyme genes, as well as those related to HSP70, ELIPs, Chaperonins in CL153, and Icatu. These changes likely favored the maintenance of reactive oxygen species (ROS) at controlled levels and contributed to mitigate of photosystem II photoinhibition at the highest temperature. Overall, our results highlighted the important role of enhanced [CO2] on the coffee crop acclimation and sustainability under predicted future global warming scenarios.

  20. Protective Response Mechanisms to Heat Stress in Interaction with High [CO2] Conditions in Coffea spp.

    PubMed

    Martins, Madlles Q; Rodrigues, Weverton P; Fortunato, Ana S; Leitão, António E; Rodrigues, Ana P; Pais, Isabel P; Martins, Lima D; Silva, Maria J; Reboredo, Fernando H; Partelli, Fábio L; Campostrini, Eliemar; Tomaz, Marcelo A; Scotti-Campos, Paula; Ribeiro-Barros, Ana I; Lidon, Fernando J C; DaMatta, Fábio M; Ramalho, José C

    2016-01-01

    Modeling studies have predicted that coffee crop will be endangered by future global warming, but recent reports highlighted that high [CO2] can mitigate heat impacts on coffee. This work aimed at identifying heat protective mechanisms promoted by CO2 in Coffea arabica (cv. Icatu and IPR108) and Coffea canephora cv. Conilon CL153. Plants were grown at 25/20°C (day/night), under 380 or 700 μL CO2 L(-1), and then gradually submitted to 31/25, 37/30, and 42/34°C. Relevant heat tolerance up to 37/30°C for both [CO2] and all coffee genotypes was observed, likely supported by the maintenance or increase of the pools of several protective molecules (neoxanthin, lutein, carotenes, α-tocopherol, HSP70, raffinose), activities of antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), catalase (CAT), and the upregulated expression of some genes (ELIP, Chaperonin 20). However, at 42/34°C a tolerance threshold was reached, mostly in the 380-plants and Icatu. Adjustments in raffinose, lutein, β-carotene, α-tocopherol and HSP70 pools, and the upregulated expression of genes related to protective (ELIPS, HSP70, Chape 20, and 60) and antioxidant (CAT, CuSOD2, APX Cyt, APX Chl) proteins were largely driven by temperature. However, enhanced [CO2] maintained higher activities of GR (Icatu) and CAT (Icatu and IPR108), kept (or even increased) the Cu,Zn-SOD, APX, and CAT activities, and promoted a greater upregulation of those enzyme genes, as well as those related to HSP70, ELIPs, Chaperonins in CL153, and Icatu. These changes likely favored the maintenance of reactive oxygen species (ROS) at controlled levels and contributed to mitigate of photosystem II photoinhibition at the highest temperature. Overall, our results highlighted the important role of enhanced [CO2] on the coffee crop acclimation and sustainability under predicted future global warming scenarios. PMID:27446174

  1. Protective Response Mechanisms to Heat Stress in Interaction with High [CO2] Conditions in Coffea spp.

    PubMed Central

    Martins, Madlles Q.; Rodrigues, Weverton P.; Fortunato, Ana S.; Leitão, António E.; Rodrigues, Ana P.; Pais, Isabel P.; Martins, Lima D.; Silva, Maria J.; Reboredo, Fernando H.; Partelli, Fábio L.; Campostrini, Eliemar; Tomaz, Marcelo A.; Scotti-Campos, Paula; Ribeiro-Barros, Ana I.; Lidon, Fernando J. C.; DaMatta, Fábio M.; Ramalho, José C.

    2016-01-01

    Modeling studies have predicted that coffee crop will be endangered by future global warming, but recent reports highlighted that high [CO2] can mitigate heat impacts on coffee. This work aimed at identifying heat protective mechanisms promoted by CO2 in Coffea arabica (cv. Icatu and IPR108) and Coffea canephora cv. Conilon CL153. Plants were grown at 25/20°C (day/night), under 380 or 700 μL CO2 L−1, and then gradually submitted to 31/25, 37/30, and 42/34°C. Relevant heat tolerance up to 37/30°C for both [CO2] and all coffee genotypes was observed, likely supported by the maintenance or increase of the pools of several protective molecules (neoxanthin, lutein, carotenes, α-tocopherol, HSP70, raffinose), activities of antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), catalase (CAT), and the upregulated expression of some genes (ELIP, Chaperonin 20). However, at 42/34°C a tolerance threshold was reached, mostly in the 380-plants and Icatu. Adjustments in raffinose, lutein, β-carotene, α-tocopherol and HSP70 pools, and the upregulated expression of genes related to protective (ELIPS, HSP70, Chape 20, and 60) and antioxidant (CAT, CuSOD2, APX Cyt, APX Chl) proteins were largely driven by temperature. However, enhanced [CO2] maintained higher activities of GR (Icatu) and CAT (Icatu and IPR108), kept (or even increased) the Cu,Zn-SOD, APX, and CAT activities, and promoted a greater upregulation of those enzyme genes, as well as those related to HSP70, ELIPs, Chaperonins in CL153, and Icatu. These changes likely favored the maintenance of reactive oxygen species (ROS) at controlled levels and contributed to mitigate of photosystem II photoinhibition at the highest temperature. Overall, our results highlighted the important role of enhanced [CO2] on the coffee crop acclimation and sustainability under predicted future global warming scenarios. PMID:27446174

  2. Oxidative stress protection and stomatal patterning as components of salinity tolerance mechanism in quinoa (Chenopodium quinoa).

    PubMed

    Shabala, Lana; Mackay, Alex; Tian, Yu; Jacobsen, Sven-Erik; Zhou, Daowei; Shabala, Sergey

    2012-09-01

    Two components of salinity stress are a reduction in water availability to plants and the formation of reactive oxygen species. In this work, we have used quinoa (Chenopodium quinoa), a dicotyledonous C3 halophyte species displaying optimal growth at approximately 150 mM NaCl, to study mechanisms by which halophytes cope with the afore-mentioned components of salt stress. The relative contribution of organic and inorganic osmolytes in leaves of different physiological ages (e.g. positions on the stem) was quantified and linked with the osmoprotective function of organic osmolytes. We show that the extent of the oxidative stress (UV-B irradiation) damage to photosynthetic machinery in young leaves is much less when compared with old leaves, and attribute this difference to the difference in the size of the organic osmolyte pool (1.5-fold difference under control conditions; sixfold difference in plants grown at 400 mM NaCl). Consistent with this, salt-grown plants showed higher Fv/Fm values compared with control plants after UV-B exposure. Exogenous application of physiologically relevant concentrations of glycine betaine substantially mitigated oxidative stress damage to PSII, in a dose-dependent manner. We also show that salt-grown plants showed a significant (approximately 30%) reduction in stomatal density observed in all leaves. It is concluded that accumulation of organic osmolytes plays a dual role providing, in addition to osmotic adjustment, protection of photosynthetic machinery against oxidative stress in developing leaves. It is also suggested that salinity-induced reduction in stomatal density represents a fundamental mechanism by which plants optimize water use efficiency under saline conditions.

  3. Novel mechanism of network protection against the new generation of cyber attacks

    NASA Astrophysics Data System (ADS)

    Milovanov, Alexander; Bukshpun, Leonid; Pradhan, Ranjit

    2012-06-01

    A new intelligent mechanism is presented to protect networks against the new generation of cyber attacks. This mechanism integrates TCP/UDP/IP protocol stack protection and attacker/intruder deception to eliminate existing TCP/UDP/IP protocol stack vulnerabilities. It allows to detect currently undetectable, highly distributed, low-frequency attacks such as distributed denial-of-service (DDoS) attacks, coordinated attacks, botnet, and stealth network reconnaissance. The mechanism also allows insulating attacker/intruder from the network and redirecting the attack to a simulated network acting as a decoy. As a result, network security personnel gain sufficient time to defend the network and collect the attack information. The presented approach can be incorporated into wireless or wired networks that require protection against known and the new generation of cyber attacks.

  4. RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia.

    PubMed

    Zhang, Yan; Wildsoet, Christine F

    2015-01-01

    Myopia is the most common type of refractive errors and one of the world's leading causes of blindness. Visual manipulations in animal models have provided convincing evidence for the role of environmental factors in myopia development. These models along with in vitro studies have provided important insights into underlying mechanisms. The key locations of the retinal pigment epithelium (RPE) and choroid make them plausible conduits for relaying growth regulatory signals originating in the retina to the sclera, which ultimately determines eye size and shape. Identifying the key signal molecules and their targets may lead to the development of new myopia control treatments. This section summarizes findings implicating the RPE and choroid in myopia development. For RPE and/or choroid, changes in morphology, activity of ion channels/transporters, as well as in gene and protein expression, have been linked to altered eye growth. Both tissues thus represent potential targets for novel therapies for myopia.

  5. Mechanisms underlying the sperm quality advantage in Drosophila melanogaster.

    PubMed

    Pattarini, James M; Starmer, William T; Bjork, Adam; Pitnick, Scott

    2006-10-01

    Contrary to early predictions of sperm competition theory, postcopulatory sexual selection favoring increased investment per sperm (e.g., sperm size, sperm quality) has been demonstrated in numerous organisms. We empirically demonstrate for Drosophila melanogaster that both sperm quality and sperm quantity independently contribute to competitive male fertilization success. In addition to these independent effects, there was a significant interaction between sperm quality and quantity that suggests an internal positive reinforcement on selection for sperm quality, with selection predicted to intensify as investment per sperm increases and the number of sperm competing declines. The mechanism underlying the sperm quality advantage is elucidated through examination of the relationship between female sperm-storage organ morphology and the differential organization of different length sperm within the organ. Our results exemplify that primary sex cells can bear secondary sexual straits.

  6. RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia

    PubMed Central

    Zhang, Yan; Wildsoet, Christine F.

    2016-01-01

    Myopia is the most common type of refractive errors and one of the world’s leading causes of blindness. Visual manipulations in animal models have provided convincing evidence for the role of environmental factors in myopia development. These models along with in vitro studies have provided important insights into underlying mechanisms. The key locations of the retinal pigment epithelium (RPE) and choroid make them plausible conduits for relaying growth regulatory signals originating in the retina to the sclera, which ultimately determines eye size and shape. Identifying the key signal molecules and their targets may lead to the development of new myopia control treatments. This section summarizes findings implicating the RPE and choroid in myopia development. For RPE and/or choroid, changes in morphology, activity of ion channels/transporters, as well as in gene and protein expression, have been linked to altered eye growth. Both tissues thus represent potential targets for novel therapies for myopia. PMID:26310157

  7. Mechanisms underlying Phalaris aquatica "sudden death" syndrome in sheep.

    PubMed

    Bourke, C A; Carrigan, M J

    1992-07-01

    Twenty outbreaks of Phalaris aquatica "sudden death" syndrome in sheep were investigated between 1981 and 1991. Four were confirmed and one was suspected, to be a cardiac disorder; 5 were confirmed and 3 were suspected, to be a polioencephalomalacic disorder; the aetiology of the remaining 7 outbreaks could not be determined. Potentially toxic levels of hydrocyanic acid (20 to 36 mg/100 g) were measured in the 3 toxic phalaris pastures tested. The measurement of potentially toxic levels of nitrate nitrogen (2920 micrograms/g) in toxic phalaris pastures by others, was noted. It is suggested that phalaris "sudden death" syndrome could have as many as 4 different underlying mechanisms, and that these might reflect the presence in the plant of a cardio-respiratory toxin, a thiaminase and amine co-substate, cyanogenic compounds, and nitrate compounds. PMID:1445081

  8. Neural mechanisms underlying human consensus decision-making

    PubMed Central

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

    2015-01-01

    SUMMARY 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 novel 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 of 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. PMID:25864634

  9. Neural mechanisms underlying nicotine addiction: acute positive reinforcement and withdrawal.

    PubMed

    Watkins, S S; Koob, G F; Markou, A

    2000-02-01

    The neurobiology of nicotine addiction is reviewed within the context of neurobiological and behavioral theories postulated for other drugs of abuse. The roles of various neurotransmitter systems, including acetylcholine, dopamine, serotonin, glutamate, gamma-aminobutyric acid, and opioid peptides in acute nicotine reinforcement and withdrawal from chronic administration are examined followed by a discussion of potential neuroadaptations within these neurochemical systems that may lead to the development of nicotine dependence. The link between nicotine administration, depression and schizophrenia are also discussed. Finally, a theoretical model of the neurobiological mechanisms underlying acute nicotine withdrawal and protracted abstinence involves alterations within dopaminergic, serotonergic, and stress systems that are hypothesized to contribute to the negative affective state associated with nicotine abstinence.

  10. Mechanical behaviour of TWIP steel under shear loading

    NASA Astrophysics Data System (ADS)

    Vincze, G.; Butuc, M. C.; Barlat, F.

    2016-08-01

    Twinning induced plasticity steels (TWIP) are very good candidate for automotive industry applications because they potentially offer large energy absorption before failure due to their exceptional strain hardening capability and high strength. However, their behaviour is drastically influenced by the loading conditions. In this work, the mechanical behaviour of a TWIP steel sheet sample was investigated at room temperature under monotonic and reverse simple shear loading. It was shown that all the expected features of load reversal such as Bauschinger effect, transient strain hardening with high rate and permanent softening, depend on the prestrain level. This is in agreement with the fact that these effects, which occur during reloading, are related to the rearrangement of the dislocation structure induced during the predeformation. The homogeneous anisotropic hardening (HAH) approach proposed by Barlat et al. (2011) [1] was successfully employed to predict the experimental results.

  11. Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives.

    PubMed

    Linhart, Birgit; Valenta, Rudolf

    2012-06-19

    Hundred years ago therapeutic vaccination with allergen-containing extracts has been introduced as a clinically effective, disease-modifying, allergen-specific and long-lasting form of therapy for allergy, a hypersensitivity disease affecting more than 25% of the population. Today, the structures of most of the disease-causing allergens have been elucidated and recombinant hypoallergenic allergen derivatives with reduced allergenic activity have been engineered to reduce side effects during allergen-specific immunotherapy (SIT). These recombinant hypoallergens have been characterized in vitro, in experimental animal models and in clinical trials in allergic patients. This review provides a summary of the molecular, immunological and preclinical evaluation criteria applied for this new generation of allergy vaccines. Furthermore, we summarize the mechanisms underlying SIT with recombinant hypoallergens which are thought to be responsible for their therapeutic effect.

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

    PubMed

    Klein, Alice Victoria; Kiat, Hosen

    2015-05-01

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

  13. Mechanisms Underlying Development of Visual Maps and Receptive Fields

    PubMed Central

    Huberman, Andrew D.; Feller, Marla B.; Chapman, Barbara

    2008-01-01

    Patterns of synaptic connections in the visual system are remarkably precise. These connections dictate the receptive field properties of individual visual neurons and ultimately determine the quality of visual perception. Spontaneous neural activity is necessary for the development of various receptive field properties and visual feature maps. In recent years, attention has shifted to understanding the mechanisms by which spontaneous activity in the developing retina, lateral geniculate nucleus, and visual cortex instruct the axonal and dendritic refinements that give rise to orderly connections in the visual system. Axon guidance cues and a growing list of other molecules, including immune system factors, have also recently been implicated in visual circuit wiring. A major goal now is to determine how these molecules cooperate with spontaneous and visually evoked activity to give rise to the circuits underlying precise receptive field tuning and orderly visual maps. PMID:18558864

  14. Animal Studies and the Mechanism of Myopia-Protection by Light?

    PubMed

    Ashby, Regan

    2016-09-01

    Epidemiological studies have demonstrated that spending time outdoors during your childhood is protective against the development of myopia. It has been hypothesized that this protective effect is associated with light-induced increases in retinal dopamine levels, a critical neuromodulator that has long been postulated to be involved in the regulation of ocular growth. This paper, along with the paper entitled "What do animal studies tell us about the mechanism of myopia-protection by light?" discusses the evidence provided by animal models for this hypothesis. PMID:27560692

  15. Data on the mechanisms underlying succinate-induced aortic contraction.

    PubMed

    Gonzaga, Natália A; Simplicio, Janaina A; Leite, Letícia N; Vale, Gabriel T; Carballido, José M; Alves-Filho, José C; Tirapelli, Carlos R

    2016-12-01

    We describe the mechanisms underlying the vascular contraction induced by succinate. The data presented here are related to the article entitled "Pharmacological characterization of the mechanisms underlying the vascular effects of succinate" (L.N. Leite, N.A. Gonzaga, J.A. Simplicio, G.T. Vale, J.M. Carballido, J.C. Alves-Filho, C.R. Tirapelli, 2016) [1]. Succinate acts as a signaling molecule by binding to a G-protein-coupled receptor termed GPR91, "Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors" (W. He, F.J. Miao, D.C. Lin, R.T. Schwandner, Z. Wang, J. Gao, J.L. Chen, H. Tian, L. Ling, 2004) [2]. Here we include data on the contractile effect of succinate in the aorta. Succinate contracted both endothelium-intact and endothelium-denuded aortic rings isolated from male Wistar rats or C57BL/6 mice. Succinate was less effective at inducing contraction in arteries isolated from GPR91-deficient mice, when compared to its vascular effect in aortas from wild type mice. SB203508 (p38MAK inhibitor), SP600125 (JNK inhibitor) and Y27632 (Rho-kinase inhibitor) reduced succinate-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, while PD98059 (ERK1/2 inhibitor) did not affect succinate-induced contraction. The contractile response induced by succinate on endothelium-intact and endothelium-denuded rat aortic rings was reduced by indomethacin (non-selective cyclooxygenase inhibitor), H7 (protein kinase C inhibitor), verapamil (Ca(2+) channel blocker) and tiron (superoxide anion scavenger). PMID:27656674

  16. Data on the mechanisms underlying succinate-induced aortic contraction.

    PubMed

    Gonzaga, Natália A; Simplicio, Janaina A; Leite, Letícia N; Vale, Gabriel T; Carballido, José M; Alves-Filho, José C; Tirapelli, Carlos R

    2016-12-01

    We describe the mechanisms underlying the vascular contraction induced by succinate. The data presented here are related to the article entitled "Pharmacological characterization of the mechanisms underlying the vascular effects of succinate" (L.N. Leite, N.A. Gonzaga, J.A. Simplicio, G.T. Vale, J.M. Carballido, J.C. Alves-Filho, C.R. Tirapelli, 2016) [1]. Succinate acts as a signaling molecule by binding to a G-protein-coupled receptor termed GPR91, "Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors" (W. He, F.J. Miao, D.C. Lin, R.T. Schwandner, Z. Wang, J. Gao, J.L. Chen, H. Tian, L. Ling, 2004) [2]. Here we include data on the contractile effect of succinate in the aorta. Succinate contracted both endothelium-intact and endothelium-denuded aortic rings isolated from male Wistar rats or C57BL/6 mice. Succinate was less effective at inducing contraction in arteries isolated from GPR91-deficient mice, when compared to its vascular effect in aortas from wild type mice. SB203508 (p38MAK inhibitor), SP600125 (JNK inhibitor) and Y27632 (Rho-kinase inhibitor) reduced succinate-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, while PD98059 (ERK1/2 inhibitor) did not affect succinate-induced contraction. The contractile response induced by succinate on endothelium-intact and endothelium-denuded rat aortic rings was reduced by indomethacin (non-selective cyclooxygenase inhibitor), H7 (protein kinase C inhibitor), verapamil (Ca(2+) channel blocker) and tiron (superoxide anion scavenger).

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

    PubMed Central

    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

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

    PubMed

    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.

  19. Developmental mechanisms underlying variation in craniofacial disease and evolution.

    PubMed

    Fish, Jennifer L

    2016-07-15

    Craniofacial disease phenotypes exhibit significant variation in penetrance and severity. Although many genetic contributions to phenotypic variation have been identified, genotype-phenotype correlations remain imprecise. Recent work in evolutionary developmental biology has exposed intriguing developmental mechanisms that potentially explain incongruities in genotype-phenotype relationships. This review focuses on two observations from work in comparative and experimental animal model systems that highlight how development structures variation. First, multiple genetic inputs converge on relatively few developmental processes. Investigation of when and how variation in developmental processes occurs may therefore help predict potential genetic interactions and phenotypic outcomes. Second, genetic mutation is typically associated with an increase in phenotypic variance. Several models outlining developmental mechanisms underlying mutational increases in phenotypic variance are discussed using Satb2-mediated variation in jaw size as an example. These data highlight development as a critical mediator of genotype-phenotype correlations. Future research in evolutionary developmental biology focusing on tissue-level processes may help elucidate the "black box" between genotype and phenotype, potentially leading to novel treatment, earlier diagnoses, and better clinical consultations for individuals affected by craniofacial anomalies. PMID:26724698

  20. The Challenge of Characterizing Operations in the Mechanisms Underlying Behavior

    PubMed Central

    Bechtel, William

    2005-01-01

    Neuroscience and cognitive science seek to explain behavioral regularities in terms of underlying mechanisms. An important element of a mechanistic explanation is a characterization of the operations of the parts of the mechanism. The challenge in characterizing such operations is illustrated by an example from the history of physiological chemistry in which some investigators tried to characterize the internal operations in the same terms as the overall physiological system while others appealed to elemental chemistry. In order for biochemistry to become successful, researchers had to identify a new level of operations involving operations over molecular groups. Existing attempts at mechanistic explanation of behavior are in a situation comparable to earlier approaches to physiological chemistry, drawing their inspiration either from overall psychology activities or from low-level neural processes. Successful mechanistic explanations of behavior require the discovery of the appropriate component operations. Such discovery is a daunting challenge but one on which success will be beneficial to both behavioral scientists and cognitive and neuroscientists. PMID:16596967

  1. Continuing to illuminate the mechanisms underlying UV-mediated melanomagenesis

    PubMed Central

    Dellinger, Ryan W.; Liu-Smith, Feng; Meyskens, Frank L.

    2014-01-01

    The incidence of melanoma is one of the fastest growing of all tumor types in the United States and the number of cases worldwide has doubled in the past 30 years. Melanoma, which arises from melanocytes, is an extremely aggressive tumor that invades the vascular and lymphatic systems to establish tumors elsewhere in the body. Melanoma is a particularly resilient cancer and systemic therapy approaches have achieved minimal success against metastatic melanoma resulting in only a few FDA-approved treatments with limited benefit. Leading treatments offer minimal efficacy with response rates generally under 15% in the long term with no clear effect on melanoma-related mortality. Even the recent success of the specific BRAF mutant inhibitor vemurafenib has been tempered somewhat since acquired resistance is rapidly observed. Thus, understanding the mechanism(s) of melanoma carcinogenesis is paramount to combating this deadly disease. Not only for the treatment of melanoma but, ultimately, for prevention. In this report, we will summarize our work to date regarding the characterization of ultraviolet radiation (UVR)-mediated melanomagenesis and highlight several promising avenues of ongoing research. PMID:25022944

  2. Understanding mechanisms underlying human gene expression variation with RNA sequencing

    PubMed Central

    Pickrell, Joseph K.; Marioni, John C.; Pai, Athma A.; Degner, Jacob F.; Engelhardt, Barbara E.; Nkadori, Everlyne; Veyrieras, Jean-Baptiste; Stephens, Matthew; Gilad, Yoav; Pritchard, Jonathan K.

    2011-01-01

    Understanding the genetic mechanisms underlying natural variation in gene expression is a central goal of both medical and evolutionary genetics, and studies of expression quantitative trait loci (eQTLs) have become an important tool for achieving this goal1. Although all eQTL studies so far have assayed messenger RNA levels using expression microarrays, recent advances in RNA sequencing enable the analysis of transcript variation at unprecedented resolution. We sequenced RNA from 69 lymphoblastoid cell lines derived from unrelated Nigerian individuals that have been extensively genotyped by the International HapMap Project2. By pooling data from all individuals, we generated a map of the transcriptional landscape of these cells, identifying extensive use of unannotated untranslated regions and more than 100 new putative protein-coding exons. Using the genotypes from the HapMap project, we identified more than a thousand genes at which genetic variation influences overall expression levels or splicing. We demonstrate that eQTLs near genes generally act by a mechanism involving allele-specific expression, and that variation that influences the inclusion of an exon is enriched within and near the consensus splice sites. Our results illustrate the power of high-throughput sequencing for the joint analysis of variation in transcription, splicing and allele-specific expression across individuals. PMID:20220758

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

    PubMed

    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.

  4. Electron transport properties of single molecular junctions under mechanical modulations

    NASA Astrophysics Data System (ADS)

    Zhou, Jianfeng; Guo, Cunlan; Xu, Bingqian

    2012-04-01

    Electron transport behaviors of single molecular junctions are very sensitive to the atomic scale molecule-metal electrode contact interfaces, which have been difficult to control. We used a modified scanning probe microscope-break junction technique (SPM-BJT) to control the dynamics of the contacts and simultaneously monitor both the conductance and force. First, by fitting the measured data into a modified multiple tunneling barrier model, the static contact resistances, corresponding to the different contact conformations of single alkanedithiol and alkanediamine molecular junctions, were identified. Second, the changes of contact decay constant were measured under mechanical extensions of the molecular junctions, which helped to classify the different single molecular conductance sets into specific microscopic conformations of the molecule-electrode contacts. Third, by monitoring the changes of force and contact decay constant with the mechanical extensions, the changes of conductance were found to be caused by the changes of contact bond length and by the atomic reorganizations near the contact bond. This study provides a new insight into the understanding of the influences of contact conformations, especially the effect of changes of dynamic contact conformation on electron transport through single molecular junctions.

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

    PubMed

    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. PMID:27247385

  6. Using Drosophila to discover mechanisms underlying type 2 diabetes

    PubMed Central

    Alfa, Ronald W.; Kim, Seung K.

    2016-01-01

    ABSTRACT 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. PMID:27053133

  7. Investigating the mechanism(s) underlying switching between states in bipolar disorder

    PubMed Central

    Young, Jared W.; Dulcis, Davide

    2015-01-01

    Bipolar Disorder (BD) is a unique disorder that transcends domains of function since the same patient can exhibit depression or mania, states with polar opposite mood symptoms. During depression, people feel helplessness, reduced energy, and risk aversion, while with mania behaviors include grandiosity, increased energy, less sleep, and risk preference. The neural mechanism(s) underlying each state are gaining clarity, with catecholaminergic disruption seen during mania, and cholinergic dysfunction during depression. The fact that the same patient cycles/switches between these states is the defining characteristic of BD however. Of greater importance therefore, is the mechanism(s) underlying cycling from one state - and its associated neural changes - to another, considered the ‘holy grail’ of BD research. Herein, we review studies investigating triggers that induce switching to these states. By identifying such triggers, researchers can study neural mechanisms underlying each state and importantly how such mechanistic changes can occur in the same subject. Current animal models of this switch are also discussed, from submissive- and dominant-behaviors to kindling effects. Focus however, is placed on how seasonal changes can induce manic and depressive states in BD sufferers. Importantly, changing photoperiod lengths can induce local switches in neurotransmitter expression in normal animals, from increased catecholaminergic expression during periods of high activity, to increased somatostatin and corticotrophin releasing factor during periods of low activity. Identifying susceptibilities to this switch would enable the development of targeted animal models. From animal models, targeted treatments could be developed and tested that would minimize the likelihood of switching. PMID:25814263

  8. Rhein protects pancreatic β-cells from dynamin-related protein-1-mediated mitochondrial fission and cell apoptosis under hyperglycemia.

    PubMed

    Liu, Jing; Chen, Zhaohong; Zhang, Yujing; Zhang, Mingchao; Zhu, Xiaodong; Fan, Yun; Shi, Shaolin; Zen, Ke; Liu, Zhihong

    2013-11-01

    Rhein, an anthraquinone compound isolated from rhubarb, has been shown to improve glucose metabolism disorders in diabetic mice. The mechanism underlying the protective effect of rhein, however, remains unknown. Here, we demonstrate that rhein can protect the pancreatic β-cells against hyperglycemia-induced cell apoptosis through stabilizing mitochondrial morphology. Oral administration of rhein for 8 or 16 weeks in db/db mice significantly reduced fasting blood glucose (FBG) level and improved glucose tolerance. Cell apoptosis assay using both pancreatic sections and cultured pancreatic β-cells indicated that rhein strongly inhibited β-cell apoptosis. Morphological study showed that rhein was mainly localized at β-cell mitochondria and rhein could preserve mitochondrial ultrastructure by abolishing hyperglycemia-induced mitochondrial fission protein dynamin-related protein 1 (Drp1) expression. Western blot and functional analysis confirmed that rhein protected the pancreatic β-cells against hyperglycemia-induced apoptosis via suppressing mitochondrial Drp1 level. Finally, mechanistic study further suggested that decreased Drp1 level by rhein might be due to its effect on reducing cellular reactive oxygen species. Taken together, our study demonstrates for the first time that rhein can serve as a novel therapeutic agent for hyperglycemia treatment and rhein protects pancreatic β-cells from apoptosis by blocking the hyperglycemia-induced Drp1 expression. PMID:23919963

  9. Possible mechanisms underlying the testicular toxicity of oxfendazole in rats.

    PubMed

    Okamura, Miwa; Watanabe, Takao; Kashida, Yoko; Machida, Noboru; Mitsumori, Kunitoshi

    2004-01-01

    To clarify the mechanisms underlying the testicular toxicity of oxfendazole (OX), adult Wistar rats were orally administered a dose of 100 mg/kg/day for 3, 7, or 14 days. Assays of sex-related hormones showed a significant decrease in only the estradiol serum level at days 3 and 7, as compared with the control group. Histopathologically, marked degeneration of meiotic spermatocytes was observed in stage XIV-I seminiferous tubules from day 3 onwards, and these spermatocytes gave positive results on terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL). Abnormalities of spermiogenesis such as megakaryospermatids and binucleated spermatids were also observed in the testes of OX-treated rats. Under the electron microscope, lipid accumulation and dilatation of the endoplasmic reticulum were frequently found in the cytoplasm of the Sertoli cells on day 3. These results strongly suggest that OX induces both apoptosis of meiotic spermatocytes, most probably due to disruption of the microtubules, and degeneration of the Sertoli cells, characterized by distended endoplasmic reticulum and prominent cytosolic lipid accumulation.

  10. Obesity and thyroid cancer: epidemiologic associations and underlying mechanisms.

    PubMed

    Pazaitou-Panayiotou, K; Polyzos, S A; Mantzoros, C S

    2013-12-01

    The incidence of thyroid cancer has been rising over the past few decades along with a parallel increase in obesity. Observational studies have provided evidence for a potential association between the two. By contrast, clinical data for a link between type 2 diabetes mellitus, a condition strongly associated with obesity, and thyroid cancer are limited and largely not supportive of such an association. Obesity leads to hypoadiponectinemia, a pro-inflammatory state, and insulin resistance, which, in turn, leads to high circulating insulin and insulin-like growth factor-1 levels, thereby possibly increasing the risk for thyroid cancer. Thus, insulin resistance possibly plays a pivotal role in underlying the observed association between obesity and thyroid cancer, potentially leading to the development and/or progression of thyroid cancer, through its interconnections with other factors including insulin-like growth factor-1, adipocytokines/cytokines and thyroid-stimulating hormone. In this review, epidemiological and clinical evidence and potential mechanisms underlying the proposed association between obesity and thyroid cancer risk are reviewed. If the association between obesity and thyroid cancer demonstrated in observational studies proves to be causal, targeting obesity (and/or downstream mediators of risk) could be of importance in the prevention and management of thyroid cancer.

