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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 Central

    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. PMID:23755276

  2. Mechanism underlying mitochondrial protection of asiatic acid against hepatotoxicity in mice.

    PubMed

    Gao, Jing; Chen, Jin; Tang, Xinhui; Pan, Liya; Fang, Feng; Xu, Lizhi; Zhao, Xiaoning; Xu, Qiang

    2006-02-01

    Asiatic acid (AA) is one of the triterpenoid components of Terminalia catappa L., which has antioxidative, anti-inflammatory and hepatoprotective activity. This research focused on the mitochondrial protection of AA against acute liver injury induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN) in mice. It was found that pretreatment with 25, 50 or 100 mg kg(-1) AA significantly blocked the LPS + D-GalN-induced increase in both serum aspartate aminotransferase (sAST) and serum alanine aminotransferase (sALT) levels, which was confirmed by ultrastructural observation under an electron microscope, showing improved nuclear condensation, ameliorated mitochondrion proliferation and less lipid deposition. Meanwhile, different doses of AA could decrease both the transcription and the translation level of voltage-dependent anion channels (VDACs), the most important mitochondrial PTP component protein, and block the translocation of cytochrome c from mitochondria to cytosol. On the other hand, pre-incubation with 25, 50 and 100 microg mL(-1) AA inhibited the Ca(2+)-induced mitochondrial permeability transition (MPT), including mitochondrial swelling, membrane potential dissipation and releasing of matrix Ca(2+) in liver mitochondria separated from normal mice, indicating the direct role of AA on mitochondria. Collectively, the above data suggest that AA could protect liver from damage and the mechanism might be related to up-regulating mitochondrial VDACs and inhibiting the process of MPT. PMID:16451751

  3. 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

  4. Renal Protective Effect of Probucol in Rats with Contrast-Induced Nephropathy and its Underlying Mechanism

    PubMed Central

    Wang, Na; Wei, Ri-bao; Li, Qing-ping; Yang, Xi; Li, Ping; Huang, Meng-jie; Wang, Rui; Cai, Guang-yan; Chen, Xiang-mei

    2015-01-01

    Background Contrast-induced nephropathy (CIN) refers to acute renal damage that occurs after the use of contrast agents. This study investigated the renal protective effect of probucol in a rat model of contrast-induced nephropathy and the mechanism of its effect. Material/Methods Twenty-eight Wistar rats were randomly divided into the control group, model group, N-acetylcysteine(NAC) group, and probucol group. We used a rat model of iopromide-induced CIN. One day prior to modeling, the rats received gavage. At 24 h after the modeling, blood biochemistry and urine protein were assessed. Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in renal tissue. Kidney sections were created for histopathological examination. Results The model group of rats showed significantly elevated levels of blood creatinine, urea nitrogen, 24-h urine protein, histopathological scores, and parameters of oxidative stress (P<0.05). Both the NAC and probucol groups demonstrated significantly lower Scr, BUN, and urine protein levels compared to the model group (P<0.05), with no significant difference between these 2 groups. The NAC group and the probucol group had significantly lower MDA and higher SOD than the model group at 24 h after modeling (P<0.05). The 8-OHdG-positive tubule of the probucol group and NAC group were significantly lower than those of the model group (p=0.046, P=0.0008), with significant difference between these 2 groups (P=0.024). Conclusions Probucol can effectively reduce kidney damage caused by contrast agent. The underlying mechanism may be that probucol accelerates the recovery of renal function and renal pathology by reducing local renal oxidative stress. PMID:26408630

  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. Autophagy Is a Protective Mechanism for Human Melanoma Cells under Acidic Stress*

    PubMed Central

    Marino, Maria Lucia; Pellegrini, Paola; Di Lernia, Giuseppe; Djavaheri-Mergny, Mojgan; Brnjic, Slavica; Zhang, Xiaonan; Hägg, Maria; Linder, Stig; Fais, Stefano; Codogno, Patrice; De Milito, Angelo

    2012-01-01

    Cyclic hypoxia and alterations in oncogenic signaling contribute to switch cancer cell metabolism from oxidative phosphorylation to aerobic glycolysis. A major consequence of up-regulated glycolysis is the increased production of metabolic acids responsible for the presence of acidic areas within solid tumors. Tumor acidosis is an important determinant of tumor progression and tumor pH regulation is being investigated as a therapeutic target. Autophagy is a cellular catabolic pathway leading to lysosomal degradation and recycling of proteins and organelles, currently considered an important survival mechanism in cancer cells under metabolic stress or subjected to chemotherapy. We investigated the response of human melanoma cells cultured in acidic conditions in terms of survival and autophagy regulation. Melanoma cells exposed to acidic culture conditions (7.0 < pH < 6.2) promptly accumulated LC3+ autophagic vesicles. Immunoblot analysis showed a consistent increase of LC3-II in acidic culture conditions as compared with cells at normal pH. Inhibition of lysosomal acidification by bafilomycin A1 further increased LC3-II accumulation, suggesting an active autophagic flux in cells under acidic stress. Acute exposure to acidic stress induced rapid inhibition of the mammalian target of rapamycin signaling pathway detected by decreased phosphorylation of p70S6K and increased phosphorylation of AMP-activated protein kinase, associated with decreased ATP content and reduced glucose and leucine uptake. Inhibition of autophagy by knockdown of the autophagic gene ATG5 consistently reduced melanoma cell survival in low pH conditions. These observations indicate that induction of autophagy may represent an adaptation mechanism for cancer cells exposed to an acidic environment. Our data strengthen the validity of therapeutic strategies targeting tumor pH regulation and autophagy in progressive malignancies. PMID:22761435

  7. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 f...

  9. 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

  10. 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

  11. 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

  12. 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

  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

    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. PMID:24566536

  15. 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

  16. Snapping mechanical metamaterials under tension.

    PubMed

    Rafsanjani, Ahmad; Akbarzadeh, Abdolhamid; Pasini, Damiano

    2015-10-21

    A snapping mechanical metamaterial is designed, which exhibits a sequential snap-through behavior under tension. The tensile response of this mechanical metamaterial can be altered by tuning the architecture of the snapping segments to achieve a range of nonlinear mechanical responses, including monotonic, S-shaped, plateau, and non-monotonic snap-through behavior. PMID:26314680

  17. Measuring cathodic protection under unbonded coatings

    SciTech Connect

    Orton, M.D.

    1986-03-01

    Corrosion protection of pipe lines by cathodic protection where unbonded coatings exist has concerned engineers for decades. Without more than theoretical considerations available, it is nearly impossible for a pipe line operator to make relevant economic decisions whether to apply additional cathodic protection or to recondition existing pipe lines. The savings realized from additional protective current versus reconditioning large diameter pipe can be significant provided adequate potentials can be achieved beneath unbonded coatings. Arabian American Oil Co. has developed a test procedure to make field measurements to determine the effectiveness of cathodic protection under unbonded coatings. The test site is in the northern part of the Eastern Province of Saudi Arabia.

  18. 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.

  19. [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

  20. 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. PMID:26718581

  1. 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.

  2. A quantum protective mechanism in photosynthesis

    PubMed Central

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

    2015-01-01

    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. PMID:25732807

  3. 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

  4. 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

  5. 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

  6. 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. PMID:25136683

  7. Neural Mechanisms Underlying Breathing Complexity

    PubMed Central

    Hess, Agathe; Yu, Lianchun; Klein, Isabelle; De Mazancourt, Marine; Jebrak, Gilles; Mal, Hervé; Brugière, Olivier; Fournier, Michel; Courbage, Maurice; Dauriat, Gaelle; Schouman-Clayes, Elisabeth; Clerici, Christine; Mangin, Laurence

    2013-01-01

    Breathing is maintained and controlled by a network of automatic neurons in the brainstem that generate respiratory rhythm and receive regulatory inputs. Breathing complexity therefore arises from respiratory central pattern generators modulated by peripheral and supra-spinal inputs. Very little is known on the brainstem neural substrates underlying breathing complexity in humans. We used both experimental and theoretical approaches to decipher these mechanisms in healthy humans and patients with chronic obstructive pulmonary disease (COPD). COPD is the most frequent chronic lung disease in the general population mainly due to tobacco smoke. In patients, airflow obstruction associated with hyperinflation and respiratory muscles weakness are key factors contributing to load-capacity imbalance and hence increased respiratory drive. Unexpectedly, we found that the patients breathed with a higher level of complexity during inspiration and expiration than controls. Using functional magnetic resonance imaging (fMRI), we scanned the brain of the participants to analyze the activity of two small regions involved in respiratory rhythmogenesis, the rostral ventro-lateral (VL) medulla (pre-Bötzinger complex) and the caudal VL pons (parafacial group). fMRI revealed in controls higher activity of the VL medulla suggesting active inspiration, while in patients higher activity of the VL pons suggesting active expiration. COPD patients reactivate the parafacial to sustain ventilation. These findings may be involved in the onset of respiratory failure when the neural network becomes overwhelmed by respiratory overload We show that central neural activity correlates with airflow complexity in healthy subjects and COPD patients, at rest and during inspiratory loading. We finally used a theoretical approach of respiratory rhythmogenesis that reproduces the kernel activity of neurons involved in the automatic breathing. The model reveals how a chaotic activity in neurons can

  8. 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.

  9. Uncovering high-strain rate protection mechanism in nacre

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

    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.

  10. 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

  11. 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

  12. Retinal Light Damage: Mechanisms and Protection

    PubMed Central

    Organisciak, Daniel T.; Vaughan, Dana K.

    2009-01-01

    By its action on rhodopsin, light triggers the well-known visual transduction cascade, but can also induce cell damage and death through phototoxic mechanisms -- a comprehensive understanding of which is still elusive despite more than 40 years of research. Herein, we integrate recent experimental findings to address several hypotheses of retinal light damage, premised in part on the close anatomical and metabolic relationships between the photoreceptors and the retinal pigment epithelium. We begin by reviewing the salient features of light damage, recently joined by evidence for retinal remodeling which has implications for the prognosis of recovery of function in retinal degenerations. We then consider select factors that influence the progression of the damage process and the extent of visual cell loss. Traditional, genetically-modified, and emerging animal models are discussed, with particular emphasis on cone visual cells. Exogenous and endogenous retinal protective factors are explored, with implications for light damage mechanisms and some suggested avenues for future research. Synergies are known to exist between our long term light environment and photoreceptor cell death in retinal disease. Understanding the molecular mechanisms of light damage in a variety of animal models can provide valuable insights into the effects of light in clinical disorders and may form the basis of future therapies to prevent or delay visual cell loss. PMID:19951742

  13. 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

  14. 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

  15. Neuro-protective Mechanisms of Lycium barbarum.

    PubMed

    Xing, Xiwen; Liu, Fenyong; Xiao, Jia; So, Kwok Fai

    2016-09-01

    Neuronal diseases, including retinal disorders, stroke, Alzheimer's disease, Parkinson's disease and spinal cord injury, affect a large number of people worldwide and cause heavy social and economic burdens. Although many efforts have been made by scientists and clinicians to develop novel drug and healthcare strategies, few of them received satisfactory outcomes to date. Lycium barbarum is a traditional homology of medicine and food in Chinese medicine, with the capability to nourish the eyes, liver and kidneys. Recent studies have also explored its powerful neuro-protective effects on a number of neuronal diseases. In the current review, we collected key recent findings regarding the neuro-protective effects and mechanisms of L. barbarum derivatives, primarily its polysaccharide (LBP) , in some common diseases of the nervous system. A comprehensive comparison with currently available drugs has also been discussed. In general, LBP is a promising neuronal protector with potent ameliorative effects on key pathological events, such as oxidative stress, inflammation, apoptosis and cell death with minimal side effects. PMID:27033360

  16. 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

  17. 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.

  18. Mechanisms of Neonatal Mucosal Antibody Protection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Following an abrupt transition at birth from the sterile uterus to an environment with abundant commensal and pathogenic microbes, neonatal mammals are protected by maternal antibodies at mucosal surfaces. We show in mice that different antibody isotypes work in distinct ways to protect the neonatal...

  19. 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.

  20. 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’, ‘...

  1. 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.

  2. Legal mechanisms for protecting riparian resource values

    SciTech Connect

    Lamb, B.L.; Lord, E. )

    1992-04-01

    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. The authors 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. They discuss the politics of implementing these policies, focusing on the difficulties in changing entrenched water and land use practices. Their 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.

  3. Protective effects and mechanisms of sirtuins in the nervous system

    PubMed Central

    Zhang, Feng; Wang, Suping; Gan, Li; Vosler, Peter S.; Gao, Yanqin; Chen, Jun

    2011-01-01

    Silent information regulator two proteins (sirtuins or SIRTs) are a group of histone deacetylases whose activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD+). They suppress genome-wide transcription, yet upregulate a select set of proteins related to energy metabolism and pro-survival mechanisms, and therefore play a key role in the longevity effects elicited by calorie restriction. Recently, a neuroprotective effect of sirtuins has been reported for both acute and chronic neurological diseases. The focus of this review is to summarize the latest progress regarding the protective effects of sirtuins, with a focus on SIRT1. We first introduce the distribution of sirtuins in the brain and how their expression and activity are regulated. We then highlight their protective effects against common neurological disorders, such as cerebral ischemia, axonal injury, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. Finally, we analyze the mechanisms underlying sirtuin-mediated neuroprotection, centering on their non-histone substrates such as DNA repair enzymes, protein kinases, transcription factors, and coactivators. Collectively, the information compiled here will serve as a comprehensive reference for the actions of sirtuins in the nervous system to date, and will hopefully help to design further experimental research and expand sirtuins as therapeutic targets in the future. PMID:21930182

  4. 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.…

  5. Physical and mechanical properties and thermal protection efficiency of intumescent coatings

    NASA Astrophysics Data System (ADS)

    Zverev, V. G.; Zinchenko, V. I.; Tsimbalyuk, A. F.

    2016-04-01

    The new engineering technique for the experimental investigation of physical and mechanical characteristics of thermal protective intumescent coatings is offered. A mathematical model is proposed for predicting the thermal behavior of structures protected by coatings; the model is closed by the studied material characteristics. The heating of a metal plate under standard thermal loading conditions is modeled mathematically. The modeling results are in good agreement with bench test results for metal temperature under the coating. The proposed technique of studying physical and mechanical characteristics can be applied to identify and monitor the state of thermal protective intumescent coatings in the long-term operation.

  6. Mechanisms underlying protective effects of trimetazidine on endothelial progenitor cells biological functions against H2O2-induced injury: involvement of antioxidation and Akt/eNOS signaling pathways.

    PubMed

    Wu, Qinqin; Qi, Benling; Liu, Yun; Cheng, Bei; Liu, Lihua; Li, Yuanyuan; Wang, Qian

    2013-05-01

    Trimetazidine (TMZ) is a widely used drug exerting cardioprotective effects against ischemic heart disease through a number of mechanisms in conditions of oxidative stress. However, there are few data regarding the effects of TMZ on endothelial lineage, especially endothelial progenitor cells (EPCs). Thus, we sought to investigate whether TMZ could protect EPCs against oxidative stress injury induced by H2O2 (100 µM) and the preliminary mechanisms involved in vitro. The results showed that pretreatment of EPCs with TMZ (10 µM) protected the proliferation, adhesion, migration, and apoptosis of EPCs against H2O2, accompanied by an increase in superoxide dismutase (SOD) activity, a decrease in malonaldehyde (MDA) content, and increases in eNOS, Akt phosphorylation, and NO production. These TMZ-mediated beneficial effects on EPCs could be attenuated by pre-incubation with the Akt inhibitor triciribine. In conclusion, the present study demonstrates that TMZ ameliorated H2O2-induced impairment of biological functions in EPCs with the involvement of antioxidation and Akt/eNOS signaling pathway. These findings suggest that TMZ mediating preservation of EPCs may contribute to its cardioprotective effects on ischemic heart disease. PMID:23528356

  7. Neurotoxins: Free Radical Mechanisms and Melatonin Protection

    PubMed Central

    Reiter, Russel J.; Manchester, Lucien C.; Tan, Dun-Xian

    2010-01-01

    Toxins that pass through the blood-brain barrier put neurons and glia in peril. The damage inflicted is usually a consequence of the ability of these toxic agents to induce free radical generation within cells but especially at the level of the mitochondria. The elevated production of oxygen and nitrogen-based radicals and related non-radical products leads to the oxidation of essential macromolecules including lipids, proteins and DNA. The resultant damage is referred to as oxidative and nitrosative stress and, when the molecular destruction is sufficiently severe, it causes apoptosis or necrosis of neurons and glia. Loss of brain cells compromises the functions of the central nervous system expressed as motor, sensory and cognitive deficits and psychological alterations. In this survey we summarize the publications related to the following neurotoxins and the protective actions of melatonin: aminolevulinic acid, cyanide, domoic acid, kainic acid, metals, methamphetamine, polychlorinated biphenyls, rotenone, toluene and 6-hydroxydopamine. Given the potent direct free radical scavenging activities of melatonin and its metabolites, their ability to indirectly stimulate antioxidative enzymes and their efficacy in reducing electron leakage from mitochondria, it would be expected that these molecules would protect the brain from oxidative and nitrosative molecular mutilation. The studies summarized in this review indicate that this is indeed the case, an action that is obviously assisted by the fact that melatonin readily crosses the blood brain barrier. PMID:21358970

  8. 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,…

  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. 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

  11. HIF-1α in heart: Protective mechanisms

    PubMed Central

    Wu, Joe; Chen, Ping; Li, Ying; Ardell, Chris; Der, Tatyana; Shohet, Ralph; Chen, Minghua

    2013-01-01

    Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that directs many of the cellular responses to hypoxia. In these studies, we have used a mouse model containing a cardiac-specific, oxygen-stabilized, doxycycline (Dox)-off regulated HIF-1α transgene to probe the role of HIF-1α in cardioprotection. Hearts used in these studies were derived from wild-type (WT), noninduced (Non-I), and 2 day (2D) and 6 day (6D) Dox-deprived mice. Whereas HIF-1α protein is undetectable in WT mice, it is present in heart tissue of “noninduced” transgenic mice, presumably because of leakiness of the promoter construct. In mice denied Dox for 2 or 6 days, HIF-1α is overexpressed to a much greater extent than Non-I or WT animals, as expected. WT and HIF-1α-expressing hearts (Non-I, 2D and 6D induced) were subjected to 30 min of ischemia, and functional recovery was measured upon reperfusion. Recovery of preischemic left ventricular developed pressure was 14% for WT, 67% for Non-I hearts, 64% for 2D-induced, and 62% for 6D-induced hearts. 6D-induced HIF hearts have increased preischemic glycogen reserves, higher glycogen synthase protein levels, and significantly higher lactic acid release during ischemia. 6D-induced HIF hearts were also better able to maintain ATP levels during ischemia compared with WT and Non-I hearts. Interestingly, Non-I hearts showed no significant increase in glycogen reserves, glycolytic flux, or greater ATP preservation during ischemia and yet were protected to a similar extent as the 6D-induced hearts. Finally, the mitochondrial membrane potential of isolated adult myocytes was monitored during anoxia or treatments with cyanide and 2-deoxyglucose. HIF-1α expression was shown to protect mitochondrial polarization during both stress treatments. Taken together these data indicate that, while HIF-1α expression in heart does induce increases in compensatory glycolytic capacity, these changes are not necessarily required for cardioprotection

  12. Growth instabilities in mechanical breakdown under mechanical and thermal stresses

    NASA Astrophysics Data System (ADS)

    Zhang, S.-Z.; Louis, E.; Plá, O.; Guinea, F.

    1995-12-01

    A linear stability analysis is used to investigate crack growth in two dimensional elastic media, and under mechanical or thermal stresses. Although in most cases a circular geometry is considered, the instability of a planar crack is also discussed. Several boundary conditions and size effects are considered. The results indicate that the tendency towards instabilities in mechanical breakdown is stronger than in the case of growth in fields governed by the Laplace equation (diffusion or electrostatic fields), in line with the smaller fractal dimensions obtained in the first case. Instabilities under thermal stresses are shown to depend on the actual thermal gradients. Finally, a model previously investigated numerically is used to show that plasticity decreases the strength of the instability. (c) 1995 The American Physical Society

  13. 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

  14. Mechanisms for glyproline protection in hypercholesterolemia.

    PubMed

    Myasoedov, Nikolay F; Lyapina, Ludmila A; Grigorjeva, Marina E; Obergan, Tamara Y; Shubina, Tatyana A; Andreeva, Ludmila A

    2016-03-01

    Comparative analysis of the hypocholesterolemic and antithrombotic action of small regulatory glyproline peptides (Pro-Gly-Pro, Arg-Pro-Gly-Pro and Pro-Gly-Pro-Leu) was performed on an experimental hypercholesterolemia model of rats. Repeated intranasal introduction of glyproline peptides to fat-diet-fed animals led to more active functioning of the anticoagulation system (the anticoagulant and fibrinolytic properties of the plasma increased and platelet aggregation decreased) and to normalization of the total cholesterol level as a parameter of lipid metabolism. The largest anticoagulant and hypocholesterolemic effect was detected for the Pro-Gly-Pro-Leu peptide. Hypothetical mechanisms of antithrombotic and hypocholesterolemic effects of glyproline peptides are presented. PMID:26631418

  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. Docking Fixture and Mechanism for a Protective Suit

    NASA Technical Reports Server (NTRS)

    Culbertson, Philip, Jr.

    2003-01-01

    A suitlock assembly that comprises a docking fixture and mechanism has been invented to facilitate and accelerate donning and doffing of a sealed protective suit and/or to enable ingress and egress between the protective suit and a sealed vessel. The sealed protective suit could be a space suit, in which case the sealed vessel could be a spacecraft. Alternatively, the sealed suit could be an environmental protective suit of a type worn on Earth during cleanup of a hazardous-material site, in which case the sealed vessel could be a vehicle equipped to maintain a safe interior environment for workers in transit to and from the site. Figure 1 depicts a typical situation in which several crewmembers are working inside such a vehicle, one is working outside in a protective suit, and one is donning or doffing a protective suit while holding onto an overhead bar for support.

  17. 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.

  18. Scleral Mechanisms Underlying Ocular Growth and Myopia

    PubMed Central

    Metlapally, Ravi; Wildsoet, Christine F.

    2015-01-01

    In the regulation of ocular growth, scleral events critically determine eye size and thus the refractive status of the eye. Increased scleral matrix remodeling can lead to exaggerated eye growth causing myopia and additionally increased risk of ocular pathological complications. Thus, therapies targeting these changes in sclera hold potential to limit such complications since sclera represents a relatively safe and accessible drug target. Understanding the scleral molecular mechanisms underlying ocular growth is essential to identifying plausible therapeutic targets in the sclera. This section provides a brief update on molecular studies that pertain to the sclera in the context of ocular growth regulation and myopia. PMID:26310158

  19. Cellular and molecular mechanisms underlying muscular dystrophy

    PubMed Central

    2013-01-01

    The muscular dystrophies are a group of heterogeneous genetic diseases characterized by progressive degeneration and weakness of skeletal muscle. Since the discovery of the first muscular dystrophy gene encoding dystrophin, a large number of genes have been identified that are involved in various muscle-wasting and neuromuscular disorders. Human genetic studies complemented by animal model systems have substantially contributed to our understanding of the molecular pathomechanisms underlying muscle degeneration. Moreover, these studies have revealed distinct molecular and cellular mechanisms that link genetic mutations to diverse muscle wasting phenotypes. PMID:23671309

  20. 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.

  1. 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

  2. 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

  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. Mechanical buckling of veins under internal pressure.

    PubMed

    Martinez, Ricky; Fierro, Cesar A; Shireman, Paula K; Han, Hai-Chao

    2010-04-01

    Venous tortuosity is associated with multiple disease states and is often thought to be a consequence of venous hypertension and chronic venous disease. However, the underlying mechanisms of vein tortuosity are unclear. We hypothesized that increased pressure causes vein buckling that leads to a tortuous appearance. The specific aim of this study was to determine the critical buckling pressure of veins. We determined the buckling pressure of porcine jugular veins and measured the mechanical properties of these veins. Our results showed that the veins buckle when the transmural pressure exceeds a critical pressure that is strongly related to the axial stretch ratio in the veins. The critical pressures of the eight veins tested were 14.2 +/- 5.4 and 26.4 +/- 9.0 mmHg at axial stretch ratio 1.5 and 1.7, respectively. In conclusion, veins buckle into a tortuous shape at high lumen pressures or reduced axial stretch ratios. Our results are useful in understanding the development of venous tortuosity associated with varicose veins, venous valvular insufficiency, diabetic retinopathy, and vein grafts. PMID:20094913

  5. Mechanical Buckling of Veins under Internal Pressure

    PubMed Central

    Martinez, Ricky; Fierro, Cesar A.; Shireman, Paula K.; Han, Hai-Chao

    2010-01-01

    Venous tortuosity is associated with multiple disease states and is often thought to be a consequence of venous hypertension and chronic venous disease. However, the underlying mechanisms of vein tortuosity are unclear. We hypothesized that increased pressure causes vein buckling that leads to a tortuous appearance. The specific aim of this study was to determine the critical buckling pressure of veins. We determined the buckling pressure of porcine jugular veins and measured the mechanical properties of these veins. Our results showed that veins buckle when the transmural pressure exceeds a critical pressure that is strongly related to the axial stretch ratio in the veins. The critical pressures of the eight veins tested were 14.2 ± 5.4 mmHg and 26.4 ± 9.0 mmHg at axial stretch ratio 1.5 and 1.7, respectively. In conclusion, veins buckle into a tortuous shape at high lumen pressures or reduced axial stretch ratios. Our results are useful in understanding the development of venous tortuosity associated with varicose veins, venous valvular insufficiency, diabetic retinopathy and vein grafts. PMID:20094913

  6. 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. PMID:24591599

  7. 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

  8. Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

    PubMed Central

    Huth, M. E.; Ricci, A. J.; Cheng, A. G.

    2011-01-01

    Aminoglycosides are commonly prescribed antibiotics with deleterious side effects to the inner ear. Due to their popular application as a result of their potent antimicrobial activities, many efforts have been undertaken to prevent aminoglycoside ototoxicity. Over the years, understanding of the antimicrobial as well as ototoxic mechanisms of aminoglycosides has increased. These mechanisms are reviewed in regard to established and potential future targets of hair cell protection. PMID:22121370

  9. Theoretical tests of the mechanical protection strategy in protein nanomechanics.

    PubMed

    Chwastyk, Mateusz; Galera-Prat, Albert; Sikora, Mateusz; Gómez-Sicilia, Àngel; Carrión-Vázquez, Mariano; Cieplak, Marek

    2014-05-01

    We provide theoretical tests of a novel experimental technique to determine mechanostability of proteins based on stretching a mechanically protected protein by single-molecule force spectroscopy. This technique involves stretching a homogeneous or heterogeneous chain of reference proteins (single-molecule markers) in which one of them acts as host to the guest protein under study. The guest protein is grafted into the host through genetic engineering. It is expected that unraveling of the host precedes the unraveling of the guest removing ambiguities in the reading of the force-extension patterns of the guest protein. We study examples of such systems within a coarse-grained structure-based model. We consider systems with various ratios of mechanostability for the host and guest molecules and compare them to experimental results involving cohesin I as the guest molecule. For a comparison, we also study the force-displacement patterns in proteins that are linked in a serial fashion. We find that the mechanostability of the guest is similar to that of the isolated or serially linked protein. We also demonstrate that the ideal configuration of this strategy would be one in which the host is much more mechanostable than the single-molecule markers. We finally show that it is troublesome to use the highly stable cystine knot proteins as a host to graft a guest in stretching studies because this would involve a cleaving procedure. PMID:24123195

  10. [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. PMID:2066589

  11. 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

  12. 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

  13. 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. PMID:26916018

  14. 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

  15. 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

  16. 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.

  17. [Mechanisms of cerebral protection from ischemia by tea constituents].

    PubMed

    Vlasov, T D

    2012-08-01

    Epidemiological and clinical studies in recent years have shown that regular consumption of green or black tea significantly reduces the risk of cardiovascular diseases, including ischemic stroke. This review presents the clinical and experimental studies of the antiatherogenic, antiplatelet, antioxidant, antiinflammatory and other mechanisms of action of tea and substances in its composition. Effects of tea and its components, are described after long-term, and a short-term consumption. The role of catechins and specific amino acid L-theanine in the possible mechanisms of protection against cerebrovascular disease are discussed. PMID:23155618

  18. 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.