  11. A Novel IL-17 Dependent Mechanism of Cross Protection: Respiratory Infection with Mycoplasma Protects Against a Secondary Listeria Infection

    PubMed Central

    Sieve, Amy N.; Meeks, Karen D.; Bodhankar, Sheetal; Lee, Suheung; Kolls, Jay K.; Simecka, Jerry W.; Berg, Rance E.

    2009-01-01

    Summary Immune responses to pathogens occur within the context of current and previous infections. Cross protection refers to the phenomena where infection with a particular pathogen provides enhanced resistance to a subsequent unrelated pathogen in an antigen independent manner. Proposed mechanisms of antigen-independent cross protection have involved the secretion of IFN-γ, which activates macrophages thus providing enhanced innate immunity against the secondary viral or bacterial pathogen. Here we provide evidence that a primary infection with the chronic respiratory pathogen, Mycoplasma pulmonis, provides a novel form of cross protection against a secondary infection with Listeria monocytogenes that is not mediated by IFN-γ, but instead relies upon IL-17 and mobilization of neutrophils. Mice infected with M. pulmonis have enhanced clearance of L. monocytogenes from the spleen and liver which is associated with increased numbers of Gr-1+CD11b+ cells and higher levels of IL-17. This enhanced clearance of L. monocytogenes was absent in mice depleted of Gr-1+ cells or in mice deficient in the IL-17 receptor. Additionally, both the IL-17 receptor and neutrophils were essential for optimal clearance of M. pulmonis. Thus, a natural component of the immune response directed against M. pulmonis was able to enhance clearance of L. monocytogenes. PMID:19180464

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

    NASA Technical Reports Server (NTRS)

    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

  13. Remote ischemic preconditioning for kidney protection: GSK3β-centric insights into the mechanism of action.

    PubMed

    Liu, Zhangsuo; Gong, Rujun

    2015-11-01

    Preventing acute kidney injury (AKI) in high-risk patients following medical interventions is a paramount challenge for clinical practice. Recent data from animal experiments and clinical trials indicate that remote ischemic preconditioning, represented by limb ischemic preconditioning, confers a protective action on the kidney. Ischemic preconditioning is effective in reducing the risk for AKI following cardiovascular interventions and the use of iodinated radiocontrast media. Nevertheless, the underlying mechanisms for this protective effect are elusive. A protective signal is conveyed from the remote site undergoing ischemic preconditioning, such as the limb, to target organs, such as the kidney, by multiple potential communication pathways, which may involve humoral, neuronal, and systemic mechanisms. Diverse transmitting pathways trigger a variety of signaling cascades, including the reperfusion injury salvage kinase and survivor activating factor enhancement pathways, all of which converge on glycogen synthase kinase 3β (GSK3β). Inhibition of GSK3β subsequent to ischemic preconditioning reinforces the Nrf2-mediated antioxidant defense, diminishes the nuclear factor-κB-dependent proinflammatory response, and exerts prosurvival effects ensuing from the desensitized mitochondria permeability transition. Thus, therapeutic targeting of GSK3β by ischemic preconditioning or by pharmacologic preconditioning with existing US Food and Drug Administration-approved drugs having GSK3β-inhibitory activities might represent a pragmatic and cost-effective adjuvant strategy for kidney protection and prophylaxis against AKI.

  14. Methylprednisolone Protects Cardiac Pumping Mechanics from Deteriorating in Lipopolysaccharide-Treated Rats

    PubMed Central

    Ko, Ya-Hui; Tsai, Ming-Shian; Chang, Ru-Wen; Chang, Chun-Yi; Wang, Chih-Hsien; Wu, Ming-Shiou; Liang, Jin-Tung; Chang, Kuo-Chu

    2015-01-01

    It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid) can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg−1 d−1) for 2 weeks. The lipopolysaccharide-challenged rats were treated on a daily basis with intraperitoneal injection of methylprednisolone (5 mg kg−1 d−1) for 2 weeks. Under conditions of anesthesia and open chest, we recorded left ventricular (LV) pressure and ascending aortic flow signals to calculate the maximal systolic elastance (Emax) and the theoretical maximum flow (Qmax), using the elastance-resistance model. Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Qmax has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in Emax associated with the increased Qmax in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased Emax, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Qmax, indicating that the drug may have normalized the LV internal resistance. In parallel, the benefits of methylprednisolone on the LV systolic pumping mechanics were associated with the reduced cardiac levels of negative inotropic molecules such as peroxynitrite, malondialdehyde, and high-mobility group box 1 protein. Based on these data, we suggested that low-dose methylprednisolone might prevent lipopolysaccharide-induced decline in cardiac intrinsic contractility and LV internal

  15. Protective effect and mechanism of hydrogen treatment on lung epithelial barrier dysfunction in rats with sepsis.

    PubMed

    Liu, L-D; Wu, X-Y; Tao, B-D; Wang, N; Zhang, J

    2016-01-01

    This study aimed to explore the protective effect of hydrogen and to investigate the underlying mechanism of its preliminary effect on the alveolar epithelial barrier function in septic rats. Forty-five male Sprague-Dawley rats were divided randomly into three groups (N = 15): control [saline injection (intraperitoneal, ip), air drawing; SA], acute lung injury group [lipopolysaccharide (LPS) injection (ip, 15 mg/kg), air drawing; LA], and acute lung injury combined with hydrogen drawing group [LPS injection (ip, 15 mg/kg), 2% hydrogen drawing; LH]. The rats were euthanized after 6 h of treatment, and the extravascular lung water (EVLW), pulmonary alveolar-arterial oxygen pressure (A-aDO2), and respiratory index (RI) of each group were measured. The aquaporin-1 (AQP-1) protein expression in the lung tissues was detected using immunohistochemistry and western blotting, and the correlation between the EVLW and AQP-1 was analyzed. The lung morphology was observed with light and electron microscopy. In the LA group, EVLW (0.87 ± 0.17), A-aDO2 (113.21 ± 13.92), RI (0.65 ± 0.26), and AQP-1 expression increased. Additionally, thickened alveolar walls, significant invasion of inflammatory cells around the vessels, capillary ectasia, hyperemia/hemorrhage in the alveolar space, significantly swollen mitochondria, and increased vacuolar degeneration were observed. A significant negative correlation between AQP-1 expression and EVLW was observed (R2 = 0.8806). Compared with the LA group, EVLW (0.71 ± 0.19), A-aDO2 (132.42 ± 17.39), RI (0.75 ± 0.24), and inflammatory reaction decreased and AQP-1 expression increased in the LH group. The damage to pulmonary epithelial cells improved after hydrogen treatment in rats with sepsis; hydrogen could protect the pulmonary epithelial barrier function by acting on AQP-1. PMID:26909920

  16. Dual mechanism of protection by live attenuated Bordetella pertussis BPZE1 against Bordetella bronchiseptica in mice.

    PubMed

    Kammoun, Hana; Feunou, Pascal Feunou; Foligne, Benoit; Debrie, Anne-Sophie; Raze, Dominique; Mielcarek, Nathalie; Locht, Camille

    2012-08-31

    Bordetella bronchiseptica, a gram-negative bacterium, causes chronic respiratory tract infections in a wide variety of mammalian hosts, including man, and no human vaccine is currently available. Acellular pertussis vaccines protect poorly against B. bronchiseptica, although they contain cross-reactive antigens. We have recently developed Bordetella pertussis BPZE1, a novel, live attenuated pertussis vaccine, currently completing phase I clinical trials in humans, and found that it protects against both B. pertussis and Bordetella parapertussis in mice. Here, we show that a single nasal administration of BPZE1 protects mice against lethal infection with B. bronchiseptica. After challenge, the vaccinated animals displayed markedly reduced lung inflammation and tissue damage, decreased neutrophil infiltration and increased levels of CD4(+)CD25(+)FoxP3(+) regulatory T cells in the lungs compared to non-immunized mice. Depletion of these cells abolished BPZE1-induced protection, indicating that BPZE1 protects against lethal inflammation through the recruitment of regulatory T cells. In addition, the B. bronchiseptica load was significantly decreased in the vaccinated animals. Using passive transfer experiments, protection was found to be essentially cell mediated, and BPZE1-induced Th1 and Th17 T cells recognize whole B. bronchiseptica extracts, although the participation of antibodies in protection cannot be discounted. Thus, a single administration of BPZE1 can confer protection against B. bronchiseptica in mice by a dual mechanism.

  17. Molecular Mechanisms Regulating Muscle Fiber Composition Under Microgravity

    NASA Technical Reports Server (NTRS)

    Rosenthal, Nadia A.

    1999-01-01

    The overall goal of this project is to reveal the molecular mechanisms underlying the selective and debilitating atrophy of specific skeletal muscle fiber types that accompanies sustained conditions of microgravity. Since little is currently known about the regulation of fiber-specific gene expression programs in mammalian muscle, elucidation of the basic mechanisms of fiber diversification is a necessary prerequisite to the generation of therapeutic strategies for attenuation of muscle atrophy on earth or in space. Vertebrate skeletal muscle development involves the fusion of undifferentiated mononucleated myoblasts to form multinucleated myofibers, with a concomitant activation of muscle-specific genes encoding proteins that form the force-generating contractile apparatus. The regulatory circuitry controlling skeletal muscle gene expression has been well studied in a number of vertebrate animal systems. The goal of this project has been to achieve a similar level of understanding of the mechanisms underlying the further specification of muscles into different fiber types, and the role played by innervation and physical activity in the maintenance and adaptation of different fiber phenotypes into adulthood. Our recent research on the genetic basis of fiber specificity has focused on the emergence of mature fiber types and have implicated a group of transcriptional regulatory proteins, known as E proteins, in the control of fiber specificity. The restriction of E proteins to selected muscle fiber types is an attractive hypothetical mechanism for the generation of muscle fiber-specific patterns of gene expression. To date our results support a model wherein different E proteins are selectively expressed in muscle cells to determine fiber-restricted gene expression. These studies are a first step to define the molecular mechanisms responsible for the shifts in fiber type under conditions of microgravity, and to determine the potential importance of E proteins as

  18. Structural basis for the nonlinear mechanics of fibrin networks under compression.

    PubMed

    Kim, Oleg V; Litvinov, Rustem I; Weisel, John W; Alber, Mark S

    2014-08-01

    Fibrin is a protein polymer that forms a 3D filamentous network, a major structural component of protective physiological blood clots as well as life threatening pathological thrombi. It plays an important role in wound healing, tissue regeneration and is widely employed in surgery as a sealant and in tissue engineering as a scaffold. The goal of this study was to establish correlations between structural changes and mechanical responses of fibrin networks exposed to compressive loads. Rheological measurements revealed nonlinear changes of fibrin network viscoelastic properties under dynamic compression, resulting in network softening followed by its dramatic hardening. Repeated compression/decompression enhanced fibrin clot stiffening. Combining fibrin network rheology with simultaneous confocal microscopy provided direct evidence of structural modulations underlying nonlinear viscoelasticity of compressed fibrin networks. Fibrin clot softening in response to compression strongly correlated with fiber buckling and bending, while hardening was associated with fibrin network densification. Our results suggest a complex interplay of entropic and enthalpic mechanisms accompanying structural changes and accounting for the nonlinear mechanical response in fibrin networks undergoing compressive deformations. These findings provide new insight into the fibrin clot structural mechanics and can be useful for designing fibrin-based biomaterials with modulated viscoelastic properties.

  19. Structural basis for the nonlinear mechanics of fibrin networks under compression.

    PubMed

    Kim, Oleg V; Litvinov, Rustem I; Weisel, John W; Alber, Mark S

    2014-08-01

    Fibrin is a protein polymer that forms a 3D filamentous network, a major structural component of protective physiological blood clots as well as life threatening pathological thrombi. It plays an important role in wound healing, tissue regeneration and is widely employed in surgery as a sealant and in tissue engineering as a scaffold. The goal of this study was to establish correlations between structural changes and mechanical responses of fibrin networks exposed to compressive loads. Rheological measurements revealed nonlinear changes of fibrin network viscoelastic properties under dynamic compression, resulting in network softening followed by its dramatic hardening. Repeated compression/decompression enhanced fibrin clot stiffening. Combining fibrin network rheology with simultaneous confocal microscopy provided direct evidence of structural modulations underlying nonlinear viscoelasticity of compressed fibrin networks. Fibrin clot softening in response to compression strongly correlated with fiber buckling and bending, while hardening was associated with fibrin network densification. Our results suggest a complex interplay of entropic and enthalpic mechanisms accompanying structural changes and accounting for the nonlinear mechanical response in fibrin networks undergoing compressive deformations. These findings provide new insight into the fibrin clot structural mechanics and can be useful for designing fibrin-based biomaterials with modulated viscoelastic properties. PMID:24840618

  20. Structural basis for the nonlinear mechanics of fibrin networks under compression

    PubMed Central

    Kim, Oleg V.; Litvinov, Rustem I.; Weisel, John W.; Alber, Mark S.

    2014-01-01

    Fibrin is a protein polymer that forms a 3D filamentous network, a major structural component of protective physiological blood clots as well as life threatening pathological thrombi. It plays an important role in wound healing, tissue regeneration and is widely employed in surgery as a sealant and in tissue engineering as a scaffold. The goal of this study was to establish correlations between structural changes and mechanical responses of fibrin networks exposed to compressive loads. Rheological measurements revealed nonlinear changes of fibrin network viscoelastic properties under dynamic compression, resulting in network softening followed by its dramatic hardening. Repeated compression/decompression enhanced fibrin clot stiffening. Combining fibrin network rheology with simultaneous confocal microscopy provided direct evidence of structural modulations underlying nonlinear viscoelasticity of compressed fibrin networks. Fibrin clot softening in response to compression strongly correlated with fiber buckling and bending, while hardening was associated with fibrin network densification. Our results suggest a complex interplay of entropic and enthalpic mechanisms accompanying structural changes and accounting for the nonlinear mechanical response in fibrin networks undergoing compressive deformations. These findings provide new insight into the fibrin clot structural mechanics and can be useful for designing fibrin-based biomaterials with modulated viscoelastic properties. PMID:24840618

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

    PubMed

    Silverman, Marni N; Deuster, Patricia A

    2014-10-01

    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 appears to buffer against stress-related disease owing to its blunting/optimizing effects on hormonal stress responsive systems, such as the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. This blunting appears to contribute to reduced emotional, physiological and metabolic reactivity as well as increased positive mood and well-being. Another mechanism whereby regular exercise and/or physical fitness may confer resilience is through minimizing excessive inflammation. Chronic psychological stress, physical inactivity and abdominal adiposity have been associated with persistent, systemic, low-grade inflammation and exert adverse effects on mental and physical health. The anti-inflammatory effects of regular exercise/activity can promote behavioural and metabolic resilience, and protect against various chronic diseases associated with systemic inflammation. Moreover, exercise may benefit the brain by enhancing growth factor expression and neural plasticity, thereby contributing to improved mood and cognition. In summary, the mechanisms whereby physical fitness promotes increased resilience and well-being and positive psychological and physical health are diverse and complex. PMID:25285199

  2. Mechanical Modeling of a WIPP Drum Under Pressure

    SciTech Connect

    Smith, Jeffrey A.

    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

  3. Proteomic analysis of Ketogulonicigenium vulgare under glutathione reveals high demand for thiamin transport and antioxidant protection.

    PubMed

    Ma, Qian; Zhang, Weiwen; Zhang, Lu; Qiao, Bin; Pan, Chensong; Yi, Hong; Wang, Lili; Yuan, Ying-jin

    2012-01-01

    Ketogulonicigenium vulgare, though grows poorly when mono-cultured, has been widely used in the industrial production of the precursor of vitamin C with the coculture of Bacillus megaterium. Various efforts have been made to clarify the synergic pattern of this artificial microbial community and to improve the growth and production ability of K. vulgare, but there is still no sound explanation. In previous research, we found that the addition of reduced glutathione into K. vulgare monoculture could significantly improve its growth and productivity. By performing SEM and TEM, we observed that after adding GSH into K. vulgare monoculture, cells became about 4-6 folds elongated, and formed intracytoplasmic membranes (ICM). To explore the molecular mechanism and provide insights into the investigation of the synergic pattern of the co-culture system, we conducted a comparative iTRAQ-2-D-LC-MS/MS-based proteomic analysis of K. vulgare grown under reduced glutathione. Principal component analysis of proteomic data showed that after the addition of glutathione, proteins for thiamin/thiamin pyrophosphate (TPP) transport, glutathione transport and the maintenance of membrane integrity, together with several membrane-bound dehydrogenases had significant up-regulation. Besides, several proteins participating in the pentose phosphate pathway and tricarboxylic acid cycle were also up-regulated. Additionally, proteins combating intracellular reactive oxygen species were also up-regulated, which similarly occurred in K. vulgare when the co-cultured B. megaterium cells lysed from our former research results. This study reveals the demand for transmembrane transport of substrates, especially thiamin, and the demand for antioxidant protection of K. vulgare.

  4. Comparison of marine and terrestrial protected areas under federal jurisdiction in the United States

    USGS Publications Warehouse

    Lindholm, J.; Barr, B.

    2001-01-01

    There is a significant disparity in the protection of terrestrial and marine environments in the United States. Despite the considerable literature dedicated to the subject of protected areas, both terrestrial and marine, in the United States, we are not aware of work explicitly describing this dichotomy. We compared marine and terrestrial areas under federal jurisdiction to provide a quantitative assessment of the differences between the conservation of land and sea in the United States. Specifically, we compared national marine sanctuaries (including sanctuary preservation areas and ecological reserves) with national parks, national forests, and national wildlife refuges (including national wilderness preservation areas). Our results suggest that marine sanctuaries are fewer in number, smaller in total area, and smaller in percentage of area covered than are terrestrial protected areas.

  5. Nutraceutical properties of Mediterranean diet and cognitive decline: possible underlying mechanisms.

    PubMed

    Frisardi, Vincenza; Panza, Francesco; Seripa, Davide; Imbimbo, Bruno P; Vendemiale, Gianluigi; Pilotto, Alberto; Solfrizzi, Vincenzo

    2010-01-01

    Recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from mild cognitive impairment to Alzheimer's disease (AD), reduced risk of AD, and decreased mortality in AD patients. Furthermore, the Mediterranean diet (MeDi) combines several foods, micro- and macronutrients already separately proposed as potential protective factors against dementia and predementia syndromes. At present, epidemiological evidence suggests a possible association between fish consumption, monounsaturated fatty acids, and polyunsaturated fatty acids (PUFA) (particularly, n-3 PUFA), and reduced risk of cognitive decline and dementia. Light to moderate alcohol use may be associated with a reduced risk of incident dementia and AD, while for vascular dementia, cognitive decline, and predementia syndromes, the current evidence is only suggestive of a protective effect. Finally, the limited epidemiological evidence available on fruit and vegetable consumption and cognition generally support a protective role of these macronutrients against cognitive decline, dementia, and AD. We reviewed evidence on the possible mechanisms underlying the suggested protective role of MeDi against age-related changes in cognitive function, predementia syndromes, and dementia, examining the possible role of macronutrients and food nutrients of the MeDi and their nutraceutical properties in modulating the risk of cognitive decline. Although vascular variables are likely to be in the causal pathway between MeDi and dementia syndromes and should be considered as possible mediators, other nonvascular biological mechanisms (i.e., metabolic, oxidative, and inflammatory) may be invoked to explain the complex epidemiological association between MeDi and cognitive decline.

  6. 3-Hydroxybutyrate methyl ester as a potential drug against Alzheimer's disease via mitochondria protection mechanism.

    PubMed

    Zhang, Junyu; Cao, Qian; Li, Shaowu; Lu, Xiaoyun; Zhao, Yongxi; Guan, Ji-Song; Chen, Jin-Chun; Wu, Qiong; Chen, Guo-Qiang

    2013-10-01

    Alzheimer's disease (AD) is induced by many reasons, including decreased cellular utilization of glucose and brain cell mitochondrial damages. Degradation product of microbially synthesized polyhydroxybutyrate (PHB), namely, 3-hydroxybutyrate (3HB), can be an alternative to glucose during sustained hypoglycemia. In this study, the derivative of 3HB, 3-hydroxybutyrate methyl ester (HBME), was used by cells as an alternative to glucose. HBME inhibited cell apoptosis under glucose deprivation, rescued activities of mitochondrial respiratory chain complexes that were impaired in AD patients and decreased the generation of ROS. Meanwhile, HBME stabilized the mitochondrial membrane potential. In vivo studies showed that HBME crossed the blood brain barrier easier compared with charged 3HB, resulting in a better bioavailability. AD mice treated with HBME performed significantly better (p < 0.05) in the Morris water maze compared with other groups, demonstrating that HBME has a positive in vivo pharmaceutical effect to improve the spatial learning and working memory of mice. A reduced amyloid-β deposition in mouse brains after intragastric administration of HBME was also observed. Combined with the in vitro and in vivo results, HBME was proposed to be a drug candidate against AD, its working mechanism appeared to be mediated by various effects of protecting mitochondrial damages.

  7. Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration

    PubMed Central

    Wang, Hui-Chen; Lee, Wen-Sen

    2016-01-01

    Progesterone (P4) was demonstrated to inhibit migration in vascular smooth muscle cells (VSMCs), but to enhance migration in T47D breast cancer cells. To investigate the mechanism responsible for this switch in P4 action, we examined the signaling pathway responsible for the P4-induced migration enhancement in breast cancer cell lines, T47D and MCF-7. Here, we demonstrated that P4 activated the cSrc/AKT signaling pathway, subsequently inducing RSK1 activation, which in turn increased phosphorylation of p27 at T198 and formation of the p27pT198-RhoA complex in the cytosol, thereby preventing RhoA degradation, and eventually enhanced migration in T47D cells. These findings were confirmed in the P4-treated MCF-7. Comparing the P4-induced molecular events in between breast cancer cells and VSMCs, we found that P4 increased p27 phosphorylation at T198 in breast cancer cells through RSK1 activation, while P4 increased p27 phosphorlation at Ser10 in VSMCs through KIS activation. P27pT198 formed the complex with RhoA and prevented RhoA degradation in T47D cells, whereas p-p27Ser10 formed the complex with RhoA and caused RhoA degradation in VSMCs. The results of this study highlight the molecular mechanism underlying P4-enhanced breast cancer cell migration, and suggest that RSK1 activation is responsible for the P4-induced migration enhancement in breast cancer cells. PMID:27510838

  8. Circadian Mechanisms Underlying Reward-Related Neurophysiology and Synaptic Plasticity

    PubMed Central

    Parekh, Puja K.; McClung, Colleen A.

    2016-01-01

    Evidence from clinical and preclinical research provides an undeniable link between disruptions in the circadian clock and the development of psychiatric diseases, including mood and substance abuse disorders. The molecular clock, which controls daily patterns of physiological and behavioral activity in living organisms, when desynchronized, may exacerbate or precipitate symptoms of psychiatric illness. One of the outstanding questions remaining in this field is that of cause and effect in the relationship between circadian rhythm disruption and psychiatric disease. Focus has recently turned to uncovering the role of circadian proteins beyond the maintenance of homeostatic systems and outside of the suprachiasmatic nucleus (SCN), the master pacemaker region of the brain. In this regard, several groups, including our own, have sought to understand how circadian proteins regulate mechanisms of synaptic plasticity and neurotransmitter signaling in mesocorticolimbic brain regions, which are known to be critically involved in reward processing and mood. This regulation can come in the form of direct transcriptional control of genes central to mood and reward, including those associated with dopaminergic activity in the midbrain. It can also be seen at the circuit level through indirect connections of mesocorticolimbic regions with the SCN. Circadian misalignment paradigms as well as genetic models of circadian disruption have helped to elucidate some of the complex interactions between these systems and neural activity influencing behavior. In this review, we explore findings that link circadian protein function with synaptic adaptations underlying plasticity as it may contribute to the development of mood disorders and addiction. In light of recent advances in technology and sophisticated methods for molecular and circuit-level interrogation, we propose future directions aimed at teasing apart mechanisms through which the circadian system modulates mood and reward

  9. Underlying Mechanisms of Tinnitus: Review and Clinical Implications

    PubMed Central

    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

  10. Circadian Mechanisms Underlying Reward-Related Neurophysiology and Synaptic Plasticity.

    PubMed

    Parekh, Puja K; McClung, Colleen A

    2015-01-01

    Evidence from clinical and preclinical research provides an undeniable link between disruptions in the circadian clock and the development of psychiatric diseases, including mood and substance abuse disorders. The molecular clock, which controls daily patterns of physiological and behavioral activity in living organisms, when desynchronized, may exacerbate or precipitate symptoms of psychiatric illness. One of the outstanding questions remaining in this field is that of cause and effect in the relationship between circadian rhythm disruption and psychiatric disease. Focus has recently turned to uncovering the role of circadian proteins beyond the maintenance of homeostatic systems and outside of the suprachiasmatic nucleus (SCN), the master pacemaker region of the brain. In this regard, several groups, including our own, have sought to understand how circadian proteins regulate mechanisms of synaptic plasticity and neurotransmitter signaling in mesocorticolimbic brain regions, which are known to be critically involved in reward processing and mood. This regulation can come in the form of direct transcriptional control of genes central to mood and reward, including those associated with dopaminergic activity in the midbrain. It can also be seen at the circuit level through indirect connections of mesocorticolimbic regions with the SCN. Circadian misalignment paradigms as well as genetic models of circadian disruption have helped to elucidate some of the complex interactions between these systems and neural activity influencing behavior. In this review, we explore findings that link circadian protein function with synaptic adaptations underlying plasticity as it may contribute to the development of mood disorders and addiction. In light of recent advances in technology and sophisticated methods for molecular and circuit-level interrogation, we propose future directions aimed at teasing apart mechanisms through which the circadian system modulates mood and reward

  11. Mechanisms underlying reduced fertility in anovular dairy cows.

    PubMed

    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

  12. Cross-Protection by Infectious Bronchitis Viruses Under Controlled Experimental Conditions.

    PubMed

    Toro, H; van Santen, V L; Ghetas, A M; Joiner, K S

    2015-12-01

    Infectious bronchitis virus (IBV) cross-protection trials were performed in healthy chickens maintained under controlled environmental conditions. Chickens primed or primed and boosted with a Massachusetts (Mass)-type attenuated vaccine were subsequently challenged with either IBV Arkansas (Ark) or GA13-type virulent strains. In addition, Ark-vaccinated chickens were challenged with IBV GA13. Spike protein 1 (S1) amino acid identities between IBV vaccine and challenge strains varied from 76.0% to 77.3%. Contrary to expectations, assessments of clinical signs, viral load, and histopathology indicated a significant level of cross-protection among these antigenically distant IBV strains. Moreover, prime and booster vaccination with Mass protected against GA13 and improved protection against Ark when compared with Mass single vaccination. These results emphasize the need to include both single vaccination control groups and control groups primed and boosted with a single serotype when testing the efficacy of IBV protectotypes and/or novel IBV vaccine combinations against heterologous serotypes under controlled experimental conditions. Such controls are of distinct importance in experiments supporting the introduction of attenuated IBV vaccine strains exotic to regions, since these exotic strains may provide new genetic material for recombination and emergence of novel IBV strains. PMID:26629628

  13. Investigation of Nucleate Boiling Mechanisms Under Microgravity Conditions

    NASA Technical Reports Server (NTRS)

    Dhir, V. K.; Qiu, D. M.; Ramanujapu, N.; Hasan, M. M.

    1999-01-01

    The present work is aimed at the experimental studies and numerical modeling of the bubble growth mechanisms of a single bubble attached to a heating surface and of a bubble sliding along an inclined heated plate. Single artificial cavity of 10 microns in diameter was made on the polished Silicon wafer which was electrically heated at the back side in order to control the surface nucleation superheat. Experiments with a sliding bubble were conducted at different inclination angles of the downward facing heated surface for the purpose of studying the effect of magnitude of components of gravity acting parallel to and normal to the heat transfer surface. Information on the bubble shape and size, the bubble induced liquid velocities as well as the surface temperature were obtained using the high speed imaging and hydrogen bubble techniques. Analytical/numerical models were developed to describe the heat transfer through the micro-macro layer underneath and around a bubble formed at a nucleation site. In the micro layer model the capillary and disjoining pressures were included. Evolution of the bubble-liquid interface along with induced liquid motion was modeled. As a follow-up to the studies at normal gravity, experiments are being conducted in the KC-135 aircraft to understand the bubble growth/detachment under low gravity conditions. Experiments have been defined to be performed under long duration of microgravity conditions in the space shuttle. The experiment in the space shuttle will provide bubble growth and detachment data at microgravity and will lead to validation of the nucleate boiling heat transfer model developed from the preceding studies conducted at normal and low gravity (KC-135) conditions.

  14. Investigation of Mechanisms Associated with Nucleate Boiling Under Microgravity Conditions

    NASA Technical Reports Server (NTRS)

    Dhir, Vijay K.

    1996-01-01

    The focus of the present work is to experimentally study and to analytically/numerically model the mechanisms of growth of bubbles attached to, and sliding along, a heated surface. To control the location of the active cavities, the number, the spacing, and the nucleation superheat, artificial cavities will be formed on silicon wafers. In order to study the effect of magnitude of components of gravitational acceleration acting parallel to, and normal to the surface, experiments will be conducted on surfaces inclined at different angles including a downward facing surface. Information on the temperature field around bubbles, bubble shape and size, and bubble induced liquid velocities will be obtained through the use of holography, video/high speed photography and hydrogen bubble techniques, respectively. Analytical/numerical models will be developed to describe the heat transfer including that through the micro-macro layer underneath and around a bubble. In the micro layer model capillary and disjoining pressures will be included. Evolution of the interface along with induced liquid motion will be modelled. Subsequent to the world at normal gravity, experiments will be conducted in the KC-135 or the Lear jet especially to learn about bubble growth/detachment under low gravity conditions. Finally, an experiment will be defined to be conducted under long duration of microgravity conditions in the space shuttle. The experiment in the space shuttle will provide microgravity data on bubble growth and detachment and will lead to a validation of the nucleate boiling heat transfer model developed from the preceding studies performed at normal and low gravity (KC-135 or Lear jet) conditions.

  15. Mechanical behavior of aluminum deformed under hot-working conditions

    SciTech Connect

    Puchi, E.S.; Staia, M.H.