  19. 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. PMID:25548660

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

    PubMed Central

    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. PMID:25548660

  1. 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.

  2. Receptor mechanisms and circuitry underlying NMDA antagonist neurotoxicity.

    PubMed

    Farber, N B; Kim, S H; Dikranian, K; Jiang, X P; Heinkel, C

    2002-01-01

    NMDA glutamate receptor antagonists are used in clinical anesthesia, and are being developed as therapeutic agents for preventing neurodegeneration in stroke, epilepsy, and brain trauma. However, the ability of these agents to produce neurotoxicity in adult rats and psychosis in adult humans compromises their clinical usefulness. In addition, an NMDA receptor hypofunction (NRHypo) state might play a role in neurodegenerative and psychotic disorders, like Alzheimer's disease and schizophrenia. Thus, understanding the mechanism underlying NRHypo-induced neurotoxicity and psychosis could have significant clinically relevant benefits. NRHypo neurotoxicity can be prevented by several classes of agents (e.g. antimuscarinics, non-NMDA glutamate antagonists, and alpha(2) adrenergic agonists) suggesting that the mechanism of neurotoxicity is complex. In the present study a series of experiments was undertaken to more definitively define the receptors and complex neural circuitry underlying NRHypo neurotoxicity. Injection of either the muscarinic antagonist scopolamine or the non-NMDA antagonist NBQX directly into the cortex prevented NRHypo neurotoxicity. Clonidine, an alpha(2) adrenergic agonist, protected against the neurotoxicity when injected into the basal forebrain. The combined injection of muscarinic and non-NMDA Glu agonists reproduced the neurotoxic reaction. Based on these and other results, we conclude that the mechanism is indirect, and involves a complex network disturbance, whereby blockade of NMDA receptors on inhibitory neurons in multiple subcortical brain regions, disinhibits glutamatergic and cholinergic projections to the cerebral cortex. Simultaneous excitotoxic stimulation of muscarinic (m(3)) and glutamate (AMPA/kainate) receptors on cerebrocortical neurons appears to be the proximal mechanism by which the neurotoxic and psychotomimetic effects of NRHypo are mediated. PMID:11803444

  3. The effectiveness of cathodic protection under unbonded coatings on pipelines

    SciTech Connect

    Orton, M.D.

    1985-06-01

    Three joints of 1.22 m (48 in.) API X-42 line pipe 8 m (26 ft) long were instrumented, wrapped with an unbonded tape coating, and buried in a saline silty-sand soil in Eastern Saudi Arabia. Various levels of cathodic protection current were applied to the buried pipe. Potential measurements were made using reference electrodes imbedded in the pipe wall and in the usual monitoring manner with the reference electrode placed over the pipe. Data is presented on the relationship of surface pipe-to-soil potentials versus potentials under an unbonded coating with reference to Ag/AgCI electrodes installed up to 20 in. from a manufactured coating holiday.

  4. 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

  5. 19 CFR 206.66 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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...

  6. 19 CFR 206.37 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... business information under administrative protective order. 206.37 Section 206.37 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO GLOBAL... business information under administrative protective order. Except in the case of an investigation...

  7. 19 CFR 206.66 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... business information under administrative protective order. 206.37 Section 206.37 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO GLOBAL... business information under administrative protective order. Except in the case of an investigation...

  10. [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

  11. 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

  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. 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

  14. 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

  15. 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.

  16. Molecular mechanisms underlying alcohol-drinking behaviours.

    PubMed

    Ron, Dorit; Barak, Segev

    2016-09-01

    The main characteristic of alcohol use disorder is the consumption of large quantities of alcohol despite the negative consequences. The transition from the moderate use of alcohol to excessive, uncontrolled alcohol consumption results from neuroadaptations that cause aberrant motivational learning and memory processes. Here, we examine studies that have combined molecular and behavioural approaches in rodents to elucidate the molecular mechanisms that keep the social intake of alcohol in check, which we term 'stop pathways', and the neuroadaptations that underlie the transition from moderate to uncontrolled, excessive alcohol intake, which we term 'go pathways'. We also discuss post-transcriptional, genetic and epigenetic alterations that underlie both types of pathways. PMID:27444358

  17. 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

  18. Mechanisms Underlying Induction of Tolerance to Foods.

    PubMed

    Berin, M Cecilia; Shreffler, Wayne G

    2016-02-01

    Oral tolerance refers to a systemic immune nonresponsiveness to antigens first encountered by the oral route, and a failure in development of this homeostatic process can result in food allergy. Clinical tolerance induced by allergen immunotherapy is associated with alterations in immune mechanisms relevant to the allergic response, including reduction of basophil reactivity, induction of IgG4, loss of effector Th2 cells, and induction of Tregs. The relative contribution of these immune changes to clinical tolerance to foods, and the duration of these immune changes after termination of immunotherapy, remains to be identified. PMID:26617229

  19. 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.

  20. 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

  1. Mechanism of protection by metallothionein against acetaminophen hepatotoxicity.

    PubMed

    Saito, Chieko; Yan, Hui-Min; 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 micromol/kg ZnCl2 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. PMID:19835899

  2. MECHANISM OF PROTECTION BY METALLOTHIONEIN AGAINST ACETAMINOPHEN HEPATOTOXICITY

    PubMed Central

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

    2009-01-01

    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 µmol/kg ZnCl2 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-benzoquinoneimine (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. PMID:19835899

  3. 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.

  4. Synaptic mechanisms underlying persistent cocaine craving.

    PubMed

    Wolf, Marina E

    2016-06-01

    Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here, I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and to further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction. PMID:27150400

  5. Biophysical mechanisms underlying olfactory receptor neuron dynamics

    PubMed Central

    Nagel, Katherine I.; Wilson, Rachel I.

    2010-01-01

    Odor responses of olfactory receptor neurons (ORNs) exhibit complex dynamics. Using genetics and pharmacology, we show that these dynamics in Drosophila ORNs can be separated into sequential steps, corresponding to transduction and spike generation. Each of these steps contributes distinct dynamics. Transduction dynamics can be largely explained by a simple kinetic model of ligand-receptor interactions, together with an adaptive feedback mechanism that slows transduction onset. Spiking dynamics are well-described by a differentiating linear filter that is stereotyped across odors and cells. Genetic knock-down of sodium channels reshapes this filter, implying that it arises from the regulated balance of intrinsic conductances in ORNs. Complex responses can be understood as a consequence of how the stereotyped spike filter interacts with odor- and receptor-specific transduction dynamics. However, in the presence of rapidly fluctuating natural stimuli, spiking simply increases the speed and sensitivity of encoding. PMID:21217763

  6. 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.

  7. 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

  8. On the physical mechanism underlying asymptotic safety

    NASA Astrophysics Data System (ADS)

    Nink, Andreas; Reuter, Martin

    2013-01-01

    We identify a simple physical mechanism which is at the heart of Asymptotic Safety in Quantum Einstein Gravity (QEG) according to all available effective average action-based investigations. Upon linearization the gravitational field equations give rise to an inverse propagator for metric fluctuations comprising two pieces: a covariant Laplacian and a curvature dependent potential term. By analogy with elementary magnetic systems they lead to, respectively, dia- and paramagnetic-type interactions of the metric fluctuations with the background gravitational field. We show that above 3 spacetime dimensions the gravitational antiscreening occurring in QEG is entirely due to a strong dominance of the ultralocal paramagnetic interactions over the diamagnetic ones that favor screening. (Below 3 dimensions both the dia- and paramagnetic effects support antiscreening.) The spacetimes of QEG are interpreted as a polarizable medium with a "paramagnetic" response to external perturbations, and similarities with the vacuum state of Yang-Mills theory are pointed out. As a by-product, we resolve a longstanding puzzle concerning the beta function of Newton's constant in 2 + ɛ dimensional gravity.

  9. Cellular and circuit mechanisms underlying spinocerebellar ataxias.

    PubMed

    Meera, Pratap; Pulst, Stefan M; Otis, Thomas S

    2016-08-15

    Degenerative ataxias are a common form of neurodegenerative disease that affect about 20 individuals per 100,000. The autosomal dominant spinocerebellar ataxias (SCAs) are caused by a variety of protein coding mutations (single nucleotide changes, deletions and expansions) in single genes. Affected genes encode plasma membrane and intracellular ion channels, membrane receptors, protein kinases, protein phosphatases and proteins of unknown function. Although SCA-linked genes are quite diverse they share two key features: first, they are highly, although not exclusively, expressed in cerebellar Purkinje neurons (PNs), and second, when mutated they lead ultimately to the degeneration of PNs. In this review we summarize ataxia-related changes in PN neurophysiology that have been observed in various mouse knockout lines and in transgenic models of human SCA. We also highlight emerging evidence that altered metabotropic glutamate receptor signalling and disrupted calcium homeostasis in PNs form a common, early pathophysiological mechanism in SCAs. Together these findings indicate that aberrant calcium signalling and profound changes in PN neurophysiology precede PN cell loss and are likely to lead to cerebellar circuit dysfunction that explains behavioural signs of ataxia characteristic of the disease. PMID:27198167

  10. 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.

  11. 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....

  12. Battle against RNA oxidation: molecular mechanisms for reducing oxidized RNA to protect cells.

    PubMed

    Li, Zhongwei; Malla, Sulochan; Shin, Brian; Li, James M

    2014-01-01

    Oxidation is probably the most common type of damage that occurs in cellular RNA. Oxidized RNA may be dysfunctional and is implicated in the pathogenesis of age-related human diseases. Cellular mechanisms controlling oxidized RNA have begun to be revealed. Currently, a number of ribonucleases and RNA-binding proteins have been shown to reduce oxidized RNA and to protect cells under oxidative stress. Although information about how these factors work is still very limited, we suggest several mechanisms that can be used to minimize oxidized RNA in various organisms. PMID:24375979

  13. BATTLE AGAINST RNA OXIDATION: Molecular mechanisms for reducing oxidized RNA to protect cells

    PubMed Central

    Li, Zhongwei; Malla, Sulochan; Shin, Brian; Li, James M.

    2014-01-01

    Oxidation is probably the most common type of damage that occurs in cellular RNA. Oxidized RNA may be dysfunctional and is implicated in the pathogenesis of age-related human diseases. Cellular mechanisms controlling oxidized RNA have begun to be revealed. Currently, a number of ribonucleases and RNA binding proteins have been shown to reduce oxidized RNA and to protect cells under oxidative stress. Although information about how these factors work is still very limited, we suggest several mechanisms that can be used to minimize oxidized RNA in various organisms. PMID:24375979

  14. 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

  15. Room temperature mechanical properties of shuttle thermal protection system materials

    NASA Technical Reports Server (NTRS)

    Sawyer, J. W.; Rummler, D. R.

    1980-01-01

    Tests were conducted at room temperature to determine the mechanical properties and behavior of materials used for the thermal protection system of the space shuttle. The materials investigated include the LI-900 RSI tiles, the RTV-560 adhesive and the .41 cm (.16 thick) strain isolator pad (SIP). Tensile and compression cyclic loading tests were conducted on the SIP material and stress-strain curves obtained for various proof loads and load cyclic conditioning. Ultimate tensile and shear tests were conducted on the RSI, RTV, and SIP materials. The SIP material exhibits highly nonlinear stress-strain behavior, increased tangent modulus and ultimate tensile strength with increased loading rate, and large short time load relaxation and moderate creep behavior. Proof and cyclic load conditioning of the SIP results in permanent deformation of the material, hysteresis effects, and much higher tensile tangent modulus values at large strains.

  16. 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.

  17. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT Protecting Tenants at Foreclosure Act: Guidance on Notification Responsibilities Under... the notice, entitled ``Protecting Tenants at Foreclosure: Notice of Responsibilities Placed...

  18. Nitrogen mineralization in soils under grasses and under trees in a protected Venezuelan savanna

    NASA Astrophysics Data System (ADS)

    Sánchez, L. F.; García-Miragaya, J.; Chacón, N.

    Nitrogen mineralization was evaluated in soils beneath the most common woody species growing isolated within the grass matrix of a Venezuelan Trachypogon savanna, which has been protected from fire and cattle grazing since 1961. Adult trees of three evergreen species, Byrsonima crassifolia (L) H. B. K., Curatella americana L., and Bowdichia virgilioides H. B. K; and two deciduous, Godmania macrocarpa Hemsley and Cochlospermun vitifolium (Wild) Spreng were selected. The amount of N mineralized (NH 4+-N+NO 3--N) during 15 weeks of laboratory incubation of soils collected from beneath trees, was significantly higher ( p<0.01) than those from under grasses. Values of N mineralized on soil from under trees were from 21.28 to 82.65% greater than for soil from under grasses. A highly significant ( p<0.01) positive correlation, for all soils, was found between Nm and SOC, and between Nm and Nt. The higher N mineralization rates under trees would reflect a higher soil biological activity, due to higher SOC and Nt, of the soils under the tree canopies than those under grasses. The N availability values obtained under all species reveal the importance these trees have for creating enriched areas on generally oligotrophic soils. Nitrogen mineralized in the soil from beneath evergreen trees was significantly ( p<0.01) higher than from under deciduous trees, being 25.87% higher on average. Similarly to the relation found for all soils, a highly significant ( p<0.01) positive correlation between Nm and SOC and between Nm and Nt was also obtained for soils beneath all trees, indicating the importance of SOC and Nt for nitrogen mineralization processes in this savanna. The higher SOC and Nt contents found under evergreen trees are probably due to the longer time they have been established on the site as compared to the deciduous ones. The chemical quality of fresh fallen leaves (as measured by their lignin/nitrogen ratio) did not seem to influence the quality of the SOM (as

  19. 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.

  20. Reduced glucose utilization underlies seizure protection with dietary therapy in epileptic EL mice.

    PubMed

    Meidenbauer, Joshua J; Roberts, Mary F

    2014-10-01

    Dietary therapy has been used to treat many individuals with epilepsy whose seizures are refractory to antiepileptic drugs. The mechanisms for how dietary therapy confers seizure protection are currently not well understood. We evaluated the acute effects of glucose and β-hydroxybutyrate (the major circulating ketone body) in conferring seizure protection to the EL mouse, a model of multifactorial idiopathic generalized epilepsy. EL mice were fed either an unrestricted standard diet or a calorie-restricted standard diet to achieve a body weight reduction of 20-23%. D-Glucose, 2-deoxy-D-glucose, and β-hydroxybutyrate were supplemented in the drinking water of calorie-restricted mice for 2.5 h prior to seizure testing to simulate the effect of increased glucose availability, decreased glucose utilization, and increased ketone availability, respectively. Seizure susceptibility, body weight, plasma glucose, and β-hydroxybutyrate were measured over a nine-week treatment period. Additionally, excitatory and inhibitory amino acids were measured in the brains of mice using (1)H NMR. Glutamate decarboxylase activity was also measured to evaluate the connection between dietary therapy and brain metabolism. We found that lowering of glucose utilization is necessary to confer seizure protection with long-term (>4 weeks) calorie restriction, whereas increased ketone availability did not affect seizure susceptibility. In the absence of long-term calorie restriction, however, reduced glucose utilization and increased ketone availability did not affect seizure susceptibility. Brain excitatory and inhibitory amino acid content did not change with treatment, and glutamate decarboxylase activity was not associated with seizure susceptibility. We demonstrated that reduced glucose utilization is necessary to confer seizure protection under long-term calorie restriction in EL mice, while acute ketone supplementation did not confer seizure protection. Further studies are needed to

  1. 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

  2. 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 certifications required from recipients of discounts under the federal universal service support mechanism for schools and libraries. 54.520 Section 54.520 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES...

  3. 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 certifications required from recipients of discounts under the federal universal service support mechanism for schools and libraries. 54.520 Section 54.520 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES...

  4. 19 CFR 206.47 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... business information under administrative protective order. 206.47 Section 206.47 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO GLOBAL... information under administrative protective order. In an investigation under section 421(b) or (o) of...

  5. 19 CFR 206.47 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... business information under administrative protective order. 206.47 Section 206.47 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO GLOBAL... information under administrative protective order. In an investigation under section 421(b) or (o) of...

  6. 19 CFR 206.47 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... business information under administrative protective order. 206.47 Section 206.47 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO GLOBAL... information under administrative protective order. In an investigation under section 421(b) or (o) of...

  7. 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

  8. 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…

  9. 78 FR 41972 - Determination Under Section 107(a) of the William Wilberforce Trafficking Victims Protection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-12

    ... Determination Under Section 107(a) of the William Wilberforce Trafficking Victims Protection Reauthorization Act... Trafficking Victims Protection Act of 2008 (Pub. L. 110-457) and Delegation of Waiver Authority Pursuant to... Section 110(b)(3)(D) of the Trafficking Victims Protection Act of 2000, as amended (Pub. L. 106-386),...

  10. 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

    ... Determination Under Section 107(a) of the William Wilberforce Trafficking Victims Protection Reauthorization Act... Trafficking Victims Protection Act of 2008 (Pub. L. 110-457) and Delegation of Waiver Authority Pursuant to... Section 110(b)(3)(D) of the Trafficking Victims Protection Act of 2000, as amended (Pub. L. 106-386),...

  11. 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

  12. 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

  13. The Intricate Interplay between Mechanisms Underlying Aging and Cancer

    PubMed Central

    Piano, Amanda; Titorenko, Vladimir I.

    2015-01-01

    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. PMID:25657853

  14. 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

  15. 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. PMID:25446567

  16. 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

  17. 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

  18. 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).

  19. The microstructure, mechanical and friction properties of protective diamond like carbon films on magnesium alloy

    NASA Astrophysics Data System (ADS)

    Zou, Y. S.; Wu, Y. F.; Yang, H.; Cang, K.; Song, G. H.; Li, Z. X.; Zhou, K.

    2011-12-01

    Protective hard coatings deposited on magnesium alloys are believed to be effective for overcoming their poor wear properties. In this work, diamond-like carbon (DLC) films as hard protective films were deposited on AZ91 magnesium alloy by arc ion plating under negative pulse bias voltages ranging from 0 to -200 V. The microstructure, composition and mechanical properties of the DLC films were analyzed by scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy and nanoindentation. The tribological behavior of uncoated and coated AZ91 magnesium alloy was investigated using a ball-on-disk tribotester. The results show that the negative pulse bias voltage used for film deposition has a significant effect on the sp3 carbon content and mechanical properties of the deposited DLC films. A maximum sp3 content of 33.3% was obtained at -100 V, resulting in a high hardness of 28.6 GPa and elastic modulus of 300.0 GPa. The DLC films showed very good adhesion to the AZ91 magnesium alloy with no observable cracks and delamination even during friction testing. Compared with the uncoated AZ91 magnesium alloy, the magnesium alloy coated with DLC films exhibits a low friction coefficient and a narrow, shallow wear track. The wear resistance and surface hardness of AZ91 magnesium alloy can be significantly improved by coating a layer of DLC protective film due to its high hardness and low friction coefficient.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  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. 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.

  6. 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

  7. The mitochondrial protective mechanism of olfactory ensheathing cells conditioned medium protects against H2O2-induced injury in astrocytes.

    PubMed

    Liu, Jinbo; Qiu, Jing; Xiong, Yuyun; Liu, Zhiyuan; Gao, Jing

    2013-10-25

    Our previous studies showed that olfactory ensheathing cells conditioned medium (OECCM), has a positive effect against apoptosis in ASTs and prevents the morphology changes in the, mitochondria, but the accurate mechanism is still unknown. In this study, we examined the mitochondrial mechanism of OECCM which may protect against H2O2-induced injury in ASTs. It was, found that OECCM could protect ASTs from the injury of 500μmol/L H2O2, decrease the intracellular, ROS and Ca(2+) level, as well inhibit apoptosis and the expression of cleaved caspase-3. Further, investigations showed that OECCM could increase both the mitochondrial membrane potential and the, ATP level, as well enhance the cell respiratory function. In summary, OECCM could protect ASTs from, damages induced by H2O2. Its mechanism may be related to the decrease of ROS generation and the, overloading of Ca(2+), then stabilization of the mitochondrial function. PMID:24036462

  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. Mechanisms Underlying Language Acquisition: Benefits from a Comparative Approach

    ERIC Educational Resources Information Center

    Weiss, Daniel J.; Newport, Elissa L.

    2006-01-01

    One of the longstanding issues in language research has been the extent to which the mechanisms underlying language acquisition are uniquely human. The primary goal of this article is to introduce the reader to some of the recent developments in comparative language research that have shed new light on this issue. To appreciate the significance of…

  12. ADP Protects Cardiac Mitochondria under Severe Oxidative Stress

    PubMed Central

    Sokolova, Niina; Pan, Shi; Provazza, Sarah; Beutner, Gisela; Vendelin, Marko; Birkedal, Rikke; Sheu, Shey-Shing

    2013-01-01

    ADP is not only a key substrate for ATP generation, but also a potent inhibitor of mitochondrial permeability transition pore (mPTP). In this study, we assessed how oxidative stress affects the potency of ADP as an mPTP inhibitor and whether its reduction of reactive oxygen species (ROS) production might be involved. We determined quantitatively the effects of ADP on mitochondrial Ca2+ retention capacity (CRC) until the induction of mPTP in normal and stressed isolated cardiac mitochondria. We used two models of chronic oxidative stress (old and diabetic mice) and two models of acute oxidative stress (ischemia reperfusion (IR) and tert-butyl hydroperoxide (t-BH)). In control mitochondria, the CRC was 344 ± 32 nmol/mg protein. 500 μmol/L ADP increased CRC to 774 ± 65 nmol/mg protein. This effect of ADP seemed to relate to its concentration as 50 μmol/L had a significantly smaller effect. Also, oligomycin, which inhibits the conversion of ADP to ATP by F0F1ATPase, significantly increased the effect of 50 μmol/L ADP. Chronic oxidative stress did not affect CRC or the effect of 500 μmol/L ADP. After IR or t-BH exposure, CRC was drastically reduced to 1 ± 0.2 and 32 ± 4 nmol/mg protein, respectively. Surprisingly, ADP increased the CRC to 447 ± 105 and 514 ± 103 nmol/mg protein in IR and t-BH, respectively. Thus, it increased CRC by the same amount as in control. In control mitochondria, ADP decreased both substrate and Ca2+-induced increase of ROS. However, in t-BH mitochondria the effect of ADP on ROS was relatively small. We conclude that ADP potently restores CRC capacity in severely stressed mitochondria. This effect is most likely not related to a reduction in ROS production. As the effect of ADP relates to its concentration, increased ADP as occurs in the pathophysiological situation may protect mitochondrial integrity and function. PMID:24349464

  13. Identification of protective innate immune mechanisms in coccidiosis and salmonellosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major stumbling block in the development of novel control strategy against many mucosal poultry pathogens in poultry is the lack of comprehensive understanding of how host immune system interact and how protective immunity develops against mucosal pathogens. For example, in coccidiosis and salmone...

  14. 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

  15. 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.

  16. Linkages of plant-soil feedbacks and underlying invasion mechanisms.

    PubMed

    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

  17. A METHOD TO MEASURE PROTECTIVE CLOTHING PERMEATION UNDER INTERMITTENT CHEIMCAL CONTACT CONDITIONS

    EPA Science Inventory

    A preliminary method was developed to measure chemical permeation under intermittent chemical contact conditions. Protective clothing permeation is presently measured using ASTM Method F739-85. Because this test measures permeation when the clothing material is in continuous cont...

  18. Thermal and mechanical response of PBX 9501 under contact excitation

    NASA Astrophysics Data System (ADS)

    Mares, J. O.; Miller, J. K.; Sharp, N. D.; Moore, D. S.; Adams, D. E.; Groven, L. J.; Rhoads, J. F.; Son, S. F.

    2013-02-01

    The thermal and mechanical responses of a cyclotetramethylene-tetranitramine-based explosive (PBX 9501) and two non-energetic mock materials (900-21 and PBS 9501) under high-frequency mechanical excitation are presented. Direct contact ultrasound transducers were used to excite samples through a frequency range of 50 kHz to 40 MHz. The mechanical response of each sample was approximated from a contact receiving transducer and trends were confirmed via laser Doppler vibrometry. The steady-state thermal response of the samples was measured at discrete excitation frequencies via infrared thermography. A maximum temperature rise of approximately 15 K was observed in PBX 9501, and the mock materials exhibited similar thermal characteristics. Temperature gradients were calculated to estimate the total heat generated within the samples due to the mechanical excitation. The active heating mechanisms were found to be highly dependent on the frequency of excitation. Possible mechanisms of heating at frequencies below 1 MHz are likely related to bulk motion. Above this frequency, the active heating mechanisms are likely related to particle-scale processes. The observed phenomena may prove useful in the aid of current trace vapor detection methods for explosives.

  19. DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism.

    PubMed

    Fan, Saijun; Meng, Qinghui; Xu, Jiaying; Jiao, Yang; Zhao, Lin; Zhang, Xiaodong; Sarkar, Fazlul H; Brown, Milton L; Dritschilo, Anatoly; Rosen, Eliot M

    2013-11-12

    DIM (3,3'-diindolylmethane), a small molecule compound, is a proposed cancer preventive agent that can be safely administered to humans in repeated doses. We report that administration of DIM in a multidose schedule protected rodents against lethal doses of total body irradiation up to 13 Gy, whether DIM dosing was initiated before or up to 24 h after radiation. Physiologic submicromolar concentrations of DIM protected cultured cells against radiation by a unique mechanism: DIM caused rapid activation of ataxia-telangiectasia mutated (ATM), a nuclear kinase that regulates responses to DNA damage (DDR) and oxidative stress. Subsequently, multiple ATM substrates were phosphorylated, suggesting that DIM induces an ATM-dependent DDR-like response, and DIM enhanced radiation-induced ATM signaling and NF-κB activation. DIM also caused activation of ATM in rodent tissues. Activation of ATM by DIM may be due, in part, to inhibition of protein phosphatase 2A, an upstream regulator of ATM. In contrast, DIM did not protect human breast cancer xenograft tumors against radiation under the conditions tested. In tumors, ATM was constitutively phosphorylated and was not further stimulated by radiation and/or DIM. Our findings suggest that DIM is a potent radioprotector and mitigator that functions by stimulating an ATM-driven DDR-like response and NF-κB survival signaling. PMID:24127581

  20. DIM (3,3′-diindolylmethane) confers protection against ionizing radiation by a unique mechanism

    PubMed Central

    Fan, Saijun; Meng, Qinghui; Xu, Jiaying; Jiao, Yang; Zhao, Lin; Zhang, Xiaodong; Sarkar, Fazlul H.; Brown, Milton L.; Dritschilo, Anatoly; Rosen, Eliot M.

    2013-01-01

    DIM (3,3′-diindolylmethane), a small molecule compound, is a proposed cancer preventive agent that can be safely administered to humans in repeated doses. We report that administration of DIM in a multidose schedule protected rodents against lethal doses of total body irradiation up to 13 Gy, whether DIM dosing was initiated before or up to 24 h after radiation. Physiologic submicromolar concentrations of DIM protected cultured cells against radiation by a unique mechanism: DIM caused rapid activation of ataxia-telangiectasia mutated (ATM), a nuclear kinase that regulates responses to DNA damage (DDR) and oxidative stress. Subsequently, multiple ATM substrates were phosphorylated, suggesting that DIM induces an ATM-dependent DDR-like response, and DIM enhanced radiation-induced ATM signaling and NF-κB activation. DIM also caused activation of ATM in rodent tissues. Activation of ATM by DIM may be due, in part, to inhibition of protein phosphatase 2A, an upstream regulator of ATM. In contrast, DIM did not protect human breast cancer xenograft tumors against radiation under the conditions tested. In tumors, ATM was constitutively phosphorylated and was not further stimulated by radiation and/or DIM. Our findings suggest that DIM is a potent radioprotector and mitigator that functions by stimulating an ATM-driven DDR-like response and NF-κB survival signaling. PMID:24127581

  1. 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. PMID:26763404

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. The mismatch negativity: a review of underlying mechanisms.