    1995-11-01

    The stress-strain behavior of aluminum 3-9 purity deformed at elevated temperatures has been analyzed on a rational basis. Emphasis has been given to the analysis of the curves corresponding to typical deformation conditions of interest for hot rolling of commercial aluminum alloys. The strain-hardening behavior has been modeled assuming the validity of the typical saturation exponential equation earlier proposed by Voce. The temperature and strain dependence of the flow stress parameters involved in such an equation has been introduced by means of a model based on the power law relationship, where the stress-sensitivity exponent of the strain rate is considered to be temperature dependent. The final constitutive equation derived provides a satisfactory reproduction of the experimental values of the flow stress and follow quite closely the strain-hardening behavior. The mean activation energy determined by the different models confirmed the predominance of both climb of edge dislocation segments and motion of jogged screw dislocations as the rate-controlling mechanisms during deformation of this material under hot-working conditions. The use of a constitutive equation which expresses the flow stress of the material in terms of the applied strain, rate of straining, and deformation temperature to calculate the power dissipation efficiency of the material ({eta}) deformed under hot-rolling conditions has shown that it could be strongly strain dependent, particularly toward the end of the rolling schedule. Hence, it has been concluded that the calculation of both the power co-content as defined in dynamic material modeling (DMM) and its maximum value, taking into consideration the constitutive equation previously developed, represents a more plausible and soundly based approach toward the determination of {eta}.

  16. Protective function of nitric oxide on marine phytoplankton under abiotic stresses.

    PubMed

    Li, Peifeng; Liu, Chun-Ying; Liu, Huanhuan; Zhang, Qiang; Wang, Lili

    2013-09-01

    As an important signaling molecule, nitric oxide (NO) plays diverse physiological functions in plants, which has gained particular attention in recent years. We investigated the roles of NO in the growth of marine phytoplankton Platymonas subcordiforms and Skeletonema costatum under abiotic stresses. The growth of these two microalgae was obviously inhibited under non-metal stress (sodium selenium, Na2SeO3), heavy metal stress (lead nitrate, Pb(NO3)2), pesticide stress (methomyl) and UV radiation stress. After the addition of different low concentrations of exogenous NO (10(-10)-10(-8) mol L(-1)) twice each day during cultivation, the growth of these two microalgae was obviously promoted. Results showed that NO could relieve the oxidative stresses to protect the growth of the two microalgae. For different environmental stress, there is a different optimum NO concentration for marine phytoplankton. It is speculated that the protective effect of NO is related to its antioxidant ability. PMID:23810732

  17. 77 FR 46948 - Respiratory Protection; Mechanical Power Presses; Scaffold Specifications; Correction and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-07

    ...) final rule, published on June 8, 2011 (76 FR 33590), OSHA revised question 2.a in the OSHA Respirator... Protection standard by removing the term ``fits'' in a question. OSHA also is correcting its Mechanical Power... (75 FR 38646, 38650). Therefore, in the final SIP-III rule, OSHA determined that (1) use of the...

  18. Formation mechanism of the protective layer in a blast furnace hearth

    NASA Astrophysics Data System (ADS)

    Jiao, Ke-xin; Zhang, Jian-liang; Liu, Zheng-jian; Xu, Meng; Liu, Feng

    2015-10-01

    A variety of techniques, such as chemical analysis, scanning electron microscopy-energy dispersive spectroscopy, and X-ray diffraction, were applied to characterize the adhesion protective layer formed below the blast furnace taphole level when a certain amount of titanium- bearing burden was used. Samples of the protective layer were extracted to identify the chemical composition, phase assemblage, and distribution. Furthermore, the formation mechanism of the protective layer was determined after clarifying the source of each component. Finally, a technical strategy was proposed for achieving a stable protective layer in the hearth. The results show that the protective layer mainly exists in a bilayer form in the sidewall, namely, a titanium-bearing layer and a graphite layer. Both the layers contain the slag phase whose major crystalline phase is magnesium melilite (Ca2MgSi2O7) and the main source of the slag phase is coke ash. It is clearly determined that solid particles such as graphite, Ti(C,N) and MgAl2O4 play an important role in the formation of the protective layer, and the key factor for promoting the formation of a stable protective layer is reasonable control of the evolution behavior of coke.

  19. Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism

    SciTech Connect

    Shao, Xue; Hu, Zhengtao; Hu, Chunyan; Bu, Qian; Yan, Guangyan; Deng, Pengchi; Lv, Lei; Wu, Dan; Deng, Yi; Zhao, Jinxuan; Zhu, Ruiming; Li, Yan; Li, Hongyu; Xu, Youzhi; Yang, Hanshuo; Zhao, Yinglan; Cen, Xiaobo

    2012-05-01

    Investigations have characterized addictive drug-induced developmental cardiovascular malformation in human, non-human primate and rodent. However, the underlying mechanism of malformation caused by drugs during pregnancy is still largely unknown, and preventive and therapeutic measures have been lacking. Using {sup 1}H NMR spectroscopy, we profiled the metabolites from human embryo endothelial cells exposed to methamphetamine (METH) and quantified a total of 226 peaks. We identified 11 metabolites modified robustly and found that taurine markedly increased. We then validated the hypothesis that this dramatic increase in taurine could attribute to its effect in inhibiting METH-induced developmental angiogenesis defect. Taurine supplement showed a more significant potential than other metabolites in protecting against METH-induced injury in endothelial cells. Taurine strongly attenuated METH-induced inhibition of proliferation and migration in endothelial cells. Furthermore, death rate and vessel abnormality of zebrafish embryos treated with METH were greatly reversed by taurine. In addition, taurine supplement caused a rapid decrease in reactive oxygen species generation and strongly attenuated the excitable arise of antioxidase activities in the beginning of METH exposure prophase. Dysregulations of NF-κB, p-ERK as well as Bax, which reflect apoptosis, cell cycle arrest and oxidative stress in vascular endothelium, were blocked by taurine. Our results provide the first evidence that taurine prevents METH-caused developmental angiogenesis defect through antioxidant mechanism. Taurine could serve as a potential therapeutic or preventive intervention of developmental vascular malformation for the pregnant women with drug use. Highlights: ► Metabonomics findings. ► Abnormal development. ► Dysregulations of key proteins.

  20. Extracellular reduction of uranium via Geobacter conductive pili as a protective cellular mechanism

    PubMed Central

    Cologgi, Dena L.; Lampa-Pastirk, Sanela; Speers, Allison M.; Kelly, Shelly D.; Reguera, Gemma

    2011-01-01

    The in situ stimulation of Fe(III) oxide reduction by Geobacter bacteria leads to the concomitant precipitation of hexavalent uranium [U(VI)] from groundwater. Despite its promise for the bioremediation of uranium contaminants, the biological mechanism behind this reaction remains elusive. Because Fe(III) oxide reduction requires the expression of Geobacter's conductive pili, we evaluated their contribution to uranium reduction in Geobacter sulfurreducens grown under pili-inducing or noninducing conditions. A pilin-deficient mutant and a genetically complemented strain with reduced outer membrane c-cytochrome content were used as controls. Pili expression significantly enhanced the rate and extent of uranium immobilization per cell and prevented periplasmic mineralization. As a result, pili expression also preserved the vital respiratory activities of the cell envelope and the cell's viability. Uranium preferentially precipitated along the pili and, to a lesser extent, on outer membrane redox-active foci. In contrast, the pilus-defective strains had different degrees of periplasmic mineralization matching well with their outer membrane c-cytochrome content. X-ray absorption spectroscopy analyses demonstrated the extracellular reduction of U(VI) by the pili to mononuclear tetravalent uranium U(IV) complexed by carbon-containing ligands, consistent with a biological reduction. In contrast, the U(IV) in the pilin-deficient mutant cells also required an additional phosphorous ligand, in agreement with the predominantly periplasmic mineralization of uranium observed in this strain. These findings demonstrate a previously unrecognized role for Geobacter conductive pili in the extracellular reduction of uranium, and highlight its essential function as a catalytic and protective cellular mechanism that is of interest for the bioremediation of uranium-contaminated groundwater. PMID:21896750

  1. Modeling of the Thermal Protection of a Multilayer Material Under Fire Conditions

    NASA Astrophysics Data System (ADS)

    Ovchinnikov, V. A.; Yakimov, A. S.

    2016-05-01

    On the basis of the theoretical and known experimental results, a refined mathematical model of the thermochemical destruction of a multilayer heat-shield coating has been developed. Account of the flow across the body has made it possible to forecast more exactly the state of the protected structure under fire conditions. A comparison between the results of numerical calculations and the known data has been made.

  2. Beyond membrane channelopathies: alternative mechanisms underlying complex human disease

    PubMed Central

    Boudoulas, Konstantinos Dean; Mohler, Peter J

    2011-01-01

    Over the past fifteen years, our understanding of the molecular mechanisms underlying human disease has flourished in large part due to the discovery of gene mutations linked with membrane ion channels and transporters. In fact, ion channel defects (“channelopathies” — the focus of this review series) have been associated with a spectrum of serious human disease phenotypes including cystic fibrosis, cardiac arrhythmia, diabetes, skeletal muscle defects, and neurological disorders. However, we now know that human disease, particularly excitable cell disease, may be caused by defects in non-ion channel polypeptides including in cellular components residing well beneath the plasma membrane. For example, over the past few years, a new class of potentially fatal cardiac arrhythmias has been linked with cytoplasmic proteins that include sub-membrane adapters such as ankyrin-B (ANK2), ankyrin-G (ANK3), and alpha-1 syntrophin, membrane coat proteins including caveolin-3 (CAV3), signaling platforms including yotiao (AKAP9), and cardiac enzymes (GPD1L). The focus of this review is to detail the exciting role of lamins, yet another class of gene products that have provided elegant new insight into human disease. PMID:21642948

  3. Metabolite Recognition Principles and Molecular Mechanisms Underlying Riboswitch Function

    PubMed Central

    Serganov, Alexander; Patel, Dinshaw J.

    2015-01-01

    Riboswitches are mRNA elements capable of modulating gene expression in response to specific binding by cellular metabolites. Riboswitches exert their function through the interplay of alternative ligand-free and ligand-bound conformations of the metabolite-sensing domain, which in turn modulate the formation of adjacent gene expression controlling elements. X-ray crystallography and NMR spectroscopy have determined three-dimensional structures of virtually all the major riboswitch classes in the ligand-bound state and, for several riboswitches, in the ligand-free state. The resulting spatial topologies have demonstrated the wide diversity of riboswitch folds and revealed structural principles for specific recognition by cognate metabolites. The available three-dimensional information, supplemented by structure-guided biophysical and biochemical experimentation, has led to an improved understanding of how riboswitches fold, what RNA conformations are required for ligand recognition, and how ligand binding can be transduced into gene expression modulation. These studies have greatly facilitated the dissection of molecular mechanisms underlying riboswitch action and should in turn guide the anticipated development of tools for manipulating gene regulatory circuits. PMID:22577823

  4. Molecular mechanisms underlying neurodevelopmental disorders, ADHD and autism.

    PubMed

    Bădescu, George Mihai; Fîlfan, Mădălina; Sandu, Raluca Elena; Surugiu, Roxana; Ciobanu, Ovidiu; Popa-Wagner, Aurel

    2016-01-01

    Neurodevelopmental disorders such as attention deficit hyperactivity disorder and autism represent a significant economic burden, which justify vigorous research to uncover its genetics and developmental clinics for a diagnostic workup. The urgency of addressing attention deficit hyperactivity disorder comorbidities is seen in the chilling fact that attention deficit hyperactivity disorder (ADHD), mood disorders, substance use disorders and obesity each increase the risk for mortality. However, data about comorbidity is mainly descriptive, with mechanistic studies limited to genetic epidemiological studies that document shared genetic risk factors among these conditions. Autism and intellectual disability affects 1.5 to 2% of the population in Western countries with many individuals displaying social-emotional agnosia and having difficulty in forming attachments and relationships. Underlying mechanisms include: (i) dysfunctions of neuronal miRNAs; (ii) deletions in the chromosome 21, subtelomeric deletions, duplications and a maternally inherited duplication of the chromosomal region 15q11-q13; (iii) microdeletions in on the long (q) arm of the chromosome in a region designated q21.1 increases the risk of delayed development, intellectual disability, physical abnormalities, and neurological and psychiatric problems associated with autism, schizophrenia, and epilepsy and weak muscle tone (hypotonia); (iv) interstitial duplications encompassing 16p13.11. PMID:27516006

  5. Cellular mechanisms underlying the interaction between cannabinoid and opioid system.

    PubMed

    Parolaro, D; Rubino, T; Viganò, D; Massi, P; Guidali, C; Realini, N

    2010-04-01

    Recently, the presence of functional interaction between the opioid and cannabinoid system has been shown in various pharmacological responses. Although there is an increasing interest for the feasible therapeutic application of a co-administration of cannabinoids and opioids in some disorders (i.e. to manage pain, to modulate immune system and emotions) and the combined use of the two drugs by drug abusers is becoming largely diffuse, only few papers focused on cellular and molecular mechanisms underlying this interaction. This review updates the biochemical and molecular underpinnings of opioid and cannabinoid interaction, both within the central nervous system and periphery. The most convincing theory for the explanation of this reciprocal interaction involves (i) the release of opioid peptides by cannabinoids or endocannabinoids by opioids, (ii) the existence of a direct receptor-receptor interaction when the receptors are co-expressed in the same cells, and (iii) the interaction of their intracellular pathways. Finally, the cannabinoid/opioid interaction might be different in the brain rewarding networks and in those accounting for other pharmacological effects (antinociception, modulation of emotionality and cognitive behavior), as well as between the central nervous system and periphery. Further insights about the cannabinoid/opioid interaction could pave the way for new and promising therapeutic approaches.

  6. Deciphering molecular mechanism underlying hypolipidemic activity of echinocystic Acid.

    PubMed

    Han, Li; Lai, Peng; Du, Jun-Rong

    2014-01-01

    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  μ M, 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. PMID:24669228

  7. Molecular mechanism underlying promiscuous polyamine recognition by spermidine acetyltransferase.

    PubMed

    Sugiyama, Shigeru; Ishikawa, Sae; Tomitori, Hideyuki; Niiyama, Mayumi; Hirose, Mika; Miyazaki, Yuma; Higashi, Kyohei; Murata, Michio; Adachi, Hiroaki; Takano, Kazufumi; Murakami, Satoshi; Inoue, Tsuyoshi; Mori, Yusuke; Kashiwagi, Keiko; Igarashi, Kazuei; Matsumura, Hiroyoshi

    2016-07-01

    Spermidine acetyltransferase (SAT) from Escherichia coli, which catalyses the transfer of acetyl groups from acetyl-CoA to spermidine, is a key enzyme in controlling polyamine levels in prokaryotic cells. In this study, we determined the crystal structure of SAT in complex with spermidine (SPD) and CoA at 2.5Å resolution. SAT is a dodecamer organized as a hexamer of dimers. The secondary structural element and folding topology of the SAT dimer resemble those of spermidine/spermine N(1)-acetyltransferase (SSAT), suggesting an evolutionary link between SAT and SSAT. However, the polyamine specificity of SAT is distinct from that of SSAT and is promiscuous. The SPD molecule is also located at the inter-dimer interface. The distance between SPD and CoA molecules is 13Å. A deep, highly acidic, water-filled cavity encompasses the SPD and CoA binding sites. Structure-based mutagenesis and in-vitro assays identified SPD-bound residues, and the acidic residues lining the walls of the cavity are mostly essential for enzymatic activities. Based on mutagenesis and structural data, we propose an acetylation mechanism underlying promiscuous polyamine recognition for SAT. PMID:27163532

  8. Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves.

    PubMed

    Ford, Kevin J; Félix, Aude L; Feller, Marla B

    2012-01-18

    Before vision, a transient network of recurrently connected cholinergic interneurons, called starburst amacrine cells (SACs), generates spontaneous retinal waves. Despite an absence of robust inhibition, cholinergic retinal waves initiate infrequently and propagate within finite boundaries. Here, we combine a variety of electrophysiological and imaging techniques and computational modeling to elucidate the mechanisms underlying these spatial and temporal properties of waves in developing mouse retina. Waves initiate via rare spontaneous depolarizations of SACs. Waves propagate through recurrent cholinergic connections between SACs and volume release of ACh as demonstrated using paired recordings and a cell-based ACh optical sensor. Perforated-patch recordings and two-photon calcium imaging reveal that individual SACs have slow afterhyperpolarizations that induce SACs to have variable depolarizations during sequential waves. Using a computational model in which the properties of SACs are based on these physiological measurements, we reproduce the slow frequency, speed, and finite size of recorded waves. This study represents a detailed description of the circuit that mediates cholinergic retinal waves and indicates that variability of the interneurons that generate this network activity may be critical for the robustness of waves across different species and stages of development.

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

    PubMed

    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.

  10. Mechanisms underlying heterologous skin scaffold-mediated tissue remodeling

    PubMed Central

    Mimura, Kallyne K. O.; Moraes, Andréia R.; Miranda, Aline C.; Greco, Rebecca; Ansari, Tahera; Sibbons, Paul; Greco, Karin V.; Oliani, Sonia M.

    2016-01-01

    Biocompatibility of two newly developed porcine skin scaffolds was assessed after 3, 14, 21 and 90 days of implantation in rats. Both scaffolds showed absence of cells, preservation of ECM and mechanical properties comparable to non-decellularised skin before implantation. Host cell infiltration was much prominent on both scaffolds when compared to Permacol (surgical control). At day 3, the grafts were surrounded by polymorphonuclear cells, which were replaced by a notable number of IL-6-positive cells at day 14. Simultaneously, the number of pro-inflammatory M1-macrophage was enhanced. Interestingly, a predominant pro-remodeling M2 response, with newly formed vessels, myofibroblasts activation and a shift on the type of collagen expression was sequentially delayed (around 21 days). The gene expression of some trophic factors involved in tissue remodeling was congruent with the cellular events. Our findings suggested that the responsiveness of macrophages after non-crosslinked skin scaffolds implantation seemed to intimately affect various cell responses and molecular events; and this range of mutually reinforcing actions was predictive of a positive tissue remodeling that was essential for the long-standing success of the implants. Furthermore, our study indicates that non-crosslinked biologic scaffold implantation is biocompatible to the host tissue and somehow underlying molecular events involved in tissue repair. PMID:27725772

  11. Mechanisms underlying subunit independence in pyramidal neuron dendrites

    PubMed Central

    Behabadi, Bardia F.; Mel, Bartlett W.

    2014-01-01

    Pyramidal neuron (PN) dendrites compartmentalize voltage signals and can generate local spikes, which has led to the proposal that their dendrites act as independent computational subunits within a multilayered processing scheme. However, when a PN is strongly activated, back-propagating action potentials (bAPs) sweeping outward from the soma synchronize dendritic membrane potentials many times per second. How PN dendrites maintain the independence of their voltage-dependent computations, despite these repeated voltage resets, remains unknown. Using a detailed compartmental model of a layer 5 PN, and an improved method for quantifying subunit independence that incorporates a more accurate model of dendritic integration, we first established that the output of each dendrite can be almost perfectly predicted by the intensity and spatial configuration of its own synaptic inputs, and is nearly invariant to the rate of bAP-mediated “cross-talk” from other dendrites over a 100-fold range. Then, through an analysis of conductance, voltage, and current waveforms within the model cell, we identify three biophysical mechanisms that together help make independent dendritic computation possible in a firing neuron, suggesting that a major subtype of neocortical neuron has been optimized for layered, compartmentalized processing under in-vivo–like spiking conditions. PMID:24357611

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

    PubMed

    Jepma, Marieke; Verdonschot, Rinus G; van Steenbergen, Henk; Rombouts, Serge A R B; Nieuwenhuis, Sander

    2012-01-01

    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 (1) the induction of perceptual curiosity, through the presentation of ambiguous visual input, activated the anterior insula and anterior cingulate cortex (ACC), brain regions sensitive to conflict and arousal; (2) the relief of perceptual curiosity, through visual disambiguation, activated regions of the striatum that have been related to reward processing; and (3) 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.

  13. Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves

    PubMed Central

    Ford, Kevin J.; Félix, Aude L.; Feller, Marla B.

    2012-01-01

    Prior to vision, a transient network of recurrently connected cholinergic interneurons, called starburst amacrine cells (SACs), generates spontaneous retinal waves. Despite an absence of robust inhibition, cholinergic retinal waves initiate infrequently and propagate within finite boundaries. Here we combine a variety of electrophysiological and imaging techniques and computational modeling to elucidate the mechanisms underlying these spatial and temporal properties of waves in developing mouse retina. Waves initiate via rare spontaneous depolarizations of SACs. Waves propagate through recurrent cholinergic connections between SACs and volume release of ACh as demonstrated using paired recordings and a cell-based ACh optical sensor. Perforated patch recordings and two-photon calcium imaging reveal that individual SACs have slow afterhyperpolarizations that induce SACs to have variable depolarizations during sequential waves. Using a computational model in which the properties of SACs are based on these physiological measurements, we reproduce the slow frequency, speed, and finite size of recorded waves. This study represents a detailed description of the circuit that mediates cholinergic retinal waves and indicates that variability of the interneurons that generate this network activity may be critical for the robustness of waves across different species and stages of development. PMID:22262883

  14. [Molecular mechanisms underlying the formation of neuromuscular junction].

    PubMed

    Higuchi, Osamu; Yamanashi, Yuji

    2011-07-01

    The neuromuscular junction (NMJ) is a synapse between a motor neuron and skeletal muscle. The contraction of skeletal muscle is controlled by the neurotransmitter acetylcholine (ACh), which is released from the motor nerve terminal. To achieve efficient neuromuscular transmission, acetylcholine receptors (AChRs) must be densely clustered on the muscle membrane of the NMJ. Failure of AChR clustering is associated with disorders of neuromuscular transmission such as congenital myasthenic syndromes (CMS) and myasthenia gravis (MG). Motoneuronal agrin and muscle-specific receptor tyrosine kinase (MuSK) are known to play essential roles in the formation and maintenance of NMJs in the central region of each muscle. However, it had been unclear how agrin activates MuSK. Recent studies have elucidated the roles of several key molecules, including the cytoplasmic adaptor protein Dok-7 and LDL receptor-related protein 4 (Lrp4), in agrin-induced MuSK activation. Moreover, new evidence indicates that cyclin-dependent kinase 5 (Cdk5) regulates postsynaptic differentiation. In this review, we summarize the latest developments in molecular mechanisms underlying NMJ formation in vertebrates. PMID:21747134

  15. Mechanisms underlying the antihypertensive effects of garlic bioactives.

    PubMed

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

    2014-02-01

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

  16. Recent experimental developments concerning the mechanisms underlying dust emission

    NASA Astrophysics Data System (ADS)

    McKenna Neuman, C. L.; Sanderson, R. S.; O'Brien, P.

    2012-12-01

    Field based studies have been invaluable in elucidating the great variability and complexity in natural surfaces that emit dust. Spanning hours to days, and meters to kilometers, measurements of the regional and global characteristics of dust emission and transport are contributing to a clearer understanding of these phenomena. This work has been complimented by the development of increasingly more sophisticated atmospheric dispersion models. Only very recently, however, has much attention been paid to the physics of dust emission from the bed surface that necessarily require precise, high frequency measurements over fractions of millimeters under carefully manipulated conditions. This paper provides an overview of recent advances in our understanding of the mechanisms of dust emission, as derived from experiments carried out in the Trent boundary layer wind tunnel by a variety of workers. Energy transfer to the bed surface through the impacts of saltating particles has long been recognized as crucial for the ejection of silt and clay sized particles from surfaces where interparticle bonding is significant. Using Particle Tracking Velocimetry (PTV) and laser Doppler anemometry (LDA), we are now able to measure the energy transfer to the surface and the consequent deformation/rupture for both loose and consolidated beds of silt. The coefficient of restitution is found to decrease with particle impact speed, although some compaction may also occur with plowing and displacement of loose bed material (Gordon and McKenna Neuman, 2009). Further consideration is given to wind pumping as an alternate mechanism for dust entrainment from surfaces that are armored; that is, where insufficient sand supply is available to the support the development of a saltation cloud. LDA and pressure tap measurements confirm that turbulent structures measured in the atmospheric boundary layer are able to penetrate into the pores of gravel sized material, and specifically, the smelter waste

  17. Guidance for applicants for state wellhead protection program assistance funds under the Safe Drinking Water Act. Appendix C. Wellhead Protection Program-applicable regulations

    SciTech Connect

    Not Available

    1987-06-01

    Appendix C is a companion document to the Guidance for Applicants for State Wellhead Protection Assistance Funds Under the Safe Drinking Water Act to explain EPA regulations applicable to the Wellhead Protection Program (WHP) and the assistance application form needed to request a program grant. These two documents are used to develop approvable assistance applications and to administer properly the funds awarded under the WHP program.

  18. Heat stress while wearing long pants or shorts under firefighting protective clothing.

    PubMed

    McLellan, T M; Selkirk, G A

    2004-01-15

    It was the purpose of this study to examine whether replacing long pants (P) with shorts (S) would reduce the heat stress of wearing firefighting protective clothing during exercise in a warm environment. Twenty-four Toronto Firefighters were allocated to one of four groups that performed heavy (H, 4.8 km x h(-1), 5% grade), moderate (M, 4.5 km x h(-1), 2.5% grade), light (L, 4.5 km x h(-1)) or very light (VL, 2.5 km x h(-1)) exercise while wearing their full protective ensemble and self-contained breathing apparatus. Participants performed a familiarization trial followed by two experimental trials at 35 degrees C and 50% relative humidity wearing either P or S under their protective overpants. Replacing P with S had no impact on the rectal temperature (Tre) or heart rate response during heavy or moderate exercise where exposure times were less than 1 h (40.8 +/- 5.8 and 53.5 +/- 9.2 min for H and M, respectively while wearing P, and 43.5 +/- 5.3 and 54.2 +/- 8.4 min, respectively while wearing S). In contrast, as exposure times were extended during lighter exercise Tre was reduced by as much as 0.4 degrees C after 80 min of exercise while wearing S. Exposure times were significantly increased from 65.8 +/- 9.6 and 83.5 +/- 11.6 min during L and VL, respectively while wearing P to 73.3 +/- 8.4 and 97.0 +/- 12.5 min, respectively while wearing S. It was concluded that replacing P with S under the firefighting protective clothing reduced the heat stress associated with wearing the protective ensemble and extended exposure times approximately 10 - 15% during light exercise. However, during heavier exercise where exposure times were less than 1 h replacing P with S was of little benefit.

  19. Study of mechanical behavior of AFM silicon tips under mechanical load

    NASA Astrophysics Data System (ADS)

    Kopycinska-Mueller, M.; Gluch, J.; Köhler, B.

    2016-11-01

    In this paper we address critical issues concerning calibration of AFM based methods used for nanoscale mechanical characterization of materials. It has been shown that calibration approaches based on macroscopic models for contact mechanics may yield excellent results in terms of the indentation modulus of the sample, but fail to provide a comprehensive and actual information concerning the tip–sample contact radius or the mechanical properties of the tip. Explanations for the severely reduced indentation modulus of the tip included the inadequacies of the models used for calculations of the tip–sample contact stiffness, discrepancies in the actual and ideal shape of the tip, presence of the amorphous silicon phase within the silicon tip, as well as negligence of the actual size of the stress field created in the tip during elastic interactions. To clarify these issues, we investigated the influence of the mechanical load applied to four AFM silicon tips on their crystalline state by exposing them to systematically increasing loads, evaluating the character of the tip–sample interactions via the load-unload stiffness curves, and assessing the state of the tips from HR-TEM images. The results presented in this paper were obtained in a series of relatively simple and basic atomic force acoustic microscopy (AFAM) experiments. The novel combination of TEM imaging of the AFM tips with the analysis of the load-unload stiffness curves gave us a detailed insight into their mechanical behavior under load conditions. We were able to identify the limits for the elastic interactions, as well as the hallmarks for phase transformation and dislocation formation and movement. The comparison of the physical dimensions of the AFM tips, geometry parameters determined from the values of the contact stiffness, and the information on the crystalline state of the tips allowed us a better understanding of the nanoscale contact.

  20. 40 CFR 2.309 - Special rules governing certain information obtained under the Marine Protection, Research and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... information obtained under the Marine Protection, Research and Sanctuaries Act of 1972. 2.309 Section 2.309... Business Information § 2.309 Special rules governing certain information obtained under the Marine Protection, Research and Sanctuaries Act of 1972. (a) Definitions. For the purposes of this section: (1)...

  1. 40 CFR 2.309 - Special rules governing certain information obtained under the Marine Protection, Research and...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... information obtained under the Marine Protection, Research and Sanctuaries Act of 1972. 2.309 Section 2.309... Business Information § 2.309 Special rules governing certain information obtained under the Marine Protection, Research and Sanctuaries Act of 1972. (a) Definitions. For the purposes of this section: (1)...

  2. A time to step in: legal mechanisms for protecting those with declining capacity.

    PubMed

    Arias, Jalayne J

    2013-01-01

    Current estimates approximate that the population over sixty-five years of age will increase from 40 million in 2010 to 72.1 million by 2030. As society ages, the number of elderly with cognitive deficits that impair decision-making abilities will also increase. This will place additional burdens on families and probate courts seeking to balance individual autonomy with necessary protections. A legal determination of incompetency is a prerequisite to a judicial order appointing a guardianship or other protective mechanism. The current legal-medical model for competency determinations fails to reflect the complexities of declining capacity in an aging population. A global structure for competency determinations leaves a critical gap between competent and incompetent. The gap between competence and incompetence not only raises concerns about how to classify those that fall between the two, but also highlights the lack of legal protections for those within the gap. A revised model is needed to provide protections to individuals who do not yet meet the threshold for incompetence but require additional protections for their personal or financial welfare. This Article provides an unprecedented examination of the legal model for determining competence through a comparison of the medical model for evaluating capacity. While a number of legal scholars have examined the appointment and oversight of guardians, fewer articles have critically examined the process by which individuals are declared incompetent. This Article presents a comprehensive overview of competency and clinical capacity determination procedures, legal mechanisms available to protect individuals with declining capacity, and policy recommendations for improving legal protections in light of inefficiencies related to legal competency determinations. PMID:23678789

  3. Sex differences in the mechanisms underlying long QT syndrome.

    PubMed

    Salama, Guy; Bett, Glenna C L

    2014-09-01

    Sexual dimorphism is a well-established phenomenon, but its degree varies tremendously among species. Since the early days of Einthoven's development of the three-lead galvanometer ECG, we have known there are marked differences in QT intervals of men and women. It required over a century to appreciate the profound implications of sex-based electrophysiological differences in QT interval on the panoply of sex differences with respect to arrhythmia risk, drug sensitivity, and treatment modalities. Little is known about the fundamental mechanism responsible for sex differences in electrical substrate of the human heart, in large part due to the lack of tissue availability. Animal models are an important research tool, but species differences in the sexual dimorphism of the QT interval, the ionic currents underlying the cardiac repolarization, and effects of sex steroids make it difficult to interpolate animal to human sex differences. In addition, in some species, different strains of the same animal model yield conflicting data. Each model has its strengths, such as ease of genetic manipulation in mice or size in dogs. However, many animals do not reproduce the sexual dimorphism of QT seen in humans. To match sex linked prolongation of QT interval and arrhythmogenic phenotype, the current data suggest that the rabbit may be best suited to provide insight into sex differences in humans. In the future, emerging technologies such as induced pluripotent stem cell derived cardiac myocyte systems may offer the opportunity to study sex differences in a controlled hormonal situation in the context of a sex specific human model system.