    PubMed

    Garrido, Marta I; Kilner, James M; Stephan, Klaas E; Friston, Karl J

    2009-03-01

    The mismatch negativity (MMN) is a brain response to violations of a rule, established by a sequence of sensory stimuli (typically in the auditory domain) [Näätänen R. Attention and brain function. Hillsdale, NJ: Lawrence Erlbaum; 1992]. The MMN reflects the brain's ability to perform automatic comparisons between consecutive stimuli and provides an electrophysiological index of sensory learning and perceptual accuracy. Although the MMN has been studied extensively, the neurophysiological mechanisms underlying the MMN are not well understood. Several hypotheses have been put forward to explain the generation of the MMN; amongst these accounts, the "adaptation hypothesis" and the "model adjustment hypothesis" have received the most attention. This paper presents a review of studies that focus on neuronal mechanisms underlying the MMN generation, discusses the two major explanatory hypotheses, and proposes predictive coding as a general framework that attempts to unify both. PMID:19181570

  8. Cellular Mechanisms Underlying Eosinophilic and Neutrophilic Airway Inflammation in Asthma

    PubMed Central

    Vatrella, Alessandro; Busceti, Maria Teresa; Gallelli, Luca; Calabrese, Cecilia; Terracciano, Rosa

    2015-01-01

    Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments. PMID:25878402

  9. Mechanical properties of graphynes under shearing and bending

    NASA Astrophysics Data System (ADS)

    Yi, Lijun; Zhang, Yingyan; Feng, Xiqiao; Chang, Tienchong; Wang, Ji; Du, Jianke; Zhou, Jianxin

    2016-05-01

    Graphynes are the allotrope of graphene. In this work, extensive molecular dynamics simulations are performed on four different graphynes ( α - , β - , γ - , and 6,6,12-graphynes) to explore their mechanical properties (shear modulus, shear strength, and bending rigidity) under shearing and bending. While the shearing properties are anisotropic, the bending rigidity is almost independent of the chirality of graphynes. We also find that the shear modulus and shear fracture strength of graphynes decrease with increasing temperature. The effect of the percentage of the acetylenic linkages on the shear mechanical properties and bending rigidity is investigated. It is shown that the fracture shear strengths and bending rigidities of the four types of graphynes decrease, while the fracture shear strain increases, with increasing percentages of the acetylenic linkages. Significant wrinkling is observed in graphyne under shear strain. The influence of the temperatures and percentages of the acetylenic linkages on the ratio of amplitude-to-wavelength in the wrinkles are examined.

  10. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma.

    PubMed

    Pelaia, Girolamo; Vatrella, Alessandro; Busceti, Maria Teresa; Gallelli, Luca; Calabrese, Cecilia; Terracciano, Rosa; Maselli, Rosario

    2015-01-01

    Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments. PMID:25878402

  11. 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

  12. Closure mechanisms of ventilated supercavities under steady and unsteady flows

    NASA Astrophysics Data System (ADS)

    Karn, Ashish; De, Rohan; Hong, Jiarong; Arndt, Roger E. A.

    2015-12-01

    The present work reports some interesting experimental results for ventilated supercavitation in steady and unsteady flows. First, a variety of closure modes obtained as a result of systematic variation in Froude number and air entrainment, are reported. The closure mechanisms were found to differ from the standard criterion reported in the literature. Further, the occurrence of a variety of stable and unstable closure mechanisms were discovered that have not been reported in the literature. Next, a hypothesis is presented to explain the cause behind these different closure mechanisms. The proposed hypothesis is then validated by synchronized high-speed imaging and pressure measurements inside and outside of the supercavity. These measurements show that the supercavity closure is a function of instantaneous cavitation number under unsteady flow conditions. (Research sponsored by Office of Naval Research, USA)

  13. 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. PMID:25003518

  14. An NMDA receptor-dependent mechanism underlies inhibitory synapse development

    PubMed Central

    Gu, Xinglong; Zhou, Liang; Lu, Wei

    2016-01-01

    Summary In the mammalian brain GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here we report that NMDA-type ionotropic glutamate receptors (NMDARs) in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, while GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain. PMID:26774487

  15. Analysis of Internal Crack Healing Mechanism under Rolling Deformation

    PubMed Central

    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. PMID:25003518

  16. 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

  17. Understanding molecular mechanism of higher plant plasticity under abiotic stress.

    PubMed

    Shao, Hong-Bo; Guo, Qing-Jie; Chu, Li-Ye; Zhao, Xi-Ning; Su, Zhong-Liang; Hu, Ya-Chen; Cheng, Jiang-Feng

    2007-01-15

    Higher plants play the most important role in keeping a stable environment on the earth, which regulate global circumstances in many ways in terms of different levels (molecular, individual, community, and so on), but the nature of the mechanism is gene expression and control temporally and spatially at the molecular level. In persistently changing environment, there are many adverse stress conditions such as cold, drought, salinity and UV-B (280-320 mm), which influence plant growth and crop production greatly. Plants differ from animals in many aspects, but the important may be that plants are more easily influenced by environment than animals. Plants have a series of fine mechanisms for responding to environmental changes, which has been established during their long-period evolution and artificial domestication. These mechanisms are involved in many aspects of anatomy, physiology, biochemistry, genetics, development, evolution and molecular biology, in which the adaptive machinery related to molecular biology is the most important. The elucidation of it will extremely and purposefully promote the sustainable utilization of plant resources and make the best use of its current potential under different scales. This molecular mechanism at least include environmental signal recognition (input), signal transduction (many cascade biochemical reactions are involved in this process), signal output, signal responses and phenotype realization, which is a multi-dimensional network system and contain many levels of gene expression and regulation. We will focus on the molecular adaptive machinery of higher plant plasticity under abiotic stresses. PMID:16914294

  18. 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

  19. 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

  20. Pharmacological Mechanisms Underlying Gastroprotective Activities of the Fractions Obtained from Polygonum minus in Sprague Dawley Rats

    PubMed Central

    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

  1. 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

  2. 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

  3. A major role for Tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions

    PubMed Central

    Violet, Marie; Delattre, Lucie; Tardivel, Meryem; Sultan, Audrey; Chauderlier, Alban; Caillierez, Raphaelle; Talahari, Smail; Nesslany, Fabrice; Lefebvre, Bruno; Bonnefoy, Eliette; Buée, Luc; Galas, Marie-Christine

    2014-01-01

    Nucleic acid protection is a substantial challenge for neurons, which are continuously exposed to oxidative stress in the brain. Neurons require powerful mechanisms to protect DNA and RNA integrity and ensure their functionality and longevity. Beside its well known role in microtubule dynamics, we recently discovered that Tau is also a key nuclear player in the protection of neuronal genomic DNA integrity under reactive oxygen species (ROS)-inducing heat stress (HS) conditions in primary neuronal cultures. In this report, we analyzed the capacity of Tau to protect neuronal DNA integrity in vivo in adult mice under physiological and HS conditions. We designed an in vivo mouse model of hyperthermia/HS to induce a transient increase in ROS production in the brain. Comet and Terminal deoxyribonucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assays demonstrated that Tau protected genomic DNA in adult cortical and hippocampal neurons in vivo under physiological conditions in wild-type (WT) and Tau-deficient (KO-Tau) mice. HS increased DNA breaks in KO-Tau neurons. Notably, KO-Tau hippocampal neurons in the CA1 subfield restored DNA integrity after HS more weakly than the dentate gyrus (DG) neurons. The formation of phosphorylated histone H2AX foci, a double-strand break marker, was observed in KO-Tau neurons only after HS, indicating that Tau deletion did not trigger similar DNA damage under physiological or HS conditions. Moreover, genomic DNA and cytoplasmic and nuclear RNA integrity were altered under HS in hippocampal neurons exhibiting Tau deficiency, which suggests that Tau also modulates RNA metabolism. Our results suggest that Tau alterations lead to a loss of its nucleic acid safeguarding functions and participate in the accumulation of DNA and RNA oxidative damage observed in the Alzheimer’s disease (AD) brain. PMID:24672431

  4. 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

  5. Mechanisms of ranolazine's dual protection against atrial and ventricular fibrillation

    PubMed Central

    Verrier, Richard L.; Kumar, Kapil; Nieminen, Tuomo; Belardinelli, Luiz

    2013-01-01

    Coronary artery disease and heart failure carry concurrent risk for atrial fibrillation and life-threatening ventricular arrhythmias. We review evidence indicating that at therapeutic concentrations, ranolazine has potential for dual suppression of these arrhythmias. Mechanisms and clinical implications are discussed. PMID:23220484

  6. 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

  7. 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

  8. 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

  9. 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…

  10. 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

  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. 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.

  13. 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.

  14. 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. PMID:27193191

  15. 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.

  16. 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

  17. 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

  18. 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. PMID:25637747

  19. Thermal and mechanical responses of PBX 9501 under contact excitation under various driving intensities

    NASA Astrophysics Data System (ADS)

    Mares, J.; Miller, J.; Moore, D.; Groven, L.; Rhoads, J.; Son, S.

    2013-06-01

    The thermal and mechanical responses of a explosive (PBX 9501) and two non-energetic mock materials (900-21 and PBS 9501) under high-frequency mechanical excitation are presented with various driving intensities. Direct contact ultrasound transducers were used to excite samples through a frequency range of 50 kHz to 40 MHz. The mechanical response of each sample was approximated from a contact receiving transducer and trends were confirmed via laser Doppler vibrometry. The steady-state thermal response of the samples was measured at discrete excitation frequencies via infrared thermography. A maximum temperature rise of approximately 15 K was observed in PBX 9501, and the mock materials exhibited similar thermal characteristics. Temperature gradients were calculated to estimate the total heat generated within the samples due to the mechanical excitation. The active heating mechanisms were found to be highly dependent on the frequency of excitation. Possible mechanisms of heating at frequencies below 1 MHz are likely related to bulk motion. Above this frequency, the active heating mechanisms are likely related to particle-scale processes. The observed phenomena may prove useful in the aid of current trace vapor detection methods for explosives. Basic Research Challenge on ``Chemical decomposition in high energy density materials induced by coupled acoustic electromagnetic energy insult'' (through Grant No. N00014-11- 379 1-0466).

  20. 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.

  1. Crystal nucleation mechanism in melts of short polymer chains under quiescent conditions and under shear flow

    NASA Astrophysics Data System (ADS)

    Anwar, Muhammad; Berryman, Joshua T.; Schilling, Tanja

    2014-09-01

    We present a molecular dynamics simulation study of crystal nucleation from undercooled melts of n-alkanes, and we identify the molecular mechanism of homogeneous crystal nucleation under quiescent conditions and under shear flow. We compare results for n-eicosane (C20) and n-pentacontahectane (C150), i.e., one system below the entanglement length and one above, at 20%-30% undercooling. Under quiescent conditions, we observe that entanglement does not have an effect on the nucleation mechanism. For both chain lengths, the chains first align and then straighten locally, then the local density increases and finally positional ordering sets in. At low shear rates the nucleation mechanism is the same as under quiescent conditions, while at high shear rates the chains align and straighten at the same time. We report on the effects of shear rate and temperature on the nucleation rates and estimate the critical shear rates, beyond which the nucleation rates increase with the shear rate. In agreement with previous experimental observation and theoretical work, we find that the critical shear rate corresponds to a Weissenberg number of order 1. Finally, we show that the viscosity of the system is not affected by the crystalline nuclei.

  2. [The mechanisms of the thermal protective action of atsefen].

    PubMed

    Badyshtov, B A; Losev, A S; Sytnik, S I; Pastushenkov, V A; Makhnycheva, A L; Kolotilinskaia, N V; Mironov, S A; Seredenin, S B

    1995-01-01

    The study of thermoprotective properties of acephen (300 mg, single dosage) showed an increase (compared to that of placebo) in the maximum endurable time under thermal loading in healthy volunteers: optimization of evaporative heat exchange regime; reduction of the final values of reactive anxiety and fatigue and decrease in the rate of skin temperature growth. In combination with the data of biochemical analysis of peripheral blood which demonstrated positive changes in hormone, lipid, protein, and energy metabolism as well as in vegetative regulation, the results testify to a substantial thermoprotective potential of acephen attributed to the wide range of its pharmacological activity. PMID:8704597

  3. Coping styles and behavioural flexibility: towards underlying mechanisms

    PubMed Central

    Coppens, Caroline M.; de Boer, Sietse F.; Koolhaas, Jaap M.

    2010-01-01

    A coping style (also termed behavioural syndrome or personality) is defined as a correlated set of individual behavioural and physiological characteristics that is consistent over time and across situations. This relatively stable trait is a fundamental and adaptively significant phenomenon in the biology of a broad range of species, i.e. it confers differential fitness consequences under divergent environmental conditions. Behavioural flexibility appears to be an important underlying attribute or feature of the coping style that might explain consistency across situations. Proactive coping is characterized by low flexibility expressed as rather rigid, routine-like behavioural tendencies and reduced impulse control (behavioural inhibition) in operant conditioning paradigms. This article summarizes some of the evidence that individual differentiation in behavioural flexibility emerges as a function of underlying variability in the activation of a brain circuitry that includes the prefrontal cortex and its key neurochemical signalling pathways (e.g. dopaminergic and serotonergic input). We argue that the multidimensional nature of animal personality and the terminology used for the various dimensions should reflect the differential pattern of activation of the underlying neuronal network and the behavioural control function of its components. Accordingly, unravelling the molecular mechanisms that give rise to individual differences in the coping style will be an important topic in biobehavioural neurosciences, ecology and evolutionary biology. PMID:21078654

  4. Alert cell strategy: mechanisms of inflammatory response and organ protection.

    PubMed

    Hatakeyama, Noboru; Matsuda, Naoyuki

    2014-01-01

    Systemic inflammatory response syndrome (SIRS) is triggered by various factors such as surgical operation, trauma, burn injury, ischemia, pancreatitis and bacterial translocation. Sepsis is a SIRS associated with bacterial infection. SIRS and sepsis tend to trigger excessive production of inflammatory cytokines and other inflammatory molecules and induce multiple organ failure, such as acute lung injury, acute kidney injury and inflammatory cardiac injury. Epithelial and endothelial cells in some major organs express inflammatory receptors on the plasma membrane and work as alert cells for inflammation, and regulation of these alert cells could have a relieving effect on the inflammatory response. In inflammatory conditions, initial cardiac dysfunction is mediated by decreased preload and adequate infusion therapy is required. Tachyarrhythmia is a complication of inflammatory conditions and early control of the inflammatory reaction would prevent the structural remodeling that is resistant to therapies. Furthermore, there seems to be crosstalk between major organs with a central focus on the kidneys in inflammatory conditions. As an alert cell strategy, volatile anesthetics, sevoflurane and isoflurane, seem to have anti-inflammatory effects, and both experimental and clinical studies have shown the beneficial effects of these drugs in various settings of inflammatory conditions. On the other hand, in terms of intravenous anesthetics, propofol and ketamine, their current status is still controversial as there is a lack of confirmatory evidence on whether they have an organ-protective effect in inflammatory conditions. The local anesthetic lidocaine suppressed inflammatory responses upon both systemic and local administration. For the control of inflammatory conditions, anesthetic agents may be a target of drug development in accordance with other treatments and drugs. PMID:25229471

  5. Mechanisms of Cross-protection by Influenza Virus M2-based Vaccines

    PubMed Central

    Lee, Yu-Na; Kim, Min-Chul; Lee, Young-Tae; Kim, Yu-Jin

    2015-01-01

    Current influenza virus vaccines are based on strain-specific surface glycoprotein hemagglutinin (HA) antigens and effective only when the predicted vaccine strains and circulating viruses are well-matched. The current strategy of influenza vaccination does not prevent the pandemic outbreaks and protection efficacy is reduced or ineffective if mutant strains emerge. It is of high priority to develop effective vaccines and vaccination strategies conferring a broad range of cross protection. The extracellular domain of M2 (M2e) is highly conserved among human influenza A viruses and has been utilized to develop new vaccines inducing cross protection against different subtypes of influenza A virus. However, immune mechanisms of cross protection by M2e-based vaccines still remain to be fully elucidated. Here, we review immune correlates and mechanisms conferring cross protection by M2e-based vaccines. Molecular and cellular immune components that are known to be involved in M2 immune-mediated protection include antibodies, B cells, T cells, alveolar macrophages, Fc receptors, complements, and natural killer cells. Better understanding of protective mechanisms by immune responses induced by M2e vaccination will help facilitate development of broadly cross protective vaccines against influenza A virus. PMID:26557805

  6. Underlying Mechanisms in the Relationship Between Africentric Worldview and Depressive Symptoms

    PubMed Central

    Neblett, Enrique W.; Seaton, Eleanor K.; Hammond, Wizdom Powell; Townsend, Tiffany G.

    2010-01-01

    This study examines underlying mechanisms in the relationship between an Africentric worldview and depressive symptoms. Participants were 112 African American young adults. An Africentric worldview buffered the association between perceived stress and depressive symptoms. The relationship between an Africentric worldview and depressive symptoms was mediated by perceived stress and emotion-focused coping. These findings highlight the protective function of an Africentric worldview in the context of African Americans’ stress experiences and psychological health and offer promise for enhancing African American mental health service delivery and treatment interventions. PMID:20445815

  7. 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

  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. Mechanisms underlying skin disorders induced by EGFR inhibitors

    PubMed Central

    Holcmann, Martin; Sibilia, Maria

    2015-01-01

    The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is frequently mutated or overexpressed in a large number of tumors such as carcinomas or glioblastoma. Inhibitors of EGFR activation have been successfully established for the therapy of some cancers and are more and more frequently being used as first or later line therapies. Although the side effects induced by inhibitors of EGFR are less severe than those observed with classic cytotoxic chemotherapy and can usually be handled by out-patient care, they may still be a cause for dose reduction or discontinuation of treatment that can reduce the effectiveness of antitumor therapy. The mechanisms underlying these cutaneous side effects are only partly understood. Important questions, such as the reasons for the correlation between the intensity of the side effects and the efficiency of treatment with EGFR inhibitors, remain to be answered. Optimized adjuvant strategies to accompany anti-EGFR therapy need to be found for optimal therapeutic application and improved quality of life of patients. Here, we summarize current literature on the molecular and cellular mechanisms underlying the cutaneous side effects induced by EGFR inhibitors and provide evidence that keratinocytes are probably the optimal targets for adjuvant therapy aimed at alleviating skin toxicities. PMID:27308503

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Sound source mechanisms in under-expanded impinging jets

    NASA Astrophysics Data System (ADS)

    Sinibaldi, Giorgia; Marino, Luca; Romano, Giovanni Paolo

    2015-05-01

    Experiments on the aeroacoustics of an under-expanded supersonic jet impinging on a flat plate are presented and thoroughly discussed. A wide range of nozzle pressure ratios and of nozzle-to-plate distances has been analyzed with particular attention to the behavior of the discrete component of the noise. The investigation has been carried out by means of acoustic, particle image velocimetry and wall pressure measurements. The analysis of the relationship between the acoustic data and the fluid dynamic fields allows to examine the different source mechanisms of the discrete component of the noise and to evaluate the link between the jet flow structure and the acoustic tone features. Specifically, two ranges of nozzle pressure ratio have been observed showing different acoustic behaviors, characterized by distinct mechanisms of discrete noise generation. These regions are separated by a range of nozzle pressure ratios where impinging tones are not observed. The present experimental data extend previously published results, improving the analysis of the connection between fluid dynamic and acoustic fields and leading to a better comprehension of the impinging tone source mechanisms.

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

    SciTech Connect

    Maddocks, J.R.

    1995-05-01

    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 {minus}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.

  20. Mechanisms underlying ICU muscle wasting and effects of passive mechanical loading

    PubMed Central

    2012-01-01

    Introduction Critically ill ICU patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decreased quality of life for survivors. Critical illness myopathy (CIM) is a frequently observed neuromuscular disorder in ICU patients. Sepsis, systemic corticosteroid hormone treatment and post-synaptic neuromuscular blockade have been forwarded as the dominating triggering factors. Recent experimental results from our group using a unique experimental rat ICU model show that the mechanical silencing associated with CIM is the primary triggering factor. This study aims to unravel the mechanisms underlying CIM, and to evaluate the effects of a specific intervention aiming at reducing mechanical silencing in sedated and mechanically ventilated ICU patients. Methods Muscle gene/protein expression, post-translational modifications (PTMs), muscle membrane excitability, muscle mass measurements, and contractile properties at the single muscle fiber level were explored in seven deeply sedated and mechanically ventilated ICU patients (not exposed to systemic corticosteroid hormone treatment, post-synaptic neuromuscular blockade or sepsis) subjected to unilateral passive mechanical loading for 10 hours per day (2.5 hours, four times) for 9 ± 1 days. Results These patients developed a phenotype considered pathognomonic of CIM; that is, severe muscle wasting and a preferential myosin loss (P < 0.001). In addition, myosin PTMs specific to the ICU condition were observed in parallel with an increased sarcolemmal expression and cytoplasmic translocation of neuronal nitric oxide synthase. Passive mechanical loading for 9 ± 1 days resulted in a 35% higher specific force (P < 0.001) compared with the unloaded leg, although it was not sufficient to prevent the loss of muscle mass. Conclusion Mechanical silencing is suggested to be a primary mechanism underlying CIM; that is

  1. 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

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Special rules governing certain information obtained under the Marine Protection, Research and Sanctuaries Act of 1972. 2.309 Section 2.309 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PUBLIC INFORMATION Confidentiality of Business Information § 2.309 Special...

  2. 40 CFR 2.309 - Special rules governing certain information obtained under the Marine Protection, Research and...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Special rules governing certain information obtained under the Marine Protection, Research and Sanctuaries Act of 1972. 2.309 Section 2.309 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PUBLIC INFORMATION Confidentiality of Business Information § 2.309 Special...

  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. Protecting resources for primary health care under fiscal federalism: options for resource allocation.

    PubMed

    Okorafor, Okore A; Thomas, Stephen

    2007-11-01

    The introduction of fiscal federalism or decentralization of functions to lower levels of government is a reform not done primarily with health sector concerns. A major concern for the health sector is that devolution of expenditure responsibilities to sub-national levels of government can adversely affect the equitable distribution of financial resources across local jurisdictions. Since the adoption of fiscal federalism in South Africa, progress towards achieving a more equitable distribution of public sector health resources (financial) has slowed down considerably. This study attempts to identify appropriate resource allocation mechanisms under the current South African fiscal federal system that could be employed to promote equity in primary health care (PHC) allocations across provinces and districts. The study uses data from interviews with government officials involved in the budgeting and resource allocation process for PHC, literature on fiscal federalism and literature on international experience to inform analysis and recommendations. The results from the study identify historical incremental budgeting, weak managerial capacity at lower levels of government, poor accounting of PHC expenditure, and lack of protection for PHC funds as constraints to the realization of a more equitable distribution of PHC allocations. Based on interview data, no one resource allocation mechanism received unanimous support from stakeholders. However, the study highlights the particularly high level of autonomy enjoyed by provincial governments with regards to decision making for allocations to health and PHC services as the major constraint to achieving a more equitable distribution of PHC resources. The national government needs to have more involvement in decision making for resource allocation to PHC services if significant progress towards equity is to be achieved. PMID:18006526

  5. Flaw tolerance of nuclear intermediate filament lamina under extreme mechanical deformation.

    PubMed

    Qin, Zhao; Buehler, Markus J

    2011-04-26

    The nuclear lamina, composed of intermediate filaments, is a structural protein meshwork at the nuclear membrane that protects genetic material and regulates gene expression. Here we uncover the physical basis of the material design of nuclear lamina that enables it to withstand extreme mechanical deformation of >100% strain despite the presence of structural defects. Through a simple in silico model we demonstrate that this is due to nanoscale mechanisms including protein unfolding, alpha-to-beta transition, and sliding, resulting in a characteristic nonlinear force-extension curve. At the larger microscale this leads to an extreme delocalization of mechanical energy dissipation, preventing catastrophic crack propagation. Yet, when catastrophic failure occurs under extreme loading, individual protein filaments are sacrificed rather than the entire meshwork. This mechanism is theoretically explained by a characteristic change of the tangent stress-strain hardening exponent under increasing strain. Our results elucidate the large extensibility of the nuclear lamina within muscle or skin tissue and potentially many other protein materials that are exposed to extreme mechanical conditions, and provide a new paradigm toward the de novo design of protein materials by engineering the nonlinear stress-strain response to facilitate flaw-tolerant behavior. PMID:21384869

  6. 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

    ... 25 Indians 1 2011-04-01 2011-04-01 false Under what authority are Indian child protection and..., 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, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Under what authority are Indian child protection and..., 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. 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

    ... 25 Indians 1 2013-04-01 2013-04-01 false Under what authority are Indian child protection and..., 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...

  9. 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. PMID:26786065

  10. Breast cancer prevention: lessons to be learned from mechanisms of early pregnancy-mediated breast cancer protection.

    PubMed

    Meier-Abt, Fabienne; Bentires-Alj, Mohamed; Rochlitz, Christoph

    2015-03-01

    Pregnancy at early, but not late age, has a strong and life-long protective effect against breast cancer. The expected overall increase in breast cancer incidence demands the development of a pharmaceutical mimicry of early-age pregnancy-mediated protection. Recently, converging results from rodent models and women on molecular and cellular mechanisms underlying the protective effect of early-age pregnancy have opened the door for translational studies on pharmacologic prevention against breast cancer. In particular, alterations in Wnt and TGFβ signaling in mammary stem/progenitor cells reveal new potential targets for preventive interventions, and thus might help to significantly reduce the incidence of breast cancer in the future. PMID:25660950

  11. 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

  12. 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

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

    PubMed

    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 1H 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. PMID:22426360

  15. CCL7 Is a Protective Factor Secreted by Mechanically Loaded Osteocytes

    PubMed Central

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

    2014-01-01

    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. PMID:25274752

  16. 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. PMID:25274752

  17. 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... Investigations for Relief From Market Disruption § 206.47 Limited disclosure of certain confidential...

  18. 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... Investigations For Action in Response to Trade Diversion; Reviews of Action Taken § 206.66 Limited disclosure...

  19. 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... Investigations Relating to Bilateral Safeguard Actions § 206.37 Limited disclosure of certain...

  20. 19 CFR 206.17 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... business information under administrative protective order. 206.17 Section 206.17 Customs Duties UNITED... Investigations Relating to Global Safeguard Actions § 206.17 Limited disclosure of certain confidential business... confidential business information properly disclosed pursuant to this section for the purpose of...

  1. 19 CFR 206.17 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... business information under administrative protective order. 206.17 Section 206.17 Customs Duties UNITED... Investigations Relating to Global Safeguard Actions § 206.17 Limited disclosure of certain confidential business... confidential business information properly disclosed pursuant to this section for the purpose of...

  2. 19 CFR 206.17 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... business information under administrative protective order. 206.17 Section 206.17 Customs Duties UNITED... Investigations Relating to Global Safeguard Actions § 206.17 Limited disclosure of certain confidential business... confidential business information properly disclosed pursuant to this section for the purpose of...

  3. 19 CFR 206.17 - 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. 206.17 Section 206.17 Customs Duties UNITED... Investigations Relating to Global Safeguard Actions § 206.17 Limited disclosure of certain confidential business... confidential business information properly disclosed pursuant to this section for the purpose of...

  4. 19 CFR 206.17 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... business information under administrative protective order. 206.17 Section 206.17 Customs Duties UNITED... Investigations Relating to Global Safeguard Actions § 206.17 Limited disclosure of certain confidential business... confidential business information properly disclosed pursuant to this section for the purpose of...

  5. 19 CFR 206.66 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 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...

  6. 19 CFR 206.47 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 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...

  7. Improving Child Protection Services to Children under Ten Who Display Sexually Reactive Behaviors.

    ERIC Educational Resources Information Center

    Verstraete, Patricia A.

    This practicum was designed to improve Child Protective Services in a western state to sexually reactive children under the age of 10 by targeting four areas of the service delivery system: screening, assessment, treatment, and foster care. A panel of agency staff from all service areas researched, designed, proposed, and implemented changes…

  8. 77 FR 44121 - Procedures for the Handling of Retaliation Complaints Under the Employee Protection Provision of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-27

    ...This document provides the final text of regulations governing employee protection (or ``whistleblower'') claims under the Surface Transportation Assistance Act of 1982 (STAA), as amended, implementing statutory changes to STAA enacted into law on August 3, 2007, as part of the Implementing Recommendations of the 9/11 Commission Act of 2007. On August 31, 2010, the Occupational Safety and......