  4. Mechanisms underlying the link between cannabis use and prospective memory.

    PubMed

    Cuttler, Carrie; McLaughlin, Ryan J; Graf, Peter

    2012-01-01

    While the effects of cannabis use on retrospective memory have been extensively examined, only a limited number of studies have focused on the links between cannabis use and prospective memory. We conducted two studies to examine the links between cannabis use and both time-based and event-based prospective memory as well as potential mechanisms underlying these links. For the first study, 805 students completed an online survey designed to assess cannabis consumption, problems with cannabis use indicative of a disorder, and frequency of experiencing prospective memory failures. The results showed small to moderate sized correlations between cannabis consumption, problems with cannabis use, and prospective memory. However, a series of mediation analyses revealed that correlations between problems with cannabis use and prospective memory were driven by self-reported problems with retrospective memory. For the second study, 48 non-users (who had never used cannabis), 48 experimenters (who had used cannabis five or fewer times in their lives), and 48 chronic users (who had used cannabis at least three times a week for one year) were administered three objective prospective memory tests and three self-report measures of prospective memory. The results revealed no objective deficits in prospective memory associated with chronic cannabis use. In contrast, chronic cannabis users reported experiencing more internally-cued prospective memory failures. Subsequent analyses revealed that this effect was driven by self-reported problems with retrospective memory as well as by use of alcohol and other drugs. Although our samples were not fully characterized with respect to variables such as neurological disorders and family history of substance use disorders, leaving open the possibility that these variables may play a role in the detected relationships, the present findings indicate that cannabis use has a modest effect on self-reported problems with prospective memory, with a

  5. Mechanisms underlying obesity resistance associated with high spontaneous physical activity.

    PubMed

    Teske, J A; Billington, C J; Kotz, C M

    2014-01-01

    Obesity resistance due to elevated orexin signaling is accompanied by high levels of spontaneous physical activity (SPA). The behavioral and neural mechanisms underlying this observation have not been fully worked out. We determined the contribution of hypothalamic orexin receptors (OXRs) to SPA stimulated by orexin A (OXA), whether OXA-stimulated SPA was secondary to arousal and whether voluntary wheel running led to compensations in 24-h SPA. We further tested whether orexin action on dopamine one receptors (DA1R) in the substantia nigra (SN) plays an important role in the generation of SPA. To test this, SPA response was determined in lean and obese rats with cannulae targeted toward the rostral lateral hypothalamus (rLH) or SN. Sleep/wake states were also measured in rats with rLH cannula and electroencephalogram/electromyogram radiotelemetry transmitters. SPA in lean rats was more sensitive to antagonism of the OX1R and in the early response to the orexin 2 agonist. OXA increased arousal equally in lean and obese rodents, which is discordant from the greater SPA response in lean rats. Obesity-resistant rats ran more and wheel running was directly related to 24-h SPA levels. The OX1R antagonist, SB-334867-A, and the DA1R antagonist, SCH3390, in SN more effectively reduced SPA stimulated by OXA in obesity-resistant rats. These data suggest OXA-stimulated SPA is not secondary to enhanced arousal, propensity for SPA parallels inclination to run and that orexin action on dopaminergic neurons in SN may participate in the mediation of SPA and running wheel activity.

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

    PubMed

    Sakellaridi, Sofia; Christova, Peka; Christopoulos, Vassilios N; Vialard, Alice; Peponis, John; Georgopoulos, Apostolos P

    2015-01-01

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

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

    PubMed Central

    de Steenhuijsen Piters, Wouter A. A.

    2016-01-01

    ABSTRACT The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem—also called “microbiome”—is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections. Recent studies using next-generation sequencing show that S. pneumoniae, as well as other potential pathogens, might be kept at bay by certain commensal bacteria, including Corynebacterium and Dolosigranulum spp. Bomar and colleagues are the first to explore a specific biological mechanism contributing to the antagonistic interaction between Corynebacterium accolens and S. pneumoniae in vitro [L. Bomar, S. D. Brugger, B. H. Yost, S. S. Davies, K. P. Lemon, mBio 7(1):e01725-15, 2016, doi:10.1128/mBio.01725-15]. The authors comprehensively show that C. accolens is capable of hydrolyzing host triacylglycerols into free fatty acids, which display antipneumococcal properties, suggesting that these bacteria might contribute to the containment of pneumococcus. This work exemplifies how molecular epidemiological findings can lay the foundation for mechanistic studies to elucidate the host-microbe and microbial interspecies interactions underlying the bacterial community structure. Next, translation of these results to an in vivo setting seems necessary to unveil the magnitude and importance of the observed effect in its natural, polymicrobial setting. PMID:26838716

  8. Sex differences in the mechanisms underlying long QT syndrome.

    PubMed

    Salama, Guy; Bett, Glenna C L

    2014-09-01

    Sexual dimorphism is a well-established phenomenon, but its degree varies tremendously among species. Since the early days of Einthoven's development of the three-lead galvanometer ECG, we have known there are marked differences in QT intervals of men and women. It required over a century to appreciate the profound implications of sex-based electrophysiological differences in QT interval on the panoply of sex differences with respect to arrhythmia risk, drug sensitivity, and treatment modalities. Little is known about the fundamental mechanism responsible for sex differences in electrical substrate of the human heart, in large part due to the lack of tissue availability. Animal models are an important research tool, but species differences in the sexual dimorphism of the QT interval, the ionic currents underlying the cardiac repolarization, and effects of sex steroids make it difficult to interpolate animal to human sex differences. In addition, in some species, different strains of the same animal model yield conflicting data. Each model has its strengths, such as ease of genetic manipulation in mice or size in dogs. However, many animals do not reproduce the sexual dimorphism of QT seen in humans. To match sex linked prolongation of QT interval and arrhythmogenic phenotype, the current data suggest that the rabbit may be best suited to provide insight into sex differences in humans. In the future, emerging technologies such as induced pluripotent stem cell derived cardiac myocyte systems may offer the opportunity to study sex differences in a controlled hormonal situation in the context of a sex specific human model system. PMID:24973386

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

    PubMed

    de Steenhuijsen Piters, Wouter A A; Bogaert, Debby

    2016-01-01

    The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem-also called "microbiome"-is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections. Recent studies using next-generation sequencing show that S. pneumoniae, as well as other potential pathogens, might be kept at bay by certain commensal bacteria, including Corynebacterium and Dolosigranulum spp. Bomar and colleagues are the first to explore a specific biological mechanism contributing to the antagonistic interaction between Corynebacterium accolens and S. pneumoniae in vitro [L. Bomar, S. D. Brugger, B. H. Yost, S. S. Davies, K. P. Lemon, mBio 7(1):e01725-15, 2016, doi:10.1128/mBio.01725-15]. The authors comprehensively show that C. accolens is capable of hydrolyzing host triacylglycerols into free fatty acids, which display antipneumococcal properties, suggesting that these bacteria might contribute to the containment of pneumococcus. This work exemplifies how molecular epidemiological findings can lay the foundation for mechanistic studies to elucidate the host-microbe and microbial interspecies interactions underlying the bacterial community structure. Next, translation of these results to an in vivo setting seems necessary to unveil the magnitude and importance of the observed effect in its natural, polymicrobial setting. PMID:26838716

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

    PubMed

    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.

  11. Key evidence of the role of desertification in protecting the underlying permafrost in the Qinghai–Tibet Plateau

    PubMed Central

    Xie, Shengbo; Qu, Jianjun; Lai, Yuanming; Xu, Xiangtian; Pang, Yingjun

    2015-01-01

    Previous research has shown that the temperature of underlying permafrost decreases after the ground surface is covered with sand. No significant conclusions have yet been drawn that explain why this happens, because the heat transfer mechanism effects of the sand layer on the underlying permafrost remain unclear. These mechanisms were studied in the present work. We found that the upward shortwave radiation flux of the Qinghai-Tibet Plateau ground surface with a sand layer covering was higher than that of the surface without sand; thus, the atmospheric heat reflected by the sand layer is greater than that reflected by the surface without sand. Therefore, the net radiation of the surface with the sand layer is lower than that of the surface without sand, which reduces the heat available to warm the sand layer. Because sand is both a porous medium and a weak pervious conductor with poor heat conductivity, less heat is conducted through the sand layer to the underground permafrost than in soil without the sand deposition layer. This phenomenon results in a decrease in the ground temperature of the permafrost under the sand layer, which plays a key role in protecting the permafrost. PMID:26468777

  12. The System Impact of Air-Conditioner Under-voltage Protection Schemes

    SciTech Connect

    Lu, Ning; Yang, Bo; Huang, Zhenyu; Bravo, Richard

    2009-03-31

    This paper presents simulation results of evaluating an under-voltage protection scheme designed to take stalled air-conditioner (a/c) units offline such that the slow voltage recovery phenomena can be solved on areas heavily loaded with a/c motors during summer peak periods. A three feeder test-bed has been first used to quantify the effectiveness of the protection scheme and the sensitivity of the under-voltage relay settings. Then two real system events of the Western US power grid have been studied to evaluate the area impact of the protection scheme proposed by Southern California Edison. The study demonstrates that by taking all or most of the stalled a/c unit offline, the feeder voltage will recover in a few seconds, much quicker than the tens of seconds that the standard thermal relays imbedded in the motors need to trip the units. The drawback of the control scheme is that after the voltage recover, it settled at a higher voltage than before the faults because a large chuck of load has been shed.

  13. Under Pressure: Mechanical Stress Management in the Nucleus

    PubMed Central

    Belaadi, Néjma; Aureille, Julien; Guilluy, Christophe

    2016-01-01

    Cells are constantly adjusting to the mechanical properties of their surroundings, operating a complex mechanochemical feedback, which hinges on mechanotransduction mechanisms. Whereas adhesion structures have been shown to play a central role in mechanotransduction, it now emerges that the nucleus may act as a mechanosensitive structure. Here, we review recent advances demonstrating that mechanical stress emanating from the cytoskeleton can activate pathways in the nucleus which eventually impact both its structure and the transcriptional machinery. PMID:27314389

  14. Injuries of the head from backface deformation of ballistic protective helmets under ballistic impact.

    PubMed

    Rafaels, Karin A; Cutcliffe, Hattie C; Salzar, Robert S; Davis, Martin; Boggess, Brian; Bush, Bryan; Harris, Robert; Rountree, Mark Steve; Sanderson, Ellory; Campman, Steven; Koch, Spencer; Dale Bass, Cameron R

    2015-01-01

    Modern ballistic helmets defeat penetrating bullets by energy transfer from the projectile to the helmet, producing helmet deformation. This deformation may cause severe injuries without completely perforating the helmet, termed "behind armor blunt trauma" (BABT). As helmets become lighter, the likelihood of larger helmet backface deformation under ballistic impact increases. To characterize the potential for BABT, seven postmortem human head/neck specimens wearing a ballistic protective helmet were exposed to nonperforating impact, using a 9 mm, full metal jacket, 124 grain bullet with velocities of 400-460 m/s. An increasing trend of injury severity was observed, ranging from simple linear fractures to combinations of linear and depressed fractures. Overall, the ability to identify skull fractures resulting from BABT can be used in forensic investigations. Our results demonstrate a high risk of skull fracture due to BABT and necessitate the prevention of BABT as a design factor in future generations of protective gear. PMID:25039407

  15. Injuries of the head from backface deformation of ballistic protective helmets under ballistic impact.

    PubMed

    Rafaels, Karin A; Cutcliffe, Hattie C; Salzar, Robert S; Davis, Martin; Boggess, Brian; Bush, Bryan; Harris, Robert; Rountree, Mark Steve; Sanderson, Ellory; Campman, Steven; Koch, Spencer; Dale Bass, Cameron R

    2015-01-01

    Modern ballistic helmets defeat penetrating bullets by energy transfer from the projectile to the helmet, producing helmet deformation. This deformation may cause severe injuries without completely perforating the helmet, termed "behind armor blunt trauma" (BABT). As helmets become lighter, the likelihood of larger helmet backface deformation under ballistic impact increases. To characterize the potential for BABT, seven postmortem human head/neck specimens wearing a ballistic protective helmet were exposed to nonperforating impact, using a 9 mm, full metal jacket, 124 grain bullet with velocities of 400-460 m/s. An increasing trend of injury severity was observed, ranging from simple linear fractures to combinations of linear and depressed fractures. Overall, the ability to identify skull fractures resulting from BABT can be used in forensic investigations. Our results demonstrate a high risk of skull fracture due to BABT and necessitate the prevention of BABT as a design factor in future generations of protective gear.

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

    PubMed

    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.

  17. Mechanisms underlying differential food-allergic response to heated egg

    PubMed Central

    Martos, Gustavo; Lopez-Exposito, Ivan; Bencharitiwong, Ramon; Berin, Cecilia; Nowak-Węgrzyn, Anna

    2011-01-01

    Background Egg white proteins are usually subjected to heating, making them edible for the majority of egg-allergic children. Objective We sought to investigate the underlying mechanisms responsible for the reduced allergenicity displayed by heat-treated egg white allergens. Methods C3H/HeJ mice were orally sensitized with ovalbumin (OVA) or ovomucoid (OM) and challenged with native or heated proteins to evaluate their allergenicity. Immunoreactivity was assessed by immunoblotting using sera from egg-allergic children. In vitro gastrointestinal digestion of native and heated OVA and OM was studied by SDS-PAGE and liquid chromatography. Intestinal uptake of intact native and heated OVA and OM by human intestinal epithelial (Caco-2) cells was investigated. Rat basophil leukemia (RBL) cells passively sensitized with mouse serum and human basophils passively sensitized with egg-allergic children’s serum were used to assess the effector cell activation by heated, digested and transported OVA and OM. Results Heated OVA and OM did not induce symptoms of anaphylaxis in sensitized mice when administered orally. Heating did not completely destroy IgE-binding capacity of OVA or OM but enhanced in vitro digestibility of OVA. Digestion of both OVA and OM diminished mediator release in RBL assay and basophil activation. Heating of allergens prevented transport across human intestinal epithelial cells in a form capable of triggering basophil activation or T cell activation. Conclusions Heat treatment reduces allergenicity of OVA and OM. This is partially due to the enhanced gastrointestinal digestibility of heated OVA and the inability of heated OVA or OM to be absorbed in a form capable of triggering basophils. Clinical implications Reduced allergenicity of heated egg white proteins partially resulting from altered digestion and absorption in the gastrointestinal tract may explain the clinical tolerance of extensively heated egg in the majority of egg-allergic children

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

    ERIC Educational Resources Information Center

    Boyd, Donald B.; Lipkowitz, Kenny B.

    1982-01-01

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

  19. Mechanism of protection against alcoholism by an alcohol dehydrogenase polymorphism: development of an animal model

    PubMed Central

    Rivera-Meza, Mario; Quintanilla, María Elena; Tampier, Lutske; Mura, Casilda V.; Sapag, Amalia; Israel, Yedy

    2010-01-01

    Humans who carry a point mutation in the gene coding for alcohol dehydrogenase-1B (ADH1B*2; Arg47His) are markedly protected against alcoholism. Although this mutation results in a 100-fold increase in enzyme activity, it has not been reported to cause higher levels of acetaldehyde, a metabolite of ethanol known to deter alcohol intake. Hence, the mechanism by which this mutation confers protection against alcoholism is unknown. To study this protective effect, the wild-type rat cDNA encoding rADH-47Arg was mutated to encode rADH-47His, mimicking the human mutation. The mutated cDNA was incorporated into an adenoviral vector and administered to genetically selected alcohol-preferring rats. The Vmax of rADH-47His was 6-fold higher (P<0.001) than that of the wild-type rADH-47Arg. Animals transduced with rAdh-47His showed a 90% (P<0.01) increase in liver ADH activity and a 50% reduction (P<0.001) in voluntary ethanol intake. In animals transduced with rAdh-47His, administration of ethanol (1g/kg) produced a short-lived increase of arterial blood acetaldehyde concentration to levels that were 3.5- to 5-fold greater than those in animals transduced with the wild-type rAdh-47Arg vector or with a noncoding vector. This brief increase (burst) in arterial acetaldehyde concentration after ethanol ingestion may constitute the mechanism by which humans carrying the ADH1B*2 allele are protected against alcoholism.—Rivera-Meza, M., Quintanilla, M. E., Tampier, L., Mura, C. V., Sapag, A., Israel, Y. Mechanism of protection against alcoholism by an alcohol dehydrogenase polymorphism: development of an animal model. PMID:19710201

  20. Epigenetic mechanisms underlying learning and the inheritance of learned behaviors.

    PubMed

    Dias, Brian G; Maddox, Stephanie A; Klengel, Torsten; Ressler, Kerry J

    2015-02-01

    Gene expression and regulation is an important sculptor of the behavior of organisms. Epigenetic mechanisms regulate gene expression not by altering the genetic alphabet but rather by the addition of chemical modifications to proteins associated with the alphabet or of methyl marks to the alphabet itself. Being dynamic, epigenetic mechanisms of gene regulation serve as an important bridge between environmental stimuli and genotype. In this review, we outline epigenetic mechanisms by which gene expression is regulated in animals and humans. Using fear learning as a framework, we then delineate how such mechanisms underlie learning and stress responsiveness. Finally, we discuss how epigenetic mechanisms might inform us about the transgenerational inheritance of behavioral traits that are being increasingly reported.

  1. Epigenetic mechanisms underlying learning and the inheritance of learned behaviors

    PubMed Central

    Klengel, Torsten; Ressler, Kerry J

    2014-01-01

    Gene expression and regulation is an important sculptor of the behavior of organisms. Epigenetic mechanisms regulate gene expression not by altering the genetic alphabet but rather by the addition of chemical modifications to proteins associated with the alphabet or of methyl marks to the alphabet itself. Being dynamic, epigenetic mechanisms of gene regulation serve as an important bridge between environmental stimuli and genotype. In this review, we outline epigenetic mechanisms by which gene expression is regulated in animals and humans. Using fear learning as a framework, we then delineate how such mechanisms underlie learning and stress responsiveness. Finally, we discuss how epigenetic mechanisms might inform us about the transgenerational inheritance of behavioral traits that are being increasingly reported. PMID:25544352

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

    PubMed

    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.

  3. Role of manganese in protection against oxidative stress under iron starvation in cyanobacterium Anabaena 7120.

    PubMed

    Kaushik, Manish Singh; Srivastava, Meenakshi; Verma, Ekta; Mishra, Arun Kumar

    2015-06-01

    The cyanobacterium Anabaena sp. PCC 7120 was grown in presence and absence of iron to decipher the role of manganese in protection against the oxidative stress under iron starvation and growth, manganese uptake kinetics, antioxidative enzymes, lipid peroxidation, electrolyte leakage, thiol content, total peroxide, proline and NADH content was investigated. Manganese supported the growth of cyanobacterium Anabaena 7120 under iron deprived conditions where maximum uptake rate of manganese was observed with lower K(m) and higher V(max) values. Antioxidative enzymes were also found to be elevated in iron-starved conditions. Estimation of lipid peroxidation and electrolyte leakage depicted the role of manganese in stabilizing the integrity of the membrane which was considered as the prime target of oxygen free radicals in oxidative stress. The levels of total peroxide, thiol, proline and NADH content, which are the representative of oxidative stress response in Anabaena 7120, were also showed increasing trends in iron starvation. Hence, the results discerned, clearly suggested the role of manganese in protection against the oxidative stress in cyanobacterium Anabaena 7120 under iron starvation either due to its antioxidative properties or involvement as cofactor in a number of antioxidative enzymes.

  4. Novel Hybrid Ablative/Ceramic Layered Composite for Earth Re-entry Thermal Protection: Microstructural and Mechanical Performance

    NASA Astrophysics Data System (ADS)

    Triantou, K.; Mergia, K.; Marinou, A.; Vekinis, G.; Barcena, J.; Florez, S.; Perez, B.; Pinaud, G.; Bouilly, J.-M.; Fischer, W. P. P.

    2015-04-01

    In view of spacecraft re-entry applications into planetary atmospheres, hybrid thermal protection systems based on layered composites of ablative materials and ceramic matrix composites are investigated. Joints of ASTERM™ lightweight ablative material with Cf/SiC (SICARBON™) were fabricated using commercial high temperature inorganic adhesives. Sound joints without defects are produced and very good bonding of the adhesive with both base materials is observed. Mechanical shear tests under ambient conditions and in liquid nitrogen show that mechanical failure always takes place inside the ablative material with no decohesion of the interface of the adhesive layer with the bonded materials. Surface treatment of the ablative surface prior to bonding enhances both the shear strength and the ultimate shear strain by up to about 60%.

  5. Towards understanding the mechanisms and the kinetics of nanoparticle penetration through protective gloves

    NASA Astrophysics Data System (ADS)

    Vinches, L.; Peyrot, C.; Lemarchand, L.; Boutrigue, N.; Zemzem, M.; Wilkinson, K. J.; Hallé, S.; Tufenkji, N.

    2015-05-01

    Parallel to the increased use of engineered nanoparticles (ENP) in the formulation of commercial products or in medicine, numerous health & safety agencies have recommended the application of the precautionary principle to handle ENP; namely, the recommendation to use protective gloves against chemicals. However, recent studies reveal the penetration of titanium dioxide nanoparticles through nitrile rubber protective gloves in conditions simulating occupational use. This project is designed to understand the links between the penetration of gold nanoparticles (nAu) through nitrile rubber protective gloves and the mechanical and physical behaviour of the elastomer material subjected to conditions simulating occupational use (i.e., mechanical deformations (MD) and sweat). Preliminary analyses show that nAu suspensions penetrate selected glove materials after exposure to prolonged (3 hours) dynamic deformations. Significant morphological changes are observed on the outer surface of the glove sample; namely, the number and the surface of the micropores on the surface increase. Moreover, nitrile rubber protective gloves are also shown to be sensitive to the action of nAu suspension and to the action of the saline solution used to simulate sweat (swelling).

  6. The protective mechanisms of paracetamol against ethanol-induced gastric mucosal damage in rats.

    PubMed

    Poon, Y K; Cho, C H; Ogle, C W

    1989-08-01

    The protective mechanisms of paracetamol against ethanol-induced gastric mucosal damage have been examined. The antiulcer action of subcutaneously (s.c.)-injected paracetamol, 250 mg kg-1, was attenuated by either subdiaphragmatic vagotomy or s.c. injection of N-ethylmaleimide, 10 mg kg-1. This attenuation was not seen in rats given paracetamol by the oral route (p.o.). Indomethacin pretreatment, 5 mg kg-1, did not influence the lesion-preventing action of paracetamol given s.c. or p.o. The findings suggest that the antiulcer effect of s.c.-administered paracetamol results from an action involving the vagal nerve and tissue sulfhydryls, but not prostaglandins. On the other hand, the protective mechanism of paracetamol p.o. is independent of the vagal system or tissue sulfhydryls and prostaglandins. It seems that paracetamol given p.o. exerts its antiulcer effect by acting directly on the mucosal cell to strengthen mucosal integrity.

  7. Mechanisms of radiation interaction with DNA: Potential implications for radiation protection

    SciTech Connect

    Sinclair, W.K.; Fry, R.J.M.

    1987-01-01

    An overview of presentations and discussions which took place at the US Department of Energy/Commission of European Communities (DOE/CEC) workshop on ''Mechanisms of Radiation Interaction with DNA: Potential Implications for Radiation Protection,'' held at San Diego, California, January 21-22, 1987, is provided. The Department has traditionally supported fundamental research on interactions of ionizing radiation with different biological systems and at all levels of biological organization. The aim of this workshop was to review the base of knowledge in the area of mechanisms of radiation action at the DNA level, and to explore ways in which this information can be applied to the development of scientifically sound concepts and procedures for use in the field of radiation protection.

  8. Bibliography of information on mechanics of structural failure (hydrogen embrittlement, protective coatings, composite materials, NDE)

    NASA Technical Reports Server (NTRS)

    Carpenter, J. L., Jr.

    1976-01-01

    This bibliography is comprised of approximately 1,600 reference citations related to four problem areas in the mechanics of failure in aerospace structures. The bibliography represents a search of the literature published in the period 1962-1976, the effort being largely limited to documents published in the United States. Listings are subdivided into the four problem areas: Hydrogen Embrittlement; Protective Coatings; Composite Materials; and Nondestructive Evaluation. An author index is included.

  9. [(-)-Epigallocatechin gallate regulates expression of apoptotic genes and protects cultured human lens epithelial cells under hyperglycemia].

    PubMed

    Ye, Panpan; Lin, Kana; Li, Zhaochun; Liu, Jian; Yao, Ke; Xu, Wen

    2013-01-01

    (-)-Epigallocatechin gallate (EGCG), the most abundant component in green tea, has a potent anti-apoptotic activity. The purpose of this study was to investigate the protective effects of EGCG and their molecular mechanisms on high glucose-induced apoptosis of human lens epithelial cells (HLEB-3). HLEB-3 cells were exposed to various concentrations of glucose and EGCG. Cell death was assessed by MTT assay and flow cytometry using annexin V and propidium iodide. The expression of the Bcl-2 family, c-fos, c-myc and p53 was measured by real-time PCR. EGCG decreased the Bcl-2/Bax expression stimulated by a high glucose. Moreover, EGCG suppressed the high glucose-induced expression of c-fos, c-myc and p53. These findings suggest that EGCG protects HLEB-3 cells from high glucose-induced apoptosis by regulating the gene expression of the Bcl-2 family, c-fos, c-myc and p53. Thus, EGCG may have a potential protective effect against diabetic cataract formation.

  10. Structural integrity and failure mechanisms of a smart piezoelectric actuator under a cyclic bending mode

    NASA Astrophysics Data System (ADS)

    Woo, Sung-Choong; Goo, Nam Seo

    2008-08-01

    Information on the onset and evolution of damage within materials is essential for guaranteeing the integrity of actuator systems. The authors have evaluated the structural integrity and the failure mechanisms of smart composite actuators with a PZT ceramic plate under electric cyclic loading. For this, two kinds of actuators, actuator 1 and actuator 2, were manufactured. Prior to the main testing, performance testing was performed on the actuators to determine their resonant frequencies. Electric cyclic tests were conducted up to twenty million cycles. An acoustic emission technique was used for monitoring the damage evolution in real time. We observed the extent of the damage after testing using scanning electron microscopy and reflected optical microscopy to support characteristics in the acoustic emission behavior that corresponded to specific types of damage mechanisms. It was shown that the initial damage mechanism of the smart composite actuator under electric cyclic loading originated from the transgranular micro-fatigue damage in the PZT ceramic layer. With increasing cycles, a local intergranular crack initiated and developed onto the surface of the PZT ceramic layer or propagated into the internal layer. Finally, short-circuiting led to the electric breakdown of the actuator. These results were different depending on the drive frequencies and the configuration of the actuators. Moreover, we differentiated between the aforementioned damage mechanisms via AE signal pattern analyses based on the primary frequency and the waveform. From our results, we conclude that the drive frequency and the existence of a protecting layer are dominant factors in the structural integrity of the smart composite actuator.

  11. Four-path multiple ∞-shaped fiber protection mechanism for cable television networks

    NASA Astrophysics Data System (ADS)

    Shih, Fu-Hung; Lai, Jiunn-Ru; Chen, Wen-Ping; Wang, Luke K.

    2015-03-01

    Traditional cable television (CATV) network configuration is mainly a branch topology. When fibers break, there are always disconnections of CATV and Internet access. Meanwhile, network service providers usually cannot be instantly informed of network breakage; network problems are noticed only after the users call for services. Network breakage location detection and repair are, in general, costly and time-consuming. This paper proposes a new framework to protect CATV fiber optic networks, where a HUB with multiple optical protection switching (OPS) is constructed between the head end and the fiber nodes. The first layer ranging from the head end to the HUB forms a 1+1 protection path ring structure. The second layer ranging from the HUB to the fiber nodes forms multiple 1+1 protection path ring structures. The framework can form a four fiber optic path protection architecture with multiple ∞-shapes between the head end and the fiber nodes. When the CATV network system experiences a malfunction, such as fiber optic cable breakage or poor signal quality, OPS can immediately switch the fiber transmission path in order to maintain uninterrupted CATV network traffic. After simulation tests on fiber path switching time automatic protection switching, frame loss, packet jitter, latency, bit errors, and system traffic flow monitoring by manually switching OPS and pulling broken fiber optic cable, results show that the fiber path protection switching mechanism can react immediately, and test data results show that network traffic is unaffected, so the proposed framework can effectively enhance the survivability and quality of service of CATV network systems.

  12. Protective mechanisms and acclimation to solar ultraviolet-B radiation in Oenothera stricta

    NASA Technical Reports Server (NTRS)

    Robberecht, R.; Caldwell, M. M.

    1981-01-01

    Plant adaptations ameliorating or repairing the damaging effects of ultraviolet-B (UV-B) radiation on plant tissue were investigated. The degree of phenotype plasticity in UV protective mechanisms and acclimation in relation to the natural solar UV-B radiation flux and in an enhanced UV-B irradiance environment was also examined. Mechanisms by which plants avoid radiation, adaptations altering the path of radiation incident on the leaf, and repair processes were considered. Attenuation of UV-B by tissues, UV-B irradiation into the leaf, and the effects of UV-B on photosynthesis were investigated.

  13. Financial protection against nuclear hazards: thirty years' experience under the Price-Anderson Act

    SciTech Connect

    Rockett, L.R.; Hayn, I.

    1984-01-01

    The purpose of this study is to evaluate the operation of the Price-Anderson Act in the light of the last 10 years' experience and the changes that have occurred during that period both in the law and regulations and in the nuclear and insurance industries, and to provide an independent analysis of various proposals to extend or amend the Act prior to its 1987 expiration. The report does not analyze the impact of the Silkwood v. Kerr McGee Corp. decision. The five chapters cover historical background, financial protection under the Price-Anderson Act and in the absence of the Act, fundamental policy issues, and alternative proposals.

  14. Risk Protection, Service Use, and Health Outcomes under Colombia's Health Insurance Program for the Poor.

    PubMed

    Miller, Grant; Pinto, Diana; Vera-Hernández, Marcos

    2013-10-01

    Unexpected medical care spending imposes considerable financial risk on developing country households. Based on managed care models of health insurance in wealthy countries, Colombia's Régimen Subsidiado is a publicly financed insurance program targeted to the poor, aiming both to provide risk protection and to promote allocative efficiency in the use of medical care. Using a "fuzzy" regression discontinuity design, we find that the program has shielded the poor from some financial risk while increasing the use of traditionally under-utilized preventive services - with measurable health gains.