  9. 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...

  10. 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

  11. Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives

    PubMed Central

    Linhart, Birgit; Valenta, Rudolf

    2015-01-01

    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. PMID:22100888

  12. 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

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

    PubMed Central

    Klein, Alice Victoria; Kiat, Hosen

    2015-01-01

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

  14. 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

  15. Lifestyle, health and disease prevention: the underlying mechanisms.

    PubMed

    Weisburger, J H

    2002-08-01

    International studies in geographic pathology provide background information that a disease may have a quite different incidence and resulting mortality as a function of area of residence. Investigations in animals can model fairly precisely what is learned through such international research, and provide the basis for examining relevant hypotheses and, more importantly, possible mechanisms of action. These approaches can yield public health recommendations and health promotion activities. Regular intake of foods rich in saturated fats, such as meat and certain dairy products, raises the risk of coronary heart disease, especially in smokers. The total mixed fat intake is associated with a higher incidence of the nutritionally linked cancers (i.e. of the postmenopausal breast, distal colon, prostate, pancreas, ovary and endometrium). Monounsaturated oils, such as olive or canola oil, are low-risk fats, as shown in animal models, and through the finding that the incidence of coronary heart and neoplastic diseases is lower in the Mediterranean region, where such oils are customarily used. Fish and fish oils are protective. The associated genotoxic carcinogens for several of these cancers, and also in heart disease causation, are heterocyclic amines, produced during the broiling and frying of creatinine-containing foods such as meats. Excessive salt intake is associated with high blood pressure and with stomach cancer, especially with inadequate intake of potassium, from fruits and vegetables, and calcium from certain vegetables and low-fat dairy products. Bran cereal fiber intake, especially with adequate calcium, yields an increased stool bulk, eliminating factors involved in colon and breast cancer. Vegetables and fruits, as well as soy products, are rich in antioxidants that are essential to lower disease risk stemming from reactive oxygen species in the body. Green and black tea are excellent sources of such beneficial antioxidants of a polyphenol nature, as are

  16. 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

  17. 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

  18. Neurosubstrates and mechanisms underlying the extinction of associative motor memory.

    PubMed

    Hu, Chen; Zhang, Li-Bin; Chen, Hao; Xiong, Yan; Hu, Bo

    2015-12-01

    Eyeblink conditioning is one of the most commonly used model systems to investigate the neural mechanisms underlying associative motor learning. It is well established that the acquisition and retention of conditioned eyeblink responses (CRs) involve neural plasticity in both the cerebellar cortex and deep cerebellar nuclei (DCN). Nevertheless, how learned CRs are extinguished remains relatively unclear. It has been suggested that extinguished CRs can recur spontaneously, can reappear by exposure to certain stimuli, and can be reacquired in fewer training trials than originally needed, indicating that associative motor memory is not merely erased by extinction training. Instead, the motor memory is preserved to some degree. Herein, we reviewed recent experimental findings demonstrating that the cerebellum subserves the preservation of learned CRs. In addition, several lines of evidence have suggested that forebrain structures (i.e., the medial prefrontal cortex and hippocampus) are involved in the CR extinction. We proposed possible mechanisms related to how preserved motor memory in the cerebellum is inhibited by the forebrain structures via the amygdalar complex. PMID:26209112

  19. Simulation of Electrical Transport in Rocks under Mechanical Action

    NASA Astrophysics Data System (ADS)

    Salgueiro da Silva, M. A.; Seixas, T. M.

    2015-12-01

    Rock's electrical properties can be changed by mechanical action, especially when deformation is accompanied by micro-fracturing processes. Knowing how electrical charge is generated in inelastically deformed rocks, the nature and properties of the generated charge carriers, and their spatial distribution and propagation is crucial to gain insight into the origin of seismo-electromagnetic signals. In this work, we describe briefly a model for the numerical simulation of electrical transport in rocks under mechanical action, assuming that high and low mobility charge carriers of opposite signs can be simultaneously generated by micro-fracturing processes and recombine, diffuse and drift across the sample rock. The electrical behavior can then be described using an adaptation of the formalism applied to semiconductors. We provide simulation results on a one-dimensional lattice using finite-difference discretization. Our results show that a large mobility contrast among charge carriers allows charge separation inside the deformation region, which leads to the formation of charged layers of alternate signs. Inside these layers, rapid electric field variations are observed which can lead to the emission of electromagnetic radiation. With proper positioning of current electrodes inside the deformation region, it is possible to collect electrical current even without any applied voltage. We discuss our results in the light of available experimental results on the generation of electrical and electromagnetic signals in deformed rocks.

  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. 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

  2. Mechanisms underlying the impacts of exotic plant invasions.

    PubMed Central

    Levine, Jonathan M; Vilà, Montserrat; D'Antonio, Carla M; Dukes, Jeffrey S; Grigulis, Karl; Lavorel, Sandra

    2003-01-01

    Although the impacts of exotic plant invasions on community structure and ecosystem processes are well appreciated, the pathways or mechanisms that underlie these impacts are poorly understood. Better exploration of these processes is essential to understanding why exotic plants impact only certain systems, and why only some invaders have large impacts. Here, we review over 150 studies to evaluate the mechanisms underlying the impacts of exotic plant invasions on plant and animal community structure, nutrient cycling, hydrology and fire regimes. We find that, while numerous studies have examined the impacts of invasions on plant diversity and composition, less than 5% test whether these effects arise through competition, allelopathy, alteration of ecosystem variables or other processes. Nonetheless, competition was often hypothesized, and nearly all studies competing native and alien plants against each other found strong competitive effects of exotic species. In contrast to studies of the impacts on plant community structure and higher trophic levels, research examining impacts on nitrogen cycling, hydrology and fire regimes is generally highly mechanistic, often motivated by specific invader traits. We encourage future studies that link impacts on community structure to ecosystem processes, and relate the controls over invasibility to the controls over impact. PMID:12737654

  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. PMID:27247385

  4. Different Neurophysiological Mechanisms Underlying Word and Rule Extraction from Speech

    PubMed Central

    De Diego Balaguer, Ruth; Toro, Juan Manuel; Rodriguez-Fornells, Antoni; Bachoud-Lévi, Anne-Catherine

    2007-01-01

    The initial process of identifying words from spoken language and the detection of more subtle regularities underlying their structure are mandatory processes for language acquisition. Little is known about the cognitive mechanisms that allow us to extract these two types of information and their specific time-course of acquisition following initial contact with a new language. We report time-related electrophysiological changes that occurred while participants learned an artificial language. These changes strongly correlated with the discovery of the structural rules embedded in the words. These changes were clearly different from those related to word learning and occurred during the first minutes of exposition. There is a functional distinction in the nature of the electrophysiological signals during acquisition: an increase in negativity (N400) in the central electrodes is related to word-learning and development of a frontal positivity (P2) is related to rule-learning. In addition, the results of an online implicit and a post-learning test indicate that, once the rules of the language have been acquired, new words following the rule are processed as words of the language. By contrast, new words violating the rule induce syntax-related electrophysiological responses when inserted online in the stream (an early frontal negativity followed by a late posterior positivity) and clear lexical effects when presented in isolation (N400 modulation). The present study provides direct evidence suggesting that the mechanisms to extract words and structural dependencies from continuous speech are functionally segregated. When these mechanisms are engaged, the electrophysiological marker associated with rule-learning appears very quickly, during the earliest phases of exposition to a new language. PMID:18000546

  5. 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

  6. 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. PMID:25814263

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

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

    PubMed Central

    Silverman, Marni N.; Deuster, Patricia A.

    2014-01-01

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

  14. 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

  15. 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.

  16. 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

  17. 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. PMID:26271146

  18. Proteomic Analysis of Ketogulonicigenium vulgare under Glutathione Reveals High Demand for Thiamin Transport and Antioxidant Protection

    PubMed Central

    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. PMID:22384164

  19. 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

  20. 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

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

    PubMed

    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

  2. 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

  3. 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

  4. Mechanism Underlying Levofloxacin Uptake by Human Polymorphonuclear Neutrophils

    PubMed Central

    Vazifeh, Doina; Bryskier, André; Labro, Marie-Thérèse

    1999-01-01

    The mechanism of radiolabeled levofloxacin ([3H]levofloxacin) uptake by human polymorphonuclear neutrophils (PMNs) was investigated by a classical velocity centrifugation technique. PMNs were incubated with levofloxacin for 5 to 180 min under various conditions before centrifugation through an oil cushion. Radioactivity was measured in the cell pellet to determine the amount of cell-associated drug. The uptake of levofloxacin was moderate with a cellular concentration/extracellular concentration ratio of about 4 to 6. Levofloxacin accumulated in PMNs parallel to the extracellular concentration, without saturation, over the range of 2.5 to 200 mg/liter (linear regression analysis: r = 0.92; P < 0.001). The activation energy was low (36 ± 7.2 kJ/mol). Levofloxacin uptake was increased in Ca2+-depleted, EGTA-containing medium by approximately 33% (P = 0.022), while Ni2+, a Ca2+ channel inhibitor, inhibited it in a concentration-dependent manner, with the concentration that inhibited 50% of control uptake being approximately 2.65 mM. Verapamil (an l-type Ca2+ channel inhibitor) and other pharmacologic agents which modify Ca2+ homeostasis did not modify levofloxacin uptake. Interestingly, Ca2+ and Mg2+ inhibited levofloxacin uptake in a concentration-dependent manner. EGTA, Ni2+, and verapamil did not modify levofloxacin efflux; thapsigargin, a Ca2+ pool-releasing agent, modestly increased the intracellular retention of levofloxacin. In addition, contrary to other fluoroquinolones, probenecid at 1 to 10 mM did not modify either levofloxacin uptake or efflux. These data are consistent with a mechanism of passive accumulation of levofloxacin in PMNs. Extracellular Ca2+ and Mg2+ may influence the structural conformation of levofloxacin or the lipophilicity of PMN membranes, thus explaining their effect on levofloxacin uptake. PMID:9925513

  5. 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

  6. 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.

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

    PubMed

    Chai, Herzl

    2014-11-01

    The mechanical properties of tooth enamel generally exhibit large variations, which reflect its structural and material complexity. Some key properties were evaluated under localized contact, simulating actual functioning conditions. Prominent cusps of extracted human molar teeth were polished down ~0.7 mm below the cusp tip and indented by tungsten carbide balls. The internal damage was assessed after unloading from longitudinal or transverse sections. The ultimate tensile stress (UTS) was determined using a novel bilayer specimen. The damage is characterized by penny-like radial cracks driven by hoop stresses and cylindrical cracks driven along protein-rich interrod materials by shear stresses. Shallow cone cracks typical of homogeneous materials which may cause rapid tooth wear under repeat contact are thus avoided. The mean stress vs. indentation strain curve is highly nonlinear, attributable to plastic shearing of protein between and within enamel rods. This curve is also affected by damage, especially radial cracks, the onset of which depends on ball radius. Several material properties were extracted from the tests, including shear strain at the onset of ring cracks γ(F) (=0.14), UTS (=119 MPa), toughness K(C) (=0.94 MPa m(1/2)), a crack propagation law and a constitutive response determined by trial and error with the aid of a finite-element analysis. These quantities, which are only slightly sensitive to anatomical location within the enamel region tested, facilitate a quantitative assessment of crown failure. Causes for variations in published UTS and K(C) values are discussed. PMID:25034644

  8. 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.

  9. Different intra- and interspecific facilitation mechanisms between two Mediterranean trees under a climate change scenario.

    PubMed

    Gimeno, Teresa E; Escudero, Adrián; Valladares, Fernando

    2015-01-01

    In harsh environments facilitation alleviates biotic and abiotic constraints on tree recruitment. Under ongoing drier climate change, we expect facilitation to increase as a driver of coexistence. However, this might not hold under extreme abiotic stress and when the outcome depends on the interaction with other drivers such as altered herbivore pressure due to land use change. We performed a field water-manipulation experiment to quantify the importance of facilitation in two coexisting Mediterranean trees (dominant Juniperus thurifera and coexisting Quercus ilex subsp. ballota) under a climate change scenario. Shifts in canopy dominance favouring Q. ilex could be based on the extension of heterospecific facilitation to the detriment of conspecific alleviation. We found that saplings of both species transplanted under the canopy of nurse trees had greater survival probability, growth and photochemical efficiency. Intra- and interspecific facilitation mechanisms differed: alleviation of abiotic stress benefited both species during summer and J. thurifera during winter, whereas browsing protection was relevant only for Q. ilex. Facilitation was greater under the dry treatment only for Q. ilex, which partially agreed with the predictions of the stress gradient hypothesis. We conclude that present rainfall availability limits neither J. thurifera nor Q. ilex establishment. Nevertheless, under current global change scenarios, imposing increasing abiotic stress together with altered herbivore browsing, nurse trees could differentially facilitate the establishment of Q. ilex due to species-specific traits, i.e. palatability; drought, heat and cold tolerance, underlying species differences in the facilitation mechanisms and eventually triggering a change from pure juniper woodlands to mixed formations. PMID:25354713

  10. 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.

  11. Mechanisms underlying subunit independence in pyramidal neuron dendrites.

    PubMed

    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. 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

  13. CFRP Mechanical Anchorage for Externally Strengthened RC Beams under Flexure

    NASA Astrophysics Data System (ADS)

    Ali, Alnadher; Abdalla, Jamal; Hawileh, Rami; Galal, Khaled

    De-bonding of carbon fiber reinforced polymers (CFRP) sheets and plates from the concrete substrate is one of the major reasons behind premature failures of beams that are externally strengthened with such CFRP materials. To delay or prevent de-bonding and therefore enhancing the load carrying capacity of strengthened beams, several anchorage systems were developed and used. This paper investigates the use of CFRP mechanical anchorage of CFRP sheets and plates used to externally strengthen reinforced concrete beams under flexure. The pin-and-fan shape CFRP anchor, which is custom-made from typical rolled fiber sheets and bundles of loose fiber is used. Several reinforced concrete beams were casted and tested in standard four-point bending scheme to study the effectiveness of this anchorage system. The beams were externally strengthened in flexure with bonded CFRP sheets and plates and then fastened to the soffit of the beams' using various patterns of CFRP anchors. It is observed that the CFRP plates begins to separate from the beams as soon as de-bonding occurs in specimens without CFRP anchors, while in beams with CFRP anchors de-bonding was delayed leading to increase in the load carrying capacity over the un-anchored strengthened beams.

  14. Mechanism of magnetic moment collapse under pressure in ferropericlase

    NASA Astrophysics Data System (ADS)

    Skorikov, N. A.; Shorikov, A. O.; Skornyakov, S. L.; Korotin, M. A.; Anisimov, V. I.

    2015-07-01

    We propose a new scenario for the magnetic collapse under pressure in ferropericlase (FP) (\\text{F}{{\\text{e}}1/4}\\text{M}{{\\text{g}}3/4} )O without the presence of intermediate spin state, which contradicts the mechanism proposed in (2013 Phys. Rev. B 87 165113). This scenario is supported by results of combined local density approximation + dynamical mean-field theory method calculations for the paramagnetic phase at ambient and high pressures. At ambient pressure, calculation gave (\\text{F}{{\\text{e}}1/4}\\text{M}{{\\text{g}}3/4} )O as an insulator with Fe 3d-shell in high-spin state. Experimentally observed high-spin to low-spin state transition of the \\text{F}{{\\text{e}}2+} ion in the pressure range of 35-75 GPa is successfully reproduced in our calculations. The spin crossover is characterized by coexistence of \\text{F}{{\\text{e}}2+} ions in high and low spin state but intermediate spin state is absent in the whole pressure range. Moreover, the probability of Fe ion {{\\text{d}}7} configuration with S=1 grows with pressure due to shortening of metal-oxygen distance. Also, no metal-insulator transition was obtained up to the pressure 140 GPa in agreement with experiment.

  15. Neural mechanisms underlying respiratory rhythm generation in the lamprey.

    PubMed

    Bongianni, Fulvia; Mutolo, Donatella; Cinelli, Elenia; Pantaleo, Tito

    2016-04-01

    The isolated brainstem of the adult lamprey spontaneously generates respiratory activity. The paratrigeminal respiratory group (pTRG), the proposed respiratory central pattern generator, has been anatomically and functionally characterized. It is sensitive to opioids, neurokinins and acetylcholine. Excitatory amino acids, but not GABA and glycine, play a crucial role in the respiratory rhythmogenesis. These results are corroborated by immunohistochemical data. While only GABA exerts an important modulatory control on the pTRG, both GABA and glycine markedly influence the respiratory frequency via neurons projecting from the vagal motoneuron region to the pTRG. Noticeably, the removal of GABAergic transmission within the pTRG causes the resumption of rhythmic activity during apnea induced by blockade of glutamatergic transmission. The same result is obtained by microinjections of substance P or nicotine into the pTRG during apnea. The results prompted us to present some considerations on the phylogenesis of respiratory pattern generation. They may also encourage comparative studies on the basic mechanisms underlying respiratory rhythmogenesis of vertebrates. PMID:25220696

  16. [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

  17. Decompaction mechanism of deep crystalline rocks under stress relief

    NASA Astrophysics Data System (ADS)

    Gorbatsevich, F. F.

    2003-07-01

    Within a geological massif in a stable geodynamical situation contacts on the grain boundaries in polycrystalline rocks at great depths are continuous and firm. The stress release of those rocks during drilling and excavation to the surface is accompanied by their disintegration (decompaction). The reason for the decompaction is generation of microcracks during stress release due to the difference between the elastic moduli of crystalline grains at their contacts. The mechanism of decompaction may occur not only in polymineral but in polycrystalline rocks as well. The method of decompaction evaluation of deep crystalline rocks under stress relief is presented. According to the calculations the initial manifestation of the decompaction effect in biotite gneisses will occur when they are extracted from the deep range of 0.8-1 km. The first microcracks arise on the grain borders between quartz-biotite and oligoclase-biotite. It is shown that the uplift of gneiss-granite varities of the rocks cut by the Kola superdeep borehole from depths exceeding 13-15 km will be possible in a form of separate mineral grains. Practical importance of the presented method is in an opportunity to evaluate the level of excavated decompaction. The method allow estimating the depth, from which the rock will be extracted only in a sludge form.

  18. Mechanical degradation of fuel cell membranes under fatigue fracture tests

    NASA Astrophysics Data System (ADS)

    Khorasany, Ramin M. H.; Sadeghi Alavijeh, Alireza; Kjeang, Erik; Wang, G. G.; Rajapakse, R. K. N. D.

    2015-01-01

    The effects of cyclic stresses on the fatigue and mechanical stability of perfluorosulfonic acid (PFSA) membranes are experimentally investigated under standard fuel cell conditions. The experiments are conducted ex-situ by subjecting membrane specimens to cyclic uniaxial tension at controlled temperature and relative humidity. The fatigue lifetime is measured in terms of the number of cycles until ultimate fracture. The results indicate that the membrane fatigue lifetime is a strong function of the applied stress, temperature, and relative humidity. The fatigue life increases exponentially with reduced stresses in all cases. The effect of temperature is found to be more significant than that of humidity, with reduced fatigue life at high temperatures. The maximum membrane strain at fracture is determined to decrease exponentially with increasing membrane lifetime. At a given fatigue life, a membrane exposed to fuel cell conditions is shown to accommodate more plastic strain before fracture than one exposed to room conditions. Overall, the proposed ex-situ membrane fatigue experiment can be utilized to benchmark the fatigue lifetime of new materials in a fraction of the time and cost associated with conventional in-situ accelerated stress testing methods.

  19. 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

  20. Psychophysiological mechanisms underlying response selection in multidimensional space

    PubMed Central

    Mückschel, Moritz; Beste, Christian

    2015-01-01

    In the outside world, response selection often requires the processing of information from different spatial dimensions. Yet, most neuroscientific approaches to the topic only employ variations in one dimension, namely the horizontal left-right axis. Hence, virtually nothing is known about the neuronal mechanisms underlying response selection in more than one dimension. We investigated this aspect with the help of a two-dimensional flanker task using EEG and source localization techniques. The data shows that response selection processes are differentially modulated across different dimensions. However, this modulation is restricted to conditions imposing increased demands on response selection. In such situations, a distributed fronto-parietal network mediates intensified conflict monitoring processes as well as response inhibition processes. In case response selection is carried out in the horizontal dimension, those brain areas are more active than during response selection in the vertical dimension. Attentional selection processes were not affected. The study's findings are of relevance to our understanding to everyday functioning where response selection is usually carried out in two or three dimensions and not a single dimension as usually investigated in cognitive neuroscience. PMID:25582443

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

    PubMed

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

    2014-03-01

    As an essential plant macronutrient, the low availability of phosphorus (P) in most soils imposes serious limitation on crop production. Plants have evolved complex responsive and adaptive mechanisms for acquisition, remobilization and recycling of phosphate (Pi) to maintain P homeostasis. Spatio-temporal molecular, physiological, and biochemical Pi deficiency responses developed by plants are the consequence of local and systemic sensing and signaling pathways. Pi deficiency is sensed locally by the root system where hormones serve as important signaling components in terms of developmental reprogramming, leading to changes in root system architecture. Root-to-shoot and shoot-to-root signals, delivered through the xylem and phloem, respectively, involving Pi itself, hormones, miRNAs, mRNAs, and sucrose, serve to coordinate Pi deficiency responses at the whole-plant level. A combination of chromatin remodeling, transcriptional and posttranslational events contribute to globally regulating a wide range of Pi deficiency responses. In this review, recent advances are evaluated in terms of progress toward developing a comprehensive understanding of the molecular events underlying control over P homeostasis. Application of this knowledge, in terms of developing crop plants having enhanced attributes for P use efficiency, is discussed from the perspective of agricultural sustainability in the face of diminishing global P supplies. PMID:24417933

  2. 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

  3. 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. PMID:20017730

  4. 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

  5. Formation and Evaluation of Protective Layer over Magnesium Melt Under CO2/Air Mixtures

    NASA Astrophysics Data System (ADS)

    Emami, Samar; Sohn, Hong Yong

    2015-02-01

    Molten magnesium oxidizes rapidly when exposed to air causing melt loss and handling difficulties. The use of certain additive gases to form a protective MgO layer over a magnesium melt has been proposed. The oxidation behavior of molten magnesium in air that contains various concentrations of CO2 was investigated, including the kinetics of the oxide layer growth. Experiments were performed using a thermogravimetric analysis unit in the temperature range of 943 K to 1043 K (670 °C to 770 °C). Results showed that a thin, coherent, and protective MgO-C layer was formed under the test conditions. The thicknesses of this layer formed under CO2/air ranged from 500 nm to 12 μm. Rate parameters were calculated and a model for the process was developed. The morphology and composition of the surface films were studied using SEM and EDS.

  6. 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

  7. 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

    ... 25 Indians 1 2010-04-01 2010-04-01 false Under what authority are Indian child protection and 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...

  8. 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... Protection, Research and Sanctuaries Act of 1972. (a) Definitions. For the purposes of this section: (1) Act means the Marine Protection, Research and Sanctuaries Act of 1972, 33 U.S.C. 1401 et seq. (2)...

  9. Parylene coatings on stainless steel 316L surface for medical applications--mechanical and protective properties.

    PubMed

    Cieślik, Monika; Kot, Marcin; Reczyński, Witold; Engvall, Klas; Rakowski, Wiesław; Kotarba, Andrzej

    2012-01-01

    The mechanical and protective properties of parylene N and C coatings (2-20 μm) on stainless steel 316L implant materials were investigated. The coatings were characterized by scanning electron and confocal microscopes, microindentation and scratch tests, whereas their protective properties were evaluated in terms of quenching metal ion release from stainless steel to simulated body fluid (Hanks solution). The obtained results revealed that for parylene C coatings, the critical load for initial cracks is 3-5 times higher and the total metal ions release is reduced 3 times more efficiently compared to parylene N. It was thus concluded that parylene C exhibits superior mechanical and protective properties for application as a micrometer coating material for stainless steel implants. PMID:23177768

  10. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

    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.

  12. 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.

  13. 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

  14. 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.

  15. Cellular mechanisms underlying the pharmacological induction of phosphenes

    PubMed Central

    Cervetto, L; Demontis, G C; Gargini, C

    2007-01-01

    Visual sensations evoked by stimuli other than luminance changes are called phosphenes. Phosphenes may be an early symptom in a variety of diseases of the retina or of the visual pathways, but healthy individuals may perceive them as well. Phosphene-like phenomena are perhaps the most common side effect reported in clinical pharmacology. Ivabradine, a novel anti-anginal drug that reduces heart-rate by inhibiting the hyperpolarization activated current expressed in cardiac sinoatrial node cells (If) induces phosphenes in some patients. One hypothesis is that ivabradine interacts with the visual system by inhibiting hyperpolarization-activated current in retinal cells (Ih). An Ih current with properties similar to cardiac If has been reported in retinal neurones. Under normal circumstances most of the random fluctuations generated within the retinal circuits do not reach the level of conscious perception because they are filtered out. Presumably, filtering occurs mostly within the retina and one serious candidate for this action is the ability of Ih to act as a negative-feedback mechanism. Ih activation in the membrane of visual cells causes dampening of responses to slow noisy inputs thus tuning the visual system to perceptually more relevant signals of higher frequency. Ih inhibition, by altering at the retinal synapses the filtering of signals generated by thermal breakdown of rhodopsin or other fluctuations, is expected to increase the probability of phosphene occurrence. It is the purpose of the present paper to outline and discuss the features of the visual system and the pharmacological conditions relevant to phosphene perception. PMID:17211458

  16. 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

  17. Mechanisms of enhanced taurine release under Ca2+ depletion.

    PubMed

    Molchanova, Svetlana M; Oja, Simo S; Saransaari, Pirjo

    2005-10-01

    The sulfur-containing amino acid taurine is an inhibitory neuromodulator in the brain of mammals, as well as a key substance in the regulation of cell volumes. The effect of Ca(2+) on extracellular taurine concentrations is of special interest in the context of the regulatory mechanisms of taurine release. The aim of this study was to characterize the basal release of taurine in Ca(2+)-free medium using in vivo microdialysis of the striatum of anesthetized rats. Perfusion of Ca(2+)-free medium via a microdialysis probe evoked a sustained release of taurine (up to 180 % compared to the basal levels). The Ca(2+) chelator EGTA (1mM) potentiated Ca(2+) depletion-evoked taurine release. The substitution of CaCl(2) by choline chloride did not alter the observed effect. Ca(2+)-free solution did not significantly evoke release of taurine from tissue loaded with the competitive inhibitor of taurine transporter guanidinoethanesulfonate (1mM), suggesting that in Ca(2+) depletion taurine is released by the transporter operating in the outward direction. The volume-sensitive chloride channel blocker diisothiocyanostilbene-2,2'-disulfonate (1mM) did not attenuate the taurine release evoked by Ca(2+) depletion. The non-specific blocker of voltage-sensitive Ca(2+) channels NiCl(2) (0.65 mM) enhanced taurine release in the presence of Ca(2+). CdCl(2) (0.25 mM) had no effect under these conditions. However, both CdCl(2) and NiCl(2) attenuated the effect of Ca(2+)-free medium on the release of taurine. The data obtained imply the involvement of both decreased influx of Ca(2+) and increased non-specific influx of Na(+) through voltage-sensitive calcium channels in the regulation of transporter-mediated taurine release in Ca(2+) depletion. PMID:15982785

  18. Neural Mechanisms Underlying Compensatory and Noncompensatory Strategies in Risky Choice.

    PubMed

    Van Duijvenvoorde, Anna C K; Figner, Bernd; Weeda, Wouter D; Van der Molen, Maurits W; Jansen, Brenda R J; Huizenga, Hilde M

    2016-09-01

    Individuals may differ systematically in their applied decision strategies, which has critical implications for decision neuroscience but is yet scarcely studied. Our study's main focus was therefore to investigate the neural mechanisms underlying compensatory versus noncompensatory strategies in risky choice. Here, we compared people using a compensatory expected value maximization with people using a simplified noncompensatory loss-minimizing choice strategy. To this end, we used a two-choice paradigm including a set of "simple" items (e.g., simple condition), in which one option was superior on all attributes, and a set of "conflict" items, in which one option was superior on one attribute but inferior on other attributes. A binomial mixture analysis of the decisions elicited by these items differentiated between decision-makers using either a compensatory or a noncompensatory strategy. Behavioral differences were particularly pronounced in the conflict condition, and these were paralleled by neural results. That is, we expected compensatory decision-makers to use an integrated value comparison during choice in the conflict condition. Accordingly, the compensatory group tracked the difference in expected value between choice options reflected in neural activation in the parietal cortex. Furthermore, we expected noncompensatory, compared with compensatory, decision-makers to experience increased conflict when attributes provided conflicting information. Accordingly, the noncompensatory group showed greater dorsomedial PFC activation only in the conflict condition. These pronounced behavioral and neural differences indicate the need for decision neuroscience to account for individual differences in risky choice strategies and to broaden its scope to noncompensatory risky choice strategies. PMID:27167399

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

    PubMed Central

    Teske, Jennifer A.; Billington, Charles J.; Kotz, Catherine M.