  15. Risk Protection, Service Use, and Health Outcomes under Colombia's Health Insurance Program for the Poor.

    PubMed

    Miller, Grant; Pinto, Diana; Vera-Hernández, Marcos

    2013-10-01

    Unexpected medical care spending imposes considerable financial risk on developing country households. Based on managed care models of health insurance in wealthy countries, Colombia's Régimen Subsidiado is a publicly financed insurance program targeted to the poor, aiming both to provide risk protection and to promote allocative efficiency in the use of medical care. Using a "fuzzy" regression discontinuity design, we find that the program has shielded the poor from some financial risk while increasing the use of traditionally under-utilized preventive services - with measurable health gains. PMID:25346799

  16. Mechanical fatigue performance of PCL-chondroprogenitor constructs after cell culture under bioreactor mechanical stimulus.

    PubMed

    Panadero, Juan Alberto; Sencadas, Vitor; Silva, Sonia C M; Ribeiro, Clarisse; Correia, Vitor; Gama, Francisco M; Gomez Ribelles, José Luis; Lanceros-Mendez, Senentxu

    2016-02-01

    In tissue engineering of cartilage, polymeric scaffolds are implanted in the damaged tissue and subjected to repeated compression loading cycles. The possibility of failure due to mechanical fatigue has not been properly addressed in these scaffolds. Nevertheless, the macroporous scaffold is susceptible to failure after repeated loading-unloading cycles. This is related to inherent discontinuities in the material due to the micropore structure of the macro-pore walls that act as stress concentration points. In this work, chondrogenic precursor cells have been seeded in poly-ε-caprolactone (PCL) scaffolds with fibrin and some were submitted to free swelling culture and others to cyclic loading in a bioreactor. After cell culture, all the samples were analyzed for fatigue behavior under repeated loading-unloading cycles. Moreover, some components of the extracellular matrix (ECM) were identified. No differences were observed between samples undergoing free swelling or bioreactor loading conditions, neither respect to matrix components nor to mechanical performance to fatigue. The ECM did not achieve the desired preponderance of collagen type II over collagen type I which is considered the main characteristic of hyaline cartilage ECM. However, prediction in PCL with ECM constructs was possible up to 600 cycles, an enhanced performance when compared to previous works. PCL after cell culture presents an improved fatigue resistance, despite the fact that the measured elastic modulus at the first cycle was similar to PCL with poly(vinyl alcohol) samples. This finding suggests that fatigue analysis in tissue engineering constructs can provide additional information missed with traditional mechanical measurements.

  17. Chemical PARP Inhibition Enhances Growth of Arabidopsis and Reduces Anthocyanin Accumulation and the Activation of Stress Protective Mechanisms

    PubMed Central

    Schulz, Philipp; Neukermans, Jenny; Van Der Kelen, Katrien; Mühlenbock, Per; Van Breusegem, Frank; Noctor, Graham; Teige, Markus; Metzlaff, Michael; Hannah, Matthew A.

    2012-01-01

    Poly-ADP-ribose polymerase (PARP) post-translationally modifies proteins through the addition of ADP-ribose polymers, yet its role in modulating plant development and stress responses is only poorly understood. The experiments presented here address some of the gaps in our understanding of its role in stress tolerance and thereby provide new insights into tolerance mechanisms and growth. Using a combination of chemical and genetic approaches, this study characterized phenotypes associated with PARP inhibition at the physiological level. Molecular analyses including gene expression analysis, measurement of primary metabolites and redox metabolites were used to understand the underlying processes. The analysis revealed that PARP inhibition represses anthocyanin and ascorbate accumulation under stress conditions. The reduction in defense is correlated with enhanced biomass production. Even in unstressed conditions protective genes and molecules are repressed by PARP inhibition. The reduced anthocyanin production was shown to be based on the repression of transcription of key regulatory and biosynthesis genes. PARP is a key factor for understanding growth and stress responses of plants. PARP inhibition allows plants to reduce protection such as anthocyanin, ascorbate or Non-Photochemical-Quenching whilst maintaining high energy levels likely enabling the observed enhancement of biomass production under stress, opening interesting perspectives for increasing crop productivity. PMID:22662141

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

    PubMed Central

    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

  19. New insights on neurobiological mechanisms underlying alcohol addiction.

    PubMed

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

    2013-04-01

    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

  20. Behavior of cracked cylinders under combined thermal and mechanical loading

    SciTech Connect

    Ignaccolo, S.

    1996-12-01

    Nuclear pressure vessels and pipings can be submitted in their life to severe mechanical and thermal loadings. Engineering methods easy to apply, but sufficiently accurate, are needed to assess the flaws. In the field of non-linear fracture mechanics a lot of work has been achieved for structures submitted to mechanical loadings. But for thermal loadings, and particularly for thermal gradients, only few contributions are available. The authors propose, here, to present the main results of a complete set of finite element computations, conducted in France by CEA, EDF and FRAMATOME, on cracked cylinders submitted to combined mechanical and thermal loads. The interaction between these two types of loads is analyzed in the cases of austenitic and ferritic structures. Moreover, these results are compared to the predictions obtained by simplified engineering methods (R6 procedure, J{sub SA16}, and J{sub EDF} approaches). Their domain of validity is also discussed.

  1. Analysis of Strains Lacking Known Osmolyte Accumulation Mechanisms Reveals Contributions of Osmolytes and Transporters to Protection against Abiotic Stress

    PubMed Central

    Murdock, Lindsay; Burke, Tangi; Coumoundouros, Chelsea; Culham, Doreen E.; Deutch, Charles E.; Ellinger, James; Kerr, Craig H.; Plater, Samantha M.; To, Eric; Wright, Geordie

    2014-01-01

    Osmolyte accumulation and release can protect cells from abiotic stresses. In Escherichia coli, known mechanisms mediate osmotic stress-induced accumulation of K+ glutamate, trehalose, or zwitterions like glycine betaine. Previous observations suggested that additional osmolyte accumulation mechanisms (OAMs) exist and their impacts may be abiotic stress specific. Derivatives of the uropathogenic strain CFT073 and the laboratory strain MG1655 lacking known OAMs were created. CFT073 grew without osmoprotectants in minimal medium with up to 0.9 M NaCl. CFT073 and its OAM-deficient derivative grew equally well in high- and low-osmolality urine pools. Urine-grown bacteria did not accumulate large amounts of known or novel osmolytes. Thus, CFT073 showed unusual osmotolerance and did not require osmolyte accumulation to grow in urine. Yeast extract and brain heart infusion stimulated growth of the OAM-deficient MG1655 derivative at high salinity. Neither known nor putative osmoprotectants did so. Glutamate and glutamine accumulated after growth with either organic mixture, and no novel osmolytes were detected. MG1655 derivatives retaining individual OAMs were created. Their abilities to mediate osmoprotection were compared at 15°C, 37°C without or with urea, and 42°C. Stress protection was not OAM specific, and variations in osmoprotectant effectiveness were similar under all conditions. Glycine betaine and dimethylsulfoniopropionate (DMSP) were the most effective. Trimethylamine-N-oxide (TMAO) was a weak osmoprotectant and a particularly effective urea protectant. The effectiveness of glycine betaine, TMAO, and proline as osmoprotectants correlated with their preferential exclusion from protein surfaces, not with their propensity to prevent protein denaturation. Thus, their effectiveness as stress protectants correlated with their ability to rehydrate the cytoplasm. PMID:24951793

  2. Protection of Lotus Seedpod Proanthocyanidins on Organs and Tissues under High-intensity Excercise

    PubMed Central

    Mengyan, Zhang

    2015-01-01

    Lotus seedpod proanthocyanidins (LSPC) as a kind of polyphenols is widely used in medicines, cosmetics, health products. High-intensity exercise can cause damage to the body's organs and tissues. Different doses of LSPC is given to mice to check the function of protect effect to the body's organs and tissues under high-intensity exercise. The hemoglobin (HB) content, red blood cell (RBC) number and white blood cell (WBC) number were tested for mice after exercise. The activity of superoxide dismutase (SOD) and the contents of glutathione (GSH) and malondialdehyde (MDA) in muscle and viscera were evaluated. The result showed that LSPC can effectively reduce inflammation reaction in the body of mice with high intensity exercise, alleviate oxidative stress-induced injury of tissues and organs, and execute protective function on skeletal muscle and cardiac muscle. And the LSPC could enhance myocardial anti-oxygen and enzymatic activity which suggests the protective effects of resveratrol against exercise-induced myocardial damage in mice. PMID:26998176

  3. Protection of Lotus Seedpod Proanthocyanidins on Organs and Tissues under High-intensity Excercise.

    PubMed

    Mengyan, Zhang

    2015-01-01

    Lotus seedpod proanthocyanidins (LSPC) as a kind of polyphenols is widely used in medicines, cosmetics, health products. High-intensity exercise can cause damage to the body's organs and tissues. Different doses of LSPC is given to mice to check the function of protect effect to the body's organs and tissues under high-intensity exercise. The hemoglobin (HB) content, red blood cell (RBC) number and white blood cell (WBC) number were tested for mice after exercise. The activity of superoxide dismutase (SOD) and the contents of glutathione (GSH) and malondialdehyde (MDA) in muscle and viscera were evaluated. The result showed that LSPC can effectively reduce inflammation reaction in the body of mice with high intensity exercise, alleviate oxidative stress-induced injury of tissues and organs, and execute protective function on skeletal muscle and cardiac muscle. And the LSPC could enhance myocardial anti-oxygen and enzymatic activity which suggests the protective effects of resveratrol against exercise-induced myocardial damage in mice. PMID:26998176

  4. Reaction mechanism underlying the in vitro transformation of thioarsenicals

    SciTech Connect

    Naranmandura, Hua; Suzuki, Noriyuki; Suzuki, Kazuo T.

    2008-09-15

    Thioarsenicals have been paid much attention due to the toxicity of arsenic, since some of them are highly toxic and commonly found in the urine of mammals. We previously reported that thioarsenicals might be produced in red blood cells (RBCs). Here, we further characterized the mechanism underlying the production and metabolism of thioarsenicals in RBCs using {sup 34}S-labeled dimethylmonothioarsinic acid ({sup 34}S-DMMTA{sup V}) and purified rat hemoglobin (Hb) or a rat RBC lysate. {sup 34}S-DMMTA{sup V} did not bind to Hb on incubation with purified rat Hb, remaining in its original form. However, when {sup 34}S-DMMTA{sup V} was incubated with a rat RBC lysate, only arsenic, i.e., not sulfur ({sup 34}S), was detected in a form bound to Hb (As-Hb). In addition, another arsenic product containing sulfur ({sup 34}S) in the molar ratio of {sup 34}S/As = 2 was detected, which was assigned as dimethyldithioarsinic acid (DMDTA{sup V}), suggesting that arsenic does not bind to Hb in the form of {sup 34}S-DMMTA{sup V} but does so in the form of dimethylarsinous acid (DMA{sup III}). Namely, DMMTA{sup V} appeared to be hydrolyzed into dimethylarsinic acid (DMA{sup V}) and H{sup 34}S{sup -}, and the released H{sup 34}S{sup -} reacted with DMMTA{sup V} to produce DMDTA{sup V}. Thus, DMMTA{sup V} was transformed into DMDTA{sup V} and DMA{sup V} (2DMMTA{sup V} - > DMDTA{sup V} + DMA{sup V}), the latter product being reduced to DMA{sup III} in the presence of GSH and bound to Hb. In a separate experiment, {sup 34}S-DMMTA{sup V} was incubated with sulfide (Na{sub 2}S) and GSH. Although DMMTA{sup V} was not transformed into DMDTA{sup V} in the presence of only Na{sub 2}S or GSH, it was transformed into DMDTA{sup V} in the presence of both Na{sub 2}S and GSH. Our results suggest that DMMTA{sup V} is hydrolyzed enzymatically into DMA{sup V} and sulfide, the former being reduced to DMA{sup III} and bound to Hb, and the latter reacting with DMMTA{sup V} to yield DMDTA{sup V}. Thus

  5. Indium oxide thin film as potential photoanodes for corrosion protection of stainless steel under visible light

    SciTech Connect

    Zhang, Yan; Yu, Jianqiang; Sun, Kai; Zhu, Yukun; Bu, Yuyu; Chen, Zhuoyuan

    2014-05-01

    Graphical abstract: If the conduction band potential of In{sub 2}O{sub 3} is more negative than the corrosion potential of stainless steel, photo-induced electrons will be transferred from In{sub 2}O{sub 3} to the steel, thus shifting the potential of the steel into a corrosion immunity region and preventing the steel from the corrosion. - Highlights: • Indium oxide performed novel application under visible light. • Indium oxide by sol–gel method behaved better photoelectrochemical properties. • Electrons were transferred to stainless steel from indium oxide once light on. - Abstract: This paper reports the photoelectrochemical cathodic protection of 304 stainless steel by In{sub 2}O{sub 3} thin-film under visible-light. The films were fabricated with In{sub 2}O{sub 3} powders, synthesized by both sol–gel (In{sub 2}O{sub 3}-sg) and solid-state (In{sub 2}O{sub 3}-ss) processes. The photo-induced open circuit potential and the photo-to-current efficiency measurements suggested that In{sub 2}O{sub 3} could be a promising candidate material for photoelectrochemical cathodic protection of metallic alloys under visible light. Moreover, the polarization curve experimental results indicated that In{sub 2}O{sub 3}-sg thin-film can mitigate the corrosion potential of 304 stainless steel to much more negative values with a higher photocurrent density than the In{sub 2}O{sub 3}-ss film under visible-light illumination. All the results demonstrated that the In{sub 2}O{sub 3}-sg thin-film provides a better photoelectrochemical cathodic protection for 304 stainless steel than In{sub 2}O{sub 3}-ss thin-film under visible-light illumination. The higher photoelectrochemical efficiency is possibly due to the uniform thin films produced with the smaller particle size of In{sub 2}O{sub 3}-sg, which facilitates the transfer of the photo-induced electrons from bulk to the surface and suppresses the charge recombination of the electrons and holes.

  6. Strain-Specific Protective Effect of the Immunity Induced by Live Malarial Sporozoites under Chloroquine Cover

    PubMed Central

    Wijayalath, Wathsala; Cheesman, Sandra; Tanabe, Kazuyuki; Handunnetti, Shiroma; Carter, Richard; Pathirana, Sisira

    2012-01-01

    The efficacy of a whole-sporozoite malaria vaccine would partly be determined by the strain-specificity of the protective responses against malarial sporozoites and liver-stage parasites. Evidence from previous reports were inconsistent, where some studies have shown that the protective immunity induced by irradiated or live sporozoites in rodents or humans were cross-protective and in others strain-specific. In the present work, we have studied the strain-specificity of live sporozoite-induced immunity using two genetically and immunologically different strains of Plasmodium cynomolgi, Pc746 and PcCeylon, in toque monkeys. Two groups of monkeys were immunized against live sporozoites of either the Pc746 (n = 5), or the PcCeylon (n = 4) strain, by the bites of 2–4 sporozoite-infected Anopheles tessellates mosquitoes per monkey under concurrent treatments with chloroquine and primaquine to abrogate detectable blood infections. Subsequently, a group of non-immunized monkeys (n = 4), and the two groups of immunized monkeys were challenged with a mixture of sporozoites of the two strains by the bites of 2–5 infective mosquitoes from each strain per monkey. In order to determine the strain-specificity of the protective immunity, the proportions of parasites of the two strains in the challenge infections were quantified using an allele quantification assay, Pyrosequencing™, based on a single nucleotide polymorphism (SNP) in the parasites’ circumsporozoite protein gene. The Pyrosequencing™ data showed that a significant reduction of parasites of the immunizing strain in each group of strain-specifically immunized monkeys had occurred, indicating a stronger killing effect on parasites of the immunizing strain. Thus, the protective immunity developed following a single, live sporozoite/chloroquine immunization, acted specifically against the immunizing strain and was, therefore, strain-specific. As our experiment does not allow us to determine the

  7. Priority threat management of invasive animals to protect biodiversity under climate change.

    PubMed

    Firn, Jennifer; Maggini, Ramona; Chadès, Iadine; Nicol, Sam; Walters, Belinda; Reeson, Andy; Martin, Tara G; Possingham, Hugh P; Pichancourt, Jean-Baptiste; Ponce-Reyes, Rocio; Carwardine, Josie

    2015-11-01

    Climate change is a major threat to global biodiversity, and its impacts can act synergistically to heighten the severity of other threats. Most research on projecting species range shifts under climate change has not been translated to informing priority management strategies on the ground. We develop a prioritization framework to assess strategies for managing threats to biodiversity under climate change and apply it to the management of invasive animal species across one-sixth of the Australian continent, the Lake Eyre Basin. We collected information from key stakeholders and experts on the impacts of invasive animals on 148 of the region's most threatened species and 11 potential strategies. Assisted by models of current distributions of threatened species and their projected distributions, experts estimated the cost, feasibility, and potential benefits of each strategy for improving the persistence of threatened species with and without climate change. We discover that the relative cost-effectiveness of invasive animal control strategies is robust to climate change, with the management of feral pigs being the highest priority for conserving threatened species overall. Complementary sets of strategies to protect as many threatened species as possible under limited budgets change when climate change is considered, with additional strategies required to avoid impending extinctions from the region. Overall, we find that the ranking of strategies by cost-effectiveness was relatively unaffected by including climate change into decision-making, even though the benefits of the strategies were lower. Future climate conditions and impacts on range shifts become most important to consider when designing comprehensive management plans for the control of invasive animals under limited budgets to maximize the number of threatened species that can be protected. PMID:26179346

  8. Priority threat management of invasive animals to protect biodiversity under climate change.

    PubMed

    Firn, Jennifer; Maggini, Ramona; Chadès, Iadine; Nicol, Sam; Walters, Belinda; Reeson, Andy; Martin, Tara G; Possingham, Hugh P; Pichancourt, Jean-Baptiste; Ponce-Reyes, Rocio; Carwardine, Josie

    2015-11-01

    Climate change is a major threat to global biodiversity, and its impacts can act synergistically to heighten the severity of other threats. Most research on projecting species range shifts under climate change has not been translated to informing priority management strategies on the ground. We develop a prioritization framework to assess strategies for managing threats to biodiversity under climate change and apply it to the management of invasive animal species across one-sixth of the Australian continent, the Lake Eyre Basin. We collected information from key stakeholders and experts on the impacts of invasive animals on 148 of the region's most threatened species and 11 potential strategies. Assisted by models of current distributions of threatened species and their projected distributions, experts estimated the cost, feasibility, and potential benefits of each strategy for improving the persistence of threatened species with and without climate change. We discover that the relative cost-effectiveness of invasive animal control strategies is robust to climate change, with the management of feral pigs being the highest priority for conserving threatened species overall. Complementary sets of strategies to protect as many threatened species as possible under limited budgets change when climate change is considered, with additional strategies required to avoid impending extinctions from the region. Overall, we find that the ranking of strategies by cost-effectiveness was relatively unaffected by including climate change into decision-making, even though the benefits of the strategies were lower. Future climate conditions and impacts on range shifts become most important to consider when designing comprehensive management plans for the control of invasive animals under limited budgets to maximize the number of threatened species that can be protected.

  9. Numerical investigation of pulmonary drug delivery under mechanical ventilation conditions

    NASA Astrophysics Data System (ADS)

    Banerjee, Arindam; van Rhein, Timothy

    2012-11-01

    The effects of mechanical ventilation waveform on fluid flow and particle deposition were studied in a computer model of the human airways. The frequency with which aerosolized drugs are delivered to mechanically ventilated patients demonstrates the importance of understanding the effects of ventilation parameters. This study focuses specifically on the effects of mechanical ventilation waveforms using a computer model of the airways of patient undergoing mechanical ventilation treatment from the endotracheal tube to generation G7. Waveforms were modeled as those commonly used by commercial mechanical ventilators. Turbulence was modeled with LES. User defined particle force models were used to model the drag force with the Cunningham correction factor, the Saffman lift force, and Brownian motion force. The endotracheal tube (ETT) was found to be an important geometric feature, causing a fluid jet towards the right main bronchus, increased turbulence, and a recirculation zone in the right main bronchus. In addition to the enhanced deposition seen at the carinas of the airway bifurcations, enhanced deposition was also seen in the right main bronchus due to impaction and turbulent dispersion resulting from the fluid structures created by the ETT. Authors acknowledge financial support through University of Missouri Research Board Award.

  10. Plant resistance mechanisms to air pollutants: rhythms in ascorbic acid production during growth under ozone stress

    SciTech Connect

    Lee, E.H. )

    1991-01-01

    Relationships between ozone (O3) tolerance and leaf ascorbic acid concentrations in O3-susceptible (O3-S) 'Hark' and O3-resistant (O3-R) 'Hood' soybean, Glycine max (L.) Merr., cultivars were examined with high-performance liquid chromatography (HPLC). Leaf samples were analyzed at 4 intervals during a 24 h period. Soybean cultivars grown in the greenhouse with charcoal filtered (CF) and nonfiltered (NF) air showed daily oscillations in ascorbic acid production. Highest ascorbic acid levels in leaves during light coincided with highest concentrations of photochemical oxidants in the atmosphere at 2:00 p.m. The resistant genotype produced more ascorbic acid in its trifoliate leaves than did the corresponding susceptible genotype. Under CF air (an O3-reduced environment) O3-S and O3-R cultivars showed rhythms in ascorbic acid production. In NF air (an O3 stress environment) the O3-R cultivar alone showed rhythms in ascorbic acid production. Results indicated that superior O3 tolerance in the Hood soybean cultivar (compared with Hark) was associated with a greater increase in endogenous levels of ascorbic acid. Ascorbic acid may scavenge free radicals and thereby protect cells from injury by O3 or other oxyradical products. Plants defend themselves against photochemical oxidant stress, such as O3, by several mechanisms. Experimental evidence indicates that antioxidant defense systems existing in plant tissues may function to protect cellular components from deleterious effects of photochemical oxidants through endogenous and exogenous controls.

  11. Temperature-induced lipocalin (TIL) is translocated under salt stress and protects chloroplasts from ion toxicity.

    PubMed

    Abo-Ogiala, Atef; Carsjens, Caroline; Diekmann, Heike; Fayyaz, Payam; Herrfurth, Cornelia; Feussner, Ivo; Polle, Andrea

    2014-02-15

    Temperature-induced lipocalins (TIL) have been invoked in the defense from heat, cold and oxidative stress. Here we document a function of TIL for basal protection from salinity stress. Heterologous expression of TIL from the salt resistant poplar Populus euphratica did not rescue growth but prevented chlorophyll b destruction in salt-exposed Arabidopsis thaliana. The protein was localized to the plasma membrane but was re-translocated to the symplast under salt stress. The A. thaliana knock out and knock down lines Attil1-1 and Attil1-2 showed stronger stress symptoms and stronger chlorophyll b degradation than the wildtype (WT) under excess salinity. They accumulated more chloride and sodium in chloroplasts than the WT. Chloroplast chloride accumulation was found even in the absence of salt stress. Since lipocalins are known to bind regulatory fatty acids of channel proteins as well as iron, we suggest that the salt-induced trafficking of TIL may be required for protection of chloroplasts by affecting ion homeostasis.

  12. Radial-interval linear programming for environmental management under varied protection levels.

    PubMed

    Tan, Qian; Huang, Guo H; Cai, Yanpeng

    2010-09-01

    In this study, a radial-interval linear programming (RILP) approach was developed for supporting waste management under uncertainty. RILP improved interval-parameter linear programming and its extensions in terms of input reasonableness and output robustness. From the perspective of modeling inputs, RILP could tackle highly uncertain information at the bounds of interval parameters through introducing the concept of fluctuation radius. Regarding modeling outputs, RILP allows controlling the degree of conservatism associated with interval solutions and is capable of quantifying corresponding system risks and benefits. This could facilitate the reflection of interactive relationship between the feasibility of system and the uncertainty of parameters. A computationally tractable algorithm was provided to solve RILP. Then, a long-term waste management case was studied to demonstrate the applicability of the developed methodology. A series of interval solutions obtained under varied protection levels were compared, helping gain insights into the interactions among protection level, violation risk, and system cost. Potential waste allocation alternatives could be generated from these interval solutions, which would be screened in real-world practices according to various projected system conditions as well as decision-makers' willingness to pay and risk tolerance levels. Sensitivity analysis further revealed the significant impact of fluctuation radii of interval parameters on the system. The results indicated that RILP is applicable to a wide spectrum of environmental management problems that are subject to compound uncertainties.

  13. Protective effects and mechanisms of curcumin on podophyllotoxin toxicity in vitro and in vivo

    SciTech Connect

    Li, Juan; Dai, Cai-Xia; Sun, Hua; Jin, Lu; Guo, Chong-Yi; Cao, Wei; Wu, Jie; Tian, Hai-Yan; Luo, Cheng; Ye, Wen-Cai; Jiang, Ren-Wang

    2012-12-01

    Podophyllotoxin (POD) is a naturally occurring lignan with pronounced antineoplastic and antiviral properties. POD binds to tubulin and prevents the formation of mitotic spindle. Although cases of overdose or accidental ingestion are quite often, no specific therapy is currently available to treat the POD intoxication. In the current investigation, the protective effects and mechanisms of curcumin (CUR) on podophyllotoxin toxicity were evaluated in vitro and in vivo. The results showed that CUR could protect POD-induced cytotoxicity by recovering the G2/M arrest and decrease the changes of membrane potential and microtubule structure in Vero cells. A significant decrease of mortality rates was observed in Swiss mice treated by intragastrical administration of POD + CUR as compared with POD alone. The POD + CUR group also exhibited decreases in plasma transaminases, alkaline phosphatase, lactate dehydrogenase, plasma urea, creatinine and malondialdehyde level but elevated superoxide dismutase and glutathione levels as compared to the POD group. Histological examination of the liver and kidney demonstrated less morphological changes in the treatment of POD + CUR as compared with POD alone. The mechanism of the protective effects might be due to the competitive binding of CUR with POD in the same colchicines binding site as revealed by the tubulin polymerization assay and the molecular docking analysis, and the antioxidant activity against the oxidative stress induced by POD. In summary, both in vitro and in vivo data indicated the promising role of CUR as a protective agent against the POD poisoning. Highlights: ► A potential antidote to treat the podophyllotoxin (POD) intoxication is found. ► Curcumin showed promising effects against POD poisoning in vitro and in vivo. ► The mechanisms lie in the antioxidant activity and competitive binding with tubulin.

  14. Mechanisms of endothelial cell protection by blockade of the JAK2 pathway.

    PubMed

    Neria, Fernando; Caramelo, Carlos; Peinado, Héctor; González-Pacheco, Francisco R; Deudero, Juan J P; de Solis, Alain J; Fernández-Sánchez, Ruth; Peñate, Silvia; Cano, Amparo; Castilla, María Angeles

    2007-03-01

    Inhibition of the JAK2/STAT pathway has been implicated recently in cytoprotective mechanisms in both vascular smooth muscle cells and astrocytes. The advent of JAK2-specific inhibitors provides a practical tool for the study of this pathway in different cellular types. An interest in finding methods to improve endothelial cell (EC) resistance to injury led us to examine the effect of JAK2/STAT inhibition on EC protection. Furthermore, the signaling pathways involved in JAK2/STAT inhibition-related actions were examined. Our results reveal, for the first time, that blockade of JAK2 with the tyrosine kinase inhibitor AG490 strongly protects cultured EC against cell detachment-dependent death and serum deprivation and increases reseeding efficiency. Confirmation of the specificity of the effects of JAK2 inhibition was attained by finding protective effects on transfection with a dominant negative JAK2. Furthermore, AG490 blocked serum deprivation-induced phosphorylation of JAK2. In terms of mechanism, treatment with AG490 induces several relevant responses, both in monolayer and detached cells. These mechanisms include the following: 1) Increase and nuclear translocation of the active, dephosphorylated form of beta-catenin. In functional terms, this translocation is transcriptionally active, and its protective effect is further supported by the stimulation of EC cytoprotection by transfectionally induced excess of beta-catenin. 2) Increase of platelet endothelial cell adhesion molecule (PECAM)/CD31 levels. 3) Increase in total and phosphorylated AKT. 4) Increase in phosphorylated glycogen synthase kinase (GSK)3alpha/beta. The present findings imply potential practical applications of JAK2 inhibition on EC. These applications affect not only EC in the monolayer but also circulating detached cells and involve mechanistic interactions not previously described. PMID:17035297

  15. Mechanisms underlying the inhibition of interferon signaling by viruses.

    PubMed

    Devasthanam, Anand S

    2014-02-15

    A hallmark of the antiviral response is the induction of interferons. First discovered in 1957 by Issac and Lindeman, interferons are noted for their ability to interfere with viral replication. Interferons act via autocrine and paracrine pathways to induce an antiviral state in infected cells and in neighboring cells containing interferon receptors. Interferons are the frontline defenders against viral infection and their primary function is to locally restrict viral propagation. Viruses have evolved mechanisms to escape the host interferon response, thus gaining a replicative advantage in host cells. This review will discuss recent findings on the mechanisms viruses use to evade the host interferon response. This knowledge is important because the treatment of viral infections is a challenge of global proportions and a better understanding of the mechanisms viruses use to persist in the host may uncover valuable insights applicable to the discovery of novel drug targets.

  16. Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases.

    PubMed

    Qureshi, Irfan A; Mehler, Mark F

    2014-10-01

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

  17. Chronic nausea and vomiting: insights into underlying mechanisms.

    PubMed

    Törnblom, H; Abrahamsson, H

    2016-05-01

    Chronic nausea and vomiting are common and debilitating symptoms in adults. There are some fundamental problems that make our understanding of mechanisms difficult, diagnostic definitions of patient-cohorts being central. As there is no unifying mechanism with a direct link to chronic nausea or vomiting, it is most likely that several mechanisms interact, e.g., pylorus function and its relation to gastric emptying, or gastric sensory and motor function. In this mini-review, we highlight the roles and evidence for brain-gut interactions as well as gastrointestinal neurophysiologic, motor, sensory, and hormonal factors involved in the pathophysiology of chronic nausea and vomiting. There are factors not mentioned in the text, mostly as they are not well characterized in the setting of chronic symptoms or only in animal models. PMID:27106677

  18. Nematodynamics modelling under extreme mechanical and electric stresses

    NASA Astrophysics Data System (ADS)

    Amoddeo, Antonino

    2015-01-01

    Nematic liquid crystals confined in asymmetric π-cells and subjected to intense electrical and mechanical stresses undergo strong distortions which can be relaxed by means of the order reconstruction, a fast switching mechanism connecting topologically different textures, assuming bulk and/or surface characteristics depending on both amplitude of the applied electric fields and anchoring angles of the nematic molecules on the confining surfaces. In the frame of the Landau-de Gennes order tensor theory, we provide a numerical model implemented with a moving mesh finite element method appropriate to describe the nematic order dynamics, allowing to map the switching properties of the nematic texture.

  19. A tomato chloroplast-targeted DnaJ protein protects Rubisco activity under heat stress.

    PubMed

    Wang, Guodong; Kong, Fanying; Zhang, Song; Meng, Xia; Wang, Yong; Meng, Qingwei

    2015-06-01

    Photosynthesis is one of the biological processes most sensitive to heat stress in plants. Carbon assimilation, which depends on ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), is one of the major sites sensitive to heat stress in photosynthesis. In this study, the roles of a tomato (Solanum lycopersicum) chloroplast-targeted DnaJ protein (SlCDJ2) in resisting heat using sense and antisense transgenic tomatoes were examined. SlCDJ2 was found to be uniformly distributed in the thylakoids and stroma of the chloroplasts. Under heat stress, sense plants exhibited higher chlorophyll contents and fresh weights, and lower accumulation of reactive oxygen species (ROS) and membrane damage. Moreover, Rubisco activity, Rubisco large subunit (RbcL) content, and CO2 assimilation capacity were all higher in sense plants and lower in antisense plants compared with wild-type plants. Thus, SlCDJ2 contributes to maintenance of CO2 assimilation capacity mainly by protecting Rubisco activity under heat stress. SlCDJ2 probably achieves this by keeping the levels of proteolytic enzymes low, which prevents accelerated degradation of Rubisco under heat stress. Furthermore, a chloroplast heat-shock protein 70 was identified as a binding partner of SlCDJ2 in yeast two-hybrid assays. Taken together, these findings establish a role for SlCDJ2 in maintaining Rubisco activity in plants under heat stress. PMID:25801077

  20. A tomato chloroplast-targeted DnaJ protein protects Rubisco activity under heat stress.

    PubMed

    Wang, Guodong; Kong, Fanying; Zhang, Song; Meng, Xia; Wang, Yong; Meng, Qingwei

    2015-06-01

    Photosynthesis is one of the biological processes most sensitive to heat stress in plants. Carbon assimilation, which depends on ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), is one of the major sites sensitive to heat stress in photosynthesis. In this study, the roles of a tomato (Solanum lycopersicum) chloroplast-targeted DnaJ protein (SlCDJ2) in resisting heat using sense and antisense transgenic tomatoes were examined. SlCDJ2 was found to be uniformly distributed in the thylakoids and stroma of the chloroplasts. Under heat stress, sense plants exhibited higher chlorophyll contents and fresh weights, and lower accumulation of reactive oxygen species (ROS) and membrane damage. Moreover, Rubisco activity, Rubisco large subunit (RbcL) content, and CO2 assimilation capacity were all higher in sense plants and lower in antisense plants compared with wild-type plants. Thus, SlCDJ2 contributes to maintenance of CO2 assimilation capacity mainly by protecting Rubisco activity under heat stress. SlCDJ2 probably achieves this by keeping the levels of proteolytic enzymes low, which prevents accelerated degradation of Rubisco under heat stress. Furthermore, a chloroplast heat-shock protein 70 was identified as a binding partner of SlCDJ2 in yeast two-hybrid assays. Taken together, these findings establish a role for SlCDJ2 in maintaining Rubisco activity in plants under heat stress.

  1. Adiponectin-Mediated Heme Oxygenase-1 Induction Protects Against Iron-Induced Liver Injury via a PPARα-Dependent Mechanism

    PubMed Central

    Lin, Heng; Yu, Chun-Hsien; Jen, Chih-Yu; Cheng, Ching-Feng; Chou, Ying; Chang, Chih-Cheng; Juan, Shu-Hui

    2010-01-01

    Protective effects of adiponectin (APN; an adipocytokine) were shown against various oxidative challenges; however, its therapeutic implications and the mechanisms underlying hepatic iron overload remain unclear. Herein, we show that the deleterious effects of iron dextran on liver function and iron deposition were significantly reversed by adiponectin gene therapy, which was accompanied by AMP-activated protein kinase (AMPK) phosphorylation and heme oxygenase (HO)-1 induction. Furthermore, AMPK-mediated peroxisome proliferator-activated receptor-α (PPARα) activation by APN was ascribable to HO-1 induction. Additionally, we revealed direct transcriptional regulation of HO-1 by the binding of PPARα to a PPAR-responsive element (PPRE) by various experimental assessments. Interestingly, overexpression of HO-1 in hepatocytes mimicked the protective effect of APN in attenuating iron-mediated injury, whereas it was abolished by SnPP and small interfering HO-1. Furthermore, bilirubin, the end-product of the HO-1 reaction, but not CO, protected hepatocytes from iron dextran-mediated caspase activation. Herein, we demonstrate a novel functional PPRE in the promoter regions of HO-1, and APN-mediated HO-1 induction elicited an antiapoptotic effect and a decrease in iron deposition in hepatocytes subjected to iron challenge. PMID:20709802

  2. Hannay Angle: Yet Another Symmetry-Protected Topological Order Parameter in Classical Mechanics

    NASA Astrophysics Data System (ADS)

    Kariyado, Toshikaze; Hatsugai, Yasuhiro

    2016-04-01

    The topological way of thinking now goes beyond quantum solids, and topological characters of classical mechanical systems obeying Newton's law are attracting current interest. To provide a physical insight into the topological numbers in mechanics, we demonstrate the use of the Hannay angle, a "classical" Berry phase, as a symmetry-protected topological order parameter. The Hannay angle is derived using a canonical transformation that maps Newton's equation to a Schrödinger-type equation, and the condition for the quantization is discussed in connection with the symmetry in mechanics. Also, we demonstrate the use of the Hannay angle for a topological characterization of a spring-mass model focusing on the bulk-edge correspondence.

  3. 25 CFR 63.32 - Under what authority are Indian child protection and family violence prevention program funds...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... family violence prevention program funds awarded? 63.32 Section 63.32 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT INDIAN CHILD PROTECTION AND FAMILY VIOLENCE PREVENTION Indian Child Protection and Family Violence Prevention Program § 63.32 Under what authority are Indian...

  4. 25 CFR 63.32 - Under what authority are Indian child protection and family violence prevention program funds...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... family violence prevention program funds awarded? 63.32 Section 63.32 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT INDIAN CHILD PROTECTION AND FAMILY VIOLENCE PREVENTION Indian Child Protection and Family Violence Prevention Program § 63.32 Under what authority are Indian...

  5. 25 CFR 63.32 - Under what authority are Indian child protection and family violence prevention program funds...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... family violence prevention program funds awarded? 63.32 Section 63.32 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT INDIAN CHILD PROTECTION AND FAMILY VIOLENCE PREVENTION Indian Child Protection and Family Violence Prevention Program § 63.32 Under what authority are Indian...

  6. 25 CFR 63.32 - Under what authority are Indian child protection and family violence prevention program funds...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... family violence prevention program funds awarded? 63.32 Section 63.32 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT INDIAN CHILD PROTECTION AND FAMILY VIOLENCE PREVENTION Indian Child Protection and Family Violence Prevention Program § 63.32 Under what authority are Indian...

  7. 25 CFR 63.32 - Under what authority are Indian child protection and family violence prevention program funds...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... family violence prevention program funds awarded? 63.32 Section 63.32 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR TRIBAL GOVERNMENT INDIAN CHILD PROTECTION AND FAMILY VIOLENCE PREVENTION Indian Child Protection and Family Violence Prevention Program § 63.32 Under what authority are Indian...

  8. 47 CFR 54.520 - Children's Internet Protection Act certifications required from recipients of discounts under the...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Children's Internet Protection Act... Libraries § 54.520 Children's Internet Protection Act certifications required from recipients of discounts... technology that blocks or filters Internet access to the material covered by a certification under...

  9. 47 CFR 54.520 - Children's Internet Protection Act certifications required from recipients of discounts under the...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 false Children's Internet Protection Act... Libraries § 54.520 Children's Internet Protection Act certifications required from recipients of discounts... technology that blocks or filters Internet access to the material covered by a certification under...

  10. 47 CFR 54.520 - Children's Internet Protection Act certifications required from recipients of discounts under the...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 false Children's Internet Protection Act... Libraries § 54.520 Children's Internet Protection Act certifications required from recipients of discounts... technology that blocks or filters Internet access to the material covered by a certification under...

  11. Mechanisms of airway protection after pharyngeal fluid infusion in healthy sleeping piglets.

    PubMed

    Page, M; Jeffery, H E; Marks, V; Post, E J; Wood, A K

    1995-05-01

    The airway protective mechanisms evoked after infusion of fluids into the pharynx were examined in the intact and healthy newborn piglet during sleep. Thirteen healthy normothermic piglets (3-6 days of age) were examined on 4 consecutive days during sleep. The fluids infused (0.05-1.5 ml) were 0.9% saline, distilled water, and HCl (pH 3 and pH 2). Respiratory rate, heart rate, oxygen saturation (SaO2), swallowing, and arousal were compared pre- and postinfusion during active (AS) and quiet sleep (QS) for each test fluid. The most common response in AS and QS was swallowing (90%) and then arousal (24%); however, no apnea occurred, and respiratory rate and SaO2 were always maintained. A significant difference occurred between HCl infusions of pH 2 and pH 3; at pH 2, the frequency of swallows and latency to the first swallow were reduced (P < 0.05) and the frequency of arousal was reduced in AS compared with that in QS (P < 0.01). Airway protection after pharyngeal fluid stimulation is achieved primarily by swallowing and arousal, without any effect on respiratory rate and SaO2. Attenuation of protective mechanisms occurred, however, when the infusate was at pH 2. PMID:7649933

  12. PROTECTION DEVICE ON THE REPAIR OF RUPTURES OF KNEE EXTENSOR MECHANISM

    PubMed Central

    Arguello Frutos, Carlos Francisco; Arbix Camargo, Osmar Pedro; Severino, Nilson Roberto; Leite Cury, Ricardo de Paula; de Oliveira, Victor Marques; Aihara, Tatsuo; Avakian, Roger

    2015-01-01

    To evaluate results obtained using the protection device technique for osteosintesis or suture of extensor mechanism lesions. Material and Methods: The authors reviewed 18 charts of patients submitted to protection device technique due to traumatic lesion of extensor mechanism that had occurred between the anterior tibial tuberosity and the apical portion of patella. Age ranged from 22 to 69 years, with a mean of 44 years. Male patients prevailed, with 67% of the cases. The most affected spot was, in 83% of the cases, the apical distal third. A protocol was created to collect data, listing the patients and the clinical history from their medical records. Results: The authors observed consolidation of the patella fracture in all 17 patients, and cicatrization of the patellar ligament in one patient. Pain was described in four patients. There were no complications related to the procedure. Conclusion: The protection device showed to be efficient when used in surgical treatment of lesions between the apical patella and the anterior tibial tuberosity, providing active and passive mobility in the early postoperative time. PMID:26998454

  13. Cruciferous vegetables: cancer protective mechanisms of glucosinolate hydrolysis products and selenium.

    PubMed

    Keck, Anna-Sigrid; Finley, John W

    2004-03-01

    Dietetic professionals urge Americans to increase fruit and vegetable intakes. The American Institute of Cancer Research estimates that if the only dietary change made was to increase the daily intake of fruits and vegetables to 5 servings per day, cancer rates could decline by as much as 20%. Among the reasons cited for this health benefit are that fruits and vegetables are excellent sources of fiber, vitamins, and minerals. They also contain nonnutritive components that may provide substantial health benefits beyond basic nutrition. Examples of the latter are the glucosinolate hydrolysis products, sulforaphane, and indole-3-carbinol. Epidemiological studies provide evidence that the consumption of cruciferous vegetables protects against cancer more effectively than the total intake of fruits and vegetables. This review describes the anticarcinogenic bioactivities of glucosinolate hydrolysis products, the mineral selenium derived from crucifers, and the mechanisms by which they protect against cancer. These mechanisms include altered estrogen metabolism, protection against reactive oxygen species, altered detoxification by induction of phase II enzymes, decreased carcinogen activation by inhibition of phase I enzymes, and slowed tumor growth and induction of apoptosis.

  14. Mechanism of Aloe Vera extract protection against UVA: shelter of lysosomal membrane avoids photodamage.

    PubMed

    Rodrigues, Daniela; Viotto, Ana Cláudia; Checchia, Robert; Gomide, Andreza; Severino, Divinomar; Itri, Rosangela; Baptista, Maurício S; Martins, Waleska Kerllen

    2016-03-01

    The premature aging (photoaging) of skin characterized by wrinkles, a leathery texture and mottled pigmentation is a well-documented consequence of exposure to sunlight. UVA is an important risk factor for human cancer also associated with induction of inflammation, immunosuppression, photoaging and melanogenesis. Although herbal compounds are commonly used as photoprotectants against the harmful effects of UVA, the mechanisms involved in the photodamage are not precisely known. In this study, we investigated the effects of Aloe Vera (Aloe barbadensis mil) on the protection against UVA-modulated cell killing of HaCaT keratinocytes. Aloe Vera exhibited the remarkable ability of reducing both in vitro and in vivo photodamage, even though it does not have anti-radical properties. Interestingly, the protection conferred by Aloe Vera was associated with the maintenance of membrane integrity in both mimetic membranes and intracellular organelles. The increased lysosomal stability led to a decrease in lipofuscinogenesis and cell death. This study explains why Aloe Vera extracts offer protection against photodamage at a cellular level in both the UV and visible spectra, leading to its beneficial use as a supplement in protective dermatological formulations.

  15. TRF2-Mediated Control of Telomere DNA Topology as a Mechanism for Chromosome-End Protection.

    PubMed

    Benarroch-Popivker, Delphine; Pisano, Sabrina; Mendez-Bermudez, Aaron; Lototska, Liudmyla; Kaur, Parminder; Bauwens, Serge; Djerbi, Nadir; Latrick, Chrysa M; Fraisier, Vincent; Pei, Bei; Gay, Alexandre; Jaune, Emilie; Foucher, Kevin; Cherfils-Vicini, Julien; Aeby, Eric; Miron, Simona; Londoño-Vallejo, Arturo; Ye, Jing; Le Du, Marie-Hélène; Wang, Hong; Gilson, Eric; Giraud-Panis, Marie-Josèphe

    2016-01-21

    The shelterin proteins protect telomeres against activation of the DNA damage checkpoints and recombinational repair. We show here that a dimer of the shelterin subunit TRF2 wraps ∼ 90 bp of DNA through several lysine and arginine residues localized around its homodimerization domain. The expression of a wrapping-deficient TRF2 mutant, named Top-less, alters telomeric DNA topology, decreases the number of terminal loops (t-loops), and triggers the ATM checkpoint, while still protecting telomeres against non-homologous end joining (NHEJ). In Top-less cells, the protection against NHEJ is alleviated if the expression of the TRF2-interacting protein RAP1 is reduced. We conclude that a distinctive topological state of telomeric DNA, controlled by the TRF2-dependent DNA wrapping and linked to t-loop formation, inhibits both ATM activation and NHEJ. The presence of RAP1 at telomeres appears as a backup mechanism to prevent NHEJ when topology-mediated telomere protection is impaired.

  16. Mechanism of Aloe Vera extract protection against UVA: shelter of lysosomal membrane avoids photodamage.

    PubMed

    Rodrigues, Daniela; Viotto, Ana Cláudia; Checchia, Robert; Gomide, Andreza; Severino, Divinomar; Itri, Rosangela; Baptista, Maurício S; Martins, Waleska Kerllen

    2016-03-01

    The premature aging (photoaging) of skin characterized by wrinkles, a leathery texture and mottled pigmentation is a well-documented consequence of exposure to sunlight. UVA is an important risk factor for human cancer also associated with induction of inflammation, immunosuppression, photoaging and melanogenesis. Although herbal compounds are commonly used as photoprotectants against the harmful effects of UVA, the mechanisms involved in the photodamage are not precisely known. In this study, we investigated the effects of Aloe Vera (Aloe barbadensis mil) on the protection against UVA-modulated cell killing of HaCaT keratinocytes. Aloe Vera exhibited the remarkable ability of reducing both in vitro and in vivo photodamage, even though it does not have anti-radical properties. Interestingly, the protection conferred by Aloe Vera was associated with the maintenance of membrane integrity in both mimetic membranes and intracellular organelles. The increased lysosomal stability led to a decrease in lipofuscinogenesis and cell death. This study explains why Aloe Vera extracts offer protection against photodamage at a cellular level in both the UV and visible spectra, leading to its beneficial use as a supplement in protective dermatological formulations. PMID:26815913

  17. Early Damage Mechanisms in Nuclear Grade Graphite under Irradiation

    SciTech Connect

    Eapen, Dr. Jacob; Krishna, Dr Ram; Burchell, Timothy D; Murty, Prof K.L.

    2014-01-01

    Using Raman and X-ray photoelectron spectroscopy,we delineate the bond and defect structures in nuclear block graphite (NBG-18) under neutron and ion irradiation. The strengthening of the defect (D) peak in the Raman spectra under irradiation is attributed to an increase in the topological, sp2-hybridized defects. Using transmission electron microscopy, we provide evidence for prismatic dislocations as well as a number of basal dislocations dissociating into Shockley partials. The non-vanishing D peak in the Raman spectra, together with a generous number of dislocations, even at low irradiation doses, indicates a dislocation-mediated amorphization process in graphite.

  18. Dislocation mechanism of deuterium retention in tungsten under plasma implantation.

    PubMed

    Dubinko, V I; Grigorev, P; Bakaev, A; Terentyev, D; van Oost, G; Gao, F; Van Neck, D; Zhurkin, E E

    2014-10-01

    We have developed a new theoretical model for deuterium (D) retention in tungsten-based alloys on the basis of its being trapped at dislocations and transported to the surface via the dislocation network with parameters determined by ab initio calculations. The model is used to explain experimentally observed trends of D retention under sub-threshold implantation, which does not produce stable lattice defects to act as traps for D in conventional models. Saturation of D retention with implantation dose and effects due to alloying of tungsten with, e.g. tantalum, are evaluated, and comparison of the model predictions with experimental observations under high-flux plasma implantation conditions is presented.

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

    PubMed

    Hvidtfeldt, Ulla Arthur

    2014-10-01

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

  20. Biological mechanisms underlying evolutionary origins of psychotic and mood disorders.

    PubMed

    Goto, Yukiori; Lee, Young-A; Yamaguchi, Yoshie; Jas, Emanuel

    2016-10-01

    Psychotic and mood disorders are brain dysfunctions that are caused by gene environment interactions. Although these disorders are disadvantageous and involve behavioral phenotypes that decrease the reproductive success of afflicted individuals in the modern human society, the prevalence of these disorders have remained constant in the population. Here, we propose several biological mechanisms by which the genes associated with psychotic and mood disorders could be selected for in specific environmental conditions that provide evolutionary bases for explanations of when, why, and where these disorders emerged and have been maintained in humans. We discuss the evolutionary origins of psychotic and mood disorders with specific focuses on the roles of dopamine and serotonin in the conditions of social competitiveness/hierarchy and maternal care and other potential mechanisms, such as social network homophily and symbiosis.

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

    PubMed Central

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

    2012-01-01

    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. PMID:23482688

  2. Neural mechanisms underlying food motivation in children and adolescents

    PubMed Central

    Holsen, Laura M.; Zarcone, Jennifer R.; Thompson, Travis I.; Brooks, William M.; Anderson, Mary F.; Ahluwalia, Jasjit S.; Nollen, Nicole L.; Savage, Cary R.

    2006-01-01

    Dramatic increases in childhood obesity necessitate a more complete understanding of neural mechanisms of hunger and satiation in pediatric populations. In this study, normal weight children and adolescents underwent functional magnetic resonance imaging (fMRI) scanning before and after eating a meal. Participants showed increased activation to visual food stimuli in the amygdala, medial frontal/orbitofrontal cortex, and insula in the pre-meal condition; no regions of interest responded in the post-meal condition. These results closely parallel previous findings in adults. In addition, we found evidence for habituation to food stimuli in the amygdala within the pre-meal session. These findings provide evidence that normal patterns of neural activity related to food motivation begin in childhood. Results have implications for obese children and adults, who may have abnormal hunger and satiation mechanisms. PMID:15993629

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

    PubMed

    Keller, Peter E

    2012-04-01

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

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

    PubMed

    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.

  5. Huntington’s disease: underlying molecular mechanisms and emerging concepts

    PubMed Central

    Labbadia, John; Morimoto, Richard I.

    2013-01-01

    Huntington’s disease (HD) is a progressive neurodegenerative disorder for which no disease modifying treatments exist. Many molecular changes and cellular consequences that underlie HD are observed in other neurological disorders suggesting that common pathological mechanisms and pathways may exist. Recent findings have enhanced our understanding of the way cells regulate and respond to expanded polyglutamine proteins such as mutant huntingtin. These studies demonstrate that in addition to effects on folding, aggregation, and clearance pathways, a general transcriptional mechanism also dictates the expression of polyglutamine proteins. Here we summarize the key pathways and networks that are important in HD in the context of recent therapeutic advances and highlight how their interplay may be of relevance to other protein folding disorders. PMID:23768628

  6. Mechanism of K-phase growth under magnesium combustion

    SciTech Connect

    Florko, A.V.; Golovko, V.V.; Kondrat`ev, E.N.

    1995-09-01

    A model is proposed for magnesia crystal growth during the combustion of single magnesium particles and in the front of laminar diffusion two-phase flame. It is shown that the basic mechanism limiting the condensation rate is the formation of Schottky defects. The energy of their formation has been determined. The results of dispersion analysis of combustion products at air pressures of (0.1-1) {sm_bullet} 10{sup 5} Pa are in good agreement with the calculation data.

  7. Grained composite materials prepared by combustion synthesis under mechanical pressure

    DOEpatents

    Dunmead, Stephen D.; Holt, Joseph B.; Kingman, Donald D.; Munir, Zuhair A.

    1990-01-01

    Dense, finely grained composite materials comprising one or more ceramic phase or phase and one or more metallic and/or intermetallic phase or phases are produced by combustion synthesis. Spherical ceramic grains are homogeneously dispersed within the matrix. Methods are provided, which include the step of applying mechanical pressure during or immediately after ignition, by which the microstructures in the resulting composites can be controllably selected.

  8. Social inequalities in health disentangling the underlying mechanisms.

    PubMed

    Goldman, N

    2001-12-01

    Differentials in health and longevity by socioeconomic status and by the nature of social relationships have been found in innumerable studies in the social and medical sciences. Three categories of explanations for the observed patterns have been proposed: causal mechanisms through which the social environment affects health status or the risk of dying; selection or reverse causal pathways whereby a person's health status affects their social position; and artifactual mechanisms, such as measurement error. The general consensus among researchers is that the observed disparities in health are driven largely by a complex set of causal processes rather than by selection or by artifactual mechanisms. This paper explores the set of arguments and strategies that researchers have used to arrive at this conclusion. As part of this undertaking, we assess whether inferences regarding the minor contribution of selection to the overall association between social factors and health are justifiable. In addition, we identify current avenues of research that are providing new insights into the causal pathways linking social factors and health.

  9. Strain-driven criticality underlies nonlinear mechanics of fibrous networks

    NASA Astrophysics Data System (ADS)

    Sharma, A.; Licup, A. J.; Rens, R.; Vahabi, M.; Jansen, K. A.; Koenderink, G. H.; MacKintosh, F. C.

    2016-10-01

    Networks with only central force interactions are floppy when their average connectivity is below an isostatic threshold. Although such networks are mechanically unstable, they can become rigid when strained. It was recently shown that the transition from floppy to rigid states as a function of simple shear strain is continuous, with hallmark signatures of criticality [Sharma et al., Nature Phys. 12, 584 (2016), 10.1038/nphys3628]. The nonlinear mechanical response of collagen networks was shown to be quantitatively described within the framework of such mechanical critical phenomenon. Here, we provide a more quantitative characterization of critical behavior in subisostatic networks. Using finite-size scaling we demonstrate the divergence of strain fluctuations in the network at well-defined critical strain. We show that the characteristic strain corresponding to the onset of strain stiffening is distinct from but related to this critical strain in a way that depends on critical exponents. We confirm this prediction experimentally for collagen networks. Moreover, we find that the apparent critical exponents are largely independent of the spatial dimensionality. With subisostaticity as the only required condition, strain-driven criticality is expected to be a general feature of biologically relevant fibrous networks.

  10. Use of wetlands under USEPA's (Environmental Protection Agency's) Region 5 Clean Lakes Program. Master's thesis

    SciTech Connect

    Landers, J.C.

    1989-05-01

    The EPA's Region V Clean Lakes Program uses several wetlands for controlling degradation of publicly owned, freshwater lakes. The study seeks to determine if the objectives of the Clean Lakes Program are being met by this use of wetlands, and if appropriate institutional arrangements and management techniques are being implemented to manage the wetlands. Conclusions regarding Revion V's use and management of wetlands include: wetland projects are not being monitored adequately for effectiveness and potential negative impacts on ecosystems; other mechanisms which may help to protect wetlands are being employed; management of most wetland projects is decentralized appropriately; most of the wetland projects provide for adequate short-term mass balance studies, prior sedimentation, plant species diversity, water level, retention time, uniform flow of water, and upland pollutant management; and existing evidence suggests that the Clean Lakes wetland projects are instrumental in meeting Program goals and objectives. Based on these conclusions several recommendations for improving wetlands management are reviewed.

  11. Electrophysiological mechanisms of antiarrhythmic protection during hypothermia in winter hibernating versus nonhibernating mammals

    PubMed Central

    Fedorov, Vadim V.; Glukhov, Alexey V.; Sudharshan, Sangita; Egorov, Yuri; Rosenshtraukh, Leonid V.; Efimov, Igor R.

    2009-01-01

    BACKGROUND Robust cell-to-cell coupling is critically important in the safety of cardiac conduction and protection against ventricular fibrillation (VF). Hibernating mammals have evolved naturally protective mechanisms against VF induced by hypothermia and reperfusion injury. OBJECTIVE We hypothesized that this protection strategy involves a dynamic maintenance of conduction and repolarization patterns through the improvement of gap junction functions. METHODS We optically mapped the hearts of summer-active (SA) and winter-hibernating (WH) ground squirrels Spermophilus undulatus from Siberia and nonhibernating rabbits during different temperatures (+3°C to +37°C). RESULTS Midhypothermia (+17°C) resulted in nonuniform conduction slowing, increased dispersion of repolarization, shortened wavelength, and consequently enhanced VF induction in SA ground squirrels and rabbits. In contrast, wavelength was increased during hypothermia in WH hearts in which VF was not inducible at any temperature. In SA and rabbit hearts, but not in WH, conduction anisotropy was significantly increased by pacing acceleration, thus promoting VF induction during hypothermia. WH hearts maintained the same rate-independent anisotropic propagation pattern even at 3°C. connexin 43 (Cx43) had more homogenous transmural distribution in WH ventricles as compared to SA. Moreover, Cx43 and N-cadherins (N-cad) densities as well as the percentage of their colocalization were significantly higher in WH compared to SA epicardium. CONCLUSION Rate-independent conduction anisotropy ratio, low dispersion of repolarization, and long wavelength—these are the main electrophysiological mechanisms of antiarrhythmic protection in hibernating mammalian species during hypothermia. This strategy includes the improved gap junction function, which is due to overexpression and enhanced colocalization of Cx43 and N-cad. PMID:18984537

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

    SciTech Connect

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

    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.

  13. Mechanical response of unidirectional boron/aluminum under combined loading

    NASA Technical Reports Server (NTRS)

    Becker, Wolfgang; Pindera, Marek-Jerzy; Herakovich, Carl T.

    1987-01-01

    Three test methods were employed to characterize the response of unidirectional Boron/Aluminum metal matrix composite material under monotonic and cyclic loading conditions, namely, losipescu shear, off-axis tension and compression. The characterization of the elastic and plastic response includes the elastic material properties, yielding and subsequent hardening of the unidirectional composite under different stress ratios in the material principal coordinate system. Yield loci generated for different stress ratios are compared for the three different test methods, taking into account residual stresses and specimen geometry. Subsequently, the yield locus for in-plane shear is compared with the prediction of an analytical, micromechanical model. The influence of the scatter in the experimental data on the predicted yield surface is also analyzed. Lastly, the experimental material strengths in tension and compression are correlated with the maximum stress and the Tsai-Wu failure criterion.

  14. Neural mechanisms underlying auditory feedback control of speech.

    PubMed

    Tourville, Jason A; Reilly, Kevin J; Guenther, Frank H

    2008-02-01

    The neural substrates underlying auditory feedback control of speech were investigated using a combination of functional magnetic resonance imaging (fMRI) and computational modeling. Neural responses were measured while subjects spoke monosyllabic words under two conditions: (i) normal auditory feedback of their speech and (ii) auditory feedback in which the first formant frequency of their speech was unexpectedly shifted in real time. Acoustic measurements showed compensation to the shift within approximately 136 ms of onset. Neuroimaging revealed increased activity in bilateral superior temporal cortex during shifted feedback, indicative of neurons coding mismatches between expected and actual auditory signals, as well as right prefrontal and Rolandic cortical activity. Structural equation modeling revealed increased influence of bilateral auditory cortical areas on right frontal areas during shifted speech, indicating that projections from auditory error cells in posterior superior temporal cortex to motor correction cells in right frontal cortex mediate auditory feedback control of speech.

  15. Silver nanoparticles: their potential toxic effects after oral exposure and underlying mechanisms--a review.

    PubMed

    Gaillet, Sylvie; Rouanet, Jean-Max

    2015-03-01

    Because of their antimicrobial properties, the use of silver nanoparticles (AgNPs) is increasing fast in industry, food, and medicine. In the food industry, nanoparticles are used in packaging to enable better conservation products such as sensors to track their lifetime, and as food additives, such as anti-caking agents and clarifying agents for fruit juices. Nanoemulsions, used to encapsulate, protect and deliver additives are also actively developed. Nanomaterials in foods will be ingested and passed through the digestive tract. Those incorporated in food packaging may also be released unintentionally into food, ending up in the gastrointestinal tract. It is therefore important to make a risk assessment of nanomaterials to the consumer. Thus, exposure to AgNPs is increasing in quantity and it is imperative to know their adverse effects in man. However, controversies still remain with respect to their toxic effects and their mechanisms. Understanding the toxic effects and the interactions of AgNPs with biological systems is necessary to handle these nanoparticles and their use. They usually generate reactive oxygen species resulting in increased pro-inflammatory reactions and oxidative stress via intracellular signalling pathways. Here, we mainly focus on the routes of exposure of AgNPs, toxic effects and the mechanisms underlying the induced toxicity.