    2013-01-01

    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 (OXR) 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 generation of SPA. To test this, SPA response was determined in lean and obese rats with cannulae targeted towards the rostral lateral hypothalamus (rLH) or SN. Sleep/wake states were also measured in rats with rLH cannula and EEG/EMG radiotelemetry transmitters. SPA in lean rats was more sensitive to antagonism of the orexin 1 receptor (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 OR 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 mediation of SPA and running wheel activity. PMID:24161277

  20. 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

  1. 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

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

    PubMed Central

    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. PMID:25852452

  3. 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

  4. Inelastic deformation mechanisms in a transverse MMC lamina under compression

    NASA Technical Reports Server (NTRS)

    Newaz, Golam M.; Majumdar, Bhaskar S.

    1992-01-01

    An investigation was undertaken to study the inelastic deformation mechanisms in (90)(sub 8) Ti 15-3/SCS-6 lamina subjected to pure compression. Both mechanical behavior and microstructural evaluation were undertaken at room temperature, 538 and 650 C. Results indicate that mechanical response and deformation characteristics are significantly different in monotonic tension and compression. The inelastic deformation mechanisms in compression are controlled by radial fiber fracture, matrix plasticity and fiber-matrix debonding. The radial fiber fracture is a new damage mode observed for metal-matrix composites (MMC).

  5. 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

  6. Key evidence of the role of desertification in protecting the underlying permafrost in the Qinghai-Tibet Plateau

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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.

  7. 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

  8. 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…

  9. 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

  10. Mechanisms of T-cell protection from death by IRX-2: a new immunotherapeutic

    PubMed Central

    Czystowska, Malgorzata; Szczepanski, Miroslaw J.; Szajnik, Marta; Quadrini, Karen; Brandwein, Harvey; Hadden, John W.

    2013-01-01

    Objectives IRX-2 is a novel immunotherapeutic containing physiologic quantities of several cytokines which protects human T lymphocytes from tumor-induced or drug-induced apoptosis. Here, we investigate the mechanisms responsible for IRX-2-mediated protection of T lymphocytes exposed to tumor-derived microvesicles (TMV). Methods Jurkat cells or primary human T cells ± IRX-2 were co-incubated with TMV and then examined by flow cytometry or Western blots for expression of molecules regulating cell survival (FLIP, Bcl-2, Bcl-xL, Mcl-1) or death (Fas, caspase 8, caspase 9, Bax, Bid). ANX V binding, caspase activation or cytochrome c release were also measured ± cycloheximide (CHX) or ± the Akt-specific inhibitor. Jurkat cells transfected with the cFLIP gene were used to evaluate the role of cFLIP in IRX-2-mediated protection. Effects of CHX on IRX-2-mediated protection and activation of NF-κB upon the TMV/IRX-2 treatment were also measured. Results IRX-2 protected T cells from apoptosis by preventing Fas overexpression induced by TMV and blocking caspase 8 activation by up-regulating cFLIP. Jurkat cells overexpressing cFLIP were more resistant to TMV-induced apoptosis than the mock-transfected cells (p < 0.02). Signaling via the PI3K/Akt pathway, IRX-2 corrected the imbalance of pro- versus anti-apoptotic proteins induced by TMV and promoted NF-κB translocation to the nucleus. CHX abolished IRX-2-mediated protection in T cells, suggesting that IRX-2 induces de novo synthesis of one or more proteins that are required for protection. Conclusions This biologic may be therapeutically useful for protection of activated T cells from tumor-induced immune suppression and death. PMID:21181158

  11. 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

  12. Synthesis of triplet-triplet annihilation upconversion nanocapsules under protective conditions.

    PubMed

    Katta, Kartheek; Busko, Dmitry; Avlasevich, Yuri; Muñoz-Espí, Rafael; Baluschev, Stanislav; Landfester, Katharina

    2015-06-01

    Triplet-triplet annihilation upconversion (TTA-UC) nanocapsules are synthesized under oxygen-protective conditions (i.e., complete darkness and argon atmosphere) by free-radical miniemulsion polymerization. These conditions help to exclude the oxidation of the emitter molecules caused by singlet oxygen, generated during the synthesis at daylight conditions and oxygen-rich environment. Subsequently, keeping all the other experimental conditions the same, samples synthesized at protective conditions demonstrate substantially increased UC efficiency. These experimental facts strongly support the hypothesis that posterior removing of oxygen from TTA-UC nanocapsules is not sufficient to obtain reproducible and sustainable UC results. The schematic representation shows the influence of sunlight on the formation of singlet oxygen and its effect on the triplet-triplet annihilation upconversion process. PMID:25630569

  13. Radiological protection in the Spanish nuclear industry under Franco, 1939-1975.

    PubMed

    Menéndez-Navarro, Alfredo; Vázquez, Luis Sánchez

    2013-01-01

    In debates about nuclear controversy, the issue of occupational safety in radioactive facilities is rarely foregrounded; it has historically been relegated to second place compared to the attention given to potential harm to the general population. Aiming for, at least, partially filling this historiographical gap, this article deals with the development of occupational radiological protection in Spain under the dictatorship of General Franco (1939-1975). It covers the rise of radiological protection measures on an international level and the subsequent development of legislation in the case of Spain, a process that paralleled the growth of the nation's nuclear program. Finally, it explores the main evidence of the impact of ionizing radiation on Spain's working population. PMID:24141916

  14. Mechanical response of collagen molecule under hydrostatic compression.

    PubMed

    Saini, Karanvir; Kumar, Navin

    2015-04-01

    Proteins like collagen are the basic building blocks of various body tissues (soft and hard). Collagen molecules find their presence in the skeletal system of the body where they bear mechanical loads from different directions, either individually or along with hydroxy-apatite crystals. Therefore, it is very important to understand the mechanical behavior of the collagen molecule which is subjected to multi-axial state of loading. The estimation of strains of collagen molecule along different directions resulting from the changes in hydrostatic pressure magnitude, can provide us new insights into its mechanical behavior. In the present work, full atomistic simulations have been used to study global (volumetric) as well as local (along different directions) mechanical properties of the hydrated collagen molecule which is subjected to different hydrostatic pressure magnitudes. To estimate the local mechanical properties, the strains of collagen molecule along its longitudinal and transverse directions have been acquired at different hydrostatic pressure magnitudes. In spite of non-homogeneous distribution of atoms within the collagen molecule, the calculated values of local mechanical properties have been found to carry the same order of magnitude along the longitudinal and transverse directions. It has been demonstrated that the values of global mechanical properties like compressibility, bulk modulus, etc. as well as local mechanical properties like linear compressibility, linear elastic modulus, etc. are functions of magnitudes of applied hydrostatic pressures. The mechanical characteristics of collagen molecule based on the atomistic model have also been compared with that of the continuum model in the present work. The comparison showed up orthotropic material behavior for the collagen molecule. The information on collagen molecule provided in the present study can be very helpful in designing the future bio-materials. PMID:25687001

  15. 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.

  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. PMID:25772257

  17. 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

  18. A model for hierarchical patterns under mechanical stresses

    NASA Astrophysics Data System (ADS)

    Corson, F.; Henry, H.; Adda-Bedia, M.

    2010-01-01

    We present a model for mechanically-induced pattern formation in growing biological tissues and discuss its application to the development of leaf venation networks. Drawing an analogy with phase transitions in solids, we use a phase field method to describe the transition between two states of the tissue, e.g. the differentiation of leaf veins, and consider a layered system where mechanical stresses are generated by differential growth. We present analytical and numerical results for one-dimensional systems, showing that a combination of growth and irreversibility gives rise to hierarchical patterns. Two-dimensional simulations suggest that such a mechanism could account for the hierarchical, reticulate structure of leaf venation networks, yet point to the need for a more detailed treatment of the coupling between growth and mechanical stresses.

  19. Triggering Mechanisms of Thermosensitive Nanoparticles Under Hyperthermia Condition.

    PubMed

    Dabbagh, Ali; Abdullah, Basri Johan Jeet; Abdullah, Hadijah; Hamdi, Mohd; Kasim, Noor Hayaty Abu

    2015-08-01

    Nanoparticle-based hyperthermia is an effective therapeutic approach that allows time- and site-specific treatment with minimized off-site effects. The recent advances in materials science have led to design a diversity of thermosensitive nanostructures that exhibit different mechanisms of thermal response to the external stimuli. This article aims to provide an extensive review of the various triggering mechanisms in the nanostructures used as adjuvants to hyperthermia modalities. Understanding the differences between various mechanisms of thermal response in these nanostructures could help researchers in the selection of appropriate materials for each experimental and clinical condition as well as to address the current shortcomings of these mechanisms with improved material design. PMID:26073304

  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. Peptide micelle-mediated curcumin delivery for protection of islet β-cells under hypoxia.

    PubMed

    Han, Jaesik; Oh, Jungju; Ihm, Sung-Hee; Lee, Minhyung

    2016-08-01

    Islet transplantation is one of many therapeutic approaches for the treatment of diabetes. During transplant procedures, the isolated islets are subjected to hypoxic conditions, and undergo the apoptotic process. Curcumin has a cytoprotective effect, and may therefore be useful for the protection of islets under hypoxia. However, curcumin is hydrophobic, and an efficient curcumin carrier is required for effective treatment. In this study, R3V6 peptide micelles, composed of a 3-arginine stretch and 6-valine stretch, were evaluated as a curcumin carrier to INS-1 insulinoma cells. Curcumin was loaded into R3V6 micelles at a weight ratio of 10:3 (R3V6:curcumin). The size and surface charge of the curcumin-loaded R3V6 micelles (R3V6-curcumin) were approximately 250 nm and 17.49 mV, respectively. R3V6-curcumin delivered curcumin to the INS-1 cells more efficiently than either curcumin alone or a simple mixture of R3V6 and curcumin. MTT assay indicated that under hypoxia, R3V6-curcumin protected INS-1 cells more efficiently than curcumin alone. TUNEL and reactive oxygen species (ROS) assays suggested that R3V6-curcumin reduced INS-1 cell apoptosis under hypoxia. These results demonstrate that R3V6 peptide micelles are an effective carrier of curcumin, and that R3V6-curcumin may improve the viability of pancreatic β-cells in islet transplantation. PMID:26768151

  2. 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%.

  3. 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

  4. 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).

  5. A role of nitric oxide mechanism involved in the protective effects of venlafaxine in sleep deprivation.

    PubMed

    Kumar, Anil; Garg, Ruchika

    2008-12-12

    The present study was designed to explore the possible nitric oxide mechanism in protective effect of venlafaxine in sleep deprivation in mice. Laca mice were sleep deprived for period of 72 h using grid suspended over water method. Venlafaxine (2.5, 5 and 10mg/kg, ip), l-arginine (50mg/kg, ip), l-NAME (10mg/kg, ip) and methylene blue (10mg/kg, ip) were administered for 5 days, starting 2 days before 72-h sleep deprivation. Various behavioral tests (plus maze, zero maze, mirror chamber tests for anxiety, and actophotometer test) followed by oxidative stress parameters (malondialdehyde level, glutathione, catalase, nitrite and protein) were assessed. The present study showed that venlafaxine (5 and 10mg/kg, ip) drug treatment significantly reversed 72-h sleep deprivation caused anxiety like behavior, impairment in locomotor activity and oxidative damage (increased lipid peroxidation and nitrite levels and depleted reduced glutathione and catalase activity) as compared to control. l-NAME (10mg/kg) and methylene blue (10mg/kg) pretreatment with lower dose of venlafaxine (5mg/kg) potentiated the protective effect of venlafaxine (5mg/kg). However, l-arginine (50mg/kg) pretreatment with venlafaxine (5mg/kg) reversed the protective effect of venlafaxine. Results of present study suggest that nitric oxide mechanism is involved in the protective effect of venlafaxine against sleep-deprivation-induced behavior alteration and oxidative damage in mice. PMID:18674568

  6. 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.

  7. 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.

  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. 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. 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.

  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. 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.

  13. Common mechanism underlies repeated evolution of extreme pollution tolerance

    PubMed Central

    Whitehead, Andrew; Pilcher, Whitney; Champlin, Denise; Nacci, Diane

    2012-01-01

    Human alterations to the environment can exert strong evolutionary pressures, yet contemporary adaptation to human-mediated stressors is rarely documented in wildlife populations. A common-garden experimental design was coupled with comparative transcriptomics to discover evolved mechanisms enabling three populations of killifish resident in urban estuaries to survive normally lethal pollution exposure during development, and to test whether mechanisms are unique or common across populations. We show that killifish populations from these polluted sites have independently converged on a common adaptive mechanism, despite variation in contaminant profiles among sites. These populations are united by a similarly profound desensitization of aryl-hydrocarbon receptor-mediated transcriptional activation, which is associated with extreme tolerance to the lethal effects of toxic dioxin-like pollutants. The rapid, repeated, heritable and convergent nature of evolved tolerance suggests that ancestral killifish populations harboured genotypes that enabled adaptation to twentieth-century industrial pollutants. PMID:21733895

  14. Cognitive interventions for addiction medicine: Understanding the underlying neurobiological mechanisms.

    PubMed

    Zilverstand, Anna; Parvaz, Muhammad A; Moeller, Scott J; Goldstein, Rita Z

    2016-01-01

    Neuroimaging provides a tool for investigating the neurobiological mechanisms of cognitive interventions in addiction. The aim of this review was to describe the brain circuits that are recruited during cognitive interventions, examining differences between various treatment modalities while highlighting core mechanisms, in drug addicted individuals. Based on a systematic Medline search we reviewed neuroimaging studies on cognitive behavioral therapy, cognitive inhibition of craving, motivational interventions, emotion regulation, mindfulness, and neurofeedback training in addiction. Across intervention modalities, common results included the normalization of aberrant activity in the brain's reward circuitry, and the recruitment and strengthening of the brain's inhibitory control network. Results suggest that different cognitive interventions act, at least partly, through recruitment of a common inhibitory control network as a core mechanism. This implies potential transfer effects between training modalities. Overall, results confirm that chronically hypoactive prefrontal regions implicated in cognitive control in addiction can be normalized through cognitive means. PMID:26822363

  15. Mechanisms underlying the inhibition of interferon signaling by viruses

    PubMed Central

    Devasthanam, Anand S

    2014-01-01

    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. PMID:24504013

  16. 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

  17. Coalescence kinetics under the action of alternative grain growth mechanisms

    SciTech Connect

    Gubanov, P. Yu. Maksimov, I. L.

    2008-01-15

    The coalescence process is considered for the case where the prevailing grain growth mechanism is block-to-block diffusion, during which the motion of atoms in a solution occurs in the form of diffusion flux along the block boundaries. Numerical and analytical investigation of the coalescence kinetics in a homogeneous supersaturated solution is performed with allowance for the finite maximum grain size, and the time evolution of the size distribution function of new-phase grains is theoretically described. Possible transition regimes arising during coalescence at a change in the dominant grain growth mechanism are considered.

  18. Underlying molecular and cellular mechanisms in childhood irritable bowel syndrome.

    PubMed

    Chumpitazi, Bruno P; Shulman, Robert J

    2016-12-01

    Irritable bowel syndrome (IBS) affects a large number of children throughout the world. The symptom expression of IBS is heterogeneous, and several factors which may be interrelated within the IBS biopsychosocial model play a role. These factors include visceral hyperalgesia, intestinal permeability, gut microbiota, psychosocial distress, gut inflammation, bile acids, food intolerance, colonic bacterial fermentation, and genetics. The molecular and cellular mechanisms of these factors are being actively investigated. In this mini-review, we present updates of these mechanisms and, where possible, relate the findings to childhood IBS. Mechanistic elucidation may lead to the identification of biomarkers as well as personalized childhood IBS therapies. PMID:26883355

  19. Endovascular stenting of symptomatic innominate artery stenosis under distal balloon protection of the internal carotid and vertebral artery for cerebral protection: a technical case report.

    PubMed

    Sakamoto, Shigeyuki; Kiura, Yoshihiro; Kajihara, Yosuke; Mukada, Kazutoshi; Kurisu, Kaoru

    2013-02-01

    The use of cerebral protection devices in endovascular treatment for innominate artery (IA) stenosis is not well established. We describe a novel technique for cerebral protection during endovascular stenting of symptomatic IA stenosis. An 82-year-old man presented with acutely scattered brain infarction by artery-to-artery embolism due to IA stenosis. Endovascular treatment for symptomatic IA stenosis was planned to prevent recurrent attacks. Endovascular stenting for IA stenosis via the right femoral artery approach was performed under simultaneous distal balloon protection of the right internal carotid artery (ICA) and vertebral artery (VA) via the right brachial artery approach. Successful treatment of symptomatic IA stenosis was achieved with no complications. The technique with simultaneous distal balloon protection of the ICA and VA provided excellent cerebral protection in stenting of IA stenosis. PMID:23263481

  20. Tree growth variability under environmental changes - identifying underlying physiological mechanisms by stable C and O isotopes

    NASA Astrophysics Data System (ADS)

    Weigt, Rosemarie; Saurer, Matthias; Siegwolf, Rolf T. W.

    2014-05-01

    Long-term variability of tree growth is a result of changing environmental factors and physiological response mechanisms. Information about these relationships can be retrieved from tree ring width, but also from tree ring isotopes as proxies of photosynthetic rates (13C), stomatal conductance (13C, 18O), and source water (18O) used by the tree. With the interdisciplinary project iTREE, we aim to identify physiological mechanisms by relating time-series of tree ring isotopes from a network of sites to environmental factors, and compare resulting growth reponses with stand surveys and vegetation models. Linking these different scales - from individual trees to site and landscape - will contribute to reduce uncertainties in modeling large-scale variability of forest biomass production under current climate change. At a high altitude site in Switzerland (Loetschental, 2100m asl), ~400 yrs old larch (Larix dedicua) trees showed enhanced tree growth towards the end of the 20th century along with increasing CO2 concentrations and temperature, but also increasing variability between individual trees. At this temperature limited site, both environmental factors seem to act as growth drivers by increasing photosynthesis and cell growth. Because δ18O and δ13C (after correction for atmospheric CO2 increase and 13C decrease) remained rather unchanged over the past ~100 yrs, the stomatal behavior did not change according to the dual isotope model, indicating relatively constant water supply over time. At other sites throughout Central Europe, physiological responses to environmental changes may result in different carbon assimilation or allocation other than stem growth. First data of different sites and species along a temperature gradient in Central Europe show that year-to-year variability of tree ring δ13C and δ18O are positively correlated at most sites indicating pronounced responsiveness of stomatal conductance. A trend of increasing isotopic values across the past

  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. Human subject protection; foreign clinical studies not conducted under an investigational new drug application. Final rule.

    PubMed

    2008-04-28

    The Food and Drug Administration (FDA) is amending its regulations on acceptance of foreign clinical studies not conducted under an investigational new drug application (IND) (non-IND foreign clinical studies) as support for an IND or application for marketing approval for a drug or biological product. The final rule replaces the requirement that these studies be conducted in accordance with ethical principles stated in the Declaration of Helsinki (Declaration) issued by the World Medical Association (WMA), specifically the 1989 version (1989 Declaration), with a requirement that the studies be conducted in accordance with good clinical practice (GCP), including review and approval by an independent ethics committee (IEC). The final rule updates the standards for the acceptance of foreign clinical studies not conducted under an IND and helps ensure the protection of human subjects and the quality and integrity of data obtained from these studies. PMID:18567164

  3. 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.

  4. 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

  5. Horizontal and Vertical Simon Effect: Different Underlying Mechanisms?

    ERIC Educational Resources Information Center

    Vallesi, A.; Mapelli, D.; Schiff, S.; Amodio, P.; Umilta, C.

    2005-01-01

    Reaction times are usually faster when stimulus and response occur at the same location than when they do not, even if stimulus location is irrelevant to the task (Simon effect). This effect was found with both horizontal and vertical stimulus-response arrangements. The same mechanisms have been proposed to be involved in either case. Here, we…

  6. Mechanical behavior of carpal tunnel subsynovial connective tissue under compression.

    PubMed

    Goetz, Jessica E; Baer, Thomas E

    2011-01-01

    Subsynovial connective tissue (SSCT) is a fluid-permeated loose connective tissue that occupies the majority of the space in the carpal tunnel not occupied by the digital flexor tendons or the median nerve. It is arranged in layers around these more discrete structures, presumably to assist with tendon gliding. As a result of this arrangement, the compressive behavior and the fluid permeability of this tissue may substantially affect the stresses in the median nerve resulting from contact with its neighboring tendons or with the walls of the tunnel itself. These stresses may contribute to damage of the median nerve and the development of carpal tunnel syndrome. In this study, the fluid permeability and the compressive behavior of the SSCT were investigated to better understand the mechanics of this tissue and how it may mediate mechanical insult to the median nerve. A custom experimental apparatus was built to allow simultaneous measurement of tissue compression and fluid flow. Using Darcy's law, the average SSCT fluid permeability was 8.78×10(15) m(4)/Ns. The compressive behavior of the SSCT demonstrated time dependence, with an initial modulus of 395kPa gradually decreasing to a value of 285kPa. These baseline tissue data may serve as a mechanical norm (toward which pathological tissue might be returned, therapeutically) and may serve as essential properties to include in future mechanical models of the carpal tunnel. PMID:22096431

  7. MECHANICAL BEHAVIOR OF CARPAL TUNNEL SUBSYNOVIAL CONNECTIVE TISSUE UNDER COMPRESSION

    PubMed Central

    Goetz, Jessica E; Baer, Thomas E

    2011-01-01

    Subsynovial connective tissue (SSCT) is a fluid-permeated loose connective tissue that occupies the majority of the space in the carpal tunnel not occupied by the digital flexor tendons or the median nerve. It is arranged in layers around these more discrete structures, presumably to assist with tendon gliding. As a result of this arrangement, the compressive behavior and the fluid permeability of this tissue may substantially affect the stresses in the median nerve resulting from contact with its neighboring tendons or with the walls of the tunnel itself. These stresses may contribute to damage of the median nerve and the development of carpal tunnel syndrome. In this study, the fluid permeability and the compressive behavior of the SSCT were investigated to better understand the mechanics of this tissue and how it may mediate mechanical insult to the median nerve. A custom experimental apparatus was built to allow simultaneous measurement of tissue compression and fluid flow. Using Darcy’s law, the average SSCT fluid permeability was 8.78×1015 m4/Ns. The compressive behavior of the SSCT demonstrated time dependence, with an initial modulus of 395kPa gradually decreasing to a value of 285kPa. These baseline tissue data may serve as a mechanical norm (toward which pathological tissue might be returned, therapeutically) and may serve as essential properties to include in future mechanical models of the carpal tunnel. PMID:22096431

  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. PMID:26179346

  9. Mechanical Solder Characterisation Under High Strain Rate Conditions

    NASA Astrophysics Data System (ADS)

    Meier, Karsten; Roellig, Mike; Wiese, Steffen; Wolter, Klaus-Juergen

    2010-11-01

    Using a setup for high strain rate tensile experiments the mechanical behavior of two lead-free tin based solders is investigated. The first alloy is SnAg1.3Cu0.5Ni. The second alloy has a higher silver content but no addition of Ni. Solder joints are the main electrical, thermal and mechanical interconnection technology on the first and second interconnection level. With the recent rise of 3D packaging technologies many novel interconnection ideas are proposed with innovative or visionary nature. Copper pillar, stud bump, intermetallic (SLID) and even spring like joints are presented in a number of projects. However, soldering will remain one of the important interconnect technologies. Knowing the mechanical properties of solder joints is important for any reliability assessment, especially when it comes to vibration and mechanical shock associated with mobile applications. Taking the ongoing miniaturization and linked changes in solder joint microstructure and mechanical behavior into account the need for experimental work on that issue is not satisfied. The tests are accomplished utilizing miniature bulk specimens to match the microstructure of real solder joints as close as possible. The dogbone shaped bulk specimens have a crucial diameter of 1 mm, which is close to BGA solder joints. Experiments were done in the strain rate range from 20 s-1 to 600 s-1. Solder strengthening has been observed with increased strain rate for both SAC solder alloys. The yield stress increases by about 100% in the investigated strain rate range. The yield level differs strongly. A high speed camera system was used to assist the evaluation process of the stress and strain data. Besides the stress and strain data extracted from the experiment the ultimate fracture strain is determined and the fracture surfaces are evaluated using SEM technique considering rate dependency.

  10. Underlying mechanisms of transient luminous events: a review

    NASA Astrophysics Data System (ADS)

    Surkov, V. V.; Hayakawa, M.

    2012-08-01

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

  11. 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.

  12. Cellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss – A Common Hereditary Deafness

    PubMed Central

    Wingard, Jeffrey C.; Zhao, Hong-Bo

    2015-01-01

    Hearing loss due to mutations in the connexin gene family, which encodes gap junctional proteins, is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2) mutations are responsible for ~50% of non-syndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate that congenital deafness mainly results from cochlear developmental disorders rather than hair cell degeneration and endocochlear potential reduction, while late-onset hearing loss results from reduction of active cochlear amplification, even though cochlear hair cells have no connexin expression. However, there is no apparent, demonstrable relationship between specific changes in connexin (channel) functions and the phenotypes of mutation-induced hearing loss. Moreover, new experiments further demonstrate that the hypothesized K+-recycling disruption is not a principal deafness mechanism for connexin deficiency induced hearing loss. Cx30 (GJB6), Cx29 (GJC3), Cx31 (GJB3), and Cx43 (GJA1) mutations can also cause hearing loss with distinct pathological changes in the cochlea. These new studies provide invaluable information about deafness mechanisms underlying connexin mutation-induced hearing loss and also provide important information for developing new protective and therapeutic strategies for this common deafness. However, the detailed cellular mechanisms underlying these pathological changes remain unclear. Also, little is known about specific mutation-induced pathological changes in vivo and little information is available for humans. Such further studies are urgently required. PMID:26074771

  13. 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

  14. 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.

  15. 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

  16. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    PubMed Central

    Luo, Guopei; Liu, Chen; Wu, Chuntao; Liu, Liang; Liu, Zuqiang; Ni, Quanxing; Long, Jiang; Yu, Xianjun

    2014-01-01

    As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs) and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer. PMID:24587996

  17. 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.

  18. Photooxidation of tetrahydrobiopterin under UV irradiation: possible pathways and mechanisms.

    PubMed

    Buglak, Andrey A; Telegina, Taisiya A; Lyudnikova, Tamara A; Vechtomova, Yulia L; Kritsky, Mikhail S

    2014-01-01

    Tetrahydrobiopterin (H4 Bip) is a cofactor for several key enzymes, including NO synthases and aromatic amino acid hydroxylases (AAHs). Normal functioning of the H4 Bip regeneration cycle is extremely important for the work of AAHs. Oxidized pterins may accumulate if the H4 Bip regeneration cycle is disrupted or if H4 Bip autoxidation occurs. These oxidized pterins can photosensitize the production of singlet molecular oxygen (1)O2 and thus cause oxidative stress. In this context, we studied the photooxidation of H4 Bip in phosphate buffer at pH 7.2. We found that UV irradiation of H4 Bip affected its oxidation rate (quantum yield Φ300 = (2.7 ± 0.4) × 10(-3)). The effect of UV irradiation at λ = 350 nm on H4 Bip oxidation was stronger, especially in the presence of biopterin (Bip) (Φ350 = (9.7 ± 1.5) × 10(-3)). We showed that the rate of H4 Bip oxidation linearly depends on Bip concentration. Experiments with KI, a selective quencher of triplet pterins at micromolar concentrations, demonstrated that the oxidation is sensitized by the triplet state biopterin (3) Bip. Apparently, electron transfer sensitization (Type-I mechanism) is dominant. Energy transfer (Type-II mechanism) and singlet oxygen generation play only a secondary role. The mechanisms of H4 Bip photooxidation and their biological meaning are discussed. PMID:24773158

  19. 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...