  16. Ageing under mechanical stress: first experiments for a silver based multilayer mirror

    NASA Astrophysics Data System (ADS)

    Lalo, Arnaud; Ravel, Guillaume; Ignat, Michel; Cousin, Bernard; Swain, Michael V.

    2004-06-01

    Improving materials and devices reliability is a major concern to the spatial industry. Results are reported for satellite mirrors-like specimens consisting in oxide-protected metal systems. Optical coatings were deposited by electron beam evaporation. Mechanical stress fields in multi-layered materials play an important role. The stress state can have far-reaching implications both in kinetics and thermodynamics. Therefore an integrated apparatus with four-point bending equipment was designed. The technique allowed us to exert stress into a film or a system of films on a substrate concurrently with thermal treatment. In order to achieve the first tests performed with the help of the apparatus, various preliminary characterizations were required. The article reports the preliminary micro-mechanical testing of the materials (ultra micro-indentation to evaluate the elastic modulus of the samples materials and wafer curvature technique to determine the specimen residual stress) and the first ageing experiment. Experimental evidence of accelerated ageing under stress is successfully reported.

  17. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    SciTech Connect

    Kover, Karen; Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu; Tasch, James; Hager, Melissa; Clements, Mark; Moore, Wayne V.

    2015-06-19

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose

  18. Generalized coherent states under deformed quantum mechanics with maximum momentum

    NASA Astrophysics Data System (ADS)

    Ching, Chee Leong; Ng, Wei Khim

    2013-10-01

    Following the Gazeau-Klauder approach, we construct generalized coherent states (GCS) as the quantum simulator to examine the deformed quantum mechanics, which exhibits an intrinsic maximum momentum. We study deformed harmonic oscillators and compute their probability distribution and entropy of states exactly. Also, a particle in an infinite potential box is studied perturbatively. In particular, unlike usual quantum mechanics, the present deformed case increases the entropy of the Planck scale quantum optical system. Furthermore, for simplicity, we obtain the modified uncertainty principle (MUP) with the perturbative treatment up to leading order. MUP turns out to increase generally. However, for certain values of γ (a parameter of GCS), it is possible that the MUP will vanish and hence will exhibit the classical characteristic. This is interpreted as the manifestation of the intrinsic high-momentum cutoff at lower momentum in a perturbative treatment. Although the GCS saturates the minimal uncertainty in a simultaneous measurement of physical position and momentum operators, thus constituting the squeezed states, complete coherency is impossible in quantum gravitational physics. The Mandel Q number is calculated, and it is shown that the statistics can be Poissonian and super-/sub-Poissonian depending on γ. The equation of motion is studied, and both Ehrenfest’s theorem and the correspondence principle are recovered. Fractional revival times are obtained through the autocorrelation, and they indicate that the superposition of a classical-like subwave packet is natural in GCS. We also contrast our results with the string-motivated (Snyder) type of deformed quantum mechanics, which incorporates a minimum position uncertainty rather than a maximum momentum. With the advances of quantum optics technology, it might be possible to realize some of these distinguishing quantum-gravitational features within the domain of future experiments.

  19. Cellular mechanisms underlying growth asymmetry during stem gravitropism

    NASA Technical Reports Server (NTRS)

    Cosgrove, D. J.

    1997-01-01

    Plant stems respond to gravitropic stimulation with a rapid, local and reversible change in cell growth rate (elongation), generally on both the upper and lower sides of the stem. The cellular and biochemical mechanisms for this differential growth are reviewed. Considerable evidence implicates an asymmetry in wall pH in the growth response. The strengths and weaknesses of the wall "loosening enzyme" concept are reviewed and the possibility of expansin involvement in the bending response of stems is considered. Also discussed is the possibility that wall stiffening processes, e.g. phenolic coupling driven by oxidative bursts or altered orientation of newly deposited cellulose, might mediate the growth responses during gravitropism.

  20. Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus

    PubMed Central

    Tse, Vivian; Yeo, Jie Ming

    2016-01-01

    Diabetes is a common endocrine disorder with an ever increasing prevalence globally, placing significant burdens on our healthcare systems. It is associated with significant cardiovascular morbidities. One of the mechanisms by which it causes death is increasing the risk of cardiac arrhythmias. The aim of this article is to review the cardiac (ion channel abnormalities, electrophysiological and structural remodelling) and extracardiac factors (neural pathway remodelling) responsible for cardiac arrhythmogenesis in diabetes. It is concluded by an outline of molecular targets for future antiarrhythmic therapy for the diabetic population. PMID:27642609

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

    SciTech Connect

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

    2015-05-15

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

    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.

  3. Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus.

    PubMed

    Tse, Gary; Lai, Eric Tsz Him; Tse, Vivian; Yeo, Jie Ming

    2016-01-01

    Diabetes is a common endocrine disorder with an ever increasing prevalence globally, placing significant burdens on our healthcare systems. It is associated with significant cardiovascular morbidities. One of the mechanisms by which it causes death is increasing the risk of cardiac arrhythmias. The aim of this article is to review the cardiac (ion channel abnormalities, electrophysiological and structural remodelling) and extracardiac factors (neural pathway remodelling) responsible for cardiac arrhythmogenesis in diabetes. It is concluded by an outline of molecular targets for future antiarrhythmic therapy for the diabetic population. PMID:27642609

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

    PubMed Central

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

    2016-01-01

    ABSTRACT 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. PMID:26950417

  5. Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus

    PubMed Central

    Tse, Vivian; Yeo, Jie Ming

    2016-01-01

    Diabetes is a common endocrine disorder with an ever increasing prevalence globally, placing significant burdens on our healthcare systems. It is associated with significant cardiovascular morbidities. One of the mechanisms by which it causes death is increasing the risk of cardiac arrhythmias. The aim of this article is to review the cardiac (ion channel abnormalities, electrophysiological and structural remodelling) and extracardiac factors (neural pathway remodelling) responsible for cardiac arrhythmogenesis in diabetes. It is concluded by an outline of molecular targets for future antiarrhythmic therapy for the diabetic population.

  6. Targets and Mechanisms Associated with Protection from Severe Plasmodium falciparum Malaria in Kenyan Children.

    PubMed

    Murungi, Linda M; Sondén, Klara; Llewellyn, David; Rono, Josea; Guleid, Fatuma; Williams, Andrew R; Ogada, Edna; Thairu, Amos; Färnert, Anna; Marsh, Kevin; Draper, Simon J; Osier, Faith H A

    2016-04-01

    Severe malaria (SM) is a life-threatening complication of infection with Plasmodium falciparum Epidemiological observations have long indicated that immunity against SM is acquired relatively rapidly, but prospective studies to investigate its immunological basis are logistically challenging and have rarely been undertaken. We investigated the merozoite targets and antibody-mediated mechanisms associated with protection against SM in Kenyan children aged 0 to 2 years. We designed a unique prospective matched case-control study of well-characterized SM clinical phenotypes nested within a longitudinal birth cohort of children (n= 5,949) monitored over the first 2 years of life. We quantified immunological parameters in sera collected before the SM event in cases and their individually matched controls to evaluate the prospective odds of developing SM in the first 2 years of life. Anti-AMA1 antibodies were associated with a significant reduction in the odds of developing SM (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.15 to 0.90; P= 0.029) after adjustment for responses to all other merozoite antigens tested, while those against MSP-2, MSP-3, Plasmodium falciparum Rh2 [PfRh2], MSP-119, and the infected red blood cell surface antigens were not. The combined ability of total IgG to inhibit parasite growth and mediate the release of reactive oxygen species from neutrophils was associated with a marked reduction in the odds of developing SM (OR = 0.07; 95% CI = 0.006 to 0.82;P= 0.03). Assays of these two functional mechanisms were poorly correlated (Spearman rank correlation coefficient [rs] = 0.12;P= 0.07). Our data provide epidemiological evidence that multiple antibody-dependent mechanisms contribute to protective immunity via distinct targets whose identification could accelerate the development of vaccines to protect against SM. PMID:26787721

  7. Targets and Mechanisms Associated with Protection from Severe Plasmodium falciparum Malaria in Kenyan Children

    PubMed Central

    Sondén, Klara; Llewellyn, David; Rono, Josea; Guleid, Fatuma; Williams, Andrew R.; Ogada, Edna; Thairu, Amos; Färnert, Anna; Marsh, Kevin; Draper, Simon J.; Osier, Faith H. A.

    2016-01-01

    Severe malaria (SM) is a life-threatening complication of infection with Plasmodium falciparum. Epidemiological observations have long indicated that immunity against SM is acquired relatively rapidly, but prospective studies to investigate its immunological basis are logistically challenging and have rarely been undertaken. We investigated the merozoite targets and antibody-mediated mechanisms associated with protection against SM in Kenyan children aged 0 to 2 years. We designed a unique prospective matched case-control study of well-characterized SM clinical phenotypes nested within a longitudinal birth cohort of children (n = 5,949) monitored over the first 2 years of life. We quantified immunological parameters in sera collected before the SM event in cases and their individually matched controls to evaluate the prospective odds of developing SM in the first 2 years of life. Anti-AMA1 antibodies were associated with a significant reduction in the odds of developing SM (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.15 to 0.90; P = 0.029) after adjustment for responses to all other merozoite antigens tested, while those against MSP-2, MSP-3, Plasmodium falciparum Rh2 [PfRh2], MSP-119, and the infected red blood cell surface antigens were not. The combined ability of total IgG to inhibit parasite growth and mediate the release of reactive oxygen species from neutrophils was associated with a marked reduction in the odds of developing SM (OR = 0.07; 95% CI = 0.006 to 0.82; P = 0.03). Assays of these two functional mechanisms were poorly correlated (Spearman rank correlation coefficient [rs] = 0.12; P = 0.07). Our data provide epidemiological evidence that multiple antibody-dependent mechanisms contribute to protective immunity via distinct targets whose identification could accelerate the development of vaccines to protect against SM. PMID:26787721

  8. Experimental Impeller Fragmentation of Iliocaval Thrombosis Under Tulip Filter Protection: Preliminary Results

    SciTech Connect

    Schmitz-Rode, Thomas; Vorwerk, Dierk; Schuermann, Karl; Guenther, Rolf W.

    1996-04-15

    Purpose: To assess the efficacy of catheter fragmentation of massive caval thrombosis and of filter protection against procedure-related pulmonary embolism. Methods: In 10 sheep, a self-expanding tulip-shaped filter made from Wallstent mesh (diameter 25 mm) was introduced from the right jugular approach into the proximal inferior vena cava. Experimentally induced massive iliocaval thrombosis was fragmented by an impeller catheter (expanded diameter 14 mm), which was advanced coaxially through the sheath of the expanded filter. Post-procedural cavography and pulmonary angiography were performed to document the extent of caval recanalization and pulmonary embolism. Results: In all cases, impeller fragmentation cleared the inferior vena cava and the iliac veins of thrombi completely. Fragments washed downstream were trapped in the filter. In two of the first cases, parts of the clots caused pulmonary embolism before the filter was in place. Further events were avoided by a modification of the experimental setup. Except for some small peripheral perfusion defects in two cases, pulmonary angiograms did not show any incidence of pulmonary embolism. Conclusion: Our preliminary results suggest that impeller fragmentation of iliocaval thrombi under tulip filter protection is effective and does not cause significant pulmonary embolism.

  9. Sequential mechanisms underlying concentration invariance in biological olfaction

    PubMed Central

    Cleland, Thomas A.; Chen, Szu-Yu T.; Hozer, Katarzyna W.; Ukatu, Hope N.; Wong, Kevin J.; Zheng, Fangfei

    2011-01-01

    Concentration invariance—the capacity to recognize a given odorant (analyte) across a range of concentrations—is an unusually difficult problem in the olfactory modality. Nevertheless, humans and other animals are able to recognize known odors across substantial concentration ranges, and this concentration invariance is a highly desirable property for artificial systems as well. Several properties of olfactory systems have been proposed to contribute to concentration invariance, but none of these alone can plausibly achieve full concentration invariance. We here propose that the mammalian olfactory system uses at least six computational mechanisms in series to reduce the concentration-dependent variance in odor representations to a level at which different concentrations of odors evoke reasonably similar representations, while preserving variance arising from differences in odor quality. We suggest that the residual variance then is treated like any other source of stimulus variance, and categorized appropriately into “odors” via perceptual learning. We further show that naïve mice respond to different concentrations of an odorant just as if they were differences in quality, suggesting that, prior to odor categorization, the learning-independent compensatory mechanisms are limited in their capacity to achieve concentration invariance. PMID:22287949

  10. Implicit Misattribution as a Mechanism Underlying Evaluative Conditioning

    PubMed Central

    Jones, Christopher R.; Fazio, Russell H.; Olson, Michael A.

    2009-01-01

    Evaluative conditioning (EC) refers to the formation or change of an attitude towards an object following that object’s pairing with positively or negatively valenced stimuli. We provide evidence that EC can occur through an implicit misattribution mechanism in which an evaluative response evoked by a valenced stimulus is incorrectly and implicitly attributed to another stimulus, forming or changing an attitude towards this other stimulus. Five studies measured or manipulated variables related to the potential for the misattribution of an evaluation, or “source confusability.” Greater EC was observed when participants’ eye gaze shifted frequently between a valenced and neutral stimulus (Studies 1 & 2), when the two stimuli appeared in close spatial proximity (Study 3), and when the neutral stimulus was made more perceptually salient than the valenced stimulus due to its larger size (Study 4). In other words, conditions conducive to source confusability increased EC. Study 5 provided evidence for multiple mechanisms of EC by comparing the effects of mildly evocative valenced stimuli (those evoking responses that might more easily be misattributed to another object) to more strongly evocative stimuli. PMID:19379028

  11. Molecular mechanisms underlying the exceptional adaptations of batoid fins

    PubMed Central

    Nakamura, Tetsuya; Klomp, Jeff; Pieretti, Joyce; Schneider, Igor; Gehrke, Andrew R.; Shubin, Neil H.

    2015-01-01

    Extreme novelties in the shape and size of paired fins are exemplified by extinct and extant cartilaginous and bony fishes. Pectoral fins of skates and rays, such as the little skate (Batoid, Leucoraja erinacea), show a strikingly unique morphology where the pectoral fin extends anteriorly to ultimately fuse with the head. This results in a morphology that essentially surrounds the body and is associated with the evolution of novel swimming mechanisms in the group. In an approach that extends from RNA sequencing to in situ hybridization to functional assays, we show that anterior and posterior portions of the pectoral fin have different genetic underpinnings: canonical genes of appendage development control posterior fin development via an apical ectodermal ridge (AER), whereas an alternative Homeobox (Hox)–Fibroblast growth factor (Fgf)–Wingless type MMTV integration site family (Wnt) genetic module in the anterior region creates an AER-like structure that drives anterior fin expansion. Finally, we show that GLI family zinc finger 3 (Gli3), which is an anterior repressor of tetrapod digits, is expressed in the posterior half of the pectoral fin of skate, shark, and zebrafish but in the anterior side of the pelvic fin. Taken together, these data point to both highly derived and deeply ancestral patterns of gene expression in skate pectoral fins, shedding light on the molecular mechanisms behind the evolution of novel fin morphologies. PMID:26644578

  12. Molecular mechanisms underlying the exceptional adaptations of batoid fins.

    PubMed

    Nakamura, Tetsuya; Klomp, Jeff; Pieretti, Joyce; Schneider, Igor; Gehrke, Andrew R; Shubin, Neil H

    2015-12-29

    Extreme novelties in the shape and size of paired fins are exemplified by extinct and extant cartilaginous and bony fishes. Pectoral fins of skates and rays, such as the little skate (Batoid, Leucoraja erinacea), show a strikingly unique morphology where the pectoral fin extends anteriorly to ultimately fuse with the head. This results in a morphology that essentially surrounds the body and is associated with the evolution of novel swimming mechanisms in the group. In an approach that extends from RNA sequencing to in situ hybridization to functional assays, we show that anterior and posterior portions of the pectoral fin have different genetic underpinnings: canonical genes of appendage development control posterior fin development via an apical ectodermal ridge (AER), whereas an alternative Homeobox (Hox)-Fibroblast growth factor (Fgf)-Wingless type MMTV integration site family (Wnt) genetic module in the anterior region creates an AER-like structure that drives anterior fin expansion. Finally, we show that GLI family zinc finger 3 (Gli3), which is an anterior repressor of tetrapod digits, is expressed in the posterior half of the pectoral fin of skate, shark, and zebrafish but in the anterior side of the pelvic fin. Taken together, these data point to both highly derived and deeply ancestral patterns of gene expression in skate pectoral fins, shedding light on the molecular mechanisms behind the evolution of novel fin morphologies. PMID:26644578

  13. Femoral nerve regeneration and its accuracy under different injury mechanisms.

    PubMed

    Aikeremujiang Muheremu; Ao, Qiang; Wang, Yu; Cao, Peng; Peng, Jiang

    2015-10-01

    Surgical accuracy has greatly improved with the advent of microsurgical techniques. However, complete functional recovery after peripheral nerve injury has not been achieved to date. The mechanisms hindering accurate regeneration of damaged axons after peripheral nerve injury are in urgent need of exploration. The present study was designed to explore the mechanisms of peripheral nerve regeneration after different types of injury. Femoral nerves of rats were injured by crushing or freezing. At 2, 3, 6, and 12 weeks after injury, axons were retrogradely labeled using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) and True Blue, and motor and sensory axons that had regenerated at the site of injury were counted. The number and percentage of Dil-labeled neurons in the anterior horn of the spinal cord increased over time. No significant differences were found in the number of labeled neurons between the freeze and crush injury groups at any time point. Our results confirmed that the accuracy of peripheral nerve regeneration increased with time, after both crush and freeze injury, and indicated that axonal regeneration accuracy was still satisfactory after freezing, despite the prolonged damage. PMID:26692867

  14. Understanding ultrasound induced sonoporation: definitions and underlying mechanisms.

    PubMed

    Lentacker, I; De Cock, I; Deckers, R; De Smedt, S C; Moonen, C T W

    2014-06-01

    In the past two decades, research has underlined the potential of ultrasound and microbubbles to enhance drug delivery. However, there is less consensus on the biophysical and biological mechanisms leading to this enhanced delivery. Sonoporation, i.e. the formation of temporary pores in the cell membrane, as well as enhanced endocytosis is reported. Because of the variety of ultrasound settings used and corresponding microbubble behavior, a clear overview is missing. Therefore, in this review, the mechanisms contributing to sonoporation are categorized according to three ultrasound settings: i) low intensity ultrasound leading to stable cavitation of microbubbles, ii) high intensity ultrasound leading to inertial cavitation with microbubble collapse, and iii) ultrasound application in the absence of microbubbles. Using low intensity ultrasound, the endocytotic uptake of several drugs could be stimulated, while short but intense ultrasound pulses can be applied to induce pore formation and the direct cytoplasmic uptake of drugs. Ultrasound intensities may be adapted to create pore sizes correlating with drug size. Small molecules are able to diffuse passively through small pores created by low intensity ultrasound treatment. However, delivery of larger drugs such as nanoparticles and gene complexes, will require higher ultrasound intensities in order to allow direct cytoplasmic entry.

  15. Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate

    PubMed Central

    Volz, T.J

    2008-01-01

    Methylphenidate is a psychostimulant that inhibits the neuronal dopamine transporter. In addition, methylphenidate has the intriguing ability to provide neuroprotection from the neurotoxic effects of methamphetamine and perhaps also Parkinson’s disease; both of which may likely involve the abnormal accumulation of cytoplasmic dopamine inside dopaminergic neurons and the resulting formation of dopamine-associated reactive oxygen species. As delineated in this review, the neuroprotective effects of methylphenidate are due, at least in part, to its ability to attenuate or prevent this abnormal cytoplasmic dopamine accumulation through several possible neuropharmacological mechanisms. These may include 1) direct interactions between methylphenidate and the neuronal dopamine transporter which may attenuate or prevent the entry of methamphetamine into dopaminergic neurons and may also decrease the synthesis of cytoplasmic dopamine through a D2 receptor-mediated signal cascade process, and 2) indirect effects upon the functioning of the vesicular monoamine transporter-2 which may increase vesicular dopamine sequestration through both vesicle trafficking and the kinetic upregulation of the vesicular monoamine transporter-2 protein. Understanding these neuropharmacological mechanisms of methylphenidate neuroprotection may provide important insights into the physiologic regulation of dopaminergic systems as well as the pathophysiology of a variety of disorders involving abnormal dopamine disposition ranging from substance abuse to neurodegenerative diseases such as Parkinson’s disease. PMID:19587858

  16. Mechanisms Underlying Carotenoid Absorption in Oxygenic Photosynthetic Proteins*

    PubMed Central

    Mendes-Pinto, Maria M.; Galzerano, Denise; Telfer, Alison; Pascal, Andrew A.; Robert, Bruno; Ilioaia, Cristian

    2013-01-01

    The electronic properties of carotenoid molecules underlie their multiple functions throughout biology, and tuning of these properties by their in vivo locus is of vital importance in a number of cases. This is exemplified by photosynthetic carotenoids, which perform both light-harvesting and photoprotective roles essential to the photosynthetic process. However, despite a large number of scientific studies performed in this field, the mechanism(s) used to modulate the electronic properties of carotenoids remain elusive. We have chosen two specific cases, the two β-carotene molecules in photosystem II reaction centers and the two luteins in the major photosystem II light-harvesting complex, to investigate how such a tuning of their electronic structure may occur. Indeed, in each case, identical molecular species in the same protein are seen to exhibit different electronic properties (most notably, shifted absorption peaks). We assess which molecular parameters are responsible for this in vivo tuning process and attempt to assign it to specific molecular events imposed by their binding pockets. PMID:23720734

  17. Mechanisms underlying carotenoid absorption in oxygenic photosynthetic proteins.

    PubMed

    Mendes-Pinto, Maria M; Galzerano, Denise; Telfer, Alison; Pascal, Andrew A; Robert, Bruno; Ilioaia, Cristian

    2013-06-28

    The electronic properties of carotenoid molecules underlie their multiple functions throughout biology, and tuning of these properties by their in vivo locus is of vital importance in a number of cases. This is exemplified by photosynthetic carotenoids, which perform both light-harvesting and photoprotective roles essential to the photosynthetic process. However, despite a large number of scientific studies performed in this field, the mechanism(s) used to modulate the electronic properties of carotenoids remain elusive. We have chosen two specific cases, the two β-carotene molecules in photosystem II reaction centers and the two luteins in the major photosystem II light-harvesting complex, to investigate how such a tuning of their electronic structure may occur. Indeed, in each case, identical molecular species in the same protein are seen to exhibit different electronic properties (most notably, shifted absorption peaks). We assess which molecular parameters are responsible for this in vivo tuning process and attempt to assign it to specific molecular events imposed by their binding pockets.

  18. Mechanisms underlying vertebrate limb regeneration: lessons from the salamander.

    PubMed

    Brockes, Jeremy P; Gates, Phillip B

    2014-06-01

    Limb regeneration in adult salamanders proceeds by formation of a mound of progenitor cells called the limb blastema. It provides several pointers for regenerative medicine. These include the role of differentiated cells in the origin of the blastema, the role of regenerating axons of peripheral nerves and the importance of cell specification in conferring morphogenetic autonomy on the blastema. One aspect of regeneration that has received less attention is the ability to undergo multiple episodes without detectable change in the outcome, and with minimal effect of aging. We suggest that, although such pointers are valuable, it is important to understand why salamanders are the only adult tetrapod vertebrates able to regenerate their limbs. Although this remains a controversial issue, the existence of salamander-specific genes that play a significant role in the mechanism of regeneration provides evidence for the importance of local evolution, rather than a purely ancestral mechanism. The three-finger protein called Prod1 is discussed in the present article as an exemplar of this approach.

  19. Protective Effectiveness of Porous Shields Under the Influence of High-Speed Impact Loading

    NASA Astrophysics Data System (ADS)

    Kramshonkov, E. N.; Krainov, A. V.; Shorohov, P. V.

    2016-02-01

    The results of numerical simulations of a compact steel impactor with the aluminum porous shields under high-speed shock loading are presented. The porosity of barrier varies in wide range provided that its mass stays the same, but the impactor has always equal (identical) mass. Here presented the final assessment of the barrier perforation speed depending on its porosity and initial shock speed. The range of initial impact speed varies from 1 to 10 km/s. Physical phenomena such as: destruction, melting, vaporization of a interacting objects are taken into account. The analysis of a shield porosity estimation disclosed that the protection effectiveness of porous shield reveals at the initial impact speed grater then 1.5 km/s, and it increases when initial impact speed growth.

  20. Financial protection against nuclear hazards: thirty years' experience under the Price-Anderson Act

    SciTech Connect

    Not Available

    1984-01-01

    Supplementing earlier reports on ways to provide financial protection against the potential hazards involved in the production of nuclear energy by analyzing the issues raised in the Silkwood v. Kerr-McGee Corporation decision, the author explores the impact of the case on the availability of funds to compensate the public and any increased exposure of the nuclear industry or the federal government to public liability. She concludes that the decision will have a significant impact on the day-to-day administration of claims, and could lead to higher premiums. The court would have to determine the priority given to claims in the event of a catastrophic accident, in which case the only significant impact would be under amendments to the Price-Anderson Act which resulted in elimination of its coverage or a substantial increase in or elimination of the limitation on liability.

  1. Computer Simulation of Blast Wall Protection under Methane-Air Explosion on an Offshore Platform

    NASA Astrophysics Data System (ADS)

    Wang, Changjian; Yan, Weigang; Guo, Jin; Guo, Changming

    An in-house explosion program is presented to evaluate blast wall protection under Methane-Air Explosion on an offshore platform, based on two-dimensional, time-dependent, reactive Navier-Stokes equations including the effects of viscosity, thermal conduction and molecular diffusion. The results show that this program can successfully produce explosion process of methane-air gas cloud. Because the overpressure behind the blast wall and on the lifeboat plate is more than 1.0atm when explosion wave passes, the current blast wall is not enough to keep the person and lifeboat safe. So the blast wall needs to be re-designed. The explosion wave of methane-air gas cloud undergoes a successive process of detonation formation, detonation transmission, shock attenuation, regular reflection and Mach reflection etc. Additionally, due to high overpressure generated in gas cloud explosion, it is extremely devastating and must be avoided at all times on offshore platform.

  2. Constitutive response of Rene 80 under thermal mechanical loads

    NASA Technical Reports Server (NTRS)

    Kim, K. S.; Cook, T. S.; Mcknight, R. L.

    1988-01-01

    The applicability of a classical constitutive model for stress-strain analysis of a nickel base superalloy, Rene' 80, in the gas turbine thermomechanical fatigue (TMF) environment is examined. A variety of tests were conducted to generate basic material data and to investigate the material response under cyclic thermomechanical loading. Isothermal stress-strain data were acquired at a variety of strain rates over the TMF temperature range. Creep curves were examined at 2 temperature ranges, 871 to 982 C and 760 to 871 C. The results provide optimism on the ability of the classical constitutive model for high temperature applications.

  3. Skeletal muscle contraction in protecting joints and bones by absorbing mechanical impacts

    NASA Astrophysics Data System (ADS)

    Rudenko, O. V.; Tsyuryupa, S.; Sarvazyan, A.

    2016-09-01

    We have previously hypothesized that the dissipation of mechanical energy of external impact is a fundamental function of skeletal muscle in addition to its primary function to convert chemical energy into mechanical energy. In this paper, a mathematical justification of this hypothesis is presented. First, a simple mechanical model, in which the muscle is considered as a simple Hookean spring, is considered. This analysis serves as an introduction to the consideration of a biomechanical model taking into account the molecular mechanism of muscle contraction, kinetics of myosin bridges, sarcomere dynamics, and tension of muscle fibers. It is shown that a muscle behaves like a nonlinear and adaptive spring tempering the force of impact and increasing the duration of the collision. The temporal profiles of muscle reaction to the impact as functions of the levels of muscle contraction, durations of the impact front, and the time constants of myosin bridges closing, are obtained. The absorption of mechanical shock energy is achieved due to the increased viscoelasticity of the contracting skeletal muscle. Controlling the contraction level allows for the optimization of the stiffness and viscosity of the muscle necessary for the protection of the joints and bones.

  4. Genetic Mechanisms of Coffee Extract Protection in a Caenorhabditis elegans Model of β-Amyloid Peptide Toxicity

    PubMed Central

    Dostal, Vishantie; Roberts, Christine M.; Link, Christopher D.

    2010-01-01

    Epidemiological studies have reported that coffee and/or caffeine consumption may reduce Alzheimer's disease (AD) risk. We found that coffee extracts can similarly protect against β-amyloid peptide (Aβ) toxicity in a transgenic Caenorhabditis elegans Alzheimer's disease model. The primary protective component(s) in this model is not caffeine, although caffeine by itself can show moderate protection. Coffee exposure did not decrease Aβ transgene expression and did not need to be present during Aβ induction to convey protection, suggesting that coffee exposure protection might act by activating a protective pathway. By screening the effects of coffee on a series of transgenic C. elegans stress reporter strains, we identified activation of the skn-1 (Nrf2 in mammals) transcription factor as a potential mechanism of coffee extract protection. Inactivation of skn-1 genetically or by RNAi strongly blocked the protective effects of coffee extract, indicating that activation of the skn-1 pathway was the primary mechanism of coffee protection. Coffee also protected against toxicity resulting from an aggregating form of green fluorescent protein (GFP) in a skn-1–dependent manner. These results suggest that the reported protective effects of coffee in multiple neurodegenerative diseases may result from a general activation of the Nrf2 phase II detoxification pathway. PMID:20805557

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Reliability of piezoceramic patch sensors under cyclic mechanical loading

    NASA Astrophysics Data System (ADS)

    Thielicke, Bärbel; Gesang, Thomas; Wierach, Peter

    2003-12-01

    Piezoceramic patch sensors have to withstand the primary stresses and strains of a structure during operation. In the leading project 'Adaptronics' a lifespan of 106 cycles at 0.1% strain was required for sensors applied on components of steel and carbon fibre reinforced plastic (CFRP). In order to test the reliability of the patches themselves and of their adhesion on the substrate, special four-point bending tests were carried out under quasistatic loading and under cyclic loading at different strain levels. The specimens consisted in sheets of steel and CFRP as substrates on which the newly developed patches with embedded piezoelectric foils and fibres were glued. In the quasistatic bending tests the performance of each sensor was characterized by measuring the sensor signal (charge) as a function of strain before and after cycling. Damage of the specimens would result in a decreasing slope of the charge-strain-curve after cycling. However, all the specimens tested survived 107 cycles up to 0.12% strain without marked loss of performance.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26006188

  8. Mechanical Behaviour of Reservoir Rock Under Brine Saturation

    NASA Astrophysics Data System (ADS)

    Shukla, Richa; Ranjith, P. G.; Choi, S. K.; Haque, A.; Yellishetty, Mohan; Hong, Li

    2013-01-01

    Acoustic emissions (AE) and stress-strain curve analysis are well accepted ways of analysing crack propagation and monitoring the various failure stages (such as crack closure, crack initiation level during rock failure under compression) of rocks and rock-like materials. This paper presents details and results of experimental investigations conducted for characterizing the brittle failure processes induced in a rock due to monocyclic uniaxial compression on loading of two types of sandstone core samples saturated in NaCl brines of varying concentration (0, 2, 5, 10 and 15 % NaCl by weight). The two types of sandstone samples were saturated under vacuum for more than 45 days with the respective pore fluid to allow them to interact with the rocks. It was observed that the uniaxial compressive strength and stress-strain behaviour of the rock specimens changed with increasing NaCl concentration in the saturating fluid. The acoustic emission patterns also varied considerably for increasing ionic strength of the saturating brines. These observations can be attributed to the deposition of NaCl crystals in the rock's pore spaces as well some minor geo-chemical interactions between the rock minerals and the brine. The AE pattern variations could also be partly related to the higher conductivity of the ionic strength of the high-NaCl concentration brine as it is able to transfer more acoustic energy from the cracks to the AE sensors.