  20. Investigations of Mechanisms Associated with Nucleate Boiling Under Microgravity Conditions

    NASA Technical Reports Server (NTRS)

    Dhir, Vijay K.; Hasan, M.; Chao, David (Technical Monitor)

    2003-01-01

    In this work a building block type of approach is used so that a basic understanding of the processes that contribute to nucleate boiling heat fluxes under microgravity conditions can be developed. This understanding will lead to development of a mechanistic model for nucleate boiling heat transfer which could eventually be used as a design tool in space applications. Task Description Task 1: Fabrication of the Experimental Setup. Under this task, the test section and liquid holding and viewing chambers will be fabricated. Artificial cylinder cavities will be formed on silicon wafers. A single cavity and two or four cavities, with a prescribed spacing and size, will be formed. The desired nucleation wall superheat will be used to determine the size of the mouth of the cavities. Task 2: Experiments. The basic experiments for flow and temperature field around single and multiple (2 or 4 separated or merged bubbles growing on downward facing or inclined surfaces) will be carried out under normal gravity conditions. The experiments will be conducted at one atmosphere pressure, but liquid subcooling will be varied from 0 to 30C. Water and PF-5050 will be used as test liquids. Task 3: Analytical/Numerical Models. In this task, transient temperature and flow field in vapor and liquid will be determined during growth of a single bubble. Analysis will include the evolution of the vapor-liquid interface and development of microlayer underneath the bubbles. For merged bubbles, detailed calculations of flow and temperature field will be carried out for transient shapes of vapor stems supporting a large bubble and the corresponding evaporation rate. Flow and temperature field for a bubble sliding along a heated wall will also be determined. Microgravity conditions will be simulated and a framework of a numerical tool for prediction of nucleate boiling heat fluxes under microgravity conditions will be developed. Task 4: Experiments in a KC-135. To understand bubble growth and

  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. Neural mechanisms underlying auditory feedback control of speech

    PubMed Central

    Reilly, Kevin J.; Guenther, Frank H.

    2013-01-01

    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 135 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. PMID:18035557

  3. 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.

  4. 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.

  5. Mitochondrial-targeted antioxidants protect against mechanical ventilation-induced diaphragm weakness

    PubMed Central

    Powers, Scott K.; Hudson, Matthew B.; Nelson, W. Bradley; Talbert, Erin E.; Min, Kisuk; Szeto, Hazel H.; Kavazis, Andreas N.; Smuder, Ashley J.

    2015-01-01

    BACKGROUND Mechanical ventilation (MV) is a life-saving intervention used to provide adequate pulmonary ventilation in patients suffering from respiratory failure. However, prolonged MV is associated with significant diaphragmatic weakness resulting from both myofiber atrophy and contractile dysfunction. Although several signaling pathways contribute to diaphragm weakness during MV, it is established that oxidative stress is required for diaphragmatic weakness to occur. Therefore, identifying the site(s) of MV-induced reactive oxygen species (ROS) production in the diaphragm is important. OBJECTIVE These experiments tested the hypothesis that elevated mitochondrial ROS emission is required for MV-induced oxidative stress, atrophy, and contractile dysfunction in the diaphragm. DESIGN Cause and effect was determined by preventing MV-induced mitochondrial ROS emission in the diaphragm of rats using a novel mitochondrial-targeted antioxidant (SS-31). MEASUREMENTS AND MAIN RESULTS Compared to mechanically ventilated animals treated with saline, animals treated with SS-31 were protected against MV-induced mitochondrial dysfunction, oxidative stress, and protease activation in the diaphragm. Importantly, treatment of animals with the mitochondrial antioxidant also protected the diaphragm against MV-induced myofiber atrophy and contractile dysfunction. CONCLUSIONS These results reveal that prevention of MV-induced increases in diaphragmatic mitochondrial ROS emission protects the diaphragm MV-induced diaphragmatic weakness. This important new finding indicates that mitochondria are a primary source of ROS production in the diaphragm during prolonged MV. These results could lead to the development of a therapeutic intervention to impede MV-induced diaphragmatic weakness. PMID:21460706

  6. 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

  7. 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. PMID:25556118

  8. 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.

  9. Chemical and Mechanical Alteration of Fractured Caprock Under Reactive Flow

    NASA Astrophysics Data System (ADS)

    Elkhoury, J. E.; Ameli, P.; Detwiler, R. L.

    2013-12-01

    Permeability evolution of fractures depends on chemical and mechanical processes. Stress perturbations lead to mechanical deformation and fracture propagation that can increase formation permeability. Chemical disequilibrium between fluids and resident minerals leads to dissolution and precipitation that further alter fracture porosity and permeability. The ability to predict whether these coupled chemical and mechanical processes will enhance or diminish fracture permeability remains elusive. Here, we present results from reactive-transport experiments in fractured anhydrite cores, with significant alteration of the rock matrix, where only the flow rate differed. For high flow rate, the transformation of anhydrite to gypsum occurred uniformly within the fracture leading to compaction and a two-order-of-magnitude decrease in permeability. For low flow rate, rock-fluid reactions proceeded to near equilibrium within the fracture with preferential flow paths persisting over the 6-month duration of the experiment and a negligible change in permeability. Anticipating such permeability evolution is critical for successful geologic CO2 sequestration and waste injection. Additionally, reactive alteration of the porous matrix bounding fractures will influence the strength of earthquake fault zones. Comparison of the aperture field before (a) and after (b) the reactive flow-through experiment at low flow rate. a) Aperture field from optical profilometry measurements of the fracture surfaces. b) Inferred aperture from x-ray computed tomography scans. Color scale I (blue) denotes mainly unaltered regions of the fracture and/or aperture < 200 μm. Color scale II (green/yellow) denotes reacted regions of the fracture surfaces and the matrix adjacent to the fracture. Persistent flow paths are clearly observed in panel (b) (color scale III corresponds to aperture > 200 μm) leading to negligible change in permeability after a 6-month run.

  10. 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.

  11. 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

  12. Granuloma Correlates of Protection Against Tuberculosis and Mechanisms of Immune Modulation by Mycobacterium tuberculosis

    PubMed Central

    Mehra, Smriti; Alvarez, Xavier; Didier, Peter J.; Doyle, Lara A.; Blanchard, James L.; Lackner, Andrew A.; Kaushal, Deepak

    2013-01-01

    Background. The BCG vaccine is ineffective against adult tuberculosis. Hence, new antituberculosis vaccines are needed. Correlates of protection against tuberculosis are not known. We studied the effects of BCG vaccination on gene expression in tuberculosis granulomas using macaques. Methods. Macaques were BCG-vaccinated or sham-vaccinated and then challenged with virulent Mycobacterium tuberculosis. Lung lesions were used for comparative transcriptomics. Results. Vaccinated macaques were protected with lower bacterial burden and immunopathology. Lesions from BCG-vaccinated nonhuman primates (NHPs) showed a better balance of α- and β-chemokine gene expression with higher levels of β-chemokine expression relative to nonvaccinated animals. Consistent with this, sham-vaccinated macaques recruited fewer macrophages relative to neutrophils in their lungs. The expression of indoleamine 2,3-dioxygenase (IDO), a known immunosuppressor, was significantly higher in both week 5 and 10 lesions from sham-vaccinated, relative to BCG-vaccinated, NHPs. IDO expression was primarily limited to the nonlymphocytic region of the lesions, within the inner ring structure surrounding the central necrosis. Conclusions. Our study defines lung gene expression correlates of protective response against tuberculosis, relative to disease, which can potentially be employed to assess the efficacy of candidate antituberculosis vaccines. Mycobacterium tuberculosis may modulate protective immune responses using diverse mechanisms, including increased recruitment of inflammatory neutrophils and the concomitant use of IDO to modulate inflammation. PMID:23255564

  13. 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. PMID:26774283

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. Analysis of thermal conductivity of polymeric nanocomposites under mechanical loading

    NASA Astrophysics Data System (ADS)

    Yu, Suyoung; Yang, Seunghwa; Cho, Maenghyo

    2013-12-01

    When the plastic deformation is applied to neat polymer, the polymer chains are aligned and the thermal conductivity of neat polymer increases linearly along the loading direction. However, the thermal conductivity change of nanocomposites consisting of polymer matrix and nanofillers during plastic deformation is not simple. The volume fraction and size of nanofillers scarcely affect the structural change of polymer chains during the plastic deformation. In this study, the structural change of polymeric materials according to the mechanical loading and its effect on the thermal transport properties are investigated through a molecular dynamics simulation. To investigate the effects of nanofiller, its volume fraction, and size on the thermal transport properties, the unit cells of neat amorphous nylon 6 and nanocomposites consisting of amorphous nylon 6 matrix and spherical silica particles are prepared. The molecular unit cells are uniaxially stretched by applying constant strain along the loading directions. Then, non-equilibrium molecular dynamics (NEMD) simulations are performed to estimate the thermal conductivities during plastic deformation. The alignment of polymer chains is analyzed by tracing the orientation correlation function of each polymer molecule and the free volume change during the mechanical loading is also analyzed.

  20. 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

  1. 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

  2. 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. PMID:23720734

  3. 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. PMID:24849229

  4. 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

  5. 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.

  6. Mechanism and kinetics of parathion degradation under ultrasonic irradiation.

    PubMed

    Yao, Juan-Juan; Gao, Nai-Yun; Li, Cong; Li, Lei; Xu, Bin

    2010-03-15

    The parathion degradation under ultrasonic irradiation in aqueous solution was investigated. The results indicate that at the conditions in question, degradation rate of parathion decreased with increasing initial concentration and decreasing power. The optimal frequency for parathion degradation was 600 kHz. The free radical reactions predominate in the sonochemical degradation of parathion and the reaction zones are predominately at the bubble interface and, to a much lesser extent, in bulk solution. The gas/liquid interfacial regions are the real effective reaction sites for sonochemical degradation of parathion. The reaction can be well described as a gas/liquid heterogeneous reaction which obeys a kinetic model based on Langmuir-Hinshelwood model. The main pathways of parathion degradation by ultrasonic irradiation were also proposed by qualitative and quantitative analysis of organic and inorganic byproducts. It is indicated that the N(2) in air takes part in the parathion degradation through the formation of NO(2) under ultrasonic irradiation. Parathion is decomposed into paraoxon and 4-nitrophenol in the first step via two different pathways, respectively, which is in agreement with the theoretical molecular orbital (MO) calculations. PMID:19854573

  7. 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.

  8. 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

  9. 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.

  10. Professional licensure protection strategies: how to keep oneself from being investigated and protect oneself if an investigation is under way.

    PubMed

    Brous, Edie

    2012-12-01

    This is the third and final article in a three-part series on nursing boards' disciplinary actions and what nurses need to know to maintain their license in good standing. This article discusses strategies for protecting your license. PMID:23190673

  11. Mechanical properties of superelastic Cu Al Be wires at cold temperatures for the seismic protection of bridges

    NASA Astrophysics Data System (ADS)

    Zhang, Yunfeng; Camilleri, Joseph A.; Zhu, Songye

    2008-04-01

    This paper examines the suitability of superelastic copper-aluminum-beryllium (Cu-Al-Be) alloy wires for the seismic protection of bridges in cold regions. Experimental results for the mechanical properties of superelastic Cu-Al-Be alloy wires at a variety of temperatures and loading rates are presented. This research is motivated by the recent use of shape memory alloys for bridge restrainers subject to harsh winter conditions, especially in cold regions. Bridge restrainers made of superelastic Cu-Al-Be wire strands are expected to be used for protecting bridge decks from excessive displacement when subjected to strong earthquakes. Using a temperature chamber, superelastic Cu-Al-Be wires with a diameter of 1.4 mm were tested under uniaxial cyclic loading at various loading rates and cold temperatures. The test results from 23 to -50 °C demonstrate that Cu-Al-Be exhibits superelastic behavior at cold temperatures down to -85 °C. It is also found that with decreasing temperature the transformation plateau stress is reduced while its fatigue life increases under cyclic testing.

  12. 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

  13. Neural Mechanisms Underlying Anxiety-Chronic Pain Interactions.

    PubMed

    Zhuo, Min

    2016-03-01

    Chronic pain is a major medical problem that is resistant to conventional medical intervention. It also causes emotional changes such as anxiety and fear. Furthermore, anxiety or fear often enhances the suffering of pain. Based on recent studies, I propose chronic anxiety triggered by injury or chronic pain is mediated through presynaptic long-term potentiation (LTP) in the anterior cingulate cortex (ACC), a key cortical region for pain perception. Conversely, NMDA receptor-dependent postsynaptic LTP plays a more important role in behavioral sensitization in chronic pain. Thus, postsynaptic and presynaptic LTP in ACC neurons are likely the key cellular mechanisms for causing chronic pain and its associated anxiety, respectively. This suggests potential targets for treating chronic pain and related anxiety. PMID:26878750

  14. Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging

    PubMed Central

    Wardlaw, JM; Smith, C; Dichgans, M

    2013-01-01

    The term “cerebral small vessel disease” (SVD) describes a range of neuroimaging, pathological and associated clinical features. The latter range from none, to discrete focal neurological symptoms (stroke), to insidious global neurological dysfunction and dementia. The public health burden is considerable. The pathogenesis is largely unknown. Although associated with vascular risk factors, and generally considered to result from an intrinsic cerebral arteriolar occlusive disease, the pathological processes leading to the arteriolar disease, how these result in brain disease, how SVD lesions contribute to neurological or cognitive symptoms and the relationship to risk factors, have been the subject of much speculation. Pathology often reflects end-stage disease making determination of the earliest stages difficult. Neuroimaging provides considerable insights: the small vessels are not easily seen themselves, but the effects of their malfunction on the brain can be tracked on detailed brain imaging. We review the growing evidence for the most likely mechanisms. PMID:23602162

  15. 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

  16. 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.

  17. The CHAIN program: forging evolutionary links to underlying mechanisms.

    PubMed

    Neuwald, Andrew F

    2007-11-01

    Proteins evolve new functions by modifying and extending the molecular machinery of an ancestral protein. Such changes show up as divergent sequence patterns, which are conserved in descendent proteins that maintain the divergent function. After multiply-aligning a set of input sequences, the CHAIN program partitions the sequences into two functionally divergent groups and then outputs an alignment that is annotated to reveal the selective pressures imposed on divergent residue positions. If atomic coordinates are also provided, hydrogen bonds and other atomic interactions associated with various categories of divergent residues are graphically displayed. Such analyses establish links between protein evolutionary divergence and functionally crucial atomic features and, as a result, can suggest plausible molecular mechanisms for experimental testing. This is illustrated here by its application to bacterial clamp-loader ATPases. PMID:17962021

  18. 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

  19. Common Mechanisms Underlying Epileptogenesis and the Comorbidities of Epilepsy.

    PubMed

    Mazarati, Andrey; Sankar, Raman

    2016-01-01

    The importance of comorbidities in determining the quality of life of individuals with epilepsy and their families has received increasing attention in the past decade. Along with it has come a recognition that in some individuals, certain comorbidities may have preexisted, and may have contributed to their developing epilepsy. Many mechanisms are capable of interconnecting different dysfunctions that manifest as distinct disorders, often diagnosed and managed by different specialists. We review the human data from the perspective of epidemiology as well as insights gathered from neurodiagnostic and endocrine studies. Animal studies are reviewed to refine our mechanistic understanding of the connections, because they permit the narrowing of variables, which is not possible when studying humans. PMID:27371669

  20. 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.

  1. 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.

  2. Mechanical behavior of enamel rods under micro-compression.

    PubMed

    Yilmaz, Ezgi D; Schneider, Gerold A

    2016-10-01

    Exploring the structural strategies behind the optimized mechanical performance of hierarchical materials has been a focal point of extensive research over the past decades. Dental enamel is one such natural material, comprising a complicated hierarchical structure with a high level of mineral content. Bundles of hydroxyapatite nanofibers (level-1) Ø: 50nm form enamel rods (level-2) Ø: 5µm, which constitute bands (level-3) Ø: 50µm. While a number of studies in the last decade using advanced fracture mechanical methods have revealed an increasing trend in the fracture toughness of enamel with each additional level of hierarchy, there is still no general agreement on how hierarchical structuring affects the stiffness and strength of enamel. In this study, we identified the stiffness and strength values of the isolated rods (level-2) via micro-compression. The rods were tested in three different orientations with respect to the loading direction: parallel, perpendicular and oblique. The highest stress level withstood before catastrophic fracture was observed to be ~1500MPa in perpendicular orientation. In the oblique loading, the specimens failed by shearing and exhibited a damage-tolerant deformation behavior, which was attributed to the conjugation spots identified between the rods and interrod sheets. The elastic modulus was ~60GPa on average and similar in all orientations. The isotropy in stiffness was attributed to the mineral contacts residing between rods. This was verified by an analytical model derived for level-1 and extended over higher hierarchical levels. The experimental results obtained at level-2 were comparable to the compressive strength and stiffness values reported for level-1 and bulk enamel in the literature. In general, our results suggest that hierarchy has only a minor influence on the compressive properties of enamel. PMID:27415405

  3. Mechanisms of Protection against Clostridium difficile Infection by the Monoclonal Antitoxin Antibodies Actoxumab and Bezlotoxumab

    PubMed Central

    Yang, Zhiyong; Ramsey, Jeremy; Hamza, Therwa; Zhang, Yongrong; Li, Shan; Yfantis, Harris G.; Lee, Dong; Hernandez, Lorraine D.; Seghezzi, Wolfgang; Furneisen, Jamie M.; Davis, Nicole M.

    2014-01-01

    Clostridium difficile infection (CDI) represents the most prevalent cause of antibiotic-associated gastrointestinal infections in health care facilities in the developed world. Disease symptoms are caused by the two homologous exotoxins, TcdA and TcdB. Standard therapy for CDI involves administration of antibiotics that are associated with a high rate of disease recurrence, highlighting the need for novel treatment paradigms that target the toxins rather than the organism itself. A combination of human monoclonal antibodies, actoxumab and bezlotoxumab, directed against TcdA and TcdB, respectively, has been shown to decrease the rate of recurrence in patients treated with standard-of-care antibiotics. However, the exact mechanism of antibody-mediated protection is poorly understood. In this study, we show that the antitoxin antibodies are protective in multiple murine models of CDI, including systemic and local (gut) toxin challenge models, as well as primary and recurrent models of infection in mice. Systemically administered actoxumab-bezlotoxumab prevents both the damage to the gut wall and the inflammatory response, which are associated with C. difficile in these models, including in mice challenged with a strain of the hypervirulent ribotype 027. Furthermore, mutant antibodies (N297Q) that do not bind to Fcγ receptors provide a level of protection similar to that of wild-type antibodies, demonstrating that the mechanism of protection is through direct neutralization of the toxins and does not involve host effector functions. These data provide a mechanistic basis for the prevention of recurrent disease observed in CDI patients in clinical trials. PMID:25486992

  4. Bradykinin in ischemic conditioning-induced tissue protection: Evidences and possible mechanisms.

    PubMed

    Sharma, Roohani; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh

    2015-12-01

    Ischemic conditioning is an intrinsic protective mechanism in which repeated short episodes of reversible ischemia protects the tissue and increases its tolerance against a subsequent longer period of ischemia (index ischemia). Bradykinin is a physiologically and pharmacologically active peptide of the kallikrein-kinin system. Besides the involvement of bradykinin in a variety of physiological and pathological responses such as pain, inflammation and in cardiovascular system as a potent vasodilator, it also acts as an endogenous cytoprotective mediator in the ischemic tissue. Pretreatment with various pharmacological modulators of bradykinin has confirmed the involvement of bradykinin in ischemic conditioning-induced protection. The protective actions of bradykinin in three major paradigms of ischemic conditioning i.e. ischemic preconditioning, ischemic postconditioning and remote ischemic preconditioning involves activation and regulation of various endogenous signaling cascades to render the heart resistant to infarction. In ischemic preconditioning, bradykinin exerts cardioprotective effect via activation of PI3K/Akt/eNOS signaling pathway and regulation of redox state via NO release. The role of bradykinin and its B2 receptors in ischemic-postconditioning induced neuroprotection has been described mainly due to its increased redox signaling cascade and activation of mitochondrial anti-apoptotic pathway. Furthermore, its cardioprotective role during remote ischemic preconditioning has been associated with activation of B2 receptors mediated neurogenic pathway and internalization of B2 receptors along with the formation of signalosomes that activates intracellular cytoprotective transduction pathways. The present review focuses on the potential role of bradykinin in mediating different forms of ischemic conditioning (pre/post/remote)-induced cardioprotection and neuroprotection along with the possible mechanisms. PMID:26499976

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Analytical assessment of woven fabrics under vertical stabbing - The role of protective clothing.

    PubMed

    Hejazi, Sayyed Mahdi; Kadivar, Nastaran; Sajjadi, Ali

    2016-02-01

    Knives are being used more commonly in street fights and muggings. Therefore, this work presents an analytical model for woven fabrics under vertical stabbing loads. The model is based on energy method and the fabric is assumed to be unidirectional comprised of N layers. Thus, the ultimate stab resistance of fabric was determined based on structural parameters of fabric and geometrical characteristics of blade. Moreover, protective clothing is nowadays considered as a strategic branch in technical textile industry. The main idea of the present work is improving the stab resistance of woven textiles by using metal coating method. In the final, a series of vertical stabbing tests were conducted on cotton, polyester and polyamide fabrics. Consequently, it was found that the model predicts with a good accuracy the ultimate stab resistance of the sample fabrics. PMID:26774251

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  16. 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

  17. Consensus Paper: Pathological Mechanisms Underlying Neurodegeneration in Spinocerebellar Ataxias

    PubMed Central

    Matilla-Dueñas, A.; Ashizawa, T.; Brice, A.; Magri, S.; McFarland, K. N.; Pandolfo, M.; Pulst, S. M.; Riess, O.; Rubinsztein, D. C.; Schmidt, J.; Schmidt, T.; Scoles, D. R.; Stevanin, G.; Taroni, F.; Underwood, B. R.; Sánchez, I.

    2014-01-01

    Intensive scientific research devoted in the recent years to understand the molecular mechanisms or neurodegeneration in spinocerebellar ataxias (SCAs) are identifying new pathways and targets providing new insights and a better understanding of the molecular pathogenesis in these diseases. In this consensus manuscript, the authors discuss their current views on the identified molecular processes causing or modulating the neurodegenerative phenotype in spinocerebellar ataxias with the common opinion of translating the new knowledge acquired into candidate targets for therapy. The following topics are discussed: transcription dysregulation, protein aggregation, autophagy, ion channels, the role of mitochondria, RNA toxicity, modulators of neurodegeneration and current therapeutic approaches. Overall point of consensus includes the common vision of neurodegeneration in SCAs as a multifactorial, progressive and reversible process, at least in early stages. Specific points of consensus include the role of the dysregulation of protein folding, transcription, bioenergetics, calcium handling and eventual cell death with apoptotic features of neurons during SCA disease progression. Unresolved questions include how the dysregulation of these pathways triggers the onset of symptoms and mediates disease progression since this understanding may allow effective treatments of SCAs within the window of reversibility to prevent early neuronal damage. Common opinions also include the need for clinical detection of early neuronal dysfunction, for more basic research to decipher the early neurodegenerative process in SCAs in order to give rise to new concepts for treatment strategies and for the translation of the results to preclinical studies and, thereafter, in clinical practice. PMID:24307138

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

    PubMed

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

    2010-07-01

    Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations--this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of gamma rays. PMID:20664639

  19. Pathological mechanisms underlying aneurysmal subarachnoid haemorrhage and vasospasm.

    PubMed

    Penn, David L; Witte, Samantha R; Komotar, Ricardo J; Sander Connolly, E

    2015-01-01

    Aneurysmal subarachnoid haemorrhage is a cerebrovascular disease associated with an overall mortality as high as 50%. Delayed ischaemic neurologic deficits are a major contributor to this statistic, as well as the significant morbidity associated with the disease. Studies examining the pathophysiologic events causing these devastating changes in cerebral blood flow have identified several mechanisms which are thought to contribute to the development of delayed ischaemic neurological deficits, perhaps the most damaging of which are increased intracranial pressure and cerebral vasospasm. In addition, the presence of blood in the subarachnoid space can trigger a myriad of reactions resulting in increased capillary permeability, breakdown of the blood-brain barrier, and inflammation in surrounding neural tissue that adds to the devastating effects of haemorrhage. A detailed understanding of the post-haemorrhagic cellular and molecular changes that contribute to the development of cerebral ischaemia and vasospasm is imperative to the formulation of treatment and prevention options for subarachnoid haemorrhage patients. Despite a large body of research within this field, a complete understanding of rupture and vasospasm remains elusive. This study reviews the role of vasoactive substances, such as endothelin-1, as well as the histochemistry and molecular pathology of post-haemorrhage inflammation in the development of vasospasm and cerebral ischaemia. PMID:25113969

  20. Improving beef color stability: practical strategies and underlying mechanisms.

    PubMed

    Suman, Surendranath P; Hunt, Melvin C; Nair, Mahesh N; Rentfrow, Gregg

    2014-11-01

    This paper overviewed the current literature on strategies to improve beef color and attempted to logically explain the fundamental mechanisms involved. Surface color and its stability are critical traits governing the marketability of fresh beef when sold, whereas internal cooked color is utilized as an indicator for doneness at the point of consumption. A multitude of exogenous and endogenous factors interact with the redox biochemistry of myoglobin in post-mortem skeletal muscles. The scientific principles of these biomolecular interactions are applied by the meat industry as interventions for pre-harvest (i.e. diet, animal management) and post-harvest (i.e. packaging, aging, antioxidants) strategies to improve color stability in fresh and cooked beef. Current research suggests that the effects of several of these strategies are specific to type of animal, feeding regimen, packaging system, and muscle source. Meat scientists should explore novel ways to manipulate these factors using a biosystems approach to achieve improved beef color stability, satisfy consumer perception, and increase market profitability. PMID:25041654

  1. 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

  2. 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

  3. Molecular mechanisms underlying KVS-1-MPS-1 complex assembly.

    PubMed

    Wang, Yi; Sesti, Federico

    2007-11-01

    Formation of heteromeric complexes between voltage-gated K(+) (Kv) channels and accessory (beta) subunits is a widespread means to generate heterogeneity of K(+) current in the nervous system. Here we investigate the principles that determine the interactions of Caenorhabditis elegans MPS-1, a bifunctional beta-subunit that possesses kinase activity, with Kv channels. MPS-1 belongs to the evolutionarily conserved family of KCNE beta-subunits that modulate the functional properties of a variety of Kv channels and that, when defective, can cause congenital and acquired disease in Homo sapiens. In Chinese hamster ovary cells, MPS-1 forms stable complexes with different alpha-subunits. The transmembrane domain of MPS-1 is necessary and sufficient for MPS-1 complex formation. The hydropathicity of the transmembrane domain is an important factor controlling MPS-1 assembly. A highly hydrophobic MPS-1 mutant fails to interact with its endogenous channel partners when transgenically expressed in living worms. The hydropathic mechanism does not require specific points of contact between interacting proteins. This may allow MPS-1 to assemble with various Kv channels, presumably modifying the electrical properties of each. PMID:17604313

  4. Risk factors for pancreatic cancer: underlying mechanisms and potential targets

    PubMed Central

    Kolodecik, Thomas; Shugrue, Christine; Ashat, Munish; Thrower, Edwin C.

    2014-01-01

    Purpose of the review: Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer. Recent findings: Intracellular activation of both pancreatic enzymes and the transcription factor NF-κB are important mechanisms that induce acute pancreatitis (AP). Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogenic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16) can ultimately lead to development of pancreatic cancer. Summary: Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions. PMID:24474939

  5. An important role of carotenoids in protection of photosynthetic apparatus under VAM inoculation on Momordica charantia.

    PubMed

    Azmat, Rafia

    2013-01-01

    The effect of mixed inoculums of VAM (Vesicular Arbuscular Mycorrhizas) fungi on seed growth and photosynthetic apparatus in green house was monitored. The plants were watered daily with tap water. Plants were cultivated in natural environment in mid of March (2011). A direct relation between root length and water contents suggests a defense mechanism of MP (microrihzal plants) against the fungal stress. It was also supported by the fact that the leaf area of MP was much greater as compared to the NMP (non microrihzal plants) with elevated concentration of all chlorophyllus pigments in 30 days. An increase in the surface area of the leaf and concentration of the pigments, may be for an acceleration in absorption of CO₂ for reduction of it into glucose through oxidation of water molecule. The non-significant decline in glucose contents support the above hypothesis of rapid redox reaction mechanism which was established to overcome the stress. The positive effects of mycorrhizal which were already mentioned in the literature were reported in this article in relations of survival strategies of the plant, adapted in stress conditions. An increase in the chlorophyll contents (30 d) and leaf area of plants possibly attributed with absorption of solar radiation for the protection of plants. It was also supported by the higher concentration of carotenoids (30 d) that may have an additional function of regulation of certain developmental responses and screening of light to save the plants from stress conditions. PMID:24372263

  6. 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

  7. Mechanisms underlying global stereopsis in fovea and periphery.

    PubMed

    Witz, Nirel; Hess, Robert F

    2013-07-19

    To better understand the pooling properties underlying global stereopsis we examined the relationship between carrier luminance spatial frequency and modulator disparity spatial frequency. Thresholds for detecting global sinusoidal disparity corrugations of spatially band-pass noise were measured as a function of modulator disparity spatial frequency for both centrally and peripherally located stimuli using a standard 2-IFC task. We found a characteristic relationship that depended on modulator disparity spatial frequency. At high modulator disparity spatial frequencies (>1c/d), there is an optimal ratio of around 2.6, whereas at low modulator disparity spatial frequencies, there is an optimal absolute carrier luminance spatial frequency (i.e., 3c/d). In the periphery, vision is restricted to modulator disparity spatial frequencies below 1c/d and, as a consequence, following the above rule, there is an optimum absolute carrier luminance spatial frequency that reduces in spatial frequency with increasing eccentricity. This finding is consistent with there being more than one channel processing global stereo that is subsequently confirmed using a 2×2 AFC detection/discrimination paradigm. Furthermore, because of the different carrier/modulator relationships in central and peripheral vision, peripheral global stereo cannot be simply related to central global stereo by a scaling factor and thus cannot be simply due to cortical magnification, as originally thought. PMID:23680486

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

    NASA Astrophysics Data System (ADS)

    Sun, Yuanxiang

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  10. Neural network mechanisms underlying stimulus driven variability reduction.

    PubMed

    Deco, Gustavo; Hugues, Etienne

    2012-01-01

    It is well established that the variability of the neural activity across trials, as measured by the Fano factor, is elevated. This fact poses limits on information encoding by the neural activity. However, a series of recent neurophysiological experiments have changed this traditional view. Single cell recordings across a variety of species, brain areas, brain states and stimulus conditions demonstrate a remarkable reduction of the neural variability when an external stimulation is applied and when attention is allocated towards a stimulus within a neuron's receptive field, suggesting an enhancement of information encoding. Using an heterogeneously connected neural network model whose dynamics exhibits multiple attractors, we demonstrate here how this variability reduction can arise from a network effect. In the spontaneous state, we show that the high degree of neural variability is mainly due to fluctuation-driven excursions from attractor to attractor. This occurs when, in the parameter space, the network working point is around the bifurcation allowing multistable attractors. The application of an external excitatory drive by stimulation or attention stabilizes one specific attractor, eliminating in this way the transitions between the different attractors and resulting in a net decrease in neural variability over trials. Importantly, non-responsive neurons also exhibit a reduction of variability. Finally, this reduced variability is found to arise from an increased regularity of the neural spike trains. In conclusion, these results suggest that the variability reduction under stimulation and attention is a property of neural circuits. PMID:22479168

  11. Mechanisms underlying angiotensin II-induced calcium oscillations

    PubMed Central

    Edwards, Aurélie; Pallone, Thomas L.

    2008-01-01

    To gain insight into the mechanisms that underlie angiotensin II (ANG II)-induced cytoplasmic Ca2+ concentration ([Ca]cyt) oscillations in medullary pericytes, we expanded a prior model of ion fluxes. ANG II stimulation was simulated by doubling maximal inositol trisphosphate (IP3) production and imposing a 90% blockade of K+ channels. We investigated two configurations, one in which ryanodine receptors (RyR) and IP3 receptors (IP3R) occupy a common store and a second in which they reside on separate stores. Our results suggest that Ca2+ release from stores and import from the extracellular space are key determinants of oscillations because both raise [Ca] in subplasmalemmal spaces near RyR. When the Ca2+-induced Ca2+ release (CICR) threshold of RyR is exceeded, the ensuing Ca2+ release is limited by Ca2+ reuptake into stores and export across the plasmalemma. If sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pumps do not remain saturated and sarcoplasmic reticulum Ca2+ stores are replenished, that phase is followed by a resumption of leak from internal stores that leads either to [Ca]cyt elevation below the CICR threshold (no oscillations) or to elevation above it (oscillations). Our model predicts that oscillations are more prone to occur when IP3R and RyR stores are separate because, in that case, Ca2+ released by RyR during CICR can enhance filling of adjacent IP3 stores to favor a high subsequent leak that generates further CICR events. Moreover, the existence or absence of oscillations depends on the set points of several parameters, so that biological variation might well explain the presence or absence of oscillations in individual pericytes. PMID:18562632

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

    PubMed Central

    Theissen, Guenter; Melzer, Rainer

    2007-01-01

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

  13. Untangling the web: Mechanisms underlying ER network formation

    PubMed Central

    Goyal, Uma; Blackstone, Craig

    2013-01-01

    The ER is a continuous membrane system consisting of the nuclear envelope, flat sheets often studded with ribosomes, and a polygonal network of highly-curved tubules extending throughout the cell. Although protein and lipid biosynthesis, protein modification, vesicular transport, Ca2+dynamics, and protein quality control have been investigated in great detail, mechanisms that generate the distinctive architecture of the ER have been uncovered only recently. Several protein families including the reticulons and REEPs/DP1/Yop1p harbor hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1p family of dynamin-related GTPases interact with the ER-shaping proteins and mediate the formation of three-way junctions responsible for the polygonal structure of the tubular ER network, with Lunapark proteins acting antagonistically. Additional classes of tubular ER proteins including some REEPs and the M1 spastin ATPase interact with the microtubule cytoskeleton. Flat ER sheets possess a different complement of proteins such as p180, CLIMP-63 and kinectin implicated in shaping, cisternal stacking and cytoskeletal interactions. The ER is also in constant motion, and numerous signaling pathways as well as interactions among cytoskeletal elements, the plasma membrane, and organelles cooperate to position and shape the ER dynamically. Finally, many proteins involved in shaping the ER network are mutated in the most common forms of hereditary spastic paraplegia, indicating a particular importance for proper ER morphology and distribution in large, highly-polarized cells such as neurons. PMID:23602970

  14. Mechanisms underlying optical spectroscopic changes in primate and human cortex

    NASA Astrophysics Data System (ADS)

    Hochman, Daryl

    2003-03-01

    The optical scattering and absorption properties of brain tissue are correlated with changes in the level of neuronal activity. These activity-evoked optical changes are known as 'intrinsic optical signals' (IOS). Such changes are thought to be generated by a combination of least three physiological mechanisms: i) changes in blood volume, ii) changes in blood oxygenation, and iii) blood-independent light scattering changes resulting from ion fluxes associated with neuronal activity. The usefulness of IOS depends upon knowledge of the spatial and temporal relationships between neuronal activity and changes in brain metabolism and cerebral hemodynamics. Our studies focus on better understanding these relationships. The two major hemodynamic changes evoked by increases in neuronal activity are i) increases in blood volume mediated by dilation of microscopic pial arterioles, and ii) increases in blood oxygenation in the veins draining regions of activated cortex. Our experimental strategy has been to acquire high-magnification data sufficient to resolve the dynamics occurring within the distinct microvascular compartments. At specific wavelengths, contributions of blood oxygenation and volume to the IOS can be directly determined by observing the optical changes occurring within the distinct microvascular compartments. In this way, we have directly identified wavelengths that are either highly 'volume-selective' or 'oxygenation-selective'. Blood volume maps correlate closely with the spatial locations of neuronal activity, while blood oxygenation maps are often maximal in the larger draining veins at sites distant to neuronal activity. We have characterized novel spatio-temporal phenomena including propagating circular waves of activity evoked by epileptic activity.

  15. Compression under a mechanical counter pressure space suit glove

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

    Background: Current gas-pressurized space suits are bulky stiff shells severely limiting astronaut function and capability. A mechanical counter pressure (MCP) space suit in the form of a tight elastic garment could dramatically improve extravehicular activity (EVA) dexterity, but also be advantageous in safety, cost, mass and volume. The purpose of this study was to verify that a prototype MCP glove exerts the design compression of 200 mmHg, a pressure similar to the current NASA EVA suit. Methods: Seven male subjects donned a pressure measurement array and MCP glove on the right hand, which was placed into a partial vacuum chamber. Average compression was recorded on the palm, the bottom of the middle finger, the top of the middle finger and the dorsum of the hand at pressures of 760 (ambient), 660 and 580 mmHg. The vacuum chamber was used to simulate the pressure difference between the low breathing pressure of the current NASA space suits (approximately 200 mmHg) and an unprotected hand in space. Results: At ambient conditions, the MCP glove compressed the dorsum of the hand at 203.5 +/- 22.7 mmHg, the bottom of the middle finger at 179.4 +/- 16.0 mmHg, and the top of the middle finger at 183.8 +/- 22.6 mmHg. The palm compression was significantly lower (59.6 +/- 18.8 mmHg, p<0.001). There was no significant change in glove compression with the chamber pressure reductions. Conclusions: The MCP glove compressed the dorsum of the hand and middle finger at the design pressure.

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

    PubMed Central

    Bellesi, Michele; Riedner, Brady A.; Garcia-Molina, Gary N.; Cirelli, Chiara; Tononi, Giulio

    2014-01-01

    Even modest sleep restriction, especially the loss of sleep slow wave activity (SWA), is invariably associated with slower electroencephalogram (EEG) activity during wake, the occurrence of local sleep in an otherwise awake brain, and impaired performance due to cognitive and memory deficits. Recent studies not only confirm the beneficial role of sleep in memory consolidation, but also point to a specific role for sleep slow waves. Thus, the implementation of methods to enhance sleep slow waves without unwanted arousals or lightening of sleep could have significant practical implications. Here we first review the evidence that it is possible to enhance sleep slow waves in humans using transcranial direct-current stimulation (tDCS) and transcranial magnetic stimulation. Since these methods are currently impractical and their safety is questionable, especially for chronic long-term exposure, we then discuss novel data suggesting that it is possible to enhance slow waves using sensory stimuli. We consider the physiology of the K-complex (KC), a peripheral evoked slow wave, and show that, among different sensory modalities, acoustic stimulation is the most effective in increasing the magnitude of slow waves, likely through the activation of non-lemniscal ascending pathways to the thalamo-cortical system. In addition, we discuss how intensity and frequency of the acoustic stimuli, as well as exact timing and pattern of stimulation, affect sleep enhancement. Finally, we discuss automated algorithms that read the EEG and, in real-time, adjust the stimulation parameters in a closed-loop manner to obtain an increase in sleep slow waves and avoid undesirable arousals. In conclusion, while discussing the mechanisms that underlie the generation of sleep slow waves, we review the converging evidence showing that acoustic stimulation is safe and represents an ideal tool for slow wave sleep (SWS) enhancement. PMID:25389394

  17. 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.

  18. 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

  19. The neural mechanisms underlying internally and externally guided task selection.

    PubMed

    Orr, Joseph M; Banich, Marie T

    2014-01-01

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

  20. Meniscal repair following meniscectomy: mechanism and protective effect. Experimental study in the dog.

    PubMed

    Berjon, J J; Munuera, L; Calvo, M

    1990-01-01

    Meniscal repair was studied to evaluate the mechanism and its potential protective effects on the articular cartilage in an experimental model consisting of 68 knees of adult dogs on which five different types of medial meniscectomy were performed. The results were assessed by macroscopic, microangiographic, and histological methods, after a sequential follow-up period of 10-450 days. Two different mechanisms of meniscal repair were observed, depending on whether meniscal section had been performed in vascular (total meniscectomy) or avascular (subtotal or partial meniscectomy) zones. It was also observed that the repaired meniscal tissue does not prevent articular cartilage degeneration. This is more closely related to the size of the meniscal fragment preserved at meniscectomy. Due to the biomechanical importance of the meniscus and the lack of functional relevance of the repaired meniscal tissue, the most conservative approach possible to meniscectomy is recommended. PMID:1703666

  1. Mystixin-7 Peptide Protects Ionotropic Glutamatergic Mechanisms against Glutamate-Induced Excitotoxicity In Vitro

    PubMed Central

    2016-01-01

    Hyperactivation of the N-methyl-D-aspartic acid type glutamate receptors (NMDARs) causes glutamate excitotoxicity, a process potentially important for many neurological diseases. This study aims to investigate protective effects of the synthetic corticotrophin-releasing factor-like peptide, mystixin-7 (MTX), on model glutamate-induced excitotoxicity in vitro. The technique online monitoring of electrophysiological parameters (excitatory glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPAR) and NMDAR-dependent postsynaptic mechanisms) in the olfactory cortex slices was used. Application of L-glutamate in toxic concentration (20 mM) on slices evoked hyperactivation of NMDARs and weaker activation of the AMPARs. Upon further action agonist, the excessive activation of glutamate receptors was replaced by their irreversible blockade. Pretreatment of the slices using MTX in different concentrations (50 and 100 mg/mL) protected both NMDARs and AMPARs from glutamate-induced damage. An enzymatic treatment of MTX reduced hyperactivation of both NMDARs and AMPARs. The present study demonstrated that MTX minipeptide protected the functioning of both NMDARs and AMPARs against glutamate-induced damage. The MTX peptide is a prospective candidate for elaborated medication in treatment of neurological diseases. PMID:27504123

  2. Exploring the support mechanisms health visitors use in safeguarding and child protection practice.

    PubMed

    Rooke, Justine

    2015-10-01

    Health visitors lead the Healthy Child Programme (HCP), a universal public health service designed to give children the best start in life. Running through the HCP are responsibilities to safeguard and protect children. Supporting the role of the health visitor is essential to ensure quality interventions and improved outcomes for children. This article describes an empirical study. It explores the experiences and views of health visitors on the mechanisms of support they use for working in child protection and safeguarding. A qualitative approach was used to collect data from two focus groups. The data produced was transcribed and a thematic analysis used to produce the results. The results demonstrate that health visitors gain the majority of their support from their colleagues and from supervision processes. Also identified from the data analysis were three factors which health visitors felt supported their role. These were support for managing the emotions associated with child protection work, feeling safe and effective in practice and having time to reflect and evaluate casework. PMID:26596133

  3. 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

  4. Probing the protective mechanism of poly-ß-hydroxybutyrate against vibriosis by using gnotobiotic Artemia franciscana and Vibrio campbellii as host-pathogen model

    PubMed Central

    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

  5. Corticonic models of brain mechanisms underlying cognition and intelligence

    NASA Astrophysics Data System (ADS)

    Farhat, Nabil H.

    underlying intelligence and other higher level brain functions.

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

    NASA Astrophysics Data System (ADS)

    Chen, Ying

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

  7. 48 CFR 3.907 - Whistleblower Protections Under the American Recovery and Reinvestment Act of 2009 (the Recovery...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Whistleblower Protections Under the American Recovery and Reinvestment Act of 2009 (the Recovery Act). 3.907 Section 3.907 Federal... Under the American Recovery and Reinvestment Act of 2009 (the Recovery Act)....

  8. 48 CFR 3.907 - Whistleblower Protections Under the American Recovery and Reinvestment Act of 2009 (the Recovery...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Whistleblower Protections Under the American Recovery and Reinvestment Act of 2009 (the Recovery Act). 3.907 Section 3.907 Federal... Under the American Recovery and Reinvestment Act of 2009 (the Recovery Act)....

  9. Changes in the protective mechanism of photosystem II and molecular regulation in response to high temperature stress in grapevines.

    PubMed

    Zha, Qian; Xi, Xiaojun; Jiang, Aili; Wang, Shiping; Tian, Yihua

    2016-04-01

    The response to high temperature stress, which influences the growth and development of grapes, varies between laboratory conditions and ambient growth conditions, and is poorly understood. In the present study, we investigated the effects of high temperature on grapevines (Vitis vinifera L. × Vitis labrusca L.) grown under artificial and ambient conditions. A temperature of 35 °C did not alter Photosystem II (PS II) activity and the expression of some heat-shock protein (HSPs) genes. These changes were, however, observed at 45 °C under artificial conditions, as well as when the ambient natural temperature was greater than 40 °C. Interestingly, these changes corresponded to shifts in PS II activity and HSPs expression. The protective mechanism of PS II was induced by temperatures greater than 40 °C. These data indicating that the expression of HSFA2, GLOS1 and some heat-shock protein (sHSPs) genes were more sensitive to the heat stress. Unlike the Kyoho grapevines, the Jumeigui grapevines showed rapid and dramatically deterioration in PS II activity and the expression of some heat response genes and HSP21, indicating that the Jumeigui grapevines could not counter the heat stress. These were some differences in PSII activity and the expression of heat response genes between the two cultivated conditions could be attributed to other environmental factors, inherent plant vigor, and the adaptation mechanism. PMID:26852109

  10. Repetitive live sporozoites inoculation under arteether chemoprophylaxis confers protection against subsequent sporozoite challenge in rodent malaria model.

    PubMed

    Bhardwaj, Jyoti; Siddiqui, Arif Jamal; Goyal, Manish; Prakash, Kirtika; Soni, Awakash; Puri, Sunil K

    2016-06-01

    Inoculation with live sporozoites under prophylactic antimalarial cover (CPS-immunization) represents an alternate approach to develop sterile, reproducible, and long-term protection against malaria. Here, we have employed arteether (ART), a semi synthetic derivative of artemisinin to explore its potential as a chemoprophylaxis candidate in CPS approach and systematically compared the protective potential of arteether with mefloquine, azithromycin and primaquine. Blood stage patency and quantitative RT-PCR of liver stage parasite load were monitored as primary key end-points for protection against malaria challenge infection. For this purpose, sequential exposures of Plasmodium yoelii sporozoites under prophylactic treatment with arteether (ART), mefloquine (MFQ), azithromycin (AZ) or primaquine (PQ) was conducted in experimental Swiss mice. Our results show that during the first three sequential exposures (1st, 2nd and 3rd challenge) no marked difference in the blood stage patency was observed between control and CPS-ART group. However, delayed patency was recorded following 4th sporozoite challenge and mice enjoyed sterile protection after 5th sporozoite challenge. A similar response was observed in CPS-MFQ group, whereas earlier protection was recorded in CPS-AZ group i.e., after 4th sprozoite challenge. However, mice under PQ cover did not show any protection/delay in patency even after five sequential sporozoite inoculations, possibly due to inhibition of liver stage development. Furthermore, protection acquired by CPS-immunization is stage-specific as the protected mice remained susceptible to challenge with blood stage parasites. In short, the present study demonstrates that sporozoite administration under ART, MFQ or AZ treatment confers strong protection against subsequent sporozoite infection and the acquired response is dependent on the presence of liver stage parasites. PMID:26925772

  11. Mechanisms of radiation interaction with DNA: Potential implications for radiation protection

    SciTech Connect

    Not Available

    1988-01-01

    The Office of Health and Environmental Research (OHER) of the US Department of Energy conducts a broad multidisciplinary research program which includes basic biophysics, biophysical chemistry, molecular and cellular biology as well as experimental animal studies and opportunistic human studies. This research is directed at understanding how low levels of radiation of various qualities produce the spectrum of biological effects that are seen for such exposures. This workshop was entitled ''Mechanisms of Radiation Interaction with DNA: Potential Implications for Radiation Protection.'' It ws jointly sponsored by the Department of Energy and the Commission of European Communities. The aim of the 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. The overview of research provided by this multidisciplinary group will be helpful to the Office in program planning. This report includes a summary of the presentations, extended abstracts, the meeting agenda, research recommendations, and a list of participants. Individual papers are processed separately for the data base.

  12. Oriented clay nanopaper from biobased components--mechanisms for superior fire protection properties.

    PubMed

    Carosio, F; Kochumalayil, J; Cuttica, F; Camino, G; Berglund, L

    2015-03-18

    The toxicity of the most efficient fire retardant additives is a major problem for polymeric materials. Cellulose nanofiber (CNF)/clay nanocomposites, with unique brick-and-mortar structure and prepared by simple filtration, are characterized from the morphological point of view by scanning electron microscopy and X-ray diffraction. These nanocomposites have superior fire protection properties to other clay nanocomposites and fiber composites. The corresponding mechanisms are evaluated in terms of flammability (reaction to a flame) and cone calorimetry (exposure to heat flux). These two tests provide a wide spectrum characterization of fire protection properties in CNF/montmorrilonite (MTM) materials. The morphology of the collected residues after flammability testing is investigated. In addition, thermal and thermo-oxidative stability are evaluated by thermogravimetric analyses performed in inert (nitrogen) and oxidative (air) atmospheres. Physical and chemical mechanisms are identified and related to the unique nanostructure and its low thermal conductivity, high gas barrier properties and CNF/MTM interactions for char formation. PMID:25723913

  13. Racial-Ethnic Protective Factors and Mechanisms in Psychosocial Prevention and Intervention Programs for Black Youth.

    PubMed

    Jones, Shawn C T; Neblett, Enrique W

    2016-06-01

    Extending previous reviews related to cultural responsiveness in the treatment of ethnic minority youth, the current review provides a critical assessment and synthesis of both basic and applied research on the integration of three racial-ethnic protective factors (racial identity, racial socialization, Africentric worldview) in psychosocial prevention and intervention programs for Black children and adolescents. Seventeen programs meeting inclusion and exclusion criteria were evaluated for the extent to which racial-ethnic protective factors and related mechanisms were integrated, applied, and tested in such programs. A systematic assessment of these programs revealed that several prevention and intervention programs drew upon the three factors, particularly Africentric worldview. In addition, a number of studies hypothesized and assessed mechanisms, both those previously identified in conceptual literature and those that emerged from the interventions themselves. A set of recommendations encouraging the implementation of these factors into future prevention and intervention programs, examples of how clinicians can infuse these factors into psychotherapy, and areas for future research are discussed. PMID:27083688

  14. Using hierarchical linear growth models to evaluate protective mechanisms that mediate science achievement

    NASA Astrophysics Data System (ADS)

    von Secker, Clare Elaine

    The study of students at risk is a major topic of science education policy and discussion. Much research has focused on describing conditions and problems associated with the statistical risk of low science achievement among individuals who are members of groups characterized by problems such as poverty and social disadvantage. But outcomes attributed to these factors do not explain the nature and extent of mechanisms that account for differences in performance among individuals at risk. There is ample theoretical and empirical evidence that demographic differences should be conceptualized as social contexts, or collections of variables, that alter the psychological significance and social demands of life events, and affect subsequent relationships between risk and resilience. The hierarchical linear growth models used in this dissertation provide greater specification of the role of social context and the protective effects of attitude, expectations, parenting practices, peer influences, and learning opportunities on science achievement. While the individual influences of these protective factors on science achievement were small, their cumulative effect was substantial. Meta-analysis conducted on the effects associated with psychological and environmental processes that mediate risk mechanisms in sixteen social contexts revealed twenty-two significant differences between groups of students. Positive attitudes, high expectations, and more intense science course-taking had positive effects on achievement of all students, although these factors were not equally protective in all social contexts. In general, effects associated with authoritative parenting and peer influences were negative, regardless of social context. An evaluation comparing the performance and stability of hierarchical linear growth models with traditional repeated measures models is included as well.

  15. Silymarin's Protective Effects and Possible Mechanisms on Alcoholic Fatty Liver for Rats.

    PubMed

    Zhang, Wei; Hong, Rutao; Tian, Tulei

    2013-07-30

    Silymarin has been introduced fairly recently as a hepatoprotective agent. But its mechanisms of action still have not been well established. The aim of this study was to make alcoholic fatty liver model of rats in a short time and investigate silymarin's protective effects and possible mechanisms on alcoholic fatty liver for rats. The model of rat's alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. Histopathological changes were assessed by hematoxylin and eosin staining (HE). The activities of alanine transarninase (ALT) and aspartate aminotransferase (AST), the levels of total bilirubin (TBIL), total cholesterol (TC) and triglyceride (TG) in serum were detected with routine laboratory methods using an autoanalyzer. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in liver homogenates were measured by spectrophotometry. The TG content in liver tissue was determined by spectrophotometry. The expression of nuclear factor-κB (NF-κB), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in the liver were analyzed by immunohistochemistry. Silymarin effectively protected liver from alcohol-induced injury as evidenced by improving histological damage situation, reducing ALT and AST activities and TBIL level in serum, increasing SOD and GPx activities and decreasing MDA content in liver homogenates and reducing TG content in liver tissue. Additionally, silymarin markedly downregulated the expression of NF-κB p65, ICAM-1 and IL-6 in liver tissue. In conclusion, Silymarin could protect against the liver injury caused by ethanol administration. The effect may be related to alleviating lipid peroxidation and inhibiting the expression of NF-κB. PMID:24244810

  16. Oral non-typable Haemophilus influenzae enhances physiological mechanism of airways protection.

    PubMed

    Clancy, R L; Dunkley, M L

    2010-07-01

    Oral immunotherapy with inactivated non-typeable Haemophilus influenzae (NTHi) prevents exacerbations of chronic obstructive pulmonary disease, but the mechanism is unclear. The aim of this study was to determine the mechanism of protection. This was a placebo versus active prospective study over 3 months in 64 smokers. The active treatment was three courses of oral NTHi given at monthly intervals, followed by measurement of bacteriological and immunological parameters. The results can be summarized: (i) NTHi-specific T cells increased in the placebo treatment group over time (P<0.05); (ii) the T cell response in the oral NTHi group started earlier than that in the placebo group (P<0.05); and (iii) serum NTHi-specific immunoglobulin (Ig)G had significantly greater variation in the placebo group (P<0.0001). The increase in antibody in placebos over time correlated with exposure to live H. influenzae (P<0.05) determined from culture of gargles; (iv) reduction in saliva lysozyme over time (P<0.05) was detected only in the oral NTHi treatment group. These data are consistent with T cell priming of gut lymphoid tissue by aspiration of bronchus content into the gut, with oral immunotherapy augmenting this process leading to enhanced bronchus protection. The evidence for protection was a stable IgG antibody level through the study in the oral NTHi treatment group, contrasting with an increase in antibody correlating with exposure of the airways to H. influenzae in the placebo group. Saliva lysozyme was a useful biomarker of mucosal inflammation, falling after oral NTHi consistent with a reduction in the level of intralumenal inflammation. PMID:20408861

  17. Global assessment of river flood protection benefits and corresponding residual risks under climate change

    NASA Astrophysics Data System (ADS)

    Lim, Wee Ho; Yamazaki, Dai; Koirala, Sujan; Hirabayashi, Yukiko; Kanae, Shinjiro; Dadson, Simon J.; Hall, Jim W.

    2016-04-01

    substantially when flood protection level exceeds 20 years. These findings might be useful for decision-makers to weight the size of water infrastructure investment and emergency response capacity under climate change. 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 Change 3: 816-821, doi: 10.1038/nclimate1911. Jongman et al., 2015. Declining vulnerability to river floods and the global benefits of adaptation. Proceedings of National Academy of the United States of America 112, E2271-E2280, doi: 10.1073/pnas.1414439112. Sadoff et al., 2015. Securing Water, Sustaining Growth: Report of the GWP/OECD Task Force on Water Security and Sustainable Growth, University of Oxford, UK, 180 pp. Yamazaki et al., 2011. A physically based description of floodplain inundation dynamics in a global river routing model. Water Resources Research 47, W04501, doi: 10.1029/2010wr009726. Yamazaki et al., 2014. Development of the Global Width Database for Large Rivers. Water Resources Research 50, 3467-3480, doi: 10.1002/2013WR014664.