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

    PubMed

    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. PMID:26006188

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

    PubMed

    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.

  11. Ecological mechanisms underlying arthropod species diversity in grasslands.

    PubMed

    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.

  12. Aging and emotional memory: cognitive mechanisms underlying the positivity effect.

    PubMed

    Spaniol, Julia; Voss, Andreas; Grady, Cheryl L

    2008-12-01

    Younger adults tend to remember negative information better than positive or neutral information (negativity bias). The negativity bias is reduced in aging, with older adults occasionally exhibiting superior memory for positive, as opposed to negative or neutral, information (positivity bias). Two experiments with younger (N=24 in Experiment 1, N=25 in Experiment 2; age range: 18-35 years) and older adults (N=24 in both experiments; age range: 60-85 years) investigated the cognitive mechanisms responsible for age-related differences in recognition memory for emotional information. Results from diffusion model analyses (R. Ratcliff, 1978) indicated that the effects of valence on response bias were similar in both age groups but that Age x Valence interactions emerged in memory retrieval. Specifically, older adults experienced greater overall familiarity for positive items than younger adults. We interpret this finding in terms of an age-related increase in the accessibility of positive information in long-term memory. PMID:19140656

  13. Mechanisms underlying the antimotion sickness effects of psychostimulants

    NASA Technical Reports Server (NTRS)

    Kohl, Randall L.; Lewis, Michael R.

    1987-01-01

    Data related to the mechanism responsible for the antimotion sickness effects of psychostimulants such as amphetamine are examined. From the analysis of current literature and new evidence, the following three hypotheses are suggested: (1) selective enhancement of dopaminergic, but not noradrenergic, transmission is sufficient to account for amphetamine-induced resistance and, perhaps, for natural resistance to motion sickness; (2) the site of this enhanced dopaminergic transmission is probably within the basal ganglia; and (3) the neuropharmacology of the basal ganglia, but not of the brain-stem vestibular areas, can account for the therapeutic synergism of scopolamine and amphetamine. The therapeutic action of psychostimulants may be dissociable from some of their side effects, particularly cardiovascular effects related to peripheral norepinephrine release.

  14. Circuit Mechanisms Underlying Motor Memory Formation in the Cerebellum

    PubMed Central

    Lee, Ka Hung; Mathews, Paul J.; Reeves, Alexander M.B.; Choe, Katrina Y.; Jami, Shekib A.; Serrano, Raul E.; Otis, Thomas S.

    2015-01-01

    SUMMARY The cerebellum stores associative motor memories essential for properly timed movement; however, the mechanisms by which these memories form and are acted upon remain unclear. To determine how cerebellar activity relates to movement and motor learning, we used optogenetics to manipulate spontaneously firing Purkinje neurons (PNs) in mouse simplex lobe. Using high-speed videography and motion tracking, we found that altering PN activity produced rapid forelimb movement. PN inhibition drove movements time-locked to stimulus onset, whereas PN excitation drove delayed movements time-locked to stimulus offset. Pairing either PN inhibition or excitation with sensory stimuli triggered the formation of robust, associative motor memories; however, PN excitation led to learned movements whose timing more closely matched training intervals. These findings implicate inhibition of PNs as a teaching signal, consistent with a model whereby learning leads first to reductions in PN firing that subsequently instruct circuit changes in the cerebellar nucleus. PMID:25843404

  15. Multiple mechanisms underlying troglitazone-induced mitochondrial permeability transition

    SciTech Connect

    Okuda, Takuya; Norioka, Misaki; Shitara, Yoshihisa; Horie, Toshiharu

    2010-11-01

    Troglitazone, a thiazolidinedione class antidiabetic drug, was withdrawn from the market because of its severe idiosyncratic hepatotoxicity. It causes a mitochondrial permeability transition (MPT), which may in part contribute to its hepatotoxicity. In the present study, the mechanism of troglitazone mitochondrial toxicity was investigated in isolated rat liver mitochondria. Mitochondrial swelling induced by 10 {mu}M troglitazone was attenuated by bromoenol lactone (BEL), an inhibitor of Ca{sup 2+}-independent phospholipase A{sub 2} (iPLA{sub 2}). In contrast, that induced by 50 {mu}M troglitazone was exacerbated by BEL. This exacerbation was diminished by addition of 2 mM glutathione, an antioxidant. Oxygen consumption by state 3 respiration in isolated mitochondria was also decreased by troglitazone, but it was not affected by BEL. Mitochondrial swelling induced by 10 {mu}M troglitazone was completely attenuated in the absence of Ca{sup 2+} while that induced by 50 {mu}M troglitazone was not affected. Addition of 1 {mu}M cyclosporin A (CsA), an inhibitor of MPT pores, completely attenuated swelling induced by 10 {mu}M troglitazone while it only partly diminished that induced by 50 {mu}M troglitazone. Thus, the MPT induced by 10 and 50 {mu}M troglitazone are regulated by different mechanism; the MPT induced by 10 {mu}M troglitazone is regulated by the activation of iPLA{sub 2} and caused by the opening of CsA-regulating MPT pores followed by accumulation of Ca{sup 2+} in mitochondria, while that induced by 50 {mu}M troglitazone is partly regulated by reactive oxygen species and mainly caused by the opening of CsA-insensitive MPT pores.

  16. Breather mechanism of the void ordering in crystals under irradiation

    NASA Astrophysics Data System (ADS)

    Dubinko, Vladimir

    2009-09-01

    The void ordering has been observed in very different radiation environments ranging from metals to ionic crystals. In the present paper the ordering phenomenon is considered as a consequence of the energy transfer along the close packed directions provided by self-focusing discrete breathers. The self-focusing breathers are energetic, mobile and highly localized lattice excitations that propagate great distances in atomic-chain directions in crystals. This points to the possibility of atoms being ejected from the void surface by the breather-induced mechanism, which is similar to the focuson-induced mechanism of vacancy emission from voids proposed in our previous paper. The main difference between focusons and breathers is that the latter are stable against thermal motion. There is evidence that breathers can occur in various crystals, with path lengths ranging from 104 to 107 unit cells. Since the breather propagating range can be larger than the void spacing, the voids can shield each other from breather fluxes along the close packed directions, which provides a driving force for the void ordering. Namely, the vacancy emission rate for "locally ordered" voids (which have more immediate neighbors along the close packed directions) is smaller than that for the "interstitial" ones, and so they have some advantage in growth. If the void number density is sufficiently high, the competition between them makes the "interstitial" voids shrink away resulting in the void lattice formation. The void ordering is intrinsically connected with a saturation of the void swelling, which is shown to be another important consequence of the breather-induced vacancy emission from voids.

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

    PubMed

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

    2015-02-26

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

  18. Algorithmic mechanisms for reliable crowdsourcing computation under collusion.

    PubMed

    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. PMID:25793524

  19. Algorithmic Mechanisms for Reliable Crowdsourcing Computation under Collusion

    PubMed Central

    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. PMID:25793524

  20. Elevated body mass index and maintenance of cognitive function in late life: exploring underlying neural mechanisms

    PubMed Central

    Hsu, Chun Liang; Voss, Michelle W.; Best, John R.; Handy, Todd C.; Madden, Kenneth; Bolandzadeh, Niousha; Liu-Ambrose, Teresa

    2015-01-01

    Background: Obesity is associated with vascular risk factors that in turn, may increase dementia risk. However, higher body mass index (BMI) in late life may be neuroprotective. The possible neural mechanisms underlying the benefit of higher BMI on cognition in older adults are largely unknown. Thus, we used functional connectivity magnetic resonance imaging (fcMRI) to examine: (1) the relationship between BMI and functional brain connectivity; and (2) the mediating role of functional brain connectivity in the association between baseline BMI and change in cognitive function over a 12-month period. Methods:We conducted a 12-month, prospective study among 66 community-dwelling older adults, aged 70 to 80 years, who were categorized as: normal weight (BMI from 18.50 to 24.99); overweight (BMI from 25.00 to 29.99); and obese (BMI ≥ 30.00). At baseline, participants performed a finger-tapping task during fMRI scanning. Relevant neural networks were initially identified through independent component analysis (ICA) and subsequently examined through seed-based functional connectivity analysis. At baseline and 12-months, we measured three executive cognitive processes: (1) response inhibition; (2) set shifting; and (3) working memory. Results:Obese individuals showed lower task-related functional connectivity during finger tapping in the default mode network (DMN) compared with their healthy weight counterparts (p < 0.01). Lower task-related functional connectivity in the DMN at baseline was independently associated with better working memory performance at 12-months (p = 0.02). Finally, DMN functional connectivity during finger tapping significantly mediated the relationship between baseline BMI and working memory at 12-months (indirect effect: −0.155, 95% confidence interval [−0.313, −0.053]). Conclusions:These findings suggest that functional connectivity of the DMN may be an underlying mechanism by which higher BMI confers protective effects to cognition in

  1. Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

    NASA Astrophysics Data System (ADS)

    Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2015-11-01

    Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

  2. Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds.

    PubMed

    Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2015-11-27

    Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

  3. Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

    PubMed Central

    Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2015-01-01

    Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO. PMID:26611622

  4. The protective effect and action mechanism of Vaccinium myrtillus L. on gastric ulcer in mice.

    PubMed

    Ogawa, Kenjirou; Oyagi, Atsushi; Tanaka, Junji; Kobayashi, Saori; Hara, Hideaki

    2011-08-01

    Vaccinium myrtillus L. anthocyanoside (VMA) is used as a folk medicine to treat diseases related to gastric ulcers in northern Europe. However, the effects of VMA and its detailed mechanism on gastric ulcer have not been investigated sufficiently. Therefore, the aim of the present study was to investigate the protective effects of VMA on gastric mucosal damage in a murine gastric ulcer model. First the effects of VMA on ethanol-induced gastric ulcers in mice were investigated. Then, the levels of lipid peroxide in murine stomach homogenates were measured to investigate the antioxidative effects of VMA. In addition, the free radical scavenging activity of VMA and its main anthocyanidins were evaluated by electron spin resonance measurement. Oral administration of VMA (10, 30 and 100 mg/kg) significantly protected gastric mucosa against HCl/ethanol-induced gastric ulcers. Furthermore, VMA inhibited lipid peroxide levels in a concentration-dependent manner and showed high scavenging activity against the superoxide anion radical (·O(2) (-) ) and the hydroxyl radical (·OH). Anthocyanidins also showed scavenging activity against the ·O(2) (-) , while only delphinidin showed high scavenging activity against the ·OH. These findings indicate that the protective effects of VMA on HCl/ethanol-induced gastric mucosal injury may be partially due to the antiperoxidative effects of anthocyanidins.

  5. The protective effect and action mechanism of Vaccinium myrtillus L. on gastric ulcer in mice.

    PubMed

    Ogawa, Kenjirou; Oyagi, Atsushi; Tanaka, Junji; Kobayashi, Saori; Hara, Hideaki

    2011-08-01

    Vaccinium myrtillus L. anthocyanoside (VMA) is used as a folk medicine to treat diseases related to gastric ulcers in northern Europe. However, the effects of VMA and its detailed mechanism on gastric ulcer have not been investigated sufficiently. Therefore, the aim of the present study was to investigate the protective effects of VMA on gastric mucosal damage in a murine gastric ulcer model. First the effects of VMA on ethanol-induced gastric ulcers in mice were investigated. Then, the levels of lipid peroxide in murine stomach homogenates were measured to investigate the antioxidative effects of VMA. In addition, the free radical scavenging activity of VMA and its main anthocyanidins were evaluated by electron spin resonance measurement. Oral administration of VMA (10, 30 and 100 mg/kg) significantly protected gastric mucosa against HCl/ethanol-induced gastric ulcers. Furthermore, VMA inhibited lipid peroxide levels in a concentration-dependent manner and showed high scavenging activity against the superoxide anion radical (·O(2) (-) ) and the hydroxyl radical (·OH). Anthocyanidins also showed scavenging activity against the ·O(2) (-) , while only delphinidin showed high scavenging activity against the ·OH. These findings indicate that the protective effects of VMA on HCl/ethanol-induced gastric mucosal injury may be partially due to the antiperoxidative effects of anthocyanidins. PMID:21290441

  6. Probing the protective mechanism of poly-ß-hydroxybutyrate against vibriosis by using gnotobiotic Artemia franciscana and Vibrio campbellii as host-pathogen model.

    PubMed

    Baruah, Kartik; Huy, Tran T; Norouzitallab, Parisa; Niu, Yufeng; Gupta, Sanjay K; De Schryver, Peter; Bossier, Peter

    2015-01-01

    The compound poly-ß-hydroxybutyrate (PHB), a polymer of the short chain fatty acid ß-hydroxybutyrate, was shown to protect experimental animals against a variety of bacterial diseases, (including vibriosis in farmed aquatic animals), albeit through undefined mechanisms. Here we aimed at unraveling the underlying mechanism behind the protective effect of PHB against bacterial disease using gnotobiotically-cultured brine shrimp Artemia franciscana and pathogenic Vibrio campbellii as host-pathogen model. The gnotobiotic model system is crucial for such studies because it eliminates any possible microbial interference (naturally present in any type of aquatic environment) in these mechanistic studies and furthermore facilitates the interpretation of the results in terms of a cause effect relationship. We showed clear evidences indicating that PHB conferred protection to Artemia host against V. campbellii by a mechanism of inducing heat shock protein (Hsp) 70. Additionally, our results also showed that this salutary effect of PHB was associated with the generation of protective innate immune responses, especially the prophenoloxidase and transglutaminase immune systems - phenomena possibly mediated by PHB-induced Hsp70. From overall results, we conclude that PHB induces Hsp70 and this induced Hsp70 might contribute in part to the protection of Artemia against pathogenic V. campbellii. PMID:25822312

  7. An AT-barrier mechanically controls DNA reannealing under tension.

    PubMed

    Bongini, L; Pongor, C; Falorsi, G; Pertici, I; Kellermayer, M; Lombardi, V; Bianco, P

    2016-09-19

    Regulation of genomic activity occurs through the manipulation of DNA by competent mechanoenzymes. Force-clamp optical tweezers that allow the structural dynamics of the DNA molecule to be measured were used here to investigate the kinetics of mechanically-driven strand reannealing. When the force on the torsionally unconstrained λ-phage DNA is decreased stepwise from above to below the overstretching transition, reannealing occurs via discrete shortening steps separated by exponentially distributed time intervals. Kinetic analysis reveals a transition barrier 0.58 nm along the reaction coordinate and an average reannealing-step size of ∼750 bp, consistent with the average bp interval separating segments of more than 10 consecutive AT bases. In an AT-rich DNA construct, in which the distance between segments of more than 10 consecutive AT is reduced to ∼210 bps, the reannealing step reduces accordingly without changes in the position of the transition barrier. Thus, the transition barrier for reannealing is determined by the presence of segments of more than 10 consecutive AT bps independent of changes in sequence composition, while the length of the reannealing strand changes according to the distance between poly-AT segments at least 10 bps long. PMID:27378772

  8. Neural mechanisms underlying social conformity in an ultimatum game

    PubMed Central

    Wei, Zhenyu; Zhao, Zhiying; Zheng, Yong

    2013-01-01

    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. PMID:24399954

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

    PubMed Central

    Hernández, Antonio F.; Menéndez, Pablo

    2016-01-01

    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. PMID:27043530

  10. Understanding the Mechanisms Underlying Gambling Behaviour and Sleep.

    PubMed

    Loft, Marisa H; Loo, Jasmine M Y

    2015-12-01

    Problem gambling and sleep difficulty threaten health. Using the basis of self-regulatory theory, potential mechanisms for these problems were investigated. Fifty-nine treatment-seeking gamblers completed the Pittsburgh Sleep Quality Index (sleep difficulty), the Sleep Hygiene Index (negative sleep habits), the Problem Gambling Severity Index and measures of self-regulatory capacity and arousability with data entered into regression analyses. Results supported the relationship between problem gambling and greater sleep difficulty (β = .18, t = 3.22, p < .01). Self-regulatory capacity mediated the relationship between problem gambling and sleep difficulty (R (2) change = .15, F(2, 57) = 12.14, β = -.45, t = -3.45, p < .001) as well as between problem gambling and negative sleep habits; R (2) change = .17, F(2, 57) = 13.57, β = -.28, t = -3.76, p < .001. Arousability predicted sleep difficulty (β = .15, t = 3.07, p < .01) and negative sleep habits (β = .40, t = 5.40, p < .01) but showed no relationship with problem gambling (r = .09, ns). Self-regulatory capacity represents an important mediator of the relationship between problem gambling and sleep-related behaviour and if targeted could reduce behavioural threats to health. PMID:25381635

  11. Synaptic mechanisms underlying sparse coding of active touch.

    PubMed

    Crochet, Sylvain; Poulet, James F A; Kremer, Yves; Petersen, Carl C H

    2011-03-24

    Sensory information is actively gathered by animals, but the synaptic mechanisms driving neuronal circuit function during active sensory processing are poorly understood. Here, we investigated the synaptically driven membrane potential dynamics during active whisker sensation using whole-cell recordings from layer 2/3 pyramidal neurons in the primary somatosensory barrel cortex of behaving mice. Although whisker contact with an object evoked rapid depolarization in all neurons, these touch responses only drove action potentials in ∼10% of the cells. Such sparse coding was ensured by cell-specific reversal potentials of the touch-evoked response that were hyperpolarized relative to action potential threshold for most neurons. Intercontact interval profoundly influenced touch-evoked postsynaptic potentials, interestingly without affecting the peak membrane potential of the touch response. Dual whole-cell recordings indicated highly correlated membrane potential dynamics during active touch. Sparse action potential firing within synchronized cortical layer 2/3 microcircuits therefore appears to robustly signal each active touch response.

  12. A candidate mechanism underlying the variance of interictal spike propagation

    PubMed Central

    Sabolek, Helen R; Swiercz, Waldemar B.; Lillis, Kyle; Cash, Sydney S.; Huberfeld, Gilles; Zhao, Grace; Marie, Linda Ste.; Clemenceau, Stéphane; Barsh, Greg; Miles, Richard; Staley, Kevin J.

    2012-01-01

    Synchronous activation of neural networks is an important physiological mechanism, and dysregulation of synchrony forms the basis of epilepsy. We analyzed the propagation of synchronous activity through chronically epileptic neural networks. Electrocortigraphic recordings from epileptic patients demonstrate remarkable variance in the pathways of propagation between sequential interictal spikes (IIS). Calcium imaging in chronically epileptic slice cultures demonstrates that pathway variance depends on the presence of GABAergic inhibition and that spike propagation becomes stereotyped following GABA-R blockade. Computer modeling suggests that GABAergic quenching of local network activations leaves behind regions of refractory neurons, whose late recruitment forms the anatomical basis of variability during subsequent network activation. Targeted path scanning of slice cultures confirmed local activations, while ex vivo recordings of human epileptic tissue confirmed the dependence of interspike variance on GABA-mediated inhibition. These data support the hypothesis that the paths by which synchronous activity spread through an epileptic network change with each activation, based on the recent history of localized activity that has been successfully inhibited. PMID:22378874

  13. Molecular mechanisms underlying genotype-dependent responses to dietary restriction

    PubMed Central

    Schleit, Jennifer; Johnson, Simon C.; Bennett, Christopher F.; Simko, Marissa; Trongtham, Natalie; Castanza, Anthony; Hsieh, Edward J.; Moller, Richard M.; Wasko, Brian M.; Delaney, Joe R.; Sutphin, George L.; Carr, Daniel; Murakami, Christopher J.; Tocchi, Autumn; Xian, Bo; Chen, Weiyang; Yu, Tao; Goswami, Sarani; Higgins, Sean; Holmberg, Mollie; Jeong, Ki-Soo; Kim, Jin R.; Klum, Shannon; Liao, Eric; Lin, Michael S.; Lo, Winston; Miller, Hillary; Olsen, Brady; Peng, Zhao J.; Pollard, Tom; Pradeep, Prarthana; Pruett, Dillon; Rai, Dilreet; Ros, Vanessa; Singh, Minnie; Spector, Benjamin L.; Wende, Helen Vander; An, Elroy H.; Fletcher, Marissa; Jelic, Monika; Rabinovitch, Peter S.; MacCoss, Michael J.; Han, Jing-Dong J.; Kennedy, Brian K.; Kaeberlein, Matt

    2013-01-01

    Summary Dietary restriction (DR) increases lifespan and attenuates age-related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here we describe a large-scale effort to define molecular mechanisms that underlie genotype-specific responses to DR. The effect of DR on lifespan was determined for 166 single-gene deletion strains in Saccharomyces cerevisiae. Resulting changes in mean lifespan ranged from a reduction of 79% to an increase of 103%. Vacuolar pH homeostasis, superoxide dismutase activity, and mitochondrial proteostasis were found to be strong determinants of the response to DR. Proteomic analysis of cells deficient in prohibitins revealed induction of a mitochondrial unfolded protein response (mtUPR) which has not previously been described in yeast. Mitochondrial proteotoxic stress in prohibitin mutants was suppressed by DR via reduced cytoplasmic mRNA translation. A similar relationship between prohibitins, the mtUPR, and longevity was also observed in Caenorhabditis elegans. These observations define conserved molecular processes that underlie genotype-dependent effects of DR that may be important modulators of DR in higher organisms. PMID:23837470

  14. Common Neural Mechanisms Underlying Reversal Learning by Reward and Punishment

    PubMed Central

    Xue, Gui; Xue, Feng; Droutman, Vita; Lu, Zhong-Lin; Bechara, Antoine; Read, Stephen

    2013-01-01

    Impairments in flexible goal-directed decisions, often examined by reversal learning, are associated with behavioral abnormalities characterized by impulsiveness and disinhibition. Although the lateral orbital frontal cortex (OFC) has been consistently implicated in reversal learning, it is still unclear whether this region is involved in negative feedback processing, behavioral control, or both, and whether reward and punishment might have different effects on lateral OFC involvement. Using a relatively large sample (N = 47), and a categorical learning task with either monetary reward or moderate electric shock as feedback, we found overlapping activations in the right lateral OFC (and adjacent insula) for reward and punishment reversal learning when comparing correct reversal trials with correct acquisition trials, whereas we found overlapping activations in the right dorsolateral prefrontal cortex (DLPFC) when negative feedback signaled contingency change. The right lateral OFC and DLPFC also showed greater sensitivity to punishment than did their left homologues, indicating an asymmetry in how punishment is processed. We propose that the right lateral OFC and anterior insula are important for transforming affective feedback to behavioral adjustment, whereas the right DLPFC is involved in higher level attention control. These results provide insight into the neural mechanisms of reversal learning and behavioral flexibility, which can be leveraged to understand risky behaviors among vulnerable populations. PMID:24349211

  15. Metal uptake by microalgae: underlying mechanisms and practical applications.

    PubMed

    Monteiro, Cristina M; Castro, Paula M L; Malcata, F Xavier

    2012-01-01

    Metal contamination of a few aquatic, atmospheric, and soil ecosystems has increased ever since the industrial revolution, owing to discharge of such elements via the effluents of some industrial facilities. Their presence to excessive levels in the environment will eventually lead to serious health problems in higher animals owing to accumulation throughout the food web. Current physicochemical methods available for recovery of metal pollutants (e.g., chemical precipitation, oxidation/reduction, or physical ion exchange) are either expensive or inefficient when they are present at very low concentrations. Consequently, removal of toxic metals by microorganisms has emerged as a potentially more economical alternative. Microalgae (in terms of both living and nonliving biomass) are an example of microorganisms suitable to recover metals and able to attain noteworthy percent removals. Their relatively high metal-binding capacities arise from the intrinsic composition of their cell walls, which contain negatively charged functional groups. Consequently, microalgal cells are particularly efficient in uptake of those contaminants when at low levels. Self-defense mechanisms developed by microalgal cells to survive in metal-containing media and environmental factors that affect their removal (e.g., pH, temperature, and biomass concentration) are reviewed here in a comprehensive way and further discussed in attempts to rationalize this form of remediation vis-a-vis with conventional nonbiological alternatives. PMID:22228490

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

    PubMed

    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.

  17. Mechanisms underlying the neuronal-based symptoms of allergy.

    PubMed

    Undem, Bradley J; Taylor-Clark, Thomas

    2014-06-01

    Persons with allergies present with symptoms that often are the result of alterations in the nervous system. Neuronally based symptoms depend on the organ in which the allergic reaction occurs but can include red itchy eyes, sneezing, nasal congestion, rhinorrhea, coughing, bronchoconstriction, airway mucus secretion, dysphagia, altered gastrointestinal motility, and itchy swollen skin. These symptoms occur because mediators released during an allergic reaction can interact with sensory nerves, change processing in the central nervous system, and alter transmission in sympathetic, parasympathetic, and enteric autonomic nerves. In addition, evidence supports the idea that in some subjects this neuromodulation is, for reasons poorly understood, upregulated such that the same degree of nerve stimulus causes a larger effect than seen in healthy subjects. There are distinctions in the mechanisms and nerve types involved in allergen-induced neuromodulation among different organ systems, but general principles have emerged. The products of activated mast cells, other inflammatory cells, and resident cells can overtly stimulate nerve endings, cause long-lasting changes in neuronal excitability, increase synaptic efficacy, and also change gene expression in nerves, resulting in phenotypically altered neurons. A better understanding of these processes might lead to novel therapeutic strategies aimed at limiting the suffering of those with allergies.

  18. An AT-barrier mechanically controls DNA reannealing under tension

    PubMed Central

    Bongini, L.; Pongor, C.; Falorsi, G.; Pertici, I.; Kellermayer, M.; Lombardi, V.; Bianco, P.

    2016-01-01

    Regulation of genomic activity occurs through the manipulation of DNA by competent mechanoenzymes. Force-clamp optical tweezers that allow the structural dynamics of the DNA molecule to be measured were used here to investigate the kinetics of mechanically-driven strand reannealing. When the force on the torsionally unconstrained λ-phage DNA is decreased stepwise from above to below the overstretching transition, reannealing occurs via discrete shortening steps separated by exponentially distributed time intervals. Kinetic analysis reveals a transition barrier 0.58 nm along the reaction coordinate and an average reannealing-step size of ∼750 bp, consistent with the average bp interval separating segments of more than 10 consecutive AT bases. In an AT-rich DNA construct, in which the distance between segments of more than 10 consecutive AT is reduced to ∼210 bps, the reannealing step reduces accordingly without changes in the position of the transition barrier. Thus, the transition barrier for reannealing is determined by the presence of segments of more than 10 consecutive AT bps independent of changes in sequence composition, while the length of the reannealing strand changes according to the distance between poly-AT segments at least 10 bps long. PMID:27378772

  19. Multiple NSAID-Induced Hits Injure the Small Intestine: Underlying Mechanisms and Novel Strategies

    PubMed Central

    Boelsterli, Urs A.

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious gastrointestinal (GI) injury including jejunal/ileal mucosal ulceration, bleeding, and even perforation in susceptible patients. The underlying mechanisms are largely unknown, but they are distinct from those related to gastric injury. Based on recent insights from experimental models, including genetics and pharmacology in rodents typically exposed to diclofenac, indomethacin, or naproxen, we propose a multiple-hit pathogenesis of NSAID enteropathy. The multiple hits start with an initial pharmacokinetic determinant caused by vectorial hepatobiliary excretion and delivery of glucuronidated NSAID or oxidative metabolite conjugates to the distal small intestinal lumen, where bacterial β-glucuronidase produces critical aglycones. The released aglycones are then taken up by enterocytes and further metabolized by intestinal cytochrome P450s to potentially reactive intermediates. The “first hit” is caused by the NSAID and/or oxidative metabolites that induce severe endoplasmic reticulum stress or mitochondrial stress and lead to cell death. The “second hit” is created by the significant subsequent inflammatory response that would follow such a first-hit injury. Based on these putative mechanisms, strategies have been developed to protect the enterocytes from being exposed to the parent NSAID and/or oxidative metabolites. Among these, a novel strategy already demonstrated in a murine model is the selective disruption of bacteria-specific β-glucuronidases with a novel small molecule inhibitor that does not harm the bacteria and that alleviates NSAID-induced enteropathy. Such mechanism-based strategies require further investigation but provide potential avenues for the alleviation of the GI toxicity caused by multiple NSAID hits. PMID:23091168

  20. Multiple NSAID-induced hits injure the small intestine: underlying mechanisms and novel strategies.

    PubMed

    Boelsterli, Urs A; Redinbo, Matthew R; Saitta, Kyle S

    2013-02-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious gastrointestinal (GI) injury including jejunal/ileal mucosal ulceration, bleeding, and even perforation in susceptible patients. The underlying mechanisms are largely unknown, but they are distinct from those related to gastric injury. Based on recent insights from experimental models, including genetics and pharmacology in rodents typically exposed to diclofenac, indomethacin, or naproxen, we propose a multiple-hit pathogenesis of NSAID enteropathy. The multiple hits start with an initial pharmacokinetic determinant caused by vectorial hepatobiliary excretion and delivery of glucuronidated NSAID or oxidative metabolite conjugates to the distal small intestinal lumen, where bacterial β-glucuronidase produces critical aglycones. The released aglycones are then taken up by enterocytes and further metabolized by intestinal cytochrome P450s to potentially reactive intermediates. The "first hit" is caused by the NSAID and/or oxidative metabolites that induce severe endoplasmic reticulum stress or mitochondrial stress and lead to cell death. The "second hit" is created by the significant subsequent inflammatory response that would follow such a first-hit injury. Based on these putative mechanisms, strategies have been developed to protect the enterocytes from being exposed to the parent NSAID and/or oxidative metabolites. Among these, a novel strategy already demonstrated in a murine model is the selective disruption of bacteria-specific β-glucuronidases with a novel small molecule inhibitor that does not harm the bacteria and that alleviates NSAID-induced enteropathy. Such mechanism-based strategies require further investigation but provide potential avenues for the alleviation of the GI toxicity caused by multiple NSAID hits.