  18. Coupled mechanical-electrical-thermal modeling for short-circuit prediction in a lithium-ion cell under mechanical abuse

    NASA Astrophysics Data System (ADS)

    Zhang, Chao; Santhanagopalan, Shriram; Sprague, Michael A.; Pesaran, Ahmad A.

    2015-09-01

    In order to better understand the behavior of lithium-ion batteries under mechanical abuse, a coupled modeling methodology encompassing the mechanical, electrical and thermal response is presented for predicting short-circuit under external crush. The combined mechanical-electrical-thermal response is simulated in a commercial finite element software LS-DYNA® using a representative-sandwich finite-element model, where electrical-thermal modeling is conducted after an instantaneous mechanical crush. The model includes an explicit representation of each individual component such as the active material, current collector, separator, etc., and predicts their mechanical deformation under quasi-static indentation. Model predictions show good agreement with experiments: the fracture of the battery structure under an indentation test is accurately predicted. The electrical-thermal simulation predicts the current density and temperature distribution in a reasonable manner. Whereas previously reported models consider the mechanical response exclusively, we use the electrical contact between active materials following the failure of the separator as a criterion for short-circuit. These results are used to build a lumped representative sandwich model that is computationally efficient and captures behavior at the cell level without resolving the individual layers.

  19. Erosion protection by calcium lactate/sodium fluoride rinses under different salivary flows in vitro.

    PubMed

    Borges, Alessandra B; Scaramucci, Taís; Lippert, Frank; Zero, Domenick T; Hara, Anderson T

    2014-01-01

    This study investigated the effect of a calcium lactate prerinse on sodium fluoride protection in an in vitro erosion-remineralization model simulating two different salivary flow rates. Enamel and dentin specimens were randomly assigned to 6 groups (n = 8), according to the combination between rinse treatments - deionized water (DIW), 12 mM NaF (NaF) or 150 mM calcium lactate followed by NaF (CaL + NaF) - and unstimulated salivary flow rates - 0.5 or 0.05 ml/min - simulating normal and low salivary flow rates, respectively. The specimens were placed into custom-made devices, creating a sealed chamber on the specimen surface connected to a peristaltic pump. Citric acid was injected into the chamber for 2 min, followed by artificial saliva (0.5 or 0.05 ml/min) for 60 min. This cycle was repeated 4×/day for 3 days. Rinse treatments were performed daily 30 min after the 1st and 4th erosive challenges, for 1 min each time. Surface loss was determined by optical profilometry. KOH-soluble fluoride and structurally bound fluoride were determined in specimens at the end of the experiment. Data were analyzed by 2-way ANOVA and Tukey tests (α = 0.05). NaF and CaL + NaF exhibited significantly lower enamel and dentin loss than DIW, with no difference between them for normal flow conditions. The low salivary flow rate increased enamel and dentin loss, except for CaL + NaF, which presented overall higher KOH-soluble and structurally bound fluoride levels. The results suggest that the NaF rinse was able to reduce erosion progression. Although the CaL prerinse considerably increased F availability, it enhanced NaF protection against dentin erosion only under hyposalivatory conditions. PMID:24480975

  20. Tuning of Redox Regulatory Mechanisms, Reactive Oxygen Species and Redox Homeostasis under Salinity Stress

    PubMed Central

    Hossain, M. Sazzad; Dietz, Karl-Josef

    2016-01-01

    Soil salinity is a crucial environmental constraint which limits biomass production at many sites on a global scale. Saline growth conditions cause osmotic and ionic imbalances, oxidative stress and perturb metabolism, e.g., the photosynthetic electron flow. The plant ability to tolerate salinity is determined by multiple biochemical and physiological mechanisms protecting cell functions, in particular by regulating proper water relations and maintaining ion homeostasis. Redox homeostasis is a fundamental cell property. Its regulation includes control of reactive oxygen species (ROS) generation, sensing deviation from and readjustment of the cellular redox state. All these redox related functions have been recognized as decisive factors in salinity acclimation and adaptation. This review focuses on the core response of plants to overcome the challenges of salinity stress through regulation of ROS generation and detoxification systems and to maintain redox homeostasis. Emphasis is given to the role of NADH oxidase (RBOH), alternative oxidase (AOX), the plastid terminal oxidase (PTOX) and the malate valve with the malate dehydrogenase isoforms under salt stress. Overwhelming evidence assigns an essential auxiliary function of ROS and redox homeostasis to salinity acclimation of plants. PMID:27242807

  1. Examination of mechanisms underlying enhanced memory performance in action video game players: a pilot study

    PubMed Central

    Li, Xianchun; Cheng, Xiaojun; Li, Jiaying; Pan, Yafeng; Hu, Yi; Ku, Yixuan

    2015-01-01

    Previous studies have shown enhanced memory performance resulting from extensive action video game playing. The mechanisms underlying the cognitive benefit were investigated in the current study. We presented two types of retro-cues, with variable intervals to memory array (Task 1) or test array (Task 2), during the retention interval in a change detection task. In Task 1, action video game players demonstrated steady performance while non-action video game players showed decreased performance as cues occurred later, indicating their performance difference increased as the cue-to-memory-array intervals became longer. In Task 2, both participant groups increased their performance at similar rates as cues presented later, implying the performance difference in two groups were irrespective of the test-array-to-cue intervals. These findings suggested that memory benefit from game plays is not attributable to the higher ability of overcoming interference from the test array, but to the interactions between the two processes of protection from decay and resistance from interference, or from alternative hypotheses. Implications for future studies were discussed. PMID:26136720

  2. Examination of mechanisms underlying enhanced memory performance in action video game players: a pilot study.

    PubMed

    Li, Xianchun; Cheng, Xiaojun; Li, Jiaying; Pan, Yafeng; Hu, Yi; Ku, Yixuan

    2015-01-01

    Previous studies have shown enhanced memory performance resulting from extensive action video game playing. The mechanisms underlying the cognitive benefit were investigated in the current study. We presented two types of retro-cues, with variable intervals to memory array (Task 1) or test array (Task 2), during the retention interval in a change detection task. In Task 1, action video game players demonstrated steady performance while non-action video game players showed decreased performance as cues occurred later, indicating their performance difference increased as the cue-to-memory-array intervals became longer. In Task 2, both participant groups increased their performance at similar rates as cues presented later, implying the performance difference in two groups were irrespective of the test-array-to-cue intervals. These findings suggested that memory benefit from game plays is not attributable to the higher ability of overcoming interference from the test array, but to the interactions between the two processes of protection from decay and resistance from interference, or from alternative hypotheses. Implications for future studies were discussed. PMID:26136720

  3. Tuning of Redox Regulatory Mechanisms, Reactive Oxygen Species and Redox Homeostasis under Salinity Stress.

    PubMed

    Hossain, M Sazzad; Dietz, Karl-Josef

    2016-01-01

    Soil salinity is a crucial environmental constraint which limits biomass production at many sites on a global scale. Saline growth conditions cause osmotic and ionic imbalances, oxidative stress and perturb metabolism, e.g., the photosynthetic electron flow. The plant ability to tolerate salinity is determined by multiple biochemical and physiological mechanisms protecting cell functions, in particular by regulating proper water relations and maintaining ion homeostasis. Redox homeostasis is a fundamental cell property. Its regulation includes control of reactive oxygen species (ROS) generation, sensing deviation from and readjustment of the cellular redox state. All these redox related functions have been recognized as decisive factors in salinity acclimation and adaptation. This review focuses on the core response of plants to overcome the challenges of salinity stress through regulation of ROS generation and detoxification systems and to maintain redox homeostasis. Emphasis is given to the role of NADH oxidase (RBOH), alternative oxidase (AOX), the plastid terminal oxidase (PTOX) and the malate valve with the malate dehydrogenase isoforms under salt stress. Overwhelming evidence assigns an essential auxiliary function of ROS and redox homeostasis to salinity acclimation of plants. PMID:27242807

  4. A target-protection mechanism of antibiotic resistance at atomic resolution: insights into FusB-type fusidic acid resistance

    PubMed Central

    Tomlinson, Jennifer H.; Thompson, Gary S.; Kalverda, Arnout P.; Zhuravleva, Anastasia; O’Neill, Alex J.

    2016-01-01

    Antibiotic resistance in clinically important bacteria can be mediated by proteins that physically associate with the drug target and act to protect it from the inhibitory effects of an antibiotic. We present here the first detailed structural characterization of such a target protection mechanism mediated through a protein-protein interaction, revealing the architecture of the complex formed between the FusB fusidic acid resistance protein and the drug target (EF-G) it acts to protect. Binding of FusB to EF-G induces conformational and dynamic changes in the latter, shedding light on the molecular mechanism of fusidic acid resistance. PMID:26781961

  5. The mechanism of laser disturbing infrared detector and its intelligent protection

    NASA Astrophysics Data System (ADS)

    Lu, Yuan; Feng, Yun-song; Ling, Yong-shun; Qiao, Ya

    2013-09-01

    Interference mechanism of laser disturbing infrared detector is analyzed. The disturbing grade was separated into four levels according to interference effect. The levels are saturation, melting, vaporization and plasma. The responsivity of a detector will drop and it can't work effectively when it was saturated. Its performance wills recovery when the interference disappeared. Melting, Vaporization and plasma will lead to permanent damage. The main damage to detector is thermal damage for induced laser. The reason is that the detector will melt or evaporate when it absorbed the energy of induced laser. For HgCdTe detector, the damage appeared as Hg precipitation. It appeared as In exfoliated from welding outlet line of HgCdTe crystal or HgCdTe melting when the temperature of detector is higher. Since Vanadium Oxide has reversible transformation characteristic between semi-conductor, metal and insulator, it can be used to protect detector from laser damage. Vanadium Oxide can be made as thin film coatings on optical system to protect the detector. the phase transformation point temperature of VO2 is 68°C,a few doping method can decrease the transformation temperature. These mean that less energy can make VO2 film's temperature increase to transformation point. VO2 film protecting HgCdTe detector was used as an example to estimate the protection effect. For an HgCdTe detector, its responsivity will drop two orders of magnitude when its temperature raises 70K. This case be regard as that the detector was disturbed. When a CO2 pulsed laser beam with 0.1μ s˜10μs pulse width was incidence an HgCdTe detector, its heat conduction depth is 0.32˜3.2μm and its thermal diffusion can be ignored. The damage energy density threshold value is Ein=1.55J/cm2. When CO2 pulsed laser beam incidence the detector through certain thickness VO2 film, the VO2 film will has transformed from semiconductor state to metallic state before the laser beam damage the detector. The energy of

  6. A Methodology for Protective Vibration Monitoring of Hydropower Units Based on the Mechanical Properties.

    PubMed

    Nässelqvist, Mattias; Gustavsson, Rolf; Aidanpää, Jan-Olov

    2013-07-01

    It is important to monitor the radial loads in hydropower units in order to protect the machine from harmful radial loads. Existing recommendations in the standards regarding the radial movements of the shaft and bearing housing in hydropower units, ISO-7919-5 (International Organization for Standardization, 2005, "ISO 7919-5: Mechanical Vibration-Evaluation of Machine Vibration by Measurements on Rotating Shafts-Part 5: Machine Sets in Hydraulic Power Generating and Pumping Plants," Geneva, Switzerland) and ISO-10816-5 (International Organization for Standardization, 2000, "ISO 10816-5: Mechanical Vibration-Evaluation of Machine Vibration by Measurements on Non-Rotating Parts-Part 5: Machine Sets in Hydraulic Power Generating and Pumping Plants," Geneva, Switzerland), have alarm levels based on statistical data and do not consider the mechanical properties of the machine. The synchronous speed of the unit determines the maximum recommended shaft displacement and housing acceleration, according to these standards. This paper presents a methodology for the alarm and trip levels based on the design criteria of the hydropower unit and the measured radial loads in the machine during operation. When a hydropower unit is designed, one of its design criteria is to withstand certain loads spectra without the occurrence of fatigue in the mechanical components. These calculated limits for fatigue are used to set limits for the maximum radial loads allowed in the machine before it shuts down in order to protect itself from damage due to high radial loads. Radial loads in hydropower units are caused by unbalance, shape deviations, dynamic flow properties in the turbine, etc. Standards exist for balancing and manufacturers (and power plant owners) have recommendations for maximum allowed shape deviations in generators. These standards and recommendations determine which loads, at a maximum, should be allowed before an alarm is sent that the machine needs maintenance. The radial

  7. Smart Multifunctional Fluids for Lithium Ion Batteries: Enhanced Rate Performance and Intrinsic Mechanical Protection

    NASA Astrophysics Data System (ADS)

    Ding, Jie; Tian, Tongfei; Meng, Qing; Guo, Zaiping; Li, Weihua; Zhang, Peng; Ciacchi, Fabio T.; Huang, Jewel; Yang, Wenrong

    2013-08-01

    Lithium ion batteries are attractive power sources for the consumer electronics market and are being aggressively developed for road transportation. Nevertheless, issues with safety and reliability need to be solved prior to the large-scale uptake of these batteries. There have recently been significant development and assessment of materials with resistance to mechanical abuse, with the aims of reinforcing the battery and preventing puncturing during a crash. Most of the work on battery mechanical safety has concentrated on the external packaging of batteries, with little attention being paid to the enclosed electrolyte. We report on smart multifunctional fluids that act as both highly conductive electrolytes and intrinsic mechanical protectors for lithium ion batteries. These fluids exhibit a shear thickening effect under pressure or impact and thus demonstrate excellent resistance to crushing. Also, the fluids show higher ionic conductivities and comparable redox stability windows to the commercial liquid electrolytes.

  8. Smart multifunctional fluids for lithium ion batteries: enhanced rate performance and intrinsic mechanical protection.

    PubMed

    Ding, Jie; Tian, Tongfei; Meng, Qing; Guo, Zaiping; Li, Weihua; Zhang, Peng; Ciacchi, Fabio T; Huang, Jewel; Yang, Wenrong

    2013-01-01

    Lithium ion batteries are attractive power sources for the consumer electronics market and are being aggressively developed for road transportation. Nevertheless, issues with safety and reliability need to be solved prior to the large-scale uptake of these batteries. There have recently been significant development and assessment of materials with resistance to mechanical abuse, with the aims of reinforcing the battery and preventing puncturing during a crash. Most of the work on battery mechanical safety has concentrated on the external packaging of batteries, with little attention being paid to the enclosed electrolyte. We report on smart multifunctional fluids that act as both highly conductive electrolytes and intrinsic mechanical protectors for lithium ion batteries. These fluids exhibit a shear thickening effect under pressure or impact and thus demonstrate excellent resistance to crushing. Also, the fluids show higher ionic conductivities and comparable redox stability windows to the commercial liquid electrolytes. PMID:23962885

  9. Mutations Causing Complex Disease May under Certain Circumstances Be Protective in an Epidemiological Sense.

    PubMed

    Siegert, Sabine; Wolf, Andreas; Cooper, David N; Krawczak, Michael; Nothnagel, Michael

    2015-01-01

    Guided by the practice of classical epidemiology, research into the genetic basis of complex disease has usually taken for granted the dictum that causative mutations are invariably over-represented among clinically affected as compared to unaffected individuals. However, we show that this supposition is not true and that a mutation contributing to the etiology of a complex disease can, under certain circumstances, be depleted among patients. Populations with defined disease prevalence were repeatedly simulated under a Wright-Fisher model, assuming various types of population history and genotype-phenotype relationship. For each simulation, the resulting mutation-specific population frequencies and odds ratios (ORs) were evaluated. In addition, the relationship between mutation frequency and OR was studied using real data from the NIH GWAS catalogue of reported phenotype associations of single-nucleotide polymorphisms (SNPs). While rare diseases (prevalence <1%) were found to be consistently caused by rare mutations with ORs>1, up to 20% of mutations causing a pandemic disease (prevalence 10-20%) had ORs<1, and their population frequency ranged from 0% to 100%. Moreover, simulation-based ORs exhibited a wide distribution, irrespective of mutation frequency. In conclusion, a substantial proportion of mutations causing common complex diseases may appear 'protective' in genetic epidemiological studies and hence would normally tend to be excluded, albeit erroneously, from further study. This apparently paradoxical result is explicable in terms of mutual confounding of the respective genotype-phenotype relationships due to a negative correlation between causal mutations induced by their common gene genealogy. As would be predicted by our findings, a significant negative correlation became apparent in published genome-wide association studies between the OR of genetic variants associated with a particular disease and the prevalence of that disease. PMID:26161957

  10. Mechanisms Underpinning Degradation of Protective Oxides and Thermal Barrier Coatings in High Hydrogen Content (HHC) - Fueled Turbines

    SciTech Connect

    Mumm, Daniel

    2013-08-31

    The overarching goal of this research program has been to evaluate the potential impacts of coal-derived syngas and high-hydrogen content fuels on the degradation of turbine hot-section components through attack of protective oxides and thermal barrier coatings. The primary focus of this research program has been to explore mechanisms underpinning the observed degradation processes, and connections to the combustion environments and characteristic non-combustible constituents. Based on the mechanistic understanding of how these emerging fuel streams affect materials degradation, the ultimate goal of the program is to advance the goals of the Advanced Turbine Program by developing materials design protocols leading to turbine hot-section components with improved resistance to service lifetime degradation under advanced fuels exposures. This research program has been focused on studying how: (1) differing combustion environments – relative to traditional natural gas fired systems – affect both the growth rate of thermally grown oxide (TGO) layers and the stability of these oxides and of protective thermal barrier coatings (TBCs); and (2) how low levels of fuel impurities and characteristic non-combustibles interact with surface oxides, for instance through the development of molten deposits that lead to hot corrosion of protective TBC coatings. The overall program has been comprised of six inter-related themes, each comprising a research thrust over the program period, including: (i) evaluating the role of syngas and high hydrogen content (HHC) combustion environments in modifying component surface temperatures, heat transfer to the TBC coatings, and thermal gradients within these coatings; (ii) understanding the instability of TBC coatings in the syngas and high hydrogen environment with regards to decomposition, phase changes and sintering; (iii) characterizing ash deposition, molten phase development and infiltration, and associated corrosive

  11. A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans.

    PubMed

    Yang, Ruilong; Ren, Mingxia; Rui, Qi; Wang, Dayong

    2016-01-01

    Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes. PMID:27558892

  12. Does mechanical stimulation really protect the architecture of trabecular bone? A simulation study.

    PubMed

    Maurer, Manfred M; Weinkamer, Richard; Müller, Ralph; Ruffoni, Davide

    2015-08-01

    Although it is beyond doubt that mechanical stimulation is crucial to maintain bone mass, its role in preserving bone architecture is much less clear. Commonly, it is assumed that mechanics helps to conserve the trabecular network since an "accidental" thinning of a trabecula due to a resorption event would result in a local increase of load, thereby activating bone deposition there. However, considering that the thin trabecula is part of a network, it is not evident that load concentration happens locally on the weakened trabecula. The aim of this work was to clarify whether mechanical load has a protective role for preserving the trabecular network during remodeling. Trabecular bone is made dynamic by a remodeling algorithm, which results in a thickening/thinning of trabeculae with high/low strain energy density. Our simulations show that larger deviations from a regular cubic lattice result in a greater loss of trabeculae. Around lost trabeculae, the remaining trabeculae are on average thinner. More generally, thin trabeculae are more likely to have thin trabeculae in their neighborhood. The plausible consideration that a thin trabecula concentrates a higher amount of strain energy within itself is therefore only true when considering a single isolated trabecula. Mechano-regulated remodeling within a network-like architecture leads to local concentrations of thin trabeculae. PMID:25501464

  13. A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans

    PubMed Central

    Yang, Ruilong; Ren, Mingxia; Rui, Qi; Wang, Dayong

    2016-01-01

    Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes. PMID:27558892

  14. Available data support protection of the Southwestern Willow Flycatcher under the Endangered Species Act

    USGS Publications Warehouse

    Theimer, Tad C.; Smith, Aaron D.; Mahoney, Sean M.; Ironside, Kirsten E.

    2016-01-01

    Zink (2015) argued there was no evidence for genetic, morphological, or ecological differentiation between the federally endangered Southwestern Willow Flycatcher (Empidonax traillii extimus) and other Willow Flycatcher subspecies. Using the same data, we show there is a step-cline in both the frequency of a mtDNA haplotype and in plumage variation roughly concordant with the currently recognized boundary between E. t. extimus and E. t adastus, the subspecies with which it shares the longest common boundary. The geographical pattern of plumage variation is also concordant with previous song analyses differentiating those 2 subspecies and identified birds in one low-latitude, high-elevation site in Arizona as the northern subspecies. We also demonstrate that the ecological niche modeling approach used by Zink yields the same result whether applied to the 2 flycatcher subspecies or to 2 unrelated species, E. t. extimus and Yellow Warbler (Setophaga petechia). As a result, any interpretation of those results as evidence for lack of ecological niche differentiation among Willow Flycatcher subspecies would also indicate no differentiation among recognized species and would therefore be an inappropriate standard for delineating subspecies. We agree that many analytical techniques now available to examine genetic, morphological, and ecological differentiation would improve our understanding of the distinctness (or lack thereof) of Willow Flycatcher subspecies, but we argue that currently available evidence supports protection of the Southwestern Willow Flycatcher under the Endangered Species Act.

  15. Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis

    SciTech Connect

    Dong, Chenglong; Zheng, Haining; Huang, Shanshan; You, Na; Xu, Jiarong; Ye, Xiaolong; Zhu, Qun; Feng, Yamin; You, Qiang; Miao, Heng; Ding, Dafa; Lu, Yibing

    2015-10-01

    Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12–24 h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy. - Highlights: • High glucose leads to increased autophagy in podocytes at an early stage. • The early autophagic response protects against high glucose-induced apoptosis. • Heme oxygenase-1 enhances autophagy and decreases high glucose -mediated apoptosis. • Heme oxygenase-1 induces autophagy through the activation of AMPK.

  16. Protective Effects of Oleic Acid Against Palmitic Acid-Induced Apoptosis in Pancreatic AR42J Cells and Its Mechanisms

    PubMed Central

    Ahn, Joung Hoon; Kim, Min Hye; Kwon, Hyung Joo; Choi, Soo Young

    2013-01-01

    Palmitic acid (PAM), one of the most common saturated fatty acid (SFA) in animals and plants, has been shown to induce apoptosis in exocrine pancreatic AR42J cells. In this study, we investigated cellular mechanisms underlying protective effects of oleic acid (OLA) against the lipotoxic actions of PAM in AR42J cells. Exposure of cells to long-chain SFA induced apoptotic cell death determined by MTT cell viability assay and Hoechst staining. Co-treatment of OLA with PAM markedly protected cells against PAM-induced apoptosis. OLA significantly attenuated the PAM-induced increase in the levels of pro-apoptotic Bak protein, cleaved forms of apoptotic proteins (caspase-3, PARP). On the contrary, OLA restored the decreased levels of anti-apoptotic Bcl-2 family proteins (Bcl-2, Bcl-xL, and Mcl-1) in PAM-treated cells. OLA also induced up-regulation of the mRNA expression of Dgat2 and Cpt1 genes which are involved in triacylglycerol (TAG) synthesis and mitochondrial β-oxidation, respectively. Intracellular TAG accumulation was increased by OLA supplementation in accordance with enhanced expression of Dgat2 gene. These results indicate that restoration of anti-apoptotic/pro-apoptotic protein balance from apoptosis toward cell survival is involved in the cytoprotective effects of OLA against PAM-induced apoptosis in pancreatic AR42J cells. In addition, OLA-induced increase in TAG accumulation and up-regulation of Dgat2 and Cpt1 gene expressions may be possibly associated in part with the ability of OLA to protect cells from deleterious actions of PAM. PMID:23440052

  17. Activation of lipid peroxidation as a mechanism of plant cell rearrangements under microgravity

    NASA Astrophysics Data System (ADS)

    Baranenko, V. V.

    Activation of the lipid peroxidation (LP) is a universal process perturbating cell membranes under different unfavourable conditions. It is suggested that the LP can be one of the important mechanisms of plant cell rearrangements under altered gravity as well. The purpose of this investigation is to study the LP intensity in pea leaves and chloroplasts under 7- and 14-day clinorotation. The intensification of the LP under both terms of clinorotation particularly under more prolonged, is detected. The adaptive increase in the unsaturated fatty acid content under 7-day clinorotation and their minor decrease under 14-day clinorotation are revealed. The lowering of electron transport rate in both photosystems, particularly in PSI, is established. The results confirm that the LPmay be one of the mechanisms of plant cell rearrangements under microgravity.

  18. Diallyl trisulfide protects against ethanol-induced oxidative stress and apoptosis via a hydrogen sulfide-mediated mechanism.

    PubMed

    Chen, Lian-Yun; Chen, Qin; Zhu, Xiao-Jing; Kong, De-Song; Wu, Li; Shao, Jiang-Juan; Zheng, Shi-Zhong

    2016-07-01

    Garlic is one natural source of organic sulfur containing compounds and has shown promise in the treatment of chronic liver disease. Dietary garlic consumption is inversely correlated with the progression of alcoholic fatty liver (AFL), although the exact underlying mechanisms are not clear. Our previous studies also have shown that diallyl trisulfide (DATS), the primary organosulfur compound from Allium sativum L, displayed anti-lipid deposition and antioxidant properties in AFL. The aim of the present study was to clarify the underlying mechanisms. In the present study, we used the intragastric infusion model of alcohol administration and human normal liver cell line LO2 cultured with suitable ethanol to mimic the pathological condition of AFL. We showed that accumulation of intracellular reactive oxygen species (ROS) was lowered significantly by the administration of DATS, but antioxidant capacity was increased by DATS. Additionally, DATS inhibited hepatocyte apoptosis via down-regulating Bax expression and up-regulating Bcl-2 expression, and attenuated alcohol-induced caspase-dependent apoptosis. More importantly, using iodoacetamide (IAM) to block hydrogen sulfide (H2S) production from DATS, we noted that IAM abolished all the above effects of DATS in ethanol-treated LO2 cells. Lastly, we found DATS could increase the expressions of cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS), the major H2S-producing enzymes. These results demonstrate that DATS protect against alcohol-induced fatty liver via a H2S-mediated mechanism. Therefore, targeting H2S may play a therapeutic role for AFL. PMID:27107369

  19. Plastic Surgery Practice Models and Research Aims Under the Patient Protection and Affordable Care Act

    PubMed Central

    Giladi, Aviram M.; Yuan, Frank; Chung, Kevin C.

    2014-01-01

    As the healthcare landscape in the United States changes under the Affordable Care Act (ACA), providers are set to face numerous new challenges. Although concerns about practice sustainability with declining reimbursement have dominated the dialogue, there are more pressing changes to the healthcare funding mechanism as a whole that must be addressed. Plastic surgeons, involved in various practice models each with different relationships to hospitals, referring physicians, and payers, must understand these reimbursement changes in order to dictate adequate compensation in the future. Here we discuss bundle payments and Accountable Care Organizations (ACOs), and how plastic surgeons might best engage in these new system designs. In addition, we review the value of a focused and driven health-services research agenda in plastic surgery, and the importance of this research in supporting long-term financial stability for the specialty. PMID:25626805

  20. Mechanisms of protection induced by attenuated simian immunodeficiency virus. I. Protection cannot be transferred with immune serum.

    PubMed

    Almond, N; Rose, J; Sangster, R; Silvera, P; Stebbings, R; Walker, B; Stott, E J

    1997-08-01

    To evaluate its role in protection, immune serum was collected from four macaques which were chronically infected with live attenuated simian immunodeficiency virus (SIVmacC8) and had resisted challenge with wild-type SIVmacJ5. The immune serum was transferred to two naive cynomolgus macaques by intraperitoneal injection (11 ml/kg). Four control macaques received an intraperitoneal injection of normal saline. One day later, all macaques were challenged with 10 MID50 of the J5M challenge stock of SIV. After challenge, all macaques became infected as determined by virus co-culture and diagnostic PCR. Virus loads in PBMC at 2 weeks post-challenge were indistinguishable between the two groups of macaques. Thus, the failure of passive immunization to transfer protection indicates that serum components alone are not sufficient to mediate the potent protection obtained using live attenuated vaccines. This is the first time that serum has been transferred from animals known to be protected against superinfection. PMID:9266988